TWI647842B - Chemical device with thin conductive element - Google Patents

Abstract

An embodiment of the invention discloses a chemical device comprising a chemically sensitive field effect transistor comprising a floating gate structure, the floating gate structure comprising a plurality of floating gate conductors electrically coupled to each other; a conductive element, And covering the floating gate conductor of the uppermost layer of the plurality of floating gate conductors, the conductive element being wider and thinner than the floating gate conductor of the uppermost layer; and a dielectric material, Its definition extends to one of the upper surfaces of one of the conductive elements.

Description

Chemical device with thin conductive elements

The present invention generally relates to sensors for chemical analysis, as well as methods of making the aforementioned sensors.

There are many types of chemical devices that have been used for the detection of chemical processes. One type is a chemically sensitive field effect transistor (chemFET). The chemically sensitive field effect transistor comprises a source and a drain separated by a channel, and a chemically sensitive region coupled to the channel region. The role of chemically sensitive field effect transistors is based on the regulation of channel conductivity caused by changes in charge in the sensitive region caused by chemical reactions occurring in the vicinity of sensitive regions. The adjustment of the conductivity of the aforementioned channel changes the threshold voltage of the chemically sensitive field effect transistor, which can be measured and used to detect and/or determine the characteristics of the aforementioned chemical reaction. The measurement of the threshold voltage can be performed, for example, by applying appropriate bias voltages to the source and drain electrodes, and then measuring the current generated by the chemically sensitive field effect transistor. For another example, by driving a known current through the chemically sensitive field effect transistor, the voltage generated at the source or drain is then measured.

An ion-sensitive field effect transistor (ISFFT) is a type of chemically sensitive field effect transistor that includes an ion sensitive layer in a sensitive region. The presence of ions in the analyte solution changes the surface potential of the interface between the ion sensitive layer and the analyte solution due to the presence of ions in the analyte solution that can cause protonation or deprotonation of the surface charge group. The change in surface potential in the sensitive region of the ion-sensitive field effect transistor affects the threshold voltage of the device, which can It is measured to indicate the presence of ions and/or the concentration of ions in the solution. An ion sensitive field effect transistor array can be used to monitor chemical reactions, such as DNA sequencing reactions, depending on the presence, generation, or use of ions during the detection reaction. For example, see U.S. Patent No. 7,948,015 to Rothberg et al., which is incorporated herein in its entirety by reference. More generally, large arrays of chemically sensitive field effect transistors or other types of chemical devices can be used to detect and measure the static and/or dynamic properties of various analytes (eg, hydrogen ions, other ions, compounds, etc.) in a variety of processes. Quantity or concentration. The process is, for example, biological or chemical reaction, cell or tissue culture or monitoring of neural activity, nucleic acid sequencing, and the like.

When operating a large-scale array of chemical devices, there is a problem that the sensor output signal is susceptible to noise. Specifically, the noise affects the correctness of the downstream signal processing, which is used to determine the characteristics of the chemical and/or biological processes detected by the sensor. Accordingly, the present invention contemplates providing a device that includes a low noise chemical device and a method for fabricating the foregoing device.

An embodiment of the invention discloses a chemical device comprising a chemically sensitive field effect transistor comprising a floating gate structure, the floating gate structure comprising a plurality of floating gate conductors electrically coupled to each other; a conductive element, And covering the floating gate conductor of the uppermost layer of the plurality of floating gate conductors, the conductive element being wider and thinner than the floating gate conductor of the uppermost layer; and a dielectric material, Its definition extends to one of the upper surfaces of one of the conductive elements. In an exemplary embodiment, the electrically conductive element comprises at least one of titanium, tantalum, titanium nitrite, and aluminum, and/or oxides and/or mixtures thereof. In an exemplary embodiment, the distance between adjacent ones of the conductive elements in the chemical device is about 0.18 microns. In an exemplary embodiment, the conductive element has a thickness of between about 0.1 and 0.2 microns. In an exemplary embodiment, the thickness of the uppermost floating gate conductor of the plurality of floating gate conductors is greater than the thickness of the other of the plurality of floating gate conductors. In an exemplary embodiment, the conductive element comprises a different material The material of the floating gate conductor at the uppermost layer. In another embodiment, an inner surface of the dielectric material and the upper surface of the electrically conductive element define an outer surface of one of the reaction regions of the chemical device. In another embodiment, the floating gate conducting systems are in a layer and the layer comprises a plurality of array lines and a plurality of bus lines. In one embodiment, the chemical device further includes a sensor region having the chemically sensitive field effect transistor and a peripheral region having a peripheral circuit for obtaining a signal from the chemically sensitive field effect transistor . In one embodiment, the conductive element is in a conductive layer and the conductive layer is only located in the sensor region. In an embodiment, the electrically conductive element comprises a material that is not located in the peripheral region. In an exemplary embodiment, the chemically sensitive field effect transistor includes a floating gate structure including a plurality of conductors, the plurality of floating gate conduction systems being electrically coupled to each other and separated by a plurality of dielectric layers, And the floating gate conductor can be the conductor of the uppermost layer of the plurality of conductors. In another embodiment, one of the first layers of the dielectric material is tantalum nitride, and the second layer is at least one of cerium oxide and tetraethyl ortho-ruthenium, the second layer Define the plurality of sidewalls of the opening. In one embodiment, the chemical device further comprises a microfluidic structure in fluid flow communication with the chemically sensitive field effect transistor and for providing an analyte for sequencing.

An exemplary embodiment of the present invention discloses a method of fabricating a chemical device, the method comprising forming a chemically sensitive field effect transistor comprising a floating gate structure, the floating gate structure comprising a plurality of mutually electrically coupled a floating gate conductor; the method further comprising forming a conductive element covering and communicating with the uppermost one of the plurality of floating gate conductors, the conductive element being higher than the uppermost floating gate The pole conductor is wider and thinner; the method further includes forming a dielectric material defining an opening extending to one of the upper surfaces of the conductive member. In an exemplary embodiment, the upper surface of the electrically conductive element defines a lower surface of one of the reaction regions of the chemical device. In another embodiment, an inner surface of the dielectric material and the upper surface of the conductive element define an outer boundary of a reaction region of the chemical device. In still another embodiment, the conductive element is formed in a conductive layer, and The conductive layer is only located in one of the sensor regions of the chemical device.

The embodiments of the present invention are described in detail in the specification and drawings, and other features, embodiments, and advantages of the present invention are described in the specification, drawings, and claims.

100‧‧‧Integrated circuit device

101‧‧‧ flow cell

102‧‧‧ entrance

103‧‧‧Export

104, 109, 111‧‧‧ channels

105‧‧‧Mobile room

106‧‧‧Waste container

107‧‧‧Microwell array

108‧‧‧ reference electrode

110‧‧‧ washing solution

112‧‧‧Valves

114‧‧‧Reagents

116‧‧‧Valve block

118‧‧‧ Fluid Controller

Lines 120, 122, 126‧‧

124‧‧‧Array controller

127‧‧‧ bus bar

128‧‧‧User Interface

205‧‧‧Sensor array

208‧‧‧reagent flow

301, 302‧‧‧Reaction area

303, 319, 1316, 503‧‧‧ dielectric materials

307‧‧‧Conductive components

307a‧‧‧ Upper surface of conductive components

312‧‧‧ Solid support

318‧‧‧Floating gate structure

320‧‧‧Sensor board

320H‧‧‧ thickness of the sensor board

320L‧‧‧the length of the sensor board

321‧‧‧ source area

322‧‧‧Bungee area

323‧‧‧Channel area

324‧‧‧Charge

333‧‧‧Distance between adjacent conductive elements in chemical installations

334‧‧‧ thickness of conductive elements

335‧‧‧The thickness of the uppermost floating gate conductor

335'‧‧‧ Thickness of other floating gate conductors

340‧‧‧Diffusion mechanism

350, 351, 1500‧ ‧ chemical devices

352‧‧‧ gate dielectric layer

354‧‧‧Semiconductor substrate

400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400‧‧‧ structures

618, 620, 1418, 1420‧‧

630‧‧‧ distance

704, 805, 1107‧‧‧ conductive materials

1006‧‧‧through hole barrier liner

1208, 1210, 1212‧‧

1220‧‧‧Interval between conductive elements

1220'‧‧‧Interval between sensor boards

1230H‧‧‧ thickness of conductive components

1230L‧‧‧The length of the conductive element

1316a‧‧‧ Inner surface of dielectric material

1501‧‧‧Sensor area

1503‧‧‧ surrounding area

1 is a block diagram of one of the components of a nucleic acid sequencing system in accordance with an exemplary embodiment.

2 is a partial cross-sectional view of an integrated circuit device and a flow cell in accordance with an exemplary embodiment.

3 is a cross-sectional view of a representative chemical device and corresponding reaction regions, in accordance with an exemplary embodiment.

4 through 14 are schematic diagrams showing stages of a fabrication process for forming an array of chemical devices and their corresponding well structures in accordance with an exemplary embodiment.

15 is a block diagram of an exemplary chemical device in accordance with an exemplary embodiment, wherein the chemical device includes an example sensor region and an exemplary peripheral region.

The chemical device of the present invention includes a low noise chemical device, such as a chemically-sensitive field effect transistor, for detecting a chemical reaction in the surface layer thereof, and operatively matching the reaction region. An inductor of a chemical device can include a plurality of floating gate conductors having a sensing layer deposited on the uppermost floating conductor of the plurality of floating gate conductors. Applicants have found, however, that the addition of additional layers on the uppermost floating conductors dedicated to sensing a plurality of floating gate conductors can have the technical challenge of overcoming and the cost advantages of additional layers. For example, Applicants have discovered that the advantages of the chemical devices described herein include providing margins for enhanced lithography processes; (eg, avoiding misalignment of openings and/or burnouts); and providing larger openings in the dielectric. So that it can set the sensing area directly on top of the uppermost floating gate conductor (for example, Larger openings accommodate more signals).

The exemplary chemical device described herein has a sensing surface area that can include a dedicated sensing layer. In the embodiments described herein, a conductive element covers and communicates with the uppermost floating gate conductor, since the uppermost floating gate conductor can be used to provide array lines (eg, word lines, bit lines, etc.) and The bus bar for accessing/powering the chemical device, the uppermost floating gate conductor should be of suitable material or mixed material and should have sufficient thickness. Since the conductive elements are disposed in different layers of the substrate of the chemical device, the conductive elements can be used as a dedicated sensing surface area, and can be independent of the material and thickness of the uppermost floating gate conductor; for example, the conductive elements can Farther than the uppermost floating gate conductor, such that the sensing surface area can be relatively large; for example, the conductive element can be thinner than the uppermost floating gate conductor, such that the sensing surface area can be improved Sensitivity. Therefore, the low noise chemistry apparatus can provide a high density array so that the reaction characteristics can be accurately detected.

In addition, the uppermost floating gate conductor does not require an impact process limitation, such as when adjacent floating gate conductors should have a suitable thickness (ie, low resistance) to carry high current between adjacent floating gate conductors. The space does not need to be the minimum space allowed by the process design rules. The material used for the uppermost floating gate conductor should be suitable for high currents. Since the conductive elements are on different layers of the uppermost floating gate conductor, the step of providing a conductive element in contact with and communicating with the uppermost floating gate conductor can provide a great degree of freedom in the selection of the material of the conductive element. .

1 is a block diagram of an element of a nucleic acid sequencing system including a flow cell 101 on an integrated circuit device 100, a reference electrode 108, and a plurality of sequences for sequencing, in accordance with an exemplary embodiment. Reagent 114, a valve block 116, a wash solution 110, a valve 112, a fluid controller 118, a line 120/122/126, a channel 104/109/111, a waste container 106, an array controller 124, and a User interface 128. Integrated circuit device 100 includes a microwell array 107 for overlaying a sensor array including as described herein Learning device. The flow cell 101 includes an inlet 102, an outlet 103, and a flow chamber 105 for defining a flow path for reagents in the microwell array 107. The reference electrode 108 can be of any suitable type or shape, including a concentric cylinder having a fluid passage or a wire inserted into the lumen of the passage 111. The reagent 114 can be driven through the fluid passage, valve, and flow cell 101 using a pump, air pressure, or other suitable method, and can be disposed of to the waste container 106 after exiting the outlet 103 of the flow cell 101. Fluid controller 118 may utilize appropriate software to control the driving force of reagent 114 and the operation of valve 112 and valve block 116. The microwell array 107 includes an array of reaction zones as described herein, also referred to herein as microwells, that operatively cooperate with chemical devices in respective sensor arrays. For example, each reaction zone can be coupled to a chemical device adapted to detect analytes of interest or reaction characteristics within the reaction zone. The microwell array 107 can be integrated into the integrated circuit device 100 such that the microwell array 107 and the sensor array are part of a single device or wafer. The flow cell 101 can have a variety of configurations for controlling the path and flow rate of the reagent 114 on the microwell array 107. The array controller 124 provides bias and timing control signals to the integrated circuit device 100 for reading the chemical devices of the sensor array. Array controller 124 also provides a reference bias applied to reference electrode 108 to bias reagent 114 flowing through microwell array 107.

In an experimental example, the array controller 124 collects signals outputted from the output ports of the integrated circuit device 100 and from the chemical devices of the sensor array through the bus bar 127, and processes the signals. The array controller 124 can be a Computer or other computing device. The array controller 124 can include memory for storing data and software applications, a processor for accessing data and executing applications, and components for facilitating communication between components of the system as shown in FIG. . The value of the output signal of the chemical device represents one or more physical and/or chemical parameters of the reaction occurring in the reaction zone in the corresponding microwell array 107. For example, in an exemplary embodiment, the value of the output signal can be U.S. Patent Application Serial No. 13/339,846, filed on Dec. 29, 2011, filed on Dec. January U.S. Patent Application Serial No. 61/429, 328, filed on filed on Jan. 3, and the disclosure of the disclosure of the entire disclosure of the disclosure of the entire disclosure of the entire disclosure of the entire disclosure of The processing of the priority of the U.S. Patent Application Serial No. 61/428,097, filed on Jan The user interface 128 can display output signals received about the flow cell 101 and the chemical devices in the sensor array of the integrated circuit device 100. The user interface 128 can also display instrument settings and controls and allow the user Enter or set instrument settings and controls.

In an exemplary embodiment, during the experiment, the fluid controller 118 may control the delivery of the individual reagents 114 to the flow cell 101 and the integrated circuit device 100, which may be performed in accordance with a predetermined sequence, a predetermined duration, a predetermined flow rate. delivery. The array controller 124 can collect and analyze the output signal of the chemical device, which indicates the chemical reaction that occurs in response to the delivered reagent 114. During the experiment, the system can also monitor and control the temperature of the integrated circuit device 100. The reaction can be carried out and measured at a known predetermined temperature; the system can be configured to allow a single fluid or reagent to contact the reference electrode 108 during the entire multi-step reaction process during operation. Valve 112 can be closed to prevent any wash solution 110 from flowing into passage 109 as reagent 114 flows. Although the flow of the wash solution can be stopped, there is still uninterrupted fluid and electrical communication between the reference electrode 108, the channel 109, and the microwell array 107, between the reference electrode 108 and the junction between the channels 109 and 111. The distance can be selected such that little or no reagent flows through the channel 109 and may diffuse into the channel 111 and reach the reference electrode 108. In an exemplary embodiment, the wash solution 110 can be selected to be in continuous contact with the reference electrode 108, a method particularly useful in multi-step reactions using frequent wash steps.

2 is a partial cross-sectional view showing the integrated circuit device 100 and the flow cell 101. During operation, the flow chamber 105 of the flow cell 101 can define a reagent stream 208 of reagent to be delivered to pass through the open end of the reaction zone in the microwell array 107, the volume, shape, aspect ratio of the reaction zone (eg, The ratio of the width of the substrate to the depth of the well), as well as other dimensional characteristics, can be based on the occurrence of a The nature of the application, as well as reagents, by-products, or labeling techniques used, if any, are selected. The chemical means of the sensor array 205 corresponds to (and produces an output signal) a chemical reaction within the associated reaction zone in the microwell array 107 to detect the analyte or reaction characteristic of interest. The chemical means of the sensor array 205 can be, for example, a chemically sensitive field effect transistor, such as an ion sensitive field effect transistor (ISFET). Examples of chemical devices and array structures that can be used in this embodiment are described in detail in U.S. Patent Application Publication No. 2010/0300559, No. 2010/0197507, No. 2010/0301398, No. 2010/0300895, Each of the documents is incorporated herein by reference in its entirety.

3 is a cross-sectional view of a representative chemical device and corresponding reaction regions, in accordance with an exemplary embodiment. Figure 3 shows two chemical devices 350 and 351 which indicate that a small portion of a sensor array can include millions of chemical devices. Chemical device 350 is coupled to respective reaction zone 301, while chemical device 351 is coupled to corresponding reaction zone 302. Chemical device 350 represents a chemical device in the array of sensors, which in this example is a chemically sensitive field effect transistor, more specifically an ion sensitive field effect transistor (ISFET). The chemical device 350 includes a floating gate structure 318 having a sensor plate 320 coupled to the reaction region 301 by a conductive element 307. As shown in FIG. 3, the sensor plate 320 is the uppermost floating gate structure in the floating gate structure 318. In this example, the floating gate structure 318 includes a plurality of patterns in the plurality of layers of dielectric material 319. Conductive material of the layer. The chemical device 350 further includes a source region 321 and a drain region 322 in a semiconductor substrate 354. The source region 321 and the drain region 322 comprise a doped semiconductor material having a conductivity type different from that of the substrate 354. For example, the source region 321 and the drain region 322 may include a P-type doped semiconductor material, and the substrate may include an N-type doped semiconductor material. The channel region 323 separates the source region 321 from the drain region 322. The floating gate structure 318 covers the channel region 323 and is separated from the substrate 354 by a gate dielectric layer 352. The gate dielectric layer 352 can be, for example, Cerium oxide; or other dielectric materials may be used to form the gate dielectric Layer 352.

As shown in FIG. 3, the dielectric material can define a reaction region 301 that can be located in an opening defined by the absence of a dielectric material. The dielectric material 303 can comprise one or more layers of material, such as hafnium oxide or tantalum nitride, or any other suitable material or mixture of materials. The size of the opening and its spacing can vary depending on the implementation. In some embodiments, the opening may have a specific diameter defined as 4 times the cross-sectional area (A) of the plan view divided by the square root of π (eg, sqrt(4*A/π)), which is not greater than 5 microns, such as no greater than 3.5 microns, no greater than 2.0 microns, no greater than 1.6 microns, no greater than 1.0 microns, no greater than 0.8 microns, no greater than 0.6 microns, no greater than 0.4 microns, no greater than 0.2 microns, or no greater than 0.1 microns.

The chemical device 350 includes a conductive element 307 that covers and communicates with the uppermost floating gate conductor of the plurality of floating gate conductors. As shown in FIG. 3, the conductive element is wider and thinner than the uppermost floating gate conductor, and in the illustrated embodiment, the dielectric material defines an opening that extends to the upper surface of the conductive element. The upper surface 307a of the conductive element 307 defines the lower surface of the reaction region of the chemical device. In another aspect, the upper surface 307a of the conductive element 307 and the lower portion of the inner surface 1316a of the dielectric material 1316 define the reaction region of the chemical device. The bottom area. Conductive element 307 can have a width W that is wider than the width W' of the reaction zone. According to an embodiment, the distance 333 between adjacent conductive elements in the chemical device is about 0.18 microns. According to another embodiment, the conductive element has a thickness 334 of between about 0.1 and 0.2 microns. In one embodiment, the thickness 335 of the uppermost floating gate conductor of the plurality of floating gate conductors may be greater than the thickness 335' of the other floating gate conductors of the plurality of floating gate conductors. In another embodiment, the material of the conductive element 307 can be different than the material of the uppermost floating gate conductor.

The upper surface 307a of the conductive element 307 can be used as the sensing surface of the chemical device 350. The conductive elements disclosed in the present specification can be formed into various shapes (width, height, etc.) according to materials/etching techniques/manufacturing procedures and the like used in the manufacturing process. The conductive element 307 can include one or more of a variety of different materials to increase sensitivity to specific ions, such as hydrogen ions. In an exemplary embodiment, the conductive element may include at least one of titanium, tantalum, titanium, titanium nitrite, aluminum, and/or an oxide thereof, and/or a mixture thereof. The conductive element 307 can provide the chemical device 350 with a sufficiently large surface area to avoid the noise problems associated with the sensing surface being too small. The plan view area of the chemical device is determined in part by the width (or diameter) of the reaction zone 301, which can be small, thereby allowing the formation of a high density array. In addition, since the reaction region 301 is defined by the upper surface 307a of the conductive member 307 and the inner surface 1316a of the dielectric material 1316, the sensing surface area may depend on the depth and circumference of the reaction region 301, and may be relatively large, resulting in The low noise chemistry 350, 351 can be arranged with a high density arrangement so that the characteristics of the reaction can be accurately detected.

During fabrication and/or operation of the device, a thin oxide of material of conductive element 307 can be grown on its upper surface 307a, which acts as a sensing material for chemical device 350 (eg, an ion sensitive sensing material), for example, In one embodiment, the conductive element can be titanium nitride, and the titanium oxide or titanium oxynitride can be exposed to the solution during manufacture and/or during use to grow on its upper surface 307a. The formation of the oxide depends on the conductive material, the process being performed, and the conditions at which the device is operated. In the illustrated embodiment, the conductive element 307 is a single layer of material, and more generally, the conductive element is actually Implementation may include a plurality of conductive materials, such as metal or ceramic, or any other suitable conductive material or mixture of materials, which may be, for example, a metallic material or an alloy thereof, or may be a ceramic material, or a combination thereof. An exemplary metallic material includes one of aluminum, copper, nickel, titanium, silver, gold, platinum, rhodium, ruthenium, iridium, tungsten, osmium, zirconium, palladium, or combinations thereof; an exemplary ceramic material A titanium nitride, titanium aluminum nitride, titanium oxynitride, tantalum nitride, or a combination thereof is included. In some alternative embodiments, another conformal sensing material (not shown) may be deposited on the upper surface 307a of the sensing material of the conductive element 307, which may include one or more of a variety of different materials to Increasing the sensitivity to specific ions, for example, tantalum nitride or hafnium oxynitride and metal oxides such as antimony oxide, aluminum oxide or antimony oxide, usually provide sensitivity to hydrogen ions, while polychlorinated chlorine containing valinomycin Ethylene sensing materials can provide sensitivity to potassium ions. Materials sensitive to other ions such as sodium, silver, iron, bromine, iodine, calcium and nitrate may also be used depending on actual needs.

Referring again to FIG. 3, during operation, reactants, wash solutions, and other reagents can be moved into or out of reaction zone 301 by diffusion mechanism 340, which corresponds to (and produces an associated output signal) adjacent to said conductive element 307. The amount of charge 324, since the ions of the analyte solution can cause protonation or deprotonation of the surface charge groups, the charge 324 present in the analyte solution can alter the analyte solution and the upper surface 307a of the conductive element 307. The surface potential on the interface between the two. A change in the charge 324 causes a change in the voltage of the floating gate structure 318, which varies sequentially in the threshold voltage of the transistor of the chemical device 350, and can utilize the channel region between the source region 321 and the drain region 322. The current of 323 is used to measure the change in this threshold voltage. The results show that the chemical device 350 can be used directly to provide a current based output signal connected to the array line of the source region 321 or the drain region 322, or indirectly to another circuit to provide a voltage based output signal.

The present invention will be described in detail below with reference to FIGS. 4 to 14. Conductive element 307 is overlying and in communication with the uppermost floating gate conductor 320, which is wider and thinner than the uppermost floating gate conductor. Since the charge 324 can be more highly concentrated at the bottom of the reaction region 301, in some embodiments, the change in size of the conductive element has a significant effect on the amplitude of the signal detected by the relative charge 324, in one embodiment. The reaction carried out in reaction zone 301 can be an analytical reaction used to identify or determine the characteristics or characteristics of the analyte of interest, such reaction can produce direct or indirect by-products that affect the charge around conductive element 307. If the by-product produces only a small amount, or decreases rapidly, or reacts with other components, multiple samples of the same analyte can be simultaneously analyzed using reaction zone 301 to increase the resulting output signal. In one embodiment, a plurality of samples of an analyte may be attached to the solid support 312 before or after deposition in the reaction zone 301. The solid support 312 may be microparticles, nanoparticles, beads. Solid or porous, including gels and the like. Solid phase support for simplicity and ease of explanation The substance 312 is also referred to herein as a particle, and as one of ordinary skill in the art will appreciate, the solid phase support can be of different sizes. Additionally, the solid support can be positioned at different locations in the opening. For nucleic acid analysis, multiple linked samples can be made by rolling cycle amplification (RCA), exponential RCA, polymerase chain reaction (PCR) or similar techniques to produce amplification products without the need for a solid support. .

In various exemplary embodiments, the methods, systems, and computer readable media may be advantageous for use in processing and/or analyzing data and signals obtained from nucleic acid sequencing of electronic or charged radicals, in electronic or In the sequencing of charged groups (eg, pH-based sequencing), nucleotide incorporation events can be determined by detecting ions (eg, hydrogen ions) that are naturally produced by polymerase-catalyzed nucleotide extension reactions. Byproducts; this can be used to sequence a sample or template nucleic acid, which can be, for example, a fragment of a nucleic acid sequence of interest, and can be attached directly or indirectly to a solid support, such as particles, microparticles, as the same clonal population. Beads, etc. The sample or template nucleic acid can be operably associated to a primer and a polymerase and can be subjected to a repetitive cycle or to the addition of a "flow" of deoxynucleoside triphosphates ("dNTPs") (which can be referred to herein as "nucleotides" Streams, which may result in concomitant nucleotides) and washing. The primer can be annealed to the sample or template, so when adding dNTPs that are complementary to the next base in the template, the polymerase can be used to extend the 3' end of the primer. The ionized concentration of each nucleotide stream can then be determined based on the known sequence of nucleotide flows and the measured output signal of the chemical device to determine the nucleoside corresponding to the sample nucleic acid coupled into the reaction zone of the chemical device. Acid type identification, sequence and quantity.

4 through 14 are schematic diagrams showing stages of a fabrication process for forming an array of chemical devices and their corresponding well structures in accordance with an exemplary embodiment. 4 shows a structure 400 including a floating gate structure (eg, floating gate structure 318) of chemical devices 350, 351 by depositing a layer of gate dielectric material on semiconductor substrate 354 and dielectric material for the gate. Depositing a layer of polysilicon (or other conductive material) to form the structure 400, and then etching the polysilicon layer and the gate dielectric layer with an etch mask to form a gate dielectric An element (eg, gate dielectric layer 352) and a lowermost conductive material element in the floating gate structure. An ion implantation mask is then formed for ion implantation to form a source region and a drain region of the chemical device (eg, source region 321 and drain region 322). The first layer of dielectric material 319 can be deposited over the underlying conductive material component. A conductive post can then be formed in the via formed in the first layer of the etch dielectric material 319 for contacting the lowermost conductive material component of the floating gate structure. A layer of electrically conductive material can then be deposited over the first layer of dielectric material 319 and patterned to form a second electrically conductive material element that is electrically coupled to the electrically conductive pillar. This process can be repeated multiple times to form the completed floating gate structure 318 shown in FIG. In addition, other and/or additional techniques may be performed to form the structure. The method of forming the structure 400 as shown in FIG. 4 may also include forming other components, such as array lines (eg, word lines, bit lines, etc.) for accessing the chemical device, other doped regions of the substrate 354, and Other circuitry (e.g., access circuitry, biasing circuitry, etc.) for operating the chemical device is based on the implementation of the components and array configurations in the chemical devices described herein. In some embodiments, the elements of the structure can be manufactured, for example, using techniques described in the following documents, such as U.S. Patent Application Publication No. 2010/0300559, No. 2010/0197507, No. 2010/0301398, No. 2010/ No. 0300895, No. 2010/013071a43, and No. 2009/0026082, and U.S. Patent No. 7,575,865, the entire disclosure of each of which is incorporated herein by reference.

As shown in FIG. 5, a dielectric material 503 can be formed on the sensor plate 320 of the field effect transistor of the chemical device 350; then, as shown in FIG. 6, the structure 500 shown in FIG. The dielectric material 503 is etched to form openings 618, 620 (as vias) that extend to the upper surface of the floating gate structure of the chemical devices 350, 351, thereby forming a structure 600 as shown in FIG. The method of forming the openings 618, 620 may, for example, use a lithography process to pattern a photoresist layer on the dielectric material 503, thereby defining the locations of the openings 618, 620, and then using the patterned photoresist layer as a mask. The mask performs an anisotropic etch on the dielectric material 503. The anisotropic etch can be performed, for example, by a dry etching process, such as a fluorine-based process. Reactive ion etching (RIE) process. In the present embodiment, the openings 618, 620 are separated by a distance 630, and the openings 618 and 620 are suitable sizes for the through holes. For example, the separated distance 630 may be a process for forming the openings 618, 620 (eg, micro The minimum feature size of the shadowing process, in this embodiment, the distance 630 can be much larger than the width 620. Next, a layer of conductive material 704 is deposited over structure 600 as shown in FIG. 6, thereby forming structure 700 as shown in FIG. 7, wherein conductive material 704 may also be referred to as a conductive pad; conductive material 704 may comprise one or more layers. The conductive material, for example, the conductive material 704 may be a titanium nitride layer or a titanium layer. In addition, other and/or additional conductive materials may be used, such as those described with reference to the conductive elements described above; in addition, more than one layer of conductive material may be deposited. Conductive material 704 can be deposited using various techniques such as sputtering, reactive sputtering, atomic layer deposition (ALD), low pressure chemical vapor deposition (LPCVD), plasma enhanced chemical vapor deposition (PECVD), metal organic chemical vapor phase. Deposition (MOCVD), etc.

Next, a layer of conductive material 805, such as tungsten, can be deposited, for example, on structure 700 as shown in FIG. 7, thereby forming structure 800 as shown in FIG. Among them, the conductive material 805 can be deposited using various techniques such as sputtering, reactive sputtering, atomic layer deposition (ALD), low pressure chemical vapor deposition (LPCVD), plasma enhanced chemical vapor deposition (PECVD), metal organic chemistry. Vapor deposition (MOCVD), etc., or any other suitable technique. Conductive material 704 and conductive material 805 can then be planarized using, for example, a chemical mechanical polishing (CMP) process to form structure 900 as shown in FIG. An additional step may be optionally performed to form a via barrier liner 1006 over the planarized conductive material 704 and conductive material 805 to form the structure 1000 of FIG. 10; for example, a via barrier The material of the pad 1006 may be titanium nitride. Although the via barrier liner 1006 is shown in FIGS. 11-14, the via barrier liner 1006 is optional.

Next, a conductive material 1107 is formed over the via barrier liner 1006 to form the structure 1100 as shown in FIG. The conductive material 1107 can be selectively formed directly on the planarized conductive material 704 and the conductive material 805, and the conductive material 1107 can be, for example, germanium. Then, right Conductive material 1107 is etched to form openings 1208, 1210, 1212 that extend to via barrier liner 1006, thereby forming structure 1200 as shown in FIG. 12, wherein the method of forming openings 1208, 1210, 1212 can be, for example, The lithography process is used to pattern the photoresist layer on the conductive material 1107, thereby defining the positions of the openings 1208, 1210, and 1212, and then using the patterned photoresist layer as a mask to align the dielectric material 503. Directional etching. The anisotropic etch of conductive material 1107 can be performed, for example, using a dry etch process, such as a fluorine based reactive ion etch (RIE) process. In the present embodiment, the openings 1208, 1210, 1212 are separated by a distance 1230L, the conductive element 1107 has a height 1230H, and the length 1230L of the conductive element 1107 is greater than the length 320L of the sensor plate 320, the thickness of the conductive element 1107. 1230H is less than the thickness 320H of the sensor plate 320, and the spacing between the conductive elements of the conductive element 1107 (eg, 1220) is less than the spacing between the sensor plates (eg, 1220'). Wherein, the conductive element may not be directly above and/or aligned with the uppermost floating gate conductor.

Next, a dielectric material 1316 can be formed on the structure 1200 as shown in FIG. 12 to form the structure 1300 as shown in FIG. 13; the dielectric material 1316 can be, for example, tetraethyl orthophthalate (TEOS) or cerium oxide. . Next, the dielectric material 1316 of the structure 1300 as shown in FIG. 13 is etched to form openings 1418, 1420 that extend to the upper surface of the floating gate structure of the chemical devices 350, 351, thereby forming the structure shown in FIG. Structure 1400.

15 is a block diagram of an exemplary chemical device including an example sensor region and an exemplary peripheral region, wherein the chemical device 1500 can include a chemically sensitive field effect device, in accordance with an exemplary embodiment. One of the crystals has a sensor region 1501 and a peripheral region 1503 of a peripheral circuit for obtaining signals from the chemically sensitive field effect transistor. In an embodiment, the conductive element is located in a conductive layer that is only within the sensor region 1501. In another embodiment, the electrically conductive element includes a material that is not disposed within the perimeter region 1503. The sensor area and peripheral area as shown in Figure 15 are merely examples and are not intended to limit the shape, size or position of the chemical device.

While the present invention has been described with reference to the preferred embodiments and examples, It is contemplated that those skilled in the art can implement and make appropriate modifications and combinations, which are still within the spirit of the invention and the scope of the following claims.

Claims (20)

A chemical device comprising: a chemically sensitive field effect transistor comprising a floating gate structure comprising a plurality of mutually electrically coupled floating gate conductors; a dielectric layer overlying the a floating via structure, wherein a conductive via is formed through the dielectric layer and communicates with the uppermost floating gate conductor of the plurality of floating gate conductors, the conductive via having less than the uppermost layer a width of the floating gate conductor; a conductive element covering and communicating with the uppermost floating gate conductor of the plurality of floating gate conductors via the conductive via, the conductive element being higher than the uppermost layer The floating gate conductor is wider and thinner; and a dielectric material defining an opening extending to one of the upper surfaces of the conductive element. The chemical device of claim 1, wherein the conductive member comprises at least one of titanium, tantalum, titanium nitrite, and aluminum and/or oxides and/or mixtures thereof. The chemical device of claim 1, further comprising a second electrically conductive element, wherein the distance between the electrically conductive element and the second electrically conductive element in the chemical device is about 0.18 microns. A chemical device according to claim 1, wherein the conductive member has a thickness of about 0.1 to 0.2 μm. The chemical device of claim 1, wherein the thickness of the uppermost floating gate conductor of the plurality of floating gate conductors is greater than the thickness of the other of the plurality of floating gate conductors. The chemical device of claim 1, wherein the conductive element comprises a material different from the material of the uppermost floating gate conductor. The chemical device of claim 1, wherein an inner surface of the dielectric material and the conductive member The upper surface defines an outer surface of one of the reaction zones of the chemical device. The chemical device of claim 1, wherein the floating gate conduction system is in a layer, and the layer comprises a plurality of array lines and a plurality of bus lines. The chemical device of claim 1, further comprising a sensor region having the chemically sensitive field effect transistor and a peripheral region having a peripheral circuit for obtaining a chemically sensitive field effect transistor Signal. The chemical device of claim 9, wherein the conductive element is in a conductive layer and the conductive layer is only located in the sensor region. The chemical device of claim 9, wherein the electrically conductive element comprises a material that is not located in the peripheral region. The chemical device of claim 1, wherein the chemically sensitive field effect transistor comprises a floating gate structure comprising a plurality of conductors, the plurality of floating gate conduction systems being electrically coupled to each other and separated by a plurality of dielectric layers And the floating gate conduction system is the conductor of the uppermost layer of the plurality of conductors. The chemical device of claim 1, wherein the first layer of the dielectric material is tantalum nitride, and the second layer is at least one of cerium oxide and tetraethyl orthosilicate, the second The layer defines the plurality of sidewalls of the opening. The chemical device of claim 1, further comprising: a microfluidic structure in fluid flow communication with the chemically sensitive field effect transistor and for providing an analyte for sequencing. The chemical device of claim 1, further comprising a conductive barrier layer overlying the conductive via, the dielectric layer, and covering the conductive element. The chemical device of claim 1, further comprising a conductive barrier layer disposed between the uppermost floating gate conductor and one of the conductive vias, the conductive barrier layer further disposed The dielectric layer and the conductive material of the conductive via are between the conductive material. A method of fabricating a chemical device comprising: forming a chemically sensitive field effect transistor comprising a floating gate structure, the floating gate structure comprising a plurality of electrically coupled floating gate conductors; forming a dielectric layer Covering the floating gate structure; forming a conductive via formed through the dielectric layer and communicating with the uppermost floating gate conductor of the plurality of floating gate conductors, the conductive via having a width smaller than the width of the uppermost floating gate conductor; forming a conductive element covering and communicating with the uppermost floating gate conductor of the plurality of floating gate conductors via the conductive via, the conductive element It is wider and thinner than the uppermost floating gate conductor; and a dielectric material is defined that extends to one of the upper surfaces of one of the conductive elements. The method of manufacturing a chemical device of claim 17, wherein the upper surface of the conductive element defines a lower surface of one of the reaction regions of the chemical device. A method of manufacturing a chemical device according to claim 17, wherein the inner surface of one of the dielectric materials and the upper surface of the conductive member define an outer boundary of a reaction region of the chemical device. A method of fabricating a chemical device according to claim 17, wherein the conductive element is formed in a conductive layer and the conductive layer is located only in one of the sensor regions of the chemical device.