GB2213269A - Microenvironmental sensor assemblies - Google Patents
Microenvironmental sensor assemblies Download PDFInfo
- Publication number
- GB2213269A GB2213269A GB8827495A GB8827495A GB2213269A GB 2213269 A GB2213269 A GB 2213269A GB 8827495 A GB8827495 A GB 8827495A GB 8827495 A GB8827495 A GB 8827495A GB 2213269 A GB2213269 A GB 2213269A
- Authority
- GB
- United Kingdom
- Prior art keywords
- sensing
- sensor assembly
- interface
- array
- sensor
- Prior art date
- 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.)
- Withdrawn
Links
- 230000000712 assembly Effects 0.000 title 1
- 238000000429 assembly Methods 0.000 title 1
- 239000000758 substrate Substances 0.000 claims abstract description 9
- 239000012620 biological material Substances 0.000 claims abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 239000000463 material Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 7
- 239000004020 conductor Substances 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 2
- 150000001768 cations Chemical class 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 238000001465 metallisation Methods 0.000 claims 1
- 238000012544 monitoring process Methods 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 4
- 206010028980 Neoplasm Diseases 0.000 abstract description 3
- 201000011510 cancer Diseases 0.000 abstract description 3
- 231100000433 cytotoxic Toxicity 0.000 abstract description 3
- 230000001472 cytotoxic effect Effects 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 229910021645 metal ion Inorganic materials 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 9
- 230000000694 effects Effects 0.000 description 7
- 238000012545 processing Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000004065 semiconductor Substances 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 229910052581 Si3N4 Inorganic materials 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 239000013626 chemical specie Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000000609 electron-beam lithography Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000012774 insulation material Substances 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000000206 photolithography Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- HQVNEWCFYHHQES-UHFFFAOYSA-N silicon nitride Chemical compound N12[Si]34N5[Si]62N3[Si]51N64 HQVNEWCFYHHQES-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/4833—Physical analysis of biological material of solid biological material, e.g. tissue samples, cell cultures
- G01N33/4836—Physical analysis of biological material of solid biological material, e.g. tissue samples, cell cultures using multielectrode arrays
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pathology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Optics & Photonics (AREA)
- Food Science & Technology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
A sensor array comprises a two dimensional array of sensing interfaces 5 connected by conductive tracks 3 of a deposited array to connecting pads (2) at which they are monitored electrically. The array is bicompatible and is deposited on a substrate and may be used for monitoring parameters such as metal ion concentration pH, oxygen and temperature of in vitro biological material which is cultured over the bicompatible sensing interfaces. Monitoring of the response of cancer cells by cytotoxic drugs is disclosed. <IMAGE>
Description
MICROENVIRONMENTAL SENSOR ASSEMBLIES
This invention relates to microenvironmental sensors and their applications.
The relatively large size (dimensions greater than 10-3 - 1O7m) of many microenvironmental sensors precludes their use for the monitoring of microenvironmental parameters since they modify the environment in which they are placed. Even with microsensors some modification of the environment can occur although the dimensions of such devices reduces this to an absolute minimum.
In one aspect the invention provides a sensor assembly comprising a conductive array deposited on a substrate, said conductive array including a sensor interface or a two-dimensional array of sensor interfaces, exposed on a surface of said assembly, said surface and the exposed portion of the or each said interface being biocompatible and the or each exposed portion having dimensions not exceeding lmm.
In another aspect the invention provides a method of sensing the state of in vitro biological material comprising culturing said material on a biocompatible surface carrying exposed biocompatible sensing interface means and sensing the electrical'state of said interface means. This allows the biological material to be monitored.
The sensors may have any required shape, for example, a square, rectangular or circular substrate carrying a single sensing interface or a predetermined array of such interfaces. Each interface is preferably of micro dimensions (less than 10 microns) and the position of the interface may be customised and specific for each application. Signal processing circuitry is required to collect and interpret the data from each interface and each sensor is used with appropriate circuitry.
By using standard semiconductor fabrication technologies and materials, microenvironmental transducers of micro dimensions may be produced that do not need to be introduced into the microenvironment to monitor it. Cells may grow over the array and create their microenvironment around the sensors, so the array is free from the disadvantages that always accompany the introduction of sensors.
The sensor array, which may consist of one or more sensing interfaces, is suitably made on a glass, polymer, plastics or silicon substrate. In addition the substrate may be rigid or flexible. The spatial geometry of the sensing interfaces can also be modified and specified for precise applications or requirements.
The sensor array is suitably defined using standard semiconductor technology, such as photolithography, or electron beam lithography, which enables great precision and repeatability in sensor interface dimensions and spatial location within the sensor array. The sensors of the invention may be designed to be used in conjunction with signal processing circuits and to be readily interfaced with such instrumentation by the use of standard interfacing methods and materials. This enables sensors of differing sensory modalities to be readily and quickly interchanged with the signal processing circuitry.
The sensors of the invention are primarily designed for use in culture dishes to monitor the growth and activity and microenvironments of living cells. The effects of added agents can be determined and the devices thus provide in addition a rapid and efficient method of screening and evaluating the effects of materials, e.g. cytotoxic drugs, on the living cells.
In this way the effects of modifications to the microenvironment of the cells can also be monitored. In the case of tumour cells the monitoring of the oxygen concentrations and the activity of other free radical stoppers within the cells and their microenvironment can be used to determine the optimum time to irradiate the cancerous cells.
A sensor array in accordance with the invention may be incorporated into the bottom of a culture vessel either as a separate substrate or as an integral part of the culture vessel and cells cultured on top of the sensing array in appropriate culture media. In this way the microenvironment of the material in the culture vessel is not disturbed by the sensors.
The sensing interface form and function (modality) can be selected prior to use thus enabling many parameters within the microenvironment to be determined at the same time, non-invasively.
The fabrication cf use of a sensor in the monitoring of humOan cancer cells growing in vitro, is described below, by way of example only, with reference to the accompanying drawings, in which:
Figure 1 is a plan view of a multisite sensor array; and
Figure 2 is a magnified surface view of the central portion of the sensor showing multi sensing interfaces.
The sensor consists of a polymer, glass, plastics or silicon substrate 1 forming a square body of dimensions 14000 microns x 14000 microns. The substrate may be 900 microns thick. The sensor array 4 illustrated has 56 sensing sites arranged in a twodimensional array. Each site contains one sensor interface 5 and any subset of these can be interrograted simultaneously from metallic connection pads 2 which are linked by metallic tracks 3 to the sensing interfaces 5 (Figure 2) which may be arranged to sense for example, pH, oxygen, temperature and other ions within or beneath cultured cells and tissues.
The arrangement of the conductors is illustrated in Figure 2, in which each sensing interface is connected by a separate and isolated conductor 3 to a respective pad 2.
The materials used for the sensor interface and insulators must be biocompatible. Preferred metals are tantalum, titanium, gold, platinum, iridium and rhodium.
The insulation material may comprise for example silicon dioxide and/or silicon nitride or biocompatible polymer.
The array can either be incorporated into a culture vessel (not shown) as an individual array or integrated into/onto the fabric of the culture vessel.
Other applications include monitoring the effects of materials added to the culture vessel and its contents. For example, In the case of in vitro growth of human cancer cells, the effects of the addition of cytotoxic drugs, chemicals and therapeutic agents on the cultured material can be monitored.
The sensing interface array pattern can be customised for specific applications and different chemical species that are to be detected.
In the described embodiment, the dimensions of the exposed portions of the sensing interfaces do not exceed 10~2mum. They are typically 2 - 6 microns and most preferably 4 microns. However, in some cases the exposed portions of the sensing interfaces may have one or more dimensions exceeding this.
Claims (11)
1. A sensor assembly comprising a conductive array deposited on a substrate, said conductive array including a sensor interface or a two-dimensional array of sensor interfaces, exposed on a surface of said assembly, said surface and the exposed portion of the or each said interface being biocompatible and the or each exposed portion having dimensions not exceeding lmm.
2. A sensor assembly as claimed in claim 1, wherein the conductive array defines a respective metallisation or other suitable conducting material track for each interface, each said track terminating in a connecticn pad.
3. A sensor assembly as claimed in claim 1 or claim 2, wherein the or at least one said sensing interface is adapted to measure temperature, pH, oxygen concentration or cation concentration.
4. A sensor assembly as claimed in any one of the preceding claims, wherein said surface is an interior surface of a culture vessel.
5. A sensor assembly as claimed in any one of the preceding claims, wherein said dimensions do not exceed 1 o -2mm
6. A sensor assembly as claimed in any one of the preceding claims, wherein the dimensions are selected not to exceed those of cells to which the surface is to be exposed.
7. A method of sensing the state of in t4tro biological material comprising culturing said material on a biocompatible surface carrying exposed biocompatible sensing interface means, and sensing the electrical state of said interface means.
8. A method as claimed in claim 7, comprising the further step of adding a cytotoxic drug to said material.
9. A method as claimed in claim 7 or 8, carried cut using a sensor assembly as claimed n any cne of claims 1 to 6.
10. A sensor assembly comprising a sensing array substantiallv as herein described with reference to the accompanying drawings.
11. A method cf sensing the state of biological material substantially as rere-n described with reference to the accompanying drawings.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8827495A GB2213269A (en) | 1987-12-01 | 1988-11-24 | Microenvironmental sensor assemblies |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878728103A GB8728103D0 (en) | 1987-12-01 | 1987-12-01 | Microenvironmental sensor assemblies & methods |
| GB878729194A GB8729194D0 (en) | 1987-12-15 | 1987-12-15 | Microenvironmental sensor assemblies & methods |
| GB8827495A GB2213269A (en) | 1987-12-01 | 1988-11-24 | Microenvironmental sensor assemblies |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB8827495D0 GB8827495D0 (en) | 1988-12-29 |
| GB2213269A true GB2213269A (en) | 1989-08-09 |
Family
ID=27263694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8827495A Withdrawn GB2213269A (en) | 1987-12-01 | 1988-11-24 | Microenvironmental sensor assemblies |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2213269A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2283572A (en) * | 1993-11-02 | 1995-05-10 | Siemens Plessey Controls Ltd | Water quality sensor apparatus |
| US5483164A (en) * | 1993-11-02 | 1996-01-09 | Siemens Plessey Controls Limited | Water quality sensor apparatus |
| US6376233B1 (en) * | 1996-11-12 | 2002-04-23 | Micronas Intermetall Gmbh | Device for conducting research on cell specimens and similar materials |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4225410A (en) * | 1978-12-04 | 1980-09-30 | Technicon Instruments Corporation | Integrated array of electrochemical sensors |
| GB2111215A (en) * | 1981-10-31 | 1983-06-29 | Alastair Sibbald | Electrochemical sensor assembly |
| WO1986006484A1 (en) * | 1985-04-19 | 1986-11-06 | The Regents Of The University Of California | Transparent multi-oxygen sensor array |
-
1988
- 1988-11-24 GB GB8827495A patent/GB2213269A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4225410A (en) * | 1978-12-04 | 1980-09-30 | Technicon Instruments Corporation | Integrated array of electrochemical sensors |
| GB2111215A (en) * | 1981-10-31 | 1983-06-29 | Alastair Sibbald | Electrochemical sensor assembly |
| WO1986006484A1 (en) * | 1985-04-19 | 1986-11-06 | The Regents Of The University Of California | Transparent multi-oxygen sensor array |
Non-Patent Citations (1)
| Title |
|---|
| Sensors and Actuators 9 (1986) pages * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2283572A (en) * | 1993-11-02 | 1995-05-10 | Siemens Plessey Controls Ltd | Water quality sensor apparatus |
| US5483164A (en) * | 1993-11-02 | 1996-01-09 | Siemens Plessey Controls Limited | Water quality sensor apparatus |
| GB2283572B (en) * | 1993-11-02 | 1997-11-12 | Siemens Plessey Controls Ltd | Improvements in or relating to water quality sensor apparatus |
| US6376233B1 (en) * | 1996-11-12 | 2002-04-23 | Micronas Intermetall Gmbh | Device for conducting research on cell specimens and similar materials |
Also Published As
| Publication number | Publication date |
|---|---|
| GB8827495D0 (en) | 1988-12-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |