Multiplexed molecular analysis apparatus and method

• US 6,331,441 B1
• Filed: 12/21/1998
• Issued: 12/18/2001
• Est. Priority Date: 12/31/1996
• Status: Expired due to Term

• Current Assignee: High Throughput Genomics, Inc.
• Original Assignee: Genometrix Genomics Inc.
• Inventors: Mendoza, Leopoldo G., Hogan, Michael E., Balch, William J.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US09/217,154
• Time in Patent Office: 1,093 Days
• Field of Search: 435/6, 435/7.1, 435/287.1, 435/287.2, 435/288.4, 435/288.7, 435/808, 436/501, 436/809, 422/55, 422/58
• US Class Current: 506/15
• 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 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• 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 2219/00617 by chemical means
• 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 3/0262 using touch-off at substrate or container
• CPC Class Codes: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• 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 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/1034 : Transferring microquantities of liquid
• CPC Class Codes: G01N 2035/1039 : Micropipettes, e.g. microcapillary tubes
• CPC Class Codes: G01N 2035/1041 : Ink-jet like dispensers
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 35/0099 : comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/1065 : Multiple transfer devices
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array
• CPC Class Codes: Y10S 435/808 : Optical sensing apparatus
• CPC Class Codes: Y10S 436/80 : Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10S 436/804 : Radioisotope, e.g. radioimmunoassay
• CPC Class Codes: Y10S 436/805 : Optical property
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/115831 : Condition or time responsive

Abstract

A method and apparatus for analyzing molecular structures within a sample substance using an array having a plurality of test sites upon which the sample substance is applied. The invention is also directed to a method and apparatus for constructing molecular arrays having a plurality of test sites. The invention allows for definitive high throughput analysis of multiple analytes in complex mixtures of sample substances. A combinatorial analysis process is described that results in the creation of an array of integrated chemical devices. These devices operate in parallel, each unit providing specific sets of data that, when taken as a whole, give a complete answer for a defined experiment. This approach is uniquely capable of rapidly providing a high density of information from limited amounts of sample in a cost-effective manner.

Claims

1. A small molecule universal array comprising a plurality of wells, wherein each well comprises a plurality of biosites, wherein each biosite comprises only one specie of immobilized small molecule and at least one biosite has a specie of small molecule differing from a second biosite, and

a bi-specific molecule comprising two domains, wherein the first domain binds to the immobilized small molecule and the second domain comprises an analyte-binding domain.

2. The small molecule universal array of claim 1, wherein each well comprises at least four biosites, wherein each biosite comprises a different specie of immobilized small molecule.

3. The small molecule universal array of claim 1, wherein the immobilized small molecules comprise haptens.

4. The small molecule universal array of claim 1, wherein the immobilized small molecules are selected from the group consisting of fluorescein, biotin, 2, 4 dinitrophenol, TRITC and digoxigenin.

5. The small molecule universal array of claim 1, wherein the immobilized small molecules are selected from the group consisting of dinitrophenol;

amphetamine;

barbiturate;

acetaminophen;

acetohexamide;

desipramine;

lidocaine;

digitoxin;

chloroquinine;

quinine;

ritalin;

phenobarbital;

phenytoin;

fentanyl;

phencyclidine;

methamphetamine;

metaniphrine;

digoxin;

penicillin;

tetrahydrocannibinol;

tobramycin;

nitrazepam;

morphine;

Texas Red;

primaquine;

progesterone;

bendazac;

carbamazepine;

estradiol;

theophylline;

methadone;

methotrexate;

aldosterone;

norethisterone;

salicylate;

warfarin;

cortisol;

testosterone;

nortrptyline;

propanolol;

estrone; and

rostenedione;

digoxigenin;

biotin;

thyroxine; and

triiodothyronine.

6. The small molecule universal array of claim 1, wherein the small molecule is selected from the group consisting of a peptide, a drug and a hapten.