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WO2025085451A1 - Système de manipulation de fluide à l'échelle micrométrique - Google Patents

Système de manipulation de fluide à l'échelle micrométrique Download PDF

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Publication number
WO2025085451A1
WO2025085451A1 PCT/US2024/051441 US2024051441W WO2025085451A1 WO 2025085451 A1 WO2025085451 A1 WO 2025085451A1 US 2024051441 W US2024051441 W US 2024051441W WO 2025085451 A1 WO2025085451 A1 WO 2025085451A1
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WO
WIPO (PCT)
Prior art keywords
thermopneumatic
interface
microfluidic chip
pneumatic
deformable layer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/051441
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English (en)
Inventor
Bruce K. Gale
Christopher J. LAMBERT
Gregory A. LIDDIARD
Bahareh KAZEMI
Sabin NEPAL
Munawar JAWAD
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Utah Research Foundation Inc
Original Assignee
University of Utah Research Foundation Inc
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Publication date
Application filed by University of Utah Research Foundation Inc filed Critical University of Utah Research Foundation Inc
Publication of WO2025085451A1 publication Critical patent/WO2025085451A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/65—Mixers with shaking, oscillating, or vibrating mechanisms the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B01F33/304—Micromixers the mixing being performed in a mixing chamber where the products are brought into contact
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B01F33/305—Micromixers using mixing means not otherwise provided for
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874—Three dimensional network
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1838—Means for temperature control using fluid heat transfer medium
    • B01L2300/185—Means for temperature control using fluid heat transfer medium using a liquid as fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1894—Cooling means; Cryo cooling
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B01L9/527—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for microfluidic devices, e.g. used for lab-on-a-chip
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00346—Heating or cooling arrangements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1044—Using pneumatic means

Definitions

  • the present disclosure relates to fluid handling devices and, more particularly, to microfluidic devices for performing assays.
  • Microfluidic systems leverage the behavior of fluids at the microscale to perform a variety of operations that are typically carried out in traditional laboratories.
  • microfluidic systems described in this specification operate with small fluid volumes, often in the microliter to nanoliter range. This not only reduces the amount of sample material required, but also the volume of expensive reagents. Reducing the consumption of reagents and generation of waste also makes microfluidic systems described in this specification more ecologically friendly compared to traditional benchtop assays.
  • microfluidic channels and chambers described in this specification also result in high surface-to-volume ratios, which can speed up reactions. For example, diffusion distances may be shorter at higher surface-to-volume ratios, so reactions that might take hours in a conventional setting can occur within minutes.
  • microfluidic systems described in this specification may have multiple channels or chambers operating in parallel, thus facilitating high-throughput analysis. Additionally, microfluidic systems described in this specification allow for the precise control over fluid flow, mixing, and/or temperatures — enhancing their performance when used with sensitive or intricate assays. The closed nature of the microfluidic systems described in this specification and their reduced need for manual handling can minimize the risk of contamination, enhancing the reliability and reproducibility of results.
  • a thermopneumatic interface includes one or more pneumatic inlet ports in fluid communication with one or more pneumatic outlet ports and a cooling loop extending through the thermopneumatic interface.
  • the cooling loop is configured to maintain the thermopneumatic interface at a baseline temperature.
  • the one or more pneumatic outlet ports are configured to contact a surface of a microfluidic chip.
  • Each pneumatic inlet port is configured to receive a change in pressure and provide the changed pressure to a corresponding pneumatic outlet port.
  • the thermopneumatic interface is configured to maintain the microfluidic chip at the baseline temperature.
  • the microfluidic chip includes one or more inlets fluidly coupled to one or more mixing chambers via a plurality of pumping chambers and a deformable layer configured to be positioned between the plurality of pumping chambers and the one or more pneumatic outlets.
  • the one or more pneumatic outlets are configured to deform portions of the deformable layer proximate the plurality of pumping chambers to change pressure within the pumping chambers.
  • the one or more pneumatic outlets are configured to sequentially deform portions of the deformable layer proximate the plurality of pumping chambers to sequentially change pressure within the pumping chambers to transport fluid from the one or more inlets to the plurality of mixing chambers.
  • the mixing chambers include a cooled chamber.
  • the thermopneumatic interface includes a heat transfer structure configured to transfer heat from the cooled chamber to coolant within the cooling loop.
  • the heat transfer structure is configured to contact a portion of the deformable layer proximate the cooled chamber and coolant within the cooling loop.
  • the heat transfer structure includes a surface configured to contact the portion of the deformable layer proximate the cooled chamber and a fin configured to contact coolant within the cooling loop.
  • the mixing chambers include a heated chamber.
  • the thermopneumatic interface includes a heating element configured to transfer heat to the heated chamber.
  • the heating element includes an electric resistance-type heater.
  • each pneumatic outlet port includes a ledge and a plurality of projections protruding from the ledge.
  • the plurality of projections are configured to substantially prevent the deformable layer from blocking an opening of the pneumatic outlet port in fluid communication with a corresponding pneumatic inlet port.
  • the thermopneumatic interface includes a raised lip portion protruding from a surface of the thermopneumatic interface, the raised lip portion surrounding one of the pneumatic outlet ports.
  • the raised lip portion is configured to deform a portion of the deformable layer to provide a fluid seal between the one pneumatic outlet port and the deformable layer.
  • the thermopneumatic interface includes an indexing feature protruding away from a surface of the thermopneumatic interface configured to face the microfluidic chip.
  • the microfluidic chip includes a corresponding indexing feature.
  • the corresponding indexing feature of the microfluidic chip is configured to engage the indexing feature of the thermopneumatic interface.
  • a microscale fluid handling system includes a thermopneumatic interface, a microfluidic chip, and a clamping mechanism.
  • the thermopneumatic interface includes one or more pneumatic inlet ports in fluid communication with one or more pneumatic outlet ports, each pneumatic inlet port being configured to receive a change in pressure and provide the changed pressure to a corresponding pneumatic outlet port and a cooling loop extending through the thermopneumatic interface, the cooling loop being configured to maintain the thermopneumatic interface at a baseline temperature.
  • the microfluidic chip includes one or more inlets fluidly coupled to one or more mixing chambers via a plurality of pumping chambers and a deformable layer.
  • the clamping mechanism is configured to position the thermopneumatic interface in removable contact with the microfluidic chip such that the one or more pneumatic outlet ports are positioned to contact the deformable layer of the microfluidic chip and deform portions of the deformable layer proximate the plurality of pumping chamber to change pressure within the pumping chambers and the thermopneumatic interface is positioned to maintain the microfluidic chip at the baseline temperature.
  • the clamping mechanism includes a top plate and a bottom plate.
  • the thermopneumatic interface and the microfluidic chip are secured between the top plate and the bottom plate.
  • the thermopneumatic interface and the microfluidic chip are removable from the clamping mechanism.
  • FIG. 1 is an exploded view of an example microfluidic system for performing assays, library preparation for mRNA sequencing, and/or other reactions.
  • FIG. 2 is an isometric view of the microfluid system of FIG. 1 in an assembled configuration.
  • FIG. 3 is a bottom view of the assembled microfluidic chip of FIGS. 1 and 2.
  • FIG. 4 is an isometric view of the thermopneumatic interface of FIGS. 1 and 2.
  • FIG. 5 is a detail view, taken at reference FIG. 5 in FIG. 4, illustrating details that may be associated with some examples of the thermopneumatic interface of FIGS. 1 and 2.
  • FIG. 6 is an isometric view of the thermopneumatic interface of FIGS. 1 and 2 showing coolant flowing through a cooling loop.
  • FIG. 7 is a cross-sectional view of a portion of the thermopneumatic interface of FIGS. 1 and 2 taken at section line 7-7 of FIG. 4.
  • FIG. 8 is a schematic illustration showing a heat transfer structure in contact with a cooled chamber and coolant within a fluid channel.
  • FIG. 9 is a cross-sectional view of a portion of the thermopneumatic interface of FIGS. 1 and 2 taken at section line 9-9 of FIG. 4.
  • FIG. 10 is a top view showing the thermopneumatic interface of FIGS. 1 and 2.
  • FIG. 11 is a perspective view showing a portion of the thermopneumatic interface of
  • FIG. 12 is a perspective view of the thermopneumatic interface of FIGS. 1 and 2.
  • FIG. 13 is a schematic illustration showing heating elements received in openings of a thermopneumatic interface.
  • FIG. 14 is an isometric view of an assembled microfluidic system.
  • FIG. 15 is a cross-sectional view of the example microfluidic system of FIG. 14 taken at line 15-15.
  • FIG. 16 is an isometric view of the thermopneumatic interface of FIGS. 14 and 15.
  • FIG. 17 is a top view of the microfluidic chip of FIGS. 14 and 15.
  • FIG. 1 is an exploded view of an example microfluidic system 100 for performing assays, library preparation for mRNA sequencing, and/or other reactions. As illustrated in FIG.
  • FIG. 1 various implementations of the system 100 include a top plate (not shown in FIG. 1), a microfluidic chip 102, a thermopneumatic interface 104, and/or a bottom plate 106.
  • FIG. 2 is an isometric view of the microfluidic system 100 of FIG. 1 in an assembled configuration. In the assembled configuration, the microfluidic chip 102 (not visible in FIG. 2) and the thermopneumatic interface 104 may be positioned between the top plate 202 and the bottom plate 106. In some embodiments, the microfluidic chip 102 may be positioned between the top plate 202 and the thermopneumatic interface 104.
  • the top plate 202 may apply pressure to a top surface of the microfluidic chip 102 and the bottom plate 106 may apply pressure to a bottom surface of the thermopneumatic interface 104 so that a bottom surface of the microfluidic chip 102 securely contacts a top surface of the thermopneumatic interface 104.
  • the top plate 202 and/or the bottom plate 106 may be formed of a polymer or a metal.
  • the top plate 202 and/or the bottom plate 106 may be formed of a material having sufficient stiffness to apply pressure to the microfluidic chip 102 and the thermopneumatic interface 104 to ensure a fluidic seal between the layers without substantial deformation.
  • the microfluidic chip 102 may be formed as a plurality of stacked laminate layers.
  • the microfluidic chip 102 includes an upper layer 110, a middle layer 112, and a bottom layer 114.
  • a biocompatible, sterile, non-cytotoxic, and/or thermally conductive and stable material may be selected for the upper layer 110, middle layer 112, and/or bottom layer 114.
  • a material having relatively low contact angles and high surface tensions with water such as a hydrophilic material
  • a material having relatively high contact angles and low surface tensions with water such as a hydrophobic material
  • the upper layer 110 may be formed from a polyester material, such as a hydrophilic polyester or a hydrophobic polyester.
  • the middle layer 112 may be formed from a polyester material, such as a hydrophilic polyester or a hydrophobic polyester. Examples of suitable polyester materials for the upper layer 110 and/or the middle layer 112 include the Microfluidic Diagnostic Film 9960 and/or the Microfluidic Diagnostic Tape 9965, both commercially available from the 3M Company of Minneapolis, Minnesota.
  • suitable materials for the upper layer 110 and the middle layer 112 may include rigid or semi-rigid biocompatible materials with chemical resistance, such as polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polycarbonate (PC), polyethylene terephthalate (PET), polyimide (PI), glass, polyethylene (PE), polypropylene (PP), thermoplastic elastomers (TPE), etc.
  • PDMS polydimethylsiloxane
  • PMMA polymethyl methacrylate
  • COC cyclic olefin copolymer
  • COP cyclic olefin polymer
  • PC polyethylene terephthalate
  • PET polyimide
  • glass glass
  • PE polyethylene
  • PP polypropylene
  • TPE thermoplastic elastomers
  • bottom layer 114 may be formed from a deformable hydrophilic polymer.
  • the bottom layer 114 may be formed as a partially crosslinked silicone layer or a fully cross-linked silicone layer.
  • suitable materials for the bottom layer 114 include PDMS, TPE, PU, other silicone rubber materials, latex rubber materials, fluorinated ethylene propylene (FEP) films, ethylene-vinyl acetate (EVA), etc.
  • the upper layer 1 10, middle layer 1 12, and/or bottom layer 114 may be formed of a substantially transparent material.
  • the upper layer 110, middle layer 112, and/or bottom layer 114 may be formed of a substantially opaque material.
  • the upper layer 110, middle layer 112, and/or bottom layer 114 may be formed of substantially transparent portions (for example, aligning with the inlets, fluid channels, valves, chambers, and/or outlets as will be described later in the specification) and substantially opaque portions. By providing substantially transparent portions, the user may be able to visually verify correct fluid transport in the microfluidic chip 102.
  • the upper layer 110 may be adhered to the middle layer 112 by an adhesive
  • the bottom layer 114 may be adhered to the middle layer 112 (e.g., on a side opposite the upper layer 110) by an adhesive.
  • suitable adhesives include pressuresensitive acrylate and/or silicone adhesives.
  • the adhesive bonds may be enhanced by plasma treatment.
  • plasma treatment may be provided to each of the layers to improve the bonding between the adhesive and the layer.
  • adhesives may be selectively removed (e.g., from portions of the layers defining the various chambers and fluid channels as will be described further on in this specification).
  • sensors may be provided on the microfluidic chip 102 (for example, at the transparent portions).
  • the upper layer 110, middle layer 112, and/or bottom layer 114 may be laser cut to form the microfluidic chip 102.
  • the upper layer 110, middle layer 112, and/or bottom layer 114 may be formed from rolls of base material in a reel-to-reel manufacturing process.
  • the microfluidic chip 102 may be a disposable one-time-use device. In some embodiments, the microfluidic chip 102 may be reusable.
  • FIG. 3 is a bottom view of the assembled microfluidic chip 102 of FIGS. 1 and 2.
  • the microfluidic chip 102 includes one or more inlets 302, one or more fluid channels 304, one or more inlet chambers (such as valves 306), one or more pumping chambers 308, one or more mixing chambers (such as cooled chambers 312 and heated chambers 314), and one or more outlets 316.
  • a fluid channel 304 may fluidly couple each inlet 302 to a corresponding valve 306.
  • One or more fluid channels 304 may fluidly couple the valves 306 to the pumping chambers 308.
  • One or more fluid channels 304 may fluidly couple the pumping chambers 308 in a sequential manner (such that an n — 1-th pumping chamber 308 is fluidly coupled to an n-th pumping chamber 308, the n-th pumping chamber 308 is fluidly coupled to an n + 1-th pumping chamber 308, and so on).
  • One or more fluid channels 304 may fluidly couple the pumping chambers 308 to the mixing chambers.
  • the pumping chambers 308 may be fluidly coupled to one or more of the cooled chambers 312 and/or one or more of the heated chambers 314 via one or more fluid channels 304.
  • each cooled chamber 312 and/or heated chamber 314 may be fluidly coupled to at least one other chamber by one or more fluid channels 304.
  • a chamber (such as valve 310) may be positioned between each pair of fluidly coupled mixing chambers 312 and/or 314.
  • Mixing chambers 312-314 may function by transporting fluid back and forth between the various chambers. For example, as shown in the example of FIG.
  • pumping chambers 308 may alternate between transporting fluid (e.g., according to mechanics that will be described further on in this specification) towards the mixing chambers 312-314 and away from mixing chambers 312-314. This fluid transport causes fluid to be passed back and forth between pairs of mixing chambers 312 and/or 314 (e.g., through corresponding fluid channels 304 and valves 310).
  • the one or more inlets 302 may be formed as openings extending through the middle layer 112 and/or the bottom layer 114. In some embodiments, the one or more inlets 302 are formed as openings extending through the upper layer 110. In some examples, the one or more fluid channels 304 may be formed between the upper layer 110 and the middle layer 112. In some embodiments, the one or more chambers and/or valves 306-314 may be formed between the upper layer 110 and the middle layer 112. In various implementations, the one or more outlets 316 may be formed as openings extending through the middle layer 112 and/or the bottom layer 114. In some embodiments, the one or more outlets 316 may be formed as openings extending through the upper layer 110.
  • one or more of the chambers and/or valves 306-314 may include one or more openings extending through the middle layer 112. [0042] By moving the bottom layer 114 away from the middle layer 112 at the one or more openings of a chamber and/or valve 306-314, the overall effective volume of the chamber and/or valve is increased, which results in a corresponding pressure decrease within the chamber and/or valve.
  • the pumping chambers 308 may use these mechanics to transport fluid across the pumping chambers 308. For example, by sequentially lowering and/or increasing the pressure within a series of pumping chambers 308, the pumping chambers 308 may form a peristaltic pump.
  • the peristaltic pump may transport fluid from each inlet 302 to a corresponding valve 306 via a fluid channel 304, from each valve 306 to the peristaltic pump via a fluid channel 304, from the peristaltic pump to the mixing chambers 312-314 via fluid channel 304, and from the mixing chambers 312-314 to the one or more outlets 316 via one or more fluid channels 304.
  • the inclusion of the bottom layer 114 pneumatically isolates fluids in the microfluidic chip 102 and fluids in the thermopneumatic interface 104. This has the technical benefit of preventing pneumatic cross-contamination between the liquids in the microfluidic chip 102 and the thermopneumatic interface 104, improving quality control and facilitating rapid reusability of the microfluidic system 100 between tests.
  • middle layer 112 may include any number of middle layers 112.
  • each new middle layer can be patterned to introduce new fluid channels, valves, pumping chambers, and/or mixing chambers.
  • adding additional middle layer 112 may allow for the construction of three-dimensional networks of fluid channels.
  • additional middle layers 112 may create additional fluid channels that cross over or under the existing fluid channels in the original middle layer 112. This crossover may be achieved by including fluid channels in separate middle layers 112 that are vertically offset but horizontally aligned, allowing fluids within the fluid channels to pass over one another without mixing.
  • Such configurations allow for additional flexibility in routing different fluids to specific destinations on the microfluidic chip 102 without interference.
  • additional middle layers 112 may be utilized to incorporate more valves within the microfluidic chip 102.
  • the microfluidic chip 102 can achieve precise control over fluid flow paths in different layers.
  • valves can be placed in different middle layers 112 to regulate the fluid flow in corresponding fluid channels. As previously described, these valves may be in fluid communication with the bottom layer 114 and may be actuated by moving the bottom layer 114 away from the middle layers 112. Placing valves in separate middle layers 112 can allow for more complex fluid routing and timing sequences, as the valves in the different pathways can open or close fluid pathways in specific layers without affecting fluid pathways in other layers.
  • multi-layer valve configurations may enhance the ability of the microfluidic chip 102 to manage multiple fluids simultaneously.
  • incorporating additional middle layers 112 allows for the inclusion of additional pumping chambers within the microfluidic chip 102 to facilitate fluid transport within each respective layer.
  • pumping chambers within a given middle layer 112 can provide fluid transport within that layer without affecting fluid transport in other layers.
  • the additional middle layers 112 can be designed with pumping chambers that work in coordination with those in other layers to allow for increased control over fluid volumes and/or provide greater flow rates. For example, by stacking pumping chambers vertically, more powerful peristaltic pumping actions can be generated.
  • incorporating additional middle layers 112 allows the addition of more mixing chambers to the microfluidic chip 102, enhancing its mixing capabilities. Structurally, by keeping mixing chambers separate within each layer, the chip benefits from improved isolation of reactions and reduced risk of cross-contamination between processes.
  • Each layer can host mixing chambers dedicated to specific functions or reagents (such as heated chambers in one layer and cooled chambers in another) allowing simultaneous processing of multiple reactions under different conditions without interference.
  • FIG. 4 is an isometric view of the thermopneumatic interface 104 of FIGS. 1 and 2.
  • the thermopneumatic interface 104 may be formed of a polymer material.
  • the thermopneumatic interface 104 may be formed of a substantially transparent polymer material. The transparency may allow for the verification of manufacturing quality as well as providing operational functionality. For example, cameras or other optical sensors may be integrated with the microfluidic system 100 to provide operational feedback.
  • the thermopneumatic interface 104 may be formed from a material having a high thermal conductivity, which ensures efficient heat transfer between the thermopneumatic interface 104 and the microfluidic chip 102.
  • the thermopneumatic interface 104 may be formed from a material capable of maintaining relatively high local thermal gradients, which allows for some local regions to be cooled and adjacent local regions to be heated.
  • thermopneumatic interface 104 may be formed from a material that that can withstand elevated temperatures (such as temperatures up to or above 70° C) without significant degradation, softening, or melting. These material properties allow for heating elements (as will be described further on in this specification) to be integrated into the thermopneumatic interface 104.
  • the thermopneumatic interface 104 may also be formed from a material that does not substantially deform under stress or strain — such when subjected to the clamping forces exerted on the thermopneumatic interface 104 by top plate 202 and/or bottom plate 106.
  • the thermopneumatic interface 104 may be formed as via an additive manufacturing process.
  • thermopneumatic interface 104 include a pneumatic system, a cooling system, and a heating system.
  • the pneumatic system includes one or more outlet ports 402.
  • Each outlet port 402 may be coupled to a corresponding inlet port 404 via a fluid channel 406.
  • each outlet port 402 of the thermopneumatic interface 104 may be co-located with a corresponding chamber and/or valve 306-314 of the microfluidic chip 102.
  • each outlet port 402 may be aligned with a corresponding chamber or valve 306-310 along an axis substantially orthogonal to a surface of the thermopneumatic interface 104 facing the microfluidic chip 102.
  • the pneumatic system may be filled with a substantially inert fluid, such as air or nitrogen gas. Fluid may be removed via an inlet port 404, which reduces the pressure within the fluid channel 406 between the inlet port 404 and a corresponding outlet port 402 and reduces the pressure at the outlet port 402. Reducing the pressure at the outlet port 402 creates a pressure differential across the deformable bottom layer 114 of the microfluidic chip 102 that causes the deformable bottom layer 114 to move away from the corresponding chamber and/or valve 306- 314 of the microfluidic chip 102. This movement increases the effective volume of the corresponding chamber and/or valve 306-314, which reduces the pressure within the chamber and/or valve 306-314.
  • a substantially inert fluid such as air or nitrogen gas. Fluid may be removed via an inlet port 404, which reduces the pressure within the fluid channel 406 between the inlet port 404 and a corresponding outlet port 402 and reduces the pressure at the outlet port 402. Reducing the pressure at the outlet
  • fluid may be introduced into the inlet port 404, and the corresponding increased pressure within the fluid channel 406 and at the outlet port 402 creates a pressure differential across the deformable bottom layer 114 that causes it to move toward the corresponding chamber and/or valve 306-314 of the microfluidic chip 102, thereby decreasing the effective volume and increasing the pressure within the chamber and/or valve 306-314.
  • fluid may be provided to the inlet port 404, which increases the pressure within the fluid channel 406 between the inlet port 404 and the corresponding outlet port 402 and increases the pressure at the outlet port 402.
  • Increasing the pressure at the outlet port 402 creates a pressure differential across the deformable bottom layer 114 of the microfluidic chip 102 that causes the deformable bottom layer 114 to move towards the corresponding chamber and/or valve 306-314 of the microfluidic chip 102. This movement decreases the effective volume of the corresponding chamber and/or valve 306-314, which increases the pressure within the chamber and/or valve 306-314.
  • fluid transport within the microfluidic chip 102 may be controlled (for example, according to the mechanics previously described with reference to the pumping chambers 308).
  • FIG. 5 is a detail view, taken at reference FIG. 5 in FIG. 4, illustrating details that may be associated with some examples of the thermopneumatic interface 104 of FIGS. 1 and 2.
  • each outlet port 402 may include a ledge 502 having a plurality of projections 504 protruding from the ledge 502.
  • the plurality of projections 504 may substantially prevent the deformable bottom layer 114 of the microfluidic chip 102 from blocking an opening 506 of the outlet port 402 leading to the fluid channel 406, thus ensuring that fluid may continue to be evacuated from the outlet port 402 even as the bottom layer 114 is deformed.
  • each outlet port 402, opening 414, and/or opening 416 may include a raised lip portion 508 the respective port or opening.
  • the raised lip portion 508 may be formed as a circular ring and protrude past the surface of the thermopneumatic interface 104 towards the bottom layer 114 of the microfluidic chip 102. [0054] In the assembled configuration, the raised lip portion 508 may deform a portion of the bottom layer 114 and create a fluid seal between the outlet port 402, opening 414, opening 416 and the portion of the bottom layer 114 within the raised lip portion 508.
  • each opening 414 and/or opening 416 may also include an annular recess 510 below the raised lip portion 508.
  • each annular recess 510 allows fluid communication between the opening 414 and/or opening 416 and the respective fluid channel 406 even as the deformable bottom layer 114 is drawn against a surface of a heat transfer structure (not shown) disposed within the opening 414 or a surface of a heating element (not shown) disposed within the opening 416.
  • thermopneumatic interface 104 include one or more connection spheres 512 at portions of the fluid channels 406 forming sharp angles (such as 90° right angles).
  • Each connection sphere 512 may be a substantially enlarged portion of the fluid channel 406 (e.g., having a radius larger than a radius of the fluid channel 406) forming a substantially spherical shape.
  • Including connections spheres 512 provides a variety of technical benefits to implementations of the thermopneumatic interface 104 formed using additive manufacturing technologies. For example, including the connection spheres 512 may substantially prevent the fluid channels 406 from becoming plugged with uncured resins at locations where the fluid channels 406 form sharp angles.
  • the cooling system of the thermopneumatic interface 104 may include a cooling loop having a first port 408, a second port 410, and a fluid channel 412 extending between the first port 408 and the second port 410.
  • a liquid coolant such as glycol/glycol-water mixture or al cohol/alcohol -water mixture
  • enters the cooling loop at the first port 408 flows through the fluid channel 412, and exits the cooling loop at the second port 410.
  • the liquid coolant enters the cooling loop at the second port 410, flows through the fluid channel 412, and exits the cooling loop at the first port 408.
  • FIG. 6 is an isometric view of the thermopneumatic interface 104 of FIGS. 1 and 2 showing coolant 602 flowing through the cooling loop.
  • the fluid channel 412 may travel through a substantial portion of the thermopneumatic interface 104 to maintain a baseline temperature at substantially all of the thermopneumatic interface 104.
  • the baseline temperature may be about 4° Celsius.
  • the temperature of the coolant may be maintained in a range of between about 3° Celsius and about -10° Celsius
  • the microfluidic chip 102 in the assembled configuration, may be in contact with the thermopneumatic interface 104, and the cooling system of the thermopneumatic interface 104 maintains the baseline temperature of the microfluidic chip 102 to be the same as the baseline temperature of the thermopneumatic interface 104.
  • the cooling system includes one or more openings 414 formed through a face of the thermopneumatic interface 104. Each opening 414 may be in fluid communication with the fluid channel 412. In various implementations, one or more of the openings 414 may be in fluid communication with an inlet port 404 of the pneumatic system (for example, via a fluid channel 406) and the opening 414 may include the previously described functionality of the outlet ports 402 of the pneumatic system.
  • the cooling system of the thermopneumatic interface 104 can function as a heating loop to elevate the temperature of the microfluidic chip 102.
  • the baseline temperature of the thermopneumatic interface 104 can be raised to a desired level.
  • the heating loop enters at either the first port 408 or the second port 410, flows through the fluid channel 412, and exits through the opposite port, similar to the cooling loop operation.
  • the temperature of the heating fluid can be precisely controlled and maintained within a range of about 25° Celsius to about 95° Celsius.
  • PCR polymerase chain reaction
  • the thermopneumatic interface 104 offers enhanced versatility for a wide range of applications. The ability to precisely control the temperature of the microfluidic chip 102 ensures optimal performance and reliability of temperature-sensitive processes, thereby expanding the functional scope of the microfluidic system.
  • FIG. 7 is a cross-sectional view of a portion of the thermopneumatic interface 104 of FIGS. 1 and 2 taken at section line 7-7 of FIG. 4.
  • some implementations of the thermopneumatic interface 104 include a heat transfer structure 702 disposed within one or more of the openings 414 of the cooling system.
  • the heat transfer structure 702 may be formed of a metal, such as stainless steel, copper, or aluminum.
  • the heat transfer structure 702 may be a heat sink having a surface 704 configured to contact a cooled chamber 312 of the microfluidic chip 102 and one or more fins 706 configured to transfer heat from the cooled chamber 312 into the coolant within the fluid channel 412.
  • the surface 704 may be a polished surface to maximize the surface area in contact with the surface of the bottom layer 114 of the microfluidic chip 102, which increases the heat transfer between the heat transfer structure 702 and the microfluidic chip 102.
  • FIG. 8 is a schematic illustration showing the heat transfer structure 702 (shown as the “Aluminum disc”) in contact with the cooled chamber 312 (shown as “Sample”) and the coolant within the fluid channel 412 (shown as “Cooling line”).
  • the heat transfer structure 702 may transfer heat away from the sample within the cooled chamber 312 into the coolant, which cools both the cooled chamber 312 and its contents.
  • the heating system of the thermopneumatic interface 104 may include openings 416 formed through the thermopneumatic interface 104.
  • FIG. 9 is a cross- sectional view of a portion of the thermopneumatic interface 104 of FIGS. 1 and 2 taken at section line 9-9 of FIG. 4.
  • the openings 416 may be formed as through-holes extending through the thermopneumatic interface 104.
  • alignment tabs 902 may be provided at the top of the openings 416 to ensure proper alignment of the heating elements (not shown) received within the openings 416.
  • the alignment tabs 902 may be formed at the top of the through-holes of the openings 416 and extend into the opening.
  • FIG. 10 is a top view showing the thermopneumatic interface 104 of FIGS. 1 and 2.
  • FIG. 11 is a perspective view showing a portion of the thermopneumatic interface 104 of FIGS. 1 and 2.
  • FIG. 12 is a perspective view of the thermopneumatic interface 104 of FIGS. 1 and 2.
  • a heating element 1002 may be received in each of the openings 416.
  • the heating element 1002 may be an electric resistance-type heater.
  • each heating element 1002 may be configured to face a corresponding heated chamber 314 of the microfluidic chip 102 (in the assembled position) and provide heat to the heated chamber 314.
  • FIG. 13 is a schematic illustration showing heating elements 1002 (shown as “Heater”) received in openings 416.
  • thermocouples shown as “TC”
  • TC thermocouples
  • the heating elements 1002 may be configured to maintain a corresponding heated chamber 314 at a temperature in a range of between about 42° Celsius to about 70° Celsius.
  • one or more of the openings 416 may be in fluid communication with an inlet port 404 of the pneumatic system (for example, via a fluid channel 406) and the opening 416 may include the previously described functionality of the outlet ports 402 of the pneumatic system.
  • FIG. 14 is an isometric view of an assembled microfluidic system 100.
  • FIG. 15 is a cross-sectional view of the example microfluidic system 100 of FIG. 14 taken at line 15-15.
  • the microfluidic chip 102 is positioned between the top plate 202 and the thermopneumatic interface 104, and the thermopneumatic interface is positioned between the microfluidic chip 102 and the bottom plate 106.
  • the top plate 202 and the bottom plate 106 may be configured to apply pressure in opposite directions to the microfluidic chip 102 and the thermopneumatic interface 104 to press the microfluidic chip 102 against the thermopneumatic interface 104.
  • the inlet ports 404 may be provided on the bottom side of the thermopneumatic interface 104.
  • the microfluidic system 100 includes a clamping device 1402 that applies controlled pressure to secure the assembly of the microfluidic chip 102 and the thermopneumatic interface 104 between the top plate 202 and the bottom plate 106.
  • the clamping device 1402 includes a frame 1404 attached to the bottom plate 106, an actuator 1406 slidably coupled to the frame 1404, an upper jaw 1408 attached to the actuator 1406, and a clamping surface 1410 attached to the upper jaw 1408.
  • the bottom plate 106 functions as the lower jaw of the clamping device 1402.
  • the actuator 1406 moves vertically within the frame 1404, it adjusts the clamping pressure by moving upward to relieve pressure and downward to increase pressure.
  • the actuator may be operated via a manual mechanism (e.g., a screw or lever system) or through an automated system, allowing precise control over the pressure applied to the microfluidic chip 102 and thermopneumatic interface 104.
  • a manual mechanism e.g., a screw or lever system
  • the actuator moves downward, it drives the upper jaw 1408 and clamping surface 1410 closer to the bottom plate 106, applying force to secure the microfluidic chip 102 and thermopneumatic interface 104.
  • the actuator moves upward, it reduces the pressure between the top and bottom plates, allowing the clamped components to be easily removed.
  • This design ensures that the clamping device 1402 securely holds the assembly in place during operation while also allowing for quick and simple removal of the top plate 202, microfluidic chip 102, and thermopneumatic interface 104.
  • the actuator 1406 By moving the actuator 1406 upward, the clamping pressure is released, creating enough clearance for the microfluidic chip 102 and thermopneumatic interface 104 to be removed or replaced without needing to disassemble the entire system.
  • thermopneumatic interface 104 in the microfluidic system 100 is designed to be easily removable from both the top plate 202 and the bottom plate 106, allowing for efficient system reconfiguration.
  • This modularity ensures that the interface 104 can be quickly swapped out or replaced, providing flexibility to accommodate various microfluidic chips 102 depending on the specific application or experimental requirements.
  • the removable nature of the thermopneumatic interface 104 allows for seamless integration with different chip designs, ensuring compatibility with a wide range of microfluidic processes.
  • the microfluidic chips 102 themselves are designed to be swappable and replaceable, further enhancing the versatility of the system by allowing users to quickly exchange microfluidic chips for different assays or sample types without having to disassemble the entire system.
  • FIG. 16 is an isometric view of the thermopneumatic interface 104 of FIGS. 14 and 15.
  • the thermopneumatic interface 104 includes one or more one or more indexing features 1602. Each indexing feature 1602 may protrude away from a surface of the thermopneumatic interface 104 facing the microfluidic chip 102 towards the microfluidic chip 102.
  • FIG. 17 is a top view of the microfluidic chip 102 of FIGS. 14 and 15.
  • the microfluidic chip 102 includes one or more indexing features 1702. Each indexing feature 1702 may be formed as a recess and correspond to an indexing feature 1602 of the thermopneumatic interface 104.
  • indexing features 1702 may be present on only one side of the microfluidic chip 102.
  • Corresponding indexing features 1602 may be present on a side of the thermopneumatic interface 104 such that the indexing features 1702 engage with the indexing features 1602 only when the microfluidic chip 102 is placed over the thermopneumatic interface 104 in the correct orientation.
  • the microfluidic chip 102 may include indexing features 318
  • the thermopneumatic interface 104 may include indexing features 418
  • the top plate 202 may include indexing features 204.
  • the indexing features 204 may also be present on the bottom plate 106.
  • the indexing feature 318 and indexing features 418 may be formed as recesses in the microfluidic chip 102 and thermopneumatic interface 104, respectively.
  • the indexing features 204 may be formed as protrusions in the top plate 202 and/or bottom plate 106 such that when the components are aligned, the indexing features 204 are received are received in indexing features 318 and 418.
  • Indexing features 204, 318, 418, 1602, and/or 1702 ensure that various components of the microfluidic system 100 are aligned properly (e.g., the indexing features may align and allow assembly of the microfluidic system 100 only when the top plate 202, microfluidic chip 102, thermopneumatic interface 104, and/or bottom plate 106 are correctly aligned).
  • thermopneumatic interface for a microscale fluid handling system, comprising: one or more pneumatic inlet ports in fluid communication with one or more pneumatic outlet ports; and a cooling loop extending through the thermopneumatic interface, the cooling loop configured to maintain the thermopneumatic interface at a baseline temperature; wherein the one or more pneumatic outlet ports are configured to contact a surface of a microfluidic chip, each pneumatic inlet port is configured to receive a change in pressure and provide the changed pressure to a corresponding pneumatic outlet port, and the thermopneumatic interface is configured to maintain the microfluidic chip at the baseline temperature.
  • Example 2 The thermopneumatic interface of example 1, wherein: the microfluidic chip includes one or more inlets fluidly coupled to one or more mixing chambers via a plurality of pumping chambers and a deformable layer configured to be positioned between the plurality of pumping chambers and the one or more pneumatic outlets; and the one or more pneumatic outlets are configured to deform portions of the deformable layer proximate the plurality of pumping chambers to change pressure within the pumping chambers.
  • Example 3 The thermopneumatic interface of example 2, wherein the one or more pneumatic outlets are configured to sequentially deform portions of the deformable layer proximate the plurality of pumping chambers to sequentially change pressure within the pumping chambers to transport fluid from the one or more inlets to the plurality of mixing chambers.
  • Example 4 The thermopneumatic interface of example 3, wherein: the mixing chambers include a cooled chamber; and the thermopneumatic interface includes a heat transfer structure configured to transfer heat from the cooled chamber to coolant within the cooling loop.
  • Example 5 The thermopneumatic interface of example 4, wherein the heat transfer structure is configured to contact a portion of the deformable layer proximate the cooled chamber and coolant within the cooling loop.
  • Example 6 The thermopneumatic interface of example 5, wherein the heat transfer structure includes a surface configured to contact the portion of the deformable layer proximate the cooled chamber and a fin configured to contact coolant within the cooling loop.
  • Example 7 The thermopneumatic interface of example 3, wherein: the mixing chambers include a heated chamber; and the thermopneumatic interface includes a heating element configured to transfer heat to the heated chamber.
  • Example 8 The thermopneumatic interface of example 7, wherein the heating element includes an electric resistance-type heater.
  • Example 9 The thermopneumatic interface of example 3, wherein each pneumatic outlet port includes a ledge and a plurality of projections protruding from the ledge.
  • Example 10 The thermopneumatic interface of example 9, wherein the plurality of projections are configured to substantially prevent the deformable layer from blocking an opening of the pneumatic outlet port in fluid communication with a corresponding pneumatic inlet port.
  • Example 11 The thermopneumatic interface of example 3, further comprising a raised lip portion protruding from a surface of the thermopneumatic interface, the raised lip portion surrounding one of the pneumatic outlet ports.
  • Example 12 The thermopneumatic interface of example 11, wherein the raised lip portion is configured to deform a portion of the deformable layer to provide a fluid seal between the one pneumatic outlet port and the deformable layer.
  • Example 13 The thermopneumatic interface of example 1, further comprising an indexing feature protruding away from a surface of the thermopneumatic interface configured to face the microfluidic chip.
  • Example 14 The thermopneumatic interface of example 13, wherein the microfluidic chip includes a corresponding indexing feature.
  • Example 15 The thermopneumatic interface of example 14, wherein the corresponding indexing feature of the microfluidic chip is configured to engage the indexing feature of the thermopneumatic interface.
  • Example 16 The thermopneumatic interface of example 1, wherein the thermopneumatic interface is removable from the microscale fluid handling system.
  • Example 17 The thermopneumatic interface of example 1, wherein microfluidic chip is removable from the thermopneumatic interface.
  • thermopneumatic interface including: one or more pneumatic inlet ports in fluid communication with one or more pneumatic outlet ports, each pneumatic inlet port being configured to receive a change in pressure and provide the change in pressure to a corresponding pneumatic outlet port, and a cooling loop extending through the thermopneumatic interface, the cooling loop being configured to maintain the thermopneumatic interface at a baseline temperature; a microfluidic chip including: one or more inlets fluidly coupled to one or more mixing chambers via a plurality of pumping chambers, and a deformable layer; and a clamping mechanism configured to position the thermopneumatic interface in removable contact with the microfluidic chip such that: the one or more pneumatic outlet ports are positioned to contact the deformable layer of the microfluidic chip and deform portions of the deformable layer proximate the plurality of pumping chamber to change pressure within the pumping chambers, and the thermopneumatic interface is positioned to maintain the microfluidic chip
  • Example 19 The microscale fluid handling system of example 18, wherein: the clamping mechanism includes a top plate and a bottom plate; and the thermopneumatic interface and the microfluidic chip are secured between the top plate and the bottom plate.
  • Example 20 The microscale fluid handling system of example 19, wherein the thermopneumatic interface and the microfluidic chip are removable from the clamping mechanism. CONCLUSION
  • a “subset” of set A may be coextensive with set A, or include elements of set A.
  • the term “subset” does not necessarily exclude the empty set.
  • the directions of arrows generally demonstrate the flow of information — such as data or instructions. The direction of an arrow does not imply that information is not being transmitted in the reverse direction. For example, when information is sent from a first element to a second element, the arrow may point from the first element to the second element. However, the second element may send requests for data to the first element, and/or acknowledgements of receipt of information to the first element.
  • the figures illustrate a number of components and/or steps, any one or more of the components and/or steps may be omitted or duplicated, as suitable for the application and setting.
  • the term computer-readable medium does not encompass transitory electrical or electromagnetic signals or electromagnetic signals propagating through a medium — such as on an electromagnetic carrier wave.
  • the term “computer-readable medium” is considered tangible and non-transitory.
  • the functional blocks, flowchart elements, and message sequence charts described above serve as software specifications that can be translated into computer programs by the routine work of a skilled technician or programmer.

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Abstract

L'invention concerne une interface thermopneumatique qui comprend un ou plusieurs orifices d'entrée pneumatiques en communication fluidique avec un ou plusieurs orifices de sortie pneumatiques et une boucle de refroidissement s'étendant à travers l'interface thermopneumatique. La boucle de refroidissement est conçue pour maintenir l'interface thermopneumatique à une température de ligne de base. Le ou les orifices de sortie pneumatiques sont conçus pour entrer en contact avec une surface d'une puce microfluidique. Chaque orifice d'entrée pneumatique est conçu pour recevoir un changement de pression et fournir le changement de pression à un orifice de sortie pneumatique correspondant. L'interface thermopneumatique est configurée pour maintenir la puce microfluidique à la température de ligne de base.
PCT/US2024/051441 2023-10-16 2024-10-15 Système de manipulation de fluide à l'échelle micrométrique Pending WO2025085451A1 (fr)

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Citations (5)

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Publication number Priority date Publication date Assignee Title
US20030173720A1 (en) * 2002-03-12 2003-09-18 Massachusetts Institute Of Technology Methods for forming articles having very small channels therethrough, and such articles, and methods of using such articles
US20060063160A1 (en) * 2004-09-22 2006-03-23 West Jay A Microfluidic microarray systems and methods thereof
US20080152543A1 (en) * 2006-11-22 2008-06-26 Hideyuki Karaki Temperature regulation method of microfluidic chip, sample analysis system and microfluidic chip
US20120077260A1 (en) * 2009-03-30 2012-03-29 Fraunhofer Usa, Inc. Reservoir-buffered mixers and remote valve switching for microfluidic devices
US11007524B2 (en) * 2019-01-18 2021-05-18 National Tsing Hua University Automatic microfluidic system for rapid personalized drug screening and testing method for personalized antibiotic susceptibility

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030173720A1 (en) * 2002-03-12 2003-09-18 Massachusetts Institute Of Technology Methods for forming articles having very small channels therethrough, and such articles, and methods of using such articles
US20060063160A1 (en) * 2004-09-22 2006-03-23 West Jay A Microfluidic microarray systems and methods thereof
US20080152543A1 (en) * 2006-11-22 2008-06-26 Hideyuki Karaki Temperature regulation method of microfluidic chip, sample analysis system and microfluidic chip
US20120077260A1 (en) * 2009-03-30 2012-03-29 Fraunhofer Usa, Inc. Reservoir-buffered mixers and remote valve switching for microfluidic devices
US11007524B2 (en) * 2019-01-18 2021-05-18 National Tsing Hua University Automatic microfluidic system for rapid personalized drug screening and testing method for personalized antibiotic susceptibility

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