System for culture and interrogation of excitable cells

Abstract

A microfluidic device includes a first microfluidic channel, a second microfluidic channel, a membrane having a plurality of excitable cells, and at least two electrodes. The membrane separates the first microfluidic channel and the second microfluidic channel. The at least two electrodes are in electrical communication with the membrane and configured to detect an electrical output of the excitable cells.

Description

SYSTEM FOR CULTURE AND INTERROGATION OF EXCITABLE CELLSCROSS-REFERENCE TO RELATED APPLICATIONS[00011 This application claims priority to U.S. provisional application Serial No. 63 / 724,733 filed November 25, 2024, the disclosure of which is hereby incorporated in its entirety by reference herein.TECHNICAL FIELD|0002J Aspects of the present disclosure generally relate to microfluidic devices used for microphy si ologi cal systems.BACKGROUND

[0003] A microphysiological system, which may also be referred to as a tissue chip or an organ- on-chip, employs microfluidic devices to mimic structure and / or function of tissues and organs. A microfluidic device can include features such as channels, chambers, and wells for culturing cells with desired tissue construct and observing / testing the cultured cells under controlled conditions.SUMMARY[0004J In one or more illustrative examples, the present disclosure is directed to a microfluidic device that includes a first microfluidic channel, a second microfluidic channel, a membrane having a plurality of excitable cells, and at least two electrodes. The membrane separates the first microfluidic channel and the second microfluidic channel. The at least two electrodes are in electrical communication with the membrane and configured to detect an electrical output of the excitable cells.

[0005] In some aspects, the at least two electrodes are configured to provide an electrical stimulus to the membrane responsive to detecting the electrical output of the excitable cells. In some aspects, the second channel is a trough. In some aspects, a portion of the first channel and aportion of the second channel overlap defining an overlapping region. In some aspects, the excitable cells are defined as monolayers provided on the membrane. In some aspects, the excitable cells are formed as a monolayer on a 3 -dimensional gel underlay. In some aspects, the excitable cells are formed as a three-dimensional cell culture. In some aspects, the membrane is a micropatterned membrane and the excitable cells are cultured on the micropatterned membrane. In some aspects, the microfluidic device further includes stromal cells in the first microfluidic channel to be provided to the excitable cells.

[0006] In one or more illustrative example, a system includes an array of microfluidic devices and a plurality of electrodes. Each microfluidic device includes a membrane having a plurality of excitable cells. For at least one microfluidic device of the array of microfluidic devices, at least two electrodes are in electrical communication with the membrane and the at least two electrodes are configured to detect an electrical output of the excitable cells.

[0007] In some aspects, the plurality of electrodes is configured to provide a stimulation pulse to the at least one microfluidic device and measure the electrical output of the excitable cells. In some aspects, the at least two electrodes are configured to provide an electrical stimulus to the membrane responsive to detecting the electrical output of the excitable cells. In some aspects, the excitable cells are defined as monolayers provided on the membrane. In some aspects, the excitable cells are formed as a monolayer on a 3-dimensional gel underlay. In some aspects, the membrane is a micropatterned membrane and the excitable cells are cultured on the micropatterned membrane. In some aspects, each microfluidic device includes a first microfluidic channel and a second microfluidic channel, and the membrane separates the first microfluidic channel and the second microfluidic channel. In some aspects, the second channel is a trough. In some aspects, each microfluidic device includes stromal cells in the first microfluidic channel to be provided to the excitable cells. In some aspects, a portion of the first channel and a portion of the second channel overlap defining an overlapping region. In some aspects, the system further includes a controller configured to receive an electrical signal indicative of the electrical output of the excitable cells. The controller is further configured to independently communicate with each microfluidic device using the at least two electrodes of the microfluidic device.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1A illustrates a well plate including an array of microfluidic devices having a first configuration.

[0009] FIG. IB illustrates a well plate including an array of microfluidic devices having a second configuration.

[0010] FIG. 2A illustrates a microfluidic device having an overlapping region with a pair of electrodes.[0011 | FIG. 2B illustrates a partial cross-sectional view of the microfluidic device of FIG. 2 A.[00121 FIG. 3 A illustrates a microfluidic device having a trough with a pair of electrodes.[00131 FIG. 3B illustrates a partial cross-sectional view of the microfluidic device of FIG. 3 A.[0014| FIG. 4A illustrates the microfluidic device having the overlapping region with a pair of electrodes on opposing sides.

[0015] FIG. 4B illustrates a partial cross-sectional view of the microfluidic device of FIG. 4 A.[0016| FIG. 5A illustrates the microfluidic device having the trough with a pair of electrodes on opposing sides.

[0017] FIG. 5B illustrates a partial cross-sectional view of the microfluidic device of FIG. 5A.

[0018] FIG. 6A illustrates the microfluidic device having the overlapping region with three electrodes.10019] FIG. 6B illustrates a partial cross-sectional view of the microfluidic device of FIG. 6A.10020] FIG. 7A illustrates the microfluidic device having the trough with three electrodes.10021] FIG. 7B illustrates a partial cross-sectional view of the microfluidic device of FIG. 7A.

[0022] FIG. 8 is an example sensor system using the microfluidic devices in accordance with the present disclosure.

[0023] FIG. 9 is a graph illustrating an example electrical response from the sensor system having an array of the microfluidic devices.

[0024] FIG. 10 is an example stimulation system including an array of electrodes and an array of the microfluidic devices in accordance with the present disclosure.DETAILED DESCRIPTION[0025| Embodiments of the present disclosure are described herein. It is to be understood, however, that the disclosed embodiments are merely examples and other embodiments can take various and alternative forms. The figures are not necessarily to scale; some features could be exaggerated or minimized to show details of particular components. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a representative basis for teaching one skilled in the art to variously employ the embodiments. As those of ordinary skill in the art will understand, various features illustrated and described with reference to any one of the figures can be combined with features illustrated in one or more other figures to produce embodiments that are not explicitly illustrated or described. The combinations of features illustrated provide representative embodiments for typical applications. Various combinations and modifications of the features consistent with the teachings of this disclosure, however, could be desired for particular applications or implementations.

[0026] Referring to FIGS. 1 A and IB, a well plate 100A, 100B includes an array of microfluidic devices 102A, 102B having excitable cells. Each well plate 100A, 100B includes a number of microfluidic devices 102A, 102B. Each well plate can have, for example, 96 microfluidic devices, 120 microfluidic devices, or any number of microfluidic devices. The microfluidic devices 102A, 102B can be arranged in an array, such as 12 by 8 grid / array. However, other configurations may be employed for the well plates 100 A, 100B, and the present disclosure should not be limited to the well plates 100A, 100B illustrated in the figures. For example, the array of microfluidic devices102A, 102B is arranged in other shapes such as circular arrangement, honeycomb arrangement, among others. In addition, the number of microfluidic devices 102A, 102B may vary.

[0027] In the following, the well plates 100A, 100B may collectively be referred to as well plates 100 and the microfluidic devices 102A, 102B may collectively be referred to as microfluidic device(s) 102.

[0028] The microfluidic device 102 is defined by a stack of layers (not shown) including a membrane having the excitable cells, a first microfluidic channel (“first channel”), and a second microfluidic channel (“second channel”). The membrane separates and provides biophysical communication between the first channel and the second channel. While not illustrated in FIGS. 1A and IB, examples of the membrane and the excitable cells are illustrated in at least FIGS 2A, 2B, 3A, and 3B, which illustrate microfluidic devices 200 and 300.

[0029] In some aspects, the microfluidic device 102A includes a first channel 104 having two ports 106A, 106B, and a second channel 108 having ports 110A, HOB. The ports 106A, 106B, of the first channel 104 are coupled to wells (not shown) of the plate 100A and the ports 110A, HOB of the second channel 108 are provided as openings in the first channel 104 to receive fluid containing the excitable cells from the first channel 104. In some configurations, one or more layers forming the first channel 104 is at a base of the device 102, and one or more layers forming the second channel 108 is arranged above the one or more layers forming the first channel 104, with the membrane provided in between. In some variations, the second channel 108 includes one or more additional ports that are coupled to wells of the plate 100A.

[0030] The microfluidic device 102A includes an overlapping region 112 in which the first channel 104 and the second channel 108 overlap one another. In a non-limiting example, the first channel 104 is disposed beneath the second channel 108, and the overlapping region 112 forms a top wall of the first channel 104, and a bottom wall of the second channel 108. The overlapping region 112 further includes the membrane having excitable cells arranged between the first channel 104 and the second channel 108. The overlapping region 112 may be porous, or otherwise semipermeable to facilitate flow of one or components of a fluid between the first channel 104 and the second channel 108, or vice versa. In some variation, an excitable cell culture (e.g., a fluidsample that includes one or more excitable cells) is provided to the second channel 108 portion of the overlapping region 112, and the overlapping region 112 is configured to trap / retain excitable cells provided in a fluid sample that passes through at least one of the second channel 108 or the first channel 104.[0031| With continuing reference to FIG. IB, in one embodiment, layers of the microfluidic device 102B defines openings 120A, 120B, a microfluidic channel 122 (e.g., a first channel), and a trough 124 (e.g., a second channel). The openings 120A, 120B connect to inlet reservoirs 126A, 126B and the trough 124 connects to a chamber inlet reservoir 128. The microfluidic channel 122 aligns and extends under the trough 124 and extends to and under the openings 120 A, 120B. The channel 122 is separated from the trough 124 via the membrane, which forms a roof of the channel 122. In some variations, the membrane is a porous membrane and fluidly couples the trough 124 and the channel 122. One or more layers forming the membrane also include apertures that align with the openings 120A,120B connecting the channel 122 and the openings 120 A, 120B.|0032] Referring to FIGS. 2A to 2B, a microfluidic device 200, which may be employed as the microfluidic device 102A, has a first channel 202 and a second channel 204, where a portion of the first and second channels 202, 204 overlap forming an overlapping region 206. The first channel 202, the second channel 204, and the overlapping region 206 are configured in a similar manner as that of the first channel 104, the second channel 108, and the overlapping region 112 of the microfluidic device 102A, respectively. Like the microfluidic device 102A, the microfluidic device 200 includes a membrane 208 having excitable cells 210, and the membrane 208 separates and provide biophysical communication between the first channel 202 and the second channel 204.[00331 Referring to FIGS. 3A and 3B, a microfluidic device 300, which may be employed as the microfluidic device 102B, has a microfluidic channel 302 (e.g., first channel), a trough 304 (e.g., a second channel 304), and openings 306A, 306B. The microfluidic channel 302, the trough 304, the openings 306A, 306B are configured in a similar manner as that of the microfluidic channel 122, the trough 124, and the openings 120A, 120B. Like the microfluidic device 102B, the microfluidic device 300 includes a membrane 308 having excitable cells 310, and the membrane308 separates and provide biophysical communication between the channel 302 and the trough 304. The membranes 208, 308 may be a microporous membrane and referred to as a scaffold.

[0034] The excitable cells 210, 310 are cells that respond to electrical or chemical stimuli by generating electrical signals. That is, the excitable cells 210, 310 propagate electrical signals through a process known as action potential, where the potential across the cell membrane (i.e., a membrane potential), changes from a resting membrane potential due to rapid depolarization and repolarization events leading to a measurable electrical signal. These electrical signals are measurable in the environment surrounding the tissue and may be used to make inferences on the state of health and maturity of the cultured excitable cells. The excitable cells 210, 310 may be provided as, but are not limited to, muscle cells (e.g., skeletal muscle cells), cardiomyocytes, or neurons. The excitable cells 210, 310 may be derived from donor cells, cell lines, or from induced pluripotent stem cells from healthy or diseased sources.

[0035] In some aspects, the first channel 104, 122, 202, 302 is configured to support the excitable cells by providing nutrients through media flow provided by an array of microfluidic pumps (not shown). In some variations, the first channel 104, 122, 202, 302 further incorporates stromal cells to support the tissue constructs of the excitable cells 210, 310.[0036| The membrane 208, 308 and the excitable cells 210, 310 may be provided in various configurations. The following is a non-limiting example of the different membrane and excitable cell configurations that may be used individually or in combination for the microfluidic devices 102, 200, and 300.

[0037] In some variations, tissue construct of the excitable cells are in the form of monolayers grown directly on the membrane.

[0038] In another variation, the membrane is coated by a thin layer of extracellular matrix including, but not limited to, collagen or fibrin.[0039| In yet another variation, the tissue construct of the excitable cells is formed as a monolayer on a 3 -dimensional gel underlay, where the gel can be an extracellular matrix material including, but not limited to, collage gel, fibrin gel, or Matrigel.

[0040] In another variation, the tissue construct is cultured on a micropatterned membrane where the pattern is either physically imparted on the membrane through, for example, microgrooves or biochemically imparted through, for example, selective deposition of the extracellular matrix proteins into desired pattern.[0041 J In yet another variation, the tissue construct of the excitable cells are in the form of an organoid or a spheroid.[0042| In one variation, the tissue construct of the excitable cells is self-assembled while in another embodiment the tissue construct is formed through molding or 3D printing.[0043J In some applications, sensors for detecting the electrical signal are provided with the microfluidic devices 102, 200, 300. In a nonlimiting example, the sensor includes one or more electrodes. For instance, in FIGS. 2A and 2B, the microfluidic device 200 includes electrodes El and E2 arranged along the second channel 204 and in FIGS. 3A and 3B, the microfluidic device 300 includes the electrodes El and E2 at the trough 304. In both devices 200, 300, the electrodes El, E2 are placed in close proximity to the excitable cell cultures. In some variations, the electrodes El, E2 may contact the tissue construct of the excitable cells 210, 310 by touching the tissue construct. In another variations, the electrodes El, E2 are in electrical contact with the tissue construct through electrically conductive culture media or buffers.[0044| In some aspects, the electrodes El, E2 measure the electrical response of the excitable cells 210, 310. The electrodes El, E2 may comprise of various suitable materials and / or configurations. For example, the electrodes El, E2 comprise stainless steel or noble metals (e.g., platinum and / or gold). In another example, the electrodes El, E2 are flexible electrodes on flexible substrates (e g., polyimide, polyetherimdie, or polyethylene terephthalate) with desired traces deposited in metals (e.g., gold, silver, or platinum) such that they are in electrical communication with the tissue construct.

[0045] In FIGS. 2A, 2B, 3A, and 3B, two electrodes are used for detecting the electrical signal and are placed on the same side of the tissue construct of the device 200, 300. However, one or more electrodes may be used and / or placed at other positions of the devices 200, 300. For example,referring to FIGS. 4A and 4B, for the device 200, the pair of electrodes El, E2 are placed on opposing sides of the tissue construct of the excitable cells 210. Similarly, in FIGS. 5A and 5B, for the device 300, the pair of electrodes El, E2 are placed on opposing sides of the tissue construct of the excitable cells 310. In another variations, three electrodes El, E2, E3 are used for measuring the electrical response and for measuring a field potential (see FIGS. 6A, 6B, 7A, and 7B).[0046| In a non-limiting example, with the electrodes, an array of the microfluidic device 102, 200, 300 forms part of a sensor system to measure an electrical field potential of the tissue construct of the excitable cells 210, 310. For example, FIG. 8 illustrates a sensor system 400 including the well plate 100) and an array of electrodes 402 arranged at the microfluidic devices 102, 200, 300 of the well plate 100, and a sensor controller 404 in communication with the array of electrodes 402. The sensor controller 404 is configured to receive electrical response of the excitable cells as electrical signals via the electrodes 402. In some applications, the electrical signal received has a magnitude and bandwidth comparable to that of an electrocardiogram. The sensor controller 404 is configured to quantitatively determine electrical activity of the tissue constructed of excitable cells 210, 310 based on the electrical signals from the cells 210, 310. In some cases, the electrical activity of the tissue construct of the excitable cells 210, 310 indicates characteristics of the cells health. For example, cardiac cells exhibit spontaneous pulses or contractions. A regularity of these pulses may correlate to the health of the cardiac cells, such that a more regular and evenly paced pulse may indicate a strength or maturity of the tissue.[0047| In some variations, a low noise, heart rate monitor integrated chip designed for wearable products and in conjunction with a potentiostat chip is multiplexed through a series of electrical cross point switches or multiplexer switches and controlled by a microcontroller to individually address each microfluidic device 102, 200, 300 of the plate 100 and to serially perform the field potential measurement. In some aspects, an array of heart rate monitor and potentiostat integrated chips are used to make parallel measurements of the field potential. In another aspect, a combination of an array of heart rate monitors and potentiostat integrated chips and cross point switches or multiplexer switches are used to make combined serial and parallel measurements of the electric field potential of the tissue constructs.

[0048] Referring to FIG. 9, a graph 500 illustrates electrical response of a cardiac tissue construct compared to blank control devices using platinum electrodes submerged in the culture media on the same side of the tissue construct. The cardiac tissue construct is provided as a monolayer of cardiac tissue cultured in a micro-trough configuration (e.g., device 102B, 300) on a microporous 0.4 micron membrane. The electrical field potential measurements using a pair of platinum electrodes submerged in the culture media on the same side of the tissue construct (line 502) measures a response different than that of blank control devices in absence of the tissue (line 504).

[0049] In addition or alternate to detecting electrical response, the microfluidic devices 102, 200, 300 can stimulate tissue constructs having the excitable cells 210, 310 to aid in the culturing of the excitable cells 210, 310. That is, electrical stimulation of excitable cells supports the growth and maturation of the cell. In some aspects, the electrodes for the array of microfluidic device 102, 200, 300 are in electrical communication with the tissue constructs of excitable cells 210, 310 and provide a desired electrical potential stimulation to the tissue constructs. In some instances, the electrical response of the excitable cells 210, 310 to the electrical stimulation is measured by the electrodes. In some cases, a feedback system comprises electrical stimulation of the excitable cells 210, 310 recordation of the electrical response of the excitable cells 210, 310, and adjustment of further stimulation based on the recordation. In some embodiments, with the electrical stimulation and the electrical response of the cells 210, 310, the strength and maturation of the cells is assessed. In an example implementation, with the excitable cells having cardiac muscle cell culture, the stimulation and spontaneous response may be used to assess the proper growth conditions to culture a more representative heart tissue.

[0050] In some aspects, the electrodes provide a stimulation pulse to the tissue constructs of the excitable cells 210, 310. Similar to detecting electrical response, the electrodes for providing the stimulation may be: placed on the same side of the excitable cells 210, 310; placed on opposing sides of the excitable cells 210, 310; are in electrical contact with the tissue construct directly by touching the tissue construct; and / or are in electrical contact with the tissue construct through electrically conductive culture media or buffers;[0051 J The stimulation pulse may have various suitable forms. The following variations may be combined or provided separately. In one variation, the electrical stimulation pulses may be: a monophasic waveform; a biphasic waveform having symmetrical or asymmetrical waveforms; or polyphasic waveforms. In another variation, the stimulation pulses have frequencies ranging from 0.1 Hz to 10 Hz. In yet another variation, the stimulation pulses have amplitudes ranging from 0.1 V to 10 V.[00521 In lieu of or in addition to separate electrodes, tubing of a pump submerged into the well plate reservoirs may serve as the stimulation electrodes. In yet another variation, the tubing of the pump coated with a noble metal could serve as the stimulation electrodes.

[0053] Referring to FIG. 10, an example stimulation system 600 includes the well plate 100 having an array of microfluidic devices 102, 200, 300, an array of electrodes 602, and a stimulation controller 604 in communication with the array of electrodes 602. The stimulation controller 604 is configured to provide a stimulation pulse to the well plate via the electrodes 602 (illustrated by arrow 606), and measures a response of the tissue construct via the electrodes 602, (illustrated by arrow 608). Using at least one of the stimulation pulse or the electrical response, the stimulation controller 604 is configured to determine health and maturity of the tissue construct. The stimulation controller 604 is configured to collectively provide the stimulation pulse to the microfluidic devices 102, 200, 300 and / or independently stimulate each of the devices 102, 200, 300.

[0054] It should be readily understood that the sensor system 400 and / or the stimulation system 600 may include other components, such as but not limited to, devices (e.g., pumps) to control the fluid in the well plate 100, signal processing devices, and / or electric pulse generator for providing stimulation pulse.

[0055] While specific applications of the microfluidic device 102, 200, 300 is provided, the device 102, 200, 300 may operate as part of other sensor systems and / or stimulation systems, and should not be limited to the examples provided herein.

[0056] Unless otherwise expressly indicated herein, all numerical values indicating mechanical / thermal properties, compositional percentages, dimensions and / or tolerances, or other characteristics are to be understood as modified by the word “about” or “approximately” in describing the scope of the present disclosure. This modification is desired for various reasons including industrial practice, material, manufacturing, and assembly tolerances, and testing capability.

[0057] In a non-limiting example, the sensor controller and / or stimulation controller may include: a hardware computing device, an Application Specific Integrated Circuit (ASIC); a digital, analog, or mixed anal og / digi tai discrete circuit; a digital, analog, or mixed anal og / digi tai integrated circuit; a combinational logic circuit; a field programmable gate array (FPGA); a processor circuit (shared, dedicated, or group) that executes code; a memory circuit (shared, dedicated, or group) that stores code executed by the processor circuit; other suitable hardware components that provide the described functionality; or a combination of some or all of the above, such as in a system-on-chip.

[0058] The term memory or memory circuit may be a subset of the term computer-readable medium. The term computer-readable medium, as used herein, does not encompass transitory electrical or electromagnetic signals propagating through a medium (such as on a carrier wave); the term computer-readable medium may therefore be considered tangible and non-transitory. Non-limiting examples of a non-transitory, tangible computer-readable medium are nonvolatile memory circuits (such as a flash memory circuit, an erasable programmable read-only memory circuit, or a mask read only circuit), volatile memory circuits (such as a static random access memory circuit or a dynamic random access memory circuit), magnetic storage media (e g., an analog or digital magnetic tape or a hard disk drive), and optical storage media (e.g., a USB, CD, a DVD, or a Blu-ray Disc).[0059J The sensor system 400 and / or the stimulation system 600 described in this application may be partially or fully implemented by a special purpose computer created by configuring a general-purpose computer to execute one or more particular functions embodied in computer programs.

[0060] As used herein, the phrase at least one of A, B, and C should be construed to mean a logical (A OR B OR C), using a non-exclusive logical OR, and should not be construed to mean “at least one of A, at least one of B, and at least one of C.”

[0061] The description of the disclosure is merely exemplary in nature and, thus, variations that do not depart from the substance of the disclosure are intended to be within the scope of the disclosure. Such variations are not to be regarded as a departure from the spirit and scope of the disclosure.

Claims

WHAT IS CLAIMED IS:

1. A microfluidic device, comprising: a first microfluidic channel and a second microfluidic channel; a membrane having a plurality of excitable cells, the membrane separating the first microfluidic channel and the second microfluidic channel; and at least two electrodes in electrical communication with the membrane, the at least two electrodes configured to detect an electrical output of the excitable cells.

2. The microfluidic device of claim 1, wherein the at least two electrodes are configured to provide an electrical stimulus to the membrane responsive to detecting the electrical output of the excitable cells.

3. The microfluidic device of claim 1, wherein the second channel is a trough.

4. The microfluidic device of claim 1, wherein a portion of the first channel and a portion of the second channel overlap defining an overlapping region.

5. The microfluidic device of claim 1, wherein the excitable cells are defined as monolayers provided on the membrane.

6. The microfluidic device of claim 1, wherein the excitable cells are formed as a monolayer on a 3-dimensional gel underlay.

7. The microfluidic device of claim 1, wherein the excitable cells are formed as a three-dimensional cell culture.

8. The microfluidic device of claim 1, wherein the membrane is a micropatterned membrane and the excitable cells are cultured on the micropatterned membrane.

9. The microfluidic device of claim 1, further comprising stromal cells in the first microfluidic channel to be provided to the excitable cells.

10. A system, comprising: an array of microfluidic devices, each microfluidic device comprising a membrane having a plurality of excitable cells; and a plurality of electrodes, wherein for at least one microfluidic device of the array of microfluidic devices, at least two electrodes are in electrical communication with the membrane and the at least two electrodes are configured to detect an electrical output of the excitable cells.

11. The system of claim 10, wherein the plurality of electrodes is configured to provide a stimulation pulse to the at least one microfluidic device and measure the electrical output of the excitable cells.

12. The system of claim 10, wherein the at least two electrodes are configured to provide an electrical stimulus to the membrane responsive to detecting the electrical output of the excitable cells.

13. The system of claim 10, wherein the excitable cells are defined as monolayers provided on the membrane.

14. The system of claim 10, wherein the excitable cells are formed as a monolayer on a 3-dimensional gel underlay.

15. The system of claim 10, wherein the membrane is a micropatterned membrane and the excitable cells are cultured on the micropatterned membrane.

16. The system of claim 10, wherein each microfluidic device includes a first microfluidic channel and a second microfluidic channel, and the membrane separates the first microfluidic channel and the second microfluidic channel.

17. The system of claim 16, wherein the second channel is a trough.

18. The system of claim 16, wherein each microfluidic device includes stromal cells in the first microfluidic channel to be provided to the excitable cells.

19. The system of claim 16, wherein a portion of the first channel and a portion of the second channel overlap defining an overlapping region.

20. The system of claim 10, further comprising a controller configured to receive an electrical signal indicative of the electrical output of the excitable cells, wherein the controller is further configured to independently communicate with each microfluidic device using the at least two electrodes of the microfluidic device.

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