Device and method for force phenotyping of cells for high-throughput screening and analysis

1. A system for assaying forces applied by cells comprising:

an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa, the optically transparent substrate having a plurality of wells formed thereon, the plurality of wells containing cells and one or more different drugs or compounds;

an array of geometrically shaped molecular patterns disposed on a surface of the optically transparent substrate in the wells, the geometrically shaped molecular patterns comprising fluorophore-conjugated patterns adherent to cells;

at least one light source configured to excite the fluorophore-conjugated patterns;

an imaging device configured to capture fluorescent light emitted from the geometrically shaped molecular patterns; and

a computing device configured to receiving images from the imaging device, the computing device further configured to measure a dimensional change of the geometrically shaped molecular patterns having cells disposed thereon.

2. The system of claim 1 , wherein the dimensional change is measured in real time.

3. The system of claim 1 , wherein the dimensional change is measured over an elapsed period of time.

4. The system of claim 1 , wherein the optically transparent substrate comprises polydimethylsiloxane (PDMS).

5. The system of claim 1 , wherein the system comprises first and second light sources emitting light at different wavelengths.

6. The system of claim 1 , wherein the geometrically shaped patterns comprise a mixture or combination of two or more proteins.

7. The system of claim 1 , wherein the array of geometrically shaped molecular patterns comprise symmetrical patterns.

8. The system of claim 1 , wherein the array of geometrically shaped molecular patterns comprise asymmetrical patterns.

9. A method for assaying forces applied by cells comprising:

providing a test plate comprising:

an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa;

an array of geometrically shaped molecular patterns disposed on a surface of the optically transparent substrate, the geometrically shaped molecular patterns comprising fluorophore-conjugated patterns adherent to cells;

a second substrate containing a plurality of apertures therein, the second substrate secured to the surface of the optically transparent substrate to form a plurality of wells wherein each well contains one or more geometrically shaped molecular patterns therein;

providing at least one light source configured to excite the geometrically shaped molecular patterns;

providing an imaging device configured to capture fluorescent light emitted from the geometrically shaped molecular patterns;

providing a computing device configured to receiving images from the imaging device, the computing device further configured to measure a dimensional change of the geometrically shaped molecular patterns having cells disposed thereon;

loading the plurality of wells with cells so that at least some of the cells adhere to the geometrically shaped molecular patterns;

loading some of the wells with a different compound or drug;

illuminating the plurality of wells with the at least one light source;

imaging the geometrically shaped molecular patterns from the plurality of wells; and

measuring a dimensional change of the geometrically shaped molecular patterns within the wells with the computing device.

10. The method of claim 9 , further comprising identifying those cells having a dimensional change within a certain range.

11. The method of claim 9 , wherein the dimensional change comprises contraction.

12. The method of claim 9 , wherein the dimensional change comprises relaxation.

13. The method of claim 9 , further comprising loading a fixation agent into the plurality of wells prior to measuring the dimensional change.

14. The method of claim 9 , wherein the dimensional change is measured in real time.

15. A method of identifying the force phenotype of cells comprising:

providing an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa, the optically transparent substrate having an array of geometrically shaped molecular patterns disposed on a surface thereof, the geometrically shaped molecular patterns comprising fluorophore-conjugated patterns adherent to cells;

loading cells on the optically transparent substrate, wherein at least some of the geometrically shaped molecular patterns have one or more cells adhered thereto;

illuminating the geometrically shaped molecular patterns; and

capturing images of fluorescent light emitted from the geometrically shaped molecular patterns with an imaging device;

measuring a dimensional change of the geometrically shaped molecular patterns with a computing device; and

categorizing the cells based at least in part on the measured dimensional change.

16. The method of claim 15 , wherein the computing device identifies those geometrically shaped molecular patterns having a single cell disposed thereon.

17. The method of claim 15 , wherein the cells are exposed to a compound or drug prior to measuring a dimensional change.