Method and apparatus for conducting multiple chemical assays

• US 5,508,200 A
• Filed: 10/19/1992
• Issued: 04/16/1996
• Est. Priority Date: 10/19/1992
• Status: Expired due to Fees

• Current Assignee: Spectrum Systems, Inc.
• Original Assignee: Spectrum Systems, Inc.
• Inventors: Thayer, Phillip, Tiffany, Thomas, Weyrauch, Bruce
• Primary Examiner(s): Warden, Robert J.
• Assistant Examiner(s): BHAT, NINA NMN
• Application Number:
  US07/963,457
• Time in Patent Office: 1,275 Days
• Field of Search: 422/56, 422/66, 422/67, 422/63-65, 436/169, 436/165, 436/166, 436/43, 436/530, 436/44, 436/46, 435/4, 435/291, 435/7.92
• US Class Current: 436/44
• 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 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00533 essentially rectangular
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• 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 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• 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 2035/00752 bar codes
• CPC Class Codes: G01N 35/00009 provided with a sample supporting tape, e.g. with absorbent zones
• CPC Class Codes: G01N 35/00029 provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: Y10T 436/110833 Utilizing a moving indicator strip or tape
• CPC Class Codes: Y10T 436/112499 with sample on test slide

Abstract

A system for high performance automated chemical analysis includes a video camera photometer with a computer-controlled interference filter wheel. A fluidics system delivers ultramicro sample and reagent volumes in the 0.05 to 5.0 microliter range to a supporting analytical media. The media is precisely positioned relative to the photometer by an x-y axis reaction media holder capable of accurate and precise positioning of the ultramicro reaction spots. The reaction media can consist of absorbent cellulose sample/reaction strips or microscopic sized multiple wells. A data and reduction system monitors multiple simultaneous reactions within a common test area of the analytical media to provide final quantitative reports. The method for conducting multiple chemical assays involves placing small volumes of sample/reagent combinations at discrete locations about a common test area on the analytical media and simultaneously measuring resulting optical changes at each discrete location.

Claims

1. A method for conducting multiple chemical assays on a liquid sample in the same time and temperature dimension, comprising the following steps:

placing a volume of liquid sample about a test area on a supporting analytical media;

adding smaller separate volumes of a plurality of liquid reagents to the liquid sample at predetermined spaced-apart locations about the test area on the supporting analytical media;

causing the liquid reagents and liquid sample to mix with one another within the test area on the supporting analytical media;

simultaneously capturing at least one complete digital image of the test area;

storing each digital image of the test area; and

processing each digital image of the test area to yield quantitative test results with respect to sample/reagent reactions at each spaced-apart location about the test area as a function of optical changes that have occurred at the spaced-apart locations within the test area.

2. The method of claim 1, wherein the liquid sample is directed onto an exposed absorbent surface of the supporting analytical media to impregnate the media and produce an exposed spot containing the sample.

3. The method of claim 1, wherein the liquid reagents are directed onto an exposed absorbent surface of the supporting analytical media to impregnate the media and produce a preselected pattern of exposed spots containing the reagents.

4. The method of claim 1, wherein the liquid reagents are simultaneously directed onto an exposed absorbent surface of the supporting analytical media.

5. The method of claim 1, wherein the liquid reagents are simultaneously directed onto an absorbent exposed surface of the supporting analytical media in individual volumes of one-half microliter or less.

6. The method of claim 1, wherein the step of applying the sample precedes the step of applying the reagents.

7. The method of claim 1, wherein the step of applying the reagents precedes the step of applying the sample.

8. The method of claim 1, wherein the capturing step is preceded by the following step:

drying the mixed reagents and sample within the test area on the supporting analytical media.

9. The method of claim 1, wherein the step of applying a volume of the liquid sample is carried out by placing liquid sample on the surface of an absorbent sheet.

10. The method of claim 1, wherein the step of applying a volume of the liquid sample is carried out by placing liquid sample on the surface of an absorbent sheet;

and further comprising the following additional step;

drying the liquid sample on the sheet prior to the step of applying the liquid reagents.

11. An apparatus for conducting multiple chemical assays on a liquid sample in the same time and temperature dimension, comprising:

a supporting analytical media;

dispensing means for placing multiple combinations of a sample and selected reagents at predetermined spaced-apart locations about a test area on the supporting analytical media;

detection means for simultaneously capturing at least one complete digital image of the test area;

storage means for storing each digital image of the test area; and

means for processing each digital image of the test area to yield quantitative test results with respect to sample/reagent reactions at each spaced-apart location about the test area as a function of optical changes that have occurred at the spaced-apart locations within the test area.

12. The apparatus of claim 11, wherein the dispensing means further includes:

multiple applicator means for simultaneously directing a plurality of liquids to the test area in predetermined spaced-apart areas.

13. The apparatus of claim 11, wherein the dispensing means further includes:

multiple reagent applicator means for simultaneously directing a plurality of reagents to the test area in predetermined space-apart locations also containing a sample.

14. The apparatus of claim 11, wherein the dispensing means further includes:

a sample applicator directing a volume of a sample within a selected test area of the supporting analytical media; and

multiple reagent applicators capable of simultaneously directing a plurality of reagents onto the supporting analytical media in predetermined spaced-apart locations within the test area.

15. The apparatus of claim 11, wherein the dispensing means further includes:

a reagent applicator directing a volume of a reagent within a selected test area of the supporting analytical media; and

multiple sample applicators capable of simultaneously directing a plurality of samples onto the supporting analytical media in predetermined spaced-apart locations within the test area.

16. A method for conducting multiple chemical assays on a liquid sample in the same time and temperature dimension, comprising the following steps:

placing a volume of a liquid reagent to a test area on a supporting analytical media;

adding smaller separate volumes of a plurality of liquid samples to the liquid reagent at predetermined spaced-apart locations about the test area on the supporting analytical media;

causing the liquid reagent and liquid samples to mix with one another within the test area on the supporting analytical media;

simultaneously capturing at least one complete digital image of the test area;

storing each digital image of the test area; and

processing each digital image of the test area to yield quantitative test results with respect to sample/reagent reactions at each spaced-apart location about the test area as a function of optical changes that have occurred at the spaced-apart locations within the test area.

17. The method of claim 16, wherein the liquid reagent is directed onto an exposed absorbent surface of the supporting analytical media to impregnate the media and produce an exposed spot containing the liquid reagent.

18. The method of claim 16, wherein the liquid samples are directed onto an exposed absorbent surface of the supporting analytical media to impregnate the media and produce a preselected pattern of exposed spots containing the liquid reagent.

19. The method of claim 16, wherein the liquid samples are simultaneously directed onto an exposed absorbent surface of the supporting analytical media.

20. The method of claim 16, wherein the liquid samples are simultaneously directed onto an absorbent exposed surface of the supporting analytical media in individual volumes of one-half microliter or less.

21. The method of claim 16, wherein the step of applying the liquid reagent precedes the step of applying the liquid samples.

22. The method of claim 16, wherein the step of applying the liquid samples precedes the step of applying the liquid reagent.

23. The method of claim 16, wherein the capturing step is preceded by the following step:

drying the mixed reagents and sample within the test area on the supporting analytical media.

24. The method of claim 16, wherein the step of applying the liquid reagent is carried out by placing it on the surface of an absorbent sheet.

25. The method of claim 16, wherein the step of applying the liquid reagent is carried out by placing it on the surface of an absorbent sheet;

and further comprising the following additional step;

drying the liquid reagent on the sheet prior to the step of applying the liquid samples.