Methods for Identifying Modulators of Ion Channels

• US 20090017488A1
• Filed: 07/11/2008
• Published: 01/15/2009
• Est. Priority Date: 07/11/2007
• Status: Active Grant

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Sru Biosystems Incorporated
• Inventors: Binder, Brant, Laing, Lance
• Granted Patent: US 9,778,267 B2
• Time in Patent Office: Days
• US Class Current: 435/29
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

The invention provides methods for identifying modulators of ion channels without the use of recombinant cell lines over-expressing the ion channel proteins or the use of detection labels.

Claims

7. A method of identifying a modulator of an ion channel comprising:

(a) applying cells, a test reagent, and a known ion channel antagonist or agonist of the cells to a first location on a surface of a colorimetric resonant reflectance optical biosensor;

(b) detecting a first PWV for the first location;

(c) applying cells and a known ion channel antagonist or agonist of the cells to a second location on a surface of a colorimetric resonant reflectance optical biosensor; and

(d) detecting a second PWV for the second location;

wherein, if the first and second PWVs are different, then the test reagent is a modulator of an ion channel and wherein if the first and second PWVs are the same or similar then the test reagent is not a modulator of an ion channel.

1. A method of identifying an antagonist or agonist of an ion channel comprising:

(a) applying cells to a first location and a second location on a surface of colorimetric resonant reflectance optical biosensor;

(b) applying a test reagent to the first location;

(c) applying a known ion channel antagonist or agonist of the cells to the second location;

(d) detecting a colorimetric resonant reflectance optical first peak wavelength value (PWV) for the first location and detecting a second PWV for the second location;

wherein if the first and second PWVs are the same or similar, then the test reagent is an antagonist or agonist of an ion channel; and

wherein if the first and second PWVs are substantially different, then the test reagent is not an antagonist or agonist.

2. The method of claim 1, wherein the cells are incubated for a period of time after their application to the first location;

after the application of the test reagent to the first location;

after the cells are applied to the second location, after the known ion channel antagonist or agonist is applied to the second location, or a combination thereof.

3. The method of claim 1, wherein the PWV is detected using a scanner with a lens having a lower limit pixel size of about 2 micrometers to about 200 micrometers.

4. The method of claim 1, wherein the first location and second location on the surface of the colorimetric resonant reflectance optical biosensor is an internal surface of a vessel selected from the group consisting of a microtiter well, microtiter plate, test tube, Petri dish, microfluidic channel, and microarray.

5. The method of claim 1, wherein the cells, test reagent, and ion channel antagonist or agonist do not comprise detection labels.

6. The method of claim 1, wherein the method is performed at a temperature of about 25, 30, or 37 degrees Celsius

8. The method of claim 7, wherein the cells are incubated for a period of time after their application to the first location;

after the application of the test reagent to the first location;

after the application of the known ion channel agonist or antagonist to the first location;

after the application of the cells to the second location, after the application of the known ion channel antagonist or agonist to the second location, or a combination thereof.

9. The method of claim 7, wherein the PWV is detected using a scanner with a lens having a lower limit pixel size of about 2 micrometers to about 200 micrometers.

10. The method of claim 7, wherein the first location and second location on the surface of the colorimetric resonant reflectance optical biosensor is an internal surface of a vessel selected from the group consisting of a microtiter well, microtiter plate, test tube, Petri dish, microfluidic channel, and microarray.

11. The method of claim 7, wherein the method is performed at a temperature of about 25, 30, or 37 degrees Celsius.

10-1. The method of claim 7, wherein the cells, test reagent, and ion channel antagonist or agonist do not comprise detection labels.