Well plate with embedded integrated circuit for assay

Abstract

A well plate can include a plastic component having an array of microwells, each defining a respective opening sized to receive and contain a volume of fluid. A printed circuit board (PCB) material can be arranged against and accessible through the microwell openings, allowing fluid contact with the PCB material at a first side. An array of integrated circuits (ICs) can be individually positioned to correspond with respective microwells and electrically interconnected via conductive interconnections within the PCB material, such as to facilitate electronic assays within standardized well plates for high-throughput screening applications.

Description

Docket No. 3867.C77WO1WELL PLATE WITH EMBEDDED INTEGRATED CIRCUIT FOR ASSAYCLAIM 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 depicts an apparatus for high throughput assay on semiconductor chips embedded in a well plate.

[0005] FIG. 2A is a cross-section view of an example of a well including an embedded integrated circuit (IC).

[0006] FIG. 2B is a cross-section view of an example of a well including an embedded IC.

[0007] FIG. 2C is a cross-section view of an example of a well including an embedded IC.

[0008] FIG. 2D is a perspective view of a well plate, corresponding with the well including the embedded IC shown in FIG. 2C.

[0009] FIG. 2E is a side view of a well plate, corresponding with the well including the embedded IC shown in FIG. 2C.

[0010] FIG. 2F is a cross-section view of an example of a well including an embedded IC formed by wafer-level packaging (WLP).

[0011] FIG. 2G is a cross-section view of an example of a well including an embedded IC.

[0012] FIG. 3A is a perspective view of an example of a well plate including an array of embedded ICs corresponding with an array of wells.Docket No. 3867.C77WO1

[0013] FIG. 3B is a perspective view of an example of a well plate including an array of embedded ICs corresponding with an array of wells.

[0014] FIG. 4 depicts an assay apparatus for executing an assay on a prepared assay surface.

[0015] FIG. 5 is a flowchart showing a process for phenotypic, high throughput screening (HTS) of biological specimens.

[0016] FIG. 6 is a block diagram of a machine.DETAILED DESCRIPTION

[0017] This document relates to high throughput screening (HTS) systems for biological specimens, particularly phenotypic screening approaches that can provide higher 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.

[0018] 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. For example, 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 certain 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.

[0019] This document relates to high throughput screening (HTS) systems for biological specimens, particularly phenotypic screening approaches that can provide higher 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.

[0020] High throughput screening approaches for biological specimens can involve well plates with standardized layouts and pitch configurations, such as plates containing 96, 384,Docket No. 3867.C77WO1 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 plate-based microelectrode array (MEA) approaches to equal to or less than about 384 wells, while other chip-based MEA approaches can be constrained to a single well due to fluidic handling limitations.

[0021] The present inventors have recognized the benefits of a technique involving a semiconductor platform which facilitates integrated electronic and mechanical high- throughput screening with 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.

[0022] 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 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 cells 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.

[0023] FIG. 1 depicts an apparatus for high throughput assay on semiconductor chips embedded in a well plate. In certain assay settings, it can be desirable to perform similar automated, HTS of biological specimens at a cell-to-cell pitch within a range of about 1-5 millimeters (mm), such as about 2-2.5 mm. For example, such a relatively large pitch canDocket No. 3867.C77WO1 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 receive samples within a specified well plate standard format. Table 1 provides examples of certain standard footprints for microwell plates.

[0024] Table 1 : Examples of Microplate Standard Parameters

[0025] In an example, a biological assay can be prepared on an assay apparatus 102. For example, surface 104 the assay apparatus 102 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 102 can include individual ICs 108 each integrated into a corresponding well 106 of the apparatus 102. 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 102 can include a bus that is arranged to electrically connect a plurality of the array of ICs 108 to a shared source of power and data. This shared bus architecture can significantly reduce a complexity and footprint of wiring and interconnects compared to individual wiring of each IC 108. As described further below with respect to the examples depicted in FIG. 2 A, FIG. 2B, FIG. 2C, FIG. 2D, FIG. 2E, FIG. 2F, and FIG. 2G, ICs 108 embedded within wells 106 of the 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) of discrete ICs 108 within the assay apparatus 102.

[0026] FIG. 2A, FIG. 2B, and FIG. 2C each show cross section views of respective examples of an individual well including an embedded integrated circuit (IC). Such wells can be included in the assay apparatus 102 as shown in FIG. 1. One primary challenge to electricalDocket No. 3867.C77WO1 assays is integration of integrated circuits (IQs within standardized high-throughput well plates, such as 1536-well plates. Such integration difficulties stem from two main factors: (1) the large number of wires that must be routed between the well plate and external instrumentation, and (2) the challenging integration of electrical and mechanical transducers into well plates while maintaining high reproducibility and feasible cost. Certain wire bonding approaches, where each individual chip is wire bonded to a PCB in the spaces between chips and then molded over, can be expensive and require numerous manual steps during fabrication.

[0027] Implementations described herein are directed to a semiconductor platform incorporating embedded integrated circuits within individual microwells 106 (also referred to herein interchangeably as wells 106) of a well plate 202 (e.g., the assay apparatus 102 depicted in FIG. 1) that share a small number of buses for power, data, clock, and other signals. Such approaches to packaging can help achieve wiring of a relatively large number of ICs 108 (as shown in FIG. 1) at relatively high densities, such as a cell-to-cell pitch within a range of about 2 millimeters (mm) and about 2.5 mm or otherwise according to a well layout of any microplate standard shown in Table 1.

[0028] In each of the examples depicted in FIG. 2A, FIG. 2B, and FIG. 2C, a well plate 202 can include a well 106 formed of a plastic component 208. An individual well 106 can define an opening sized and shaped to receive and contain a volume of fluid (e.g., a volume within a range of about 0.001 milliliters to about 6 mL, such as withing a range of about 0.005 mL to about 0.1 mL). The number of wells 106 included in the well plate 202 can total a multiple of 96 microwells, such as within a range of about 384 wells 106 to about 1536 wells, with the array of wells 106 sized and shaped for high-throughput screening of biological samples (such as according to a standard well plate footprint specified by the examples listed above in Table 1). For example, the well plate 202 can include an array of wells 106 (each similar to the well 106 depicted in FIG. 2A) arranged to substantially resemble a 1536-well plate for HTS applications.

[0029] A printed circuit board (PCB) material 218 can be arranged against and accessible through the respective openings of wells 106 in the array, such that the respective volumes of fluid contact the PCB material 218 at a first side. Specifically with respect to each of FIG. 2A, FIG. 2B, and FIG. 2C, the PCB material 218 can include a rigidized, flexible printed circuit (FPC). In an example, the PCB materials 218 can be disposed beneath a plastic component 208, with a bonding material (e.g., welding 214) disposed between the plastic component 208 and the PCB material. In an example, one or more layers of coverlay 216 material can also be disposed between the plastic component 208 and the PCB material 218.Docket No. 3867.C77WO1In an example, an electrically conductive epoxy can be included such as to facilitate waterproofing and bonding of various components 208, 216, 218, etc. to one another.

[0030] A plurality of integrated circuits (IC) or semiconductor chip 210 can be individually arranged in the well plate 202 to correspond with (e.g., at or near a 1 : 1 ratio) individual wells 106 of the array. An individual semiconductor chip 210 can be electrically interconnected to other semiconductor chips 210 in the array via electrically conductive interconnections in the PCB material 218. As depicted in FIG. 2A and FIG. 2B, the semiconductor chip 210 can include through-silicon vias (TSVs) 228 to facilitate electrical connections.

[0031] In a first configuration, as depicted in FIG. 2 A, an individual semiconductor chip 210 of the array of semiconductor chips 210 is arranged beneath the PCB material 218 against an underside of the PCB material 218, such that a coverlay 216 of the PCB material 218 separates a respective volume of fluid, received by the corresponding well 106, from its respective semiconductor chip 210. Such an approach shown in FIG. 2A can provide isolation of the electronics from fluids.

[0032] In a second configuration, as depicted in FIG. 2B, an individual semiconductor chip 210 of the array of semiconductor chips 210 is arranged above the PCB material 218 against the first side of the PCB material 218, such that a respective volume of fluid, received by the corresponding well 106, contacts a corresponding semiconductor chip 210 directly. Such an arrangement can involve placing electrodes mounted on the semiconductor chip 210 directly on top of the chip rather than manufacturing them separately, which can promote ease of manufacturing and can promote desired physical and electrical contact of such electrodes with the fluid received in the corresponding well 106.

[0033] In a third configuration, as depicted in FIG. 2C, the PCB material 218 includes an array of openings corresponding with the array of wells 106. Here, the array of semiconductor chips 210 are arranged below the PCB material 218 such that fluid received by the corresponding well 106 contacts a corresponding semiconductor chip 210 through a corresponding opening of the PCB material 218. Such a “hybrid” approach to semiconductor chip 210 arrangement, provides that the semiconductor chip 210 itself forms an interface between upper and lower regions of the well plate 202.

[0034] In an example, the well plate 202C formed in the third configuration, as depicted in FIG 2C, FIG. 2D, and FIG. 2E, can include a fluid channel 238 formed beneath or within the semiconductor chip 210. The fluid channel 238 can be accessible via a port to provide fluid exchange beneath the PCB material 218, such as to facilitate an automated patch-clamp technique for high throughput electrophysiology recordings using the well plate 202C.Docket No. 3867.C77WO1

[0035] FIG. 2F is a cross-section view of an example of a well including an embedded IC formed by wafer-level packaging (WLP). As an alternative to the flexible PCB approach shown in the examples of FIG. 2A, FIG. 2B, and FIG. 2C, the well plate 202F shown in FIG. 2F can be formed using a wafer-level packaging (WLP) technique. Here, the PCB material 218 includes a rigid material and the array of ICs are formed in a wafer-level packaging layout, including ball grid array (BGA) 240 surface-mount packaging. Such a wafer-level packaging approach can involve taking ICs from a standard wafer, placing them on a separate carrier wafer with relatively large pitch spacing, and encapsulating them with mold material 246 to establish appropriately spaced chips for well plate integration.

[0036] FIG. 2G is a side view of an example of a well 202G, including an array of embedded circuitry regions with surface features mounted to the PCB material 218, rather than discrete ICs. In an example, each embedded circuitry region corresponds with a respective microwell and includes electrodes and surface functionalization embedded on a flexible printed circuit substrate. This "non-silicon" solution places surface features such as electrodes, magnetic loops, surface topography, surface functionalization, or other sensors directly on the substrate surface, with amplifiers and DACs located on a module on the plate or in external instrumentation.

[0037] FIG. 3 A and FIG. 3B each provide perspective view of respective examples of a well plate including an array of embedded ICs corresponding with an array of wells. Wireless communication capabilities may be incorporated through one or more wireless transceivers for wirelessly communicating data from a set of the ICs. For example, as shown in FIG. 3B, a single wireless transceiver wirelessly communicates data from each IC of the array to a location remote from the well plate. Such wireless approaches can simplify manufacturing by eliminating the need to wire certain chips to external connections, allowing certain chips to operate independently from one another while being wired to common interconnects for power and clock signals.

[0038] FIG. 4 depicts an assay apparatus for executing an assay on a prepared assay surface. The assay apparatus 402 can be similar to the assay apparatus 102 described with respect to FIG. 1. Here, a plurality of sites 406 (e.g., wells, spots, cells, etc.) can each include a droplet including a biological sample 408 for assaying.

[0039] In an example, the processing circuitry 412 can commence performing (e.g., “execute”) the biological assay including receiving impedance tomography data via an electrode array 410 of an individual site 406. The processing circuitry 412 can determine, e.g., using an impedance model and the impedance tomography data as input to the impedanceDocket No. 3867.C77WO1 model, a biological characteristic of respective biological materials disposed in the array of 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 include a morphology of a biological material disposed in an individual droplet of the array of liquid droplets.

[0040] The processing circuitry can control (e.g., drive, measure a voltage or impedance, multiplex etc.) the electrode array 410 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 backproj ection (FBP), iterative reconstruction, etc.). Based on the 3D impedance model, the processing circuitry 412 can determine a fraction indicative of an amount of the biological specimen that contains living tissue cultures. In an example, the electrode array 410 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 410, such as to facilitate post-processing of electrodes via the processing circuitry 412 at a plurality of different heights and to enable 3D electrode configurations.

[0041] In an example, the electrode array 410 is a microelectrode array (MEA), and the processing circuitry 412 is configured for executing the biological assay including driving the MEA to assess electrical activity of electrogenic cells included in the biological sample 408. Here, the assay apparatus 402 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 412 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 406.

[0042] In an example, the assay apparatus 402 can support 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 412 of the assay apparatus 402 can facilitate executing the cell migration assay, including monitoring impedance via theDocket No. 3867.C77WO1 electrode array 410 over time to determine real-time cell migration over a period. In an example, the processing circuitry 412 of the assay apparatus 402 can facilitate executing the wound healing assay, including operating one or more MEMS heaters embedded in an individual sites 306 (e.g., within a biological interface region 310 of the site 406, similar to that depicted in FIG. 3 A). Such MEMS heaters can be controlled to cause tissue insults, and concurrently the processing circuitry 412 can control the electrode array 410 to perform impedance measurement, e.g., to measuring cell migration during healing processes.

[0043] FIG. 5 is a flowchart showing a process 500 for phenotypic, high throughput screening (HTS) of biological specimens on a well plate including embedded ICs.

[0044] At 502, the process 500 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 includes 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 as 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.

[0045] At 504, the process 502 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 the biological assay includes receiving impedance tomography data, via the electrode array, ofDocket No. 3867.C77WO1 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.

[0046] The process 500 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 500 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.

[0047] FIG. 6 illustrates generally an example of a block diagram of a machine 601 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 601 may operate as a standalone device or may be connected (e.g., networked) to other machines. In a networked deployment, the machine 601 may operate in the capacity of a server machine, a client machine, or both in server-client network environments. In an example, the machine 601 may act as a peer machine in peer-to-peer (P2P) (or other distributed) network environment. The machine 601 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.

[0048] 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., transistors, circuits, etc.) and a computer readable medium containing instructions, where theDocket No. 3867.C77WO1 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.

[0049] Machine (e.g., computer system) 601 may include a hardware processor 602 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), a hardware processor core, or any combination thereof), a main memory 603 and a static memory 604, some or all of which may communicate with each other via an interlink (e.g., bus) 605. The machine 601 may further include a display unit 606, an alphanumeric input device 607 (e.g., a keyboard), and a user interface (UI) navigation device 608 (e.g., a mouse). In an example, the display unit 606, alphanumeric input device 607 and ui navigation device 608 may be a touch screen display. The machine 601 may additionally include a storage device (e.g., drive unit) 609, a signal generation device 610 (e.g., a speaker), a network interface device 611, and one or more sensors 612, such as a global positioning system (GPS) sensor, compass, accelerometer, or other sensor. The machine 601 may include an output controller 616, 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.).

[0050] The storage device 609 may include a machine readable medium 613 that is non- transitory on which is stored one or more sets of data structures or instructions 614 (e.g., software) embodying or utilized by any one or more of the techniques or functions described herein. The instructions 614 may also reside, completely or at least partially, within the main memory 603, within static memory 604, or within the hardware processor 602 during execution thereof by the machine 601. In an example, one or any combination of the hardware processor 602, the main memory 603, the static memory 604, or the storage device 609 may constitute machine readable media.

[0051] While the machine readable medium 613 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 614.Docket No. 3867.C77WO1

[0052] The term “machine readable medium” may include any medium that is capable of storing, encoding, or carrying instructions for execution by the machine 601 and that cause the machine 601 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.

[0053] The instructions 614 may further be transmitted or received over a communications network 615 using a transmission medium via the network interface device 611 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 611 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 615. In an example, the network interface device 611 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 601, and includes digital or analog communications signals or other intangible medium to facilitate communication of such software.

Claims

Docket No. 3867.C77WO1CLAIMSWhat is claimed is:

1. A well plate with an embedded integrated circuit (IC) for electrical assay, the well plate comprising: a plastic component including an array of microwells, each microwell defining a respective opening sized and shaped to receive and contain a respective volume of fluid; a printed circuit board (PCB) material arranged against and accessible through the respective openings of microwells in the array of microwells, such that the respective volumes of fluid contact the PCB material at a first side of the PCB material; an array of integrated circuits (ICs), each IC individually arranged to correspond with a respective microwell of the array of microwells and electrically interconnected to one another via an electrically conductive interconnection in the PCB material; and a bus electrically arranged to electrically connect a plurality of the array of ICs to a shared source of power and data; wherein an interface between the plastic component and the PCB material establishes a fluid-tight seal.

2. The well plate of claim 1, wherein a number of microwells of the array of microwells of the plastic component total a multiple of 96 microwells, within a range of a 384 microwells to 1536 microwells, the array of microwells sized and shaped for high-throughput screening (HTS) of a plurality of biological samples received within the array of microwells.

3. The well plate of any one of claims 1-2, wherein the array of microwells is sized and shaped as a 1536-well-plate for HTS.

4. The well plate of any one of claims 1-3, wherein the PCB material includes a rigidized, flexible printed circuit (FPC).

5. The well plate of claim 4, wherein the array of ICs are arranged beneath the PCB material against a second side of the PCB material, such that a coverlay layer of the FPC separates a respective volume of fluid, received at an individual microwell, from a corresponding IC of the array of ICs.

6. The well plate of claim 4, wherein the array of ICs are arranged above the PCB material against the first side of the PCB material, such that a respective volume of fluid, received at an individual microwell, contacts a corresponding IC of the array of ICs.Docket No. 3867.C77WO17. The well plate of claim 4, wherein the PCB material includes an array of openings corresponding with the array of microwells, wherein the array of ICs are arranged below the PCB material against a second side of the PCB material such that a respective volume of fluid, received at an individual microwell, contacts a corresponding IC of the array of ICs through a corresponding opening of the PCB material.

8. The well plate of any one of claims 1-7, wherein an individual IC includes a through- silicon via (TSV).

9. The well plate of any one of claims 1-8, wherein the PCB material includes a rigid material, and the array of ICs is formed in a wafer-level packaging (WLP) layout, including ball grid array (BGA) surface-mount packaging.

10. The well plate of claim 9, wherein the array of ICs are arranged above the PCB material against the first side of the PCB material, such that a respective volume of fluid, received at an individual microwell, contacts a corresponding IC of the array of ICs.

11. The well plate of any one of claims 1-10, comprising one or more wireless transceivers for wirelessly communicating data from a set of the ICs included in the array of ICs.

12. The well plate of any one of claims 1-11, comprising a single wireless transceiver for wirelessly communicating data from each IC of the array of ICs to a location remote from the well plate.

13. A well plate with an embedded integrated circuit (IC) for electrical assay, the well plate comprising: a plastic component including an array of microwells, each microwell defining a respective opening sized and shaped to receive and contain a respective volume of fluid; a printed circuit board (PCB) material arranged against and accessible through the respective openings of microwells in the array of microwells, such that the respective volumes of fluid contact the PCB material at a first side of the PCB material; an array of embedded circuitry regions including surface features mounted to the PCB, each embedded circuitry region individually arranged to correspond with a respective microwell of the array of microwells and electrically interconnected to one another via an electrically conductive interconnection in the PCB material; and a bus electrically arranged to electrically connect a plurality of the array of embedded circuitry regions to a shared source of power and data;Docket No. 3867.C77WO1 wherein an interface between the plastic component and the PCB material establishes a fluid-tight seal.

14. The well plate of claim 13, wherein a number of microwells of the array of microwells of the plastic component total a multiple of 96 microwells, within a range of a 384 microwells to 1536 microwells, the array of microwells sized and shaped for high- throughput screening (HTS) of a plurality of biological samples received within the array of microwells.

15. The well plate of any one of claims 13-14, wherein an individual embedded circuitry region of the array of embedded circuitry regions includes electrodes and surface functionalization embedded on a flexible printed circuit (FPC) substrate included in the PCB material.

16. A well plate with embedded integrated circuit (IC) for electrical assay, the well plate comprising: a plastic component including an array of microwells, each microwell defining a respective opening sized and shaped to receive and contain a respective volume of fluid; a printed circuit board (PCB) material arranged against and accessible through the respective openings of microwells in the array of microwells; an array of integrated circuits (ICs), each IC individually arranged to correspond with a respective microwell of the array of microwells and electrically interconnected to one another via an electrically conductive interconnection in the PCB material; and a bus electrically arranged to electrically connect a plurality of the array of ICs to a shared source of power and data.

17. The well plate of claim 16, wherein a number of microwells of the array of microwells of the plastic component total a multiple of 96 microwells, within a range of a 384 microwells to 1536 microwells, the array of microwells sized and shaped for high- throughput screening (HTS) of a plurality of biological samples received within the array of microwells.

18. The well plate of claim 17, wherein the array of microwells is sized and shaped as a 1536-well-plate for HTS.

19. The well plate of any one of claims 16-18, wherein the PCB material includes a rigidized, flexible printed circuit (FPC).Docket No. 3867.C77WO120. The well plate of claim 19, wherein the array of ICs are arranged beneath and against the PCB material, opposite the received volume of fluid, such that a coverlay layer of the FPC separates a respective volume of fluid, received at an individual microwell, from a corresponding IC of the array of ICs.

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