Methods for Screening Cells and Antibodies

• US 20100196925A1
• Filed: 04/13/2010
• Published: 08/05/2010
• Est. Priority Date: 09/09/2002
• Status: Active Grant

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Sru Biosystems Incorporated
• Inventors: Lin, Bo, Li, Peter, Laing, Lance G., Karl, William C., Smith, Timothy F., Genick, Christine C., Madison, Lara
• Granted Patent: US 8,202,735 B2
• Time in Patent Office: Days
• US Class Current: 435/7.2
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C40B 30/04 by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: C40B 30/10 by measuring physical properties, e.g. mass
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/255 Details, e.g. use of specially adapted sources, lighting or optical systems
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide
• CPC Class Codes: G01N 33/5026 on cell morphology
• CPC Class Codes: G01N 33/5029 on cell motility
• CPC Class Codes: G01N 33/5032 on intercellular interactions
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G02B 5/1809 with pitch less than or comparable to the wavelength
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays

Abstract

The invention provides methods of detecting a change in cell growth patterns, methods of screening many different antibodies in one receptacle, and methods of detecting specific binding of an antibody to a protein or cell, wherein the antibody is in a mixture of many different antibodies.

Claims

1. A method of detecting a change in a cell growth pattern comprising:

a) applying one or more cells to a location on a surface of a colorimetric resonant reflectance optical biosensor;

b) detecting a colorimetric resonant reflectance optical peak wavelength value (PWV) for the location;

c) incubating the one or more cells for a period of time or applying a test reagent or stimulus to the one or more cells;

d) detecting the colorimetric resonant reflectance optical PWV for the location; and

e) comparing the PWV of step b) to the PWV of step d);

wherein a difference between the colorimetric resonant reflectance optical PWV of step b) in relation to the colorimetric resonant reflectance optical PWV of step d) indicates a change in the cell growth pattern in the one or more cells.

2. The method of claim 1, wherein the change in cell growth pattern is a change in cell morphology, change in cell adhesion, change in cell migration, change in cell proliferation, change in cell death, change in velocity of cell movement, change in directional movement, or a combination thereof.

3. The method of claim 1, wherein the change in cell growth pattern is a change in cell size, a change in cell shape, a change in cell height, or a change in cell surface uniformity or combination thereof.

4. 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 15 micrometers.

5. The method of claim 1, wherein the location on a surface of a 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.

6. The method of claim 1, wherein the change in cell growth pattern is a change in microtubule structure, change in microfilament structure, granule exocytosis, respiratory burst, cell differentiation, lamellopodia structure, stress fiber structure, or a combination thereof.

7. The method of claim 1, wherein before or after applying the test reagent or stimulus to the one or more cells, the one or more cells are incubated for a period of time.

8. The method of claim 1, wherein the one or more cells and the test reagent or stimulus do not comprise detection labels.

9. The method of claim 1, wherein the method is completed in less than 3 hours or in less than 1 hour.

10. The method of claim 1, wherein in the one or more cells are present in a complex background.

11. The method of claim 1, wherein the one or more cells applied to the biosensor become immobilized to the biosensor.

12. The method of claim 11, wherein the one or more cells are immobilized to the biosensor surface in an array of one or more distinct locations and a colorimetric resonant reflectance optical PWV is detected for each distinct location of the array.