Systems and methods for continuous flow

Abstract

The present disclosure relates to a chip for continuous flow, comprising a chip substrate assembly defining a closed fluid channel. The chip substrate assembly includes an air side for receiving one or more pressurized air inputs and a liquid side configured to receive a pressurized liquid flow for the closed fluid channel. The chip further includes one or more diaphragm / valve complexes interposed along the closed fluid channel on the liquid side of the chip substrate assembly. Each diaphragm / valve complex comprises at least one diaphragm pump and at least two air-pressure actuated, individually-controllable, elastomeric valves. The closed fluid channel includes an input pathway and a dispense pathway. The chip enables continuous flow of fluids with precise control over the flow rate and direction.

Description

SYSTEMS AND METHODS FOR CONTINUOUS FLOWCROSS-REFERENCE TO RELATED APPLICATIONS[1] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 448,209 filed February 24, 2023 and titled “METERING ASSEMBLY AND METHOD OF DISPENSING FLUID.” The contents of the above application are incorporated by reference in their entirety.FIELD[2] This disclosure relates to systems and methods for continuous flow and, in particular, to assemblies, valves, pumps, and pathways for continuous flow.BACKGROUND[3] Systems and methods for continuous flow are configured to deliver a steady and uninterrupted stream (or flow) of fluid. Generally, various methods and systems have been developed for attempting to achieve efficient, effective, and sustainable / durable fluidic and microfluidic continuous flow. However, conventional systems and methods for continuous flow encounter several issues, deficiencies, limitations, and problems.[4] For example, conventional systems may suffer from dead volumes (e.g., wasted fluid), where residual fluids remain trapped in the system, leading to sample loss, contamination, and inaccurate fluid dispensing.[5] Moreover, in another example, improper sealing or connections in a fluidic pathway can result in leakage, leading to loss of fluids, contamination, and instability in flow rates.[6] Moreover, in another example, conventional fluidic pumps and fluidic valves mayoffer limited precision and control over flow rates, especially at low volumes and high pressures, which can impact the accuracy and reproducibility of fluid-channeling and dispensing.[7] Moreover, in another example, high shear stress generated by conventional pumps and conventional structures can damage sensitive biological samples or alter the properties of the fluids, particularly in microfluidic applications where flow rates tend to be low.[8] Moreover, in another example, clogging due to the small dimensions of fluidic channels, along with the presence of particulates or biomolecules in the fluids, can lead to flow obstruction and possible system failure.[9] Moreover, in another example, surface interactions between the fluids and the walls or structures of the system can cause adsorption, fouling, or non-specific binding, affecting the behavior and performance of the system.

[0010] Moreover, in another example, fabrication of conventional fluidic and microfluidic systems and assemblies may involve complex and costly processes, limiting accessibility and scalability for widespread adoption.[U] Moreover, in another example, some materials commonly used in conventional fluidic and microfluidic systems may not be compatible with certain fluids or applications, limiting the range of practical implementations.

[0012] As such, none of the existing approaches for achieving continue flow have provided a comprehensive solution that combines the features described in this disclosure.SUMMARY

[0013] In some aspects, the techniques described herein relate to a chip for continuous flow, including: (a) a chip substrate assembly defining a closed fluid channel, the chip substrate assembly comprising: (i) an air side, whereby one or more pressurized air inputs are received; and(ii) a liquid side, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and (b) one or more unitary elastomeric components between the air side and the liquid side of the chip substrate assembly forming one or more diaphragm / valve complexes interposed along the closed fluid channel on the liquid side of the chip substrate assembly; wherein each of the one or more diaphragm / valve complexes comprises at least one diaphragm pump and at least two air-pressure actuated, individually-controllable, elastomeric valves; and wherein the closed fluid channel comprises at least an input pathway and a dispense pathway.

[0014] In some aspects, the techniques described herein relate to a chip for continuous flow, comprising: (a) a chip substrate assembly defining a closed fluid channel, the chip substrate assembly comprising: (i) an air side, whereby one or more pressurized air inputs are received; and (ii) a liquid side, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and (b) one or more unitary elastomeric components between the air side and the liquid side of the chip substrate assembly forming one or more diaphragm / valve complexes interposed along the closed fluid channel on the liquid side of the chip substrate assembly; wherein, each of the one or more diaphragm / valve complexes comprises two adjacent valve clusters, wherein, each of the two adjacent valve clusters comprises one diaphragm pump and one air-pressure actuated, individually-controllable, elastomeric valve; and wherein the closed fluid channel comprises an input pathway and a dispense pathway.

[0015] In some aspects, the techniques described herein relate to a chip for continuous flow, comprising: a chip substrate assembly defining a closed fluid channel, the chip substrate assembly comprising: an air side, whereby one or more pressurized air inputs are received; and a liquid side, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and two or more unitary elastomeric components between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly; wherein, each of the plurality of valve clusters comprises one diaphragm pump and three air-pressure actuated, individually- controllable, bi-directional, elastomeric valves; and wherein the closed fluid channel comprises aninput pathway, a recirculation / recovery pathway, and a dispense pathway.

[0016] In some aspects, the techniques described herein relate to a method for achieving continuous flow in a chip, including: (a) assembling a chip substrate assembly, wherein assembling the chip substrate assembly includes: (i) providing an air side configured to receive one or more pressurized air inputs; (ii) providing a liquid side; (iii) providing one or more diaphragm / valve complexes; and (iv) stacking the air side and the liquid side, with the one or more diaphragm / valve complexes therebetween, such that a closed fluid channel is defined between the air side and liquid side, and such that the one or more diaphragm / valve complexes are interposed along the closed fluid channel on the liquid side of the chip substrate assembly; (b) providing a pressurized liquid flow to the closed fluid channel of the chip substrate assembly, the closed fluid channel including an input pathway and a dispense pathway; and (c) actuating the one or more diaphragm / valve complexes.

[0017] Throughout this specification and the claims, the terms “air” and “air side” are used for convenience and simplicity and not to limit the scope of the present disclosure. In one aspect, gases other than air are envisioned, such as carbon dioxide, nitrogen, etc., and, therefore, an air side is not limited to receiving only pressurized air inputs and, in one aspect, may receive pressurized gas inputs. Similarly, air-pressure actuated valves, in one aspect, may be gas actuated valves.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Many aspects of the present disclosure will be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, with emphasis instead being placed upon clearly illustrating the principles of the disclosure. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views. It should be recognized that these implementations and embodiments are merely illustrative of the principles of the present disclosure. Therefore, in the drawings:

[0019] FIG. 1 is an elevated front view of an illustration of an example microfluidic dispensing system for continuous flow, according to the present disclosure.

[0020] FIG. 2 is a magnified, elevated front view of an illustration of an example microfluidic dispensing system for continuous flow, according to the present disclosure.

[0021] FIG. 3A is an elevated side view of an illustration of an example continuous flow chip with corresponding pressurized reservoir, according to the present disclosure.

[0022] FIG. 3B is a magnified, see-through, elevated side view of an illustration of an example continuous flow chip, according to the present disclosure.

[0023] FIG. 4A is a magnified, exploded, bottom perspective view of an illustration of an example continuous flow chip, according to the present disclosure.

[0024] FIG. 4B is a magnified, exploded, top perspective view of an illustration of the example continuous flow chip, according to the present disclosure.

[0025] FIG. 5A is a top view of an illustration of an example diaphragm / valve complex for a continuous flow chip, according to the present disclosure.

[0026] FIG. 5B is a perspective view of an illustration of the example diaphragm / valve complex for a continuous flow chip, according to the present disclosure.

[0027] FIG. 6A is a cut-away, perspective view of an illustration of an example diaphragm / valve complex of a plurality of diaphragm / valve complexes for a continuous flow chip, according to the present disclosure.

[0028] FIG. 6B is a cut-away, perspective view of an illustration of the example diaphragm / valve complex of a plurality of diaphragm / valve complexes for a continuous flow chip, according to the present disclosure.

[0029] FIG. 7A is a top view of an illustration of an example first half of a continuous flow chip according to the present disclosure.

[0030] FIG. 7B is a top view of an illustration of an example second half of a continuous flow chip according to the present disclosure.

[0031] FIG. 8 is an elevated side view of an illustration of an example continuous flow chip, according to the present disclosure.

[0032] FIG. 9A is an exploded, bottom perspective view of an illustration of an example continuous flow chip, according to the present disclosure.

[0033] FIG. 9B is an exploded, top perspective view of an illustration of the example continuous flow chip, according to the present disclosure.

[0034] FIG. 10A is a top view of an illustration of an example diaphragm / valve complex for a continuous flow chip, according to the present disclosure.

[0035] FIG. 10B is a perspective, wireframe view of an illustration of the example diaphragm / valve complex for a continuous flow chip, according to the present disclosure.

[0036] FIG. 11A is a cut-away, schematic view of an illustration of an example diaphragm / valve complex having two adjacent valve clusters, each with a valve in a closed configuration, and having a primed closed fluid channel, according to the present disclosure.

[0037] FIG. 11B is a cut-away, schematic view of an illustration of the example diaphragm / valve complex having two adjacent valve clusters, each with a valve in an open configuration for continuous flow dispense, and having a primed closed fluid channel, according to the present disclosure.

[0038] FIG. 11C is a cut-away, schematic view of an illustration of the examplediaphragm / valve complex having two adjacent valve clusters, each with a valve in the closed configuration for stopping the continuous flow dispense, and having a primed closed fluid channel, according to the present disclosure.

[0039] FIG. 11D is a cut-away, schematic view of an illustration of the example diaphragm / valve complex having two adjacent valve clusters, one with an output valve in an open configuration for opening access to a dispense pathway without dispensing, according to the present disclosure.

[0040] FIG. HE is a cut-away, schematic view of an illustration of the example diaphragm / valve complex having two adjacent valve clusters, one with the output valve in an open configuration and one with a small diaphragm pump in an open configuration for drawing liquid from the dispense pathway, according to the present disclosure.

[0041] FIG. HF is a cut-away, schematic view of an illustration of the example diaphragm / valve complex having two adjacent valve clusters, one with the output valve in an open configuration and one with a large diaphragm pump in open configuration for drawing liquid from the dispense pathway, according to the present disclosure.

[0042] FIG. 12 is an illustration of a flowchart of an example method for achieving continuous flow in a chip, according to the present disclosure.DETAILED DESCRIPTION

[0043] The presently disclosed subject matter now will be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all embodiments of the presently disclosed subject matter are shown. Like numbers refer to like elements throughout. The presently disclosed subject matter may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Indeed, many modifications andother embodiments of the presently disclosed subject matter set forth herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be understood that the presently disclosed subject matter is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims.

[0044] Throughout this specification and the claims, the terms “comprise,” “comprises”, and “comprising” are used in a non-exclusive sense, except where the context requires otherwise. Likewise, the term “includes” and its grammatical variants are intended to be non-limiting, such that recitation of items in a list is not to the exclusion of other like items that can be substituted or added to the listed items.

[0045] Moreover, throughout this specification and the claims, the terms “air” and “air side” are used for convenience and simplicity and not to limit the scope of the present disclosure. In one aspect, gases other than air are envisioned, such as carbon dioxide, nitrogen, etc., and, therefore, an air side is not limited to receiving only pressurized air inputs and, in one aspect, may receive pressurized gas inputs. Similarly, air-pressure actuated valves, in one aspect, may be gas actuated valves.

[0046] Systems and methods for continuous flow are configured to deliver a steady and uninterrupted fluid flow. Other systems and methods are intended to timely deliver a specific volume of fluid to a destination. Generally, systems for continuous flow typically comprise precise control mechanisms to regulate the flow rate (or throughput per unit of time) of fluid, and / or to regulate the volume of fluid being channeled. Some systems also typically comprise other common components, sub-systems, or sub-assemblies.

[0047] For example, some systems include a fluid source or reservoir, and include related components, sub-systems, or sub-assemblies such as filter media or filtration systems to ensurepurity or sterility and prevent contamination.

[0048] Other systems include pumps like peristaltic pumps or syringe pumps for generating fluid flow and / or for driving a fluid through the system.

[0049] Other systems include a fluid channel through which the fluid travels from the source through the system.

[0050] Other systems include one or more dispensing tip(s) / nozzle(s) through which the fluid is dispensed from or out of the system. The configuration of these tips or nozzles may vary depending on factors such as the size and geometry of the final fluid receptacle, as well as the viscosity of the fluid.

[0051] Other systems include an integration for chip handling equipment. In some cases, for example, the system may be integrated with robotic or automated equipment that handles or tracks laboratory chips, and which facilitates high-throughput experimentation.

[0052] Other systems include a user interface where an operator, for example, can set parameters such as the flow rate, the volume, and / or the dispensing sequence, or where an operator can initiate an autonomous or semi -autonomous system mode.

[0053] Other conventional systems include specific control mechanisms comprising, for example, sensor systems that monitor flow rate and that adjust pump speed, etc.

[0054] In the context of microfluidics and microfluidic systems, the definition of a system for continuous flow retains many of the core components and considerations outlined above and herein, but there are some nuances and additional factors to consider. For example, microfluidic systems are characterized by their small scale, with channels and wells typically on the milli-, micro-, or even nano- scale. This requires miniaturization of components such as pumps, valves, and fluidic pathways to achieve precise control and manipulation of fluids; however, this creates its own unique set of problems, issues, and deficiencies.

[0055] Although various methods and systems have been developed for attempting to achieve efficient, effective, and sustainable / durable fluidic and microfluidic continuous flow, these existing approaches have limitations and drawbacks that have hindered their effectiveness and accuracy.I. Example Use Case Scenario

[0056] The systems and methods for continuous flow according to the present disclosure present a novel approach, and one or more technical steps and / or solutions, to addressing the challenges and deficiencies in the prior art.

[0057] For example, in one aspect, systems and methods according to the present disclosure provide for a disposable (e.g., consumable) assembly or chip for continuous flow, or preferably a non-disposable (or reusable or) assembly or chip for continuous flow, that benefits from the other advantages and improvements described herein.

[0058] In another aspect, systems and methods according to the present disclosure provide for an assembly or chip for continuous flow with broad practical applications and implementations, e.g., High Throughput Screening (HTS); Assay Development and Design of Experiment (DoE); Enzyme-Linked Immunosorbent Assays (ELISA); Polymerase Chain-reaction (PCR) Workflows (Real-time and Digital); Biochemical assay development and screening; Cell Culture and Bead- Based Assays; and for Next Generation Sequencing (NGS) (e.g., library preparation).

[0059] In another aspect, systems and methods according to the present disclosure provide for an assembly or chip for continuous flow that also allows for channeling and dispensing fluids.

[0060] In another aspect, systems and methods according to the present disclosure provide for a chip for continuous flow that also allows for channeling, recirculating / recovering, and dispensing fluids.

[0061] In another aspect, systems and methods according to the present disclosure providefor a chip for continuous flow that also allows with automated recirculation that ensures cells and beads, for example, remain in suspension.

[0062] In another aspect, systems and methods according to the present disclosure provide for a chip for continuous flow configured to return excess fluid back to the reagent container or reservoir.

[0063] In another aspect, systems and methods according to the present disclosure include one direction valve(s) and bi-directional valve(s).

[0064] In another aspect, systems and methods according to the present disclosure include a fluidic or microfluidic valve configured as a diaphragm / valve complex.

[0065] In another aspect, systems and methods according to the present disclosure include a diaphragm / valve complex configured as two separate side-by-side valve clusters.

[0066] In another aspect, systems and methods according to the present disclosure include valve cluster(s) each configured as individual unitary elastomeric piece(s) having separate regions defining valve(s) and / or diaphragm pump(s).

[0067] In another aspect, systems and methods according to the present disclosure include a diaphragm / valve complex having differently configured valve clusters, e.g., wherein one of the valve cluster(s) has a small diaphragm pump and another has a large diaphragm pump.

[0068] In another aspect, systems and methods according to the present disclosure include a diaphragm / valve complex configured as two or more valve clusters.

[0069] In another aspect, systems and methods according to the present disclosure include a plurality of valve cluster(s) merged together into a single unitary elastomeric piece(s) having separate regions defining valve(s) and / or diaphragm pump(s).

[0070] In another aspect, systems and methods according to the present disclosure include a plurality of valve clusters each having one diaphragm pump and three individually-controllable elastomeric valves.

[0071] In another aspect, systems and methods according to the present disclosure include a valve cluster(s) configured as a hybrid between a diaphragm pump and a timed-valve that, acting alone or in combination with other similar valve cluster(s), allows for continuous flow to be achieved within the chip(s), as well as for priming, recovering, recirculating, washing, and / or aspirating to be achieved within the chip(s), without necessarily having to dispense fluid from the flow.

[0072] In another aspect, systems and methods according to the present disclosure include air-pressure actuated, elastomeric, timed valves.

[0073] In another aspect, systems and methods according to the present disclosure provide for a low shear-force flow and dispensing that promotes cell viability, and that is soft-acting on live cells / small organisms / organics.

[0074] In another aspect, systems and methods according to the present disclosure provide chip assemblies for continuous flow that have good sealing performance and long lifetime / durability .

[0075] In another aspect, systems and methods according to the present disclosure provide chip assemblies for continuous flow that resist being clogged by thick liquids or liquids with beads / solid components.

[0076] In another aspect, systems and methods according to the present disclosure provide for chip(s) with one or multiple continuous flow dispensing outlets / nozzles, each independently controlled.

[0077] In another aspect, systems and methods according to the present disclosure allowfor easy cleaning of between uses without disassembly.

[0078] In another aspect, systems and methods according to the present disclosure provide for an automated wash cycle that cleans the entire fluid channel without user intervention, e.g., a forward or reverse wash cycle capable of forcing fluid backward through increasingly larger channels for thorough, clog-free cleaning.

[0079] In another aspect, systems and methods according to the present disclosure include diaphragm pumps having a top-hat configuration, a multi-level configuration, or a dome diaphragm configuration.

[0080] In another aspect, systems and methods according to the present disclosure provide for the ability to prime a chip(s) without any waste fill liquid.

[0081] In another aspect, systems and methods according to the present disclosure provide for the ability to prime a nozzle without initiating a dispense.

[0082] In another aspect, systems and methods according to the present disclosure provide for the ability to recover liquid from a chip(s).

[0083] In another aspect, systems and methods according to the present disclosure provide for the ability to recirculate flow through any number of pathways of a fluid channel(s) (for mixing, temperature, other reagent conditioning reasons, or exchanging liquids, for example).

[0084] In another aspect, systems and methods according to the present disclosure provide for the ability to aspirate substances from the nozzle to push through upstream (used for the automatic wash / cleaning cycle(s), for example).

[0085] In another aspect, systems and methods according to the present disclosure provide for a chip that can perform precise droplet metering and dispensing and / or continuous flow.

[0086] In another aspect, systems and methods according to the present disclosure provides for a fluidic or microfluidic dispensing system. In particular, in one aspect, systems and methods according to the present disclosure provide for a non-contact, multipurpose dispenser that leverages positive displacement, ensuring high accuracy and precision across a broad range of reagent types, including cells and beads, that supports all SBS plate types (e.g., 24-, 96-, 384-, and 1536-well plates), that easily integrates with other robotic automation systems, and that has optional plate stacker(s) and barcode reader(s).

[0087] In another aspect, systems and methods according to the present disclosure provide low dead-volume, i.e., non-recoverable dead volume, as low as about 48.0 pL per chip.

[0088] In another aspect, systems and methods according to the present disclosure provides for a fluidic or microfluidic dispensing system having compact dimensions (e.g., about 555.0 mm x about 309.67 mm x about 266.56 mm), that allows for the system to be used in various biosafety cabinets to accommodate workflows that require ventilation or isolation.

[0089] In another aspect, systems and methods according to the present disclosure provides for a fluidic or microfluidic dispensing system having 12 chips, each featuring eight independently-controlled dispensing nozzles.

[0090] In another aspect, systems and methods according to the present disclosure provides for a fluidic or microfluidic dispensing system that includes a pressurized reservoir to dispense a constant stream of liquid from all eight nozzle positions, and that achieves a CV of less than or equal to 3% across all eight nozzles when filling a 96-well plate, for example, and that achieves adjustable flow rates capable of greater than or equal to 400 pL per second (or that can fill a 96- deep-well plate with 2 mb per well in under 2 minutes).

[0091] In another aspect, systems and methods according to the present disclosure provides for a fluidic or microfluidic dispensing system that includes a pressurized reservoir to dispense a constant stream of liquid from a nozzle, and that achieves a CV of less than or equal to 2% at 100nL, for example, and that achieves adjustable flow rates capable of greater than or equal to 600 pL per second.

[0092] In another aspect, systems and methods according to the present disclosure provides for a fluidic or microfluidic dispensing system that includes a pressurized reservoir configured as a 50 mb Falcon™ tube, a 250 mL Nalgene™ media bottle, or a GL45™ capped glassware.

[0093] In another aspect, systems and methods according to the present disclosure include several unitary elastomeric pieces compressed between two rigid components such that open channels or ports or opening on each of the rigid components are sealed by the elastomer or mate to form closed fluid channels. In either case, these form the basis of the air side and the liquid side of a continuous flow chip, wherein the liquid side is configured to receive a pressurized liquid flow and the air side is configured to receive air pressure inputs for controlling / actuating the unitary elastomeric pieces. In particular, in one aspect, each unitary elastomeric part, along with the rigid components, create structures that operate as, for example, three individually controlled elastomeric valves and one individually controlled diaphragm pump, with fluid access, on the on the liquid side of the continuous flow chip. Moreover, in one aspect, all of the valves act to block access to a central chamber and the central volume is acted on by a diaphragm membrane. In this way, in one aspect, the valve regulate access to an input pathway, a recovery / recirculation pathway, and dispense pathway.

[0094] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, including: (a) a chip substrate assembly defining a closed fluid channel, the chip substrate assembly including: (i) an air side, whereby one or more pressurized air inputs are received; and (ii) a liquid side, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and (b) one or more diaphragm / valve complexes interposed along the closed fluid channel on the liquid side of the chip substrate assembly; wherein each of the one or more diaphragm / valve complexes includes at least one diaphragm pump and at least two air- pressure actuated, individually-controllable, elastomeric valves; and wherein the closed fluidchannel includes an input pathway and a dispense pathway.

[0095] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein each of the one or more diaphragm / valve complexes includes two adjacent valve clusters, and wherein each of the two adjacent valve clusters includes one diaphragm pump and at least one air-pressure actuated, individually-controllable, elastomeric valve.

[0096] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein each of the two adjacent valve clusters is configured as a single unitary elastomeric component between the air side and the liquid side of the chip.

[0097] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the chip substrate assembly includes a top substrate layer and a bottom substrate layer, the top substrate layer corresponding to the air side and the bottom substrate layer corresponding to the liquid side, and wherein the chip substrate assembly defines the closed fluid channel therebetween.

[0098] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the chip substrate assembly includes a top substrate layer, an intermediate substrate layer, and a bottom substrate layer, the top substrate layer corresponding to the air side and the bottom substrate layer corresponding to the liquid side, and wherein the chip substrate assembly defines the closed fluid channel therebetween.

[0099] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the closed fluid channel is defined at least in part by the intermediate substrate layer and a fluid recess on a surface of the bottom substrate layer.

[0100] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the top substrate layer includes ports configured to receive theone or more pressurized air inputs.

[0101] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein each of the two adjacent valve clusters has a corresponding port.

[0102] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the one diaphragm pump and each of the at least one air- pressure actuated, individually-controllable, elastomeric valves of each of the two adjacent valve clusters has a corresponding port.

[0103] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the chip includes two or more diaphragm / valve complexes, wherein each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, wherein each of the plurality of valve clusters includes one diaphragm pump and three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves; and wherein the closed fluid channel also includes a recirculation / recovery pathway.

[0104] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the chip substrate assembly includes a top substrate layer and a bottom substrate layer, the top substrate layer corresponding to the air side and the bottom substrate layer corresponding to the liquid side, and wherein the chip substrate assembly defines the closed fluid channel therebetween.

[0105] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the closed fluid channel is defined at least in part by the top substrate layer and a fluid recess on a surface of the bottom substrate layer.

[0106] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the top substrate layer includes ports configured to receive the one or more pressurized air inputs.

[0107] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein each of the two or more diaphragm / valve complexes has a corresponding port.

[0108] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein each of the plurality of valve clusters has a corresponding port.

[0109] In another aspect, systems and methods according to the present disclosure include a chip for continuous flow, wherein the one diaphragm pump and each of the three air-pressure actuated, individually-controllable, bi-directional elastomeric valves of each of the plurality of valve clusters has a corresponding port.

[0110] In another aspect, systems and methods according to the present disclosure involve a method for achieving continuous flow in a chip, including: (a) assembling a chip substrate assembly, wherein assembling the chip substrate assembly includes: (i) providing an air side configured to receive one or more pressurized air inputs; (ii) providing a liquid side; (iii) providing one or more diaphragm / valve complexes; and (iv) stacking the air side and the liquid side, with the one or more diaphragm / valve complexes therebetween, such that a closed fluid channel is defined between the air side and liquid side, and such that the one or more diaphragm / valve complexes are interposed along the closed fluid channel on the liquid side of the chip substrate assembly; (b) providing a pressurized liquid flow to the closed fluid channel of the chip substrate assembly, the closed fluid channel including an input pathway and a dispense pathway; and (c) actuating the one or more diaphragm / valve complexes.[Hl] In another aspect, systems and methods according to the present disclosure involve a method, wherein each of the one or more diaphragm / valve complexes includes two adjacentvalve clusters, and wherein actuating the one or more diaphragm / valve complexes includes actuating the two adjacent valve clusters.

[0112] In another aspect, systems and methods according to the present disclosure involve a method, wherein the chip includes two or more diaphragm / valve complexes, wherein each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, and wherein actuating the one or more diaphragm / valve complexes includes actuating the plurality of valve clusters.

[0113] In another aspect, systems and methods according to the present disclosure involve a method, wherein the chip includes two or more diaphragm / valve complexes, wherein each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, wherein each of the plurality of valve clusters includes one diaphragm pump and three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves, and wherein actuating the one or more diaphragm / valve complexes includes actuating at least two of the three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves.II. Systems and Methods

[0114] In one aspect, the present disclosure provides for a fluidic or microfluidic dispensing system including a fluidic or microfluidic chip(s) for continuous flow having a diaphragm pump(s). In another aspect, a diaphragm pump(s) allows for priming of a fluid channel within the chip. In another aspect the diaphragm, pump allows for metering and dispensing of discrete volumes of ingredients through outlets such as, for example, nozzles and / or tips. In another aspect, supply lines are associated with the diaphragm pump(s), providing an arrangement fordelivering a corresponding ingredient(s) to the diaphragm pump(s), with the ingredients coming from a pressurized reservoir(s), for example.

[0115] In one aspect, along with diaphragm pump(s), a chip for continuous flow includes a fluid channel(s) that serve to provide a passageway for a flow between various components of the chip(s). For example, in another aspect, a fluid channel may provide for fluid communication between a supply line, a diaphragm pump, a valve, and an outlet.

[0116] In one aspect, along with diaphragm pump(s) and fluid channel(s), a chip for continuous flow also includes valves that provide for opening and closing of fluid channels leading to and from diaphragm pumps, or to and from the outlets / nozzles, or to and from a pressurized reservoir, for example. Although valves allow for control of a pressurized fluid flow to and from, for example, a fluid channel or a diaphragm pump, other arrangements for valves for controlling flow and achieving continuous flow may be employed, as this disclosure is not limited in this respect.

[0117] In one aspect, diaphragm pumps and / or valves are arranged or formed into groups as diaphragm / valve complexes. In another aspect, diaphragm pumps and / or valves are arranged or formed into groups as valve clusters. In another aspect, a chip includes a plurality of diaphragm / valve complexes and / or valve clusters. In another aspect, two or more valve clusters are arranged or configured as diaphragm / valve complexes. In another aspect, diaphragm pumps and / or valves are formed together as a unitary elastomeric piece or component. In another aspect, each diaphragm pump and / or valve is separately and individually controlled or actuated.

[0118] In one aspect, diaphragm pump(s) and valves are controlled by any suitable method, such as, for example, a pressure control approach. In another aspect, diaphragm pumps and / or valves are actuated by pneumatic or hydraulic methods and, therefore, a chip includes pressure ports whereby pressure within the ports causes membranes of the diaphragm pumps and / or valves to actuate such that a diaphragm pump and / or valve may open or close or pump. Other suitableactuation arrangements may be employed, as the present disclosure is not limited in this respect.

[0119] In one aspect, for example, the present disclosure provides diaphragm pumps and / or valves that are controlled through a pressure inlet that either serves to push air against a flexible membrane, closing the diaphragm pump and / or valve, or that serves to refrain from applying pressure to a flexible membrane, resulting in the opening of a diaphragm pump and / or valve. In another aspect, a vacuum is applied to further facilitate opening of a diaphragm pump and / or valve, allowing for improved flow through a diaphragm pump and or valve. In another aspect, a diaphragm pump and / or valve is configured such that application of pressure through an inlet to a flexible membrane serves to open a diaphragm pump and / or valve and that not applying pressure, or applying a vacuum through an inlet serves to close a diaphragm pump and / or valve. In another aspect, actuation of the diaphragm / valve complexes and / or the valve clusters includes: a pumping actuation via, for example, the diaphragm pump(s) (in any number or combination), that may be repeated as desired for priming a fluid channel with a chip(s); and includes an opening actuation via, for example, the timed-valves, for achieving continuous flow.

[0120] It should be understood that diaphragm pumps and / or valves may be formed out of a wide variety of suitable materials. Thus, in one aspect, diaphragm pumps and / or valves are made of an elastomeric material such as silicone, rubber, polyurethane, polydimethylsiloxane, polytetrafluoroethylene (PFE), or any suitable polymeric equivalent or suitable combinations thereof. In another aspect, diaphragm pumps and / or valves are made of a suitable rigid material such as a metal or a ceramic, that can be actuated through any appropriate arrangement, whether electrical or mechanical in nature. If a rigid material is used, in another aspect, a hinge or gateway that can be opened or closed is employed.

[0121] In one aspect, diaphragm / valve complexes and / or valve clusters are formed of any suitable material and in any suitable arrangement or combinations of materials, such as those described above with respect to the diaphragm pumps and / or valves. For example, in another aspect, diaphragm / valve complexes and / or valve clusters may be molded together or in anycombination as a single unitary elastomeric piece or component or as a split elastomeric piece or component.

[0122] It should be appreciated that a number of alternative embodiments exist for diaphragm / valve complexes and / or valve clusters. Thus, in one aspect, a cluster of diaphragm pumps and / or valves are used to control a particular pump region of a chip associated with an outlet (e.g., nozzle) for dispensing. In another aspect, a cluster of diaphragm pumps and / or valves are in fluid communication with only a portion of a fluid channel of a chip. In another aspect, a cluster of diaphragm pumps and / or valves are in fluid communication with a number of fluid channels of a chip.

[0123] In one aspect, the present disclosure also provides outlets that can be of any form, as the present disclosure is not limited in this respect. Thus, in one aspect, outlets are configured as nozzles. In another aspect, outlets are configured as tubes or fluid channels that lead to other regions or portions of a chip(s) or to a broader dispensing system that may include outlets / nozzles themselves. In another aspect, nozzles include tips. In another aspect, tips are preferably disposable while the chip(s) are not. In another aspect, tips are preferably disposable and the chip(s) are disposable after one or several uses. In another aspect, tips are configured to be detachably engaged to a chip.

[0124] In one aspect, tips are configured to be suitably placed in contact with appropriate ingredient sources, so that a corresponding ingredient may be aspirated into each tip. In another aspect, upon placing the tips in fluid communication with the fluid channels of the chip, through appropriate actuation of the diaphragm / valve complexes and / or the valve clusters, for example, fluids may be drawn or aspirated into the tips. In another aspect, actuation of the diaphragm / valve complexes and / or the valve clusters includes: a pumping actuation via, for example, the diaphragm pump(s) (in any number or combination), that may be repeated as desired for priming a fluid channel with a chip(s); and includes an opening actuation via, for example, the timed-valves, for achieving continuous flow. Once the desired volume is aspirated through each tip and into a fluidchannel and / or diaphragm pump, for example, the ingredient may be appropriately introduced into the broader chip(s) or dispensing system.

[0125] In one aspect, the present disclosure provides for a fluidic or microfluidic dispensing system for continuous flow including a housing that provides support for a chip. In another aspect, the housing also provides structure for the chip to be manipulated, such as in allowing for movement with respect to the pressurized reservoir, supply sources, or receiving regions. In another aspect, a pressurized reservoir is configured as a supply bottle having a pressurization harness including pressurization cap with supply lines (feed and return, for example). In another aspect, any suitable pressurization means and configuration or arrangement may be used for the pressurized reservoir.

[0126] In one aspect, the present disclosure provides for a fluidic or microfluidic dispensing system for continuous flow including a bottom manipulator, a top manipulator, and a wash station, for suitably interacting with a chip(s). In another aspect, the bottom manipulator and the top manipulator are constructed to appropriately manipulate or orientate a plate, for example. In another aspect, the bottom manipulator is constructed to hold a multiwell plate, from or into which ingredients may be aspirated or dispensed. In another aspect, the top manipulator is used to hold a chip(s) relative to the multiwell plate, for example. In another aspect, the bottom manipulator translates or orientates the multiwell plate in both a horizontal (y-axis) and a vertical (Z-axis) direction as desired. In another aspect, the top manipulator translates or orientates the chip in a horizontal (X-axis) direction that is perpendicular to that of the bottom manipulator. It can be appreciated that the bottom and top manipulators may be configured to move in any suitable manner such that the chip may be appropriately positioned. In another aspect, the bottom manipulator is configured to translate in any direction while the top manipulator is configured to remain stationary. In another aspect, the bottom manipulator and the top manipulator are both configured to individually translate and / or articulate in any appropriate direction or manner. In another aspect, the top manipulator is configured to translate and / or articulate in any direction while the bottom manipulator remains stationary.

[0127] In one aspect, the present disclosure also provides a fluidic and microfluidic dispensing system equipped with a sub-system for cleaning the fluid channel(s) of a chip(s). In another aspect, the wash fluid is run through supply lines, diaphragm pumps, fluid channels, valves, and outlets / nozzles once or any number of times. In another aspect, the wash fluid flows at a high pressure to suitably wash the components. In another aspect, diaphragm pumps and valves are appropriately actuated back and forth to suitably run or drive wash fluid. In another aspect, wash fluid may be flowed several times forward and / or backward through the supply lines, diaphragm pumps, fluid channels, valves, and / or outlets.

[0128] It should be appreciated that the wash fluid used for forward and / or reverse wash can include one or a combination of a variety of materials, such as, for example air and / or water. When ingredients to be dispensed are not suitably washed with air and / or water, then different types of purge ingredients may be used, such as acetone, ethanol, nitrogen, carbon dioxide, or other Suitable gaseous or fluidic ingredients or combinations thereof.

[0129] It should also be appreciated that the above aspects may be employed in any suitable combination, as the present disclosures are not limited in this respect. Also, any or all of the above aspects may be employed in a fluidic dispensing system for use with dispensing fluid to wells of a microplate; however, the present disclosures are not limited in this respect, as aspects may be used with any fluid channeling system, especially, those benefitting from continuous flow. Various aspects and embodiments of the disclosures will now be described in more detail with respect to the accompanying drawing figures. The disclosures are not, however, limited to the aspects and embodiments shown.III. With Reference to the Figures

[0130] United States Patent Grant Publications US8016260B2, US8100293B2, US8205856B2, and US8550298B2, are assigned to the Applicant of the present application, and are incorporated herein in their entirety by reference.

[0131] Turning now to the figures, FIG. 1 is an elevated front view of an illustration of an example microfluidic dispensing system for continuous flow, according to the present disclosure. The microfluidic dispensing system 10 includes a housing 1 that provides support for a continuous flow chip(s) 100 (best seen in FIG. 2). The housing 1 also provides a mechanized structure(s) for a multiwell plate 20 to be translated, oriented, and / or manipulated, such as in allowing for movement with respect to a pressurized reservoir 30 and the chip(s) 100.

[0132] In one aspect, the housing 1 also provides many sub-systems and sub-assemblies, for example, a pressure management sub-system at least for pressurizing the pressurized reservoir 30. As illustrated in FIG. 1, the pressurized reservoir 30 is configured as a supply bottle 31 having a pressurization harness 33 including pressurization cap 35 with a feed line 37 and a return line 39.

[0133] Moreover, as illustrated in FIG. 1, the housing 1 also provides a plate manipulator 40 configured to engage with and slide the plate 20 from the left side of the system 10 to the right side of the system 10 or in reverse. The plate manipulator 40 also is configured to translate or orientate the multiwell plate 20 in both a horizontal (e.g., slide direction) and a vertical direction (stack or unstack direction), as desired.

[0134] FIG. 2 is a magnified, elevated front view of an illustration of an example microfluidic dispensing system for continuous flow, according to the present disclosure. The microfluidic dispensing system 50 of FIG. 2 is similar to the system 10 of FIG. 1 except for the following differences.

[0135] Specifically, the microfluidic dispensing system 50 of FIG. 2 has a plurality of chips 200. The chips 200 include a continuous flow chip 200a and a precision dispensing chip 200b. The remainder of the chips 200 may be any other type of chip known to a person having ordinary skill in the art, including other continuous flow chips or precision dispensing chips.

[0136] As illustrated in FIG. 2, the system 50 also has a multiwell plate 20 and a platemanipulator 40 configured to engage with and slide the plate 20 from the right side of the system 50 to the left side of the system 50 as continuous flow dispense 201 is used to fill the wells 21 of the multiwell plate 20. Moreover, in another aspect, the system 50 also has a feed line 37 and a return line 39 corresponding to a pressurized reservoir 30 and that together establish a pressurized fluid circuit with the closed fluid channel (not shown, best seen in FIGS. 6A-7B) defined by the continuous flow chip 200a.

[0137] FIG. 3A is an elevated side view of an illustration of an example continuous flow chip with corresponding pressurized reservoir, according to the present disclosure. The pressurized reservoir 30 is similar to the reservoir 30 of FIG. 1 in that it is configured as a supply bottle 31 having a pressurization harness 33 including pressurization cap 35 with a feed line 37 and a return line 39. The feed line 37 and the return line 39 together establish a pressurized fluid circuit with a closed fluid channel (not shown, best seen in FIGS. 6A and 6B) within the continuous flow chip 300, such that a pressurized liquid flow (not shown, best seen in FIGS. 7A and 7B) can be introduced into the closed fluid channel. In this way, the continuous flow chip 300 is configured to achieve continuous flow dispense 201 (best seen FIG. 2) through one or more of its nozzles 302.

[0138] In one aspect, the continuous flow chip 300 also includes a chip substrate assembly 303 including an air side 305, whereby one or more pressurized air inputs are received (the source of the air pressure is not shown), and a liquid side 307 configured to receive the pressurized liquid flow for the closed fluid channel. As illustrated in FIG. 3A, the chip 300 also includes a plurality of diaphragm / valve complexes 320.

[0139] FIG. 3B is a magnified, see-through, elevated side view of an illustration of an example continuous flow chip, according to the present disclosure. The continuous flow chip 300 of FIG. 3B is similar to the chip 400 of FIGS. 4A and 4B except for the following differences.

[0140] The chip 400 defines therein a closed fluid channel (not shown, best seen in FIGS. 6A and 6B) such that a pressurized liquid flow (not shown, best seen in FIGS. 7A and 7B) can beintroduced into the closed fluid channel. In this way, the continuous flow chip 400 is configured to achieve continuous flow dispense 201 (best seen FIG. 2) through one or more of its nozzles 402.

[0141] In one aspect, the chip 400 also includes a chip substrate assembly 403 including an air side 405 and a liquid side 407, and a plurality of diaphragm / valve complexes 420. As illustrated in FIG. 3B, the chip 400 also includes a pressurized flow manifold 410 upon which a feed line 37 and a return line 39 of a pressurized reservoir (not shown; best seen in FIGS. 1 and 3 A) may engage to establish fluid communication with the chip substrate assembly 403. In this way, the chip 400 is configured to receive the pressurized liquid flow for the closed fluid channel.

[0142] FIG. 4A is a magnified, exploded, bottom perspective view of an illustration of an example continuous flow chip, according to the present disclosure. FIG. 4B is a magnified, exploded, top perspective view of an illustration of the example continuous flow chip, according to the present disclosure. The continuous flow chip 500 of FIG. 4A and FIG. 4B is similar to the chip 400 of FIG. 3B except for the following differences.

[0143] The chip 500 includes a nozzle piece 502, a chip substrate assembly 503 including an air side 505 and a liquid side 507, a pressurized flow manifold 510, and a plurality of diaphragm / valve complexes 520, with fluid access interposed along the closed fluid channel (not shown, best seen in FIGS. 6A-7B), on the liquid side 507 of the chip substrate assembly 503. As illustrated in FIG. 4A and FIG. 4B, the pressurized flow manifold 450 is the component of the chip 500 upon which a feed line 37 and a return line 39 of a pressurized reservoir (not shown; best seen in FIGS. 1 and 3A) may engage to establish fluid communication with the liquid side 507, in particular, of the chip substrate assembly 503. In this way, the chip 500 is configured to receive the pressurized liquid flow for the closed fluid channel defined by the chip substrate assembly.

[0144] In one aspect, the chip substrate assembly 503 specifically includes a top substrate layer 511, an intermediate substrate layer 513, and a bottom substrate layer 515. As illustrated in FIGS 4A and 4B, the top substrate layer 511 corresponds to the air side 505 and the intermediatesubstrate layer 513 and the bottom substrate layer 515 correspond to the liquid side 507. Moreover, as illustrated best in FIG. 4B, the closed fluid channel is defined at least in part by the intermediate substrate layer 513 and a fluid recess 522 on a surface of the bottom substrate layer 515.

[0145] In another aspect, the top substrate layer 511 includes ports 550 configured to receive one or more pressurized air inputs. As illustrated best in FIG. 4A, each of the plurality of diaphragm / valve complexes 520 has at least one corresponding port 550.

[0146] In another aspect, the air side 505 of the chip substrate assembly 503 may be made up of multiple stacked layers. Similarly, the liquid side 507 of the chip substrate assembly 503 may include the intermediate substrate layer 513, the bottom substrate layer 515, and other components or layers.

[0147] In another aspect, as illustrated in FIGS. 4A and 4B, the chip 500 may be assembled by: (i) providing an air side 505 configured to receive one or more pressurized air inputs, (ii) providing a liquid side 507, (iii) providing one or more diaphragm / valve complexes 520; (iv) stacking the air side 505 and the liquid side 507, with the one or more diaphragm / valve complexes 520 therebetween, such that a closed fluid channel is defined between the air side 505 and liquid side 507, and such that the one or more diaphragm / valve complexes 520 are interposed along the closed fluid channel on the liquid side of the chip substrate assembly; and (v) using bolts, screws, and / pegs to assemble the chip 500.

[0148] FIG. 5A is a top view of an illustration of an example diaphragm / valve complex for a continuous flow chip, according to the present disclosure. FIG. 5B is a perspective view of an illustration of the example diaphragm / valve complex for a continuous flow chip, according to the present disclosure. In particular, the diaphragm / valve complex 620 is for a continuous flow chip like that illustrated in FIGS. 1-4B, which includes a plurality of diaphragm valve complexes 620.

[0149] In one aspect, the diaphragm / valve complex 620 is configured as a single unitaryelastomeric valve cluster having one diaphragm pump 622 and three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves 623. As illustrated in FIGS. 5A and 5B, the valve 623a is configured as an input valve, the valve 623b is configured as an output valve, and the valve 623c is configured as a purge valve.

[0150] In another aspect, the one diaphragm pump 622 of the valve cluster allows for priming of the pathways (not shown, best seen in FIGS. 6A and 6B) within the valve cluster and, therefore, each diaphragm / valve complex 620 can facilitate priming of a closed fluid channel (not shown, best seen in FIGS. 7A-7B) within a broader continuous flow chip, for example.

[0151] FIG. 6A is a cut-away, perspective view of an illustration of an example diaphragm / valve complex of a plurality of diaphragm / valve complexes for a continuous flow chip, according to the present disclosure. FIG. 6B is a cut-away, perspective view of an illustration of the example diaphragm / valve complex of a plurality of diaphragm / valve complexes for a continuous flow chip, according to the present disclosure. In particular, the diaphragm / valve complex 720 (also referred to as the valve cluster) is for a continuous flow chip like that illustrated in FIGS. 1-5B, which includes a plurality of diaphragm / valve complexes 720.

[0152] In particular, FIG. 6A and 6B are cut-away perspective views of an illustration of an example unitary valve cluster, resting on the liquid side 707 of a continuous flow chip 700, having fluid access to (e.g., in fluid communication with) a closed fluid channel 721, and having one diaphragm pump 722 and an air-pressure actuated, individually-controllable, bi-directional, elastomeric input valve 723a, output valve 723b, and purge valve 723c. In FIG. 6A, the input valve 723a is illustrated as open and the output valve 723b and the purge valve 723c are illustrated as closed. In FIG. 6B, the input valve 723a, the output valve 723b, and the purge valve 723c are illustrated as open. In one aspect, the closed fluid channel 721 is defined at least in part by the intermediate substrate layer 713 and the bottom substrate layer 715.

[0153] In another aspect, the closed fluid channel 721 includes an input pathway 725(shown with arrows), and the input pathway 725 is defined in part by the diaphragm / valve complex 720. In particular, as illustrated in FIG. 6A, the input pathway 725 extends through the input valve 723 a and, therefore, the input pathway 725 can be opened based on actuation (e.g., opening) of the input valve 723a. Moreover, the closed fluid channel 721 also includes a dispense pathway 727 and a recirculation pathway 729, and the dispense pathway 727 and the recirculation pathway 729 are each defined in part by the diaphragm / valve complex 720. In particular, as illustrated in FIG. 6B, the dispense pathway 727 extends through the output valve 723b and, therefore, the dispense pathway 727 can be opened using the output valve 723b. Similarly, as illustrated in FIG. 6B, the recirculation pathway 729 extends through the purge valve 723c (“purge” in that it exits / purges from the valve cluster) and, therefore, the recirculation pathway 729 can be opened using the output valve 723b.

[0154] FIG. 7A is a top view of an illustration of an example first half of a continuous flow chip according to the present disclosure. FIG. 7B is a top view of an illustration of an example second half of a continuous flow chip according to the present disclosure. The chip 800 includes a chip substrate assembly 803 including an air side 805 and a liquid side 807 (not shown; best seen in FIGS. 4A and 4B), and a pressurized flow manifold 810 upon which a feed line 37 and a return line 39 engage to establish fluid communication with the liquid side 807.

[0155] In particular, in one aspect, the chip 800 is configured to receive a pressurized liquid flow in a closed fluid channel 821 defined by the chip substrate assembly 803. As illustrated in FIGS. 7A and 7B, the chip 800 is primed with pressurized liquid within all of the pathways of the closed fluid channel 821, and the pressurized liquid circulating / recirculating in a counter clockwise direction through the circuit established by the closed fluid channel 821. In another aspect, the pressurized liquid is circulating / recirculating in a clockwise direction (not shown) through the circuit established by the closed fluid channel 821. In another aspect, the pathways of the closed fluid channel 821 include an input pathway 825, a dispense pathway 827, and a recirculation pathway 829 for each of the eight (8) diaphragm / valve complexes (not shown; best seen in FIGS. 4 A and 4B).

[0156] In another aspect, the chip 800 has a recovery pathway (not shown) instead of a recirculation pathway 829, and, therefore, the pressurized liquid is capable of being recovered back to the pressurized reservoir from the closed fluid circuit established by the closed fluid channel 821. In this state, the pressurized liquid is neither flowing clockwise or counter clockwise; instead, it is recovered through both the feed line 37 and the return line 39, for example.

[0157] FIG. 8 is an elevated side view of an illustration of an example continuous flow chip, according to the present disclosure. The chip 900 defines therein a closed fluid channel (not shown, best seen in 11A-11F) such that a pressurized liquid flow (not shown, best seen in 11A- 1 IF) can be introduced into the closed fluid channel. In this way, the continuous flow chip 900 is configured to achieve continuous flow dispense (not shown; best seen FIG. 2) through its nozzles 902.

[0158] In one aspect, the chip 900 also includes a chip substrate assembly 903 including an air side 905 and a liquid side 907, and a diaphragm / valve complex (not shown; best see in 11 A- 1 IF). As illustrated in FIG. 8, the chip 900 also includes an input component 910 upon which a feed line of a pressurized reservoir (not shown; best seen in FIGS. 1 and 3A) may engage to establish fluid communication with the chip substrate assembly 903. In this way, the chip 900 is configured to receive the pressurized liquid flow for the closed fluid channel.

[0159] FIG. 9A is an exploded, bottom perspective view of an illustration of an example continuous flow chip, according to the present disclosure. FIG. 9B is an exploded, top perspective view of an illustration of the example continuous flow chip, according to the present disclosure. The chip 1000 includes a nozzle piece 1002, a chip substrate assembly 1003 including an air side 1005 and a liquid side 1007, an input component 1010, and a diaphragm / valve complex 1020 including two adjacent valve clusters 1030.

[0160] In one aspect, the diaphragm / valve complex 1020 has fluid access interposed along the closed fluid channel (not shown, best seen in FIGS. 11A-11F), and is situated on the liquidside 1007 of the chip substrate assembly 1003. As illustrated in FIGS. 9A and 9B, the valve cluster 1030a and the valve cluster 1030b are each configured as a single unitary elastomeric component.

[0161] In another aspect, the chip substrate assembly 1003 specifically includes a top substrate layer 1011, an intermediate substrate layer 1013, and a bottom substrate layer 1015. As illustrated in FIGS 9A and 9B, the top substrate layer 1011 corresponds to the air side 1005 and the intermediate substrate layer 1013 and the bottom substrate layer 1015 correspond to the liquid side 1007. Moreover, as illustrated best in FIG. 9B, the closed fluid channel is defined at least in part by the intermediate substrate layer 1013 and a fluid recess 1022 on a surface of the bottom substrate layer 1015.

[0162] In another aspect, the top substrate layer 1011 includes ports 1050 configured to receive one or more pressurized air inputs. As illustrated best in FIG. 9A, each of the two adjacent valve clusters 1030 has at least one corresponding port 1050.

[0163] In another aspect, as illustrated in FIGS. 9A and 9B, the chip 1000 may be assembled by: (i) providing an air side 1005 configured to receive one or more pressurized air inputs, (ii) providing a liquid side 1007, (iii) providing two adjacent valve clusters 1030; (iv) stacking the air side 1005 and the liquid side 1007, with the valve cluster 1030a and the valve cluster 1030b therebetween, such that a closed fluid channel is defined between the air side 1005 and liquid side 1007, and such that the valve cluster 1030a and the valve cluster 1030b are interposed along the closed fluid channel on the liquid side of the chip substrate assembly; and (v) snapping or friction fitting the air side 1005 to the liquid side 1007 (or vice versa) to assemble the chip 1000. In another aspect, not illustrated, the air side 1005 and the liquid side 1007 may be engaged via an adhesive, an ultrasonic method, laser bonding, or mechanical bolts or screws or pegs.

[0164] FIG. 10A is a top view of an illustration of an example diaphragm / valve complex for a continuous flow chip, according to the present disclosure. FIG. 10B is a perspective,wireframe view of an illustration of the example diaphragm / valve complex for a continuous flow chip, according to the present disclosure. In particular, the diaphragm / valve complex 1120 is for a continuous flow chip like that illustrated in FIGS. 8-9B, which includes a single diaphragm valve complex 1120.

[0165] In one aspect, the diaphragm / valve complex 1120 includes two adjacent valve clusters 1130 with each configured as a single unitary elastomeric valve cluster having one diaphragm pump 1122 and one air-pressure actuated, individually-controllable, elastomeric valve 1123. As illustrated in FIGS. 10A and 10B, the valve 1123a is part of valve cluster 1130a and is configured as an input valve for the diaphragm / valve complex 1120. Similarly, the valve 1123b is part of valve cluster 1130b and is configured as an output valve for the diaphragm / valve complex 1120.

[0166] In another aspect, the diaphragm pump 1122a or the diaphragm pump 1122b allows for priming of the pathways (not shown, best seen in FIGS. 11A-11F) of the diaphragm / valve complex 1120 and, therefore, each the valve cluster 1130a and the valve cluster 1130b can facilitate priming of a closed fluid channel (not shown, best seen in 1 1 A-l IF) within a broader continuous flow chip, for example. Moreover, in another aspect, the diaphragm pumps 1122 allow for metering and dispensing of discrete volumes of ingredients through outlets such as, for example, a nozzle and / or tip, and, therefore, the valve cluster 1130a and the valve cluster 1130b can facilitate metering and dispensing of discrete volumes from the closed fluid channel, for example. Furthermore, in another aspect, the diaphragm pumps 1122 allow for recovering fluids / liquids from pathways of the closed fluid channel such as, for example, from the nozzle and / or tip, and, therefore, the valve cluster 1130a and the valve cluster 1130b can facilitate recovering fluid from the closed fluid channel, for example.

[0167] FIG. 11A is a cut-away, schematic view of an illustration of an example diaphragm / valve complex having two adjacent valve clusters, each with a valve in a closed configuration, and having a primed closed fluid channel, according to the present disclosure. FIG.1 IB is a cut-away, schematic view of an illustration of the example diaphragm / valve complex having two adjacent valve clusters, each with a valve in an open configuration for continuous flow dispense, and having a primed closed fluid channel, according to the present disclosure. FIG. 11C is a cut-away, schematic view of an illustration of the example diaphragm / valve complex having two adjacent valve clusters, each with a valve in the closed configuration for stopping the continuous flow dispense, and having a primed closed fluid channel, according to the present disclosure. FIG. 11D is a cut-away, schematic view of an illustration of the example diaphragm / valve complex having two adjacent valve clusters, one with an output valve in an open configuration for opening access to a dispense pathway without dispensing, according to the present disclosure. FIG. HE is a cut-away, schematic view of an illustration of the example diaphragm / valve complex having two adjacent valve clusters, one with the output valve in an open configuration and one with a small diaphragm pump in an open configuration for drawing liquid from the dispense pathway, according to the present disclosure. FIG. 1 IF is a cut-away, schematic view of an illustration of the example diaphragm / valve complex having two adjacent valve clusters, one with the output valve in an open configuration and one with a large diaphragm pump in open configuration for drawing liquid from the dispense pathway, according to the present disclosure. As illustrated in FIGS. 11A-11F, the prime closed fluid channel is represented with slanted cross hatching, and the open configuration is represented by horizontal cross hatching.

[0168] FIG. 12 is a flowchart of an example method 1200 for achieving continuous flow in a chip, comprising:

[0169] At step 1210, assembling a chip substrate assembly, wherein assembling the chip substrate assembly comprises: (i) providing an air side configured to receive one or more pressurized air inputs, (ii) providing a liquid side, (iii) providing one or more diaphragm / valve complexes; and (iv) stacking the air side and the liquid side, with the one or more diaphragm / valve complexes therebetween, such that a closed fluid channel is defined between the air side and liquid side, and such that the one or more diaphragm / valve complexes are interposed along the closed fluid channel on the liquid side of the chip substrate assembly;

[0170] At step 1220, providing a pressurized liquid flow to the closed fluid channel of the chip substrate assembly, the closed fluid channel comprising an input pathway and a dispense pathway; and

[0171] At step 1230, actuating the one or more diaphragm / valve complexes.

[0172] In one aspect, each of the one or more diaphragm / valve complexes includes two adjacent valve clusters, and step 1230 includes actuating the two adjacent valve clusters.

[0173] In another aspect, the chip includes two or more diaphragm / valve complexes, and each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, and step 1230 includes actuating the plurality of valve clusters or any combination thereof.

[0174] In another aspect, the chip includes two or more diaphragm / valve complexes, and each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, and each of the plurality of valve clusters includes one diaphragm pump and three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves, and step 1230 includes actuating at least two of the three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves.IV. Embodiments

[0175] Clause 1. A chip for continuous flow, comprising: (a) a chip substrate assembly defining a closed fluid channel, the chip substrate assembly comprising: (i) an air side, whereby one or more pressurized air inputs are received; and (ii) a liquid side, the liquid side configured toreceive a pressurized liquid flow for the closed fluid channel; and (b) one or more diaphragm / valve complexes interposed along the closed fluid channel on the liquid side of the chip substrate assembly; wherein each of the one or more diaphragm / valve complexes comprises at least one diaphragm pump and at least two air-pressure actuated, individually-controllable, elastomeric valves; and wherein the closed fluid channel comprises an input pathway and a dispense pathway.

[0176] Clause 2. The chip for continuous flow of clause 1, wherein each of the one or more diaphragm / valve complexes comprises two adjacent valve clusters, and wherein each of the two adjacent valve clusters comprises one diaphragm pump and one air-pressure actuated, individually-controllable, elastomeric valve.

[0177] Clause 3. The chip for continuous flow of clause 2, wherein each of the two adj acent valve clusters is configured as a single unitary elastomeric component between the air side and the liquid side of the chip.

[0178] Clause 4. The chip for continuous flow of clause 2, wherein the chip substrate assembly comprises a top substrate layer and a bottom substrate layer, the top substrate layer corresponding to the air side and the bottom substrate layer corresponding to the liquid side, and wherein the chip substrate assembly defines the closed fluid channel therebetween.

[0179] Clause 5. The chip for continuous flow of clause 2, wherein the chip substrate assembly comprises a top substrate layer, an intermediate substrate layer, and a bottom substrate layer, the top substrate layer corresponding to the air side and the bottom substrate layer corresponding to the liquid side, and wherein the chip substrate assembly defines the closed fluid channel therebetween.

[0180] Clause 6. The chip for continuous flow of clause 5, wherein the closed fluid channel is defined at least in part by the intermediate substrate layer and a fluid recess on a surface of the bottom substrate layer.

[0181] Clause 7. The chip for continuous flow of clause 4, wherein the top substrate layer comprises ports configured to receive the one or more pressurized air inputs.

[0182] Clause 8. The chip for continuous flow of clause 7, wherein each of the two adjacent valve clusters has a corresponding port.

[0183] Clause 9. The chip for continuous flow of clause 8, wherein the one diaphragm pump and the one air-pressure actuated, individually-controllable, elastomeric valve of each of the two adjacent valve clusters has a corresponding port.

[0184] Clause 10. The chip for continuous flow of clause 1, wherein the chip comprises two or more diaphragm / valve complexes, wherein each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, wherein each of the plurality of valve clusters comprises one diaphragm pump and three air-pressure actuated, individually- controllable, bi-directional, elastomeric valves; and wherein the closed fluid channel also comprises a recirculation / recovery pathway.

[0185] Clause 11. The chip for continuous flow of clause 10, wherein the chip substrate assembly comprises a top substrate layer and a bottom substrate layer, the top substrate layer corresponding to the air side and the bottom substrate layer corresponding to the liquid side, and wherein the chip substrate assembly defines the closed fluid channel therebetween.

[0186] Clause 12. The chip for continuous flow of clause 11, wherein the closed fluid channel is defined at least in part by the top substrate layer and a fluid recess on a surface of the bottom substrate layer.

[0187] Clause 13. The chip for continuous flow of clause 11, wherein the top substrate layer comprises ports configured to receive the one or more pressurized air inputs.

[0188] Clause 14. The chip for continuous flow of clause 13, wherein each of the two or more diaphragm / valve complexes has a corresponding port.

[0189] Clause 15. The chip for continuous flow of clause 13, wherein each of the plurality of valve clusters has a corresponding port.

[0190] Clause 16. The chip for continuous flow of clause 15, wherein the one diaphragm pump and each of the three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves of each of the plurality of valve clusters has a corresponding port.

[0191] Clause 17. A method for achieving continuous flow in a chip, comprising: (a) assembling a chip substrate assembly, wherein assembling the chip substrate assembly comprises: (i) providing an air side configured to receive one or more pressurized air inputs; (ii) providing a liquid side; (iii) providing one or more diaphragm / valve complexes; and (iv) stacking the air side and the liquid side, with the one or more diaphragm / valve complexes therebetween, such that a closed fluid channel is defined between the air side and liquid side, and such that the one or more diaphragm / valve complexes are interposed along the closed fluid channel on the liquid side of the chip substrate assembly; and (b) providing a pressurized liquid flow to the closed fluid channel of the chip substrate assembly, the closed fluid channel comprising an input pathway and a dispense pathway; and (c) actuating the one or more diaphragm / valve complexes.

[0192] Clause 18. The method of clause 17, wherein each of the one or more diaphragm / valve complexes comprises two adjacent valve clusters, and wherein actuating the one or more diaphragm / valve complexes comprises actuating the two adjacent valve clusters.

[0193] Clause 19. The method of clause 17, wherein the chip comprises two or more diaphragm / valve complexes, wherein each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, and wherein actuating the one or morediaphragm / valve complexes comprises actuating the plurality of valve clusters.

[0194] Clause 20. The method of clause 17, wherein the chip comprises two or more diaphragm / valve complexes, wherein each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, wherein each of the plurality of valve clusters comprises one diaphragm pump and three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves, and wherein actuating the one or more diaphragm / valve complexes comprises actuating at least two of the three air-pressure actuated, individually- controllable, bi-directional, elastomeric valves.

[0195] Clause 21. A chip for continuous flow, comprising: (a) a chip substrate assembly defining a closed fluid channel, the chip substrate assembly comprising: (i) an air side, whereby one or more pressurized air inputs are received; and (ii) a liquid side, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and (b) one or more unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming one or more diaphragm / valve complexes interposed along the closed fluid channel on the liquid side of the chip substrate assembly; wherein each of the one or more diaphragm / valve complexes comprises two adjacent valve clusters, and wherein each of the two adjacent valve clusters comprises one diaphragm pump and one air-pressure actuated, individually-controllable, elastomeric valve; and wherein the closed fluid channel comprises an input pathway and a dispense pathway.

[0196] Clause 22. A chip for continuous flow, comprising: (a) a chip substrate assembly defining a closed fluid channel, the chip substrate assembly comprising: (i) an air side, whereby one or more pressurized air inputs are received; and (ii) a liquid side, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and (b) two or more unitary elastomeric component between the air side and the liquid side of the chip substrate assemblyforming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, wherein each of the plurality of valve clusters comprises one diaphragm pump and three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves; and wherein the closed fluid channel comprises an input pathway, a recirculation / recovery pathway, and a dispense pathway.

[0197] Clause 23. A chip for channeling and dispensing fluids, comprising: a substrate sub-assembly, comprising: a top substrate layer; and a bottom substrate layer defining a fluid recess, wherein the substrate sub-assembly defines a closed fluid channel therebetween; and wherein the substrate sub-assembly comprises an air side incorporating the top substrate layer, whereby one or more pressurized air inputs are received, and a liquid side incorporating the bottom substrate layer, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and one or more unitary elastomeric components between the top substrate layer and the bottom substrate layer forming one or more diaphragm / valve complexes with fluid access interposed along the closed fluid channel of the substrate sub-assembly; wherein each of the one or more diaphragm / valve complexes comprises at least one diaphragm pump and at least two air- pressure actuated, individually-controllable, elastomeric valves; and wherein the closed fluid channel comprises at least an input pathway and a dispense pathway.

[0198] Clause 24. A chip for channeling and dispensing fluids, comprising: a substrate sub-assembly, comprising: a top substrate layer; and a bottom substrate layer defining a fluid recess, wherein the substrate sub-assembly defines a closed fluid channel therebetween; and wherein the substrate sub-assembly comprises an air side incorporating the top substrate layer, whereby one or more pressurized air inputs are received, and a liquid side incorporating the bottom substrate layer, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and one or more unitary elastomeric components between the top substrate layer and the bottom substrate layer forming one or more diaphragm / valve complexes with fluid access interposed along the closed fluid channel of the substrate sub-assembly; wherein each of the one or more diaphragm / valve complexes comprises two adjacent valve clusters, and wherein each ofthe two adjacent valve clusters comprises one diaphragm pump and one air-pressure actuated, elastomeric valve; and wherein the closed fluid channel comprises an input pathway and a dispense pathway.

[0199] Clause 25. A chip for channeling, recovering, and dispensing fluids, comprising: a substrate sub-assembly, comprising: a top substrate layer; and a bottom substrate layer defining a fluid recess, wherein the substrate sub-assembly defines a closed fluid channel therebetween; and wherein the substrate sub-assembly comprises an air side incorporating the top substrate layer, whereby one or more pressurized air inputs are received, and a liquid side incorporating the bottom substrate layer, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and two or more unitary elastomeric components between the top substrate layer and the bottom substrate layer forming a plurality of valve clusters with fluid access interposed along the closed fluid channel of the substrate sub-assembly; wherein each of the plurality of valve clusters comprises one diaphragm pump and three air-pressure actuated, individually-controllable, bidirectional, elastomeric valves; and wherein the closed fluid channel comprises an input pathway, a recirculation / recovery pathway, and a dispense pathway.

[0200] Clause 26. A chip for channeling, recovering, and dispensing fluids, comprising: a substrate sub-assembly, comprising: a top substrate layer; and a bottom substrate layer defining a fluid recess, wherein the substrate sub-assembly defines a closed fluid channel therebetween; and wherein the substrate sub-assembly comprises an air side incorporating the top substrate layer, whereby one or more pressurized air inputs are received, and a liquid side incorporating the bottom substrate layer, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and two or more unitary elastomeric components between the top substrate layer and the bottom substrate layer forming a plurality of valve clusters with fluid access interposed along the closed fluid channel of the substrate sub-assembly; wherein each of the plurality of valve clusters comprises two diaphragm pumps and two air-pressure actuated, individually-controllable, bidirectional, elastomeric valves; and wherein the closed fluid channel comprises an input pathway, a recirculation / recovery pathway, and a dispense pathway.

[0201] It should be emphasized that the above-described embodiments of the present disclosure are merely possible examples of implementations set forth for a clear understanding of the principles of the disclosure. Many variations and modifications may be made to the abovedescribed embodiment(s) without departing substantially from the spirit and principles of the disclosure. All such modifications and variations are intended to be included herein within the scope of this disclosure and protected by the following claims.

Claims

CLAIMSTherefore, the following is claimed:

1. A chip for continuous flow, comprising: a. a chip substrate assembly defining a closed fluid channel, the chip substrate assembly comprising: i. an air side, whereby one or more pressurized air inputs are received; and ii. a liquid side, the liquid side configured to receive a pressurized liquid flow for the closed fluid channel; and b. one or more diaphragm / valve complexes interposed along the closed fluid channel on the liquid side of the chip substrate assembly; wherein each of the one or more diaphragm / valve complexes comprises at least one diaphragm pump and at least two air-pressure actuated, individually-controllable, elastomeric valves; and wherein the closed fluid channel comprises an input pathway and a dispense pathway.

2. The chip for continuous flow of claim 1, wherein each of the one or more diaphragm / valve complexes comprises two adjacent valve clusters, and wherein each of the two adjacent valve clusters comprises one diaphragm pump and one air-pressure actuated, individually-controllable, elastomeric valve.

3. The chip for continuous flow of claim 2, wherein each of the two adjacent valve clusters is configured as a single unitary elastomeric component between the air side and the liquid side of the chip.

4. The chip for continuous flow of claim 2, wherein the chip substrate assembly comprises a top substrate layer and a bottom substrate layer, the top substrate layer corresponding to the air side and the bottom substrate layer corresponding to the liquid side, and wherein the chip substrate assembly defines the closed fluid channeltherebetween.

5. The chip for continuous flow of claim 2, wherein the chip substrate assembly comprises a top substrate layer, an intermediate substrate layer, and a bottom substrate layer, the top substrate layer corresponding to the air side and the bottom substrate layer corresponding to the liquid side, and wherein the chip substrate assembly defines the closed fluid channel therebetween.

6. The chip for continuous flow of claim 5, wherein the closed fluid channel is defined at least in part by the intermediate substrate layer and a fluid recess on a surface of the bottom substrate layer.

7. The chip for continuous flow of claim 4, wherein the top substrate layer comprises ports configured to receive the one or more pressurized air inputs.

8. The chip for continuous flow of claim 7, wherein each of the two adjacent valve clusters has a corresponding port.

9. The chip for continuous flow of claim 8, wherein the one diaphragm pump and the one air-pressure actuated, individually-controllable, elastomeric valve of each of the two adjacent valve clusters has a corresponding port.

10. The chip for continuous flow of claim 1, wherein the chip comprises two or more diaphragm / valve complexes, wherein each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, wherein each of the plurality of valve clusters comprises one diaphragm pump and three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves; and wherein the closed fluid channel also comprises a recirculation / recovery pathway.

11. The chip for continuous flow of claim 10, wherein the chip substrate assembly comprises a top substrate layer and a bottom substrate layer, the top substrate layer corresponding to the air side and the bottom substrate layer corresponding to the liquid side, and wherein the chip substrate assembly defines the closed fluid channeltherebetween.

12. The chip for continuous flow of claim 11, wherein the closed fluid channel is defined at least in part by the top substrate layer and a fluid recess on a surface of the bottom substrate layer.

13. The chip for continuous flow of claim 11 , wherein the top substrate layer comprises ports configured to receive the one or more pressurized air inputs.

14. The chip for continuous flow of claim 13, wherein each of the two or more diaphragm / valve complexes has a corresponding port.

15. The chip for continuous flow of claim 13, wherein each of the plurality of valve clusters has a corresponding port.

16. The chip for continuous flow of claim 15, wherein the one diaphragm pump and each of the three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves of each of the plurality of valve clusters has a corresponding port.

17. A method for achieving continuous flow in a chip, comprising: a. assembling a chip substrate assembly, wherein assembling the chip substrate assembly comprises: i. providing an air side configured to receive one or more pressurized air inputs; ii. providing a liquid side; iii. providing one or more diaphragm / valve complexes; and iv. stacking the air side and the liquid side, with the one or more diaphragm / valve complexes therebetween, such that a closed fluid channel is defined between the air side and liquid side, and such that the one or more diaphragm / valve complexes are interposed along the closed fluid channel on the liquid side of the chip substrate assembly; and b. providing a pressurized liquid flow to the closed fluid channel of the chip substrate assembly, the closed fluid channel comprising an input pathway and a dispense pathway; andc. actuating the one or more diaphragm / valve complexes.

18. The method of claim 17, wherein each of the one or more diaphragm / valve complexes comprises two adjacent valve clusters, and wherein actuating the one or more diaphragm / valve complexes comprises actuating the two adjacent valve clusters.

19. The method of claim 17, wherein the chip comprises two or more diaphragm / valve complexes, wherein each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, and wherein actuating the one or more diaphragm / valve complexes comprises actuating the plurality of valve clusters.

20. The method of claim 17, wherein the chip comprises two or more diaphragm / valve complexes, wherein each of the two or more diaphragm / valve complexes is configured as a single unitary elastomeric component between the air side and the liquid side of the chip substrate assembly forming a plurality of valve clusters interposed along the closed fluid channel on the liquid side of the chip substrate assembly, wherein each of the plurality of valve clusters comprises one diaphragm pump and three air-pressure actuated, individually-controllable, bi-directional, elastomeric valves, and wherein actuating the one or more diaphragm / valve complexes comprises actuating at least two of the three air- pressure actuated, individually-controllable, bi-directional, elastomeric valves.

Images