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WO2008044779A1 - Micro-pixelated fluid-assay structure, micro-pixelated fluid-assay precursor structure, and making method and performing method thereof - Google Patents

Micro-pixelated fluid-assay structure, micro-pixelated fluid-assay precursor structure, and making method and performing method thereof Download PDF

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Publication number
WO2008044779A1
WO2008044779A1 PCT/JP2007/070021 JP2007070021W WO2008044779A1 WO 2008044779 A1 WO2008044779 A1 WO 2008044779A1 JP 2007070021 W JP2007070021 W JP 2007070021W WO 2008044779 A1 WO2008044779 A1 WO 2008044779A1
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WIPO (PCT)
Prior art keywords
assay
pixel
micro
digitally
creating
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
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PCT/JP2007/070021
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French (fr)
Inventor
John W. Hartzell
Pooran C. Joshi
Paul J. Schuele
Andrei Gindilis
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Sharp Corp
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Sharp Corp
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Publication date
Priority claimed from US11/827,174 external-priority patent/US8231831B2/en
Priority claimed from US11/827,335 external-priority patent/US8236245B2/en
Priority claimed from US11/827,175 external-priority patent/US8236571B2/en
Priority claimed from US11/827,176 external-priority patent/US8232108B2/en
Priority claimed from US11/888,491 external-priority patent/US8232109B2/en
Application filed by Sharp Corp filed Critical Sharp Corp
Publication of WO2008044779A1 publication Critical patent/WO2008044779A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0636Integrated biosensor, microarrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0645Electrodes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0819Microarrays; Biochips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877Flow chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1805Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/18Means for temperature control
    • B01L2300/1805Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components

Definitions

  • This invention relates to a pixelated, fluid-assay, precursor structure, and a pixelated, fluid-assay structure, and also relates to making methods of such a precursor micro-structure and a micro-structure, and a performance of fluid-material assay.
  • This invention concerns a pixelated, thin-film-based, fluid-assay, active-matrix structure, and more particularly to a row-and-column micro-structure of active, individually digitally-addressable pixels which have been prepared on a supporting substrate as "blank slates" for later, selective, assay-specific, assay-site functionalization, also referred to interchangeably as pixel functionalization, to enable the performance of at least one kind of a fluid-material assay.
  • This invention also concerns a method for producing a pixelated, thin-film-based, fluid-assay, precursor, active-matrix structure, and more particularly to a method for producing a precursor row-and-column micro-structure of active, remotely individually digitally-addressable pixels which have been prepared on a supporting substrate as "blank slates" (shortly to be described) for later, selective, assay-specific, assay-site functionalization to enable the performance of at least one kind of a fluid-material assay.
  • This invention also concerns the field of fluid-material assays, and especially to a significantly improved assay-response , thin-film-based pixel matrix which offers a very high degree of controlled, assay-response, pixel-specific sensitivity with respect to which an assay response (a) can be output-read on a precision, pixel-by-pixel basis, and (b) can additionally be examined along uniquely accessible, special, plural and freely selectable, independent-variable
  • information-gathering axes such as a time-sampling axis, and an electromagnetic-field-variable (light, heat, non-uniform electrical) axis.
  • This invention also concerns a method for producing a pixelated, thin-film-based, fluid-assay, active-matrix structure . More particularly, it pertains to a method for producing a row-and-column micro-structure array of active, remotely individually digitally-addressable pixels which have been prepared on a supporting substrate, each with (a) an included assay sensor (at least one) possessing an assay site (at least one) , and (b) an also included digitally-addressable, electromagnetic field-creating structure.
  • This field-creating structure is energizable to bathe the associated pixel with an ambient electromagnetic field which is one or more of a field of light, a field of heat, and a non-uniform electrical field.
  • the pixels' respective assay sites are functionalized to possess respective assay-material-specificity so as each to have a defined, specific affinity for at least one kind of a fluid-assay material.
  • This invention also concerns the field of fluid-material assays. More particularly, it relates to the performance of such an assay in the specific context of employing a significantly improved type of thin-film-based, active-pixel, pixelated assay-response matrix for "Micro-Pixelated Fluid-Assay Structure".
  • the invention preferably takes the form of a relatively inexpensive , consumer-level-affordable, thin-film-based assay structure which features a low-cost substrate that will readily accommodate low-cost, and preferably "low-temperature-condition” , fabrication thereon of substrate- supported matrix-pixel “components", and a method of creating such a precursor assay structure .
  • Low temperature is defined herein as a being a characteristic of processing that can be done on substrate material having a transition temperature (Tg) which is less than about 850°C , i. e . , less than a temperature which, if maintained during sustained material processing, would cause the subject material to lose dimensional stability.
  • the preferred supporting substrate material is one made of lower-expense glass or plastic materials.
  • glass and plastic employed herein to describe a preferred substrate material should be understood to be referring also to other suitable "low-temperature materials
  • Such substrate materials while importantly contributing on one level to relatively low, overall, end-product cost, also allow specially for the compatible employment, with respect to the fabrication of supported pixel structure, of processes and methods that are based on amorphous, micro-crystal and polysilicon thin-film-transistor (TFT) technology.
  • TFT thin-film-transistor
  • these substrate materials uniquely accommodate the use of the just-mentioned TFT technology in such a way that electrical, mechanical and electromagnetic field-creating devices - devices that are included variously in the structure of the invention -- can be fabricated simultaneously in a process flow which is consistent with the temperature tolerance of such substrate materials.
  • low-temperature TFT devices are formed through deposition processes that deposit silicon-based (or other-material-based, as mentioned below herein, and as referred to at certain points within this text with the expression "etc.") thin film semiconductor material
  • TFT transistors can be fabricated cheaply with a relatively few number of process steps. Further, thin-film deposition processes permit TFT devices to be formed on alternate substrate materials, such as transparent glass substrates, for use , as an example, in liquid crystal displays.
  • TFT device fabrication may variously involve the use typically of amorphous Si (a-Si) , of micro-crystalline Si, and or of polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si.
  • a-Si amorphous Si
  • micro-crystalline Si amorphous Si
  • polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si.
  • the invention preferably takes the form of a method for creating a relatively inexpensive, consumer-level-affordable, thin-film-based, assay structure which features a low-cost substrate that will readily accommodate low-cost, and preferably
  • Low-temperature-condition fabrication thereon of substrate- supported matrix-pixel “components” .
  • Low temperature is defined herein as a being a characteristic of processing that can be done on substrate material having a transition temperature (Tg) which is less than about 850°C, i.e. , less than a temperature which, if maintained during sustained material processing, would cause the subject material to lose dimensional stability.
  • Tg transition temperature
  • the matrix-pixel technology which is involved with practice of the methodology of this invention, if so desired, can be implemented on more costly supporting silicon substrates
  • the preferred supporting substrate material employed in the practice of the invention is one made of lower-expense glass or plastic materials.
  • glass and plastic employed herein to describe a preferred substrate material should be understood to be referring also to other suitable "low-temperature materials.
  • substrate materials while importantly contributing on one level to relatively low, overall, end-product cost, also allow specially for the compatible employment, with respect to the fabrication of supported pixel structure, of processes and methods that are based on amorphous, micro-crystal and polysilicon thin-film-transistor
  • TFT thin film spectroscopy
  • these substrate materials uniquely accommodate the use of the just-mentioned, low-temperature TFT technology in such a way that electrical, mechanical and electromagnetic field-creating devices - devices that are included variously in the structure produced by the invention -- can be fabricated simultaneously in a process flow which is consistent with the temperature tolerance of such substrate materials.
  • low-temperature TFT devices are formed through deposition processes that deposit silicon-based (or other-material-based, as mentioned below herein, and as referred to at certain points within this text with the expression "etc.") thin film semiconductor material
  • TFT transistors can be fabricated cheaply with a relatively few number of process steps. Further, thin-film deposition processes permit TFT devices to be formed on alternate substrate materials, such as transparent glass substrates, for use, as an example, in liquid crystal displays.
  • low-temperature TFT device fabrication may variously involve the use typically of amorphous Si (a-Si) , of micro-crystalline Si, and or of polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si.
  • a-Si amorphous Si
  • micro-crystalline Si amorphous Si
  • polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si.
  • the active-pixel matrix which is a digitally accessible and controllable structure linkable to a suitable digital computer, offers a very high degree of controlled, assay-response, pixel-specific sensitivity with respect to which an assay response (a) can be output-read on a precision, pixel-by-pixel basis, and (b) can additionally be examined along uniquely accessible, special, plural and freely selectable, independent-variable "information-gathering axes", such as a time-based axis, and an electromagnetic-field-variable (light, heat, non-uniform electrical) axis.
  • the matrix structure with its included electronically active pixels which structure is preferably employed in the assay-performance practice of the present invention, is formed conveniently on a low-temperature substrate material, such as glass, and may involve, in its underlying construction, low-temperature, internal crystalline-structural processing of a material, such as amorphous silicon, to create some of its pixel-borne structural features.
  • a low-temperature substrate material such as glass
  • Such crystalline-structural processing is described in U . S. Patent No. 7, 125 ,45 1 B2 , the disclosure content of which patent is also hereby incorporated herein by reference.
  • the present invention may be described as a method of performing a fluid-material assay employing an appropriately provided (i. e . , made available) computer-accessible device (note the discussion above) -- preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable assay site functionalized for selected fluid-assay material, with the key steps of this method including, following, of course, providing such a device, exposing the pixel's sensor assay site to such material, and in conjunction with such exposing, and employing the computer-accessible, active nature of the provided device's pixel, remotely and digitally requesting from the pixel's sensor assay site an assay-result output report.
  • an appropriately provided i. e . , made available
  • a computer-accessible device preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable as
  • the basic methodology further includes, in relation to the mentioned employing step, creating, relative to the sensor's assay site in the at least one pixel, a predetermined, pixel-specific electromagnetic field environment.
  • the creation of such an environment is enabled by the type of matrix structure of this invention, and is specifically enabled by the presence in the described matrix pixels of one or several digitally accessible and energizable electromagnetic field-creating structure(s) .
  • Fig. 1 is a simplified, fragmentary, block/ schematic view of a portion of a digitally-addressable, pixelated, fluid-assay, active-matrix micro-structure formed in accordance with a preferred and best mode embodiment of the present invention.
  • Fig. 2 is similar to Fig. 1 , except that it provides a slightly more detailed view of the structure shown in Fig. 1 .
  • Fig. 3 which is prepared on a somewhat larger scale than those scales employed in Fig. 1 and Fig. 2 , illustrates, schematically, different, single, overall, matrix-organizational ways in which precursor fluid-assay pixels in the matrix micro-structure of this invention may be organized, user-selectively, into different functionalized arrangements for different fluid-assays that are ultimately to be performed.
  • Fig. 4 is a fragmentary, block/ schematic diagram illustrating one form of an electromagnetic field-creating structure prepared in accordance with practice of the present invention, and specifically such a structure which is intended to create an ambient, electromagnetic, pixel-bathing field environment characterized by light.
  • Fig. 5 is similar to Fig. 4, except that it illustrates another field-of-light-environment-creating structure.
  • Fig. 6 provides a fragmentary, schematic illustration of one form of a heat-field-creating structure .
  • Fig. 7 illustrates fragmentarily another form of a heat-field-creating structure which has been prepared on the body of a mechanical cantilever beam which also carries an electrical signaling structure that responds to beam deflection to produce a related electrical output signal.
  • Fig. 8 is an isometric view of a pixel-bathing, non-uniform electrical-field-creating structure prepared through a recently developed process, touched upon later in this specification, involving internal crystalline-structure processing of substrate material.
  • Fig. 9 provides a simplified side elevation of the structure presented in Fig. 8 , schematically picturing, also, a pixel-bathing, non-uniform electrical field.
  • Figs. 1 OA, 1 OB and 1 OC illustrate, in greatly simplified forms, three different kinds of three-dimensional spike features which may be created in relation to what is shown generally in Fig. 8 and Fig. 9 for the production of a non-uniform electrical field.
  • Fig 1 1 provides a fragmentary view, somewhat like that presented in Fig. 1 , but here showing a pixel which has been created in accordance with practice of the present invention to include two (plural) assay sensors, each of which is designed to receive and host a single, potential fluid-material assay site.
  • Fig. 12 is somewhat similar to Fig. 1 1 , except that this figure shows a pixel which has been prepared in accordance with practice of the present invention to include a single fluid-assay sensor which possesses, or hosts, two (plural) potential fluid-material assay sites.
  • Fig. 13 to Fig. 18 provide block/ schematic diagrams illustrating the various methodological steps which characterize the preferred and best mode manner of practicing the present invention.
  • Fig. 19 to Fig. 26, inclusive provide block/ schematic diagrams illustrating the various methodological steps which characterize the preferred and best mode manner of practicing the present invention.
  • Fig. 27 to Fig. 31 , inclusive provide block-schematic diagrams that illustrate different ways of viewing the methodologic practice steps of the present invention.
  • Fig. 32 to Fig. 36, inclusive help to describe various aspects of the above-mentioned, illustrative DNA fluid assay, with respect to which a controlled heat field may be employed, and also time sampling may be used, to furnish different axes of assay-result output information obtainable from practice of the present invention.
  • Fig. 1 and Fig. 2 indicated generally at 20 is a fragmentary portion of a precursor, digitally-addressable, pixelated, fluid-assay, active-matrix micro-structure .
  • Micro-structure 20 takes the form herein of a column-and-row array 22 of plural, individually externally addressable pixels, such as those shown at 24 , 26, 28 , 30 , 32 , formed, as will shortly be described, on an appropriate supporting, conventional-material, preferably glass or plastic, substrate 34.
  • substrate 34 will be considered to be a glass substrate.
  • an internal crystalline-structure processing approach may be employed to create certain desired mechanical characteristics, such as the bending characteristics of a cantilever beam like that pictured in Fig. 1 , or the configurations of a collection of material spikes, like that collection which appears in Fig. 8 to Fig. 1 OC, inclusive .
  • Such internal crystalline-structure processing methodology is fully described in U . S . Patent No . 7, 125 ,45 1 B2 , and accordingly, the disclosure content of that patent is hereby incorporated herein by reference in order to provide background information respecting such processing methodology.
  • various non-critical dimensions may be chosen, for example, to define the overall lateral size of a precursor micro-structure, such as micro-structure 20.
  • the number of pixels organized into the relevant, overall row-and-column matrix may readily be chosen by one practicing the present invention.
  • a precursor micro-structure, such as micro-structure 20 might have lateral dimensions lying in a range of about 0.4 x 0.4-inches to about 2 x 2-inches, and might include an equal row-and-column array of pixels including a total pixel count lying in a range of about 100 to about 10 ,000. These size and pixel-count considerations are freely choosable by a practicer of the present invention.
  • a bracket 36 and a double-headed, broad arrow 38 represent an appropriate communication/ addressing connection, or path, between pixels in micro-structure 20 and a suitable digital computer, such as the computer shown in block form in Fig. 1 at 40.
  • a suitable digital computer such as the computer shown in block form in Fig. 1 at 40.
  • Such a path exists and is employed under circumstances where a precursor micro-structure, such as micro-structure 20 , is being (a) functionalized, or (b) "read” after the performance of a fluid-material assay.
  • This inclusion of computer 40 in Fig. 1 has been done to help illustrate and describe the completed precursor-micro-structure utility of the present invention.
  • each of the mentioned precursor pixels is essentially identical to each other pixel, although, as will later be explained herein, this is not a necessary requirement of the present invention.
  • This "not-necessary" statement regarding the characteristics of the present invention is based upon a clear understanding that there are various end-result fluid-assay applications with respect to which appropriately differentiated precursor pixels might be fabricated in a single, precursor micro-structure array.
  • pixel 24 In general terms, and using pixel 24 as an illustration to explain the basic construction of each of the precursor pixels shown in array 22 , included in pixel 24 are several, fully integrated, pixel-specific components, or substructures. These include, as part of more broadly inclusive pixel-specific electronic structure , ( 1 ) thin-film, digitally-addressable electronic switching structure, (2) a non-functionalized, precursor, individually remotely digitally-addressable and accessible assay sensor 24a which hosts a prospective, functionalizable assay site 24a 1 ? and (3) what is referred to herein as a pixel-bathing, ambient environmental, electromagnetic-field-creating structure 24b.
  • Field-creating structure 24b which is also remotely, or externally, individually digitally-addressable and accessible, is constructed to create, when energized, any one or more of three different kinds of assay-site-bathing, pixel-bathing, ambient, environmental electromagnetic fields in the vicinity of sensor 24a, including a light field, a heat field, and a non-uniform electrical field. While structure 24b, as was just mentioned, may be constructed to create one or more of these three different kinds of fields, in the micro-structure pictured in Fig. 1 and Fig. 2, field-creating structure 24b has been designed with three field-creating subcomponents 24b 1 ⁇ 24b2 and 24b3.
  • Subcomponent 24bi is capable of creating a pixel-bathing light field, subcomponent 24b2 a pixel-bathing heat field, and subcomponent 24b3 a pixel-bathing non-uniform electrical field. More will be said about these three different kinds of pixel-bathing, field-creating subcomponents shortly.
  • a bathing electromagnetic field of an appropriate selected character during pixel functionalization operates to create, within a pixel and adjacent an assay site, an ambient environmental condition wherein relevant chemical, biochemical, etc. reactions regarding functionalization flow material can take place , at least at the prepared, sensor-possessed assay site, or sites, to ensure proper functionalization at that site.
  • a "prepared assay site” might typically, i. e. , conventionally, be defined by a sensor borne area of plated gold.
  • each precursor pixel is appropriately prepared with one or more conventional electronic switching device(s) (part of the mentioned electronic switching structure) relevant to accessing and addressing its included sensor and assay site, and to energizing its field-creating structure . Illustrations of such devices are given later herein.
  • Fig. 2 indicated generally at 42 , 44 are two different communication line systems which are suitably created, and operatively connected to the field-creating structures in the illustrated pixels, and to the assay sensors and assay sites shown in these pixels.
  • the upper, fragmented ends of line systems 42 , 44 in Fig. 2 are embraced by a bracket marked with the two reference numerals 36, 38, which bracket represents the previously mentioned "path" of operative connection shown to exist in Fig. 1 between micro-structure 20 and computer 40.
  • Line system 42 is utilized by such a computer to energize pixel-bathing, field-creating subcomponents during a functionalization procedure, and also to energize these same field-creating subcomponents, where appropriate, during reading-out of the results of a performed assay.
  • Line system 44 on a pixel-by-pixel basis, directly couples to computer 40 output responses derived from ultimately functionalized assay sites.
  • Fig. 3 illustrates several different ways in which ultimately functionalized pixels (i. e . , non-precursor pixels) , such as fully functionalized versions of the pixels in array 22 , may, as enabled by the methodology of the invention, be organized and even differentiated in the hands of a user who is provided with a resulting, fully-rendered (i.e . , functionalized) matrix.
  • functionalized pixels i. e . , non-precursor pixels
  • dots which appear throughout in a row-and-column arrangement in Fig. 3, represent the locations of full-matrix, next-adjacent pixels constructed during practice of this invention.
  • One way of visualizing utilization of the full-matrix precursor structure, as represented by the full array of "dots" in Fig. 3, is to recognize that every pixel thus represented by one of the mentioned dots may be commonly functionalized to respond to a single, specific fluid-assay material.
  • marked regions A, B , C in Fig. 3 illustrate three other, representative, possible pixel functionalization patterns (specifically lower-pixel-count, submatrix patterns) that are accommodated by the utility of the present invention.
  • region A which is but a small, or partial, region, or patch, of the overall matrix array 22 of pixels
  • a functionalized submatrix pattern has been created, as illustrated by solid, horizontal and vertical intersecting lines, such as lines 48, 50, respectively, including rows and columns of next-adjacent pixels, which pixels are all commonly functionalized for a particular fluid-material assay.
  • lines 48, 50 intersecting lines
  • next-adjacent pixels which pixels are all commonly functionalized for a particular fluid-material assay.
  • different patches, or fragmentary areas, of next-adjacent pixels may be differently functionalized so that a single matrix array can be used differently with these kinds of patch submatrices to perform, for example, plural, different, fluid-material assays.
  • intersecting, solid, horizontal and vertical lines, such as lines 52 , 54 , respectively, and intersecting, dashed, horizontal and vertical lines, such as lines 56, 58 , respectively, illustrate two, different lower-pixel-count, submatrix functionalization patterns which fit each into the category mentioned earlier herein as a ⁇ bi-alternate" functionalization pattern which effectively creates two, large-area-distribution submatrices within the overall matrix array 22 of pixels.
  • These two pixel submatrices are distributed across the entire area of the overall matrix array, and are characterized by rows and columns of pixels which "sit" two pixel spacings away from one another.
  • Fig. 3 illustrates another lower-pixel-count, submatrix functionalization pattern wherein intersecting, light, solid, horizontal and vertical lines, such as lines 60, 62 , respectively, intersecting dashed, horizontal and vertical lines, such as lines 64 , 66, respectively, and intersecting, thickened, solid, horizontal and vertical lines, such as lines 68, 70, respectively, represent what was referred to herein earlier as a "tri-alternate" functionalization arrangement distributed over the entire matrix array 22 of pixels -- effectively dividing that array into three overlapping submatrices.
  • FIG. 4 and Fig. 5 these two figures illustrate, schematically and fragmentarily, two different kinds of pixel-bathing, light-field-creating subcomponents creatable in the practice of the invention.
  • FIG. 4 shown specifically in Fig. 4 is a fabricated, energizable, optical medium 72 which is energized/ switched directly by the operation of a control transistor (an electronic switching device) shown in block form at 74.
  • This control transistor has an operative connection to previously mentioned line system 42.
  • a sinuous arrow 76 extends from medium 72 toward prospective assay site 24ai which is hosted on sensor 24a. Arrow 76 schematically pictures the creation of a pixel-bathing, field of light in the vicinity of site 24ai .
  • an appropriately constructed optical beam device 78 having a light output port 78a, is switched on and off by means of an optical switching device 80 (an electronic switching device) which is fed light through an appropriately formed optical beam structure 82 which in turn is coupled to an off-pixel source of light.
  • Switching of optical switching device 80 is performed by a computer, such as previously mentioned computer 40, and via previously mentioned line system 42.
  • a sinuous arrow 84 represents a path of light flow to create a pixel-bathing field of light in the vicinity of prospective assay site 24ai .
  • optical media In each of the possible optical field-creating structures shown in Fig. 5 and Fig. 6, there are different specific arrangements of optical media, well-known to those skilled in the art, which may be built during practice of the invention and employed herein .
  • one such medium might have a horizontal-style configuration, and another arrangement might be characterized by a vertical- style arrangement.
  • Such arrangements are well-known and understood by those skilled in the relevant art.
  • Fig. 6 and Fig. 7 there are illustrated, schematically, two different, electronically switchable , pixel-bathing, heat-field-creating subcomponents, one of which, namely that one which is pictured in Fig. 6, may be used at the location designated 24b2 in Fig. 1 , and the other of which, namely that one which is shown in Fig. 7 , may be used at the location of an on-sensor-24a site 24d which is shown only in Fig. 7.
  • FIG. 7 As was mentioned earlier herein, entirely conventional and well-known, or recently introduced (see above-referred-to U. S. Patent No. 7, 125,451 B2 with regard to portions of the structure shown in Fig. 7) , specific processes may be employed, in the overall practice of this invention, to produce the switchable heat-field-creating subcomponents illustrated in these two figures.
  • the first-mentioned version of a heat-field-creating subcomponent is shown generally at 86 in Fig. 6.
  • This subcomponent (86) is also labeled 24b2 (in Fig. 6) in order to indicate its relationship to what has already been discussed above regarding the illustrations provided in Fig. 1 and Fig. 2.
  • the heat-field-creating subcomponent version illustrated generally at 88 in Fig. 7 is one which is shown as having been formed directly adjacent prospective assay site 24ai on a portion of assay sensor 24a, and specifically, formed directly on the beam 90a of a cantilever-type micro-deflection device 90 whose basic material body has been formed specifically utilizing the process mentioned above referred to as internal crystalline- structure processing.
  • an electrical signaling structure 92 which may take the form of any suitable electrical device that responds to bending in beam 90a to produce a related electrical output signal which may be coupled from the relevant pixel ultimately to an external computer, such as computer 40.
  • FIG. 8 illustrate various aspects of an electronically switchable, pixel-bathing, non-uniform-electrical- field-creating structure 94 which may be created within a pixel, such as within pixel 24 at the site shown at 24b3 in Fig. 1 and Fig. 2.
  • the mechanical spike structures seen in these figures have been fabricated employing the crystalline-structure-processing methodology described in the above-referred U. S. Patent No. 7, 125,451 B2.
  • the structure suggested herein for the creation of a non-uniform electrical field takes the form of a sub-array of very slender, approximately equal-height micro-spikes, such as those shown at 94a in Fig. 9 , with regard to which electrical energization, as by a computer, such as computer 40 , results in the production of an appropriate pixel-bathing, non-uniform electrical field, shown generally and very schematically in a cloud-like fashion at 96 in Fig. 9.
  • Figs . 1 OA, 1 OB and 1 OC illustrate several, different, representative micro-spike configurations and arrangements which might be used to characterize a non-uniform electrical field-creating subcomponent.
  • Such micro-spikes are simply illustrative of one of various kinds of different, electronically switchable structures which may be created within a field-creating structure in a pixel to develop, when energized, a suitable , non-uniform electrical field.
  • Fig. 1 OA illustrates modified micro-spike structures 94a regarding which distributed micro-spikes may have, either uniformly, or differentially, different heights lying within a user-selectable height range generally indicated at H .
  • Fig. 1 OB illustrates an arrangement wherein micro-spikes 94a are configured like those shown in Fig. 8 and Fig. 9, except for the fact that these Fig. 17B micro-spikes are more densely organized, as indicated by next-adjacent, interspike distance D .
  • Such an interspike distance is freely chooseable by a user, and need not be uniform throughout a full sub-array of micro-spikes.
  • What is illustrated in Fig. 1 OC is an arrangement wherein the pictured micro-spikes 94a may have several differentiating characteristics, such as differentiating heights and sharpnesses (i.e . , pointednesses) .
  • FIG. 1 1 is a modified fragmentary region drawn from the fragmentary illustration of Fig. 1.
  • This figure specifically illustrates a pixel 98, constructed as a part of practice of the present invention, and possessing two assay sensors 98a, 98b, each of which hosts but a single prospective assay site 98ai , 98b i , respectively.
  • the modification illustrated in Fig. 12 shows an arrangement wherein a pixel 100 , also constructed as a part of practice of the present invention, possesses a single sensor 100a which is structured so as to host two, different, potential assay sites 10Oa 1 and 100a2.
  • a precursor pixel-matrix structure which is formed utilizing the above-mentioned low-temperature TFT and Si technology, is provided preferably on a glass or plastic substrate, whereby, ultimately, and completely under the control of a recipient-user's selection, each pixel in that matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • a precursor pixel-matrix structure which is formed utilizing the above-mentioned low-temperature TFT and Si technology, is provided preferably on a glass or plastic substrate, whereby, ultimately, and completely under the control of a recipient-user's selection, each pixel in that matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • the invention thus takes the form of an extremely versatile and relatively low-cost matrix assay precursor structure, also referred to herein interchangeably as a microstructure . It is a precursor structure in the sense that, as has just been mentioned above , it is not yet an assay-material-specific-functionalized assay structure .
  • the structure of this invention is therefore one which is providable, as a singularity, to a user, in a special status which enables that user selectively to functionalize pixels in the structure, with great versatility, to perform one, or even plural different (as will be explained) , type(s) of fluid-material assay(s) .
  • active-matrix refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s) , operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating structure -- all formed preferably by low-temperature TFT and Si technology as mentioned above .
  • bi-alternate refers to a possible matrix condition enabled by the present invention, wherein every other pixel in each row and column of pixels may selectively become commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of the overall matrix of the invention, two differently functionalizable submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition) .
  • tri-alternate refers to a similar condition, but one wherein every third pixel in each row and column may selectively become commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of the overall matrix, three , differently functionalizable submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition) .
  • submatrices are, of course, possible, and one other type of submatrix arrangement is specifically mentioned hereinbelow.
  • a submatrix functionalization approach regarding an overall matrix made in accordance with the present invention that approach may be employed to enable either (a) several, successive same-assay-material matrix-assay uses with the same overall matrix, or (b) several successive different-assay-material submatrix-assay uses also employing the same overall matrix.
  • assay-site functionalization is in all other respects essentially conventional in practice .
  • Such functionalization is, therefore , insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay-sensor-functional processes.
  • Each prepared "precursor" pixel which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, digitally-addressable assay sensor which is designed to possess, or host, at least one ultimately to-be-functionalized fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material.
  • Each such pixel also includes, as earlier indicated, an ⁇ on-board” , digitally-addressable, assay-site-bathing (also referred to as "pixel-bathing") , electromagnetic-field-creating structure (part of a thin-film electronic switching structure) which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such an assay site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the output reading of the result of a particular assay.
  • an ⁇ on-board digitally-addressable, assay-site-bathing (also referred to as “pixel-bathing")
  • electromagnetic-field-creating structure part of a thin-film electronic switching structure
  • This field-creating structure is capable, via the inclusion therein of suitable, different, field-creating subcomponents, and in accordance with the present invention, of producing, as an ambient, pixel-bathing field environment within its respective, associated pixel, any one or more of (a) a light field, (b) a heat field, and (c) a non-uniform electrical field.
  • the invention thus offers an extremely flexibly employable , staple-like, pixelated, precursor, fluid-assay, active-matrix structure, or micro-structure, wherein the individual pixels are not initially pre-ordained to function responsively with any specific fluid-assay material, but rather are poised with a readiness to have their respective , associated assay sensors later user-functionalized to respond with specificity to such an assay material.
  • each pixel includes a least one, and may include more than one, assay sensor(s) , with each such assay sensor being ultimately functionalizable to host, or possess, at least one, but optionally and selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
  • subj ect precursor structure of this invention it is entirely possible for a user of the subj ect precursor structure of this invention to create plural, different unified areas (i.e. , unified lower-pixel-count submatrices defined by next-adjacent, side-by-side pixels) within the overall, entire matrix structure which have their respective submatrix pixels functionalized to respond to a specific type of fluid-assay material, with each such different submatrix area being capable of responding to respective , different assay materials.
  • unified areas i.e. , unified lower-pixel-count submatrices defined by next-adjacent, side-by-side pixels
  • pixels in a group included in full matrix, or in a smaller-pixel-count submatrix may be functionalized for assay use utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and/ or non-uniform electrical fields.
  • Such differentiated field-intensity functionalization can yield, following an assay, information regarding how an assay's results are affected by such "field-differentiated" pixel functionalization.
  • assay results may be observed by reading pixel output responses successively under different (changed) ambient field conditions that are then presented as "bathing" fields seriatim to information-outputting pixels.
  • time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
  • a unique, precursor (“blank-slate-style”) , pixelated active matrix, useable ultimately in a fluid-material assay, has been illustrated and described.
  • This matrix has a structure whereby, ultimately, and completely under the control of a matrix-recipient-user's selection, each pixel in that matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • the matrix structure of the invention utilizes a low-cost substrate material, such as glass or plastic, and features the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures, all formed preferably by low-temperature TFT and Si technology as discussed above .
  • the matrix of the invention has the characteristics of a "staple" in commerce -- a key factor which contributes to its special versatility with respect to how it can freely be functionalized in many ways by a user for employment in a fluid-material assay.
  • Independent digital addressability of each pixel introduces interesting opportunities (not offered by prior art structures) for preparing to conduct, and ultimately conducting, such assays in many new ways, including ways that include examining assay results on kinetic and time-based axes of information.
  • a single matrix may be employed in one-to-many fluid-material assays .
  • a novel fluid-material assay matrix structure also referred to herein as a microstructure, which takes the form of a pixelated, active-matrix, row-and-column, fluid-assay, micro-structure characterized by a selected grouping of individually electronically-digitally-addressable pixels, which pixel, and their contents, are formed preferably on a glass or plastic substrate utilizing the above-mentioned low-temperature TFT and Si technology.
  • the concepts of digital addressability and energizing expressed herein are intended to refer to computer-controlled addressability and energizing.
  • the pixels in this selected grouping which may include either an entire matrix of pixels, or one of a number of possible lower-pixel-count submatrices (later to be described herein) within an overall matrix, have been appropriately prepared on a supporting substrate, with each pixel therein possessing, in addition to appropriate, relevant, computer-accessible electronic switching structure, an included assay sensor which hosts an assay site that has been affinity-functionalized to assist in the performance of a particular kind of fluid-material-specific assay.
  • assay-site functionalization is in all other respects essentially conventional in practice .
  • Such functionalization is, therefore , insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay- sensor-functional processes.
  • Each pixel which is an active-matrix pixel as that language is employed herein, also includes, as was mentioned, a special, pixel-specific, digitally and controllably energizable and employable, assay-site-bathing (also referred to as "pixel-bathing”) electromagnetic field-creating structure which may be used, selectively and optionally, as a special assistant in the above-mentioned, "special-information-axis" reading-out of assay results, to generate a selected type of environmentally-pixel-bathing electromagnetic field, such as a light field, a heat field, and a non-uniform electrical field.
  • pixel-by-pixel assay-result output reading may also be accomplished in appropriate circumstances without any use of the field-creating structure.
  • This interesting and unique field-creating feature of the invention coupled with the invention's enablement of pixel-by-pixel, assay-result output reading, are what introduce and promote, among other things, the possibility of deriving assay-result data, including time-based and kinetic assay-reaction data, effectively along the above-suggested, special information axes not enabled by prior art devices.
  • pixels in an appropriately functionalized group of pixels may have been, before matrix delivery to a user, initially functionalized utilizing plural different intensities of functionalization-assist electromagnetic fields, such as intensity-differentiated heat and/ or non-uniform electrical fields.
  • Such differentiated field-intensity functionalization which becomes reflected in a final matrix, and which was performed by pixel-on-board electromagnetic field-creating structures, can, in an assay output-reading situation, yield information regarding how an assay's results are affected by "field-differentiated" prepared-pixel functionalization, also referred to herein as assay-site functionalization .
  • assay results may be observed by reading pixel output responses successively under different ambient field conditions that are then "presented" seriatim as spatial bathing fields to information-outputting pixels.
  • time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
  • the invention thus takes the form of an extremely versatile and relatively low-cost fluid-material assay structure , which, because of its pixel-by-pixel functionalization characteristic, may be constructed, and delivered to an assay-performing user (as will be seen from discussion text presented hereinbelow) in a variety of different pre-assay conditions .
  • a finished, user-delivered matrix structure constructed in accordance with the present invention may be delivered with all of its pixels functionalized to handle a single, specific assay.
  • such a matrix structure may be delivered to a user with different pixels functionalized differently (i.e . , submatrix functionalization) so as to enable a single matrix to be employed in the conducting of plural, different assays.
  • each pixel in that matrix is originally individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • Independent digital addressability of each pixel introduces interesting opportunities (not offered by prior art structures) for conducting fluid-material assays in many new ways, including ways that include examining assay results on kinetic and time-based axes of information.
  • a single matrix may be employed in one-to-many fluid-material assays.
  • the matrix structure of the invention preferably utilizes a low-cost substrate material, such as glass or plastic, and features the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures, all formed preferably by low-temperature TFT and Si technology as discussed above.
  • Fig. 13 to Fig. 18, inclusive and respectively these six figures illustrate the several, key, high-level steps which characterize the preferred and best mode manners of practicing the present invention to produce the precursor micro-structure, and its various unique features, set forth and discussed above. What is shown in these figures, therefore, will be presented now in the context of those key, contributed, methodologic invention steps - recalling that the specifics of these steps' individual implementations may be , and preferably are, carried out in various conventional ways, such as the earlier mentioned, or suggested, micro-structure, photolithographic (and other) patterning and fabrication practices used widely in, for example , the making of all kinds of thin-film, micro-device (e.g. , transistor device) structures.
  • micro-device e.g. , transistor device
  • the invention can be seen to be describable as being a method for producing a precursor, active-matrix, fluid-assay micro-structure including the steps of establishing (or alternatively establishing by way of utilizing low-temperature TFT and Si technology) a matrix array of non-functionalized pixels, and preparing at least one of these pixels for individual, digitally-addressed (a) functionalization, and (b) reading out, ultimately, of completed assay results.
  • the preparing step includes providing each pixel in the established array with a digitally-addressable ( 1 ) non-functionalized assay sensor, and (2) independent, electromagnetic field-creating structure disposed adjacent that pixel.
  • the invention may be seen as utilizing low-temperature TFT and Si technology to implement the providing step on and in relation to a glass or plastic substrate.
  • Fig. 13 which includes blocks, or steps, 102 (PRODUCING) , 104 (ESTABLISHING) and 106 (PREPARING) provides another kind of overview, even somewhat more specific than what was just stated immediately above, of the methodology of the present invention.
  • blocks(steps) 104 , 106 are shown to be functionally included within block(step) 102 , and interconnected therein by a sequence-indicating arrow 108.
  • the invention can be expressed verbally as a method for PRODUCING (step 102) a remotely digitally-addressable, pixelated, precursor, active-matrix, fluid-assay micro-structure , including the steps of (a) ESTABLISHING (step 104) , on a supporting substrate, an array of plural, non-assay-functionalized pixels, and then (b) PREPARING (step 106) each established pixel with electronically digitally-addressable electronic structure designed to effect, for and with respect to that pixel, and under the selection and control of a user, at least one of (a) selective, independent, fluid-assay-material-specific functionalization, and (b) assay-result output reading, utilizing, at least in part, communicative, electronic interaction between that pixel and a digital computer.
  • Fig. 14 further pictures the step of electronic-switching-structure PREPARING, i.e. , block 106. More specifically, this electronic-switching-structure PREPARING step is shown to include the companion, but not necessarily sequential, blocks, or steps, 1 10 (PROVIDING) and 1 12 (FORMING) .
  • Fig. 14 effectively describes the invention as taking the form of what is expressed in and by Fig. 13 , wherein, further, the PREPARING step, block 106, includes (a) PROVIDING (step 1 10) each pixel with at least one electronically, digitally-addressable assay sensor operatively connected to also provided electronically digitally-addressable electronic switching structure, and constructed to host at least one electronically, digitally-addressable, ultimately functionalizable assay site, and (b) FORMING (step 1 12) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure also operatively connected to the also provided electronic switching structure, and which is selectively energizable by the mentioned computer to participate in at least one of ( 1) pixel functionalization, and (2) assay-result output reading with regard to a functionalized pixel.
  • PROVIDING step 1 10
  • each pixel with at least one electronically, digitally-addressable assay sensor operatively connected to also provided electronically digitally-
  • Fig. 15 relates to Fig. 14 in somewhat, though not completely, the same manner that Fig. 14 relates to Fig. 13 , in the sense that Fig. 15 further characterizes the methodology of the invention expressed in Fig. 14 by describing something more about the included functional content of one of the blocks/ steps pictured in Fig. 14.
  • Fig. 15 further characterizes the invention by elaborating the functional content of the step of PROVIDING, i. e. , block 1 10 - indicating that the PROVIDING step includes, as will be more fully set forth below, the step of FABRICATING (block 1 14) , and additionally includes the further step of
  • PRODUCING (block 1 16) .
  • a connecting line 1 18 indicates the just-mentioned "further step" relationship between blocks 1 14, 1 16.
  • FIG. 15 illustrates that, with respect to the invention as pictured in Fig. 14, the
  • PROVIDING of each pixel with the mentioned at least one electronically digitally-addressable assay sensor includes FABRICATING that sensor within the pixel as a micro-deflection device.
  • Fig. 15 also illustrates that the step of PROVIDING further includes the step of PRODUCING, on the fabricated micro-deflection device, a remotely, electronically, digitally-addressable electrical signaling structure which is operable to generate an electrical signal related to deflection of the micro-deflection device .
  • Fig. 16, in pictured blocks/ steps 1 14, 120 illustrates that the step of FABRICATING (block 1 14) the mentioned micro-deflection device takes the form of CREATING (block 120) a cantilever structure.
  • Fig. 17 employs blocks/ steps 1 12 (FORMING) and 122 (CONSTRUCTING) , along with "produced-precursor-structure" blocks 124, 126, 128 (still to be described) , to elaborate, somewhat, the functional content of the step of FORMING within each pixel an electronically, digitally-addressable electromagnetic field-creating structure.
  • Fig. 17 describes the functional condition that the step of
  • FORMING a field-creating structure includes CONSTRUCTING, within each pixel, at least one of (a) a light-field-creating (L) subcomponent (block 124) , (b) a heat-field-creating (H) subcomponent (block 126) , and (c) a non-uniform-electrical-field-creating (E) subcomponent(block
  • Fig. 18 further characterizes the CONSTRUCTING (L) step (blocks 122 , 124) of the invention by pointing out that it can take two different forms of a step referred to as MAKING (block 130) .
  • the step of CONSTRUCTING (L) (blocks 122 , 124) of a light-field-creating subcomponent involves the MAKING either of a pixel on-board light (POB) source, block 132, or of a pixel-communicative, on-substrate, optical beam structure (OBS), block 134, adapted for optical coupling to an off-pixel light source.
  • POB pixel on-board light
  • OBS optical beam structure
  • a precursor pixel-matrix structure which is formed utilizing the above-mentioned low-temperature TFT and Si technology, is created and provided preferably on a glass or plastic substrate, whereby, ultimately, and completely under the control of a recipient-user's selection, each pixel in that created matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
  • the invention thus takes the form of a method for creating an extremely versatile and relatively low-cost assay precursor structure .
  • the precursor structure, also referred to herein interchangeably as a micro-structure, resulting from this method is a precursor structure in the sense , as has just been mentioned above, that it is not yet an assay-material-specific-functionalized assay structure.
  • the structure created by the methodology of this invention is one which is providable, as a singularity, to a user, in a special status which enables that user selectively to functionalize assay sites in its pixels with great versatility, to perform one, or even plural different (as will be explained) , type(s) of fluid-material assay(s) .
  • the methodology which is contributed to the state of the relevant sensor assay art by the present invention is a very high-level methodology.
  • it consists of a unique, high-level organization of steps which are cooperatively linked to produce a unique fluid-assay precursor structure.
  • Detailed features of the several high-level steps involved in the practice of this invention are , or may be, drawn from well-known and conventional practices aimed at producing various micro-structure devices and features, such as semiconductor matrixes, or arrays .
  • the invention does not reside in, or include, any of these feature details. Rather, it resides in the overall arrangement of steps that are capable of leading to the fabrication of the desired, end-result assay precursor micro-structure mentioned above .
  • assay-site functionalization is in all other respects essentially conventional in practice.
  • Such functionalization is, therefore, insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use , in many functionalization procedures, of conventional flow-cell assay- sensor-functional processes.
  • the subject end-result product takes the form of a micro-structure pixelated array, or matrix, of active pixels which are designed to be individually, i.e . , pixel-specifically, addressed and accessed, for at least two important purposes, by a digital computer.
  • the first of these purposes is to enable user-selectable functionalization of assay sites in pixels to become responsive to particular fluid-assay materials.
  • the second involves implementing user-selectable access to assay-site-functionalized pixels to obtain output readings of responses generated by those pixels regarding the result(s) of a performed fluid-material assay.
  • the end-result structure generally created by the methodology of this invention acts importantly as a kind of blank slate useable by a user to characterize an entire matrix array, or even simply portions of such an array, for the performance of a specific, or plural specific (different or same) , user-chosen fluid-material assay(s) .
  • active-matrix refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s) , operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating structure-- all formed preferably by low-temperature TFT and Si technology as mentioned above .
  • bi-alternate refers to a possible , user-selectable matrix condition enabled by practice of the present invention, wherein every other pixel in each row and column of pixels may selectively become commonly functionalized for one, specific type of fluid-material assay.
  • This condition effectively creates, across the entire area of an overall matrix made by practice of the invention, two differently and/ or separately functionalizable , lower-pixel-count submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition) .
  • tri-alternate refers to a similar condition, but one wherein every third pixel in each row and column may selectively become commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of an overall matrix, three, differently and/ or separately functionalizable, lower-pixel-count submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition) .
  • submatrix functionalization approach regarding an overall matrix made in accordance with the present invention
  • that approach may be employed to enable either (a) several, successive same-assay-material matrix-assay uses with the same overall matrix, or (b) several successive different-assay-material submatrix-assay uses, also employing the same overall matrix.
  • the use of a submatrix functionalization approach with respect to the precursor matrix structure produced by practice of the present invention enables a user to elect to perform selected assays at different pixel-distribution "granularities".
  • Each prepared "precursor" pixel which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, electronically, digitally-addressable assay sensor which is designed to possess, or host, at least one ultimately functionalized, electronically digitally-addressable fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material.
  • Each such pixel also includes, as earlier indicated, an "on-board”, digitally-addressable, assay-site-bathing (also referred to as “pixel-bathing”) , preferably thin-film, electromagnetic-field-creating structure which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such a site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the output reading of the result of a particular assay.
  • an "on-board”, digitally-addressable, assay-site-bathing also referred to as “pixel-bathing”
  • thin-film, electromagnetic-field-creating structure which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such a site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the output reading of the
  • This pixel-bathing, field-creating structure is capable, via the inclusion therein (by • way of practice of the present invention) of suitable, different, field-creating subcomponents, and in accordance with aspects of the present invention, of producing, as a pixel-bathing, ambient field environment within its respective, associated pixel, any one or more of (a) an ambient light field, (b) an ambient heat field, and (c) an ambient non-uniform electrical field.
  • the invention thus offers a methodology for producing an extremely flexibly employable , blank-slate, staple-like, pixelated, precursor, fluid-assay, active-matrix structure, or micro-structure, wherein the individual pixels are not initially pre-ordained to function responsively with any specific fluid-assay material, but rather are poised with a readiness to have their respective, associated assay sensors later user-functionalized to respond with specificity to such an assay material.
  • each pixel includes a least one, and may include more than one, assay sensor(s) , with each such assay sensor being ultimately functionalizable to host, or possess, at least one, but selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
  • a precursor micro-structure user to create (i.e. , functionalize) plural, different, internally unified (all internally alike) subareas (i. e. , unified lower-pixel-count submatrices defined by next-adj acent, side-by-side pixels) within an overall, entire matrix, and to functionalize such pixels to respond to one specific type of fluid-assay material, with each such different, internally unified area being functionalized to respond to respective, different assay materials.
  • pixels in a group of pixels contained in a full matrix, or in a lower-pixel-count submatrix may be functionalized utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and / or non-uniform electrical fields.
  • Such differentiated field-intensity functionalization can yield assay-result output information regarding how an assay's results are affected by "field-differentiated" pixel functionalization.
  • assay results may be observed by reading pixel output responses successively under different, pixel-bathing ambient electromagnetic field conditions that are then presented seriatim to information-outputting pixels .
  • time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
  • the precursor matrix structure made by practice of the methodology of the invention utilizes, preferably, a low-cost substrate material, such as glass or plastic, and features, also preferably, the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures, all formed preferably by TFT and Si technology as discussed above .
  • a low-cost substrate material such as glass or plastic
  • TFT and Si technology preferably, silicon on glass or plastic technology.
  • the unique matrix which is created by practice of the methodology of the present invention has the characteristics of a "staple" in commerce -- a key factor which contributes to its special, end-result versatility with respect to how it can freely be functionalized in many ways by a user for employment in a fluid-material assay.
  • a single matrix may be user-employed in "one-to-many" fluid-material assays.
  • TIRD EMBODIMENT The following will explain another embodiment of the present invention in reference to Figs 1 to 12 , and Figs 19 to 26.
  • the same reference numerals are given, and explanations thereof are omitted here.
  • micro-device e.g. , transistor-device
  • the ESTABLISHING step may be expressed in the context of utilizing low-temperature TFT and Si technology in relation to forming devices preferably on a glass or plastic substrate.
  • a selected pixel includes individually and controllably BATHING (block 206)
  • Fig. 2 1 which includes blocks, or steps, 202 (PRODUCING) , 204 (ESTABLISHING) and 2 10
  • blocks 210, 2 12 , 2 14, 216 are shown to be functionally included within block 202 , and interconnected therein by sequence-indicating arrows 2 18 , 220, 222 , 224.
  • the invention can be expressed verbally as a method for PRODUCING (block 202) a remotely digitally-addressable, pixelated, active-matrix, fluid-assay micro- structure, including the steps of (a) ESTABLISHING (block 204) , on a supporting substrate, an array of plural pixels, (b) PREPARING (block 2 10) each established pixel with digitally-addressable electronic structure designed to effect, for and with respect to that pixel, and under the control of an appropriately operatively connected digital computer, at least one of ( 1) selective, independent, fluid-assay-material-specific functionalization, and (2) assay-result output reading, (c) operatively CONNECTING (block 2 12) such a computer to the electronic structure which is associated with at least one of the established and prepared pixels, (d) employing the operatively connected computer, digital
  • Fig. 22 further pictures the step of PREPARING (block 2 10) . More specifically, this PREPARING step (block 2 10) is shown to include the companion, but not necessarily sequential, 226 (PROVIDING) and 228 (FORMING) steps. In the language of words, Fig. 22 therefore effectively describes the invention as taking the form of what is expressed in and by Fig.
  • the PREPARING step includes (a) PROVIDING (block 226) each pixel with at least one electronically, digitally-addressable assay sensor operatively connected to also provided electronically digitally-addressable electronic switching structure, and constructed to host at least one electronically, digitally-addressable, ultimately functionalizable assay site , and (b) FORMING (block 228) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure also operatively connected to the also provided electronic switching structure, and which is selectively energizable by the mentioned computer to participate in at least one of ( 1 ) pixel functionalization, and
  • Fig. 23 relates to Fig. 22 in somewhat, though not completely, the same manner that Fig. 22 relates to Fig. 2 1 , in the sense that Fig. 23 further characterizes the methodology of the invention expressed in Fig. 22 by describing something more about the included functional content of one of the blocks/ steps pictured in Fig. 22. In particular, Fig. 23 further characterizes the invention by elaborating the functional content of the step of PROVIDING,
  • the PROVIDING (block 226) step includes, as will be more fully set forth below, the step of FABRICATING (block 230) , and additionally includes the further step of PRODUCING (block 232) .
  • a connecting line 234 indicates the just-mentioned "further step" relationship between blocks 230 , 232.
  • Fig. 23 illustrates that, with respect to the invention as pictured in Fig. 22 , the PROVIDING (block 226) of each pixel with the mentioned at least one electronically digitally-addressable assay sensor includes
  • FABRICATING (block 230) that sensor within the pixel as a micro-deflection device.
  • Fig. 23 also illustrates that the step of PROVIDING (block 226) further includes the step of PRODUCING (block 232) , on the fabricated micro-deflection device, a remotely, electronically, digitally-addressable electrical signaling structure which is operable to generate an electrical signal related to deflection of the micro-deflection device .
  • Fig. 24 in pictured blocks/ steps 230 , 236 illustrates that the step of FABRICATING (block 230) the mentioned micro-deflection device takes the form of CREATING (block 236) a cantilever structure.
  • Fig. 25 employs blocks/ steps 228 (FORMING) and 238 (CONSTRUCTING) , along with "produced -structure" blocks 240, 242 , 244 (still to be described) , to elaborate, somewhat, the functional content of the step of FORMING (block 228) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure .
  • Fig. 25 employs blocks/ steps 228 (FORMING) and 238 (CONSTRUCTING) , along with "produced -structure" blocks 240, 242 , 244 (still to be described) , to elaborate, somewhat, the functional content of the step of FORMING (block 228) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure .
  • Fig. 25 employs/ steps 228 (FORMING) and 238 (CONSTRUCTING) , along with "produced -structure" blocks 240, 242 , 244 (still to be described) , to elaborate, somewhat, the functional content of the step of
  • a field-creating structure includes CONSTRUCTING (block 238) , within each pixel, at least one of (a) a light-field-creating (L) subcomponent (block 240) , (b) a heat-field-creating (H) subcomponent (block 242) , and (c) a non-uniform-electrical-field-creating (E) subcomponent(block 244) .
  • Fig. 26 further characterizes the CONSTRUCTING (L) step (blocks 238, 240) of the invention by pointing out that it can take two different forms of a step referred to as MAKING (block 246) .
  • the step of CONSTRUCTING (L) (blocks 238 , 240) of a light-field-creating subcomponent involves the MAKING (block 246) either of a pixel on-board light (POB) source (block 248) , or of a pixel-communicative, on-substrate, optical beam structure (OBS) (block 250) , adapted for optical coupling to an off-pixel light source.
  • POB pixel on-board light
  • OBS optical beam structure
  • pixel functionalization may be performed under circumstances wherein it is aided by the presence and use , in each pixel, of the included pixel-bathing electromagnetic field-creating structure which is, when so used, remotely and controllably energized under the management of an appropriate digital computer, to bathe the pixel-associated assay sensor and its possessed assay site(s) with such a field (light, heat and / or non-uniform electrical) .
  • electromagnetic field-creating structure which is, when so used, remotely and controllably energized under the management of an appropriate digital computer, to bathe the pixel-associated assay sensor and its possessed assay site(s) with such a field (light, heat and / or non-uniform electrical) .
  • this same field-creating structure has later utility, where appropriate, in relation to participating selectively in the reading-out of ultimately achieved, completed-assay results. More will be said about this invention-enabled later utility shortly.
  • Digitally addressed, pixel-by-pixel functionalization allows for the production of highly specialized and individualized fluid-material assays.
  • Such functionalization performed in the context of also employing, as an aid, the mentioned electromagnetic field-creating structure, enables a very high, selective versatility to be associated with finally functionalized pixels.
  • this same, per-pixel, digitally-addressable electromagnetic field-creating structure opens the door to permitting a number of highly specialized assay-result output reading practices.
  • the present invention utilizing the above-mentioned low-temperature TFT and "Si on glass or plastic substrate” technology, thus takes the form of a method for creating an extremely versatile and relatively low-cost digitally-addressable assay structure, also referred to herein interchangeably as a micro-structure .
  • the structure created by the methodology of this invention is one which is providable, as a singularity, to a user, in a status which enables that user to perform one, or even plural different (as will be explained) , type(s) of fluid-material assay(s) . It is also a structure which enables the useful reading out of completed assay results completely on a precision, pixel-by-pixel basis.
  • the methodology which is contributed to the state of the relevant sensor assay art by the present invention is a very high-level methodology.
  • it consists of a unique, high-level organization of steps which are cooperatively linked to produce a unique fluid-assay structure.
  • Detailed features of the several high-level steps involved in the practice of this invention are, or may be, drawn from well-known and conventional practices aimed at producing various micro-structure devices and features, such as semiconductor matrices, or arrays.
  • the invention does not reside in, or include , any of these feature details. Rather, it resides in the overall arrangement of steps that are capable of leading to the fabrication of the desired, end-result assay micro-structure mentioned above.
  • assay-site functionalization is in all other respects essentially conventional in practice .
  • Such functionalization is, therefore , insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay- sensor-functional processes.
  • the subject end-result product takes the form of a micro-structure pixelated array, or matrix, of active pixels which are designed to be individually, i.e. , pixel-specifically, addressed and accessed, for at least two important purposes, by a digital computer.
  • the first of these purposes is to enable selective functionalization of assay sites in pixels to become responsive to particular fluid-assay materials.
  • the second involves enabling user-selectable access to functionalized pixels to obtain output readings of responses generated by those pixels regarding the result(s) of a performed fluid-material assay.
  • the structure generally created by the methodology of this invention allows for selective characterization of an entire matrix array, or even simply portions of such an array, for the performance of a specific, or plural specific (different or same) , user-chosen fluid-material assay(s) .
  • active-matrix refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s) , operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating structure-- all formed preferably by low-temperature TFT and Si technology as mentioned above.
  • bi-alternate refers to a possible , selectable matrix condition enabled by practice of the present invention, wherein every other pixel in each row and column of pixels is selectively commonly functionalized for one, specific type of fluid-material assay.
  • This condition effectively creates, across the entire area of an overall matrix made by practice of the invention, two differently and/ or separately functionalized, lower-pixel-count submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition) .
  • tri-alternate refers to a similar condition, but one wherein every third pixel in each row and column is selectively commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of an overall matrix, three, differently and/ or separately functionalized, lower-pixel-count submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition) .
  • Each prepared "precursor" pixel which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, electronically, digitally-addressable assay sensor which is designed to possess, or host, at least one functionalized, electronically digitally-addressable fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material.
  • Each such pixel also includes, as earlier indicated, an "on-board” , digitally-addressable, assay-site-bathing (also referred to as “pixel-bathing”) , preferably thin-film, electromagnetic-field-creating structure which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such a site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the later output reading of the result of a particular assay.
  • This pixel-bathing, electronic, field-creating structure is capable, via the inclusion therein (by way of practice of the present invention) of suitable, different, field-creating subcomponents, and in accordance with aspects of the present invention, of producing, as a pixel-bathing, ambient field environment within its respective , associated pixel, any one or more of (a) an ambient light field, (b) an ambient heat field, and (c) an ambient non-uniform electrical field.
  • each pixel includes a least one , and may include more than one, assay sensor(s) , with each such assay sensor being ultimately functionalized to host, or possess, at least one, but selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
  • submatrices it is possible to create (i.e. , to functionalize) plural, different, internally unified (all internally alike) subareas (i. e . , unified lower-pixel-count submatrices defined by next-adj acent, side-by-side pixels) within an overall, entire matrix, and to functionalize such pixels to respond to one specific type of fluid-assay material, with each such different, internally unified area being functionalized to respond to respective, different assay materials.
  • plural, different, internally unified (all internally alike) subareas i. e . , unified lower-pixel-count submatrices defined by next-adj acent, side-by-side pixels
  • pixels in a group of pixels contained in a full matrix, or in a lower-pixel-count submatrix may be functionalized utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and/ or non-uniform electrical fields.
  • Such differentiated field-intensity functionalization can yield assay-result output information regarding how an assay's results are affected by "field-differentiated" pixel functionalization.
  • assay results may be observed by reading pixel output responses successively under different, pixel-bathing ambient electromagnetic field conditions that are then presented seriatim to information-outputting pixels.
  • time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
  • Pixel- specific, digitally-addressable, electromagnetic field-creating structures enable widely-varied, controlled pixel functionalization under different kinds of ambient field conditions, and also enable, ultimately, a rich range (time-sampling-based, and on additional, uniquely permitted information axes, such as field-intensity varying axes) of assay-result output reading possibilities, some of which have been specifically mentioned above .
  • the matrix structure made by practice of the methodology of the invention utilizes, preferably, a low-cost substrate material, such as glass or plastic, and features, also preferably, the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures , all formed preferably by TFT and Si technology as discussed above.
  • FIG. 27 Fig. 27 to Fig. 3 1 , inclusive, and recognizing that assay performance in accordance with practice of the present invention is based upon use of a suitably provided, i. e. , made-available, device like micro-structure 20 shown in Fig. 1 and Fig. 2 , these five drawing figures illustrate the basic high-level methodology of the invention which is practiceable in conjunction with such a device .
  • a device like micro-structure 20 with appropriately functionalized pixels, sensors and assay sites is provided for use, and is placed in an assay-fluid environment, such as within a conventional flow-cell.
  • a computer like computer 40, is appropriately linked to the sensors, assay sites and field-creating structures in the device's pixels via communication/ addressing path structure 36, 38 shown in Fig. 1 and Fig. 2, and the device's pixels are then appropriately exposed to assay-fluid in the assay environment.
  • the pixels are digitally addressed/ accessed to request from their respective sensors and assay sites assay-reaction output results/ information so as to obtain, collect and store if desired, and report on, that information.
  • This pixel-by-pixel digital addressing may also be accompanied very effectively by simultaneous accessing and energizing of pixel-specific field-creating subcomponents to produce one or more kind(s) of field(s) , such as light, heat and electrical potential (or electrical gradient) fields, in the vicinities of addressed sensor assay sites in order to enhance assay-result information output.
  • field(s) such as light, heat and electrical potential (or electrical gradient) fields
  • output readings may be acquired at different, computer-controlled, static, or varying, electromagnetic field conditions, such as varying field-intensity conditions, and this may also be done in a sampling fashion on a time base, thus to open opportunities for gaining multiple "axes" of assay-result output information.
  • Fig. 27 which includes three blocks 300 , 302 , 304 , illustrates one specific way of visualizing the practice of the invention.
  • the invention can be expressed as being a method of performing a fluid-material assay utilizing a device including at least one active pixel having a sensor with an assay site functionalized for selected fluid-assay material, including the steps, following providing of the mentioned device, of (a) exposing the pixel's sensor assay site to such material (block 300) , and in conjunction with such exposing, and (b) employing the active nature of the pixel
  • Fig. 29 shows, in four blocks 308, 3 10 , 3 12 , 3 14 , several other ways of visualizing the practice of the assay performance methodology of the present invention.
  • the invention can be expressed as being a method for performing a fluid-material assay utilizing a pixelated assay matrix wherein each pixel possesses an assay sensor with a functionalized assay site, and is individually and remotely digitally addressable via the presence in the pixel of an active, selectively energizable electronic switching structure which is operatively connected to the sensor and its assay site.
  • the method steps from this viewpoint include , following providing of mentioned matrix device, (a) subjecting the matrix to an environment containing assay fluid in order to effect pixel-sensor assay-site reactions (block 308) , in connection with this subjecting step, (b) remotely, digitally and individually addressing selected pixel's included electronic switching structure (block 3 10) , and (c) , by that addressing step, requesting from the sensors' assay sites in the addressed pixels pixel-specific assay-result output information (block 312) .
  • this additional block (3 14) illustrates the additional step, which is a consequence of the requesting step, of obtaining from each of the selected pixels' sensors' assay sitess a result-output reading of any reaction associated with that pixel's included assay-sensor assay site .
  • Fig. 30 in the drawings illustrates, at least partially by blocks 3 10, 316, 3 18, a further description of the invention methodology which is based upon use of an assay support device wherein each pixel further includes individually remotely and digitally accessible and energizable electromagnetic field-creating structure that is both associated with the pixel's assay sensor, and also operatively connected to the pixel's included electronic switching structure.
  • This figure describes the methodology, as expressed above in relation to Fig. 29 in an augmented fashion by stating that the addressing step (block 3 10) further includes remotely, digitally and individually accessing and energizing a selected pixel's field-creating structure
  • Fig. 31 illustrates with a block 320 that, from an additional perspective the just-described "creating" step includes the step of providing at least one of (a) a singular, stable, and (b) a staged, time-variant, electromagnetic field environment of the type generally mentioned in relation to the description of Fig. 30. It is also the case that this producing (block 320) step includes the selectable practice of providing different pixel-specific electromagnetic field environments with respect to different pixels.
  • the illustration now to be described relates to the performance of a DNA fluid-material assay utilizing a matrix constructed in accordance with the above-described features of micro- structure 20 , and with the pixels in this micro-structure more specifically constructed in accordance with a sensor structure of the cantilever style which is illustrated in Fig. 35 in the drawings.
  • a DNA assay is performed utilizing a provided, pixelated matrix including appropriately functionalized sensors possessing predetermined (and not necessarily all the same) oligonucleotide probes.
  • This matrix is placed in a suitable fluid-assay environment, such as within a conventional flow-cell, and fluid-assay material is introduced into that environment.
  • a computer which is suitably connected operatively to the matrix's active pixels is employed, as desired, to request assay-result output information on a pixel-by-pixel basis, and also to access and energize the associated, pixel-specific heat-field-creating structures on a time-stable or time-varying basis to add interesting and highly informative output information.
  • a major issue relating to conventional DNA-assay arrays is so-called background signal associated with non-specific binding of labeled targets.
  • Such binding can be caused by cross-hybridization of targets with similar heterologous probes, and by random non-specific attachment of targets to probes distributed over a matrix array surface.
  • Cross-hybridization to heterologous probes depends on hybridization temperature, and can be decreased by precise temperature adjustment in the vicinity of probes.
  • non-specific binding differs from ' specific target-probe hybridization in terms of temperature dependence, and these two processes can be clearly distinguished by utilizing the "additional information axis" capability of the present invention, thereby obtaining a temperature-to-binding dependence category of output information.
  • a detected binding signal that does not match a profile for the specific, intended interaction can be considered to be a false positive signal.
  • the ability, thus, to perform hybridization of a target DNA or RNA molecule with multiple identical probes at different temperatures allows one to characterize the temperature dependence of target hybridization.
  • This dependence can be used as a fingerprint approach for specific target-probe interactions, and it can be used to discriminate false positive signals on a matrix array.
  • SNP Single Nucleotide Polymorphism
  • DNA assay applications in basic research and clinical diagnostics The ability to distinguish the so-called wild-type DNA target molecule from one that has a single sequence mismatch is based on different target-to-probe binding behaviors at different temperatures. For example,
  • Fig. 32 shows the typical expected temperature dependence of target-to-probe binding for a wild-type DNA (Owt) , and for three, corresponding mismatches OAt, OAc, and OAg.
  • Fig. 33 which illustrates this, shows representative temperature-to-binding-dependence curves, or plots, that would be obtained typically by using an array of numerous oligonucleotide assay probes for such a set of targets where different probes in this array are designed for, and are hybridized at, different temperatures.
  • Temperature variation in this setting will typically be performed independently for groups of assay sites (probes) that have been commonly functionalized to possess replicates of the same probe.
  • Fig. 33 indicates that the measurement (and plotting) of temperature-to-binding dependence will permit discrimination between the wild type and mismatching sequences as well as among different mismatches.
  • Assay-site-specific sets of heating elements will contribute to a way to perform hybridizations at different temperatures for individual probes within one pixelated matrix array, and will result in accommodating the obtaining of temperature-to-binding profiles, like those pictured in Fig. 33 , in a single test assay.
  • Fig. 34A shows a typical, expected hybridization signal for two different target and probe pairs at a constant temperature.
  • Saturation of the signal corresponds to the stage where hybridization equilibrium is achieved. If the two, pictured target-probe pairs I and II have a closely similar sequence (for example, in the case of an SNP assay) , the plots obtained for pairs I and II are difficult to distinguish. If, however, hybridization is performed at time-varying temperatures (Fig. 34B) , the resultant signal-to-time dependence plots have more complicated and perceivably different patterns. Such temperature variations
  • target-to-probe hybridization will cause an increase in a detected binding signal.
  • hybridization temperature exceeds the melting point for the subject target-probe pair, hybrids start to denature, causing a corresponding decrease in signal (see generally the right-side portion of Fig. 33) .
  • real-time detection of hybridization signals at time-varying temperatures can provide unique and readily distinguishable individual characteristics for each target-probe pair.
  • the upper "turn points" of plots I and II in Fig. 34B can be used to distinguish highly similar target sequences .
  • Temperature time varying can also be performed independently for several sensing elements (assay sites) that contain (have been functionalized to contain) replicates of the same probe.
  • DNA assay they also illustrate that characteristic of the present invention which enables the obtaining of assay-result output information on a time-based axis, as by sampling on such an axis.
  • a relevant cantilever "transducer signal" is associated with detection of a cantilever deflection that is caused by a surface-tension change due to bio-interactions occurring on the cantilever surface at the location of a functionalized assay site.
  • the ability, offered during practice of the present invention, to vary, over time, the temperature in the cantilever vicinity allows for generation of a changing cantilever deflection.
  • a "temperature oscillation” results in a related, basic oscillation of cantilever response (see the darker, upper solid line in Fig.
  • the present invention may be described as a method of performing a fluid-material assay employing an appropriately provided (i.e . , made available) computer-accessible device (note the discussion above) -- preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable assay site functionalized for selected fluid-assay material, with the key steps of this method including, following, of course, providing such a device, exposing the pixel's sensor assay site to such material, and in conjunction with such exposing, and employing the computer-accessible, active nature of the provided device's pixel, remotely and digitally requesting from the pixel's sensor assay site an assay-result output report.
  • an appropriately provided (i.e . , made available) computer-accessible device note the discussion above) -- preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable
  • the basic methodology further includes, in relation to the mentioned employing step, creating, relative to the sensor's assay site in the at least one pixel, a predetermined, pixel-specific electromagnetic field environment.
  • the creation of such an environment is enabled by the type of matrix structure of this invention, and is specifically enabled by the presence in the described matrix pixels of one or several digitally accessible and energizable electromagnetic field-creating structure(s) .
  • the embodiments and concrete examples of implementation discussed in the foregoing detailed explanation serve solely to illustrate the technical details of the present invention, which should not be narrowly interpreted within the limits of such embodiments and concrete examples, but rather may be applied in many variations within the spirit of the present invention, provided such variations do not exceed the scope of the patent claims set forth below.

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Abstract

A pixel-by-pixel, digitally-addressable, pixelated, precursor, fluid-assay, active-matrix micro-structure including plural pixels formed preferably on a glass or plastic substrate, wherein each pixel, formed utilizing low-temperature TFT and Si technology, includes (a) at least one non-functionalized, digitally-addressable assay sensor, and (b), disposed operatively adjacent this sensor, digitally-addressable and energizable electromagnetic field-creating structure which is selectively energizable to create, in the vicinity of the at least one assay sensor, an ambient electromagnetic field environment which is structured to assist in functionalizing, as a possession on said at least one assay sensor, at least one digitally-addressable assay site which will display an affinity for a selected fluid-assay material.

Description

DESCRIPTION
MICRO-PIXELATED FLUID-ASSAY STRUCTURE, MICRO-PIXELATED FLUID-ASSAY PRECURSOR STRUCTURE,
AND MAKING METHOD AND PERFORMING METHOD THEREOF
TECHNICAL FIELD
This invention relates to a pixelated, fluid-assay, precursor structure, and a pixelated, fluid-assay structure, and also relates to making methods of such a precursor micro-structure and a micro-structure, and a performance of fluid-material assay.
BACKGROUND ART This invention concerns a pixelated, thin-film-based, fluid-assay, active-matrix structure, and more particularly to a row-and-column micro-structure of active, individually digitally-addressable pixels which have been prepared on a supporting substrate as "blank slates" for later, selective, assay-specific, assay-site functionalization, also referred to interchangeably as pixel functionalization, to enable the performance of at least one kind of a fluid-material assay.
This invention also concerns a method for producing a pixelated, thin-film-based, fluid-assay, precursor, active-matrix structure, and more particularly to a method for producing a precursor row-and-column micro-structure of active, remotely individually digitally-addressable pixels which have been prepared on a supporting substrate as "blank slates" (shortly to be described) for later, selective, assay-specific, assay-site functionalization to enable the performance of at least one kind of a fluid-material assay.
This invention also concerns the field of fluid-material assays, and especially to a significantly improved assay-response , thin-film-based pixel matrix which offers a very high degree of controlled, assay-response, pixel-specific sensitivity with respect to which an assay response (a) can be output-read on a precision, pixel-by-pixel basis, and (b) can additionally be examined along uniquely accessible, special, plural and freely selectable, independent-variable
"information-gathering axes" , such as a time-sampling axis, and an electromagnetic-field-variable (light, heat, non-uniform electrical) axis.
This invention also concerns a method for producing a pixelated, thin-film-based, fluid-assay, active-matrix structure . More particularly, it pertains to a method for producing a row-and-column micro-structure array of active, remotely individually digitally-addressable pixels which have been prepared on a supporting substrate, each with (a) an included assay sensor (at least one) possessing an assay site (at least one) , and (b) an also included digitally-addressable, electromagnetic field-creating structure. This field-creating structure is energizable to bathe the associated pixel with an ambient electromagnetic field which is one or more of a field of light, a field of heat, and a non-uniform electrical field.
On a pixel-by-pixel basis, in accordance with preferred and best mode practice of the invention, and utilizing digital-computer-implemented, pixel-specific digital addressing, the pixels' respective assay sites are functionalized to possess respective assay-material-specificity so as each to have a defined, specific affinity for at least one kind of a fluid-assay material.
This invention also concerns the field of fluid-material assays. More particularly, it relates to the performance of such an assay in the specific context of employing a significantly improved type of thin-film-based, active-pixel, pixelated assay-response matrix for "Micro-Pixelated Fluid-Assay Structure".
DISCLOSURE OF INVENTION
According to one aspect, the invention preferably takes the form of a relatively inexpensive , consumer-level-affordable, thin-film-based assay structure which features a low-cost substrate that will readily accommodate low-cost, and preferably "low-temperature-condition" , fabrication thereon of substrate- supported matrix-pixel "components", and a method of creating such a precursor assay structure . "Low temperature" is defined herein as a being a characteristic of processing that can be done on substrate material having a transition temperature (Tg) which is less than about 850°C , i. e . , less than a temperature which, if maintained during sustained material processing, would cause the subject material to lose dimensional stability. Accordingly, while the matrix-pixel technology of this invention, if so desired, can be implemented on more costly supporting silicon substrates, the preferred supporting substrate material is one made of lower-expense glass or plastic materials. The terms "glass" and "plastic" employed herein to describe a preferred substrate material should be understood to be referring also to other suitable "low-temperature materials Such substrate materials, while importantly contributing on one level to relatively low, overall, end-product cost, also allow specially for the compatible employment, with respect to the fabrication of supported pixel structure, of processes and methods that are based on amorphous, micro-crystal and polysilicon thin-film-transistor (TFT) technology. In particular, these substrate materials uniquely accommodate the use of the just-mentioned TFT technology in such a way that electrical, mechanical and electromagnetic field-creating devices - devices that are included variously in the structure of the invention -- can be fabricated simultaneously in a process flow which is consistent with the temperature tolerance of such substrate materials.
Regarding the preference herein for the use of low-temperature TFT technology, and briefly describing aspects of that technology, low-temperature TFT devices are formed through deposition processes that deposit silicon-based (or other-material-based, as mentioned below herein, and as referred to at certain points within this text with the expression "etc.") thin film semiconductor material
(which, for certain applications, may, of course, later be laser crystallized) . This is quite different from classic silicon CMOS device technology that utilizes a single-crystal silicon wafer bulk material as its semiconductor material. While the resulting TFT devices may not have the switching speed and drive capability of transistors formed on single-crystal substrates, TFT transistors can be fabricated cheaply with a relatively few number of process steps. Further, thin-film deposition processes permit TFT devices to be formed on alternate substrate materials, such as transparent glass substrates, for use , as an example, in liquid crystal displays.
In this context, it will be understood that TFT device fabrication may variously involve the use typically of amorphous Si (a-Si) , of micro-crystalline Si, and or of polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si. Such processing is described in U . S . Patent No . 7, 125 ,451 B2 , the contents of which patent are hereby incorporated herein by reference . For the sake simply of convenience of expression regarding the present invention, and in order to emphasize the "low-temperature" formation possibility which is associated with the invention in its preferred form, all aspects of assay-matrix pixel fabrication and resulting structure are referred to herein in the context and language of
"low-temperature silicon on glass or plastic" construction, and also in the context and language of "low-temperature TFT and Si technology" .
According to another aspect, the invention preferably takes the form of a method for creating a relatively inexpensive, consumer-level-affordable, thin-film-based, assay structure which features a low-cost substrate that will readily accommodate low-cost, and preferably
"low-temperature-condition" , fabrication thereon of substrate- supported matrix-pixel "components" . "Low temperature" is defined herein as a being a characteristic of processing that can be done on substrate material having a transition temperature (Tg) which is less than about 850°C, i.e. , less than a temperature which, if maintained during sustained material processing, would cause the subject material to lose dimensional stability. Accordingly, while the matrix-pixel technology which is involved with practice of the methodology of this invention, if so desired, can be implemented on more costly supporting silicon substrates, the preferred supporting substrate material employed in the practice of the invention is one made of lower-expense glass or plastic materials. The terms "glass" and "plastic" employed herein to describe a preferred substrate material should be understood to be referring also to other suitable "low-temperature materials. Such substrate materials, while importantly contributing on one level to relatively low, overall, end-product cost, also allow specially for the compatible employment, with respect to the fabrication of supported pixel structure, of processes and methods that are based on amorphous, micro-crystal and polysilicon thin-film-transistor
(TFT) technology. In particular, these substrate materials uniquely accommodate the use of the just-mentioned, low-temperature TFT technology in such a way that electrical, mechanical and electromagnetic field-creating devices - devices that are included variously in the structure produced by the invention -- can be fabricated simultaneously in a process flow which is consistent with the temperature tolerance of such substrate materials.
Regarding the preference herein for the use of low-temperature TFT technology, and briefly describing aspects of that technology, low-temperature TFT devices are formed through deposition processes that deposit silicon-based (or other-material-based, as mentioned below herein, and as referred to at certain points within this text with the expression "etc.") thin film semiconductor material
(which, for certain applications, may, of course, later be laser crystallized) . This is quite different from classic silicon CMOS device technology that utilizes a single-crystal silicon wafer bulk material as its semiconductor material. While the resulting TFT devices may not have the switching speed and drive capability of transistors formed on single-crystal substrates, TFT transistors can be fabricated cheaply with a relatively few number of process steps. Further, thin-film deposition processes permit TFT devices to be formed on alternate substrate materials, such as transparent glass substrates, for use, as an example, in liquid crystal displays. In this context, it will be understood that low-temperature TFT device fabrication may variously involve the use typically of amorphous Si (a-Si) , of micro-crystalline Si, and or of polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si. Such processing is described in U . S. Patent No. 7, 125 ,451 B2 , the contents of which patent are hereby incorporated herein by reference. The active-pixel matrix, which is a digitally accessible and controllable structure linkable to a suitable digital computer, offers a very high degree of controlled, assay-response, pixel-specific sensitivity with respect to which an assay response (a) can be output-read on a precision, pixel-by-pixel basis, and (b) can additionally be examined along uniquely accessible, special, plural and freely selectable, independent-variable "information-gathering axes", such as a time-based axis, and an electromagnetic-field-variable (light, heat, non-uniform electrical) axis.
The matrix structure with its included electronically active pixels, which structure is preferably employed in the assay-performance practice of the present invention, is formed conveniently on a low-temperature substrate material, such as glass, and may involve, in its underlying construction, low-temperature, internal crystalline-structural processing of a material, such as amorphous silicon, to create some of its pixel-borne structural features. Such crystalline-structural processing is described in U . S. Patent No. 7, 125 ,45 1 B2 , the disclosure content of which patent is also hereby incorporated herein by reference.
More will be stated below herein regarding the interesting features of this representative matrix structure which make it so conveniently useable in the practice of the present invention. So as to describe fully the important practice aspects of the present method invention, those practice aspects are illustrated and discussed herein in relation to a specific form of pixelated matrix device of this invention. It should be understood, and it will become apparent, that other device forms may be employed, so long as these other forms include and display certain important structural and behavioral features principally focused on the possession of what are referred to herein as individually, digitally computer addressable active pixels, or the like.
In general terms, the present invention may be described as a method of performing a fluid-material assay employing an appropriately provided (i. e . , made available) computer-accessible device (note the discussion above) -- preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable assay site functionalized for selected fluid-assay material, with the key steps of this method including, following, of course, providing such a device, exposing the pixel's sensor assay site to such material, and in conjunction with such exposing, and employing the computer-accessible, active nature of the provided device's pixel, remotely and digitally requesting from the pixel's sensor assay site an assay-result output report. The basic methodology further includes, in relation to the mentioned employing step, creating, relative to the sensor's assay site in the at least one pixel, a predetermined, pixel-specific electromagnetic field environment. The creation of such an environment is enabled by the type of matrix structure of this invention, and is specifically enabled by the presence in the described matrix pixels of one or several digitally accessible and energizable electromagnetic field-creating structure(s) .
The various features and advantages of the present invention, including those generally set forth above, will become more fully apparent as the description of the invention which now follows below in detail is read in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF DRAWINGS
Fig. 1 is a simplified, fragmentary, block/ schematic view of a portion of a digitally-addressable, pixelated, fluid-assay, active-matrix micro-structure formed in accordance with a preferred and best mode embodiment of the present invention. Fig. 2 is similar to Fig. 1 , except that it provides a slightly more detailed view of the structure shown in Fig. 1 .
Fig. 3, which is prepared on a somewhat larger scale than those scales employed in Fig. 1 and Fig. 2 , illustrates, schematically, different, single, overall, matrix-organizational ways in which precursor fluid-assay pixels in the matrix micro-structure of this invention may be organized, user-selectively, into different functionalized arrangements for different fluid-assays that are ultimately to be performed.
Fig. 4 is a fragmentary, block/ schematic diagram illustrating one form of an electromagnetic field-creating structure prepared in accordance with practice of the present invention, and specifically such a structure which is intended to create an ambient, electromagnetic, pixel-bathing field environment characterized by light. Fig. 5 is similar to Fig. 4, except that it illustrates another field-of-light-environment-creating structure.
Fig. 6 provides a fragmentary, schematic illustration of one form of a heat-field-creating structure .
Fig. 7 illustrates fragmentarily another form of a heat-field-creating structure which has been prepared on the body of a mechanical cantilever beam which also carries an electrical signaling structure that responds to beam deflection to produce a related electrical output signal.
Fig. 8 is an isometric view of a pixel-bathing, non-uniform electrical-field-creating structure prepared through a recently developed process, touched upon later in this specification, involving internal crystalline-structure processing of substrate material.
Fig. 9 provides a simplified side elevation of the structure presented in Fig. 8 , schematically picturing, also, a pixel-bathing, non-uniform electrical field.
Figs. 1 OA, 1 OB and 1 OC illustrate, in greatly simplified forms, three different kinds of three-dimensional spike features which may be created in relation to what is shown generally in Fig. 8 and Fig. 9 for the production of a non-uniform electrical field.
Fig 1 1 provides a fragmentary view, somewhat like that presented in Fig. 1 , but here showing a pixel which has been created in accordance with practice of the present invention to include two (plural) assay sensors, each of which is designed to receive and host a single, potential fluid-material assay site.
Fig. 12 is somewhat similar to Fig. 1 1 , except that this figure shows a pixel which has been prepared in accordance with practice of the present invention to include a single fluid-assay sensor which possesses, or hosts, two (plural) potential fluid-material assay sites.
Fig. 13 to Fig. 18 provide block/ schematic diagrams illustrating the various methodological steps which characterize the preferred and best mode manner of practicing the present invention.
Fig. 19 to Fig. 26, inclusive, provide block/ schematic diagrams illustrating the various methodological steps which characterize the preferred and best mode manner of practicing the present invention. Fig. 27 to Fig. 31 , inclusive, provide block-schematic diagrams that illustrate different ways of viewing the methodologic practice steps of the present invention.
Fig. 32 to Fig. 36, inclusive, help to describe various aspects of the above-mentioned, illustrative DNA fluid assay, with respect to which a controlled heat field may be employed, and also time sampling may be used, to furnish different axes of assay-result output information obtainable from practice of the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION [FIRST EMBODIMENT]
Turning attention now to the drawings with a view toward understanding, first of all, the nature of the end-result precursor product which results from implementation of the preferred and best mode manner of practicing the methodology of the present invention, and beginning with Fig. 1 and Fig. 2 , indicated generally at 20 is a fragmentary portion of a precursor, digitally-addressable, pixelated, fluid-assay, active-matrix micro-structure .
Micro-structure 20 takes the form herein of a column-and-row array 22 of plural, individually externally addressable pixels, such as those shown at 24 , 26, 28 , 30 , 32 , formed, as will shortly be described, on an appropriate supporting, conventional-material, preferably glass or plastic, substrate 34. For the purpose of illustration herein, substrate 34 will be considered to be a glass substrate.
As was mentioned earlier herein, the detailed and specific, as distinguished from the high-level, low-cost and low-temperature methodologies and practices which are, or may be, utilized to create the overall precursor structure illustrated in Fig. 1 and Fig. 2 are entirely conventional in nature, are well understood by those generally skilled in the relevant art, and thus may easily be practiced in well-known manners to produce the various structural aspects of micro-structure 20. For example, conventional Si-based, thin-film TFT patterning practices, such as well-known photolithographic practices, may be employed in ways that are familiar to those generally skilled in the art. Additionally, and for certain structures present in micro-structure 20, an internal crystalline-structure processing approach may be employed to create certain desired mechanical characteristics, such as the bending characteristics of a cantilever beam like that pictured in Fig. 1 , or the configurations of a collection of material spikes, like that collection which appears in Fig. 8 to Fig. 1 OC, inclusive . Such internal crystalline-structure processing methodology is fully described in U . S . Patent No . 7, 125 ,45 1 B2 , and accordingly, the disclosure content of that patent is hereby incorporated herein by reference in order to provide background information respecting such processing methodology.
In the practice of the present invention, various non-critical dimensions may be chosen, for example, to define the overall lateral size of a precursor micro-structure, such as micro-structure 20. Also, the number of pixels organized into the relevant, overall row-and-column matrix may readily be chosen by one practicing the present invention. As an illustration, a precursor micro-structure, such as micro-structure 20 , might have lateral dimensions lying in a range of about 0.4 x 0.4-inches to about 2 x 2-inches, and might include an equal row-and-column array of pixels including a total pixel count lying in a range of about 100 to about 10 ,000. These size and pixel-count considerations are freely choosable by a practicer of the present invention.
Continuing with a description of what is shown in Fig. 1 and Fig. 2 , a bracket 36 and a double-headed, broad arrow 38 (see Fig. 1 ) represent an appropriate communication/ addressing connection, or path, between pixels in micro-structure 20 and a suitable digital computer, such as the computer shown in block form in Fig. 1 at 40. Such a path exists and is employed under circumstances where a precursor micro-structure, such as micro-structure 20 , is being (a) functionalized, or (b) "read" after the performance of a fluid-material assay. This inclusion of computer 40 in Fig. 1 has been done to help illustrate and describe the completed precursor-micro-structure utility of the present invention.
Regarding the illustrated operative presence of a digital computer, such as computer 40, it should be understood that such a computer, while "remote and external" with respect to the internal structures of the pixels, per se, might actually be formed directly on-board substrate 34 , or might be external to this substrate . In this context, it should be clearly understood that computer presence, location and/ or formation are not any part of the present invention .
In the particular preferred and best mode embodiment of precursor micro- structure 20 which is illustrated in Fig. 1 and Fig. 2 , which embodiment is fabricated in accordance with preferred and best mode practice of the present invention, each of the mentioned precursor pixels is essentially identical to each other pixel, although, as will later be explained herein, this is not a necessary requirement of the present invention. This "not-necessary" statement regarding the characteristics of the present invention is based upon a clear understanding that there are various end-result fluid-assay applications with respect to which appropriately differentiated precursor pixels might be fabricated in a single, precursor micro-structure array. Some of these differentiated-pixel concepts, and their fabrications, will be discussed and become more fully apparent later herein. In general terms, and using pixel 24 as an illustration to explain the basic construction of each of the precursor pixels shown in array 22 , included in pixel 24 are several, fully integrated, pixel-specific components, or substructures. These include, as part of more broadly inclusive pixel-specific electronic structure , ( 1 ) thin-film, digitally-addressable electronic switching structure, (2) a non-functionalized, precursor, individually remotely digitally-addressable and accessible assay sensor 24a which hosts a prospective, functionalizable assay site 24a1 ? and (3) what is referred to herein as a pixel-bathing, ambient environmental, electromagnetic-field-creating structure 24b. Field-creating structure 24b, which is also remotely, or externally, individually digitally-addressable and accessible, is constructed to create, when energized, any one or more of three different kinds of assay-site-bathing, pixel-bathing, ambient, environmental electromagnetic fields in the vicinity of sensor 24a, including a light field, a heat field, and a non-uniform electrical field. While structure 24b, as was just mentioned, may be constructed to create one or more of these three different kinds of fields, in the micro-structure pictured in Fig. 1 and Fig. 2, field-creating structure 24b has been designed with three field-creating subcomponents 24b 1 } 24b2 and 24b3. Any one or more of these subcomponents may be energized to create, within pixel 24 , an associated pixel-bathing, ambient electromagnetic field condition. Subcomponent 24bi is capable of creating a pixel-bathing light field, subcomponent 24b2 a pixel-bathing heat field, and subcomponent 24b3 a pixel-bathing non-uniform electrical field. More will be said about these three different kinds of pixel-bathing, field-creating subcomponents shortly.
The use of a bathing electromagnetic field of an appropriate selected character during pixel functionalization, understood by those skilled in the art, and typically used with a functionalizing flow-cell process under way, operates to create, within a pixel and adjacent an assay site, an ambient environmental condition wherein relevant chemical, biochemical, etc. reactions regarding functionalization flow material can take place , at least at the prepared, sensor-possessed assay site, or sites, to ensure proper functionalization at that site. A "prepared assay site" might typically, i. e. , conventionally, be defined by a sensor borne area of plated gold.
Given the active-matrix nature of end-result precursor micro-structure 20, prepared as a consequence of practice of the present invention, it should be understood at this point that each precursor pixel is appropriately prepared with one or more conventional electronic switching device(s) (part of the mentioned electronic switching structure) relevant to accessing and addressing its included sensor and assay site, and to energizing its field-creating structure . Illustrations of such devices are given later herein.
Looking for a moment specifically at Fig. 2 , indicated generally at 42 , 44 are two different communication line systems which are suitably created, and operatively connected to the field-creating structures in the illustrated pixels, and to the assay sensors and assay sites shown in these pixels. The upper, fragmented ends of line systems 42 , 44 in Fig. 2 are embraced by a bracket marked with the two reference numerals 36, 38, which bracket represents the previously mentioned "path" of operative connection shown to exist in Fig. 1 between micro-structure 20 and computer 40. Line system 42 is utilized by such a computer to energize pixel-bathing, field-creating subcomponents during a functionalization procedure, and also to energize these same field-creating subcomponents, where appropriate, during reading-out of the results of a performed assay. Line system 44, on a pixel-by-pixel basis, directly couples to computer 40 output responses derived from ultimately functionalized assay sites.
Having thus now described generally the arrangement and makeup of a preferred precursor micro-structure fabricated in accordance with practice of the present invention, and having done this in the context of how that structure is illustrated in Fig. 1 and Fig. 2 , we now shift attention to Fig. 3 in the drawings. Fig. 3 illustrates several different ways in which ultimately functionalized pixels (i. e . , non-precursor pixels) , such as fully functionalized versions of the pixels in array 22 , may, as enabled by the methodology of the invention, be organized and even differentiated in the hands of a user who is provided with a resulting, fully-rendered (i.e . , functionalized) matrix. To begin with, the obvious, large dots, which appear throughout in a row-and-column arrangement in Fig. 3, represent the locations of full-matrix, next-adjacent pixels constructed during practice of this invention. One way of visualizing utilization of the full-matrix precursor structure, as represented by the full array of "dots" in Fig. 3, is to recognize that every pixel thus represented by one of the mentioned dots may be commonly functionalized to respond to a single, specific fluid-assay material.
By way of contrast, marked regions A, B , C in Fig. 3 illustrate three other, representative, possible pixel functionalization patterns (specifically lower-pixel-count, submatrix patterns) that are accommodated by the utility of the present invention.
In region A, which is but a small, or partial, region, or patch, of the overall matrix array 22 of pixels, a functionalized submatrix pattern has been created, as illustrated by solid, horizontal and vertical intersecting lines, such as lines 48, 50, respectively, including rows and columns of next-adjacent pixels, which pixels are all commonly functionalized for a particular fluid-material assay. With this kind of an arrangement, different patches, or fragmentary areas, of next-adjacent pixels may be differently functionalized so that a single matrix array can be used differently with these kinds of patch submatrices to perform, for example, plural, different, fluid-material assays.
In region B, intersecting, solid, horizontal and vertical lines, such as lines 52 , 54 , respectively, and intersecting, dashed, horizontal and vertical lines, such as lines 56, 58 , respectively, illustrate two, different lower-pixel-count, submatrix functionalization patterns which fit each into the category mentioned earlier herein as a βbi-alternate" functionalization pattern which effectively creates two, large-area-distribution submatrices within the overall matrix array 22 of pixels. These two pixel submatrices are distributed across the entire area of the overall matrix array, and are characterized by rows and columns of pixels which "sit" two pixel spacings away from one another.
Fig. 3 illustrates another lower-pixel-count, submatrix functionalization pattern wherein intersecting, light, solid, horizontal and vertical lines, such as lines 60, 62 , respectively, intersecting dashed, horizontal and vertical lines, such as lines 64 , 66, respectively, and intersecting, thickened, solid, horizontal and vertical lines, such as lines 68, 70, respectively, represent what was referred to herein earlier as a "tri-alternate" functionalization arrangement distributed over the entire matrix array 22 of pixels -- effectively dividing that array into three overlapping submatrices.
Those skilled in the art, looking at the illustrative, suggested functionalization patterns illustrated in Fig. 3, will understand how these, and perhaps other, functionalization patterns interestingly tap the utility of the precursor structure prepared by the methodology of the present invention.
Turning attention now to Fig. 4 and Fig. 5 , these two figures illustrate, schematically and fragmentarily, two different kinds of pixel-bathing, light-field-creating subcomponents creatable in the practice of the invention.
These illustrated subcomponents, with respect to what has been shown and discussed earlier herein regarding Fig. 1 and Fig. 2 , might sit at the field-creating subcomponent location which is labeled 24b], in Fig. 1 and Fig. 2. Fig. 4 and Fig. 5, in relation to the appearances of things in Fig. 1 and Fig. 2 , have been drawn somewhat differently for illustration purposes.
Thus, shown specifically in Fig. 4 is a fabricated, energizable, optical medium 72 which is energized/ switched directly by the operation of a control transistor (an electronic switching device) shown in block form at 74. This control transistor has an operative connection to previously mentioned line system 42. A sinuous arrow 76 extends from medium 72 toward prospective assay site 24ai which is hosted on sensor 24a. Arrow 76 schematically pictures the creation of a pixel-bathing, field of light in the vicinity of site 24ai .
In Fig. 5 , an appropriately constructed optical beam device 78, having a light output port 78a, is switched on and off by means of an optical switching device 80 (an electronic switching device) which is fed light through an appropriately formed optical beam structure 82 which in turn is coupled to an off-pixel source of light. Switching of optical switching device 80 is performed by a computer, such as previously mentioned computer 40, and via previously mentioned line system 42. A sinuous arrow 84 represents a path of light flow to create a pixel-bathing field of light in the vicinity of prospective assay site 24ai .
In each of the possible optical field-creating structures shown in Fig. 5 and Fig. 6, there are different specific arrangements of optical media, well-known to those skilled in the art, which may be built during practice of the invention and employed herein . For example , one such medium might have a horizontal-style configuration, and another arrangement might be characterized by a vertical- style arrangement. Such arrangements are well-known and understood by those skilled in the relevant art.
Directing attention now to Fig. 6 and Fig. 7 , here there are illustrated, schematically, two different, electronically switchable , pixel-bathing, heat-field-creating subcomponents, one of which, namely that one which is pictured in Fig. 6, may be used at the location designated 24b2 in Fig. 1 , and the other of which, namely that one which is shown in Fig. 7 , may be used at the location of an on-sensor-24a site 24d which is shown only in Fig. 7. As was mentioned earlier herein, entirely conventional and well-known, or recently introduced (see above-referred-to U. S. Patent No. 7, 125,451 B2 with regard to portions of the structure shown in Fig. 7) , specific processes may be employed, in the overall practice of this invention, to produce the switchable heat-field-creating subcomponents illustrated in these two figures.
The first-mentioned version of a heat-field-creating subcomponent is shown generally at 86 in Fig. 6. This subcomponent (86) is also labeled 24b2 (in Fig. 6) in order to indicate its relationship to what has already been discussed above regarding the illustrations provided in Fig. 1 and Fig. 2.
From a brief look at the schematic illustration presented in
Fig. 6, those generally skilled in the relevant art will easily recognize how to fabricate an appropriate, similar heat-field-creating organization. Accordingly, and because of the fact that many different, particular heat-field-creating arrangements may be employed, no specific details for such an arrangement are described or illustrated herein.
The heat-field-creating subcomponent version illustrated generally at 88 in Fig. 7 is one which is shown as having been formed directly adjacent prospective assay site 24ai on a portion of assay sensor 24a, and specifically, formed directly on the beam 90a of a cantilever-type micro-deflection device 90 whose basic material body has been formed specifically utilizing the process mentioned above referred to as internal crystalline- structure processing.
Also formed on beam 90a is an electrical signaling structure 92 which may take the form of any suitable electrical device that responds to bending in beam 90a to produce a related electrical output signal which may be coupled from the relevant pixel ultimately to an external computer, such as computer 40.
Directing attention now to Fig. 8 to Fig. 1 OC, inclusive , these figures illustrate various aspects of an electronically switchable, pixel-bathing, non-uniform-electrical- field-creating structure 94 which may be created within a pixel, such as within pixel 24 at the site shown at 24b3 in Fig. 1 and Fig. 2. The mechanical spike structures seen in these figures have been fabricated employing the crystalline-structure-processing methodology described in the above-referred U. S. Patent No. 7, 125,451 B2.
As can be seen in Fig. 8 and Fig. 9 , the structure suggested herein for the creation of a non-uniform electrical field takes the form of a sub-array of very slender, approximately equal-height micro-spikes, such as those shown at 94a in Fig. 9 , with regard to which electrical energization, as by a computer, such as computer 40 , results in the production of an appropriate pixel-bathing, non-uniform electrical field, shown generally and very schematically in a cloud-like fashion at 96 in Fig. 9.
Figs . 1 OA, 1 OB and 1 OC illustrate several, different, representative micro-spike configurations and arrangements which might be used to characterize a non-uniform electrical field-creating subcomponent. Such micro-spikes are simply illustrative of one of various kinds of different, electronically switchable structures which may be created within a field-creating structure in a pixel to develop, when energized, a suitable , non-uniform electrical field.
Fig. 1 OA illustrates modified micro-spike structures 94a regarding which distributed micro-spikes may have, either uniformly, or differentially, different heights lying within a user-selectable height range generally indicated at H .
Fig. 1 OB illustrates an arrangement wherein micro-spikes 94a are configured like those shown in Fig. 8 and Fig. 9, except for the fact that these Fig. 17B micro-spikes are more densely organized, as indicated by next-adjacent, interspike distance D . Such an interspike distance is freely chooseable by a user, and need not be uniform throughout a full sub-array of micro-spikes. What is illustrated in Fig. 1 OC is an arrangement wherein the pictured micro-spikes 94a may have several differentiating characteristics, such as differentiating heights and sharpnesses (i.e . , pointednesses) .
Those skilled in the art will understand that the specific configuration of a non-uniform-electrical-field-creating subcomponent utilizing spikes, such as those just discussed, may be created in any one of a number of different ways.
Addressing attention now to Fig. 1 1 and Fig. 12 , what is shown in Fig. 1 1 is a modified fragmentary region drawn from the fragmentary illustration of Fig. 1. This figure specifically illustrates a pixel 98, constructed as a part of practice of the present invention, and possessing two assay sensors 98a, 98b, each of which hosts but a single prospective assay site 98ai , 98b i , respectively. The modification illustrated in Fig. 12 shows an arrangement wherein a pixel 100 , also constructed as a part of practice of the present invention, possesses a single sensor 100a which is structured so as to host two, different, potential assay sites 10Oa1 and 100a2. As described, for the general description of the features of the present invention, a precursor pixel-matrix structure, which is formed utilizing the above-mentioned low-temperature TFT and Si technology, is provided preferably on a glass or plastic substrate, whereby, ultimately, and completely under the control of a recipient-user's selection, each pixel in that matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
For the general description of the features of the present invention, a precursor pixel-matrix structure, which is formed utilizing the above-mentioned low-temperature TFT and Si technology, is provided preferably on a glass or plastic substrate, whereby, ultimately, and completely under the control of a recipient-user's selection, each pixel in that matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
The invention thus takes the form of an extremely versatile and relatively low-cost matrix assay precursor structure, also referred to herein interchangeably as a microstructure . It is a precursor structure in the sense that, as has just been mentioned above , it is not yet an assay-material-specific-functionalized assay structure . As will become apparent from the invention description which is provided herein, the structure of this invention is therefore one which is providable, as a singularity, to a user, in a special status which enables that user selectively to functionalize pixels in the structure, with great versatility, to perform one, or even plural different (as will be explained) , type(s) of fluid-material assay(s) .
While there are many ways in which the core characteristics of this invention may be visualized, one way of thinking about it is to recognize its analogy to those kinds of commercial products which are considered to be "staples" in commerce, i. e . , base products which lie as key ingredients in a vast range of final products into which they are processed and incorporated. The structure of the present invention, in the context of its associated field of art and technology regarding the performances of fluid-material assays, is such a product. This analogy should clearly stand out as one reads the full description of the invention presented herein.
There is certain terminology, other than the "low-temperature" terminology defined above , which is employed in the description and characterization of this invention which should here be explained. The concepts of, and terms relating to, "digital addressability" and "energizing" expressed herein are intended to refer to computer-controlled addressability and energizing. The term "active-matrix" as used herein refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s) , operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating structure -- all formed preferably by low-temperature TFT and Si technology as mentioned above . The term "bi-alternate" refers to a possible matrix condition enabled by the present invention, wherein every other pixel in each row and column of pixels may selectively become commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of the overall matrix of the invention, two differently functionalizable submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition) .
The term "tri-alternate" refers to a similar condition, but one wherein every third pixel in each row and column may selectively become commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of the overall matrix, three , differently functionalizable submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition) .
Individual digital addressability of each pixel permits these and other kinds of matrix-distributed functionalization options, if desired.
Other kinds of submatrices are, of course, possible, and one other type of submatrix arrangement is specifically mentioned hereinbelow. Whenever a user elects to employ a submatrix functionalization approach regarding an overall matrix made in accordance with the present invention, that approach may be employed to enable either (a) several, successive same-assay-material matrix-assay uses with the same overall matrix, or (b) several successive different-assay-material submatrix-assay uses also employing the same overall matrix.
It should be apparent that the use of a submatrix functionalization approach with respect to the matrix structure of the present invention enables a user to elect to perform selected assays at different pixel-distribution "granularities" .
With respect to the concept of assay-site functionalization, except for the special features enabled by practice of the present invention that relate (a) to "pixel-specific" functionalization capability, and (b) functionalization under the "control" of a "digitally energized and character-managed", "assay-site-bathing" ambient electromagnetic field of a selected nature, assay-site functionalization is in all other respects essentially conventional in practice . Such functionalization is, therefore , insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay-sensor-functional processes.
While ultimately-enabled functionalization specificity for a particular selected assay site (resident within a given pixel) , in accordance with practice of the present invention in certain instances, is generally and largely controlled by ambient "bathing" of that site with selected-nature electromagnetic-field energy received from an invention-prepared, digitally-energized, appropriately positionally located electromagnetic field-creating subcomponent, it turns out that site-precision specificity is not a critical operational factor. In other words, it is entirely appropriate if the entirety of a pixel becomes ultimately "functionalized" . Accordingly, terminology referring to pixel functionalization and to assay-site functionalization is used herein interchangeably.
Each prepared "precursor" pixel, which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, digitally-addressable assay sensor which is designed to possess, or host, at least one ultimately to-be-functionalized fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material. Each such pixel also includes, as earlier indicated, an αon-board" , digitally-addressable, assay-site-bathing (also referred to as "pixel-bathing") , electromagnetic-field-creating structure (part of a thin-film electronic switching structure) which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such an assay site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the output reading of the result of a particular assay. This field-creating structure is capable, via the inclusion therein of suitable, different, field-creating subcomponents, and in accordance with the present invention, of producing, as an ambient, pixel-bathing field environment within its respective, associated pixel, any one or more of (a) a light field, (b) a heat field, and (c) a non-uniform electrical field. The invention, as suggested above , thus offers an extremely flexibly employable , staple-like, pixelated, precursor, fluid-assay, active-matrix structure, or micro-structure, wherein the individual pixels are not initially pre-ordained to function responsively with any specific fluid-assay material, but rather are poised with a readiness to have their respective , associated assay sensors later user-functionalized to respond with specificity to such an assay material.
In the proposed row-and-column arrangement of precursor assay pixels prepared in accordance with the practice of the present invention, each pixel includes a least one, and may include more than one, assay sensor(s) , with each such assay sensor being ultimately functionalizable to host, or possess, at least one, but optionally and selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
Additionally, and with respect to the important and striking versatility which is offered by the present invention, and thinking about the concept generally mentioned above regarding submatrices, it is entirely possible for a user of the subj ect precursor structure of this invention to create plural, different unified areas (i.e. , unified lower-pixel-count submatrices defined by next-adjacent, side-by-side pixels) within the overall, entire matrix structure which have their respective submatrix pixels functionalized to respond to a specific type of fluid-assay material, with each such different submatrix area being capable of responding to respective , different assay materials.
It should be understood that while the structure of the present invention, as will become apparent, is built in such a fashion that all addressable field-creating subcomponents within each pixel are remotely digitally addressable to assist in pixel functionalization, actual overall functionalization of an assay site on a pixel assay sensor may involve, additionally, as mentioned briefly earlier, the utilization of conventional flow-cell processes in order to implement a full correct functionalization procedure. For example, where an assay site in such a pixel is to become functionalized to respond in a DNA-type assay, conventional flow-cell technology may be used, in cooperation with functionalization assistance provided by the on-board field-creating structure, to carry out such full assay-site functionalization.
As will become apparent, one especially interesting feature of this invention is that it introduces the possibility of deriving assay-result data, including kinetic assay-reaction data, effectively along plural, special axes not enabled by prior art devices. For example, and with respect to the performance, or performances, of a selected, particular type of fluid-material assay, pixels in a group included in full matrix, or in a smaller-pixel-count submatrix, may be functionalized for assay use utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and/ or non-uniform electrical fields. Such differentiated field-intensity functionalization can yield, following an assay, information regarding how an assay's results are affected by such "field-differentiated" pixel functionalization. Similarly, assay results may be observed by reading pixel output responses successively under different (changed) ambient field conditions that are then presented as "bathing" fields seriatim to information-outputting pixels.
Further in relation to the versatile utility of the present invention following user-pixel-functionalization and the performance of a relevant assay, and with respect specifically to the reading-out of completed-assay response information, time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel- specific, digital output sampling.
Regarding the making of a precursor matrix micro-structure as proposed by the present invention, an important point to note is that the processes, procedures and methodologies which are employed specifically to fabricate this precursor structure may be drawn entirely from now-conventional micro-array fabrication practices, such as the earlier-mentioned TFT, Si, low-temperature, and low-cost-substrate technology practices, well known to those generally skilled the art. Accordingly, further details of these practices, which form no part of the present invention, are not set forth herein. Those generally skilled in the relevant art will understand, from a reading of the present specification text, taken along with the accompanying drawing figures, exactly how to practice the present invention, i.e. , will be fully enabled by the disclosure material in this application to practice the invention in all of its unique facets. Thus, according to the present invention, a unique, precursor ("blank-slate-style") , pixelated active matrix, useable ultimately in a fluid-material assay, has been illustrated and described. This matrix has a structure whereby, ultimately, and completely under the control of a matrix-recipient-user's selection, each pixel in that matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results.
The matrix structure of the invention utilizes a low-cost substrate material, such as glass or plastic, and features the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures, all formed preferably by low-temperature TFT and Si technology as discussed above .
The matrix of the invention has the characteristics of a "staple" in commerce -- a key factor which contributes to its special versatility with respect to how it can freely be functionalized in many ways by a user for employment in a fluid-material assay. Independent digital addressability of each pixel introduces interesting opportunities (not offered by prior art structures) for preparing to conduct, and ultimately conducting, such assays in many new ways, including ways that include examining assay results on kinetic and time-based axes of information. Depending upon how user-performed pixel functionalization is done , a single matrix may be employed in one-to-many fluid-material assays .
Returning now to the more detailed, preliminary view of the invention, it pertains to a novel fluid-material assay matrix structure , also referred to herein as a microstructure, which takes the form of a pixelated, active-matrix, row-and-column, fluid-assay, micro-structure characterized by a selected grouping of individually electronically-digitally-addressable pixels, which pixel, and their contents, are formed preferably on a glass or plastic substrate utilizing the above-mentioned low-temperature TFT and Si technology. The concepts of digital addressability and energizing expressed herein are intended to refer to computer-controlled addressability and energizing. The pixels in this selected grouping, which may include either an entire matrix of pixels, or one of a number of possible lower-pixel-count submatrices (later to be described herein) within an overall matrix, have been appropriately prepared on a supporting substrate, with each pixel therein possessing, in addition to appropriate, relevant, computer-accessible electronic switching structure, an included assay sensor which hosts an assay site that has been affinity-functionalized to assist in the performance of a particular kind of fluid-material-specific assay.
With respect to the concept of assay-site functionalization, except for the special features enabled by practice of the present invention that relate (a) to "pixel-specific" functionalization capability, and (b) functionalization under the "control" of a "digitally energized and character-managed" , "assay-site-bathing" ambient electromagnetic field of a selected nature, assay-site functionalization is in all other respects essentially conventional in practice . Such functionalization is, therefore , insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay- sensor-functional processes. While ultimately-enabled functionalization specificity for a particular selected assay site (resident within a given pixel) , in accordance with practice of the present invention in certain instances, is generally and largely controlled by ambient "bathing" of that site with selected-nature electromagnetic-field energy received from an invention-prepared, digitally-energized, appropriately positionally located electromagnetic field-creating subcomponent, it turns out that site-precision specificity is not a critical operational factor. In other words, it is entirely appropriate if the entirety of a pixel becomes ultimately "functionalized" . Accordingly, terminology referring to pixel functionalization and to assay-site functionalization is used herein interchangeably. Each pixel, which is an active-matrix pixel as that language is employed herein, also includes, as was mentioned, a special, pixel-specific, digitally and controllably energizable and employable, assay-site-bathing (also referred to as "pixel-bathing") electromagnetic field-creating structure which may be used, selectively and optionally, as a special assistant in the above-mentioned, "special-information-axis" reading-out of assay results, to generate a selected type of environmentally-pixel-bathing electromagnetic field, such as a light field, a heat field, and a non-uniform electrical field. Of course, pixel-by-pixel assay-result output reading may also be accomplished in appropriate circumstances without any use of the field-creating structure.
This interesting and unique field-creating feature of the invention, coupled with the invention's enablement of pixel-by-pixel, assay-result output reading, are what introduce and promote, among other things, the possibility of deriving assay-result data, including time-based and kinetic assay-reaction data, effectively along the above-suggested, special information axes not enabled by prior art devices. For example, and with respect to the performance, or performances, of a selected, particular type of fluid-material assay, pixels in an appropriately functionalized group of pixels may have been, before matrix delivery to a user, initially functionalized utilizing plural different intensities of functionalization-assist electromagnetic fields, such as intensity-differentiated heat and/ or non-uniform electrical fields. Such differentiated field-intensity functionalization which becomes reflected in a final matrix, and which was performed by pixel-on-board electromagnetic field-creating structures, can, in an assay output-reading situation, yield information regarding how an assay's results are affected by "field-differentiated" prepared-pixel functionalization, also referred to herein as assay-site functionalization . Similarly, assay results may be observed by reading pixel output responses successively under different ambient field conditions that are then "presented" seriatim as spatial bathing fields to information-outputting pixels. Further, time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling. The invention thus takes the form of an extremely versatile and relatively low-cost fluid-material assay structure , which, because of its pixel-by-pixel functionalization characteristic, may be constructed, and delivered to an assay-performing user (as will be seen from discussion text presented hereinbelow) in a variety of different pre-assay conditions . A finished, user-delivered matrix structure constructed in accordance with the present invention may be delivered with all of its pixels functionalized to handle a single, specific assay. Alternatively, such a matrix structure may be delivered to a user with different pixels functionalized differently (i.e . , submatrix functionalization) so as to enable a single matrix to be employed in the conducting of plural, different assays. More will be said about this "submatrix" feature of the invention later herein. Regarding the making of a matrix micro-structure as proposed by the present invention, an important point to note is that the processes, procedures and methodologies which are employed specifically to fabricate this structure may be drawn entirely from conventional micro-array fabrication practices, such as the earlier-mentioned TFT, Si, low-temperature, and low-cost- substrate technology practices, well known to those generally skilled the art. Accordingly, the details of these practices, which form no part of the present invention, are not set forth herein. Those generally skilled in the relevant art will understand, from a reading of the present specification text, taken along with the accompanying drawing figures, exactly how to practice the present invention, i. e . , will be fully enabled by the disclosure material in this application to practice the invention in all of its unique facets.
According to the present invention which is now fully described, a unique, pixelated active matrix, useable ultimately in a fluid-material assay, has been illustrated and described. This matrix has a structure wherein each pixel in that matrix is originally individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results. Independent digital addressability of each pixel introduces interesting opportunities (not offered by prior art structures) for conducting fluid-material assays in many new ways, including ways that include examining assay results on kinetic and time-based axes of information. Depending upon how initial pixel functionalization has been done, a single matrix may be employed in one-to-many fluid-material assays.
Under circumstances where a submatrix functionalization approach has been used to characterize a user-received overall matrix made in accordance with the present invention, that approach enables either (a) several, successive , same-assay-material, matrix-assay uses to take place with respect to the same, single, overall matrix, or (b) several, successive, different-assay-material, matrix-assay uses to occur also with respect to the same , single, overall matrix. It will also be apparent that the use of a submatrix functionalization approach with respect to the matrix structure of the present invention enables a user to perform selected assays at different pixel-distribution "granularities" . The matrix structure of the invention preferably utilizes a low-cost substrate material, such as glass or plastic, and features the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures, all formed preferably by low-temperature TFT and Si technology as discussed above. [SECOND EMBODIMENT]
The following will explain another embodiment of the present invention in reference to Figures 1 to 18. For the members having the same functions and structures as those explained in the first embodiment, the same reference numerals are given, and explanations thereof are omitted here .
Turning attention now to Fig. 13 to Fig. 18, inclusive and respectively, these six figures illustrate the several, key, high-level steps which characterize the preferred and best mode manners of practicing the present invention to produce the precursor micro-structure, and its various unique features, set forth and discussed above. What is shown in these figures, therefore, will be presented now in the context of those key, contributed, methodologic invention steps - recalling that the specifics of these steps' individual implementations may be , and preferably are, carried out in various conventional ways, such as the earlier mentioned, or suggested, micro-structure, photolithographic (and other) patterning and fabrication practices used widely in, for example , the making of all kinds of thin-film, micro-device (e.g. , transistor device) structures.
Additionally, and as will be seen, the various drawing-figure-illustrated steps of the invention pictured in these figures, and the associated block/ schematic ways presented there for "viewing" of the relevant invention methodology (from somewhat different vantage points , drawing figure by drawing figure) , are word-labeled only with the appropriate single words which are the "lead" words of full methodologic statements. These full methodologic statements of the respectively block-diagram-represented method steps are presented completely, however, in the specification text set forth immediately hereinbelow. From a high-level overview of what is shown regarding the nature of the present invention by Fig. 13 to Fig. 18 , inclusive, collectively, and as is made evident from the text material presented hereinabove, the invention can be seen to be describable as being a method for producing a precursor, active-matrix, fluid-assay micro-structure including the steps of establishing (or alternatively establishing by way of utilizing low-temperature TFT and Si technology) a matrix array of non-functionalized pixels, and preparing at least one of these pixels for individual, digitally-addressed (a) functionalization, and (b) reading out, ultimately, of completed assay results.
This method overview can also be seen, from a slightly more specific point of view, to be one wherein the preparing step includes providing each pixel in the established array with a digitally-addressable ( 1 ) non-functionalized assay sensor, and (2) independent, electromagnetic field-creating structure disposed adjacent that pixel. Even more specifically, the invention, from this point of view, may be seen as utilizing low-temperature TFT and Si technology to implement the providing step on and in relation to a glass or plastic substrate.
Looking now more particularly at what appears in Fig. 13 to Fig. 18, inclusive, Fig. 13 , which includes blocks, or steps, 102 (PRODUCING) , 104 (ESTABLISHING) and 106 (PREPARING) provides another kind of overview, even somewhat more specific than what was just stated immediately above, of the methodology of the present invention. In this setting, blocks(steps) 104 , 106 are shown to be functionally included within block(step) 102 , and interconnected therein by a sequence-indicating arrow 108.
In relation to what is shown visually in Fig. 13, and with appropriate reference made back to the structural discussion provided earlier herein, the invention, as here illustrated, can be expressed verbally as a method for PRODUCING (step 102) a remotely digitally-addressable, pixelated, precursor, active-matrix, fluid-assay micro-structure , including the steps of (a) ESTABLISHING (step 104) , on a supporting substrate, an array of plural, non-assay-functionalized pixels, and then (b) PREPARING (step 106) each established pixel with electronically digitally-addressable electronic structure designed to effect, for and with respect to that pixel, and under the selection and control of a user, at least one of (a) selective, independent, fluid-assay-material-specific functionalization, and (b) assay-result output reading, utilizing, at least in part, communicative, electronic interaction between that pixel and a digital computer.
Fig. 14 further pictures the step of electronic-switching-structure PREPARING, i.e. , block 106. More specifically, this electronic-switching-structure PREPARING step is shown to include the companion, but not necessarily sequential, blocks, or steps, 1 10 (PROVIDING) and 1 12 (FORMING) .
In the language of words, Fig. 14 effectively describes the invention as taking the form of what is expressed in and by Fig. 13 , wherein, further, the PREPARING step, block 106, includes (a) PROVIDING (step 1 10) each pixel with at least one electronically, digitally-addressable assay sensor operatively connected to also provided electronically digitally-addressable electronic switching structure, and constructed to host at least one electronically, digitally-addressable, ultimately functionalizable assay site, and (b) FORMING (step 1 12) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure also operatively connected to the also provided electronic switching structure, and which is selectively energizable by the mentioned computer to participate in at least one of ( 1) pixel functionalization, and (2) assay-result output reading with regard to a functionalized pixel. Fig. 15 relates to Fig. 14 in somewhat, though not completely, the same manner that Fig. 14 relates to Fig. 13 , in the sense that Fig. 15 further characterizes the methodology of the invention expressed in Fig. 14 by describing something more about the included functional content of one of the blocks/ steps pictured in Fig. 14. In particular, Fig. 15 further characterizes the invention by elaborating the functional content of the step of PROVIDING, i. e. , block 1 10 - indicating that the PROVIDING step includes, as will be more fully set forth below, the step of FABRICATING (block 1 14) , and additionally includes the further step of
PRODUCING (block 1 16) . A connecting line 1 18 indicates the just-mentioned "further step" relationship between blocks 1 14, 1 16.
Thus, in narrative form, Fig. 15 illustrates that, with respect to the invention as pictured in Fig. 14, the
PROVIDING of each pixel with the mentioned at least one electronically digitally-addressable assay sensor includes FABRICATING that sensor within the pixel as a micro-deflection device. Fig. 15 also illustrates that the step of PROVIDING further includes the step of PRODUCING, on the fabricated micro-deflection device, a remotely, electronically, digitally-addressable electrical signaling structure which is operable to generate an electrical signal related to deflection of the micro-deflection device . Fig. 16, in pictured blocks/ steps 1 14, 120 illustrates that the step of FABRICATING (block 1 14) the mentioned micro-deflection device takes the form of CREATING (block 120) a cantilever structure.
Fig. 17 employs blocks/ steps 1 12 (FORMING) and 122 (CONSTRUCTING) , along with "produced-precursor-structure" blocks 124, 126, 128 (still to be described) , to elaborate, somewhat, the functional content of the step of FORMING within each pixel an electronically, digitally-addressable electromagnetic field-creating structure. In particular, Fig. 17 describes the functional condition that the step of
FORMING a field-creating structure includes CONSTRUCTING, within each pixel, at least one of (a) a light-field-creating (L) subcomponent (block 124) , (b) a heat-field-creating (H) subcomponent (block 126) , and (c) a non-uniform-electrical-field-creating (E) subcomponent(block
124) (block 128) .
Finally, Fig. 18 further characterizes the CONSTRUCTING (L) step (blocks 122 , 124) of the invention by pointing out that it can take two different forms of a step referred to as MAKING (block 130) . More specifically, the step of CONSTRUCTING (L) (blocks 122 , 124) of a light-field-creating subcomponent involves the MAKING either of a pixel on-board light (POB) source, block 132, or of a pixel-communicative, on-substrate, optical beam structure (OBS), block 134, adapted for optical coupling to an off-pixel light source.
For the general description of the preferred "silicon on glass or plastic" practice features of the present invention, a precursor pixel-matrix structure, which is formed utilizing the above-mentioned low-temperature TFT and Si technology, is created and provided preferably on a glass or plastic substrate, whereby, ultimately, and completely under the control of a recipient-user's selection, each pixel in that created matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results. The invention thus takes the form of a method for creating an extremely versatile and relatively low-cost assay precursor structure . The precursor structure, also referred to herein interchangeably as a micro-structure, resulting from this method is a precursor structure in the sense , as has just been mentioned above, that it is not yet an assay-material-specific-functionalized assay structure. As will become apparent from the invention description which is provided herein, the structure created by the methodology of this invention is one which is providable, as a singularity, to a user, in a special status which enables that user selectively to functionalize assay sites in its pixels with great versatility, to perform one, or even plural different (as will be explained) , type(s) of fluid-material assay(s) .
As will be seen, the methodology which is contributed to the state of the relevant sensor assay art by the present invention is a very high-level methodology. In this context, it consists of a unique, high-level organization of steps which are cooperatively linked to produce a unique fluid-assay precursor structure. Detailed features of the several high-level steps involved in the practice of this invention are , or may be, drawn from well-known and conventional practices aimed at producing various micro-structure devices and features, such as semiconductor matrixes, or arrays . The invention does not reside in, or include, any of these feature details. Rather, it resides in the overall arrangement of steps that are capable of leading to the fabrication of the desired, end-result assay precursor micro-structure mentioned above .
With respect to the concept of assay-site functionalization, except for the special features enabled by practice of the present invention that relate (a) to "pixel-specific" functionalization capability, and (b) functionalization under the "control" of a "digitally energized and character-managed", "assay-site-bathing" ambient electromagnetic field of a selected nature, assay-site functionalization is in all other respects essentially conventional in practice. Such functionalization is, therefore, insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use , in many functionalization procedures, of conventional flow-cell assay- sensor-functional processes.
While ultimately-enabled functionalization specificity for a particular selected assay site (resident within a given pixel) , in accordance with practice of the present invention in certain instances, is generally and largely controlled by ambient "bathing" of that site with selected-nature electromagnetic-field energy received from an invention-prepared, digitally-energized, appropriately positionally located, preferably thin-film, electromagnetic field-creating subcomponent, it turns out that site-precision specificity is not a critical operational factor. In other words, it is entirely appropriate if the entirety of a pixel becomes ultimately "functionalized*. Accordingly, terminology referring to pixel functionalization and to assay-site functionalization is used herein interchangeably.
While there are many ways in which the core characteristics of this methodologic invention may be visualized and understood, one good way to accomplish this is to focus attention upon the important characteristics of the intended, end-result product of the proposed precursor-structure-producing methodology. Accordingly, we lead into the description of this methodologic invention through a description of that end-result product, with reference made to several embodiments/ modifications of such a product. The methodologic steps of the invention are set forth following this product discussion .
One of the first important things to note about the subject end-result product is that it takes the form of a micro-structure pixelated array, or matrix, of active pixels which are designed to be individually, i.e . , pixel-specifically, addressed and accessed, for at least two important purposes, by a digital computer. The first of these purposes is to enable user-selectable functionalization of assay sites in pixels to become responsive to particular fluid-assay materials. The second involves implementing user-selectable access to assay-site-functionalized pixels to obtain output readings of responses generated by those pixels regarding the result(s) of a performed fluid-material assay. In this context, the end-result structure generally created by the methodology of this invention acts importantly as a kind of blank slate useable by a user to characterize an entire matrix array, or even simply portions of such an array, for the performance of a specific, or plural specific (different or same) , user-chosen fluid-material assay(s) .
This blank slate nature of the product resulting from practice of the present invention also leads one to recognize an important analogy that exists between this proposed end-result methodololgic product and those various kinds of well-known commercial products which are considered to be "staples" in commerce, i. e. , base products which lie as key ingredients in a vast range of final products into which they are processed and incorporated. The end-result structure coming from practice of the present invention, in the context of its associated field of art and technology regarding fluid-material assays, is indeed such a "staple-like" product.
This analogy, which should clearly stand out very understandably as one reads the full description of the invention practice which is presented herein, directs attention to a key and unique contributed versatility feature that is offered by practice of the methodology of the present invention.
A full description of the preferred and best mode methodology of the invention herein will follow (a) a completion of this introductory text, (b) the then-presented
Description of the Drawings, and (c) the thereafter-presented, detailed, end-result product description.
Before continuing, however, certain definitions relating to terminology employed herein are set forth. The term "active-matrix" as used herein refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s) , operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating structure-- all formed preferably by low-temperature TFT and Si technology as mentioned above .
The term "bi-alternate" refers to a possible , user-selectable matrix condition enabled by practice of the present invention, wherein every other pixel in each row and column of pixels may selectively become commonly functionalized for one, specific type of fluid-material assay.
This condition effectively creates, across the entire area of an overall matrix made by practice of the invention, two differently and/ or separately functionalizable , lower-pixel-count submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition) .
The term "tri-alternate" refers to a similar condition, but one wherein every third pixel in each row and column may selectively become commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of an overall matrix, three, differently and/ or separately functionalizable, lower-pixel-count submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition) .
Individual digital addressability of each pixel permits these and other kinds of lower-pixel-count, submatrix functionalization options, if desired.
Because of the "blank-slate" nature of a precursor micro-structure matrix which results from implementation of the methodology of the present invention, other kinds of submatrices are, of course, possible, and one other type of submatrix arrangement is specifically mentioned hereinbelow.
Whenever a user elects to employ a submatrix functionalization approach regarding an overall matrix made in accordance with the present invention, that approach may be employed to enable either (a) several, successive same-assay-material matrix-assay uses with the same overall matrix, or (b) several successive different-assay-material submatrix-assay uses, also employing the same overall matrix. It should be apparent, also, that the use of a submatrix functionalization approach with respect to the precursor matrix structure produced by practice of the present invention enables a user to elect to perform selected assays at different pixel-distribution "granularities". Each prepared "precursor" pixel, which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, electronically, digitally-addressable assay sensor which is designed to possess, or host, at least one ultimately functionalized, electronically digitally-addressable fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material. Each such pixel also includes, as earlier indicated, an "on-board", digitally-addressable, assay-site-bathing (also referred to as "pixel-bathing") , preferably thin-film, electromagnetic-field-creating structure which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such a site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the output reading of the result of a particular assay. This pixel-bathing, field-creating structure is capable, via the inclusion therein (by • way of practice of the present invention) of suitable, different, field-creating subcomponents, and in accordance with aspects of the present invention, of producing, as a pixel-bathing, ambient field environment within its respective, associated pixel, any one or more of (a) an ambient light field, (b) an ambient heat field, and (c) an ambient non-uniform electrical field.
The invention, as suggested above, thus offers a methodology for producing an extremely flexibly employable , blank-slate, staple-like, pixelated, precursor, fluid-assay, active-matrix structure, or micro-structure, wherein the individual pixels are not initially pre-ordained to function responsively with any specific fluid-assay material, but rather are poised with a readiness to have their respective, associated assay sensors later user-functionalized to respond with specificity to such an assay material.
In the proposed row-and-column arrangement of precursor assay pixels prepared in accordance with the practice of the present invention, each pixel includes a least one, and may include more than one, assay sensor(s) , with each such assay sensor being ultimately functionalizable to host, or possess, at least one, but selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
Additionally, and with respect to the issue of ultimate versatility as it relates to the concept regarding submatrices, it is possible for a precursor micro-structure user to create (i.e. , functionalize) plural, different, internally unified (all internally alike) subareas (i. e. , unified lower-pixel-count submatrices defined by next-adj acent, side-by-side pixels) within an overall, entire matrix, and to functionalize such pixels to respond to one specific type of fluid-assay material, with each such different, internally unified area being functionalized to respond to respective, different assay materials.
It should be understood, regarding functionalization, that while the end-result structure created by practice of the present invention is built in such a fashion that all addressable, pixel-bathing field-creating subcomponents within each pixel are remotely digitally addressable to assist in pixel functionalization, actual overall functionalization of an assay site on a pixel assay sensor may involve, additionally, as mentioned briefly earlier, the utilization of conventional flow-cell processes in order to implement a full correct functionalization procedure . For example, where an assay site in such a pixel is to become functionalized to respond in a DNA-type assay, conventional flow-cell technology may be used, in cooperation with functionalization assistance provided by the on-board field-creating structure, to carry out such full assay-site functionalization.
As will become apparent, one especially interesting feature of a precursor matrix micro-structure produced by practice of this invention is that it introduces the possibility of deriving assay-result data, including kinetic assay-reaction data, effectively on or along plural, special axes not enabled by prior art devices. For example, and with respect to the performance, or performances, of a selected, particular type of fluid-material assay, pixels in a group of pixels contained in a full matrix, or in a lower-pixel-count submatrix, may be functionalized utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and / or non-uniform electrical fields. Such differentiated field-intensity functionalization can yield assay-result output information regarding how an assay's results are affected by "field-differentiated" pixel functionalization. Similarly, assay results may be observed by reading pixel output responses successively under different, pixel-bathing ambient electromagnetic field conditions that are then presented seriatim to information-outputting pixels .
Further in relation to the versatile matrix utility enabled ultimately by practice of methodology of the present invention, following user-pixel-functionalization and the performance of a relevant assay, and with respect specifically to the reading-out of completed-assay response information, time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
Regarding the making of a precursor matrix micro-structure as proposed by the present invention, an important point to note , as suggested earlier herein, is that the particular details of the processes, procedures and specific methodologic steps which are employed specifically to fabricate the subject precursor structure may be drawn entirely from conventional micro-array fabrication practices, such as the earlier-mentioned TFT, Si, low-temperature , and low-cost-substrate technology practices, well known to those generally skilled the art. Accordingly, while the high-level, overall organization of cooperative steps proposed by the invention is unique, the details of these steps, which form no part of the present invention, are not set forth herein. Those generally skilled in the relevant art will understand, from a reading of the present specification text, taken along with the accompanying drawing figures, exactly how to practice the present invention, i.e. , will be fully enabled by the disclosure material in this text and the accompanying drawings to practice the invention in all of its unique facets.
Thus, a unique, high-level methodologic practice for producing a likewise unique, precursor ("blank-slate- style") , pixelated, active-matrix, fluid-assay micro-structure, useable ultimately in a fluid-material assay, has been illustrated and described. This invention methodology produces such a micro-structure whereby ultimately, and completely under the control of a matrix-recipient-user's selection, each pixel in that produced precursor matrix is individually and independently functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results. The precursor matrix structure made by practice of the methodology of the invention utilizes, preferably, a low-cost substrate material, such as glass or plastic, and features, also preferably, the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures, all formed preferably by TFT and Si technology as discussed above . Thus one can think about this invention as involving, preferably, silicon on glass or plastic technology. The unique matrix which is created by practice of the methodology of the present invention has the characteristics of a "staple" in commerce -- a key factor which contributes to its special, end-result versatility with respect to how it can freely be functionalized in many ways by a user for employment in a fluid-material assay. Fabrication of the described precursor matrix to possess independent digital addressability of each pixel, and further to include special pixel-bathing, ambient electromagnetic field-creating structure, introduces interesting opportunities to a user (not offered by the prior art s) for preparing to conduct, and ultimately for conducting, such assays in many new ways, including ways that include examining assay results on kinetic and time-based axes of information.
And, very specially, depending upon how user-performed pixel functionalization is ultimately done (as enabled by the fabrication methodology contributed to the art by the present invention) , a single matrix may be user-employed in "one-to-many" fluid-material assays. [THIRD EMBODIMENT] The following will explain another embodiment of the present invention in reference to Figs 1 to 12 , and Figs 19 to 26. For the members having the same functions and structures as those explained in the first and second embodiments, the same reference numerals are given, and explanations thereof are omitted here.
Turning attention now to Fig. 19 to Fig. 26, inclusive and respectively, these eight figures illustrate the several, key, high-level steps (shown as blocks) which characterize the preferred and best mode manners of practicing the present invention to produce the micro-structure, and its various unique features, set forth and discussed above . What is shown in these figures, therefore, will be presented now in the context of those key, contributed, methodologic invention steps - recalling that the specifics of these steps' individual implementations may be, and preferably are, carried out in various conventional ways, such as the earlier mentioned, or suggested, micro-structure, photolithographic (and other) patterning and fabrication practices used widely in, for example, the making of all kinds of thin-film, micro-device (e.g. , transistor-device) structures. Additionally, and as will be seen, the various drawing-figure-illustrated steps of the invention pictured in these figures, and the associated block/ schematic ways presented there for "viewing" of the relevant invention methodology (from somewhat different vantage points, drawing figure by drawing figure) , are word-labeled only with the appropriate single words which are the "lead" words of full methodologic statements . These full methodologic statements of the respectively block-diagram-represented method steps are presented completely, however, in the specification text set forth immediately hereinbelow.
From a high-level overview of what is shown regarding the nature of the present invention by Fig. 19 and Fig. 20 , and as is made evident from the text material presented hereinabove, the invention can be seen to be describable (Fig.
19) as being a method for PRODUCING (block 202) an active-matrix, fluid-assay micro-structure , including the steps of (a) ESTABLISHING (block 204) an array of digitally- addressable, assay-material- specific-functionalizable pixels, and (b) employing pixel-specific digital addressing for selected array-established pixels, individually
FUNCTIONALIZING (block 206) these pixels. In a more particular sense, the ESTABLISHING step may be expressed in the context of utilizing low-temperature TFT and Si technology in relation to forming devices preferably on a glass or plastic substrate.
This high-level method overview can also be seen, from a slightly more specific point of view in Fig. 20 , to be one wherein the step of FUNCTIONALIZING (block 206) a selected pixel includes individually and controllably BATHING (block
208) that pixel with a selected-character electromagnetic field.
Looking now more particularly at what appears in Fig. 2 1 to Fig. 24, inclusive, Fig. 2 1 , which includes blocks, or steps, 202 (PRODUCING) , 204 (ESTABLISHING) and 2 10
(PREPARING) , 2 12 (CONNECTING) , 2 14 (ADDRESSING) , and 2 16 (EFFECTING) provides another kind of overview, even somewhat more specific than what was just stated immediately above, of the methodology of the present invention. In this setting, blocks 210, 2 12 , 2 14, 216 are shown to be functionally included within block 202 , and interconnected therein by sequence-indicating arrows 2 18 , 220, 222 , 224.
Thus, in accordance with what is specifically shown in Fig. 2 1 , and with appropriate reference made back to the structural discussion provided earlier herein, the invention, as here illustrated, can be expressed verbally as a method for PRODUCING (block 202) a remotely digitally-addressable, pixelated, active-matrix, fluid-assay micro- structure, including the steps of (a) ESTABLISHING (block 204) , on a supporting substrate, an array of plural pixels, (b) PREPARING (block 2 10) each established pixel with digitally-addressable electronic structure designed to effect, for and with respect to that pixel, and under the control of an appropriately operatively connected digital computer, at least one of ( 1) selective, independent, fluid-assay-material-specific functionalization, and (2) assay-result output reading, (c) operatively CONNECTING (block 2 12) such a computer to the electronic structure which is associated with at least one of the established and prepared pixels, (d) employing the operatively connected computer, digitally ADDRESSING (block 2 14) the electronic structure in the at least one associated pixel, and (e) by that ADDRESSING (block 2 14) step, EFFECTING (block 2 16) at least one of ( 1 ) selected fluid-assay-material- specific functionalizing, and (2) assay-result output reading of at least one pixel.
Fig. 22 further pictures the step of PREPARING (block 2 10) . More specifically, this PREPARING step (block 2 10) is shown to include the companion, but not necessarily sequential, 226 (PROVIDING) and 228 (FORMING) steps. In the language of words, Fig. 22 therefore effectively describes the invention as taking the form of what is expressed in and by Fig. 2 1 , wherein further, the PREPARING step (block 2 10) includes (a) PROVIDING (block 226) each pixel with at least one electronically, digitally-addressable assay sensor operatively connected to also provided electronically digitally-addressable electronic switching structure, and constructed to host at least one electronically, digitally-addressable, ultimately functionalizable assay site , and (b) FORMING (block 228) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure also operatively connected to the also provided electronic switching structure, and which is selectively energizable by the mentioned computer to participate in at least one of ( 1 ) pixel functionalization, and
(2) assay-result output reading with regard to a functionalized pixel.
Fig. 23 relates to Fig. 22 in somewhat, though not completely, the same manner that Fig. 22 relates to Fig. 2 1 , in the sense that Fig. 23 further characterizes the methodology of the invention expressed in Fig. 22 by describing something more about the included functional content of one of the blocks/ steps pictured in Fig. 22. In particular, Fig. 23 further characterizes the invention by elaborating the functional content of the step of PROVIDING,
(block 226) - indicating that the PROVIDING (block 226) step includes, as will be more fully set forth below, the step of FABRICATING (block 230) , and additionally includes the further step of PRODUCING (block 232) . A connecting line 234 indicates the just-mentioned "further step" relationship between blocks 230 , 232.
. In narrative form, Fig. 23 illustrates that, with respect to the invention as pictured in Fig. 22 , the PROVIDING (block 226) of each pixel with the mentioned at least one electronically digitally-addressable assay sensor includes
FABRICATING (block 230) that sensor within the pixel as a micro-deflection device. Fig. 23 also illustrates that the step of PROVIDING (block 226) further includes the step of PRODUCING (block 232) , on the fabricated micro-deflection device, a remotely, electronically, digitally-addressable electrical signaling structure which is operable to generate an electrical signal related to deflection of the micro-deflection device .
Fig. 24 , in pictured blocks/ steps 230 , 236 illustrates that the step of FABRICATING (block 230) the mentioned micro-deflection device takes the form of CREATING (block 236) a cantilever structure.
Fig. 25 employs blocks/ steps 228 (FORMING) and 238 (CONSTRUCTING) , along with "produced -structure" blocks 240, 242 , 244 (still to be described) , to elaborate, somewhat, the functional content of the step of FORMING (block 228) within each pixel an electronically, digitally-addressable electromagnetic field-creating structure . In particular, Fig. 25 describes the functional condition that the step of FORMING (block 228) a field-creating structure includes CONSTRUCTING (block 238) , within each pixel, at least one of (a) a light-field-creating (L) subcomponent (block 240) , (b) a heat-field-creating (H) subcomponent (block 242) , and (c) a non-uniform-electrical-field-creating (E) subcomponent(block 244) .
Finally, Fig. 26 further characterizes the CONSTRUCTING (L) step (blocks 238, 240) of the invention by pointing out that it can take two different forms of a step referred to as MAKING (block 246) . More specifically, the step of CONSTRUCTING (L) (blocks 238 , 240) of a light-field-creating subcomponent involves the MAKING (block 246) either of a pixel on-board light (POB) source (block 248) , or of a pixel-communicative, on-substrate, optical beam structure (OBS) (block 250) , adapted for optical coupling to an off-pixel light source.
Further in accordance with preferred and best mode , preferably "silicon on glass or plastic" practice features of the invention, pixel functionalization may be performed under circumstances wherein it is aided by the presence and use , in each pixel, of the included pixel-bathing electromagnetic field-creating structure which is, when so used, remotely and controllably energized under the management of an appropriate digital computer, to bathe the pixel-associated assay sensor and its possessed assay site(s) with such a field (light, heat and / or non-uniform electrical) . Beyond the specific practice of the present invention, this same field-creating structure has later utility, where appropriate, in relation to participating selectively in the reading-out of ultimately achieved, completed-assay results. More will be said about this invention-enabled later utility shortly.
Digitally addressed, pixel-by-pixel functionalization allows for the production of highly specialized and individualized fluid-material assays. Such functionalization, performed in the context of also employing, as an aid, the mentioned electromagnetic field-creating structure, enables a very high, selective versatility to be associated with finally functionalized pixels. Additionally, and as will be more fully explained later herein, this same, per-pixel, digitally-addressable electromagnetic field-creating structure opens the door to permitting a number of highly specialized assay-result output reading practices.
The present invention, utilizing the above-mentioned low-temperature TFT and "Si on glass or plastic substrate" technology, thus takes the form of a method for creating an extremely versatile and relatively low-cost digitally-addressable assay structure, also referred to herein interchangeably as a micro-structure . As will become apparent from the invention description which is provided herein, the structure created by the methodology of this invention is one which is providable, as a singularity, to a user, in a status which enables that user to perform one, or even plural different (as will be explained) , type(s) of fluid-material assay(s) . It is also a structure which enables the useful reading out of completed assay results completely on a precision, pixel-by-pixel basis.
As will be seen, the methodology which is contributed to the state of the relevant sensor assay art by the present invention is a very high-level methodology. In this context, it consists of a unique, high-level organization of steps which are cooperatively linked to produce a unique fluid-assay structure. Detailed features of the several high-level steps involved in the practice of this invention are, or may be, drawn from well-known and conventional practices aimed at producing various micro-structure devices and features, such as semiconductor matrices, or arrays. The invention does not reside in, or include , any of these feature details. Rather, it resides in the overall arrangement of steps that are capable of leading to the fabrication of the desired, end-result assay micro-structure mentioned above.
With respect to the concept of assay-site functionalization, except for the special features enabled by practice of the present invention that relate (a) to "pixel-specific" functionalization, and (b) possible functionalization under the influence of an assay-site-bathing, ambient electromagnetic field of a selected nature, assay-site functionalization is in all other respects essentially conventional in practice . Such functionalization is, therefore , insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay- sensor-functional processes. While ultimately-enabled functionalization specificity for a particular selected assay site (resident within a given pixel) , in accordance with practice of the present invention in certain instances, is generally and largely controlled by ambient "bathing" of that site with selected-nature electromagnetic-field energy received from the earlier-mentioned, and of course appropriately positioned electromagnetic field-creating structure, it turns out that "site-precision" functionalization-bathing specificity is not a critical operational factor. In other words, it is entirely appropriate if the entirety of a pixel is field-bathed, and thereby becomes ultimately "overall functionalized" . Accordingly, terminology referring to pixel functionalization and to assay-site functionalization is used herein interchangeably. While there are many ways in which the core characteristics of this methodologic invention may be visualized and understood, one good way to accomplish this is to focus attention upon the important characteristics of the intended, end-result product of the proposed assay-structure-producing methodology. Accordingly, we lead into the description of this methodologic invention through a description of that end-result product, with reference made to several embodiments/ modifications of such a product. The methodologic steps of the invention are set forth following this product discussion .
One of the first important things to note about the subject end-result product is that it takes the form of a micro-structure pixelated array, or matrix, of active pixels which are designed to be individually, i.e. , pixel-specifically, addressed and accessed, for at least two important purposes, by a digital computer. The first of these purposes is to enable selective functionalization of assay sites in pixels to become responsive to particular fluid-assay materials. The second involves enabling user-selectable access to functionalized pixels to obtain output readings of responses generated by those pixels regarding the result(s) of a performed fluid-material assay. In this context, the structure generally created by the methodology of this invention allows for selective characterization of an entire matrix array, or even simply portions of such an array, for the performance of a specific, or plural specific (different or same) , user-chosen fluid-material assay(s) .
A full description of the preferred and best mode methodology of the invention herein will follow (a) a completion of this introductory text, (b) the then-presented
Description of the Drawings, and (c) the thereafter-presented, detailed, end-result product description.
Before continuing, however, certain definitions relating to terminology employed herein are set forth. The term "active-matrix" as used herein refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s) , operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating structure-- all formed preferably by low-temperature TFT and Si technology as mentioned above. The term "bi-alternate" refers to a possible , selectable matrix condition enabled by practice of the present invention, wherein every other pixel in each row and column of pixels is selectively commonly functionalized for one, specific type of fluid-material assay. This condition effectively creates, across the entire area of an overall matrix made by practice of the invention, two differently and/ or separately functionalized, lower-pixel-count submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition) .
The term "tri-alternate" refers to a similar condition, but one wherein every third pixel in each row and column is selectively commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of an overall matrix, three, differently and/ or separately functionalized, lower-pixel-count submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition) .
Individual digital addressability of each pixel permits these and other kinds of lower-pixel-count, submatrix functionalization options, if desired. Other kinds of submatrices are, of course, possible, and one other type of submatrix arrangement is specifically mentioned hereinbelow.
Whenever the present invention is practiced to create a submatrix functionalization of an overall matrix, that approach, depending upon functionalization "strategy" , enables either (a) several, successive same-assay-material matrix-assay uses to take place with the same overall matrix, or (b) several successive different-assay-material submatrix-assay uses to occur, also employing the same overall matrix. It should be apparent also that the implementation, in the practice of the invention, of different submatrix-functionalization pixel distributions with respect to one-only, or to different, matrix structure(s) can enable a end user to perform selected assays with such different distributions at different pixel-distribution "granularities" .
Each prepared "precursor" pixel, which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, electronically, digitally-addressable assay sensor which is designed to possess, or host, at least one functionalized, electronically digitally-addressable fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material.
Each such pixel also includes, as earlier indicated, an "on-board" , digitally-addressable, assay-site-bathing (also referred to as "pixel-bathing") , preferably thin-film, electromagnetic-field-creating structure which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such a site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the later output reading of the result of a particular assay. This pixel-bathing, electronic, field-creating structure is capable, via the inclusion therein (by way of practice of the present invention) of suitable, different, field-creating subcomponents, and in accordance with aspects of the present invention, of producing, as a pixel-bathing, ambient field environment within its respective , associated pixel, any one or more of (a) an ambient light field, (b) an ambient heat field, and (c) an ambient non-uniform electrical field.
In the proposed row-and-column arrangement of assay pixels prepared in accordance with the practice of the present invention, each pixel includes a least one , and may include more than one, assay sensor(s) , with each such assay sensor being ultimately functionalized to host, or possess, at least one, but selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
Additionally, and with respect to the issue of ultimate versatility as it relates to the concept regarding submatrices, it is possible to create (i.e. , to functionalize) plural, different, internally unified (all internally alike) subareas (i. e . , unified lower-pixel-count submatrices defined by next-adj acent, side-by-side pixels) within an overall, entire matrix, and to functionalize such pixels to respond to one specific type of fluid-assay material, with each such different, internally unified area being functionalized to respond to respective, different assay materials.
It should be understood, regarding functionalization, that while the end-result structure created by practice of the present invention is built in such a fashion that all addressable, pixel-bathing field-creating subcomponents within each pixel are remotely digitally addressable to assist in pixel functionalization, actual overall functionalization of an assay site on a pixel assay sensor may involve, additionally, and as was mentioned briefly earlier, the utilization of conventional flow-cell processes in order to implement a full correct functionalization procedure. For example , where an assay site in such a pixel is to become functionalized to respond in a DNA-type assay, conventional flow-cell technology may be used, in cooperation with functionalization assistance provided by the on-board field-creating structure, to carry out such full assay-site functionalization.
As will become apparent, one especially interesting feature of a matrix micro-structure produced by practice of this invention is that it introduces the possibility of deriving assay-result data, including kinetic assay-reaction data, effectively on or along plural, special axes not enabled by prior art devices . For example, and with respect to the performance, or performances, of a selected, particular type of fluid-material assay, pixels in a group of pixels contained in a full matrix, or in a lower-pixel-count submatrix, may be functionalized utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and/ or non-uniform electrical fields. Such differentiated field-intensity functionalization can yield assay-result output information regarding how an assay's results are affected by "field-differentiated" pixel functionalization. Similarly, assay results may be observed by reading pixel output responses successively under different, pixel-bathing ambient electromagnetic field conditions that are then presented seriatim to information-outputting pixels.
Further in relation to the versatile matrix utility enabled in a finished matrix array ultimately by practice of methodology of the present invention, following the performance of an assay with that array, and with respect specifically to the reading-out of completed-assay response information, time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
Regarding the making of a matrix micro-structure as proposed by the present invention, an important point to note, as suggested earlier herein, is that the particular details of the processes, procedures and specific methodologic steps which are employed specifically to fabricate the subject micro-structure may be drawn entirely from conventional micro-array fabrication practices, such as the earlier-mentioned TFT, Si, low-temperature, and low-cost-substrate technology practices, well known to those generally skilled the art. Accordingly, while the high-level, overall organization of cooperative steps proposed by the invention is unique, the details of these steps, which form no part of the present invention, are not set forth herein. Those generally skilled in the relevant art will understand, from a reading of the present specification text, taken along with the accompanying drawing figures, exactly how to practice the present invention, i. e. , will be fully enabled by the disclosure material in this text and the accompanying drawings to practice the invention in all of its unique facets.
Thus, a unique, high-level methodologic practice for producing a likewise unique, digitally-addressable, pixelated, functionalized, active-matrix, fluid-assay micro-structure , useable ultimately in a fluid-material assay, has been illustrated and described. The invention methodology produces such a micro-structure wherein each pixel is individually and independently digitally-addressable and functionalizable to display an affinity for at least one specific fluid-assay material, and following such functionalization, and the subsequent performance of a relevant assay, individually and independently digitally readable to assess assay results. Pixel- specific, digitally-addressable, electromagnetic field-creating structures enable widely-varied, controlled pixel functionalization under different kinds of ambient field conditions, and also enable, ultimately, a rich range (time-sampling-based, and on additional, uniquely permitted information axes, such as field-intensity varying axes) of assay-result output reading possibilities, some of which have been specifically mentioned above . The matrix structure made by practice of the methodology of the invention utilizes, preferably, a low-cost substrate material, such as glass or plastic, and features, also preferably, the low-temperature fabrication on such a substrate of supported pixel structures, including certain kinds of special internal components or substructures , all formed preferably by TFT and Si technology as discussed above. Thus one can think about this invention as involving, preferably, silicon on glass or plastic technology. [FOURTH EMBODIMENT] The following will explain another embodiment of the present invention in reference to Fig 1 to Fig. 6, and Fig 27 to Fig. 31 . For the members having the same functions and structures as those explained in the first and second embodiments, the same reference numerals are given, and explanations thereof are omitted here.
Turning attention now to Fig. 27 to Fig. 3 1 , inclusive, and recognizing that assay performance in accordance with practice of the present invention is based upon use of a suitably provided, i. e. , made-available, device like micro-structure 20 shown in Fig. 1 and Fig. 2 , these five drawing figures illustrate the basic high-level methodology of the invention which is practiceable in conjunction with such a device .
Speaking about the invention methodology, in the simplest terms, a device, like micro-structure 20 with appropriately functionalized pixels, sensors and assay sites is provided for use, and is placed in an assay-fluid environment, such as within a conventional flow-cell. A computer, like computer 40, is appropriately linked to the sensors, assay sites and field-creating structures in the device's pixels via communication/ addressing path structure 36, 38 shown in Fig. 1 and Fig. 2, and the device's pixels are then appropriately exposed to assay-fluid in the assay environment. In conjunction with such exposure, and typically, though not necessarily, beginning at the start of this exposure, under the control of the relevant computer, one-by-one the pixels are digitally addressed/ accessed to request from their respective sensors and assay sites assay-reaction output results/ information so as to obtain, collect and store if desired, and report on, that information.
This pixel-by-pixel digital addressing may also be accompanied very effectively by simultaneous accessing and energizing of pixel-specific field-creating subcomponents to produce one or more kind(s) of field(s) , such as light, heat and electrical potential (or electrical gradient) fields, in the vicinities of addressed sensor assay sites in order to enhance assay-result information output. For example , with respect to a given pixel assay site , output readings may be acquired at different, computer-controlled, static, or varying, electromagnetic field conditions, such as varying field-intensity conditions, and this may also be done in a sampling fashion on a time base, thus to open opportunities for gaining multiple "axes" of assay-result output information. With this general practice description in mind, Fig. 27 , which includes three blocks 300 , 302 , 304 , illustrates one specific way of visualizing the practice of the invention. From this point of view, the invention can be expressed as being a method of performing a fluid-material assay utilizing a device including at least one active pixel having a sensor with an assay site functionalized for selected fluid-assay material, including the steps, following providing of the mentioned device, of (a) exposing the pixel's sensor assay site to such material (block 300) , and in conjunction with such exposing, and (b) employing the active nature of the pixel
(block 302) , (c) remotely requesting from the pixel's sensor assay site an assay-result output report (block 304) .
Adding, to what is shown in Fig. 27 , the presence of block 306 shown in Fig. 28, the method pictured effectively in Fig. 27, and just expressed above , can be viewed as further including, in relation to the employing (block 304) step, the included, or related, or linked, step of creating, relative to the mentioned sensor's assay site (in the at least one pixel) a predetermined electromagnetic field environment (block 306) . Fig. 29 shows, in four blocks 308, 3 10 , 3 12 , 3 14 , several other ways of visualizing the practice of the assay performance methodology of the present invention. Looking at this figure from a point of view which focuses on blocks 308 , 3 10 , 3 12 , the invention can be expressed as being a method for performing a fluid-material assay utilizing a pixelated assay matrix wherein each pixel possesses an assay sensor with a functionalized assay site, and is individually and remotely digitally addressable via the presence in the pixel of an active, selectively energizable electronic switching structure which is operatively connected to the sensor and its assay site. The method steps from this viewpoint include , following providing of mentioned matrix device, (a) subjecting the matrix to an environment containing assay fluid in order to effect pixel-sensor assay-site reactions (block 308) , in connection with this subjecting step, (b) remotely, digitally and individually addressing selected pixel's included electronic switching structure (block 3 10) , and (c) , by that addressing step, requesting from the sensors' assay sites in the addressed pixels pixel-specific assay-result output information (block 312) . Adding block 3 14 into the method statement described with regard to blocks 308 , 310 , 312 , this additional block (3 14) illustrates the additional step, which is a consequence of the requesting step, of obtaining from each of the selected pixels' sensors' assay sties a result-output reading of any reaction associated with that pixel's included assay-sensor assay site .
Fig. 30 in the drawings illustrates, at least partially by blocks 3 10, 316, 3 18, a further description of the invention methodology which is based upon use of an assay support device wherein each pixel further includes individually remotely and digitally accessible and energizable electromagnetic field-creating structure that is both associated with the pixel's assay sensor, and also operatively connected to the pixel's included electronic switching structure. This figure describes the methodology, as expressed above in relation to Fig. 29 in an augmented fashion by stating that the addressing step (block 3 10) further includes remotely, digitally and individually accessing and energizing a selected pixel's field-creating structure
(block 3 16) , and by that accessing and energizing step , creating, with respect to each selected pixel, a predetermined, pixel-specific electromagnetic field environment which exists within that pixel in operative proximity to the pixel's associated assay sensor and its associated assay site (block 318) .
Fig. 31 illustrates with a block 320 that, from an additional perspective the just-described "creating" step includes the step of providing at least one of (a) a singular, stable, and (b) a staged, time-variant, electromagnetic field environment of the type generally mentioned in relation to the description of Fig. 30. It is also the case that this producing (block 320) step includes the selectable practice of providing different pixel-specific electromagnetic field environments with respect to different pixels.
Turning attention now to Fig. 32 to Fig. 36, inclusive, and to discussion relevant thereto, these six figures are provided to illustrate issues, and resolutions thereof, involving a specific type of fluid-material assay which is performable in accordance with practice of the present invention. Recognizing that the methodology of the invention may be used with a wide variety of different fluid-material assays, this particular-assay-type illustration will serve , in conjunction with the description of the invention which has been given so far herein, to inform those generally skilled in the art about the versatile utility of the present invention.
Very specifically, the illustration now to be described relates to the performance of a DNA fluid-material assay utilizing a matrix constructed in accordance with the above-described features of micro- structure 20 , and with the pixels in this micro-structure more specifically constructed in accordance with a sensor structure of the cantilever style which is illustrated in Fig. 35 in the drawings.
Even more specifically, the description of this illustrative practice of the invention will be given in the context of utilizing a computer-controlled, environmental heat field employed during the performance of an assay to enrich the obtainability of useful assay-result output information from the illustrative DNA assay. The description given now with respect to utilizing a heat-field device with respect to creating an ambient electromagnetic field in the vicinity of functionalized assay sites, should illustrate, successfully to those skilled in the art, how such a field, or others of the three different types of electromagnetic fields referred to herein, utilized either singly or in different combinations, may help to offer significantly improved output information with respect to the conducting of fluid-material assays.
Additionally, the illustration which now follows respecting a DNA-type assay will be described, at least in part, in the context of varying a heat-field condition during the performance of an assay, and additionally, in the context of taking time-spaced readings, as, for example, by a sampling technique, to include, in addition to a heat-field axis of assay-result output information, also a time-based axis of such information. The area of, and tasks involved with, DNA assays, the issues that this assay field has raised in conventional practice, and the strikingly successful moves toward resolutions of those issues offered by the present invention, dictate why we choose this DNA assay field for a certain amount of illustrative focused discussion herein. These DNA "issues", and our invention's moves toward addressing them resolutely will serve well to convey how the practice of the present invention is shaped to deal especially and innovatively with other fluid-assay areas. Accordingly, the specific DNA assay description which now follows steps briefly into the conventional background of the performance of DNA assays, and does so in a manner, and in a context, which compares the novel utility and versatility of the present invention with prior art DNA assay practice.
In broad-brush terms, a DNA assay, aspects of which are now to be discussed, is performed utilizing a provided, pixelated matrix including appropriately functionalized sensors possessing predetermined (and not necessarily all the same) oligonucleotide probes. This matrix is placed in a suitable fluid-assay environment, such as within a conventional flow-cell, and fluid-assay material is introduced into that environment. A computer which is suitably connected operatively to the matrix's active pixels is employed, as desired, to request assay-result output information on a pixel-by-pixel basis, and also to access and energize the associated, pixel-specific heat-field-creating structures on a time-stable or time-varying basis to add interesting and highly informative output information. We now progress a somewhat more detailed discussion regarding DNA assays through five topical zones, A-E, inclusive, identified by relevant side headings below. The texts relating to these "zones" variously blend the issues of the "past" with resolutions of the "now" offered by the present invention.
A language-term family of DNA art which appears in these texts -- hybridize, hybridized and hybridization -- refers to the assay-important act of affinity bonding which occurs during assay performance between a functionalized assay-site (an oligonucleotide probe in the DNA world) and an assay-fluid component (a DNA or RNA molecule, referred to as a target) .
A. Functionalized Assay Site
Currently, and here discussing conventional heating-based DNA assays, all oligonucleotide probes employed in DNA-assay arrays can only be hybridized at substantially the same temperature, since each such whole array is heated simultaneously during assay performance . Thus, to obtain optimum array performance in the past, it has been essential to design oligonucleotide probes with melting temperatures that lie within a relatively narrow melt-temperature window, usually of about 5°C . This requirement for substantially uniform probe melting temperatures reduces assay flexibility, and puts serious constraints on probe-design algorithms.
Individual heating devices positioned in close vicinity to probes, such as the heat-field-creating structures proposed herein for use in the practice of our present invention, will enable one to hybridize each probe at a different temperature. Thus, instead of initially preparing, within an array of probes, probes with melting temperatures that lie within narrow temperature windows, it becomes possible to utilize individual hybridization temperatures matched to melting temperatures for different probes. Recognizing that practice of the present invention contemplates, in part, pre-assay-per-se-performance provision of a device prepared in advance to have suitably functionalized assay sites associated with pixel-specific assay sensors, one intending to perform a particular DNA assay with such differently melt-temperature functionalized probes may readily specify an appropriate matrix functionalization "pattern" designed to accommodate this requirement. While a matrix supplier may choose different ways to meet such a request, one very effective way for doing so is described in U. S . Patent Application Serial No. 1 1 / 827 , 173 for "Micro-Pixelated Fluid-Assay Structure With On-Board, Addressable, Pixel-Specific Functionalization". The full disclosure content of that patent application is hereby incorporated herein by reference. This option of using melt-temperature differentiation is very significant for some DNA-assay applications where, for example, probes are designed for really short sequences, and there is no easy opportunity for probe selection. A typical example of such an application involves one aimed at the detection of micro-RNA expression important for cancer research.
B. Assay confidence
A major issue relating to conventional DNA-assay arrays is so-called background signal associated with non-specific binding of labeled targets. Such binding can be caused by cross-hybridization of targets with similar heterologous probes, and by random non-specific attachment of targets to probes distributed over a matrix array surface. Cross-hybridization to heterologous probes depends on hybridization temperature, and can be decreased by precise temperature adjustment in the vicinity of probes. In addition, non-specific binding differs from ' specific target-probe hybridization in terms of temperature dependence, and these two processes can be clearly distinguished by utilizing the "additional information axis" capability of the present invention, thereby obtaining a temperature-to-binding dependence category of output information. A detected binding signal that does not match a profile for the specific, intended interaction can be considered to be a false positive signal.
The ability, thus, to perform hybridization of a target DNA or RNA molecule with multiple identical probes at different temperatures, as is readily accommodated by the present invention, allows one to characterize the temperature dependence of target hybridization. This dependence can be used as a fingerprint approach for specific target-probe interactions, and it can be used to discriminate false positive signals on a matrix array. For so-called SNP (Single Nucleotide Polymorphism) assays, those skilled in the relevant art will appreciate that this approach will result in robust distinguishing between mutant and wild-type alleles.
C. SNP Assay
SNP discovery and detection is a very important area of
DNA assay applications in basic research and clinical diagnostics. The ability to distinguish the so-called wild-type DNA target molecule from one that has a single sequence mismatch is based on different target-to-probe binding behaviors at different temperatures. For example,
Fig. 32 shows the typical expected temperature dependence of target-to-probe binding for a wild-type DNA (Owt) , and for three, corresponding mismatches OAt, OAc, and OAg.
This theoretical plot demonstrates that a clear difference in binding for so-called wild-types and mismatches can only be obtained in a relatively broad, rather than in a very narrow, temperature range. If a whole matrix array of probes (of functionalized assay sites) is heated simultaneously, it will thus most probably be quite difficult to achieve optimum distinction for all probes. Each set of probes may require a certain temperature range that is different from those required by other sets of probes.
Generally, the temperature-dependence profiles of target-probe hybridizations, if acquired in accordance with the practice of the present invention where different individual probes essentially "function" at different predetermined temperatures, can readily be read to distinguish not only between wild-type oligonucleotides and mismatches, but also between mismatches. Fig. 33 , which illustrates this, shows representative temperature-to-binding-dependence curves, or plots, that would be obtained typically by using an array of numerous oligonucleotide assay probes for such a set of targets where different probes in this array are designed for, and are hybridized at, different temperatures. Temperature variation in this setting will typically be performed independently for groups of assay sites (probes) that have been commonly functionalized to possess replicates of the same probe. Thus Fig. 33 indicates that the measurement (and plotting) of temperature-to-binding dependence will permit discrimination between the wild type and mismatching sequences as well as among different mismatches.
Assay-site-specific sets of heating elements, as proposed for use in certain pixelated assay devices provided in conjunction with practice of the present invention, will contribute to a way to perform hybridizations at different temperatures for individual probes within one pixelated matrix array, and will result in accommodating the obtaining of temperature-to-binding profiles, like those pictured in Fig. 33 , in a single test assay.
D. Target-to-probe hybridization at time -vary ing temperatures accompanied with real time, time-axis detection
Real-time, time-axis detection that is performed by a sensor and its functionalized assay site at time-varying hybridization temperatures allows one to obtain a unique individual pattern for each target-to-probe interaction. Fig. 34A shows a typical, expected hybridization signal for two different target and probe pairs at a constant temperature.
Saturation of the signal, illustrated in this figure, corresponds to the stage where hybridization equilibrium is achieved. If the two, pictured target-probe pairs I and II have a closely similar sequence (for example, in the case of an SNP assay) , the plots obtained for pairs I and II are difficult to distinguish. If, however, hybridization is performed at time-varying temperatures (Fig. 34B) , the resultant signal-to-time dependence plots have more complicated and perceivably different patterns. Such temperature variations
(field-intensity variations/ variants) are contemplated, of course, as a useful possibility in the practice of the present invention.
At low temperatures, target-to-probe hybridization will cause an increase in a detected binding signal. When the hybridization temperature exceeds the melting point for the subject target-probe pair, hybrids start to denature, causing a corresponding decrease in signal (see generally the right-side portion of Fig. 33) . Thus, real-time detection of hybridization signals at time-varying temperatures can provide unique and readily distinguishable individual characteristics for each target-probe pair. For example, the upper "turn points" of plots I and II in Fig. 34B can be used to distinguish highly similar target sequences . Temperature time varying can also be performed independently for several sensing elements (assay sites) that contain (have been functionalized to contain) replicates of the same probe. In such a case, the rate of temperature increase (ΔT/ Δ time) is different for different replicates . Thus, several signal-to-time dependence plots can be obtained for a particular target-probe pair (see Fig. 35) . These plots form a virtual three-dimensional surface that is a fingerprint characteristic of an analyzed target-probe pair.
These temperature time-varying illustrations not only describe herein a temperature-axis method for performing a
DNA assay, they also illustrate that characteristic of the present invention which enables the obtaining of assay-result output information on a time-based axis, as by sampling on such an axis. E. Active thermal oscillation of a cantilever transducer
Commonly, where a cantilever-style sensor is employed, a relevant cantilever "transducer signal" is associated with detection of a cantilever deflection that is caused by a surface-tension change due to bio-interactions occurring on the cantilever surface at the location of a functionalized assay site. The ability, offered during practice of the present invention, to vary, over time, the temperature in the cantilever vicinity allows for generation of a changing cantilever deflection. Thus, a "temperature oscillation" (see the light-colored, lower solid line in Fig. 36 in relation to the temperature-level axis which appears on the right side of this figure) results in a related, basic oscillation of cantilever response (see the darker, upper solid line in Fig. 36 in relation to the signal-level axis which appears on the left side of this figure) . Binding of bio-molecules to such a cantilever surface at the location of a functionalized assay site changes the signal-axis pattern of the cantilever oscillation (see the dashed line in Fig. 36) . Thus, such an oscillation pattern change can be used for quantification of bio-molecules which are assay-site-captured during an assay.
From the above-discussion regarding the performing of a representative DNA assay wherein pixel-specific electromagnetic-field heat plays a role, and from the invention description given herein, it will be evident to those skilled in the art how other performance approaches may be employed for conducting a DNA assay. For example, instead of using a cantilever-type sensor in a device provided for the purpose of performing such an assay, one could alternatively employ a device having pixels featuring non-cantilever, functionalized assay sites, and offering the use of a pixel-specific light field, and pixel-specific optical detection, to query an assay-site for reaction-output information during a DNA assay. Above-mentioned U . S . Patent Application Serial No . 1 1 / 827, 173 fully describes this kind of DNA-assay approach. Further evident to those skilled in the art will be the fact that more than a single type of electromagnetic field may be employed in the practice of a DNA assay. For example, combined fields of light and heat, or other plural-combined fields, may be utilized. The DNA-specific-assay discussion just presented above will also arm those skilled in the art with a clear understanding of how various non-DNA fluid-material assays may be conducted using the methodology proposed by the present invention. Accordingly, a preferred and best mode manner of practicing the present invention, and several modifications thereof, have been illustrated and described herein. From these disclosures, those skilled in the relevant art will appreciate the numerous advances and advantages which are offered by the invention in relation to the carrying out of various different types of fluid-material assays.
In general terms, the present invention may be described as a method of performing a fluid-material assay employing an appropriately provided (i.e . , made available) computer-accessible device (note the discussion above) -- preferably a pixelated matrix device, including at least one active digitally-addressable pixel having a sensor with a digitally-addressable assay site functionalized for selected fluid-assay material, with the key steps of this method including, following, of course, providing such a device, exposing the pixel's sensor assay site to such material, and in conjunction with such exposing, and employing the computer-accessible, active nature of the provided device's pixel, remotely and digitally requesting from the pixel's sensor assay site an assay-result output report. The basic methodology further includes, in relation to the mentioned employing step, creating, relative to the sensor's assay site in the at least one pixel, a predetermined, pixel-specific electromagnetic field environment. The creation of such an environment is enabled by the type of matrix structure of this invention, and is specifically enabled by the presence in the described matrix pixels of one or several digitally accessible and energizable electromagnetic field-creating structure(s) . The embodiments and concrete examples of implementation discussed in the foregoing detailed explanation serve solely to illustrate the technical details of the present invention, which should not be narrowly interpreted within the limits of such embodiments and concrete examples, but rather may be applied in many variations within the spirit of the present invention, provided such variations do not exceed the scope of the patent claims set forth below.

Claims

1. A pixel-by-pixel, digitally-addressable, pixelated, precursor, fluid-assay, active-matrix micro-structure including plural pixels formed on a substrate, wherein each pixel comprises: at least one non-functionalized, digitally-addressable assay sensor, and disposed operatively adjacent said sensor, digitally-addressable and energizable electromagnetic field-creating structure which is selectively energizable to create, in the vicinity of said at least one assay sensor, an ambient electromagnetic field environment which is structured to assist in functionalizing, as a possession on said at least one assay sensor, at least one digitally-addressable assay site which will display an affinity for a selected fluid-assay material.
2. The micro-structure of claim 1 , wherein: the mentioned ambient electromagnetic field environment is characterized by at least one of (a) light, (b) heat, and (c) electrical non-uniformity.
3. The micro-structure of claim 2 , wherein: with respect to the mentioned plurality of pixels, the respective field-creating structures included within these pixels are selectively energizable in functionalizing-assistance manners whereby different assay sites, on different, associated pixel-assay sensors, may be functionalized to display respective affinities for different fluid-assay materials.
4. The micro-structure of claim 1 , wherein: with respect to the mentioned plurality of pixels, the respective field-creating structures included within these pixels are selectively energizable in functionalizing-assistance manners whereby different assay sites, on different, associated pixel-assay sensors, may be functionalized to display respective affinities for different fluid-assay materials.
5. The micro-structure of claim 4 , wherein: the mentioned, respective field-creating structures are constructed in such a fashion that different selected pixels may include respective assay sensors which are structured each to possess, ultimately, plural functionalized assay sites.
6. The micro-structure of claim 1 , wherein: at least one of said pixels includes a plurality of non-functionalized, digitally-addressable assay sensors.
7. The micro-structure of claim 1 , wherein: said at least one assay sensor includes a micro-deflection device.
8. The micro-structure of claim 7, wherein: at least one of the plural pixels further comprises digitally-addressable electrical signaling structure which is
(a) operatively associated with said micro-deflection device, and (b) operable to produce an electrical signal which is related to any deflection of the micro-deflection device.
9. The micro-structure of claim 7, wherein: said micro-deflection device takes the form of a cantilever structure.
10. The micro-structure of claim 9 , wherein: said cantilever structure takes the form of a crystalline-structure-processed portion of an internal crystalline-structure-processable material body which has been (a) volume-and-configuration-defined in a selected region of that body, and (b) , in that selected region, processed by internal crystalline-structure processing to possess predetermined mechanical deflection characteristics.
1 1 . The micro-structure of claim 2 , wherein: the electromagnetic field-creating structure which is energizable to create an ambient electromagnetic field environment characterized by light takes the form of a light source possessing an optical medium and a light-source-energizing semiconductor device.
12. The micro-structure of claim 1 1 , wherein: said optical medium is organized in a vertical-stack-style light-emitting device.
13. The micro-structure of claim 1 1 , wherein: said optical medium is organized in a horizontal-style light-emitting device .
14. The micro-structure of claim 1 , wherein: the electromagnetic field-creating structure which is energizable to create an ambient electromagnetic field environment characterized by light takes the form of a light source characterized as an output port in an optical beam device which is supplied, via a pixel-integrated optical switching device, with a thereby selectively switchable flow of light furnished via a substrate-supported optical beam structure which is operatively coupleable with an off-pixel light supply.
15. The micro-structure of claim 1 , wherein: said substrate is a glass or plastic substrate, and each pixel is formed on said substrate utilizing low-temperature TFT and Si technology.
16. The micro-structure of claim 10 , wherein: said internal crystalline-structure-processable material body is a Si-material body, and said Si-material body has been processed by low-temperature internal crystalline-structure processing.
17. Fluid-material assay precursor structure comprising: a low-temperature substrate having a surface, and a matrix distribution of precursor assay pixels formed on said surface, each pixel including thin-film, digitally addressable electronic switching structure activatable to play an operative role in at least one of (a) pixel functionalization and, ultimately (b) assay-result information outputting.
18. A method of producing on a supporting substrate a precursor, active-matrix, fluid-assay micro-structure comprising: establishing a matrix array of non-functionalized pixels, and preparing at least one of these pixels for individual and internal, digitally-addressed (a) functionalization, and (b) reading out, ultimately, of completed assay results.
19. The method of claim 18, wherein said preparing includes providing each pixel in the established array with a digitally-addressable (a) non-functionalized assay sensor, and
(b) independent, electromagnetic field-creating structure disposed adjacent that pixel.
20. A method for producing a remotely digitally-addressable, pixelated, precursor, active-matrix, fluid-assay micro-structure comprising: establishing, on a supporting substrate, an array of plural, non-assay-functionalized pixels, and preparing each substrate-established pixel with electronically digitally-addressable electronic structure designed to effect, for and with respect to that pixel, and under the selection and control of a user, at least one of (a) selective, independent, fluid-assay-material-specific functionalization, and (b) assay-result output reading, utilizing, at least in part, communicative, electronic interaction between that pixel and a digital computer.
2 1 . The method of claim 20 , wherein: said preparing includes ( 1 ) providing each pixel with at least (a) one electronically, digitally-addressable assay sensor operatively connected to (b) also so provided electronically digitally-addressable electronic switching structure, with the provided assay sensor being thereby constructed to host at least one electronically, digitally-addressable, ultimately functionalizable assay site, and (2) forming within each pixel an electronically, digitally-addressable electromagnetic field-creating structure also operatively connected to the provided electronic switching structure, and which is selectively energizable by such a computer to participate in at least one of ( 1 ) pixel functionalization, and (2) assay-result output reading with regard to a functionalized pixel.
22. The method of claim 2 1 , wherein: said forming of a field-creating structure includes constructing, within each pixel, at least one of (a) a light-field-creating subcomponent, (b) a heat-field-creating subcomponent, and (c) a non-uniform-electrical-field-creating subcomponent.
23. The method of claim 22 , wherein: said constructing, if of a light-field-creating subcomponent, includes making a pixel on-board light source .
24. The method of claim 22 , wherein: said constructing, if of a light-field-creating subcomponent, includes making a pixel-communicative , on-substrate, optical beam structure adapted for optical coupling to an off-pixel light source.
25. The method of claim 2 1 , wherein: said providing of each pixel with the mentioned at least one assay sensor includes fabricating that sensor within the pixel as a micro-deflection device .
26. The method of claim 25 , wherein: said providing further includes producing, on the fabricated micro-deflection device, a remotely, electronically, digitally-addressable electrical signaling structure which is operable to generate an electrical signal related to deflection of the micro-deflection device.
27. The method of claim 25 , wherein: said fabricating of the mentioned micro-deflection device takes the form of creating a cantilever structure .
28. The method of claim 18, wherein: said step of establishing the matrix array on the substrate is carried out using low-temperature TFT and Si technology.
29. The method of claim 20, wherein: said step of establishing the array is carried out using low-temperature TFT and Si technology on the supporting substrate made of glass or plastic.
30. A method of producing a fluid-material assay precursor structure comprising: providing a low-temperature substrate having a surface , and forming a matrix distribution of precursor assay pixels on said surface, with each pixel including thin-film, digitally addressable electronic switching structure activatable to play an operative role in at least one of (a) pixel functionalization and, ultimately, (b) assay-result information outputting.
31 . A pixel-by-pixel digitally-addressable, pixelated, fluid-as l say, active-matrix micro- structure including plural pixels formed on a substrate, wherein each pixel comprises : at least one functionalized, digitally-addressable assay sensor including at least one functionalized, digitally-addressable assay site which has been affinity-functionalized to respond to a selected, specific fluid-assay material, and disposed operatively adjacent said at least one assay sensor and its associated at least one assay site, - I l l -
digitally-addressable and energizable electromagnetic field-creating structure which is selectively energizable to create, in the vicinity of said at least one assay sensor and its associated at least one assay site, a selected, ambient, electromagnetic field environment which is structured to assist, selectively and optionally only, in the reading-out of an assay-result response from said at least one assay sensor and its associated said at least one assay site.
32. The micro- structure of claim 3 1 , wherein: said electromagnetic field-creating structure is designed to create an electromagnetic field environment which is characterized by at least one of (a) light, (b) heat, and (c) electrical non-uniformity.
33. The micro-structure of claim 32 , wherein: said electromagnetic field-creating structure includes field-creating subcomponents each structured to create one of (a) a field of light, (b) a field of heat, and (c) a field of electrical non-uniformity.
34. The micro-structure of claim 3 1 , wherein: at least certain ones of the plural, digitally-addressable pixels are constructed each to include a functionalized, digitally-addressable assay sensor which possesses plural, digitally-addressable, differently-affinity-functionalized assay sites.
35. The micro-structure of claim 31 , wherein: at least certain ones of the plural, digitally-addressable pixels are constructed each to include plural, functionalized, digitally-addressable assay sensors, each of which possesses at least one functionalized, digitally-addressable assay site .
36. The micro-structure of claim 31 , wherein: said at least one assay sensor includes a micro-deflection device.
37. The micro-structure of claim 36, which further comprises digitally-addressable electrical signaling structure
(a) operatively associated with said micro-deflection device, and (b) operable to produce an electrical signal related to any deflection of the micro-deflection device.
38. The micro-structure of claim 36, wherein: said micro-deflection device takes the form of a cantilever structure.
39. The micro-structure of claim 38, wherein: said cantilever structure takes the form of a crystalline-structure-processed portion of an internal crystalline-structure-processable material body which has been (a) volume-and-configuration-defined in a selected region of that body, and (b) , in that selected region, processed by internal crystalline-structure processing to possess predetermined mechanical deflection characteristics.
40. The micro-structure of claim 33 , wherein: the electromagnetic field-creating subcomponent which is structured to create an ambient electromagnetic field environment characterized by light takes the form of a light source possessing an optical medium and a light-source-energizing semiconductor device.
41. The micro-structure of claim 40 , wherein: said optical medium is organized in a vertical-stack-style light-emitting device.
42. The micro-structure of claim 40, wherein: said optical medium is organized in a horizontal-style light-emitting device.
43. The micro-structure of claim 33 which further includes a substrate-supported, optical beam structure which is operatively coupleable with an off-pixel light supply, and wherein the electromagnetic field-creating subcomponent which is structured to create an ambient electromagnetic field environment characterized by light takes the form of an output port in a digitally-addressable and switchable optical beam device which is operatively coupled to said optical beam structure.
44. The micro-structure of claim 3 1 , wherein: said substrate is a glass or plastic substrate, and each pixel is formed on said substrate utilizing low-temperature
TFT and Si technology.
45. The micro-structure of claim 39 , wherein: said internal crystalline-structure-processable material body is a Si-material body, and said Si-material body has been processed by low-temperature internal crystalline-structure processing.
46. A fluid-material assay structure comprising: a low-temperature substrate having a surface , and a matrix distribution of functionalized assay pixels formed on said surface, each pixel including thin-film, digitally addressable electronic switching structure activatable to play an operative role in assay-result information outputting.
47. A method for producing on a supporting substrate an active-matrix, fluid-assay micro-structure comprising: establishing an array of digitally-addressable , assay-material-specific, internally-functionalizable pixels, and employing pixel-specific digital addressing for selected, array-established pixels, individually functionalizing these pixels.
48. The method of claim 47, wherein: said functionalizing of a selected pixel includes individually and controllably bathing that pixel with a selected-character electromagnetic field.
49. A method for producing a remotely digitally-addressable, pixelated, active-matrix, fluid-assay micro-structure comprising: establishing, on a supporting substrate, an array of plural pixels, preparing each established pixel with included, digitally-addressable electronic structure designed to effect, for and with respect to that pixel, and under the control of an appropriately operatively connected digital computer, at least one of (a) selective, independent, fluid-assay-material-specific functionalization, and (b) assay-result output reading, operatively connecting such a computer to the electronic structure which is associated with at least one of the established and prepared pixels, employing the operatively connected computer, digitally addressing the electronic structure in the at least one associated pixel, and by said addressing, effecting at least one of (a) selected fluid-assay-material-specific functionalizing, and (b) assay-result output reading of at least one pixel.
50. The method of claim 49, wherein: said preparing includes providing each pixel with an electronically, digitally-addressable assay sensor, and which further comprises forming within each pixel an electronically, digitally-addressable electromagnetic field-creating structure.
51. The method of claim 50, wherein: said forming of a field-creating structure includes constructing, within each pixel, at least one of (a) a light-field-creating subcomponent, (b) a heat-field-creating subcomponent, and (c) a non-uniform-electrical-field-creating subcomponent.
52. The method of claim 51 , wherein: said constructing, if of a light-field-creating subcomponent, includes making a pixel on-board light source.
53. The method of claim 5 1 , wherein: said constructing, if of a light-field-creating subcomponent, includes making a pixel-communicative , on-substrate, optical beam structure adapted for optical coupling to an off-pixel light source.
54. The method of claim 50, wherein: said providing of each pixel with the mentioned at least one assay sensor includes fabricating that sensor within the pixel as a micro-deflection device .
55. The method of claim 54, wherein: said providing further includes producing, on the fabricated micro-deflection device, a remotely, electronically, digitally-addressable electrical signaling structure which is operable to generate an electrical signal related to deflection of the micro-deflection device.
56. The method of claim 54, wherein: said fabricating of the mentioned micro-deflection device takes the form of creating a cantilever structure.
57. The method of claim 47 , wherein: said step of establishing the matrix array on the substrate is carried out using low-temperature TFT and Si technology.
58. The method of claim 49 , wherein: said step of establishing the array is carried out using low-temperature TFT and Si technology on the supporting substrate made of glass or plastic.
59. A method of making a fluid-material assay structure comprising : providing a low-temperature substrate having a surface, and forming a matrix distribution of assay pixels on said surface, with each pixel including thin-film, digitally addressable electronic switching structure activatable to play an operative role in pixel functionalization, and respecting each pixel, digitally activating the associated switching structure in a process involving functionalizing of the pixel.
60. A method of performing a fluid-material assay employing a device including at least one active pixel having a sensor with an assay site functionalized for selected fluid-assay material comprising: exposing the pixel's sensor assay site to such material, and in conjunction with said exposing, and employing the active nature of the pixel, remotely requesting from the pixel's sensor assay site an assay-result output report.
61 . The method of claim 60 which further comprises, in relation to said employing, creating, relative to the sensor's assay site in the at least one pixel, a predetermined, pixel-specific electromagnetic field environment.
62. The method of claim 61 , where said creating is a linked function of said employing.
63. A method for performing a fluid-material assay utilizing a pixelated assay matrix wherein: each pixel possesses an assay sensor with a functionalized assay site, and is individually remotely digitally addressable via the presence in the pixel of an active, selectively energizable electronic switching structure which is operatively connected to the sensor and its assay site, said method comprising: subjecting the matrix to an environment containing assay fluid in order to effect pixel- sensor assay-site assay reactions, in conjunction with said subjecting, remotely, digitally and individually addressing selected pixels' included electronic switching structures, and by said addressing, requesting from the sensors' assay sites in the addressed pixels' pixel-specific assay-result output information.
64. The method of claim 63, wherein each pixel further includes individually remotely and digitally accessible and energizable electromagnetic field-creating structure which is both associated with the pixel's assay sensor, and operatively connected to the pixel's included electronic switching structure, and said addressing further includes remotely, digitally and individually accessing and energizing the selected pixels' respective field-creating structures, and by said accessing and energizing, creating, with respect to each such selected pixel, a predetermined, pixel-specific electromagnetic field environment which exists within that pixel in operative proximity to the pixel's associated assay sensor and the associated assay site.
65. The method of claim 63 which further comprises, as a consequence of said requesting, obtaining from each of such selected pixels' sensors' assay sites a result-output reading of any assay reaction associated with that pixel's included assay-sensor assay site.
66. The method of claim 65, wherein: each pixel further includes individually remotely and digitally accessible and energizable electromagnetic field-creating structure which is both associated with the pixel's assay sensor, and operatively connected to the pixel's included electronic switching structure, and said addressing further includes remotely, digitally and individually accessing and energizing the selected pixels' respective field-creating structures, and by said accessing and energizing, creating, with respect to each such selected pixel, a predetermined, pixel-specific electromagnetic field environment which exists within that pixel in operative proximity to the pixel's associated assay sensor and the associated assay site.
67. The method of claim 66, wherein: said creating includes producing at least one of (a) a singular, stable, and (b) a staged, time-variant, electromagnetic field environment in the vicinity of the associated assay sensor's assay site .
68. The method of claim 66, wherein: said creating includes producing different pixel-specific electromagnetic field environments with respect to different pixels.
69. The method of claim 68 , wherein: said producing involves specifically producing, with respect to each of such different pixels, at least one of (a) a singular stable, and (b) a staged, time-variant, electromagnetic field environment in the vicinity of the associated assay sensor's assay site.
70. The method of claim 63 , wherein: each pixel further includes individually remotely and digitally accessible and energizable electromagnetic field-creating structure which is both associated with the pixel's assay sensor, and operatively connected to the pixel's included electronic switching structure, with each such field-creating structure taking the form of at least one of ( 1 ) a heat source, (2) a light source , and (3) a non-uniform electrical field source, and said addressing further includes remotely, digitally and individually accessing and energizing the selected pixels' respective field-creating structures, and by said accessing and addressing, creating, with respect to each such selected pixel, a predetermined, pixel-specific electromagnetic field environment which exists within that pixel in operative proximity to the pixel's associated assay sensor and the associated assay site.
71. The method of claim 65, wherein: each pixel further includes individually remotely and digitally accessible and energizable electromagnetic field-creating structure which is both associated with the pixel's assay sensor, and operatively connected to the pixel's included electronic switching structure, with each such field-creating structure taking the form of at least one of ( 1 ) a heat source, (2) a light source, and (3) a non-uniform electrical field source, and said addressing further includes remotely, digitally and individually accessing and energizing the selected pixels' respective field-creating structures, and by said accessing and energizing, creating, with respect to each such selected pixel, a predetermined, pixel-specific electromagnetic field environment which exists within that pixel in operative proximity to the pixel's associated assay sensor and the associated assay site .
72. The method of claim 71 , wherein: said creating includes producing at least one of (a) a singular, stable, and (b) a staged, time-variant, electromagnetic field environment in the vicinity of the associated assay sensor's assay site .
73. The method of claim 71 , wherein: said creating includes producing different, pixel-specific electromagnetic field environments with respect to different pixels.
74. The method of claim 73, wherein: said producing involves specifically producing, and with respect to each of such different pixels, at least one of (a) a singular, stable, and (b) a staged, time-variant, electromagnetic field environment in the vicinity of the associated assay sensor's assay site.
75. A method of performing a fluid-material assay comprising: providing a device including at least one active pixel having a sensor with an assay site functionalized for selected fluid-assay material, exposing the pixel's sensor assay site to such material, and in conjunction with said exposing, and employing the active nature of the pixel, remotely requesting from the pixel's sensor assay site an assay-result output report.
76. The method of claim 75 , wherein: said providing further includes furnishing such a device which additionally includes energizable electromagnetic field-creating structure, and which further comprises, in relation to said employing, creating, relative to the sensor's assay site in the at least one pixel, a predetermined, pixel-specific electromagnetic field environment.
PCT/JP2007/070021 2006-10-06 2007-10-05 Micro-pixelated fluid-assay structure, micro-pixelated fluid-assay precursor structure, and making method and performing method thereof Ceased WO2008044779A1 (en)

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US84987506P 2006-10-06 2006-10-06
US60/849,875 2006-10-06
US11/827,174 US8231831B2 (en) 2006-10-06 2007-07-10 Micro-pixelated fluid-assay structure
US11/827,335 US8236245B2 (en) 2006-10-06 2007-07-10 Micro-pixelated fluid-assay precursor structure
US11/827,176 2007-07-10
US11/827,335 2007-07-10
US11/827,175 US8236571B2 (en) 2006-10-06 2007-07-10 Method of making micro-pixelated fluid-assay precursor structure
US11/827,174 2007-07-10
US11/827,175 2007-07-10
US11/827,176 US8232108B2 (en) 2006-10-06 2007-07-10 Method of making micro-pixelated fluid-assay structure
US11/888,491 US8232109B2 (en) 2006-10-06 2007-07-31 Micro-pixelated active-matrix fluid-assay performance
US11/888,491 2007-07-31

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