Well plate array pitch reduction

Abstract

An apparatus for microfluidic transfer of fluids comprises an electrowetting on dielectric (EWOD) fluid system, can include a set of first electrodes spaced apart, a first hydrophobic layer defining a surface, and a dielectric layer disposed between the electrodes and hydrophobic layer. The surface can receive spaced-apart fluid droplets from respective sample cells in a first array. Processing circuitry can modulate respective potentials of individual first electrodes to establish or adjust electro wetting properties on the EWOD surface, and controls these properties to urge the droplets to translate toward each other on the surface, toward a configuration having a reduced pitch.

Description

Docket No. 3867.C73WO1WELL PLATE ARRAY PITCH REDUCTIONCLAIM OF PRIORITY

[0001] This application claims priority to and the benefit of U.S. Provisional Application Serial No. 63 / 696,688, 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 example of assay wells for assaying of biological materials, in first and second configurations and showing pitch demagnification.

[0005] FIG. 2A depicts an example of an electrowetting on an open electrowetting on dielectric (EWOD) apparatus for reducing the pitch of assay wells.

[0006] FIG. 2B depicts an example of an electrowetting on an enclosed electrowetting on dielectric (EWOD) apparatus for reducing the pitch of assay wells.Docket No. 3867.C73WO1

[0007] FIG. 2C depicts an example of an electrowetting on a partially enclosed electrowetting on dielectric (EWOD) apparatus for reducing the pitch of assay wells.

[0008] FIG. 2D depicts a transfer of spaced-apart fluid droplets 211 from an external surface to an EWOD apparatus 201.

[0009] FIG. 3A depicts an example of microfluidic apparatus for reducing the pitch of assay wells.

[0010] FIG. 3B depicts an example of microfluidic apparatus for reducing the pitch of assay wells.

[0011] FIG. 3C depicts an example of microfluidic apparatus for reducing the pitch of assay wells.

[0012] FIG. 4 A depicts an example of microfluidic apparatus for reducing the pitch of assay wells.

[0013] FIG. 4B is a close view of the example of microfluidic apparatus for reducing the pitch of assay wells depicted in FIG. 4A.

[0014] FIG. 5A depicts an example of microfluidic apparatus for reducing the pitch of assay wells.

[0015] FIG. 5B is a close view of the example of microfluidic apparatus for reducing the pitch of assay wells depicted in FIG. 5A.

[0016] FIG. 5C depicts an example of microfluidic apparatus for reducing the pitch of assay wells.

[0017] FIG. 5D depicts an example of microfluidic apparatus for reducing the pitch of assay wells.

[0018] FIG. 6A depicts an example of a sliding pin demagnification apparatus for reducing the pitch of assay wells.

[0019] FIG. 6B depicts an example of a sliding pin demagnification apparatus for reducing the pitch of assay wells.

[0020] FIG. 7 is a flowchart showing a process for transfer of fluids

[0021] FIG. 8 is a block diagram of a machine.Docket No. 3867.C73WO1DETAILED DESCRIPTION

[0022] This document relates to microfluidic systems and methods for transferring biological fluids between different spatial configurations, particularly for achieving pitch reduction of fluid droplets to enable cost- effective implementation of semiconductor-based consumables in life science applications.

[0023] Biological specimen assaying can involve methodologies for analyzing and processing biological samples in controlled laboratory environments. For example, well plates represent a fundamental component in laboratory automation infrastructure, providing standardized platforms for containing and organizing biological fluids during analytical procedures. Such well plates are manufactured with specified configurations, e g., standardized formats having approximately 96, 384, or 1536 wells per plate or multiples thereof. Here each “well” of a well plate is sized and shaped to accommodate individual fluidic volumes in predetermined spatial arrangements. The standardized nature of these platforms has enabled widespread adoption across laboratory equipment and analytical workflows, particularly in high- throughput screening (HTS) applications where multiple samples require simultaneous processing.

[0024] Certain approaches to fluid handling in laboratory automation rely on mechanical systems designed around these standardized well plate formats, which can involve a limited throughput in performing an assay. Producing a semiconductor chip at the full size of a standard well plate, e.g., to leverage semiconductor technologies for promoting quality and throughput in electronic assays, can be challenging or cost prohibitive for certain implementations. It can be also challenging to efficiently transfer fluids from the larger pitch formats of standard well plates to the much smaller pitches for cost-effective semiconductor implementation.

[0025] FIG. 1 depicts an example of assay wells for assaying of biological materials, in first and second configurations and showing pitch demagnification. Implementations described herein provide the benefits of techniques for achieving liquid pitch "de-magnification" or layout pitch reduction, enabling transfer of spatial arrays from well plates with largerDocket No. 3867.C73WO1 center-to-center pitches to semiconductor chips with significantly smaller center-to-center pitches. In an example, such a technique can involve an electrowetting on dielectric (EWOD) apparatus with electrodes spaced at a first pitch, a hydrophobic layer, and dielectric layer. Here, processing circuitry can modulate electrode potentials to translate droplets from a first configuration to a second configuration with reduced spacing, e.g., greater than a 5X pitch reduction ratio. Alternatively or additionally, such a technique can involve a microfluidic apparatus including wells at a first pitch, connected via microfluidic channels to outlet lumens at a smaller second pitch. In an example, the microfluidic apparatus can include a manipulator configured for semiconductor chip positioning. Such automated techniques for reducing a pitch of a well plate (e.g., having a center-to-center pitch of about 1-10 millimeters (mm), about 2-8 mm, about 3-6 mm, about 2-4 mm, about 4-6 mm, about 6-8 mm, or about 8-10 mm down to a pitch acceptable by a semiconductor chip (e g., having a center-to-center pitch of about 10 microns to about 0.5 mm) can promote throughput and accuracy of assaying biological materials originating in a standard well plate, while retaining compatibility with infrastructure designed around specified well plate dimensions.

[0026] Dielectric, microfluidic, pin transfer, and other apparatuses described herein can facilitate transfer of fluid in individual w^ells 110 of a well plate 108 tow ard corresponding spots 112 of an integrated circuit 106, such that a layout of the wells 110 is transferred to the spots 112 at the reduced pitch. For example, as depicted in FIG. 1, the well plate 108 can include wells 110 having about 96, about 384, or about 1536 wells (e.g., having about 1536 wells) at a first pitch within a range of about 2,000 micrometers (pm) to about 3000 pm (e g., a first pitch at about 2,500 pm). The dielectric, microfluidic, pin transfer, and other apparatuses described herein can facilitate cell-to-cell (or spot-to- spot) pitch reduction from the first pitch toward the second pitch receivable on the integrated circuit 106, such as at a second pitch within a range of 150 pm and 250 pm, such as about 200 pm.

[0027] FIG. 2A depicts an example of an electrow'etting on an open electrowetting on dielectric (EWOD) apparatus for reducing the pitch of assay wells. In an example as depicted in FIG. 2A, the EWOD apparatus 201 can include a set of first electrodes 212 spaced apart from each other at a firstDocket No. 3867.C73WO1 pitch, with a first hydrophobic layer 202 defining the surface of the EWOD apparatus 201. and a dielectric layer 203 disposed between the set of first electrodes 212 and the first hydrophobic layer 202. The surface of the EWOD apparatus 201 can be arranged to receive spaced-apart fluid droplets 211, in a first configuration, e.g., from respective sample cells in an array of sample cells (e.g., transferred from a well plate). For example, nanoliter-scale droplets can be deposited on the surface via at least one of a pin array or acoustic liquid transfer.

[0028] Processing circuitry 214 can be communicatively coupled with the electrodes 212 such as to modulate respective potentials of individual ones of the first set of electrodes 212 to establish or adjust electrowetting properties on the surface of the EWOD apparatus 201. For example, the processing circuitry' 214 can control such electrowetting properties to cause the respective fluid droplets 211 to be translated on the surface of the EWOD apparatus 201 toward each other, thereby defining a second configuration wherein the respective fluid droplets 211 remain spaced-apart but at a reduced pitch. In an example, the processing circuitry' 214 controls the electrowetting properties (e g., polarity’ change of electrodes to cause molecules in droplets to become more attracted to one another) to introduce the translated respective fluid droplets in the second configuration, where the spaced-apart fluid droplets in the first configuration have a cell-to-cell pitch greater than 3 times, 4 times, 5 times. 6 times. 7 times, 8 times, 9 times, 10 times, or more the cell-to-cell pitch of the respective droplets in the second configuration. In an example, following a pitch reduction of the fluid droplets 211 via the electrodes 212, the fluid droplets 211 arranged in the second configuration can be transferred to an integrated circuit 106 (as depicted in FIG. 1), such as via a microfluidic transfer device, surface contact with the integrated circuit 106, or another suitable process.

[0029] FIG. 2B and FIG. 2C each depict an example of an electrowetting on an enclosed electrowetting on dielectric (EWOD) apparatus 201 for reducing the pitch of assay wells, similar to the EWOD apparatus 201 as shown in FIG. 2A. In the example depicted in FIG. 2B and FIG. 2C, the EWOD apparatus 201 further includes a second hydrophobic layer 213 spaced apart from the first hydrophobic layer 202 and arranged to hold an individual fluid dropletDocket No. 3867.C73WO1211 between the first hydrophobic layer 202 and the second hydrophobic layer 213. In an example, the EWOD apparatus 201 can include one or more second electrodes 206 arranged opposing the set of first electrodes 212 to hold an individual fluid droplet 211 between the set of first electrodes 212 and the one or more second electrodes 206. For example, the one or more second electrodes 206 can be a common electrode 206 arranged to provide a reference potential. The enclosed EWOD apparatus 201 can include a top plate 207. such that the substrate 205, the dielectric layer 203, and the first hydrophobic layer 202 form a first component and the second hydrophobic layer 213, the common electrode 206, and the top plate 207 form a second component. For example, at least one of the first component or the second component can be moveable relative to each other, such that a distance between the first hydrophobic layer 202 and the second hydrophobic layer 213 can be modulated (e.g., to affect a size, spread, or travel characteristic of an of the fluid droplets 211 held therebetween. Specifically with respect to FIG. 2C., the second component can include a plurality of lumens 210 or channels extending through each of the second hydrophobic layer 213, common electrode 206, top plate 207, such that a fluid droplet 211 disposed between the first hydrophobic layer 202 and the second hydrophobic layer 213 is at least partially exposed to an ambient environment about the EWOD apparatus 201 . Further, the partially-enclosed EWOD apparatus 201 as depicted in FIG. 2C can include a top plate 207 having or defining individual polymer wells, e.g., for receiving the spaced-apart fluid droplet 211 from a well plate.

[0030] FIG. 2D depicts process 230 for transferring of spaced-apart fluid droplets 211 from an external surface to an EWOD apparatus 201.

[0031] At 216, an external surface 225 carrying a plurality of donor droplets 226 at a specified pitch can be brought adjacent to the EWOD apparatus 201 . In an example, the EWOD apparatus 201 can be “primed” or otherwise prepared for receiving the donor droplets 226, e.g., via a plurality of priming droplets 227 at or near the specified pitch of the donor droplets donor droplet 226 and corresponding with a pitch of electrodes 212 of the EWOD apparatus 201.Docket No. 3867.C73WO1

[0032] At 217, the electrodes 212 can be activated such as to modulate a surface property of the EWOD apparatus 201, such as to reduce a surface tension of the priming droplet 227 and increase a surface area across which the priming droplet 227 on a surface of the EWOD apparatus 201.

[0033] At 218, the external surface 225 can be moved toward the EWOD apparatus 201 such that the donor droplet 226 is placed in fluid contact with the priming droplet 227. Here, the donor droplet 226 and the priming droplet 227 can combine to form a combined droplet 228.

[0034] At 219, the external surface 225 can be moved away from the EWOD apparatus 201 such as to release the combined droplet 228 from contacting the external surface 225.

[0035] At 220, the electrodes 212 can be deactivated such as to return the surface property of the EWOD apparatus 201 toward a natural state, such that a surface tension of the combined droplet 228 is no longer affected.

[0036] FIG. 3 A and FIG. 3B depict top views of an example of microfluidic apparatus 308 for reducing the pitch of assay wells. FIG. 3C depicts a side view of the example microfluidic apparatus 308 of FIG. 3A and FIG. 3B. In an example, the microfluidic apparatus 308 can include, define, or otherwise receive a well plate defining a first set of wells 312. The first set of wells 312 can each be sized and shaped to receive fluid at a first side of the well plate (e.g., receive fluid from a direction into the page with respect to FIG. 3 A), with the individual wells 314 spaced apart from each other at a first pitch. The microfluidic apparatus 308 can further define a first set of outlet lumens 318. In an example, an individual outlet lumen 318 can be sized and shaped to receive fluid from a corresponding well 314 and hold the fluid at a second side of the well plate, with the outlet lumens 318 spaced apart from each other at a second pitch smaller than the first pitch. Individual wells 314 can be microfluidically coupled via respective microfluidic channels 320 to corresponding individual outlet lumens 318. In an example, the microfluidic channels 320 can be formed using photo-patternable laminate films, e.g., polyamide or other dry film photoresists, with one microfluidic channel 320 per well 314 routing fluid toward the destination site outlet lumen 318.Docket No. 3867.C73WO1

[0037] In an example, the microfluidic apparatus 308 can include, define, or otherwise receive a plurality of sets of wells 312 and corresponding outlet lumens 318 to enable sequential processing of different droplet groups. For example, the microfluidic apparatus 308 can include or use a manipulator 306, arranged to translate at least one of an integrated circuit 106 or the wells 314 of the microfluidic apparatus 308 with respect to each other. As such, the manipulator 306 can help facilitate the integrated circuit 106 to be movable between different positions for receiving fluids from different sets of outlet lumens, e.g., between the first set of outlet lumens 324 and the second set of outlet lumens 326. In an example, the manipulator 306 can include a linear track, a robotic arm, a gantry, or another suitable mechanism for automated manipulation of at least one of the integrated circuit 106 or the well 314 with respect to each other. In an example, the processing circuitry 214 can control the positioning of the manipulator 306, such as to align specific regions of the semiconductor chip with the appropriate outlet lumen sets and e.g., incorporating sensor or camera feedback to aid in positioning of the manipulator 306.

[0038] FIG. 3C depicts a side view of the example of microfluidic apparatus of FIG. 3A and FIG. 3B. In an example, fluid displacement at the outlet lumens 318 can be achieved through pressurization, such as via a pressurization circuit 340 where at least one of the microfluidic channels 320 or the first set of outlet lumens 318 are fluidly connected to a pressurization outlet 346. Such a pressurization circuit 340 can facilitate controlled ejection of fluid from individual outlet lumens upon pressure changes supplied (e.g., via a pressure source 344) toward the pressurization outlet and onto a location of the integrated circuit 106. Similar to that described above with respect to the EWOD apparatus 201. the microfluidic apparatus 308 can translate a fluid array at a first cell-to-cell pitch within a range of 2,000 micrometers (pm) and 2,500 pm, toward a second cell-to-cell or spot-to-spot pitch within a range of 150 pm and 250 pm, achieving the necessary' pitch reduction for semiconductor compatibility and to facilitate high throughput screening (HTS) or ultra high throughput screening (UHTS) when performing the assay.

[0039] FIG. 4A depicts as side view of an example of a microfluidic apparatus for reducing the pitch of assay wells. FIG. 4B is a close view of theDocket No. 3867.C73WO1 example of the microfluidic apparatus for reducing the pitch of assay wells depicted in FIG. 4A. In an example, the microfluidic apparatus 408 can include similar features and operate similarly to that previously described with respect to the microfluidic apparatus 308 of FIG. 3A. Here, microfluidic channels can be formed between various layers of the microfluidic apparatus 408, such as to define a plurality of stepped channels by which fluid can travel from a well toward a corresponding outlet lumen.

[0040] FIG. 4B is a close view of the example of microfluidic apparatus for reducing the pitch of assay wells depicted in FIG. 4A.

[0041] FIG. 5A and FIG. 5B each depict an example of microfluidic apparatus 508 for reducing the pitch of assay wells. FIG. 5C and FIG. 5D each depict examples of a microfluidic apparatus 510 and a microfluidic apparatus 512, respectively, each for reducing the pitch of assay wells. In an example, the microfluidic apparatus 508, microfluidic apparatus 510, and microfluidic apparatus 512 can each include similar features and operate similarly to those previously described with respect to the microfluidic apparatus 308 and the microfluidic apparatus 408 in FIG. 3A and FIG. 4A, respectively.

[0042] FIG. 6A and FIG. 6B each depict an example of a sliding pin demagnification apparatus for reducing the pitch of assay wells. While FIG. 6A and FIG. 6B each depict drawing fluid from an array of wells on a source plate and reducing the pitch of the resulting array, a similar needle transfer technique can be used to transfer fluids from one source to another without a significant reduction in pitch. With specific reference to FIG. 6B, individual pins can be manipulated (e.g., via a magnet or other drive) along a track or trench, such that a pin-to-pin pitch between a plurality of pins becomes reduced as the pins travel from one side of the track or trench to an opposing side. The droplets coupled to the pins in the reduced pitch configuration can then be deposited on an additional surface having a pitch that is less than the initial pitch of the well plate.

[0043] FIG. 7 is a flowchart showing a process for transfer of fluids. The process 700 for microfluidic transfer of fluids can be illustrated through a flowchart depicting the sequential steps for achieving pitch reduction using electrowetting on dielectric (EWOD) fluid systems.Docket No. 3867.C73WO1

[0044] At 702, the process 700 can include receiving, from respective sample cells in a first array of sample cells, spaced-apart fluid droplets in a first configuration at a first pitch along an electrowetting on a surface dielectric (EWOD) fluid system, the EWOD fluid system including a set of first electrodes spaced-apart from each other at a second pitch, a first hydrophobic layer defining the surface of the EWOD fluid system, and a dielectric layer disposed between the set of first electrodes and the first hydrophobic layer. For example, the spaced-apart fluid droplets in the first configuration have a cell-to-cell pitch greater than 5X a cell-to-cell pitch of the respective droplets in the second configuration. In an example, spaced-apart fluid droplets in the first configuration substantially correspond with a well configuration of a 96- well, 384-well, or 1536-well plate, sized and shaped for high-throughput screening (HTS).

[0045] At 704, the process 700 can include modulating respective potentials of individual ones of the first set of first electrodes to establish or adjust electrowetting properties on the surface of the EWOD system.

[0046] At 706, the process 700 can include controlling the electrowetting properties to cause the respective droplets to be translated, on the surface of the EWOD, toward each other to define a second configuration wherein the respective droplets remain spaced-apart at a third pitch.

[0047] In an example, the process 700 can additionally include introducing the translated respective fluid droplets in the second configuration, each in respective nanoliter (nL) volumes, to a destination substrate (e.g., a semiconductor material). Further, the process 700 can include providing a reference potential via a one or more second electrodes arranged opposing the set of first electrodes such that an individual fluid droplet becomes disposed between the set of first electrodes and the one or more second electrodes.

[0048] FIG. 8 illustrates generally an example of a block diagram of a machine 801 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 801 may operate as a standalone device or may be connected (e.g., networked) to other machines. In a networked deployment, the machine 801 may operate in the capacity of aDocket No. 3867.C73WO1 server machine, a client machine, or both in server-client network environments. In an example, the machine 801 may act as a peer machine in peer-to-peer (P2P) (or other distributed) network environment. The machine 801 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.

[0049] 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 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.

[0050] Machine (e.g., computer system) 801 may include a hardware processor 802 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), a hardware processor core, or any combination thereof), a main memory 803 and a static memory 804, some or all of which may communicate with each other via an interlink (e.g., bus) 805. The machine 801 may furtherDocket No. 3867.C73WO1 include a display unit 806, an alphanumeric input device 807 (e.g., a keyboard), and a user interface (UI) navigation device 808 (e.g., a mouse). In an example, the display unit 806, alphanumeric input device 807 and ui navigation device 808 may be a touch screen display. The machine 801 may additionally include a storage device (e.g., drive unit) 809, a signal generation device 810 (e.g., a speaker), a network interface device 811, and one or more sensors 812. such as a global positioning system (GPS) sensor, compass, accelerometer, or other sensor. The machine 801 may include an output controller 816, 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.).

[0051] The storage device 809 may include a machine readable medium 813 that is non-transitory on which is stored one or more sets of data structures or instructions 814 (e.g., software) embodying or utilized by any one or more of the techniques or functions described herein. The instructions 814 may also reside, completely or at least partially, within the main memory 803, within static memory 804, or within the hardware processor 802 during execution thereof by the machine 801. In an example, one or any combination of the hardware processor 802, the main memory 803, the static memory 804, or the storage device 809 may constitute machine readable media.

[0052] While the machine readable medium 813 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 814.

[0053] The term “machine readable medium” may include any medium that is capable of storing, encoding, or carry ing instructions for execution by the machine 801 and that cause the machine 801 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. Nonlimiting 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 semiconductorDocket No. 3867.C73WO1 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.

[0054] The instructions 814 may further be transmitted or received over a communications network 815 using a transmission medium via the network interface device 811 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 811 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 815. In an example, the network interface device 811 may include a plurality7of antennas to wirelessly communicate using at least one of singleinput 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 carry ing instructions for execution by the machine 801, and includes digital or analog communications signals or other intangible medium to facilitate communication of such software.

Claims

Docket No. 3867.C73WO1CLAIMSWhat is claimed is:

1. An apparatus for transfer of fluids, the apparatus comprising: an electro wetting on dielectric (EWOD) fluid system, including a set of first electrodes spaced-apart from each other at a first pitch, a first hydrophobic layer defining a surface of the EWOD fluid system, and a dielectric layer disposed between the set of first electrodes and the first hydrophobic layer, wherein the surface of the EWOD fluid system is configured for receiving, from respective sample cells in a first array of sample cells, spaced-apart fluid droplets in a first configuration; and processing circuitry configured to: modulate respective potentials of individual ones of the set of first electrodes to establish or adjust electro wetting properties on the surface of the EWOD fluid system; control the electrowetting properties to urge the respective droplets to be translated, on the surface of the EWOD fluid system, toward each other to define a second configuration wherein the respective droplets remain spaced- apart at a second pitch.

2. The apparatus of claim 1, wherein the processing circuitry is configured to control the electrowetting properties to introduce the translated respective fluid droplets in the second configuration, each in respective nanoliter (nL) volumes, to a semiconductor material.

3. The apparatus of claim 2. wherein the spaced-apart fluid droplets in the first configuration have a cell-to-cell pitch greater than 5X a cell-to-cell pitch of the respective droplets in the second configuration.

4. The apparatus of claim 1. wherein spaced-apart fluid droplets in the first configuration substantially correspond with a well configuration of at least one of a 96-well, a 384-well, or a 1536-well plate, sized and shaped for high- throughput screening (HTS).Docket No. 3867.C73WO15. The apparatus of claim 1, comprising a second hydrophobic layer, spaced apart from the first hydrophobic layer and arranged such as to hold an individual fluid droplet between the first and second hydrophobic layers.

6. The apparatus of claim 1, comprising one or more second electrodes arranged opposing the set of first electrodes such as to hold an individual fluid droplet between the set of first electrodes and the one or more second electrodes, wherein the one or more second electrodes is configured to provide a reference potential.

7. The apparatus of claim 6, wherein the one or more second electrodes include a plurality of electrodes, the plurality of second electrodes arranged spaced apart from each other and opposing corresponding electrodes of the set of first electrodes.

8. An apparatus for transfer of fluids, the apparatus comprising: a well plate defining: a first set of wells, each sized and shaped to receive fluid at a first side of the well plate, wherein the first set of wells are spaced apart from each other at a first pitch; a first set of outlet lumens, each sized and shaped to receive fluid from a corresponding well of the first set of wells and hold the fluid at a second side of the well plate, wherein the first set of outlet lumens are spaced apart from each other at a second pitch smaller than the first pitch; wherein individual wells of the first set of wells are microfluidically coupled, via respective microfluidic channels, to corresponding individual outlet lumens of the first set of outlet lumens.

9. The apparatus of claim 8, wherein the well plate further defines: a second set of wells, each sized and shaped to receive fluid at the first side of the well plate, wherein the second set of wells are spaced apart from each other at the first pitch; a second set of outlet lumens, each sized and shaped to receive fluid from a corresponding well of the second set of wells and hold the fluid at the second side of the well plate, wherein the second set of outlet lumens are spaced apart from each other at the second pitch smaller than the first pitch;Docket No. 3867.C73WO1 wherein individual wells of the second set of wells are microfluidically coupled, via respective microfluidic channels, to corresponding individual outlet lumens of the second set of outlet lumens.

10. The apparatus of claim 9, further comprising: a manipulator arranged to translate at least one of a destination substrate or the well plate with respect to each other, such that the destination substrate is movable between: a first position where the destination substrate is arranged to receive respective fluids from each of the first set of outlet lumens at the second pitch; and a second position where the destination substrate is arranged to receive respective fluids from each of the second set of outlet lumens at the second pitch.

11. The apparatus of claim 10, comprising controller circuitry configured to: control the manipulator, in the first position, to align a first region of the destination substrate to receive the respective fluids from each of the first set of outlet lumens at the second pitch; control the manipulator, in the second position, to align a second region of the destination substrate to receive the respective fluids from each of the second set of outlet lumens at the second pitch.

12. The apparatus of claim 8, wherein at least one of the microfluidic channels or the first set of outlet lumens are fluidly connected to a pressurization outlet, such that fluid held at the first set of outlet lumens is displaced and ejected from an individual outlet lumen upon a change in pressure supplied via the pressurization outlet.

13. The apparatus of claim 8, wherein the first pitch is within a range of 2,000 micrometers (pm) and 2,500 pm and the second pitch is within a range of 150 pm and 250 pm.

14. A method for transfer of fluids, the method comprising: receiving, from respective sample cells in a first array of sample cells, spaced-apart fluid droplets in a first configuration at a first pitch alongDocket No. 3867.C73WO1 an electro wetting on dielectric (EWOD) fluid system, the EWOD fluid system including a set of first electrodes spaced-apart from each other at a second pitch, a first hydrophobic layer defining the surface of the EWOD fluid system, and a dielectric layer disposed between the set of first electrodes and the first hydrophobic layer; modulating respective potentials of individual ones of the first set of first electrodes to establish or adjust electrowetting properties on the surface of the EWOD system; and controlling the electrowetting properties to urge the respective droplets to be translated, on the surface of the EWOD, toward each other to define a second configuration wherein the respective droplets remain spaced- apart at a third pitch.

15. The method of claim 14, comprising introducing the translated respective fluid droplets in the second configuration, each in respective nanoliter (nL) volumes, to a semiconductor material.

16. The method of claim 15, wherein the spaced-apart fluid droplets in the first configuration have a cell-to-cell pitch greater than 5X a cell-to-cell pitch of the respective droplets in the second configuration.

17. The method of claim 14, wherein spaced-apart fluid droplets in the first configuration substantially correspond with a well configuration of at least one of a 96-well, a 384-well, or a 1536-well plate, sized and shaped for high- throughput screening (HTS).

18. The method of claim 14, comprising contacting the spaced-apart fluid droplets with a second hydrophobic layer, spaced apart from the first hydrophobic layer, such that an individual fluid droplet becomes disposed between the first and second hydrophobic layers.

19. The method of claim 14, providing a reference potential via a one or more second electrodes arranged opposing the set of first electrodes such that an individual fluid droplet becomes disposed between the set of first electrodes and the one or more second electrodes.Docket No. 3867.C73WO120. The method of claim 19, wherein the one or more second electrodes include a plurality of electrodes, the plurality of second electrodes arranged spaced apart from each other and opposing corresponding electrodes of the set of first electrodes.

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