US5846708A — Optical and electrical methods and apparatus for …

Claim 1

Independent Claim 125 words

Apparatus comprising: a) multiple test sites formed on a substrate for receiving a sample substance containing molecular structures, each test site having row and column electrodes formed therein and having row and column leads extending to a respective electrode at each site; b) probes formed in said test sites, probes of different test sites being of various known structures selected to bind with molecular structures of known binding characteristics which may be in the sample; c) circuitry for applying an electronic signal to the electrodes of the test sites; and d) circuitry for measuring physical properties of the molecular structures in the sample substance which selectively bind to the probes; wherein said physical properties are selected from the group consisting of electromagnetic and acoustic properties.

Claim 2

Dependent Claim 125 words

Apparatus comprising: a) multiple test sites formed on a substrate for receiving a sample substance containing molecular structures, each test site having row and column electrodes formed therein and having row and column leads extending to a respective electrode at each site; b) probes formed in said test sites, probes of different test sites being of various known structures selected to bind with molecular structures of known binding characteristics which may be in the sample; c) circuitry for applying an electronic signal to the electrodes of the test sites; and d) circuitry for measuring physical properties of the molecular structures in the sample substance which selectively bind to the probes; wherein said physical properties are selected from the group consisting of electromagnetic and acoustic properties.

Claim 3

Dependent Claim 15 words

The apparatus of claim 1 including an array of resistors formed beneath the test sites.

Claim 4

Dependent Claim 18 words

The apparatus of claim 1 wherein said electrodes comprise a plurality of conductive fingers extending from a base.

Claim 5

Dependent Claim 50 words

The apparatus of claim 3 wherein a first of said plurality of conductive fingers is disposed in a lower portion of a plurality of wells formed in said substrate and a second of said plurality of conductive fingers is disposed on said substrate above the fingers on the lower portion.

Claim 6

Dependent Claim 16 words

The apparatus of claim 1 wherein said probes comprise oligonucleotide probes targeted for DNA or RNA.

Claim 7

Dependent Claim 141 words

Apparatus comprising: a) a test site array formed on a substrate for receiving a sample substance containing molecular structures; b) probes formed in the test sites, probes of different test sites being of various known structures selected to bind with molecular structures of known binding characteristics which may be in the sample; and c) a detector array having a plurality of detectors, each respective detector having an electrode disposed adjacent to a respective test site and wherein radiation is propagated through said test sites and is absorbed to a different degree by sites in which the molecular structures bind to the probes than sites in which the molecular structures did not bind to the probes, and such difference is sensed by the detectors and used to generate a signal to identify the presence of the molecular structures within the sample substance.

Claim 8

Dependent Claim 141 words

Apparatus comprising: a) a test site array formed on a substrate for receiving a sample substance containing molecular structures; b) probes formed in the test sites, probes of different test sites being of various known structures selected to bind with molecular structures of known binding characteristics which may be in the sample; and c) a detector array having a plurality of detectors, each respective detector having an electrode disposed adjacent to a respective test site and wherein radiation is propagated through said test sites and is absorbed to a different degree by sites in which the molecular structures bind to the probes than sites in which the molecular structures did not bind to the probes, and such difference is sensed by the detectors and used to generate a signal to identify the presence of the molecular structures within the sample substance.

Claim 9

Dependent Claim 23 words

The apparatus of claim 6 wherein said test site array is formed of a disposable plate which is separable from the detector array.

Claim 10

Dependent Claim 22 words

The apparatus of claim 6 wherein the test site array is formed integral with the detector array to form an integrated structure.

Claim 11

Dependent Claim 21 words

The apparatus of claim 7 wherein the disposable plate is formed of quartz, glass, plastic, Al 2 O 3 or polyimide.

Claim 12

Dependent Claim 19 words

The apparatus of claim 1 wherein the electrodes in each test site are coupled together by a transmission line.

Claim 13

Dependent Claim 128 words

A circuit comprising: a) a substrate; b) a plurality of test sites formed in said substrate; c) at least two electrodes formed in each of the test sites; d) leads extending to each of the electrodes; e) probes formed on at least one of the electrodes of a respective test site, said probes of each respective test site being identical in structure, and probes of different test sites being of various known structures selected to bind with respective molecular structures of known binding characteristics which may be in a sample substance, and f) detectors coupled to said electrodes for measuring a physical property of a molecular structure which selectively attaches to said probes; wherein said physical property is selected from the group consisting of electromagnetic and acoustic properties.

Claim 14

Dependent Claim 128 words

A circuit comprising: a) a substrate; b) a plurality of test sites formed in said substrate; c) at least two electrodes formed in each of the test sites; d) leads extending to each of the electrodes; e) probes formed on at least one of the electrodes of a respective test site, said probes of each respective test site being identical in structure, and probes of different test sites being of various known structures selected to bind with respective molecular structures of known binding characteristics which may be in a sample substance, and f) detectors coupled to said electrodes for measuring a physical property of a molecular structure which selectively attaches to said probes; wherein said physical property is selected from the group consisting of electromagnetic and acoustic properties.

Claim 15

Dependent Claim 20 words

The apparatus of claim 1 further including an address lead coupled to one of said electrodes via a transistor switch.

Claim 16

Dependent Claim 21 words

The apparatus of claim 6 wherein the radiation is generated by secondary emission stimulated by photon irradiation of the test sites.

Claim 17

Dependent Claim 17 words

The apparatus of claim 6 wherein the radiation is infrared radiation and the detectors sense thermal energy.

Claim 18

Dependent Claim 157 words

Apparatus comprising: a) multiple test sites formed on a substrate for receiving a sample substance containing molecular structures, each test site having row and column electrodes formed therein and having row and column leads extending to a respective electrode at each site; b) a source of a said sample substance containing unknown molecular structures; c) a plurality of sources of solutions containing known molecules which bind uniquely with molecular structures of known binding characteristics which may be in the source substance; and d) mixing means for selectively mixing each of said solutions with said substance; and e) a detector coupled to the electrodes for detecting the occurrence in the mixed solutions of binding between the known molecules and molecular structures in the substance by measuring a physical property of the mixed solutions resulting from the binding between the known molecules and the substance; wherein said physical property is selected from the group consisting of electromagnetic and acoustic.

Claim 19

Dependent Claim 157 words

Apparatus comprising: a) multiple test sites formed on a substrate for receiving a sample substance containing molecular structures, each test site having row and column electrodes formed therein and having row and column leads extending to a respective electrode at each site; b) a source of a said sample substance containing unknown molecular structures; c) a plurality of sources of solutions containing known molecules which bind uniquely with molecular structures of known binding characteristics which may be in the source substance; and d) mixing means for selectively mixing each of said solutions with said substance; and e) a detector coupled to the electrodes for detecting the occurrence in the mixed solutions of binding between the known molecules and molecular structures in the substance by measuring a physical property of the mixed solutions resulting from the binding between the known molecules and the substance; wherein said physical property is selected from the group consisting of electromagnetic and acoustic.

Claim 20

Dependent Claim 16 words

The apparatus of claim 15 wherein the detector detects binding by observing change in electrical properties.

Claim 21

Dependent Claim 31 words

The apparatus of claim 15 wherein the plurality of sources are contained in respective capillaries, each capillary having a valve for connecting a respective source to a stream of said substance.

Claim 22

Dependent Claim 25 words

The apparatus of claim 17 wherein the capillaries and valves are formed in silicon and have diameters in the range of 1 to 10 microns.

Claim 23

Dependent Claim 15 words

The apparatus of claim 1 wherein the test sites comprise wells formed in the substrate.

Claim 24

Dependent Claim 14 words

The apparatus of claim 19 wherein the wells are formed with a textured surface.

Claim 25

Dependent Claim 12 words

The apparatus of claim 20 wherein the textured surface consists of corrugations.

Claim 26

Dependent Claim 14 words

The apparatus of claim 21 wherein the surface of the electrodes are also corrugated.

Claim 27

Dependent Claim 11 words

The method of claim 16 wherein the electrical property is permittivity.

Claim 28

Dependent Claim 12 words

The apparatus of claim 1 wherein the electrodes are formed within wells.

Claim 29

Dependent Claim 12 words

The apparatus of claim 24 wherein a surface of the is textured.

Claim 30

Dependent Claim 14 words

The apparatus of claim 25 wherein the texture is in the form of corrugations.

Claim 31

Dependent Claim 13 words

The apparatus of claim 24 wherein a surface of the electrode is textured.

Claim 32

Dependent Claim 11 words

The apparatus of claim 27 wherein the texture consists of corrugations.

Claim 33

Dependent Claim 11 words

The apparatus of claim 1 wherein the physical property is permittivity.

Claim 34

Dependent Claim 12 words

The apparatus of claim 1 wherein the physical property is dissipation factor.

Claim 35

Dependent Claim 12 words

The apparatus of claim 1 wherein the physical property is AC conductance.

Claim 36

Dependent Claim 12 words

The apparatus of claim 1 wherein the physical property is signal loss.

Claim 37

Dependent Claim 12 words

The apparatus of claim 1 wherein the physical property is relaxation frequency.

Claim 38

Dependent Claim 19 words

The apparatus of claim 6 wherein the detector detects the different degree of absorption by detecting an electrical property.

Claim 39

Dependent Claim 24 words

The apparatus of claim 34 wherein the electrical property is taken from the group consisting of permittivity, dissipation factor, AC conductance and signal loss.

Claim 40

Dependent Claim 142 words

Apparatus comprising: a) a test site array formed on a disposable substrate for receiving a sample substance containing molecular structures; b) probes formed in the test sites, probes of different test sites being of various known structures selected to bind with molecular structures of known binding characteristics which may be in the sample; and c) a detector array separable from said substrate having a plurality of charge-coupled device detectors, each respective detector having an electrode disposed adjacent to a respective test site on said substrate and wherein when excitation radiation is propagated through said test sites and is absorbed to a different degree by sites containing binding probes than non-binding probe test sites, such difference in degree of absorption is sensed by the detectors and used to generate a signal to identify the presence of the molecular structures within the sample substance.

Claim 41

Dependent Claim 142 words

Apparatus comprising: a) a test site array formed on a disposable substrate for receiving a sample substance containing molecular structures; b) probes formed in the test sites, probes of different test sites being of various known structures selected to bind with molecular structures of known binding characteristics which may be in the sample; and c) a detector array separable from said substrate having a plurality of charge-coupled device detectors, each respective detector having an electrode disposed adjacent to a respective test site on said substrate and wherein when excitation radiation is propagated through said test sites and is absorbed to a different degree by sites containing binding probes than non-binding probe test sites, such difference in degree of absorption is sensed by the detectors and used to generate a signal to identify the presence of the molecular structures within the sample substance.

Claim 42

Dependent Claim 12 words

The apparatus of claim 36 wherein said sample substance contains tagged targets.

Claim 43

Dependent Claim 36 words

The apparatus of claim 36 in which a dielectric layer is formed over the detectors and a filter is interposed between the test sites and layer to prevent passage of said excitation radiation to said detectors.

Claim 44

Dependent Claim 130 words

Apparatus comprising: a) a test site array formed on a disposable substrate for receiving a sample substance containing tagged molecular targets; b) probes formed in the test sites; probes of different test sites in the array being of various known structures selected to bind with tagged targets of known binding characteristics which may be in the sample; and c) a detector array separable from said substrate having a plurality of charge-coupled device detectors, each respective detector having an electrode disposed adjacent to a respective test site on said substrate and wherein excitation radiation is propagated through said test sites causing the tagged targets to emit radiation which is sensed by the detectors and used to generate a signal to identify the presence of the molecular structures within the sample substance.

Claim 45

Dependent Claim 130 words

Apparatus comprising: a) a test site array formed on a disposable substrate for receiving a sample substance containing tagged molecular targets; b) probes formed in the test sites; probes of different test sites in the array being of various known structures selected to bind with tagged targets of known binding characteristics which may be in the sample; and c) a detector array separable from said substrate having a plurality of charge-coupled device detectors, each respective detector having an electrode disposed adjacent to a respective test site on said substrate and wherein excitation radiation is propagated through said test sites causing the tagged targets to emit radiation which is sensed by the detectors and used to generate a signal to identify the presence of the molecular structures within the sample substance.

Claim 46

Dependent Claim 36 words

The apparatus of claim 39 in which a dielectric layer is formed over the detectors and a filter is interposed between the test sites and layer to prevent passage of said excitation radiation to said detectors.

Claim 47

Dependent Claim 127 words

Apparatus comprising: a) a test site array formed on a disposable substrate for receiving a sample substance containing molecular targets tagged with material which spontaneously emits radiation; b) probes formed in the test sites; probes of different test sites in the array being of various known structures selected to bind with tagged targets of known binding characteristics which may be in the sample; and c) a detector array separable from said substrate having a plurality of charge-coupled device detectors each having an electrode, each respective detector disposed adjacent to a respective test site on said substrate and wherein the targets spontaneously emit radiation which is sensed by the detectors and used to generate a signal to identify the presence of the molecular structures within the sample substance.

Claim 48

Dependent Claim 127 words

Apparatus comprising: a) a test site array formed on a disposable substrate for receiving a sample substance containing molecular targets tagged with material which spontaneously emits radiation; b) probes formed in the test sites; probes of different test sites in the array being of various known structures selected to bind with tagged targets of known binding characteristics which may be in the sample; and c) a detector array separable from said substrate having a plurality of charge-coupled device detectors each having an electrode, each respective detector disposed adjacent to a respective test site on said substrate and wherein the targets spontaneously emit radiation which is sensed by the detectors and used to generate a signal to identify the presence of the molecular structures within the sample substance.

Claim 49

Dependent Claim 21 words

The apparatus of claim 1 wherein the surface of said electrodes comprises gold, niobium oxide, iridium oxide, platinum, titanium, or tungsten.

Claim 50

Dependent Claim 21 words

The apparatus of claim 24 wherein the surface of said electrodes comprises gold, niobium oxide, iridium oxide, platinum, titanium, or tungsten.

Claim 51

Dependent Claim 14 words

The apparatus of claim 1, wherein said probes comprise antibody probes targeted for cells.

Claim 52

Dependent Claim 14 words

The apparatus of claim 1, wherein said probes comprise antigen probes targeted for antibodies.

Claim 53

Dependent Claim 15 words

The apparatus of claim 1, wherein said probes comprise hormone probes targeted for hormone receptors.

Claim 54

Dependent Claim 14 words

The apparatus of claim 1, wherein said probes comprise biotin probes targeted for anidin.

Claim 55

Dependent Claim 14 words

The apparatus of claim 6, wherein the detector array is comprised of charged-couple devices.

Claim 56

Dependent Claim 27 words

The apparatus of claim 6, wherein the detector array is aligned with the test sites and radiation is projected through the test sites onto the detector array.

Claim 57

Dependent Claim 17 words

The apparatus of claim 49, wherein the radiation is in the form of photons, or radioactive particles.

Claim 58

Dependent Claim 22 words

The apparatus of claim 6, wherein the radiation is generated within the test sites by radioactive, chemical, thermal, chemiluminescent or luminescent reaction.

Claim 59

Dependent Claim 18 words

The apparatus of claim 6, wherein the detectors detect thermal energy occurring when a bonding reaction takes place.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2001-12-07	2002-06-08	2002-12-08	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2005-12-07	2006-06-08	2006-12-08	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2009-12-07	2010-06-08	2010-12-08	$7700.00	Window Closed / Lapsed

Optical and electrical methods and apparatus for molecule detection

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