Performing a biological assay on an integrated circuit

Abstract

An apparatus for phenotypic screening of biological specimens can include an integrated circuit (IC) having an array of hydrophilic regions on its surface. The array of hydrophilic regions can be arranged such that upon contacting the IC surface with a liquid medium and a biological specimen to be assayed, an array of liquid droplets is formed. The apparatus can also include an electrode array arranged within a footprint of a first hydrophilic region of the array, and processing circuitry configured to drive the electrode array to execute a biological assay on the IC.

Description

Docket No. 3867.C74WO1PERFORMING A BIOLOGICAL ASSAY ON AN INTEGRATED CIRCUITCLAIM OF PRIORITY

[0001] This application claims priority to and the benefit of U.S. Provisional Application Serial No. 63 / 696,703, filed September 19, 2024, which is hereby incorporated herein by reference, and the benefit of priority of which is claimed herein.BACKGROUND

[0002] Certain approaches to assaying biological specimens involve well plates, e.g., having a standardized layout and pitch of individual fluidic volumes. For example, certain processes for phenotypic screening involve a well plate (e.g., arranged according to a specified layout of about 96, 384, or 1536 wells per plate).BRIEF DESCRIPTION OF THE DRAWINGS

[0003] In the drawings, which are not necessarily drawn to scale, like numerals can describe similar components in different views. Like numerals having different letter suffixes can represent different instances of similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.

[0004] FIG. 1 A depicts a top view of an example of an apparatus for high throughput assay on a monolithic chip.

[0005] FIG. IB depicts an exploded, perspective view of an example of an apparatus for high throughput assay on a monolithic chip.

[0006] FIG. 2 depicts an apparatus for high throughput assay on semiconductor chips embedded in a well plate.

[0007] FIG. 3 depicts an assay apparatus for executing an assay on a prepared assay surface.

[0008] FIG. 4 is a flowchart showing a process for phenotypic, high throughput screening (HTS) of biological specimens.

[0009] FIG. 5 is a block diagram of a machine.DETAILED DESCRIPTION

[0010] This document relates to high throughput screening (HTS) systems for biological specimens, particularly phenotypic screening approaches that can provide higherDocket No. 3867.C74WO1 physiological relevance than certain other target-based screening approaches. Electronic and mechanical phenotypic screening techniques can be particularly valuable for studying diseases involving electrogenic cells, as these approaches can assess electrical properties and mechanical characteristics of biological specimens.

[0011] High throughput screening approaches for biological specimens can involve well plates with standardized layouts and pitch configurations, such as plates containing 96, 384, or 1536 wells per plate. Performing assays on such well plates can involve certain challenges in the context of electronic and mechanical phenotypic screening. For example, certain electronic and mechanical phenotypic screening methods face throughput limitations compared to, e.g., optical screening. To illustrate, electronic and mechanical methods require direct contact with the biological material, which presents challenges based on the large number of wires that must be brought between individual wells of the well plate and external instrumentation. Certain physical wiring considerations can limit other plate-based microelectrode array (MEA) approaches to equal to or less than about 384 wells, while certain other chip-based MEA approaches can be constrained to a single well due to fluidic handling limitations.

[0012] Implementations described herein involving a semiconductor platform which facilitates integrated electronic and mechanical high-throughput screening provides significantly improved capabilities as compared with certain other assay approaches. For example, systems and apparatuses described herein can facilitate concurrent testing of hundreds or thousands of biological samples, such as human or animal cells or tissue. In an example, a semiconductor chip can include a plurality of hydrophilic regions, arranged to facilitate forming of small droplets when liquid containing biological samples is added. Here, each droplet can act as a miniaturized “test tube” that keeps different samples separate from each other. Built-in electrodes of the semiconductor chip can function as tiny electrical sensors that can measure cellular electrical activity or determine cell health and structure via impedance tomography.

[0013] Exemplary apparatuses for electronic and mechanical high-throughput screening include a monolithic chip configuration with fluidic demagnification or, alternatively a plurality of semiconductor chiplets each embedded in a corresponding well of a well plate. Such semiconductor platforms can facilitate assaying at a plurality of independent sites, potentially ranging as high as about 1,000 or even exceeding about 1,000,000 sites for high- throughput electronic and mechanical assays. For example, in certain monolithic chip examples described herein, approximately 10,000 measurement sites can be achieved on a single semiconductor chip. Such measurement sites can measure electronic properties of cellsDocket No. 3867.C74WO1 as well as mechanical, chemical, or other modalities. Accordingly, apparatuses and techniques described herein can help facilitate efficient and cost-effective drug discovery and medical research.

[0014] FIG. 1A and FIG. IB each depict an example of an apparatus for high throughput assay on a monolithic chip. An assay apparatus 102 can include an integrated circuit (IC) 104 having an array of hydrophilic regions 106 on its surface. The array of hydrophilic regions 106 can be arranged within a hydrophobic region 108, such that each hydrophilic region 106 is separated by hydrophobic material of the hydrophobic region 108. Such an arrangement can provide that upon contacting the surface of the IC 104 with a liquid medium and a biological specimen to be assayed, an array of liquid droplets is formed on the IC 104. Here, each droplet corresponds with an individual hydrophilic region 106 of the array of hydrophilic regions 106 and maintaining physical and electrical isolation between individual assay sites. The assay apparatus 102 can be arranged to facilitate a fluid preparation process for creating the array of liquid droplets, such as to receive the liquid medium ("flooding" the surface of the IC 104), and ultimately purging at least a portion of the liquid medium to form the array of liquid droplets. The assay apparatus 102 can be sized and shaped to permit the purging of at least a portion of the liquid medium, such as via tilting the assay apparatus 102 to accumulate bulk fluid in one location for pipette-based removal from the IC 104 or dragging a larger "mother droplet" across the IC 104 such as to accumulate excess liquid medium for removal from the IC 104.

[0015] In an example, the assay apparatus 102 can include an array of biological interface regions 110, an individual biological interface region 110 arranged within a footprint of a corresponding hydrophilic region 106 of the array of hydrophilic regions 106. For example, the biological interface region 110 can include electrodes (e.g., a microelectrode array (MEA)), micro-electromechanical systems (MEMS) structures, sensors, etc. for interfacing with a biological specimen suspended within a droplet of a corresponding hydrophilic region 106. Such interfacing can include recording a voltage or impedance of the biological specimen, stimulating the biological specimen (e.g., physically or electrically), driving the MEA to execute a biological assay on the IC 104, or assessing an electrical or mechanical parameter of the biological specimen included in the individual droplet. In an example, the assay apparatus 102 can include or use processing circuitry 112 communicatively coupled with the array of biological interface regions 110 and configured to control operation of a MEA, MEMS structure, or sensor included within an individual biological interface region 110. The processing circuitry 112 can be embedded on the IC 104 or alternatively can beDocket No. 3867.C74WO1 located remote from the chip and can access the array of biological interface regions 110 via an electrical interconnect 114.

[0016] As shown in the exploded, perspective view of FIG. IB, the IC can be formed of several layers, e.g., an active, semiconductor layer 116 and a passive layer 118. The semiconductor layer 116 can be formed according to a complementary metal-oxide- semiconductor (CMOS) process. The passive layer 118 can be formed atop the semiconductor layer 116, e.g., following fabrication of the semiconductor layer 116, and can include the hydrophilic regions 106, the hydrophobic region 108, and the biological interface regions 110. In an example, individual biological interface regions 110 can include electrical connections 124 for electrically interfacing with a corresponding readout and actuation circuitry 126 formed on the semiconductor layer 116. In an example, the semiconductor layer 116 can include common circuitry connections 128 to supply any of power, digital, or analog signals to and from the readout and actuation circuitry 126 and the processing circuitry 112.

[0017] The assay apparatus 102 can be arranged to facilitate various assay types, e.g., microelectrode array (MEA) assessment, three-dimensional (3D) impedance tomography, cardiac organoid pacing and sensing, cell migration assays, wound healing assays, cell killing assays, etc. For example, certain MEMS-based mechanical assay systems can facilitate cardiac contractility measurements using semiconductor chips with MEMS-based mechanical force measurement structures. The assay apparatus 102 can provides a plurality of independent sites for performing such assays with integrated readout capabilities.

[0018] FIG. 2 depicts an apparatus for high throughput assay on semiconductor chips embedded in a well plate. The assay apparatus 102 described with respect to FIG. 1A and FIG. IB can facilitate performing an assay of an array of biological samples, laid out on the IC 104 of the assay apparatus 102 at a relatively small cell-to-cell pitch (e.g., about 150-250 micrometers (pm)). In certain assay settings, it can be desirable to perform similar automated, HTP screening of biological specimens at a relatively larger cell-to-cell pitch (e.g., about 2- 2.5 millimeters(mm)). For example, a relatively larger pitch can help facilitate efficient and precise transfer of biological specimens onto an assay apparatus and can promote compatibility with certain systems, devices, and other infrastructure designed to work around a specified well plate standard format. Table 1 provides examples of certain standard footprints for microwell plates.Docket No. 3867.C74WO1

[0019] Table 1 : Examples of Microplate Standard Parameters

[0020] In an example, a biological assay can be prepared on an assay apparatus 202, which can be similar in many respects to the assay apparatus 102 described with respect to FIG. 1 A and FIG. IB. Here, however, a surface 204 of the assay apparatus 202 can be arranged to substantially resemble a form factor of a standard footprint of a microwell plate (e.g., according to a number, arrangement, etc. of at least one of the examples listed in Table 1, and the assay apparatus 202 can include individual ICs 208 each integrated into a corresponding well 206 of the apparatus 202. Herein, the terms “well”, “cell”, “spot”, etc. can be used interchangeably to describe a destination site for a biological specimen in an assay array. The assay apparatus 202, as compared with assay apparatus 102, can provide certain advantages in loading biological samples while overcoming a technical challenge of fabricating and embedding a plurality (e.g., in some cases, about 1536) discrete ICs 208 within the assay apparatus 202. A similar arrangement is described in PCT Application Serial No. PCT / US2025 / 047229 (Attorney Docket No. 3867.C77WO1), entitled "WELL PLATE WITH EMBEDDED INTEGRATED CIRCUIT FOR ASSAY", which is incorporated by reference herein for its teaching of various implementations of integrated circuits within individual wells of a well plate.

[0021] FIG. 3 depicts an assay apparatus for executing an assay on a prepared assay surface. The assay apparatus 302 can be similar to the assay apparatus 102 and the assay apparatus 202 described with respect to FIG. 1 A and FIG. 2, respectively. Here, a plurality of sites 306 (e.g., wells, spots, cells, etc.) can each include a droplet including a biological sample 308 for assaying.

[0022] In an example, the processing circuitry 112 can commence performing (e.g., “execute”) the biological assay including receiving impedance tomography data via an electrode array 310 of an individual site 306. The processing circuitry 112 can determine, e.g., using an impedance model and the impedance tomography data as input to the impedance model, a biological characteristic of respective biological materials disposed in the array ofDocket No. 3867.C74WO1 liquid droplets. For example, biological characteristics that can be determined include the amount of live cell tissue that is included in a biological material disposed in an individual droplet of the array of liquid droplets. Alternatively or additionally, the biological characteristic includes a morphology of a biological material disposed in an individual droplet of the array of liquid droplets.

[0023] The processing circuitry 112 can control (e.g., drive, measure a voltage or impedance, multiplex, etc.) the electrode array 310 according to a specified electrical driving scheme (e.g., pairwise electrode combinations, one-to-many electrode combinations, adjacent, polar, diagonal, trigonometric, etc.) such as to image biological material included in the array of liquid droplets according to a plurality of views. For example, such imaging can be performed to help create a three-dimensional (3D) impedance model of the biological specimen using the impedance tomography data as input to a reconstruction model (e.g., filtered b ackprojection (FBP), iterative reconstruction, etc.). Based on the 3D impedance model, the processing circuitry 112 can determine a fraction indicative of an amount of the biological specimen that contains living tissue cultures, e.g., based on impedance of areas having living tissue being higher than areas having dead tissue. In an example, the electrode array 310 can be arranged with relatively high electrode density (e.g., at an electrode-to- electrode pitch of about 5-15 pm), including individual signal chain circuitry necessary to drive the electrode array 310, such as to facilitate post-processing of electrodes via the processing circuitry 112 at a plurality of different heights and to enable 3D electrode configurations.

[0024] In an example, the electrode array 310 is a microelectrode array (MEA), and the processing circuitry 112 is configured for executing the biological assay including driving the MEA to assess electrical activity of electrogenic cells included in the biological sample 308. Here, the assay apparatus 302 can facilitate driving individual electrodes of the MEA independently from each other and measuring signals indicative of action potentials or field potentials between the electrogenic cells and the individual electrodes of the MEA. The processing circuitry 112 can monitor or determine electrical activity of electrogenic cells, e.g., neurons and cardiomyocytes, with high compound throughput, e.g., by nature of isolating each site electrically and fluidically within nanoliter-scale droplets in their respective sites 306.

[0025] In an example, the assay apparatus 302 can supports a plurality of assay types, such as impedance tomography, MEA, a MEMS-based mechanical assay to measure cardiac contractility, a cell migration assay, a wound healing assay, a cell killing assay, or a combination thereof. For example, the processing circuitry 112 of the assay apparatus 302Docket No. 3867.C74WO1 can facilitate executing the cell migration assay, including monitoring impedance via the electrode array 310 over time to determine real-time cell migration over a period. In an example, the processing circuitry 112 of the assay apparatus 302 can facilitate executing the wound healing assay, including operating one or more MEMS heaters embedded in individual sites 306 (e.g., within a biological interface region 110 of the site 306, similar to that depicted in FIG. 1A). Such MEMS heaters can be controlled to cause tissue insults, and concurrently the processing circuitry 112 can control the electrode array 310 to perform impedance measurement, e.g., to measure cell migration during healing processes.

[0026] FIG. 4 is a flowchart showing a process 400 for phenotypic, high throughput screening (HTS) of biological specimens.

[0027] At 402, the process 400 can include preparing a biological assay on an integrated circuit (IC) that includes an array of hydrophilic regions on a surface of the integrated circuit. In an example, such a preparation can include contacting the surface of the IC with a liquid medium, establishing a fluid environment for the subsequent biological assay operations. For example, the liquid medium can provide a suitable aqueous environment for biological specimen suspension and assay execution. The preparing the biological assay can also include contacting the surface of the IC with a biological specimen to be assayed, such as to introduce the target biological material that will be subjected to analysis during the assay execution phase. For example, the biological specimen can be brought into contact with the IC surface in the presence of the liquid medium. Additionally, the preparing the biological assay can include forming an array of liquid droplets, each corresponding with an individual hydrophilic region of the array of hydrophilic regions. Here, an individual droplet can include the biological specimen suspended within the liquid medium. Such a droplet formation step can maintain fluidic isolation between individual assay sites, such as to facilitate parallel processing of multiple biological specimens simultaneously across the array.

[0028] At 404, the process 402 can include executing or performing the biological assay, including controlling an electrode array that is arranged within a footprint of a first hydrophilic region of the array of hydrophilic regions. For example, an electrode array can be controlled such as to assess at least one electrical or mechanical parameter of the biological specimen included in the individual droplet. In an example, the electrode array includes a microelectrode array (MEA), and executing the biological assay includes driving the MEA to assess electrical activity of electrogenic cells included in the biological specimen. The process can include, e.g., driving individual electrodes of the MEA independently from each other and measuring a signal indicative of an action potential or field potential between the electrogenic cells and the individual electrodes of the MEA. In an example, the executing theDocket No. 3867.C74WO1 biological assay includes receiving impedance tomography data, via the electrode array, of individual droplets of the array of liquid droplets, and determining, using an impedance model and the impedance tomography data as an input to the impedance model, a biological characteristic of respective biological materials disposed in the array of liquid droplets. For example, the biological characteristic can be an amount of live cell tissue that is included in a biological material disposed in an individual droplet of the array of liquid droplets, or a morphology of a biological material disposed in an individual droplet of the array of liquid droplets.

[0029] The process 400 can additionally include driving the electrode array according to a specified electrical driving scheme to image biological material included in the array of liquid droplets according to a plurality of views. In an example, the process 400 can include creating a three dimensional (3D) impedance model of the biological specimen using the impedance tomography data as an input to a reconstruction model, and determining, based on the 3D impedance model, a fraction indicative of an amount of the biological specimen contains living tissue cultures.

[0030] FIG. 5 illustrates generally an example of a block diagram of a machine 501 upon which any one or more of the techniques (e.g., methodologies) discussed herein may perform in accordance with some examples. In alternative embodiments, the machine 501 may operate as a standalone device or may be connected (e.g., networked) to other machines. In a networked deployment, the machine 501 may operate in the capacity of a server machine, a client machine, or both in server-client network environments. In an example, the machine 501 may act as a peer machine in peer-to-peer (P2P) (or other distributed) network environment. The machine 501 may be a personal computer (PC), a tablet PC, a set -top box (STB), a personal digital assistant (PDA), a mobile telephone, a web appliance, a network router, switch or bridge, or any machine capable of executing instructions (sequential or otherwise) that specify actions to be taken by that machine. Further, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein, such as cloud computing, software as a service (SaaS), other computer cluster configurations.

[0031] Examples, as described herein, may include, or may operate on, logic or a number of components, modules, or mechanisms. Modules are tangible entities (e.g., hardware) capable of performing specified operations when operating. A module includes hardware. In an example, the hardware may be specifically configured to carry out a specific operation (e.g., hardwired). In an example, the hardware may include configurable execution units (e.g.,Docket No. 3867.C74WO1 transistors, circuits, etc.) and a computer readable medium containing instructions, where the instructions configure the execution units to carry out a specific operation when in operation. The configuring may occur under the direction of the executions units or a loading mechanism. Accordingly, the execution units are communicatively coupled to the computer readable medium when the device is operating. In this example, the execution units may be a member of more than one module. For example, under operation, the execution units may be configured by a first set of instructions to implement a first module at one point in time and reconfigured by a second set of instructions to implement a second module.

[0032] Machine (e.g., computer system) 501 may include a hardware processor 502 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), a hardware processor core, or any combination thereof), a main memory 503 and a static memory 504, some or all of which may communicate with each other via an interlink (e.g., bus) 505. The machine 501 may further include a display unit 506, an alphanumeric input device 507 (e.g., a keyboard), and a user interface (UI) navigation device 508 (e.g., a mouse). In an example, the display unit 506, alphanumeric input device 507 and ui navigation device 508 may be a touch screen display. The machine 501 may additionally include a storage device (e.g., drive unit) 509, a signal generation device 510 (e.g., a speaker), a network interface device 511, and one or more sensors 512, such as a global positioning system (GPS) sensor, compass, accelerometer, or other sensor. The machine 501 may include an output controller 516, such as a serial (e.g., universal serial bus (USB), parallel, or other wired or wireless (e.g., infrared (IR), near field communication (NFC), etc.) connection to communicate or control one or more peripheral devices (e.g., a printer, card reader, etc.).

[0033] The storage device 509 may include a machine readable medium 513 that is non- transitory on which is stored one or more sets of data structures or instructions 514 (e.g., software) embodying or utilized by any one or more of the techniques or functions described herein. The instructions 514 may also reside, completely or at least partially, within the main memory 503, within static memory 504, or within the hardware processor 502 during execution thereof by the machine 501. In an example, one or any combination of the hardware processor 502, the main memory 503, the static memory 504, or the storage device 509 may constitute machine readable media.

[0034] While the machine readable medium 513 is illustrated as a single medium, the term “machine readable medium” may include a single medium or multiple media (e.g., a centralized or distributed database, or associated caches and servers) configured to store the one or more instructions 514.Docket No. 3867.C74WO1

[0035] The term “machine readable medium” may include any medium that is capable of storing, encoding, or carrying instructions for execution by the machine 501 and that cause the machine 501 to perform any one or more of the techniques of the present disclosure, or that is capable of storing, encoding or carrying data structures used by or associated with such instructions. Non-limiting machine-readable medium examples may include solid-state memories, and optical and magnetic media. Specific examples of machine-readable media may include: non-volatile memory, such as semiconductor memory devices (e.g., Electrically Programmable Read-Only Memory (EPROM), Electrically Erasable Programmable Read- Only Memory (EEPROM)) and flash memory devices; magnetic disks, such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

[0036] The instructions 514 may further be transmitted or received over a communications network 515 using a transmission medium via the network interface device 511 utilizing any one of a number of transfer protocols (e.g., frame relay, internet protocol (IP), transmission control protocol (TCP), user datagram protocol (UDP), hypertext transfer protocol (HTTP), etc.). Example communication networks may include a local area network (LAN), a wide area network (WAN), a packet data network (e.g., the Internet), mobile telephone networks (e.g., cellular networks), Plain Old Telephone (POTS) networks, and wireless data networks (e.g., Institute of Electrical and Electronics Engineers (IEEE) 802.11 family of standards known as Wi-Fi®, IEEE 802.16 family of standards known as WiMax®), IEEE 802.15.4 family of standards, peer-to-peer (P2P) networks, among others. In an example, the network interface device 511 may include one or more physical jacks (e.g., Ethernet, coaxial, or phone jacks) or one or more antennas to connect to the communications network 515. In an example, the network interface device 511 may include a plurality of antennas to wirelessly communicate using at least one of single-input multiple-output (SIMO), multiple-input multiple-output (MIMO), or multiple-input single-output (MISO) techniques. The term “transmission medium” shall be taken to include any intangible medium that is capable of storing, encoding or carrying instructions for execution by the machine 501, and includes digital or analog communications signals or other intangible medium to facilitate communication of such software.

Claims

Docket No. 3867.C74WO1CLAIMSWhat is claimed is:

1. An apparatus for phenotypic, high throughput screening (HTS) of biological specimens, the apparatus comprising: an integrated circuit (IC) including an array of hydrophilic regions on a surface of an integrated circuit (IC), the array of hydrophilic regions configured such that upon contacting the surface of the IC with a liquid medium and a biological specimen to be assayed, an array of liquid droplets is formed in the IC, each droplet corresponding with an individual hydrophilic region of the array of hydrophilic regions, wherein an individual droplet includes the biological specimen suspended within the liquid medium; an electrode array, arranged within a footprint of a first hydrophilic region of the array of hydrophilic regions; and processing circuitry configured to drive the electrode array to execute a biological assay on the IC, including driving the electrode array to assess at least one electrical or mechanical parameter of the biological specimen included in the individual droplet.

2. The apparatus of claim 1, wherein: the electrode array includes a microelectrode array (MEA); and the processing circuitry is configured for executing the biological assay including driving the MEA to assess electrical activity of electrogenic cells included in the biological specimen.

3. The apparatus of any one of claims 1-2, wherein: individual electrodes of the MEA are driven independently from each other; and the apparatus is configured to measure a signal indicative of an action potential or field potential between the electrogenic cells and the individual electrodes of the MEA.

4. The apparatus of any one of claims 1-3, wherein the processing circuitry is configured for executing the biological assay including: receiving impedance tomography data, via the electrode array, of individual droplets of the array of liquid droplets; and determining, using an impedance model and the impedance tomography data as an input to the impedance model, a biological characteristic of respective biological materials disposed in the array of liquid droplets.Docket No. 3867.C74WO15. The apparatus of claim 4, wherein the biological characteristic is an amount of live cell tissue that is included in a biological material disposed in an individual droplet of the array of liquid droplets.

6. The apparatus of any one of claims 4-5, wherein the biological characteristic is a morphology of a biological material disposed in an individual droplet of the array of liquid droplets.

7. The apparatus of any one of claims 4-6, wherein the processing circuitry is configured to drive the electrode array according to a specified electrical driving scheme to image biological material included in the array of liquid droplets according to a plurality of views.

8. The apparatus of claim 7, wherein the processing circuitry is configured for creating a three-dimensional (3D) impedance model of the biological specimen using the impedance tomography data as an input to a reconstruction model.

9. The apparatus of claim 8, wherein the processing circuitry is configured for determining, based on the 3D impedance model, a fraction indicative of an amount of the biological specimen that contains living tissue cultures.

10. A method for phenotypic, high throughput screening (HTS) of biological specimens, the method comprising: preparing a biological assay on an integrated circuit (IC), the IC including an array of hydrophilic regions on a surface of an integrated circuit (IC), the preparing including: contacting the surface of the IC with a liquid medium; contacting the surface of the IC with a biological specimen to be assayed; and forming an array of liquid droplets, each corresponding with an individual hydrophilic region of the array of hydrophilic regions, wherein an individual droplet includes the biological specimen suspended within the liquid medium; and executing the biological assay, including driving an electrode array, arranged within a footprint of a first hydrophilic region of the array of hydrophilic regions, to assess at least one electrical or mechanical parameter of the biological specimen included in the individual droplet.

11. The method of claim 10, wherein: the electrode array includes a microelectrode array (MEA); and executing the biological assay includes driving the MEA to assess electrical activity of electrogenic cells included in the biological specimen.Docket No. 3867.C74WO112. The method of claim 11, comprising: driving individual electrodes of the MEA independently from each other; and measuring a signal indicative of an action potential or field potential between the electrogenic cells and the individual electrodes of the MEA.

13. The method of claim 10, wherein the executing the biological assay includes: receiving impedance tomography data, via the electrode array, of individual droplets of the array of liquid droplets; and determining, using an impedance model and the impedance tomography data as an input to the impedance model, a biological characteristic of respective biological materials disposed in the array of liquid droplets.

14. The method of claim 13, wherein the biological characteristic is an amount of live cell tissue that is included in a biological material disposed in an individual droplet of the array of liquid droplets.

15. The method of any one of claims 13-14, wherein the biological characteristic is a morphology of a biological material disposed in an individual droplet of the array of liquid droplets.

16. The method of any one of claims 13-15, including driving the electrode array according to a specified electrical driving scheme to image biological material included in the array of liquid droplets according to a plurality of views.

17. The method of claim 16, comprising creating a three-dimensional (3D) impedance model of the biological specimen using the impedance tomography data as an input to a reconstruction model.

18. The method of claim 17, comprising determining, based on the 3D impedance model, a fraction indicative of an amount of the biological specimen that contains living tissue cultures.

19. The method of any one of claims 10-18, wherein the contacting the surface of the IC with the liquid medium includes flooding the surface of the IC with the liquid medium and forming the array of liquid droplets array includes purging the liquid medium to form the array of liquid droplets.

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