Optical biosensor method for cell-cell interaction

• US 20090181409A1
• Filed: 01/10/2008
• Published: 07/16/2009
• Est. Priority Date: 01/10/2008
• Status: Abandoned Application

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Li, Guangshan, Fang, Ye
• Application Number:
  US12/008,309
• Publication Number:
  US 20090181409A1
• Time in Patent Office: Days
• US Class Current: 435/7.210
• 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 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/554 the carrier being a biological cell or cell fragment, e.g. bacteria, yeast cells

Abstract

An apparatus and non-invasive method to measure cell-cell interactions, such as T-cell and stem cell interactions, under physiologically relevant conditions, and optionally measure the effects of stimuli on the cell-cell interactions, as defined herein.

Claims

1. A method for characterizing a live cell-cell interaction, the method comprising:

providing a biosensor system having a target cell immobilized on the biosensor;

contacting the immobilized target cell with an effector cell; and

detecting the dynamic mass redistribution of the target cell with the biosensor

2. The method of claim 1 further comprising contacting the target cell with a stimulus prior to contacting with the effector cell.

3. The method of claim 2 wherein the stimulus is selected from the group consisting of a Golgi apparatus disrupter, a cell-cycle blocker, an apoptosis inducer, an actin polymerization inhibitor, a GTPase modulator, a phosphatidylinositol 3-kinase inhibitor, an apoptosis inhibitor, a cell surface receptor modulator, and combinations thereof.

4. The method of claim 2 wherein the stimulus is selected from the group consisting of brefeldin A, camptothecin, latrunculin A, Rac1 inhibitor, wortmannin, Kp7-6, and combinations thereof.

5. The method of claim 1 further comprising contacting the target cell with a stimulus after contacting with the effector cell.

6. The method of claim 5 wherein the stimulus is selected from the group consisting of a Golgi apparatus disrupter, a cell-cycle blocker, an apoptosis inducer, an actin polymerization inhibitor, a GTPase modulator, a phosphatidylinositol 3-kinase inhibitor, an apoptosis inhibitor, a cell surface receptor modulator, and combinations thereof.

7. The method of claim 5 wherein the stimulus is selected from the group consisting of brefeldin A, camptothecin, latrunculin A, Rac1 inhibitor, wortmannin, Kp7-6, or combinations thereof.

8. The method of claim 1 wherein the target cell comprises at least one of a tumor cell, an infected cell, a normal cell, a stem cell, a cancerous cell, or mixtures thereof.

9. The method of claim 1 wherein the effector cell comprises at least one of a T cell, a helper T cell, a B cell, a transmitter-producing cell, or mixtures thereof.

10. The method of claim 9 wherein the transmitter-producing cell comprises at least one of an insulin-producing cell, an islet cell, a mast cell, a monocyte, and mixtures thereof.

11. The method of claim 1 wherein the target cell immobilized on the biosensor'"'"'s surface has a confluency of from about 0.5% to about 100%.

12. The method of claim 1 wherein the biosensor system comprises a swept wavelength optical interrogation imaging system for a resonant waveguide grating biosensor, an angular interrogation system for a resonant waveguide grating biosensor, a spatially scanned wavelength interrogation system, surface plasmon resonance system, surface plasmon resonance imaging, or a combination thereof.

13. The method of claim 1 wherein the dynamic mass redistribution signal comprises an optical signal that measures real-time kinetics of an effector cell contact-induced cellular response as a function of time.

14. The method of claim 1 wherein the dynamic mass redistribution signal comprises an optical signal that measures an endpoint or multiple points of an effector cell contact-induced cellular response over time and throughout an effector cell contact-induced event.

15. The method of claim 1 wherein the biosensor imaging system provides biosensor output comprising at least one of:

the overall dynamics, the phase, the amplitude and kinetics of the phase, the transition time from one phase to another of the dynamic mass redistribution signal, or a combination thereof.

16. A method for characterizing a live cell-cell response to a stimulus, the method comprising:

providing a biosensor imaging system having a target cell immobilized on the biosensor;

contacting the immobilized target cell with a first stimulus;

contacting the first stimulus-contacted immobilized target cell with an effector cell;

detecting the dynamic mass redistribution of the target cell with the biosensor; and

determining the cell-signaling difference effect of contacting the stimulus- contacted target cell with the effector cell.

17. The method of claim 16 further comprising contacting with a second stimulus the first stimulus-contacted immobilized target cell and the effector cell.

18. The method of claim 16 wherein the second stimulus is the same as the first stimulus or the second stimulus is different from the first stimulus.

19. A method for characterizing a live cell-cell response to a stimulus, the method comprising:

providing a biosensor imaging system having a target cell and an effector cell immobilized on the biosensor'"'"'s surface;

contacting the immobilized effector cell with a stimulus; and

detecting the dynamic mass redistribution signals of the target cell and the effector cell.

20. The method of claim 19 wherein the effector cell is a transmitter-releasing cell, the released transmitter activates the target cell and triggers signaling of the target cell.