Multi site molecule detection method

• US 5,670,322 A
• Filed: 06/01/1995
• Issued: 09/23/1997
• Est. Priority Date: 11/19/1991
• Status: Expired due to Term

• Current Assignee: Daniel J. Ehrlich, John Shumaker, Kenneth Loren Beattie, Mark Hollis, Michael E. Hogan, Mitchell D. Eggers
• Original Assignee: Daniel J. Ehrlich, John Shumaker, Kenneth Loren Beattie, Mark Hollis, Michael E. Hogan, Mitchell D. Eggers
• Inventors: Hollis, Mark, Hogan, Michael E., Eggers, Mitchell D., Shumaker, John, Ehrlich, Daniel J., Beattie, Kenneth Loren
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/457,096
• Time in Patent Office: 845 Days
• Field of Search: 204/400, 204/403, 422/82.01, 422/82.02, 435/6, 435/7.1, 435/7.2, 435/287.1, 435/287.2, 436/518, 436/524, 436/525, 436/527, 436/806, 436/809
• US Class Current: 506/3
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00713 Electrochemical synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6825 : Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6832 : Enhancement of hybridisation reaction
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6874 : involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2565/607 : being a sensor, e.g. electrode
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 27/221 : by investigating the dielectric properties using microwaves G01N22/00; measuring loss factors or dielectric constants per se G01R27/26
• CPC Class Codes: G01N 27/226 : Construction of measuring vessels; Electrodes therefor
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/5438 : Electrodes
• CPC Class Codes: Y10S 436/806 : Electrical property or magnetic property
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays

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.

Claims

1. A method for identifying molecular structures within a sample substance, comprising the steps of:

applying the substance to 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;

applying an electronic signal to the test sites at multiple frequencies with circuitry coupled to a plurality of electrodes associated with the test sites, each test site having at least one electrode attached thereto for electrical coupling with another electrode;

detecting a frequency dependent electrical property of the test sites to determine which probes have bound to an associated target molecular structure such that a plurality of different targets can be detected.

2. The method of claim 1 wherein said probes are oligonucleotide probes.

3. The method of claim 1 wherein said probes are antibody probes.

4. The method of claim 1 wherein said probes are anti-antibody probes.

5. The method of claim 1 wherein said probes are peptide probes.

6. The method of claim 1 wherein said step of detecting comprises the step of detecting dielectric properties of the test site.

7. The method of claim 1 wherein said step of applying an electronic signal comprises the step of applying a signal over a predetermined range of frequency.

8. The method of claim 7 wherein said detecting step comprises the step of detecting a relaxation frequency within said range.

9. The method of claim 8 wherein said detecting step further comprises the step comparing said detected relaxation frequency to a known frequency for a test site with unbonded probes.

10. The method of claim 1 wherein said step of applying an electronic signal comprises applying a signal at predetermined discrete frequencies at a selected test site.

11. The method of claim 10 wherein said detecting step comprises measuring dispersion at said selected test site at each of said predetermined discrete frequencies and comparing the dispersion between said frequencies to determine whether bonding has occurred at said selected test site.

12. The method of claim 1 and further comprising the step of determining a molecular structure within the sample substance based on the test sites having bonded probes.