Comparative phenotype analysis for assessment of biologically active compounds such as antimicrobials

• US 6,436,631 B1
• Filed: 02/02/2001
• Issued: 08/20/2002
• Est. Priority Date: 04/20/2000
• Status: Expired due to Term

• Current Assignee: Biolog, Inc.
• Original Assignee: Biolog, Inc.
• Inventors: Bochner, Barry
• Primary Examiner(s): Leary, Louise N.
• Application Number:
  US09/776,332
• Time in Patent Office: 564 Days
• Field of Search: 435/4, 435/29, 435/975, 435/32, 435/822
• US Class Current: 435/4
• CPC Class Codes: C12Q 1/18 Testing for antimicrobial activity of a material
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: Y10S 435/822 using bacteria or actinomycetales
• CPC Class Codes: Y10S 435/975 Kit

Abstract

The present invention relates to using multitest panels to improve the effectiveness, throughput, and efficiency of testing and commercial development of biologically active compounds, in particular those useful in human, animal, and plant health. In particular, the present invention provides phenotype microarrays suitable for testing biologically active compounds for their potential application in clinical, veterinary, and plant health.

Claims

1. A method for testing the response of at least one cell to at least one biologically active chemical comprising the steps of:

(a) providing;

i) a testing device having at least two wells, wherein each well of said testing device contains at least one substrate selected from the group consisting of carbon sources, nitrogen sources, phosphorus sources, sulfur sources, growth stimulating nutrients, antimicrobials, and chromogenic testing substrates; and

ii) a suspension comprising at least one cell and at least one biologically active chemical;

(b) inoculating said suspension into said wells of said testing device; and

(c) observing the response of said at least one cell to said at least one biologically active chemical.

2. The method of claim 1, wherein said testing device is selected from the group consisting of microtiter plates and microcards.

3. The method of claim 1, wherein said suspension further comprises a gelling agent.

4. The method of claim 1, wherein said testing device further comprises a gel-initiating agent in said wells.

5. The method of claim 1, wherein said suspension further comprises a colorimetric indicator.

6. The method of claim 1, wherein said testing device further comprises a colorimetric indicator in said wells.

7. The method of claim 1, wherein said observing is visual.

8. The method of claim 1, wherein said observing is performed by an instrument.

9. A method for comparing the effect of at least two biologically active chemicals comprising:

a) providing;

i) a first cell suspension comprising at least one cell type and at least one biologically active chemical,

ii) a second cell suspension comprising the same said at least one cell type in step i) and at least one biologically active chemical wherein said biologically active chemical is different from said biologically active chemical in said first cell suspension,

iii) a first testing device having wells, wherein said wells contain at least one substrate selected from the group consisting of carbon sources, nitrogen sources, phosphorus sources, sulfur sources, growth stimulating nutrients, antimicrobials, and chromogenic testing substrates,

iv) a second testing device having wells, wherein said wells contain at least one substrate selected from the group consisting of carbon sources, nitrogen sources, phosphorus sources, sulfur sources, growth stimulating nutrients, antimicrobials, and chromogenic testing substrates, and

b) adding said first cell suspension to said wells of said first testing device to provide a first phenotype array;

c) adding said second cell suspension to said wells of said second testing device to provide a second phenotype array;

d) incubating said first and said second phenotype arrays;

e) observing the response of said cell suspension in said first and said second phenotype arrays; and

f) comparing the response of said cell suspension in said first phenotype array with the response of said cell suspension in said second phenotype array.

10. The method of claim 9, wherein said first and second testing devices are selected from the group consisting of microtiter plates and microcards.

11. The method of claim 9, wherein said first and second cell suspensions further comprise a gelling agent.

12. The method of claim 9, wherein said first and second testing devices further comprise a gel-initiating agent in said wells.

13. The method of claim 9, wherein said first and second cell suspensions further comprise a calorimetric indicator.

14. The method of claim 9, wherein said first and second testing devices further comprise a colorimetric indicator in said wells.

15. The method of claim 9, wherein said first testing device contains the same substrates as said second testing device.

16. The method of claim 9, wherein said observing is visual.

17. The method of claim 9, wherein said observing is performed by an instrument.

18. The method of claim 9, wherein said comparison of said response is performed using multi-dimensional pattern analysis.

19. A multiwell kit for testing the effect of at least one biologically active chemical comprising:

i) at least one testing device having at least two wells, wherein said wells contain at least one substrate selected from the group consisting of carbon sources, nitrogen sources, phosphorus sources, sulfur sources, growth stimulating nutrients, antimicrobials, and chromogenic substrates; and

ii) a cell suspension medium containing at least one biologically active chemicals.

20. The method of claim 19, wherein said at least one testing device is selected from the group consisting of microtiter plates and microcards.

21. The kit of claim 19, wherein said cell suspension medium further comprises a gelling agent.

22. The kit of claim 19, wherein said testing device further comprises a gel-initiating agent in said wells.

23. The kit of claim 19, wherein said cell suspension medium further comprises a colorimetric indicator.

24. The kit of claim 19, wherein said testing device further comprises a colorimetric indicator in said wells.