Cell classification based on mechanical signature of nucleus

1. A method for determining a mechanical property of a nucleus of at least one cell in a sample comprising:

acquiring the at least one cell's mechanical signatures using label-free cytometry enabled by Brillouin spectroscopy; and

classifying cells based on the cells mechanical signatures of the at least one nuclei.

2. The method of claim 1 , wherein the label-free cytometry comprises the steps of:

illuminating the sample by a light beam along a first direction;

collecting a Brillouin scattered light emitted from the sample in response to the illuminating light beam;

sending the Brillouin scattered light to an optical arrangement to induce a spectral dispersion and to a detection unit to generate a spatio-spectral pattern of the Brillouin scattered light, wherein the optical arrangement and the detection unit are positioned along a second direction;

detecting the spatio-spectral pattern of the Brillouin scattering light onto the detection unit, wherein multiple points of the sample along the illuminating light beam are measured simultaneously; wherein at least one of the multiple points of the sample is a cell nucleus;

calibrating the spectral pattern at each spatial point at the detection unit; and calculating the one or more Brillouin metrics at each measured sample point based on the detected spatio-spectral pattern.

3. The method of claim 2 , wherein the one or more Brillouin metrics are selected from the group consisting of: Brillouin frequency shift, Brillouin spectrum line width, Brillouin gain or loss spectrum, and a combination thereof.

4. The method of claim 2 , wherein the angle between the first direction and the second direction is any angle greater than 0°.

5. The method of claim 2 , wherein the optical arrangement to induce a spectral dispersion includes a virtually imaged phased array (VIPA), a Fabry-Perot etalon, or an echelle grating.

6. The method of claim 2 , wherein the optical arrangement to induce a spectral dispersion further comprises optical elements to modify size, shape, and/or angular spread of the spatio-spectral pattern in an optical path from the sample to the detection unit.

7. The method of claim 1 , wherein the sample is a biological sample including biological organism, tissue, or biological cells including living cells.

8. The method of claim 7 , wherein the biological cells are suspended, adherent to 2D substrates, cultured within 3D extracellular matrices, or flows through one or more channels of a microfluidic chip.

9. The method of claim 1 , wherein the mechanical property of the nucleus is selected from the group comprising elasticity, viscosity, and nuclear stiffness.

10. The method of claim 9 , wherein the scanned cell is classified based on the nucleus' measured mechanical property.

11. The method of claim 10 , wherein the scanned cell is classified as a cancer cell.

12. The method of claim 1 , wherein the at least one cell is a living eukaryotic cells.

13. The method of claim 1 , wherein the classification is based on either cell population or single cell.

14. The method of claim 1 , wherein the at least one cell is

(i) flowing inside a microfluidic channel,

(ii) immobilized in suspension, or

(iii) encapsulated in droplets of 3D gels.

15. A system for obtaining one or more Brillouin metrics associated with a Brillouin scattering spectrum at multiple points, wherein a least one point is within a nucleus of at least one cell in a sample, the system comprising:

an illumination source illuminating the sample by a light beam along a first direction;

one or more lenses collecting a Brillouin scattered light emitted from the sample in response to the illuminating light beam;

an optical arrangement to receive the Brillouin scattered light from the one or more lenses, the optical arrangement to induce a spectral dispersion;

a detection unit to detect a spatio-spectral pattern of the Brillouin scattered light, wherein the one or more lenses, the optical arrangement, and the detection unit are positioned along a second direction, wherein multiple points of the sample along the illuminating light beam are measured simultaneously;

a processor executing instructions for:

calibrating the spectral pattern at each spatial point at the detection unit; and

calculating the one or more Brillouin metrics at each measured sample point based on the detected spatio-spectral pattern.

16. The system of claim 15 wherein the one or more Brillouin metrics are selected from the group consisting of: Brillouin frequency shift, Brillouin spectrum line width, Brillouin gain or loss spectrum, and a combination thereof.

17. The system of claim 16 , wherein the one or more Brillouin metrics determine a mechanical property of the at least one nucleus, wherein the mechanical property is selected from the group comprising elasticity, viscosity, and nuclear stiffness.

18. The system of claim 17 , wherein the scanned cell is classified based on the nucleus' measured mechanical property.

19. The system of claim 18 , wherein the scanned cell is classified as a cancer cell.

20. The system of claim 15 , wherein the second direction is orthogonal to the first direction.

21. A method of identifying a cancerous cell in a sample, comprising:

illuminating the sample by a light beam along a first direction;

collecting a Brillouin scattered light emitted from the sample in response to the illuminating light beam;

sending the Brillouin scattered light to an optical arrangement to induce a spectral dispersion and to a detection unit to generate a spatio-spectral pattern of the Brillouin scattered light, wherein the optical arrangement and the detection unit are positioned along a second direction;

detecting the spatio-spectral pattern of the Brillouin scattering light onto the detection unit, wherein multiple points of the sample along the illuminating light beam are measured simultaneously; wherein at least one of the multiple points of the sample is a cell nucleus;

calibrating the spectral pattern at each spatial point at the detection unit; and calculating the one or more Brillouin metrics at each measured sample point based on the detected spatio-spectral pattern;

identifying cancerous cells present in the sample by comparing the calculated Brillouin metrics to those of normal cells.

22. The method of claim 21 , wherein the one or more Brillouin metric provide information regarding a mechanical property of the nucleus, wherein the mechanical property is selected from the group comprising elasticity, viscosity, and nuclear stiffness.

23. The method of claim 21 , wherein the second direction is orthogonal to the first direction.