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US5532128A Expired / Lapsed US ⏱️ 0.0 years remaining

Multi-site detection apparatus

Assignee: Houston Advanced Research Center
•
Filing: 1994-12-12
•
Granted: 1996-07-02
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Expires: 2014-12-12
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Abstract

Abstract A method and apparatus for identifying molecular structures within a sample substance using an array having a plurality of test sites upon which the sample substance is applied. Each test site includes a probe formed therein to bond with an associated target molecular structure. An electrical signal is applied to the test site and the electrical properties of the test sites are detected to determine which probes have bonded to an associated target molecular structure.

Inventors

  • 👤 Mitchell D. Eggers
  • 👤 Michael E. Hogan
  • 👤 Kenneth L. Beattie
  • 👤 John Shumaker
  • 👤 Daniel J. Ehrlich
  • 👤 Mark Hollis

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-06 23:19
CPC Classifications
B; B82; B82Y; B82Y30/00; B01; B01J; B01J19/00; B01J19/0046; B01J19/0093; C; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6813; C12Q1/6816; C12Q1/6825; C12Q1/6832; C12Q1/6834; C12Q1/6837; C12Q1/6869; C12Q1/6874; G; G01; G01N; G01N21/00; G01N21/17; G01N21/25; G01N21/251; G01N21/253; G01N27/00; G01N27/02; G01N27/22; G01N27/221; G01N27/226; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/543; G01N33/54366; G01N33/54373; G01N33/5438; B01J2219/00; B01J2219/00274; B01J2219/00277; B01J2219/00279; B01J2219/00306; B01J2219/00313; B01J2219/00315; B01J2219/00317; B01J2219/00497; B01J2219/00511; B01J2219/00527; B01J2219/00583; B01J2219/00585; B01J2219/00596; B01J2219/00603; B01J2219/00605; B01J2219/0061; B01J2219/00612; B01J2219/00614; B01J2219/00621; B01J2219/00623; B01J2219/00626; B01J2219/00632; B01J2219/00637; B01J2219/00653; B01J2219/00659; B01J2219/0068; B01J2219/00702; B01J2219/00709; B01J2219/00711; B01J2219/00713; B01J2219/00718; B01J2219/0072; B01J2219/00722; C40; C40B; C40B40/00; C40B40/04; C40B40/06; C40B60/00; C40B60/14; Y; Y10; Y10S; Y10S436/00; Y10S436/806; Y10S436/807; Y10S436/809

Claims Analysis

Total Claims: 37
Claim 1
Independent Claim 179 words
Apparatus for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate, said test sites having respective probes attached thereto which specifically bind to a target molecular structure, such that different test sites have probes which specifically bind to different target molecular structures; a plurality of electrodes associated with the test sites, each test site having at least one electrode attached thereto for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; circuitry, coupled to said electrodes, for applying an electronic signal to the test sites at multiple frequencies; and circuitry for detecting one of a plurality of frequency dependent electrical properties of the test sites to determine which probes have bound to an associated target molecular structure by measuring a dielectric property over a range of frequencies, wherein the plurality of frequency dependent electrical properties comprises permittivity, a dielectric relaxation frequency, and a dispersion of the test sites.
Claim 2
Dependent Claim 179 words
Apparatus for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate, said test sites having respective probes attached thereto which specifically bind to a target molecular structure, such that different test sites have probes which specifically bind to different target molecular structures; a plurality of electrodes associated with the test sites, each test site having at least one electrode attached thereto for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; circuitry, coupled to said electrodes, for applying an electronic signal to the test sites at multiple frequencies; and circuitry for detecting one of a plurality of frequency dependent electrical properties of the test sites to determine which probes have bound to an associated target molecular structure by measuring a dielectric property over a range of frequencies, wherein the plurality of frequency dependent electrical properties comprises permittivity, a dielectric relaxation frequency, and a dispersion of the test sites.
Claim 3
Dependent Claim 17 words
The apparatus of claim 1 wherein one or more of said probes bind to a DNA molecule.
Claim 4
Dependent Claim 14 words
The apparatus of claim 2 wherein said one or more probes comprise oligonucleotide probes.
Claim 5
Dependent Claim 17 words
The apparatus of claim 1 wherein one or more of said probes bind to a RNA molecule.
Claim 6
Dependent Claim 16 words
The apparatus of claim 1 wherein one or more of said probes bind to a cell.
Claim 7
Dependent Claim 14 words
The apparatus of claim 5 wherein said one or more probes comprise antibody probes.
Claim 8
Dependent Claim 16 words
The apparatus of claim 1 wherein one or more of said probes bind to an antibody.
Claim 9
Dependent Claim 14 words
The apparatus of claim 7 wherein said one or more probes comprise anti-antibody probes.
Claim 10
Dependent Claim 14 words
The apparatus of claim 8 wherein said one or more probes comprise peptide probes.
Claim 11
Dependent Claim 57 words
The apparatus of claim 1 wherein said test sites comprise: a plurality of wells formed in the substrate, said wells defined by side and bottom walls; probes for binding with a desired molecular structure formed in each well; wherein said electrodes are disposed adjacent to said walls to form a capacitor in conjunction with the sample substance.
Claim 12
Dependent Claim 28 words
The apparatus of claim 10 wherein said capacitors each comprise a plate formed in each well which is capacitively coupled to a ground plate common to each well.
Claim 13
Dependent Claim 21 words
The apparatus of claim 11 wherein said capacitors each comprise first and second plates formed on the sidewalls of the wells.
Claim 14
Dependent Claim 25 words
The apparatus of claim 1 wherein said circuitry for applying an electronic signal comprises circuitry for applying a signal over a predetermined range of frequency.
Claim 15
Dependent Claim 22 words
The apparatus of claim 13 wherein said detecting circuitry comprises circuitry for measuring capacitance to determine said relaxation frequency within said range.
Claim 16
Dependent Claim 28 words
The apparatus of claim 14 wherein said detecting circuitry further comprises circuitry for comparing said relaxation frequency to a known frequency for a test site with unbound probes.
Claim 17
Dependent Claim 28 words
The apparatus of claim 1 wherein said circuitry for applying an electronic signal comprises circuitry for applying a signal at discrete predetermined frequencies at a selected test site.
Claim 18
Dependent Claim 61 words
The apparatus of claim 16 wherein said detecting circuitry comprises circuitry for measuring capacitance of the sample substance at said selected test site at each of said discrete predetermined frequencies to determine said dispersion at the predetermined frequencies and comparing the dispersion between said frequencies to determine whether binding with a target molecular structure has occurred at said selected test site.
Claim 19
Dependent Claim 21 words
The apparatus of claim 1 and further comprising circuitry for determining a structure based on the test sites having bonded probes.
Claim 20
Dependent Claim 15 words
The apparatus of claim 1 wherein said test sites are formed on a semiconductor surface.
Claim 21
Dependent Claim 165 words
An integrated circuit for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate; a plurality of electrodes associated with the test sites, each test site having at least one electrode attached thereto for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; probes attached to respective test sites, said probes being of various structures in order to specifically bind with respective predetermined molecular structures; and circuitry, coupled to said electrodes, for measuring capacitive parameters at multiple frequencies detect one of a plurality of frequency dependent electrical properties of the test sites to determine whether the probes associated with the test sites have bound with the respective predetermined molecular structures, wherein the plurality of frequency dependent electrical properties of the test sites comprises permittivity a dielectric relaxation frequency, and a dispersion of the tests sites.
Claim 22
Dependent Claim 165 words
An integrated circuit for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate; a plurality of electrodes associated with the test sites, each test site having at least one electrode attached thereto for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; probes attached to respective test sites, said probes being of various structures in order to specifically bind with respective predetermined molecular structures; and circuitry, coupled to said electrodes, for measuring capacitive parameters at multiple frequencies detect one of a plurality of frequency dependent electrical properties of the test sites to determine whether the probes associated with the test sites have bound with the respective predetermined molecular structures, wherein the plurality of frequency dependent electrical properties of the test sites comprises permittivity a dielectric relaxation frequency, and a dispersion of the tests sites.
Claim 23
Dependent Claim 18 words
The integrated circuit of claim 20 and further comprising processing circuitry for processing information from said measuring circuitry.
Claim 24
Dependent Claim 30 words
The integrated circuit of claim 20 wherein each of said test sites comprise first and second conducting plates formed with a well, said probes being disposed between said conductive surfaces.
Claim 25
Dependent Claim 14 words
The integrated circuit of claim 22 wherein said first and second plates are parallel.
Claim 26
Dependent Claim 44 words
The integrated circuit of claim 22 wherein said measuring circuitry is operable to generate a signal over a range of frequencies to said plates of each of said test sites and measure capacitance responsive thereto to determine the dispersion over said range of frequencies.
Claim 27
Dependent Claim 40 words
The integrated circuit of claim 22 wherein said detecting circuitry is operable to generate a signal at discrete frequencies to said plates of each of said test sites and measure capacitance responsive thereto to determine dispersion at said discrete frequencies.
Claim 28
Dependent Claim 169 words
Apparatus for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate, said test sites having respective probes attached thereto which specifically bind to a target molecular structure, such that different test sites have probes which specifically bind to different target molecular structures; a plurality of electrodes associated with the test sites, each test site having at least one electrode formed therein for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; circuitry, coupled to said electrodes, for applying an electronic signal to the test sites over a range of frequencies; and circuitry for detecting capacitive parameters of the test sites within said range of frequencies to determine a relaxation frequency and comparing said relaxation frequency to a known frequency for a test site with unbound probes to determine which probes have bound to an associated target molecular structure.
Claim 29
Dependent Claim 169 words
Apparatus for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate, said test sites having respective probes attached thereto which specifically bind to a target molecular structure, such that different test sites have probes which specifically bind to different target molecular structures; a plurality of electrodes associated with the test sites, each test site having at least one electrode formed therein for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; circuitry, coupled to said electrodes, for applying an electronic signal to the test sites over a range of frequencies; and circuitry for detecting capacitive parameters of the test sites within said range of frequencies to determine a relaxation frequency and comparing said relaxation frequency to a known frequency for a test site with unbound probes to determine which probes have bound to an associated target molecular structure.
Claim 30
Dependent Claim 164 words
Apparatus for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed as respective wells in a single substrate, said test sites having respective probes attached to said wells to specifically bind to an associated target molecular structure, such that different test sites have probes which specifically bind to different target molecular structures; a plurality of electrodes formed on sidewalls of said wells; a ground plate common to each well for providing a capacitive coupling to said electrodes; circuitry, coupled to said electrodes, for applying an electronic signal to the test sites over a range of frequencies; and circuitry for detecting one of a plurality of frequency dependent electrical properties of the test sites by measuring capacitive parameters and dissipation of the test sites at multiple frequencies to determine which probes have bonded to an associated target molecular structure, wherein the plurality of frequency dependent electrical properties comprises permittivity, a dielectric relaxation frequency, and a dispersion of the test sites,
Claim 31
Dependent Claim 164 words
Apparatus for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed as respective wells in a single substrate, said test sites having respective probes attached to said wells to specifically bind to an associated target molecular structure, such that different test sites have probes which specifically bind to different target molecular structures; a plurality of electrodes formed on sidewalls of said wells; a ground plate common to each well for providing a capacitive coupling to said electrodes; circuitry, coupled to said electrodes, for applying an electronic signal to the test sites over a range of frequencies; and circuitry for detecting one of a plurality of frequency dependent electrical properties of the test sites by measuring capacitive parameters and dissipation of the test sites at multiple frequencies to determine which probes have bonded to an associated target molecular structure, wherein the plurality of frequency dependent electrical properties comprises permittivity, a dielectric relaxation frequency, and a dispersion of the test sites,
Claim 32
Dependent Claim 166 words
Apparatus for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate, said test sites attached to respective probes which specifically bind to a target molecular structure, such that different test sites have probes which specifically bind to different target molecular structures; a plurality of electrodes associated with the test sites, each test site having a least one electrode formed therein for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; circuitry, coupled to said electrodes, for applying an electronic signal to the test sites at multiple frequencies; and circuitry for detecting a frequency dependent capacitive property of the test sites by measuring capacitive parameters of the test sites at multiple frequencies to determine which probes have bound to an associated target molecular structure, wherein the frequency despondent capacitive property of the tests sites is permittivity.
Claim 33
Dependent Claim 166 words
Apparatus for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate, said test sites attached to respective probes which specifically bind to a target molecular structure, such that different test sites have probes which specifically bind to different target molecular structures; a plurality of electrodes associated with the test sites, each test site having a least one electrode formed therein for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; circuitry, coupled to said electrodes, for applying an electronic signal to the test sites at multiple frequencies; and circuitry for detecting a frequency dependent capacitive property of the test sites by measuring capacitive parameters of the test sites at multiple frequencies to determine which probes have bound to an associated target molecular structure, wherein the frequency despondent capacitive property of the tests sites is permittivity.
Claim 34
Dependent Claim 156 words
An integrated circuit for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate; a plurality of electrodes associated with the test sites, each test site having at least one electrode formed therein for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; probes attached to respective test sites, said probes being of various structures in order to specifically bind with respective predetermined molecular structures; and circuitry, coupled to said electrodes, for detecting a frequency dependent capacitive property of the test sites by measuring capacitive parameters at multiple frequencies to determine whether the probes associated with the test sites have bound with the respective predetermined molecular structures, wherein the frequency dependent capacitive property of the tests sites is a dielectric relaxation frequency of the test sites.
Claim 35
Dependent Claim 156 words
An integrated circuit for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate; a plurality of electrodes associated with the test sites, each test site having at least one electrode formed therein for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; probes attached to respective test sites, said probes being of various structures in order to specifically bind with respective predetermined molecular structures; and circuitry, coupled to said electrodes, for detecting a frequency dependent capacitive property of the test sites by measuring capacitive parameters at multiple frequencies to determine whether the probes associated with the test sites have bound with the respective predetermined molecular structures, wherein the frequency dependent capacitive property of the tests sites is a dielectric relaxation frequency of the test sites.
Claim 36
Dependent Claim 154 words
An integrated circuit for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate; a plurality of electrodes associated with the test sites, each test site having at least one electrode formed therein for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; probes attached to respective test sites, said probes being of various structures in order to specifically bind with respective predetermined molecular structures; and circuitry, coupled to said electrodes, for detecting a frequency dependent capacitive property of the test sites by measuring capacitive parameters at multiple frequencies to determine whether the probes associated with the test sites have bound with the respective predetermined molecular structures, wherein the frequency dependent capacitive property of the tests sites is a dispersion of the test sites.
Claim 37
Dependent Claim 154 words
An integrated circuit for identifying molecular structures within a sample substance, comprising: a plurality of test sites formed in a single substrate; a plurality of electrodes associated with the test sites, each test site having at least one electrode formed therein for electrical coupling with a second electrode, wherein the one electrode and the second electrode are disposed adjacent to said test sites to form a capacitor in conjunction with the sample substance; probes attached to respective test sites, said probes being of various structures in order to specifically bind with respective predetermined molecular structures; and circuitry, coupled to said electrodes, for detecting a frequency dependent capacitive property of the test sites by measuring capacitive parameters at multiple frequencies to determine whether the probes associated with the test sites have bound with the respective predetermined molecular structures, wherein the frequency dependent capacitive property of the tests sites is a dispersion of the test sites.

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Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1999-07-02 2000-01-01 2000-07-02 $2000.00 Window Closed / Lapsed
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