Automated system for high-throughput all-optical dynamic electrophysiology
Bio-photonic devices or target cells and cell cultures including bio-photonic devices and target cells are provided. Methods of preparing cell cultures including bio-photonic devices and target cells are also provided. Methods of analyzing the electrophysiology of target cells using the cell cultures are provided. Systems for analyzing the electrophysiology of target cells are also provided.
1. A method of testing an effect of a compound on the electrophysiology of a target cell, the method comprising:
exposing a cell culture to a compound, the cell culture comprising:
a target cell without genetic transformation to make it light-sensitive; and
a bio-photonic device comprising:
a non-biological cell body; and
at least one of a photon-sensitive entity or a combination of a photon-sensitive entity and a photon-generating entity disposed in the non-biological cell body, wherein the bio-photonic device is configured to activate the target cell;
exposing the cell culture to photonic energy; and
measuring an electrophysiological signal in the target cell.
2. The method of claim 1 , further comprising:
using at least one of a fluorescent reporter disposed in the cell culture or an optical phenomenon to measure the electrophysiological signal in the target cell.
3. The method of claim 1 , wherein the electrophysiological signal is selected from at least one of a level of intracellular calcium, a membrane potential, a level of an electrophysiology-associated ion, or a mechanical contraction.
4. The method of claim 1 , wherein the photonic energy is provided by an external source.
5. The method of claim 1 , wherein the photonic energy is provided by an internal source.
6. The method of claim 5 , wherein the internal source is a photon-generating entity disposed in the cell body.
7. The method of claim 1 , wherein the photonic energy is provided in pulses, continuously, and/or at a desired frequency.
8. The method of claim 7 , wherein the photon-sensitive entity is configured to induce a local electric field change and/or convert photons having a first energy to photons having a second energy.
9. The method of claim 8 , wherein the photon-sensitive entity is selected from at least one of a chromophore or a combination of a chromophore and a nanoparticle.
10. The method of claim 8 , wherein the local electric field change is configured to change a membrane potential of the target cell disposed adjacent the bio-photonic device.
11. The method of claim 7 , wherein the photon-generating entity is configured to emit photons in the absence of external photons and wherein the emitted photons activate the photon-sensitive entity to induce a local electric field change.
12. The method of claim 11 , wherein the local electric field change is configured to change a membrane potential of the target cell disposed adjacent the bio-photonic device.
13. The method of claim 7 , wherein the photon-sensitive entity is configured to absorb photonic energy between about 100 nm and about 1,300 nm and wherein the photon-generating entity is configured to emit photonic energy between about 100 nm and about 1,300 nm.
14. The method of claim 7 , wherein the non-biological cell body is a synthetic vesicle.
15. The method of claim 7 , wherein the non-biological cell body is selected from at least one of a liposome or a bio-compatible encapsulated entity, and wherein the non-biological cell body contains at least one of a protein or a light sensitive structure configured to convert optical radiation to a local electric field change.
16. The method of claim 1 , wherein the target cell is a cardiomyocyte.
17. The method of claim 1 , wherein the cardiomyocyte is derived from at least one of an induced pluripotent stem cell or an embryonic stem cell.
18. The method of claim 1 , wherein the method is a high-throughput method.
19. The method of claim 1 , wherein the method is an automated method.