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Title:
LABEL-FREE OPTICAL DETECTION OF BIOELECTRIC POTENTIALS USING ELECTROCHROMIC MATERIALS
Document Type and Number:
WIPO Patent Application WO/2021/231635
Kind Code:
A1
Abstract:
The invention pertains to a method for assessing near a surface a change in electrical activity, such as a change in electrical potential. The methods comprise measuring a change in an absorption parameter of an electrochromic material on the surface. The measured absorption parameter can be absorbance, absorption maximum, or relative reflectivity of the electrochromic material. The electrochromic material can be on a transparent, substantially transparent, or translucent substrate. The methods could be used to detect changes in electrical activity at an area between 0.1 mm2 and 1 mm2 and over a period of between 1 millisecond and 100 milliseconds. The preferred electrochromic material is Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS). These methods could be used to measure electrical activity of a cell cultured on a surface comprising the electrochromic material. The cell can be is a neuronal cell or a muscle cell.

Inventors:
CUI BIANXIAO (US)
ALFONSO FELIX (US)
MUELLER HOLGER (US)
Application Number:
PCT/US2021/032074
Publication Date:
November 18, 2021
Filing Date:
May 12, 2021
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
UNIV LELAND STANFORD JUNIOR (US)
UNIV CALIFORNIA (US)
International Classes:
G01N21/64; C12M1/28; C12M3/04; G01N21/78
Foreign References:
US20200123218A12020-04-23
US20040143091A12004-07-22
US20170166862A12017-06-15
US20080122428A12008-05-29
US20180334646A12018-11-22
US20050259249A12005-11-24
Other References:
ALFONSO FELIX S., ZHOU YUECHENG, LIU ERICA, MCGUIRE ALLISTER F., YANG YANG, KANTARCI HUSNIYE, LI DONG, COPENHAVER ERIC, ZUCHERO J.: "Label-free optical detection of bioelectric potentials using electrochromic thin films", BIORXIV, 17 May 2020 (2020-05-17), pages 1 - 22, XP055875912, DOI: 10.1101/2020.05.16.099002
Attorney, Agent or Firm:
KEDDIE, James (US)
Download PDF:
Claims:
WE CLAIM: 1. A method for assessing electrical activity near a surface comprising an electrochromic material, comprising measuring a change in an absorption parameter of the electrochromic material. 2. The method of claim 1, wherein the assessing comprises measuring a change in an electrical potential near the surface. 3. The method of claim 1 or 2, wherein the absorption parameter comprises absorbance of the electrochromic material. 4. The method of claim 1 or 2, wherein the absorption parameter comprises absorption maximum of the electrochromic material. 5. The method of claim 1 or 2, wherein the absorption parameter comprises relative reflectivity change of the electrochromic material. 6. The method of any of preceding claims, wherein the surface comprises a layer of the electrochromic material on a transparent, substantially transparent, or translucent substrate. 7. The method of claim 5, wherein the layer of electrochromic material has a thickness of between 50 nm and 500 nm. 8. The method of any of preceding claims, wherein the absorption parameter is analyzed using a light beam incident on the surface at an angle. 9. The method of claim 8, wherein the incident angle is between 55o and 75o. 10. The method of claim 8 or 9, comprising focusing the laser beam onto the surface through a prism-coupled total internal reflection configuration.

11. The method of any of preceding claims, wherein the area of the surface in which the change in the absorption parameter is measured is between 0.1 mm2 to 1 mm2. 12. The method of any of preceding claims, comprising measuring the change in the absorption parameter of the electrochromic material over a period of between 1 millisecond to 100 milliseconds. 13. The method of any of preceding claims, wherein the electrochromic material comprises a metal-organic frameworks, metal oxide, or conductive polymer. 14. The method of any of preceding claims, wherein the electrochromic material comprises Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS). 15. The method of any of preceding claims, comprising measuring the change in the absorption parameter of the electrochromic material at a plurality of locations near the surface. 16. The method of any of preceding claims, comprising measuring the change in the absorption parameter of the electrochromic material at two wavelengths. 17. The method of claim 16, wherein the two wavelengths are selected such that the change in the absorption parameter of the electrochromic material for one of the two wavelengths is opposite to the change in the absorption parameter for the other wavelength. 18. A method for assessing electrical activity of a cell, comprising culturing the cell on a surface comprising an electrochromic material and measuring a change in an absorption parameter of the electrochromic material. 19. The method of claim 18, wherein the assessing comprises measuring a change in an electrical potential near the surface. 20. The method of claim 18 or 19, wherein the absorption parameter comprises absorbance of the electrochromic material.

21. The method of claim 18 or 19, wherein the absorption parameter comprises absorption maximum of the electrochromic material. 22. The method of claim 18 or 19, wherein the absorption parameter comprises relative reflectivity change of the electrochromic material. 23. The method of any of claims 18 to 22, wherein the surface comprises a layer of the electrochromic material on a transparent, substantially transparent, or translucent substrate. 24. The method of claim 23, wherein the layer of electrochromic material has a thickness of between 50 nm and 500 nm. 25. The method of any of claims 18 to 24, wherein the absorption parameter is analyzed using a light beam incident on the surface at an angle. 26. The method of claim 25, wherein the incident angle is between 55o and 75o. 27. The method of claim 25 or 26, comprising focusing the laser beam onto the surface through a prism-coupled total internal reflection configuration. 28. The method of any of claims 18 to 27, wherein the area of the surface in which the change in the absorption parameter is measured is between 0.1 mm2 and 1 mm2. 29. The method of any of claims 18 to 28, comprising measuring the change in the absorption parameter of the electrochromic material over a period of between 1 millisecond and 100 milliseconds. 30. The method of any of claims 18 to 29, wherein the electrochromic material comprises a metal-organic frameworks, metal oxide, or conductive polymer. 31. The method of any of claims 18 to 30, wherein the electrochromic material comprises Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS).

32. The method of any of claims 18 to 31, wherein the cell is a neuronal cell or a muscle cell. 33. The method of any of claims 18 to 32, wherein the cell is not genetically modified. 34. A device comprising optical system providing a beam and a prism abutting a first side of substrate, wherein the other side of the substrate comprises a layer of an electrochromic material. 35. The device of claim 34, wherein the substrate is transparent, substantially transparent, or translucent. 36. The device of claim 34 or 35, wherein the substrate comprises a glass or a plastic. 37. The device of any of claims 34 to 36, wherein the substrate comprises a culture plate onto which a cell or a tissue slice is cultured. 38. A culture plate comprising a transparent, substantially transparent, or translucent substrate coated with an electrochromic material. 39. The culture plate of claim 38, wherein the substrate comprises a glass or a plastic. 40. The culture plate of claim 38 or 39, comprising cultured thereon a cell or a tissue slice. 41. The culture plate of claim 40, wherein the cell is a neuronal cell or a muscle cell. 42. The culture plate of claim 40, wherein the tissue slice is a brain slice.

Description:
LABEL-FREE OPTICAL DETECTION OF BIOELECTRIC POTENTIALS USING ELECTROCHROMIC MATERIALS CROSS-REFERENCE TO RELATED APPLICATIONS The present application claims the benefit of and priority to U.S. Provisional Patent Application No.63/025,003, filed May 14, 2020, which is hereby incorporated by reference in its entirety. GOVERNMENT SUPPORT This invention was made with government support under the grant number 1R01GM125737 awarded by the National Institutes of Health and the grant number ECCS-1542152 awarded by the National Science Foundation. The government has certain rights in the invention. INTRODUCTION Reliable detection of neuroelectric activities has been instrumental in deciphering how neurons encode information, expanding the understanding of how electrical activities lead to physiological outcomes. Several categories of recording methods have been developed, each with its own advantages and limitations. With high sensitivity and fast temporal response, electrodes have been the gold standard for detecting neuroelectric activities. Intracellular recording, using the patch clamp or sharp electrode, affords large signals and recording from user-selected cells, is invasive and limited to recording only one or two cells. Extracellular recording using multielectrode arrays (MEAs) is non-invasive and compatible with parallel and long-term recording. The development of high-density MEA and CMOS technology has enabled parallel recording of a large number of cells. However, prefabricated electrode arrays are fixed in space and not flexible to record user-selected sites. Optical detection of electrical activities provides the spatial flexibility of choosing the target cells or areas of interest. The GCaMP family of calcium sensors has been widely used to optically read out neuronal activities with excellent signal to noise ratio. In the last decade, the development of voltage-sensitive fluorescent proteins and small potentiometric dyes has advanced optical recording. These voltage-sensitive fluorophores exhibit faster kinetics than the GCaMP calcium sensors and are thus able to record discrete action potentials. Voltage-sensitive proteins are also genetically encodable to allow recording from a specific cell population. Although their operational mechanisms vary, voltage-sensitive fluorophores rely on inserting optically active molecules into the cell membrane through genetic modification or chemical incorporation, which sometimes lead to membrane capacitance overloading. Compared with GCaMPs, voltage-sensitive fluorophores are usually less bright. When recording at a high frame rate such as 500-1000 frames/sec, fluorescence-based voltage sensors photobleach in seconds to minutes. A label-free optical detection of neuroelectric activities would avoid limitations associated with fluorescence-based molecular probes while still allowing spatial flexibility. A number of techniques are being explored in this area. Surface plasmon resonance (SPR) imaging has been shown to be able to detect mechanical motions of the neuron in response to current injection-triggered action potentials, which was similarly detected by optical coherence tomography in Aplysia ganglia neurons, by atomic-force microscopy in mammalian neurohypophysis, and by full-field interferometric imaging in spiking HEK cells. The fact that cellular mechanical motion can also be induced by other cellular mechanisms such as cell migration or mechanical contraction in cardiomyocytes makes these methods sensitive to artifacts. In a different approach, an elegant study using nitrogen-vacancy centers near the surface of a diamond has directly detected the magnetic fields caused by current injection-triggered action potentials in excised giant axons. However, the method currently requires averaging hundreds of events, and is thus not yet able to detect individual and spontaneous activities in a complex network of cells, or record single spikes. The ultimate goal of label-free optical recording, and eventually even imaging, of spontaneous cell electric activities in a complex neural network has yet to be achieved. SUMMARY Optical recording is highly desirable to detect bioelectric activities, as it can flexibly record a variety of user-selected locations. The disclosure provides Electro- Chromic Optical REcording (ECORE), a new label-free optical recording method that is using different principles than fluorescence-based voltage recording, and offering independent advantages. Thus, ECORE for label-free optical detection of cellular action potentials is disclosed. Electrochromic materials reversibly change their optical absorption spectrum in response to an externally applied voltage. The change in the voltage-dependent absorption in these materials is used to achieve optical readout of electrical signals applied by cells. By building a sensitive optical detection setup, ECORE can be used to for a label-free optical detection of spontaneous neuronal action potentials, for example, in cultures and in brain slices. ECORE utilizes voltage-dependent absorption of an electrochromic thin film and thus is not affected by photobleaching. ECORE offers spatial flexible and long-term optical recording without genetic or molecular perturbation. Accordingly, certain embodiments of the invention provide a method for assessing near a surface a change in electrical activity, such as a change in electrical potential. The methods comprise measuring a change in an absorption parameter of the electrochromic material coated on the surface. The absorption parameter can be absorbance, absorption maximum, or relative reflectivity of the electrochromic material. The electrochromic material can be coated on a transparent, substantially transparent, or translucent substrate. The methods could be used to detect changes in electrical activity at an area between 0.1 mm 2 and 1 mm 2 and over a period of between 1 millisecond and 100 milliseconds. The preferred electrochromic material is Poly(3,4- ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS). These methods could be used to measure electrical activity of a cell cultured on a surface comprising the electrochromic material. Thus, these methods could be used to assess electrical of a neuronal cell or a muscle cell cultured on a surface comprising an electrochromic material. BRIEF DESCRIPTION OF THE FIGURES FIGS. 1A-1E. Characterization of the PEDOT:PSS film for ECORE optical recording. A) Schematics of MEA-recording and ECORE-recording from electrogenic cells. B) Optical set-up of ECORE with total internal reflection. The zoomed-in picture illustrates the interface and the electrical modulation of the electrochromic-film using a potentiostat. C) Cyclic voltammogram of PEDOT thin film in 0.1 M HEPES/KCl at a scan speed of 50 mV/s, D) UV-VIS absorption spectrum of the PEDOT:PSS film at three different applied voltages. E) The relative reflectivity change (ΔR/R, red curve) is seen to be modulated by a 1-mV square wave applied to the film (Potential, black curve). M: Mirror, PBS: polarizing beam splitter, WP: Wollaston Prism, L: lens, OI: optical isolator, and λ/2: half-wave plate. FIGS. 2A-2F Optimization of ECORE. Change in reflectance (ΔR/R) as a function of A) incident angle θ (V0= 0 and ΔV = 1 mV at 10 Hz), B) film thickness (V0= 0 and ΔV = 1 mV at 10 Hz), and C) bias voltage (θ = 67o and ΔV = 1 mV at 10 Hz). D) ΔR/R as a function of ΔV (d =120 nm, V0= 0 and θ = 67o). E) The film response time scales with the square root of the film’s surface area. F) The change in reflectance (ΔR/R) decreases as the laser spot moves away from the microelectrode that locally applies 1-mV square wave voltage. FIGS.3A-3F. ECORE optical recording in stem cell-derived cardiomyocytes. A) Bright-field image of stem-cell derived cardiomyocytes cultured in a PEDOT film. B) Typical ECORE optical recording of cardiomyocytes. C) Enlarged part of B) shows the electrical signal as a small spike occurring about 15 ms before the onset of the cell’s mechanical contraction. D) ECORE recording shows a gradually decreased signal upon the application of 12.5 μM blebbistatin over 10 min. E) Enlarged parts of d) at 0 min, 5 min, and 10 min, respectively, show a drastic decrease of the mechanical contraction. F) Zoomed parts of (e) show that electric spikes remain the same at 0, 5, and 10 min. FIGS.4A-4C. ECORE provides high S/N that is comparable to MEA recording. A) MEA electric recording shows both monophasic and biphasic signals with indicated S/N and B) ECORE optical recording also shows both monophasic and biphasic signals with an S/N that is comparable to MEA recording. C) ECORE allows multiple days in vitro (DIV) recordings of the same batch of cardiomyocytes cells. FIGS.5A-5G. ECORE optical recording in cultured hippocampal neurons and dorsal root ganglion (DRG) neurons. A) Bright-field image of the hippocampal neurons cultured on a PEDOT film, B) ECORE optical recording of spontaneous activity in hippocampal neurons. C) At the same recording site in B), the application of 20 μM of carbachol significantly increased the firing frequency. D) Bright-field image of DRG neurons cultured on a PEDOT film. E) No spontaneous DRG activity was observed at the standard ECORE recording power of 28 W/cm 2 . F) Induced electric activity can be observed at an optical density of 56 W/cm 2 . G) A continuous ECORE recording of the same location while the laser power was modulated from 63 to 28, 42, 56, 28, and 56 W/cm 2 , with each period lasting 25-30 s. Each vertical short line indicates an electric activity at the indicated time. FIGS. 6A-6F. ECORE optical recording and MEA electric recording of hippocampal brain slices with insets showing representative electrical activities. A) Brightfield image of a cultured hippocampal brain slice. B) MEA electric recording shows sporadic spikes of neuronal activities from a brain slice. C) After a brain slice is exposed to 20 μM of carbachol, MEA recording shows a strong increase in the spiking frequency. D) ECORE optical recording shows sparse and spontaneous spiking activities from a brain slice. E) ECORE optical recording shows a drastic increase in spiking frequency after 20 μM of carbachol treatment. F) ECORE optical recording shows the carbachol- induced high spiking frequency gradually decreases during hypoxia. FIG. 7. Scanning electron microscope image of electrodeposited PEDOS:PSS film. FIGS.8A-8B. Photographic image of the electrodeposited PEDOT:PSS film in the A) reduced state and B) oxidized state. FIG.9. Measured reflectivity (dots) compared with theory (lines) as a function of the incident angle θ of light into the prism for four different thicknesses of the PEDOT:PSS film. Note that the PEDOT:PSS sample used here was in the pristine state with a higher extinction coefficient κ ~0.4, while voltage sensing is usually performed with zero bias or -50 mV open circuit where PEDOT having κ ~0.2. FIGS. 10A-10D. A) Measured reflectivity as a function of bias, for the same sample used for Fig.2C. B) Extinction coefficient κ as a function of bias voltage inferred from this data. Dots have been derived from the measurements shown in (A) while the solid line represents a fit, κ =0.204 -0.291V +2.433V 2 -4.890V 3, where V is the applied potential in Volt. C) Fractional reflectivity change |ΔR/R| for a 1-mV applied square waves signal as a function of bias electrode potential. The dots are the measurement from FIG.2C. The blue line is the prediction of our model, using the extinction coefficient as determined in (B). D) Fractional reflectivity change |ΔR/R| for a 1-mV applied square waves signal as a function of incident angle (from FIG. 2A) compared to theory (blue line). FIGS.11A-11D. Impedance spectroscopy of the PEDOT thin films, A) Bode plot demonstrating an increase in the impedance with a decrease in the surface area B) phase angle C) equivalent circuit model used to estimate the expected rise time D) expected rise time as a function of active area. FIGS.12A-12B. Hippocampal brain slices exposed to carbachol. A) Recovery of electrical spikes after re-saturation of the ACSF solution by carbogen, B) close-up of the biphasic optical spikes. FIGS. 13A-13D. (A) Signal to noise ratio of scanning ECORE is the same, whether in non-scanning mode or while scanning five locations. (B) Bright field imaging shows ECORE scanning over five selected locations on the same cell. (c) Overlay of recorded signals from five spots shown in B. Electrical signals at five scanning locations have similar shape and are clearly distinguished in time and shape from the mechanical signals. (D) Scanning of a raster of 30 and targeted scanning using the Red Pitaya with dwell time of 10 μs at each spot.. FIGS. 14A-14D. (A) Scanning ECORE (schematic). (B) A microscope can observe the scanning from the top of the sample. (C) Photodetector signal while scanning 4 locations with 100 µs per location. (D) Separating the signal into four channels yields shows a 1 mV p-p square wave applied to the PEDOT surface. FIG.15. Wavelength dependent sensitivity of PEDOT to electrical potentials. FIG.16. Measured optical response of a PEDOT film for wavelengths of 830 nm and 532 nm shows opposite polarity. Both sensitivities are about 2-3 times as high as the one of the same film at 660 nm. FIG. 17. Readout with two wavelengths: 532 nm (top) and 830 nm (bottom). This is two-color simultaneous recording from the same cell. The top trace is 532 nm, where the action potential shows as upward jump, while the bottom trace is 830nm, where the same action potential shows as a downward jump. The anti-correlation is the signature of electric activity. The two-color imaging allows us to reject artifacts. DETAILED DESCRIPTION Certain embodiments of the invention provide methods for assessing electrical activity near a surface comprising an electrochromic material. The methods comprise measuring a change in an absorption parameter of the electrochromic material. The electrical activity near the surface can be a change in electric potential near the surface. An example of the electrochromic material is Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS). The methods disclosed herein allow measuring a change in electrical activity in an area as small as between 0.1 mm 2 and 1 mm 2 . Therefore, the methods disclosed herein could be used to measure electrical activity of a cell cultured on a surface comprising an electrochromic material. Such cell could be a neuronal cell or a muscle cell. Before the methods and devices of the present disclosure are described in greater detail, it is to be understood that the methods and devices are not limited to the embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing the embodiments only, and is not intended to be limiting, since the scope of the methods and devices will be limited only by the appended claims. As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only,” and the like in connection with the recitation of claim elements or use of a “negative” limitation. Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both the limits, ranges excluding either or both of those included limits are also included. Certain parameters are presented herein with numerical values being preceded by the term “about.” The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the methods and devices belong. Although any methods and devices similar or equivalent to those described herein can also be used in the practice or testing of the methods and devices, representative illustrative methods and devices are now described. All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the materials and/or methods in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present methods and devices are not entitled to antedate such publication, as the date of publication provided may be different from the actual publication date which may need to be independently confirmed. It is appreciated that certain features of the methods and devices, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the methods and devices, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. All combinations of the embodiments are specifically embraced by the present disclosure and are disclosed herein just as if each combination was individually and explicitly disclosed, to the extent that such combinations embrace operable processes and/or compositions. In addition, all sub-combinations listed in the embodiments describing such variables are also specifically embraced by the present methods and devices and are disclosed herein just as if each such sub-combination was individually and explicitly disclosed herein. As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present methods and devices. Any recited method can be carried out in the order of events recited or in any other order that is logically possible. Understanding how a network of interconnected neurons receives, stores, and processes information in the human brain is one of the outstanding scientific challenges of our time. The ability to reliably detect neuroelectric activities is essential to addressing this challenge. Optical recording using voltage-sensitive fluorescent probes has provided unprecedented flexibility for choosing regions of interest in recording neuronal activities. However, when recording at a high frame rate such as 500-1000 Hz, fluorescence-based voltage sensors often suffer from photobleaching and phototoxicity, which limit the recording duration. Here, we report a new approach, Electro-Chromic Optical REcording (ECORE), that achieves label-free optical recording of spontaneous neuroelectrical activities. ECORE utilizes the electrochromism of PEDOT:PSS thin films, whose optical absorption can be modulated by an applied voltage. Being based on optical reflection instead of fluorescence, ECORE offers the flexibility of an optical probe without suffering from photobleaching or phototoxicity. Using ECORE, spontaneous action potentials were optically recorded in cardiomyocytes, cultured hippocampal and dorsal root ganglion neurons, and brain slices. With minimal perturbation to cells, ECORE allows long-term optical recording over multiple days. METHODS As noted above, certain embodiments of the disclosure provide a method for assessing electrical activity near a surface comprising an electrochromic material. The electrical activity is assessed by measuring a change in an absorption parameter of the electrochromic material. The electrical activity can be a change in an electrical potential near the surface. The absorption parameter of the electrochromic material measured in the methods disclosed herein can be absorbance of the electrochromic material. For example, a change in an electrical potential near a surface comprising an electrochromic material can induce a change in the absorbance of the electrochromic material. As shown in FIG. 1D, absorbance of a PEDOT:PSS film at a particular wavelength varies with voltage present at the surface of the film. Thus, measuring absorbance or a change of absorbance of a PEDOT:PSS film at a particular wavelength could be used to measure the voltage or a change in voltage present at the surface of the film. Also, the absorption parameter of the electrochromic material measured in the methods disclosed herein can be absorption maximum of the electrochromic material. For example, a change in an electrical potential near a surface comprising an electrochromic material can induce a change in the absorption maximum of the electrochromic material. Again, as shown in FIG. 1D, absorption maximum of a PEDOT:PSS film varies with voltage present at the surface of the film. Thus, measuring the absorption maximum or a change in the absorption maximum of a PEDOT:PSS film could be used to measure the voltage or a change in voltage present at the surface of the film. Further, the absorption parameter of the electrochromic material measured in the methods disclosed herein can be relative reflectivity of the electrochromic material. For example, a change in an electrical potential near a surface comprising an electrochromic material can induce a change in the relative reflectivity of the electrochromic material. As shown in FIG.1E, relative reflectivity of a PEDOT:PSS film varies with voltage present at the surface of the film. Thus, measuring the relative reflectivity or a change in the relative reflectivity of a PEDOT:PSS film could be used to measure the voltage or a change in voltage present at the surface of the film. In certain embodiments, the surface comprises a layer of the electrochromic material on a transparent, substantially transparent, or translucent substrate. The transparent, substantially transparent, or translucent material can be comprised of a glass, such as ITO glass or a plastic, such as polystyrene, polycarbonate, polyvinyl chloride, polypropylene, or a combination thereof. Additional examples of transparent, substantially transparent, or translucent materials that could be used in the methods disclosed herein could be readily identified by a person of ordinary skill in the art and use of such embodiments are within the purview of the invention. As shown in FIGS. 1A-1B, the absorption parameter of the layer of the electrochromic material is measured through the transparent, substantially transparent, or translucent substrate. Thus, assessing a change in the electrical activity on one side of a surface comprising an electrochromic material could be done by measuring an absorbance parameter of the surface from the other side of the surface. The layer of electrochromic material on the substrate can have a thickness of between 50 nm and 500 nm, preferably, between 60 nm and 450 nm, between 70 nm and 400 nm, between 80 nm and 350 nm, between 90 nm and 300 nm, between 100 nm and 200 nm, between 110 nm and 150 nm, or about 125 nm. In one embodiment, the electrochromic material is PEDOT-PSS and the thickness of the layer is 115 nm. The absorption parameter of the electrochromic material can be analyzed using a light beam incident on the surface at an angle. In certain embodiments, the incident angle is between 55 o and 75 o , between 60 o and 70 o , or about 65 o . In one embodiment, the electrochromic material is PEDOT-PSS and the incident angle is about 67 o . To measure an absorption parameter of the electrochromic material, a laser beam can be focused onto the surface through a prism-coupled total internal reflection configuration, as shown in FIG.1B. The method disclosed herein could be used to assess electrical activity at a surface as small as 0.1 mm 2 to 1 mm 2 . Thus, in certain embodiments, the area of the surface in which the change in the absorption parameter is measured is: between 0.1 mm 2 to 1 mm 2 , preferably, 0.2 mm 2 to 0.5 mm 2 , even more preferably, about 0.25 mm 2 . Because the electrochromic material is highly responsive to quick changes in the electric activity near the surface, the methods disclosed herein could be used to asses the electrical activity over a period of: between 1 millisecond and 100 milliseconds, preferably, between 10 milliseconds and 50 milliseconds, and even more preferably, about 25 milliseconds. The electrochromic material that could be used in the methods disclosed herein can be a metal-organic frameworks, metal oxide, or conductive polymer. In preferred embodiments, the electrochromic material is Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS). Certain electrochromic materials that could be used in the methods and devices disclosed herein are described in United States Patent Application Publication NOs. 20200089073 and 20200050071. These publications are incorporated herein by reference in their entireties. Because the methods disclosed herein facilitate assessing electrical activity at a small area of a fraction of a square millimeter and over a very short period of time of 1 to 100 milliseconds, the methods disclosed herein could be used to assess electrical activity of a cell cultured on a surface comprising an electrochromic material. Accordingly, certain embodiments of the disclosure provide a method for assessing electrical activity of a cell. In such methods, a cell is cultured on a surface comprising an electrochromic material and a change in an absorption parameter of the electrochromic material is measured. Certain details of the electrochromic material, measured absorption parameter, substrate on which the electrochromic material is coated, thickness of the electrochromic layer, methods of measuring the absorption parameters, area of the surface measured, and frequency of measurements, are also applicable to the methods envisioned herein of assessing electrical activity of a cell. Certain such details are described in Embodiments 15 to 30, listed below. In preferred embodiments, the cell is a neuronal cell or a muscle cell. A neuronal cell can be a nerve, such as a dorsal root ganglion neuron or hippocampal neuron. A muscle cell can be a cardiomyocyte. A neuronal or a muscle cell can be produced by culturing a pluripotent cell under conditions that induce differentiation of the cell into a neuronal or muscle cell. A cell can also be present in a tissue sample, such as a brain slice, such as a hippocampal brain slice. Because the methods disclosed herein can facilitate continuous monitoring of electrical activity over an area, these methods could be used to assess electrical activity of a plurality of cells, for example, in a layer of cells or a slice of a tissue, to assess electrical communications between different cells. The methods disclosed herein negate the need for genetically transforming the cells to monitor the cell’s electrical activity. Such genetic transformation typically results in the expression in the cell of a genetically engineered protein responsive to changes in the electrical activity of the cell. The methods disclosed herein negate such genetic transformation and, hence, in certain embodiments, the cell is not genetically transformed, particularly, the cell is not genetically transformed to encode a protein responsive to the cell’s electrical activity. DEVICES AND KITS Further embodiments of the invention provide kits and devices suitable for performing the methods disclosed herein. An example of such device is disclosed in FIG. 1B. Accordingly, certain embodiments of the disclosure provide a device comprising optical system providing a beam and a prism abutting a first side of substrate, wherein the other side of the substrate comprises a layer of an electrochromic material. The device can further comprise optical detectors for detecting an absorption parameter, such as absorbance, absorption maximum, or relative reflectivity. The substrate is transparent, substantially transparent, or translucent. Accordingly, the substrate can be comprised or a glass, such as ITO glass, or plastic, such as polystyrene, polycarbonate, polyvinyl chloride, polypropylene, or a combination thereof. In certain embodiments, the substrate comprises a culture plate onto which a cell, such as a neuronal cell, muscle cell, or a tissue slice is cultured. Certain details of the electrochromic material, measured absorption parameter, substrate on which the electrochromic material is coated, thickness of the electrochromic layer, measured absorption parameters, area of the surface measured, and frequency of measurements, are also applicable to the devices envisioned herein. Certain such details are described in Embodiments 31 to 34, listed below. Additional embodiments of the disclosure provide plates that could be used to measure electrical activity of cells or tissue slices. Such plates comprise a transparent, substantially transparent, or translucent substrate coated with an electrochromic material. Accordingly, the substrate can be comprised or a glass, such as ITO glass, or plastic, such as polystyrene, polycarbonate, polyvinyl chloride, polypropylene, or a combination thereof. Additional details of the electrochromic material, substrate on which the electrochromic material is coated, and thickness of the electrochromic layer, are also applicable to the plates envisioned herein. Certain such details are described in Embodiments 35 to 39, listed below. EXPERIMENTAL Materials and Methods Electrodeposition, cyclic voltammogram, and electrochemical impedance characterization of PEDOT:PSS (referred as PEDOT hereafter) films A 2% aqueous solution of poly(sodium 4-styrene sulfonate) (Mw = 70,000) (w/w%) was mixed with 10 μL of 3,4 ethylenedioxythiophene (EDOT) to make a 10 mM solution. Prior to deposition, ITO-coated unpolished float glass (Rs = 70-100 Ω/sq, 15- 30 nm ITO thickness) from Delta Technologies were cleaned using UV-Ozone. The monomer was electropolymerized by applying a constant voltage of 950 mV on ITO vs. Ag/AgCl resulting in the polymer PEDOT on the ITO surface. The thickness of the PEDOT film was measured using a Bruker Dektak XT profilometer. Cyclic voltammogram measurements of the PEDOT film were taken with a scan rate of 50 mV/s restricted by the potential window of -500 mV to +500 mV vs Ag/AgCl in HEPES buffered Tyrode’s salt solution. ECORE Optical instrumentation The ECORE optical setup consisted of PEDOT:PSS (nPEDOT:PSS =1.4 @ 660 nm) thin layer deposited onto ITO (n ITO =1.7 @ 660 nm) glass. The sample was mounted onto a translational stage holding a BK-7 (nBK7 =1.5142 @ 660 nm) equilateral prism. A thin layer of Type F immersion oil (n oil =1.5124 @ 660 nm) was applied to the bottom of the ITO glass for index matching with the prism and suppression of the back reflection from the ITO-coated glass. A 20-mW, 660-nm laser diode (ThorLabs LP633-SF50), pigtailed with a single-mode fiber, was mounted on a temperature controlled laser diode mount (Thorlabs, Inc.) equipped with a current and temperature controller. The laser beam polarization was cleaned up by a combination of two half-wave plates, a broadband polarizing beamsplitter cube and a Wollaston prism. The Wollaston prism separated polarized light into two orthogonal linearly polarized outgoing beams. The amount p- and s-polarized light was manually controlled by the preceding half-wave plate. The balancing of the light intensity consisted of manually rotating the half-wave plate. The laser was focused on the film as an elliptical spot (58 μm × 112 μm half width at half maximum). The sample and the reference beam were redirected to the two diodes of a homemade differential photodiode detector. The output was amplified using an amplifier (Axon Instruments Axopatch-1D Patch Clamp amplifier) and digitized at 10 kHz using Axon Digidata 1440A low noise digitizer. Patterning of the ITO through lithography to control the area of PEDOT film. ITO glass was cleaned using Samco ozone cleaner which used a UV producing light bulb and a molecular ozone source to generate ozone and remove organic molecules on the substrate surface. Following the cleaning, the surface was coated with hexamethyldisilazane (HMDS) using the YES prime oven. Shipley 3612 positive resist was spin coated at 5.5K RPM for 30 seconds to produce a 1 µm thick film. The photoresist is prebacke at 90 o C for 1 minute. The pattern was designed and transferred onto the substrate using Heidelberg maskless aligner (MLA150). After exposure to square patterns with areas of either 9 mm 2 ,4 mm 2 ,1 mm 2 ,0.56 mm 2 , and 0.25 mm 2 , the film was post exposure baked at 115 0 C for 1 minute. Then, the substrate was developed using MEGAPOSIT TM MF TM -26A developer and rinsed with water. The patterned ITO substrates were used to electrodeposited PEDOT:PSS films with defined film areas. Optimization of incident angle, thickness, bias potential Commercial ITO substrates were patterned using standard photolithography techniques to define the surface area of interest. PEDOT films were electrodeposited onto the patterned ITO substrate. Using a potentiostat (Bio-Logic, SP200) and a 3- electrode cell setup, the film was subjected to periodic electric pulses with an amplitude of ΔV = 1 mV, at a constant bias V0 = 0 mV, and a frequency of 10 Hz, and the measured ΔR/R peak-to-peak amplitude recorded. This method was used during the optimization of the incident angle and film thickness. The prism attached to a rotation stage was adjusted manually during the optimization of the incident angle. Different film thickness was acquired by holding the potential (950 mV) constant and limiting the charge consumed during the electrodeposition. For the optimization of the bias potential V0 the film is subjected to periodic electric pulses with an amplitude of ΔV = 1 mV, and a frequency of 10 Hz. Finally, at V0=0, the optical response of the PEDOT system is characterized by applying square-waves of varying amplitudes. Due to hardware limitations of the potentiostat, we are unable to apply electric pulses smaller than 1 mV. Preparation of cultured monolayer of cells: stem cells derived cardiomyocytes, and Primary hippocampal neurons Cryopreserved hiPSC-CM (Cor.4U [Axiogenesis AG, Cologne, Germany] were kept in liquid nitrogen until culture. The cells were thawed and plated according to the instructions provided by the manufacturer. The cells were cultured in Geltrex TM treated PEDOT:PSS film in a humidified incubator at 37 o C. The subsequent maintenance protocols followed manufacturer’s instructions and use of corresponding maintenance media (Cor. 4U-maintenance media) supplemented with ciprofloxacin (2 mg/ mL). Experiments were performed between days 4-7 after plating as recommended by the manufacturer. All plated cells showed regular contractions after 3h of the initial plating. During optical measurements of the electric potential, the maintenance medium was replaced with modified Tyrode solution (4.2 mM K + instead of the standard 2.7 mM K + ). Primary embryonic rat Hippocampal neurons were isolated from Sprague- Dawley fetal rats (age E-15-E16). Briefly, hippocampal neurons of rat embryos were dissected in Hank’s buffer solution and enzymatically treated in 0.25% trypsin at 37 o C for 30 minutes followed by mechanical dissociation by passing through a fire polished Pasteur pipette for less than 10 minutes. DEM containing 15% FBS was used to stop the trypsinization process and cells were spun down at the bottom of the collection tube. Dissociated Hippocampal neurons were resuspended, counted and plated on either culture dish or the PEDOT:PSS film coated with poly-L-lysine. Cultures were maintained in a neurobasal medium supplemented with B27. All cultures were housed in a humidified incubator at 37 o C supplied with 5% CO2 and neurons were selected by applying 4 µM cytosine arabinoside (1-b-D-arabinofuranosylcytosine) for 24 hours to cultures 2 days after plating cells. This method produces neuronal cultures that are free of non-neuronal cells. Purification of primary embryonic rat dorsal root ganglion neurons (DRGs). DRGs were performed by a method adapted from that described in Zuchero’s publications. Preparation of samples for plating neurons: 1 mg/ml of Poly-D-Lysine hydrobromide stock (Sigma-Aldrich, Cat#P6407) was diluted 100-fold in sterile ddH2O and added to plates for 30 mins at room temperature. Plates were rinsed with sterile ddH2O three times and coated with 1 mg/ml Laminin (R&D Systems Cat#3400-010-02) diluted 1:200 in neurobasal media (Thermo Fisher Scientific, Cat# 21103049). Laminin coating was done at 37 °C for 4 to 24 hours. Laminin was removed from the plates immediately before plating neurons and replaced with DRG base media to prevent drying. Preparation of immunopanning plates: BSL-1 plate: One 15 cm petri dish was coated with 40 ml of 2 mg/ml BSL-1 (Vector Labs, Cat #L-1100) in 20 ml PBS overnight at 4 °C. The plate was rinsed three times with sterile PBS and coated with 9 ml of 0.2% BSA (Sigma-Aldrich, Cat#A-8806) at room temperature for at least 2 hours before using. CD9 plate: One 15 cm petri dish was coated with 90 ml of goat-anti-mouse IgG+ IgM (H+L) secondary antibody (Jackson ImmunoResearch, Cat# 115-005-044) in 20 ml of Tris-HCl (pH 9.5) overnight at 4°C.The plate was rinsed three times with sterile PBS and coated with anti-rat CD9 antibody (Thermo Fisher Scientific, #BDB551808) diluted 1:200 in 0.2% BSA. Dissections: All animal procedures were approved by the Stanford University’s Administrative Panel on Laboratory Animal Care. Two timed pregnant Sprague-Dawley rats (Charles Rivers) with E15 embryos were euthanized by CO2 inhalation. The placentas were dissected out and placed in Leibovitz’s L15 dissection medium (Thermo Fisher Scientific, 11415114) supplemented with 10% FCS (Thermo Fisher Scientific, A3160401). Embryos were carefully removed from the amniotic sacs and placed in a separate 10 cm dish with the dissection medium. Following decapitation, all of the organs and the spinal column on the ventral side of the embryos were carefully removed until the spinal cord was entirely exposed along the anteroposterior axis. This step dissociates the spinal cord from remaining ventral tissues and allows separation and visualization of DRGs. The embryos were then flipped so that the dorsal side was facing up. The skin above the spinal cord was peeled off with two forceps revealing DRGs lateral to the spinal column across its entire length. DRGs were then cut out at their bases using small scissors. 20-30 embryos were pooled for each prep, and each prep was treated as one biological replica. Immunopanning: Dissected DRGs were manually collected into D-PBS. The immunopanning protocol was performed essentially as described in Zuchero’s publication. Briefly, dissociated cells were passed serially over a BSL-1 plate (to remove blood and endothelial cells) and a CD9 plate (to remove glial cells). This protocol yields a single- cell suspension of 1.5-2 million DRGs with higher than 98% purity, devoid of contaminating glia, blood cells or fibroblasts. Plating and Culturing: Isolated DRG neurons were resuspended at 1000 cells/ml volume and plated in densities ranging from 10,000 to 60,000 cells per plate. Neurons were placed on the bottom of the plates containing 1 ml of DRG base media to achieve dispersed plating. DRG base medium (Zuchero, 2014a, 2014b) was supplemented with 100 ng/ml NGF (Neuromics, Cat#gt15057), 50 ng/ml BDNF (PeproTech, Cat#450-02) and 1 ng/ml NT3 (PeproTech, Cat#450-03) before each feeding (half volume media change) every 2-3 days. Preparation of hippocampal brain slices All animal procedures conformed to the NIH guide for the Care and Use of Laboratory Animals and were approved by the Stanford University Administrative Panel on Laboratory Animal Care. Hippocampal slices from Sprague-Dawley rat pups were prepared according to the protocol established by C. Fourie et al. Briefly, the brain slice culture dishes were prepared before the animal dissection by placing 1 mL of culture media into each 35 mm culture dish and carefully putting the membrane insert at a roughly 45 degree angle to the culture media to avoid air bubbles being added under the membrane insert. Six to eight of the 35 mm culture dishes were placed into one 150 mm petri dish followed by a transfer to a CO2 incubator for a 1 hour incubation prior to the dissection. Rat Pups at Postnatal Day 7 (P7) were euthanized by rapid decapitation. Afterwards, the brain was removed and placed into a chilled dissection medium. The cortex was removed from the midbrain to expose the hippocampus. The isolated hippocampus was removed and trimmed from the rest of the brain. Transfer the hippocampi into a new dish containing chilled dissection medium. Using a manual tissue slice to slice the hippocampi transversely into 400 μm sections. The hippocampal slices were transferred into dissection medium and inspected under a dissection microscope for the purpose of removing damaged brain slices. Place 3 to 4 individual slices onto a membrane filter insert in the culture dishes that were pre-warmed in the incubator. The slices were maintained in a 5% CO2 incubator at 37 o C and exchanged the medium on the second day. Make sure to pre-warm the culture medium before exchange: add 1 mL of fresh culture medium to each culture dish and place the culture dishes in the CO2 incubator for at least one hour. Transfer the membrane insert into a pre-warmed petri dish containing culture medium. Repeat these steps on the third day after making cultures and then transfer the cultures to an incubator set at 34 o C. The medium was changed twice each week and maintained in vitro for 7-21 days before recording. Electrical and Optical measurements of cultured monolayer of cells and hippocampal brain slices For the electrical measurements, a low-noise amplifier with sixty channels (MEA1060-Inv-BC, Multi-Channel Systems MCS GmbH) was used for the electrophysiology measurements with a sampling rate of 5 kHz. A Ag/AgCl pellet electrode (E200, Warner Instruments) grounded the amplifiers in the bath medium. All measurements with the cultured monolayer cells were made in a tyrode solution initially heated to 37 o C. PEDOT-ITO glass was sterilized using a solution of 70% ethanol. Afterwards, the film was coated with fibronectin, Geltrex™, or Poly-L- lysine to promote the adhesion of the cells onto the surface. Optical measurements of the device were taken after 3-5 days after cell plating with the exception of neuronal cells which were plated up to 4 weeks. Optical measurements with brain slices were made in an ACSF solution initially heated to 37 o C. After sterilization, the film was coated with Poly-L-lysine to promote the adhesion of the cells onto the surface. The PEDOT film was incubated in the cell incubator overnight with cell medium to allow for sufficient time for the reduction of the PEDOT by the cell medium from blue to purple state. The hippocampal brain slices were cut from the millicell insert and placed upside down onto the surface and gentle force was applied using a 3D-printed adapter terminated with a nylon mesh Example 1 – Optical detection of electric potentials with electrochromic PEDOT films Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS), a widely-used conductive polymer that is chemically stable, easy to process, and biocompatible, was used as a electrochromic material. PEDOT:PSS is used as an electrode coating material in electrophysiology MEA recording. A cell that fires an action potential induces a local voltage fluctuation in the range of a hundred microvolts that can be detected by an extracellular electrode in its vicinity (FIG.1A). If the cell is near a PEDOT:PSS thin film, its action potential would induce small changes in the absorption of the film, which can be detected optically (FIG.1A). For sensitive optical detection, a laser beam was focused onto the region of interest (ROI) through a prism- coupled total internal reflection configuration (FIG. 1B). A balanced differential photodetector rejects laser intensity noise by comparing the reflection of the sample against a reference beam derived from the same laser. Detecting the total-internal reflection rather the transmission leaves the upper surface of the specimen accessible (e.g, for imaging). Because the probing light does not pass through the culture medium, this approach is insensitive to spurious signals such as floaters in the medium or air- liquid surface ripples induced by vibrations. PEDOT:PSS thin films were produced (referred to as PEDOT hereafter) by electrodeposition directly from monomers onto an ITO-coated glass substrate. PEDOT films are chemically stable and have been shown to be stable in cell culture medium for months or longer. The film is stable for >3 months without any indication of decay but that delamination could occur if improperly handled. The electrochemical properties were characterized of PEDOT by cyclic voltammetry. The cyclic voltammogram shows no pronounced peaks indicative of faradaic current (FIG.1C). Therefore, the PEDOT film resembles a pseudocapacitor electrochemically. The electrochromism of PEDOT arises from modulation of its π-conjugated system by an electric potential (FIGS.7-8). Absorption spectra of the film show a clear voltage-dependent shift in the absorption maximum. A -500 mV (all potentials are vs. Ag/AgCl electrode) results in a maximum absorption at λmax = 580 nm, while a positive bias of +500 mV results in λmax = 850 nm (FIG. 1D). Upon application of a train of 1 mV square waves to a 1 cm 2 film, a clear change was detected in the reflection signal using a 660-nm probing laser. The fractional reflectance change (ΔR/R) shows a train of optical responses that closely follow the train of applied electric voltages (FIG.1E). Although the 660 nm wavelength does not lead to the highest sensitivity for voltage-changes, it is sufficient to detect small changes induced by cellular electrical signals as we show below. Example 2 – Characterization and optimization of ECORE Detecting cellular electrical signals requires a sensitivity of 10 μV or better, 4-5 orders of magnitude less than the voltage (hundreds of mV) required to induce a color change of PEDOT:PSS that would be visible to the naked eye. To maximize the relative reflectivity change, and thus the optical detection sensitivity, a four-layer (glass:ITO:PEDOT:water) model was built to study how the light reflectivity is modulated by changes in the extinction coefficient of the PEDOT film (FIGS.9-10). ΔR/R was first optimized by tuning the incident angle. As the incident angle increases, the measured ΔR/R first increases and then decreases (FIG.2A). The optimal incident angle is about 67.0 o , which is larger than the critical angle of 62.5 and in good agreement with the model. ΔR/R was further optimized by precisely controlling the thickness of the PEDOT layer. The optical contrast first increases with the film thickness as more sensing material is added, but then starts to decrease roughly when the thickness exceeds the penetration of evanescent light at the interface. The optimal thickness to achieve the highest contrast is determined to be about 115 nm (FIG. 2B). By fixing the optimal incident angle and the film thickness, the optical contrast ΔR/R was measured as a function of bias voltage (V0) while maintaining ΔV=1 mV (FIG.2C). The contrast shows a maximum at V0 = -100 mV, a minimum at V0 = +100 mV, and a good sensitivity V0= 0 mV. In the cell culture medium, the open-circuit potential of our system (-50 mV) brings the film closer to the optimum sensitivity without any active bias. Finally, the optical contrast ΔR/R is linearly proportional to the applied voltage ΔV over a wide range at bias V0 = 0 (FIG. 2D). This linear dependence allows quantitative conversion of optical responses to voltages if the film is calibrated. For this work, ΔR/R was directly used instead of converting to voltages. Due to the instrument limit of the potentiostat, electric pulses smaller than 1 mV could not be applied. With a typical signal ΔR/R ~3.0 × 10 -3 per 1 mV applied voltage and a typical standard deviation of the noise at 2.0 ×10 -5 or less, a detection sensitivity was estimated as 6.7 μV with zero bias with an electrical bandwidth of 10 kHz. The temporal response of the film must be sufficiently fast to capture cellular electric potentials in the order of 1 ms. However, the long response time of macroscopic electrochromic coatings, typically on the order of seconds, is too slow for capturing millisecond neuroelectric activities. Therefore, the temporal response may be determined by charging of the active electrode area and the bulk diffusion of the counter ions necessary for charge stabilization. To test the hypothesis and establish a relationship between the film area and the temporal resolution, the optical response time vs. PEDOT film areas was measured. The response time is defined as the time for ΔR/R to rise from 10% to 90% of its final value after subjecting the film to a 1 mV square-wave at 0 mV bias potential. The PEDOT film area is precisely controlled from 9 mm 2 to 0.25 mm 2 by patterning the ITO area through photolithography. The measured temporal response of the film scales with the square-root of the PEDOT area A 1/2 (Fig 2e). This measurement agrees with an RC circuit model for microelectrodes, where τ=RC, where R is the electrolyte resistance proportional to 1/A 1/2 and C the double-layer capacitance, proportional to A. Also measured was the electrochemical impedance spectrum for each film and impedance data was modeled using the equivalent circuit described above (FIG.11, Table 1). Table 1. Temporal dependence on the response time as a function of surface area. The calculated response time from the impedance data agrees very well with direct optical measurement. Therefore, the temporal resolution improves significantly when the active area becomes smaller. For a cell cultured on a PEDOT film, the active film area that is affected by cellular action potentials is similar to the cell size. Thus, a response time of less than 0.2 ms is expected for a cell area of 400 μm 2 . The spatial resolution of the PEDOT:PSS film must be sufficient to detect individual cells. When a cell is in close contact with the film, the cell’s electrical activity will charge the film locally. The reported charge mobility in PEDOT:PSS indicates that the charge diffusion in 1 ms is about 10 -3 -10 -1 µm 2 , much smaller than the size of a cell. The spatial resolution was experimentally determined by measuring optical responses at different film locations when an electrical pulse is applied locally through a microelectrode a few micrometers above the film surface (FIG. 8F). The optical response decays quickly as the laser spot moves away from the microelectrode. The measured half width at half maximum for the optical response is 25 µm, which is the size of the laser spot. Therefore, the spatial resolution of the EC film is limited not by the charge diffusion, but by the size of the probing laser spot. This size has been chosen to match the approximate size of the cell and can be further reduced if desired. For all the cell studies, the ECORE measurements were carried out in an open circuit configuration (-50 mV open circuit potential) without any active electrode in the solution. Cells were cultured on 1 cm 2 PEDOT films for a few days to weeks before ECORE measurements. ECORE was first used to detect action potentials in monolayers of human iPSC-derived cardiomyocytes (FIG.3A). Using ECORE with a 10 kHz sampling frequency, large and periodic optical signals were optically detect (FIG. 3B). However, these large signals are due to the mechanical contraction of these cells that accompanies each action potential through excitation-contraction coupling. These mechanical signals arise when the movement of the cell membrane modifies the boundary conditions at the interface; they can be measured in the absence of the PEDOT layer. Careful examination of the ECORE trace reveals that, about 15 ms before the start of each mechanical contraction, there is a sharp spike resembling extracellularly-recorded action potentials (arrows, FIG.3C). To confirm that these sharp spikes were indeed action potentials, cardiomyocytes were treated with 12.5 μM blebbistatin (12.5 μM) while the cells were being continuously recorded by ECORE (FIG.3D). Blebbistatin is a potent myosin inhibitor that is known to inhibit cardiomyocyte contraction without eliminating its action potential. Magnified parts of the ECORE data after 0 min, 5 min, and 10 min of drug treatment show a drastic decrease of the mechanical signal at 5 min and then an almost complete elimination at 10 min (FIG. 3E). However, the sharp spikes corresponding to action potentials were unaffected by the blebbistatin treatment (FIG.3F, magnified parts of the corresponding spikes in FIG. 3E). This confirms that ECORE is able to reliably detect individual action potentials in cardiomyocytes. The electrical and mechanical signals are clearly distinguished by their timing and shape. Standard multi-electrode array (MEA) recording technique was used to confirm that the iPSC-derived cardiomyocytes exhibited spontaneous and periodical action potentials (FIG. 4A). MEA recording shows both monophasic spikes and biphasic electrical spikes at 10 kHz bandwidth. As previously reported, the amplitude and waveform of action potential spikes strongly depends on the coupling and the relative location between the electrode and the cell. Using ECORE, both monophasic action potential signals (e.g. ROI 1 trace in FIG.4B) and biphasic action potential signals were detected (e.g. ROI 2 trace in FIG.4B). Similar to MEA, the waveform and amplitude of ECORE depends on the coupling of the cells to the surface and the resulting ionic currents. The signal-to-noise ratio for ECORE recording (FIG. 4B) is similar to that of MEAs (FIG.4A) at 10 kHz recording bandwidth and is better than fluorescence-based optical recording by voltage-sensitive proteins or dyes at the maximum 1kHz bandwidth. It is also orders of magnitude better than previous label-free optical recording methods and thus enables recording of single, spontaneous, and un-averaged action potentials. ECORE is well-suited for long term recording of the electrical activities in cardiomyocytes since it requires no modification of the cell and does not suffer from photo bleaching. With a 10 kHz recording bandwidth, 10 min or more for each optical recording session were measured. This duration, limited only by the lack of an appropriate culture chamber, is much longer than what can be achieved using voltage- sensitive fluorophores. Furthermore, the same culture could be measured for many days over multiple recording sessions. FIG. 4C shows ECORE recordings from the same culture of cardiomyocytes at different locations at 6, 7, and 9 days on the PEDOT surface cultured in vitro (DIV). After validating the platform with cardiomyocytes, neuronal action potentials were recorded in cultured hippocampal neurons (FIG. 5A). Dissociated hippocampal neurons from embryonic E18 rats were cultured on the PEDOT film until they formed a network in vitro and exhibited spontaneous action potentials. ECORE measurements were made three weeks after plating when hippocampal neurons exhibit spontaneous and sparse electric activities (FIG.5B). To confirm that the recorded signals in FIG.5B were indeed neural electrical activity, the same culture was treated with carbachol, an activator of muscarinic acetylcholine receptors (mAChRs) that is known to increase the firing rate of hippocampal neurons. Upon 20 μM bath application of carbachol, the hippocampal neurons exhibited an increase in complex and unsynchronized electric signals (FIG. 5C). The increase in the firing rate by application of carbachol was accompanied by a decrease in the amplitude of the electrical spikes. Dorsal root ganglion (DRG) neurons are sensory neurons known for the sensitivity to mechanical, chemical, thermal and noxious stimuli. Embryonic rat DRG neurons were dissected, isolated, purified, and cultured according to the protocol established by the Zuchero group. DRG neurons were cultured on PDL/laminin coated PEDOT film using the same protocol. After a week of culture, the brightfield image shows a cell body about 30 μm in diameter with long axons that are projecting out (FIG. 5D). Embryonic DRG neurons have been reported to exhibit low spontaneous activities. Indeed, even with repeated effort, spontaneous activity could not detected from these DRG neurons using the standard light intensity at 28 W/cm 2 (FIG.5E). However, when the optical power was doubled to 56 W/cm 2 , an increase was observed in the electric activities from these neurons (FIG.5F). The firing pattern of each DRG neuron tested (n = 21) differed between cells; however, an increase was always observed in the electric activities at high optical power. Light-absorbing materials can convert light to heat for opto-thermal stimulation of neurons. PEDOT absorbs 660 nm light strongly, thus it was hypothesized that higher optical power might be locally heating up PEDOT and thus thermally activate the DRG neurons. To confirm that electric activities of DRG neurons were indeed modulated by the laser power, the laser intensity was sequentially changed from 63 to 28, 42, 56, 28, and 56 W/cm 2 with each period lasting 25-30 s during a continuous 5-min ECORE session of the same DRG neuron (FIG. 5G, horizontal lines). The firing activity appears to be strongly dependent on the laser power (FIG.5G, each vertical short line indicating an electric activity at the indicated time). No activity is detected during the two periods at 28 W/cm 2 and mild activities are detected at the three periods with 42 and 56 W/cm 2 . No long-term effect was observed such as changes in the morphology of the cell using laser intensities of up to 56 W/cm 2 . However, at 63 W/cm 2 , DRG neurons exhibited an accelerated activity pattern that then completely and irreversibly stopped after a few minutes, likely due to cell damage induced by over-stimulation. However, with a short ~1 min illumination duration such as shown in FIG.5G, the thermo-activation effect was reversible even at the highest power of 63 W/cm 2 . A previous report showed that photo illumination at 5900 W/cm 2 , λ = 640 nm for 240 s led to minimal phototoxicity in cultured mammalian U2OS cells. For ECORE recording, 28 W/cm 2 at λ = 660 nm was used, well below the threshold that would cause direct cell damage; however, the conversion of light to heat by the PEDOT film can have detrimental effects on cell health at high laser intensity. Therefore, at moderate optical powers (42-56 W/cm 2 ), it was hypothesized that ECORE can be used to photothermally stimulate and electrochemically record cells without any genetic manipulation. The brain slice is a widely-used model in the field of molecular and cellular neuroscience (FIG. 6A). With their local circuits and the cyto-architecture relatively intact, they have been employed in pharmacological studies in controlled environments and electrophysiological studies to characterize properties of individual neurons and neuronal networks. The electrical activity was measured of hippocampal brain slices obtained from P7 rats and cultured using Stoppini’s method. After 10 days of culture on a semipermeable membrane, the brain slice is flipped onto either a PEDOT film or a MEA device. The tissue is gently pressed onto the surface using a 3D-printed adapter terminated with a nylon mesh and immersed in artificial cerebrospinal fluid (ACSF) saturated with carbogen gas. These brain slices were first confirmed to exhibit spontaneous electric activities by using the conventional MEA device. MEA recording shows sparse and sporadic spikes (FIG. 6B), which is typical of hippocampus slice recording. After application of 20 μM carbachol, an agonist of the acetylcholine receptor, a significant increase was observed in the spike frequency by MEA recording (FIG.6C). Similar to the MEA recording, the ECORE recording shows sparse and spontaneous spiking patterns from brain slices (FIG.6D). The spikes are sometimes monophasic and sometimes biphasic. The peak-to-peak amplitude of ΔR/R=3×10 -5 can be observed with a S/N ratio of 14 at 1 kHz (-3dB) bandwidth. To confirm that the optically-recorded spikes are indeed from the electrical activity of the brain slice, 20 μM carbachol was applied to the brain tissue while it was being continuously recorded on the optical setup. A sudden and pronounced increase was observed in the optically-recorded spiking frequency (FIG.6E), in agreement with the MEA measurements (FIG.6C). Lastly, the electrical activity of brain slices depends on the availability of oxygen; hence hypoxic conditions decrease the electrical activity of brain slices. Indeed, the optical signal of a brain slice exposed to 20 μM carbachol without a continuous supply of carbogenated ACSF gradually decreases and ceases (FIG. 6F). Re-saturating the ACSF with carbogen restores the electrical activity of the same brain slice (FIG.12). These results demonstrate that label-free optical recording of hippocampal brain slices was achieved. Methods for label-free optical detection of bioelectric activities are disclosed. Using electrochromism, a unique material property, ECORE provides the spatial flexibility of optical detection without requiring molecular insertions or genetic modifications to the cells. ECORE is an extracellular method like MEAs. The methods offer complementary advantages to fluorescence-based voltage recording and would be valuable for measuring cells that are sensitive to molecular perturbation or difficult to modify genetically, such as human stem cell derived neurons for disease modeling. This work demonstrates the feasibility to optically detect action potentials via electrochromic materials using a single point of detection. Extending this work to imaging can be achieved by utilizing an acousto-optic deflector (AOD) to steer the beam to scan multiple sites of interest for simultaneous detection of many cells. For example, two-dimensional AODs could scan 100 spots at a rate of 1 kHz. For example, AOD can be used to scan over 100 arbitrary points within the field of view, spending approximately 10 microseconds on each point, so that each point is read out 1000 times per second. If the average optical power on each scanned site is the same as the optical power in a single-punt readout, scanning will not reduce the signal-to-noise ratio (FIG.13A). When scanning, a cell-free location can be selected as a control location, which can help identify artifacts or cancel technical noise. Also, scanning can be coupled with bright-field microscopy, to also allow users to manually select probing locations by a mouse-click on the image. The probing laser is slightly visible through a top-mounted camera due to weak scattering at the interface. This can be used to determine the probed location (x, y) on the specimen corresponding to each pair of frequencies (fx, fy) sent to the AOD. This can also be used to construct a transformation matrix that maps the AOD modulation frequencies to the corresponding beam locations in the field of view. The transformation matrix will convert cellular locations on the CCD image into a list of frequency pairs with which one can drive the AOD to the appropriate deflection angles. Moreover, software can be used to automatically identify cellular locations from a brightfield image. To identify probing locations, an image can be captured through a microscope objective and a CCD camera, mounted above the sample. The image will be fed into a software that automatically identifies cellular locations using thresholding and image segmentation. The sensitivity of ECORE can be further improved by choosing an optimal wavelength, polarization, and by using multiple probing wavelengths for noise rejection. The fast kinetics, long-term stability, and non-invasive nature makes ECORE an attractive candidate as a complementary tool applied toward the growing field of all- optical electrophysiology. Also, the sensitivity of PEDOT to electrical potentials is wavelength-dependent and can even have the opposite sign for two wavelengths, for example 532 nm and 780 nm (FIGS.15-17). A genuine electrical signal is thus expected to generate the opposite optical response when read out with two such wavelengths. Reading out with two wavelengths can be used to discriminate against artifacts and reject technical noise. Thus, certain embodiments of the invention provide measuring absorbance or a change of absorbance of a electrochromic film, such as PEDOT:PSS film, at two different wavelengths to measure the voltage or a change in voltage present at the surface of the film. The two wavelengths used to measure the voltage or a change in voltage are selected so that the two wavelengths are generate the opposite optical response to the same voltage or a change in voltage. Example 3 – Modeling the light reflection at the glass:ITO:PEDOT:water interface A theoretical study of the reflectivity of the PEDOT:PSS layer can help the understanding of how to maximize the signal-to-noise ratio of optically detecting a given voltage change ΔV. The basic physics is reflection at the boundary between media having different refractive indices n = n+iκ, where n is the usual refractive index and κ the extinction coefficient. Applied voltages change the absorptivity or extinction coefficient of the PEDOT:PSS layer by Δκ = (dκ/dV)ΔV, which in turn change the reflectivity of the layer by ΔR = (dR/dκ)Δκ. Background signals from technical sources (such as vibrations, air currents, or dust particles) are generally proportional to the detected power, and thus to the reflectivity R. To maximize the signal-to-noise-ratio, ΔR/R was maximized as ΔR/R = SΔκ, where S = (1/R)(dR/dκ). If S ≫ 1, the reflectivity change is optically enhanced relative to the change in κ. The is a four-layer structure (FIG.1C) in which light enters from glass BK-7 (n0 = 1.51 at 660 nm and incident angle θ0) into the ITO layer (n1 = 1.84 + i0.061, thickness d1, incident angle θ1), then into the PEDOT:PSS layer (n2 = 1.4 + iκ, thickness d2, incident angle θ2) , and finally into water (n3 = 1.33, incident angle θ3). The total reflectivity of the multilayer system is determined by interference between reflections from all layers. It can be calculated using the transfer matrix method. The wavenumber is defined as k = ω/c in vacuum as well as the z-components of the wavenumbers in material, k i ,z = kn i cos(θ i ), where n i and θ i are the index of refraction and incident angle in the i th layer. The angles can be calculated iteratively from θ0 by applying θi+1 = arcsin[ni sin(θ i )/n i +1]. They must be allowed to be complex, given that some of the n i are complex. The (amplitude) reflection coefficients for a beam in medium i going into medium j are given by rij p = (nj cos θj - ni cos θi)/(nj cosθj + ni cos θi) (p-polarization), rij s = (nj cos θ i - ni cos θj)/(nj cosθi + ni cos θj) (s-polarization). In the experiment, s-polarization was use. It was observed that it leads to low background reflectivities and thus a high contrast ΔR/R for a given electrical potential difference. For each boundary between layer i and i+1 (i=0, 1, and 2) a matrix was defined as: where δ0 =0 and δi =diki,z for i=1 and 2. To obtain the reflectivity of the entire system, we calculate the product where t01 is the transmission coefficient at the first boundary. The reflectivity of the entire system is the ratio of the elements in the first column of the matrix, r = M21/M11. The absolute square R = |r| 2 gives the power reflectivity. The angle θ0 is the incident angle of the beam from the prism into ITO. It is related to the incident angle θ of the beam going into the prism by θ0 = arccos[cos(β/2 +θ)/n0] - β/2, where β is the apex angle of the prism, 60° in these experiments. For vanishing ITO and PEDOT:PSS thicknesses, d1 = d2 = 0, the model reproduces the results of simple theory, such as the onset of total internal reflection at an angle of θ0 = arcsin[n3/n0] = 61.7° (which corresponds to θ = 62.3° measured outside the prism). The model was compared to observation at a wavelength of λ = 660 nm. To validate the model, the measured and predicted reflectivities were compare as a function of angle θ for various PEDOT:PSS thicknesses (FIG. 9), obtaining good qualitative agreement. The shape of the curves obtained from the model, i.e. the reflectivity, first increasing as the angle increases and then decreasing sharply after the total internal reflection angle, closely follows the experimental measurements. The samples were prepared with thicknesses of 30, 60, and 100 nm, but the PEDOT:PSS layer thickness can be inhomogeneous, and so the exact thickness at the point probed by the beam has a relatively high variance. Thus, the thickness of the PEDOT:PSS layer was determined to be 34, 59, and 77 nm by fitting the measured reflectivity (FIG. 9). The dependence of the reflectivity on the applied bias potential was also measured. FIG.10A shows a measurement of the reflectivity of a PEDOT:PSS film as a function of the bias voltage of the data. Matching the theoretically calculated reflectivity (with d1 =30 nm ITO and d2 =120 nm PEDOT:PSS) with the measured one allows the calculation of the extinction coefficient κ as a function of voltage (FIG.10B). Mathematically, for each measured reflectivity, this yields two solutions for κ, of which only one is physical. When using PEDOT:PSS to sense action potentials, any external bias was not applied and the layer adopts an open-circuit potential of -50 mV. At this operating point, it was found that κ0 ~ 0.22 and dκ/dV = -0.57/V. The model was also used to predict the signal strength |ΔR/R| of the optical readout as a function of the bias voltage on the PEDOT:PSS layer (FIG.10C) as well as the incident angle (FIG.10D). For a PEDOT:PSS layer that is d2 = 120 nm thick, for a 1 mV change, it was predicted that the sensitivity |ΔR/R| will first increase with bias and then decrease with the bias voltage. At about 80 mV, ΔR/R has a zero crossing; at higher bias, |ΔR/R| will increase again. This prediction is verified in detail by the experimental data (FIG. 10C). The modeled signal strength as a function of angle is compared with the data shown in FIG.2A (FIG.10D). It peaks at an incident angle θ =67 o (measured outside the prism), showing good agreement between the model and the data. Note that the measured reflectivity changes ΔR/R can be larger than the changes in the extinction coefficients Δκ by as much as ten-fold, i.e., S = (1/R)(dR/dκ) ≫ 1. Such optical enhancement is a key factor in the sensitivity of ECORE. The model disclosed herein predicts that S can reach values of 100, indicating that there is much room for optimizing the sensitivity of ECORE further. Example 4 – The electrochromism of PEDOT 3,4-ethylenedioxythiophene (EDOT) is a colorless, viscous compound which upon oxidative polymerization forms the better known insoluble blue solid poly-(3,4- ethylenedioxythiophene) (PEDOT). This organic polymer belongs to the class of conductive polymers due to its ability to support electronic and ionic transport, which are not typically displayed by their insulating organic counterparts. Electronic conductivity is achieved by the extended π-conjugated system along the backbone of the polymer. Extended conjugated electron systems like dyes and pigments typically absorb in the visible light range of the optical spectrum corresponding to a π-π* and/or a nonbonding-π* electronic transition; the same extended conjugated system gives rise to PEDOT’s color. Upon oxidation of the polymer backbone, an electron is removed from the π- conjugated system. This newly created positive charge is stabilized by the delocalization of the charge over several EDOT constituents and the recruitment of anions from the electrolyte solution. Doping or introduction of poly(styrene sulfonic acid) (PSS) impurities during the synthesis improves the water processability of the polymer and assists in the stabilization of the positive charge by providing an excess of negative charge from the sulfonate groups but requiring cations from the electrolyte for charge compensation. The effect of twisting present in all polymers in solution restricts the length of the conjugated system creating a distinct localized charge state known as a polaron. The creation of a polaron alters the optical properties of the polymer by creating a lower energy state available in which optical transitions can occur at a lower energy cost thus leading to a greater absorption of lower energy light in the near-infrared range of the electromagnetic spectrum. The electrochromism of PEDOT:PSS originates from the low charge or potential required to reversibly remove an electron from the backbone of the polymer thus affecting the optical transitions available due to the creation of the polaron. Images of the electrodeposited film obtained through scanning electron microscopy display a flat surface with granular domains on the order of 100 nm (FIG. 7). Visual inspection of the electrodeposited PEDOT:PSS film shows that the film appears blue at positive potentials such as +500 mV, while it appears purple at negative potentials such as -500mV (FIG. 8). The optical properties of electrodeposited PEDOT:PSS films are different from those of spin-coated PEDOT:PSS films from pre- formed polymer solutions. For instance, in the reduced state, electrodeposited PEDOT:PSS has a maximum absorbance at λmax = 580 nm while the spin-coated film has a maximum absorbance at λmax = 650 nm. This red-shifted optical spectrum of the spin-coated film can be attributed to a longer conjugation length and increased planarity of the pre-formed PEDOT:PSS polymer chains through chemically oxidative polymerization. Example 5 – Spatial-temporal response of PEDOT Temporal Resolution The temporal response of the film must also be sufficiently fast to capture cellular electric potentials in the order of 1 ms. The limit on the temporal resolution is given by the τ = RC product of the electrolyte resistance R and the double-layer capacitance C of the PEDOT:PSS film. Electrochemical impedance spectroscopy (FIG.11) measures the resistance and capacitance properties of an electroactive material via application of a sinusoidal AC voltage signal. A 10-mV sinusoidal signal with a DC bias of 0 mV vs. Ag/AgCl was used to measure the impedance Z of films deposited on patterned ITO in the frequency range of 100 mHz to 100 kHz. FIG. 11 shows the impedance |Z| as a function of the frequency for PEDOT samples of different surface areas. The results were fitted with a resistor-capacitor series connection Z = R+1/(iωC), where ω is the angular frequency, using the EC-Lab software (Bio-Logic), where R represents the electrolyte resistance and C the double layer capacitance. At low frequencies, Z is dominated by the capacitive term 1/(iωC) and thus proportional while at high frequencies, the constant resistance R dominates. Thus, the data allows to independently determine R and C (Table 1). The double layer capacitance C = (8.11±0.44) µF/mm 2 ×A is found to be proportional to the PEDOT surface area A as expected. The resistance is expected to be proportional to 1/A 1/2 if the PEDOT surface area is small compared to the dimensions of the rest of the system. These measurements reproduce this, with R = (532±15) Ω mm/A 1/2 , in good agreement with expectations from the specific resistance of the medium of 69 Ω cm for a 0.9% saline solution at 22°C. Since R and C are proportional to 1/A 1/2 and A, respectively, the RC time constant is proportional to A 1/2 , i.e., it decreases with the square-root of the surface area when the surface area is decreased. The 10%-90% rise-time for square-wave signals is tr =2.2RC; we find it to be tr =9.5 ms mm/A 1/2 (Table.1). Spatial resolution The spatial resolution of the PEDOT:PSS film must be sufficient to detect electrical activity from individual cells. When a cell is in close contact with the film, the cell’s electrical activity will charge the film locally; however, the PEDOT:PSS film is electrically conductive and the charge diffusion may degrade the spatial resolution. The reported charge mobility in PEDOT polymer is around 10 -4 to 10 -6 cm 2 /V/s, which implies a diffusion constant D = kBTµ/e between 2.5×10 -3 and 2.5×10 -1 μm 2 /ms. After 1 ms, the diffusion area will be between 10 -3 and 10 -1 µm 2 , much smaller than a cell. Nevertheless, the spatial resolution of the film was experimentally measured by measuring the optical response at different film locations when a 20 mV electrical pulse of 50 ms duration is applied through a microelectrode 10 µm above the film. The measured half width at half maximum for the optical response is 50 µm by 70 µm, which is approximately the size of the laser spot (FIG. 2F). The optical response decayed quickly as the microelectrode was moved away from the laser spot. Therefore, the spatial resolution of the electrochromic film is limited not by charge diffusion, but by the size of the probing laser spot. Example 6 – Certain modifications and preferred embodiments of the invention ECORE is fundamentally different from previous approaches in that the electrical action potential is read out optically through the voltage-sensitive optical absorption of an electrochromic film outside the cell; the cells do not incorporate any molecular probes. Electrochromic materials have been used in commercial applications including "smart windows” for aircraft and glass facades for energy efficient buildings, but has not been used to detect bioelectric potentials. The unique voltage-dependent absorption of electrochromic material is used to achieve optical readout of electrical signals in cells including neurons, cardiomyocytes, spiking HEK cells, and brain slices. Specific electrochromic materials, such as PEDOT:PSS, Prussian blue, iridium oxide, vanadium oxide, poly(aniline), and poly(pyrrole)) that are long-term biocompatible, not toxic, and long-term stable in the biological environment, and exhibit high sensitivity to electric potentials at zero bias. PEDOT and iridium oxide have been used as a coating material for electrodes in electrophysiology for its biocompatibility and electrical conductivity, but its electrochromic optical properties have not been exploited so far in electrophysiology. They allow using the open-circuit potential, rather than active bias, to achieve high sensitivity to electric potentials, without any electrodes in the solution. The reflection of the electrochromic layer, rather than the transmission, can be measured. This leaves the other side of the specimen completely free for imaging and other purposes, and avoids signal fluctuations and noise from wiggles on the surface of the solution. Using an optimized incident angle of the laser beam, usually close to the onset of total internal reflection (TIRF), can maximize sensitivity and signal-to-noise ratio. Using a multilayer arrangement of the electrochromic film and other transparent media (such as glass, iridium-tin oxide, and aqueous solution) can also be used to maximize these figures of merit, and may be beneficial for ease of manufacturing. Sensitivity can be enhanced by using an optimized wavelength and matching the size of the laser beam on the specimen to the size of a cell. Using a balanced photodetector to suppress artifacts and laser noise by a differential measurement. Differential measurements could be made between the reflected beam from the electrochromic layer and a sample of the unreflected laser beam, or between light of different wavelengths both reflected by the electrochromic film, using the fact that the reflectivity change for different wavelengths (such as red versus green) can be opposite, which allows telling a true signal apart from noise and artifacts. In a similar way, a differential measurement between light of different polarizations, both reflected by the electrochromic film, can be used, since the reflectivity change in response to the same stimulus may be opposite for different polarizations. The invention can be used in an imaging configuration to record multiple recording sites in parallel. For example, ECORE can be extended into an imaging platform that enables parallel and label-free detection of neuronal electric activities over a large field of view, e.g. simultaneous recording up to many (100 or more) sites in parallel with 1-ms time resolution. Imaging could be done, e.g., by scanning, which would allow using a differential photodetector for noise suppression, reaching a high dynamic range, and use the above differential detection methods to suppress noise and optimize sensitivity. As an alternative to raster-scanning, one can scan the regions of interest, e.g., with acousto-optic deflectors. This allows concentrating the available laser power on specific sites and thus attain a better sensitivity. It would enable parallel readout of cell activities at user-selected, arbitrary regions of interest by combining the system with optical microscopy. For example, as shown in FIG.13B, five locations can be selected on the same cell for scanning. Also, FIG.13E shows scanning of an array of 5x6 points and targeted stanning of 11 points with dwell time of 10 µs at each spot. Another version of the invention would apply the electrochromic material at an optical fiber whose reflection is used to measure electrical potentials in vivo. It can also be developed into an optical fiber-based method that enables simultaneous optical stimulation by optogenetics and optical recording by electrochromic materials in living brains, based on an electrochromic film applied to the end of a single optical fiber. This will result in an entirely new class of electrophysiological tools. This fiber-based readout can be combined with dual-wavelength readout or dual-polarization readout, as described above, to enhance the sensitivity and suppress artifacts. ECORE (both fiber- based and not fiber-based) can also be combined with optogenetics stimulation of neuronal activity. In some cases, one can use blue light for optogenetic stimulation and green and longer-wavelength light for electrical recording. Electrochromic materials such as PEDOT are less susceptible than metal electrodes to the photoelectric artifact, enabling simultaneous stimulation and readout. Example 7 – Applications and advantages of the disclosed methods and devices Applications of the methods and devices disclosed herein include (1) electrophysiology recording in the brain; (2) electrophysiology recording in the heart; (3) electrophysiology recording in cultured cells such neurons and cardiomyocytes; (4) electrophysiology recording in stem-cell derived cardiomyocytes or neurons; (5) drug toxicity screening of small molecule drugs affect cardiomyocyte or stem-cell derived cardiomyocyte action potentials; (6) investigation of drug effect on neuronal activities. Advantages & improvements over existing methods, devices or materials include: Compared with intracellular electrophysiological recording (such as patch clamp), ECORE is noninvasive and can be used to measure many cells at once, and over long periods of time. Compared with extracellular electrophysiological recording (multi-electrode array), ECORE can be flexibly directed to record any cell within a sample, rather than recording at pre-determined sites. Compared with voltage-sensitive protein electrophysiological recording, ECORE does not require genetic modification of cells, and does not perturb the cell physiology with molecular probes. There is no membrane-capacitance loading or phototoxicity or photobleaching, which enables long-term recording with ECORE. Compared with voltage-sensitive dye electrophysiological recording, ECORE does not perturb the cell physiology with molecular probes. There is no membrane- capacitance loading or phototoxicity or photobleaching, which enables long-term recording with ECORE. Compared to nitrogen vacancy centers in diamond, ECORE does not require averaging over many cells, and therefore enables readout of the unstimulated, spontaneous activity of individual cells, rather than being restricted to stimulated events or cell ensembles. Compared to optical methods (Full-field interferometric imaging, surface plasmon resonance imaging, and optical coherence tomography) that read out mechanical movement of cell membrane accompanying action potentials, ECORE directly read out electric signals and is thus not subject to other mechanical signal contamination such as cell movement or cardiomyocyte contraction. Also, unlike these methods, all of which requires averaging of many trials, ECORE does not require averaging over many cells, and therefore enables readout of the unstimulated, spontaneous activity of individual cells, rather than being restricted to stimulated events or cell ensembles. ECORE does not require any bias or other electrodes, which helps ease of application, biocompatibility, and avoids damage to the cells from the application of electrical voltages. Notwithstanding the appended claims, the disclosure is also defined by the following embodiments: Embodiment 1. A method for assessing electrical activity near a surface comprising an electrochromic material, comprising measuring a change in an absorption parameter of the electrochromic material. Embodiment 2. The method of embodiment 1, wherein the assessing comprises measuring a change in an electrical potential near the surface. Embodiment 3. The method of embodiment 1 or 2, wherein the absorption parameter comprises absorbance of the electrochromic material. Embodiment 4. The method of embodiment 1 or 2, wherein the absorption parameter comprises absorption maximum of the electrochromic material. Embodiment 5. The method of embodiment 1 or 2, wherein the absorption parameter comprises relative reflectivity change of the electrochromic material. Embodiment 6. The method of any of preceding embodiments, wherein the surface comprises a layer of the electrochromic material on a transparent, substantially transparent, or translucent substrate. Embodiment 7. The method of embodiment 5, wherein the layer of electrochromic material has a thickness of between 50 nm and 500 nm. Embodiment 8. The method of any of preceding embodiments, wherein the absorption parameter is analyzed using a light beam incident on the surface at an angle. Embodiment 9. The method of embodiment 8, wherein the incident angle is between 55 o and 75 o . Embodiment 10. The method of embodiment 8 or 9, comprising focusing the laser beam onto the surface through a prism-coupled total internal reflection configuration. Embodiment 11. The method of any of preceding embodiments, wherein the area of the surface in which the change in the absorption parameter is measured is between 0.1 mm 2 to 1 mm 2 . Embodiment 12. The method of any of preceding embodiments, comprising measuring the change in the absorption parameter of the electrochromic material over a period of between 1 millisecond to 100 milliseconds. Embodiment 13. The method of any of preceding embodiments, wherein the electrochromic material comprises a metal-organic frameworks, metal oxide, or conductive polymer. Embodiment 14. The method of any of preceding embodiments, wherein the electrochromic material comprises Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS). Embodiment 15. The method of any of preceding embodiments, comprising measuring the change in the absorption parameter of the electrochromic material at a plurality of locations near the surface. Embodiment 16. The method of any of preceding embodiments, comprising measuring the change in the absorption parameter of the electrochromic material at two wavelengths. Embodiment 17. The method of embodiment 16, wherein the two wavelengths are selected such that the change in the absorption parameter of the electrochromic material for one of the two wavelengths is opposite to the change in the absorption parameter for the other wavelength. Embodiment 18. A method for assessing electrical activity of a cell, comprising culturing the cell on a surface comprising an electrochromic material and measuring a change in an absorption parameter of the electrochromic material. Embodiment 19. The method of embodiment 18, wherein the assessing comprises measuring a change in an electrical potential near the surface. Embodiment 20. The method of embodiment 18 or 19, wherein the absorption parameter comprises absorbance of the electrochromic material. Embodiment 21. The method of embodiment 18 or 19, wherein the absorption parameter comprises absorption maximum of the electrochromic material. Embodiment 22. The method of embodiment 18 or 19, wherein the absorption parameter comprises relative reflectivity change of the electrochromic material. Embodiment 23. The method of any of embodiments 18 to 22, wherein the surface comprises a layer of the electrochromic material on a transparent, substantially transparent, or translucent substrate. Embodiment 24. The method of embodiment 23, wherein the layer of electrochromic material has a thickness of between 50 nm and 500 nm. Embodiment 25. The method of any of embodiments 18 to 24, wherein the absorption parameter is analyzed using a light beam incident on the surface at an angle. Embodiment 26. The method of embodiment 25, wherein the incident angle is between 55 o and 75 o . Embodiment 27. The method of embodiment 25 or 26, comprising focusing the laser beam onto the surface through a prism-coupled total internal reflection configuration. Embodiment 28. The method of any of embodiments 18 to 27, wherein the area of the surface in which the change in the absorption parameter is measured is between 0.1 mm 2 and 1 mm 2 . Embodiment 29. The method of any of embodiments 18 to 28, comprising measuring the change in the absorption parameter of the electrochromic material over a period of between 1 millisecond and 100 milliseconds. Embodiment 30. The method of any of embodiments 18 to 29, wherein the electrochromic material comprises a metal-organic frameworks, metal oxide, or conductive polymer. Embodiment 31. The method of any of embodiments 18 to 30, wherein the electrochromic material comprises Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS). Embodiment 32. The method of any of embodiments 18 to 31, wherein the cell is a neuronal cell or a muscle cell. Embodiment 33. The method of any of embodiments 18 to 32, wherein the cell is not genetically modified. Embodiment 34. A device comprising optical system providing a beam and a prism abutting a first side of substrate, wherein the other side of the substrate comprises a layer of an electrochromic material. Embodiment 35. The device of embodiment 34, wherein the substrate is transparent, substantially transparent, or translucent. Embodiment 36. The device of embodiment 34 or 35, wherein the substrate comprises a glass or a plastic. Embodiment 37. The device of any of embodiments 34 to 36, wherein the substrate comprises a culture plate onto which a cell or a tissue slice is cultured. Embodiment 38. A culture plate comprising a transparent, substantially transparent, or translucent substrate coated with an electrochromic material. Embodiment 39. The culture plate of embodiment 38, wherein the substrate comprises a glass or a plastic. Embodiment 40. The culture plate of embodiment 38 or 39, comprising cultured thereon a cell or a tissue slice. Embodiment 41. The culture plate of embodiment 40, wherein the cell is a neuronal cell or a muscle cell. Embodiment 42. The culture plate of embodiment 40, wherein the tissue slice is a brain slice. Additional embodiments As described above and below, ECORE that is able to detect spontaneous single-cell action potentials in primary neurons, stem-cell-derived cardiomyocytes, and brain slices. The probing laser can be focused to a single spot for single-cell recording. Several additional embodiments are described below. These embodiments increase the sensitivity, allow for parallel recording, and enhance spatial resolution for, e.g., subcellular recording. 1. Increasing signal to noise and sensitivity. a. Wavelength multiplex. PEDOT reflectivity at 532 nm and 850 nm wavelength changes in opposite directions in response to electrical potentials. This anti-correlation will allow this method to discriminate real signals against artifacts. b. Polarization multiplex. It has has demonstrated that the PEDOT reflectivity for s and p-polarized light changes differently in response to electrical signals. This difference can be used to discriminate real signals against artifacts. 2. Scanning ECORE for parallel and label-free detection of neuronal electric activities. The system can, e.g., simultaneously record 50 locations at 1-kHz sampling rate each. This is yet to be achieved by fluorescence-based voltage recording methods, which usually record less than two dozen cells at 500-1000 Hz frame rate. a. The beam will be steered across the specimen, e.g., using an acousto- optic deflector (AOD). Instead of imaging with a camera, this allows us to leverage the high signal to noise, dynamic range, and laser-noise rejection of balanced photodetectors. It allows directing the available laser power only to the recording sites of interest rather than evenly distributing it, thus increasing signal to noise at a given laser power. b. ECORE can be combined with brightfield imaging through a microscope objective positioned above the sample. c. The brightfield image can be observed on a computer screen; software will automatically identify cells using thresholding and image segmentation. Alternatively, users can manually select scanning sites. d. The probing laser is weakly visible through the top-mounted camera. For each input pair of frequencies (fx, fy) sent to the AOD (which steers the beam across the specimen), we measure the laser location (x, y) in the camera image to map the modulation frequencies to the corresponding beam locations. e. The signal from the photodetector will be parsed into a number of channels (e.g., 50), each of which now consists of, e.g., 1000 measurements at one location per second. 3. A scanning or non-scanning ECORE microscope for subcellular measurement of neuroelectric activities. The spatial resolution of ECORE can be drastically increased for, e.g., multisite subcellular recording in axons and dendrites. a. We will integrate ECORE with a total-internal reflection (TIRF) microscope, enabling us to focus the probing beam to, e.g., 1 micrometer. The same objective can be used for collecting the reflected beam b. Microscope-based ECORE can be combined with fluorescence or other imaging modules, using the same objective for both, such as observing a brightfield image of a cell culture or brain slice and use automated as well as manual selection of probing locations (see above) to easily identify cells and display ECORE-recordings of their action potentials. c. The large number of lenses inside the microscope objective increases the number of stray beams. Parasitic interference between these beams causes intensity fluctuations (“speckle”) and technical noise. To eliminate this noise, we will use a superluminescent diode as a light source. It delivers light having a single spatial mode like a laser, but with a short coherence length. This eliminates the interference and thus, the associated noise. d. The scanning ECORE microscope can utilize the entire field of view of the microscope objective: An AOD can resolve, e.g., 300 × 300 spots. With the beam collimated to 2 μm, we can address arbitrary probing locations within a field of view 0.6 × 0.6 mm 2 . e. A brightfield image will be generated through the TIRF objective. As above, this will allow the software to accurately correlate the exact locations of the scanning beam with the frequencies sent to the AOD. f. For noise reduction, the AOD can switch the beam location between multiple locations. We can thus interleave measurements of the recording site with measurements of one or more close-by reference locations, at which no cells are present. Subtracting the respective signals should further cancel out the background signals. In addition, 1. For scanning, an agile signal generator, such as Red Pitaya, will convert the list of frequency pairs (fx, fy) generated by the software into a sequence of radiofrequency signals to drive the AOD that is repeated, e.g., 1000 times per second. 2. In scanning, whenever the beam moves between locations, we ignore the signal for a few μs to allow the beam and the signal to settle, to improve signal to noise. 3. Intracellular recording. Currently, ECORE is designed for extracellular measurement. However, we have preliminary data to support that opto-poration allows ECORE transient intracellular access, thus enhancing the signal to noise of our measurement. 4. Finally, a compact ECORE module is designed that can fit into a standard microscope port, so that the technology can be adapted by collaborators and other researchers. The probing laser will be introduced, e.g., into the back port of a Nikon Ti microscope and reflected upward into the objective through a dichroic mirror inside the filter cube. The preceding merely illustrates the principles of the present disclosure. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments of the invention as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. The scope of the present invention, therefore, is not intended to be limited to the exemplary embodiments shown and described herein.