Method and system for determining analyte activity

• US 6,350,369 B1
• Filed: 04/13/1999
• Issued: 02/26/2002
• Est. Priority Date: 04/14/1998
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Vaid, Thomas P., Lewis, Nathan S.
• Primary Examiner(s): Tung, T.
• Assistant Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US09/291,932
• Time in Patent Office: 1,050 Days
• Field of Search: 204/403, 204/400, 204/412, 204/406, 205/775, 205/777.5, 205/787, 205/792, 205/793.5, 422/82.01, 422/82.02
• US Class Current: 205/777.5
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/007 Simulation or vitual synthesis
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: G01N 27/126 comprising organic polymers
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

Chemical sensors for detecting the activity of a molecule or analyte of interest is provided. The chemical sensors comprise and array or plurality of chemically-sensitive resistors that are capable of interacting with the molecule of interest, wherein the interaction provides a resistance fingerprint. The fingerprint can be associated with a library of similar molecules of interest to determine the molecule'"'"'s activity.

Claims

1. A method for screening analytes for a specific activity, chemical or physical property, or function, comprising the steps of:

a) contacting an array comprising a plurality of different differentially responsive sensors with an analyte of interest comprising an activity, property, or function, wherein each of the pluraity of sensors in the array are responsive to a plurality of analytes having differing properties;

b) measuring a signal output from each sensor of the plurality of different differentially responsive sensors;

c) using the results of said measuring to obtain a signal profile related to a change in the signal output from each sensor; and

d) comparing the signal profile to at least one previously-obtained signal profile obtained from a standard sample not including the analyte of interest and which has a known specific activity, chemical or physical property, or function, wherein such comparison is used to indicate a specific activity, function, or chemical or physical property of the analyte of interest.

2. The method of claim 1, wherein the analyte of interest is a chemical.

3. The method of claim 2, wherein the chemical is a biochemical.

4. The method of claim 3, wherein the biochemical is selected from the group consisting of a lipid, hormone, fatty acids, nucleic acid, polypeptide, and carbohydrate.

5. The method of claim 4, wherein the polypeptide is selected from the group consisting of an antibody, enzyme, and protein.

6. The method of claim 5, wherein the antibody is a monoclonal antibody, polyclonal antibody, humanized antibody, or fragments thereof.

7. The method of claim 5, wherein the enzyme is selected from the group consisting of lipases, esterases, proteases, glycosidases, glycosyl transferases, phosphatases, kinases, mono- and dioxygenases, haloperoxidases, lignin peroxidases, diarylpropane peroxidases, eposide hydrolases, nitrile hydrotases, nitrilases, transaminases, amidases, and acylases.

8. The method of claim 2, wherein the chemical is an organic selected from the group consisting of alkanes, alkenes, alkynes, dienes, alicyclic hydrocarbons, arenes, alcohols, ethers, ketones, aldehydes, carbonyls, carbanions, polynuclear aromatics and derivatives thereof.

9. The method of claim 1, wherein the specific activity is selected from the group consisting of enzymatic activity, binding activity, inhibitory activity, and modulating activity.

10. The method of claim 1, wherein the different differentially responsive sensors change optically, electrically, magnetically, mechanically, physically, or combinations thereof.

11. The method of claim 1, wherein the different differentially responsive sensor is selected form the group consisting of crystalline colloidal array (CCA) containing sensors, metal oxide sensors, dye-impregnated polymers coated onto beads or optical fibers, bulk conducting organic polymers, capacitance sensors, chemically-sensitive resistor sensors, and combinations thereof.

12. The method of claim 1, wherein the chemical or physical property is selected from the group consisting of side groups, charge, hydrophobicity, polarity, molecular size or shape, and chirality.

13. The method of claim 1, wherein the different differentially responsive sensors are chemically sensitive resistors.

14. A method of screening an analyte for a specific activity, chemical or physical property, or function comprising the steps of:

a) measuring outputs from an array comprising a plurality of chemically-sensitive resistors, each resistor comprising a conductive material and a non-conductive material, wherein the plurality of chemically sensitive resistor in the array are responsive to a plurality of analytes;

b) using results of said measuring to obtain a signal profile, related to a change in resistance in the plurality of resistors; and

c) comparing the signal profile to at least one previously-obtained signal profile obtained from a standard sample not including the analyte of interest and which has a known specific activity, chemical or physical property, or function, wherein such comparison is used to indicate a specific activity, function, or chemical or physical property of the analyte of interest.

15. The method of claim 14, wherein the analyte is a chemical.

16. The method of claim 15, wherein the chemical is a biochemical.

17. The method of claim 16, wherein the biochemical is selected from the group consisting of a lipid, hormone, fatty acids, nucleic acid, polypeptide, and carbohydrate.

18. The method of claim 17, wherein the polypeptide is selected from the group consisting of an antibody, enzyme, and protein.

19. The method of claim 18, wherein the antibody is a monoclonal antibody, polyclonal antibody, humanized antibody, or fragments thereof.

20. The method of claim 18, wherein the enzyme is selected from the group consisting of lipases, esterases, proteases, glycosidases, glycosyl transferases, phosphatases, kinases, mono- and dioxygenases, haloperoxidases, lignin peroxidases, diarylpropane peroxidases, eposide hydrolases, nitrile hydrotases, nitrilases, transaminases, amidases, and acylases.

21. The method of claim 15, wherein the chemical is an organic selected from the group consisting of alkanes, alkenes, alkynes, dienes, alicyclic hydrocarbons, arenes, alcohols, ethers, ketones, aldehydes, carbonyls, carbanions, polynucliear aromatics and derivatives thereof.

22. The method of claim 14, wherein the specific activity is selected from the group consisting of enzymatic activity, binding activity, inhibitory activity, and modulating activity.

23. The method of claim 14, wherein the resistor comprised of regions of a non-conductive material and regions of a conductive material compositionally different than the non-conductive material, each resistor providing an electrical path through the regions of conductive and non-conductive material, wherein interaction of the sample with the resistor provides a change in resistance in the material.

24. The method of claim 14, wherein the signal profile of the standard sample is derived from a library.

25. The method of claim 24, wherein the library is generated by a neural network.

26. The method of claim 14, wherein the chemical or physical property is selected from the group consisting of side groups, charge, hydrophobicity, polarity, molecular size or shape, and chirality.