WO2023146521A1 - Dispositifs microfluidiques numériques à fluides en phase continue - Google Patents

Dispositifs microfluidiques numériques à fluides en phase continue Download PDF

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Publication number
WO2023146521A1
WO2023146521A1 PCT/US2022/013992 US2022013992W WO2023146521A1 WO 2023146521 A1 WO2023146521 A1 WO 2023146521A1 US 2022013992 W US2022013992 W US 2022013992W WO 2023146521 A1 WO2023146521 A1 WO 2023146521A1
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WIPO (PCT)
Prior art keywords
phase fluid
fluid
electrodes
well region
droplet
Prior art date
Application number
PCT/US2022/013992
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English (en)
Inventor
Viktor Shkolnikov
Michael W. Cumbie
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Hewlett-Packard Development Company, L.P.
Priority date (The priority date 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 date listed.)
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Publication date
Application filed by Hewlett-Packard Development Company, L.P. filed Critical Hewlett-Packard Development Company, L.P.
Priority to PCT/US2022/013992 priority Critical patent/WO2023146521A1/fr
Publication of WO2023146521A1 publication Critical patent/WO2023146521A1/fr

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Classifications

    • 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
    • B01L3/502769—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 multiphase flow arrangements
    • B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B01L3/502792—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics for moving individual droplets on a plate, e.g. by locally altering surface tension
    • 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
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427—Electrowetting

Definitions

  • Digital microfluidic (DMF) devices may be used to perform operations on volumes of fluid, such as the manipulation of fluid droplets to facilitate handling and testing of various fluids on a small scale.
  • DMF Digital microfluidic
  • Such devices may be used in the medical industry, for example to analyze proteins, analyze deoxyribonucleic acid (DNA), detect pathogens, perform clinical diagnostic testing, and/or for synthetic chemistry, among other types of industries and/or for other purposes.
  • FIG. 1 illustrates an example digital microfluidic (DMF) device, in accordance with examples of the present disclosure.
  • FIGS. 2A-2C illustrate different example DMF devices, in accordance with examples of the present disclosure.
  • FIG. 3 illustrates an example apparatus including a DMF device and coupled circuitry, in accordance with examples of the present disclosure.
  • FIG. 4 illustrates an example method for flowing a droplet phase fluid within a well region and a primary chamber of a DMF device, in accordance with examples of the present disclosure.
  • FIGS. 5A-5E illustrate further example DMF devices, in accordance with examples of the present disclosure.
  • FIGs. 6A-6B illustrate example DMF devices with two different continuous phase fluids, in accordance with examples of the present disclosure.
  • FIGS. 7A-7C illustrate different views of example DMF devices, in accordance with examples of the present disclosure.
  • Digital microfluidic (DMF) devices may be used to perform large numbers of chemical processing operations on different fluids in parallel.
  • DMF devices may be designed to implement biochemical reactions on chemical components within a sample carried in a fluid by performing chemical processing operations on the sample, such as a sample containing proteins, nucleic acids, antibodies, and/or other components.
  • a sample includes and/or refers to any biological material collected, such as from a subject or other source. Control of surface chemistries may impact performance of the DMF device.
  • DMF devices may include a multiphase flow comprising a chemical component in one thermodynamic phase and another chemical component in another thermodynamic phase. As an example, a continuous phase fluid may be used to carry a droplet phase fluid throughout the DMF device.
  • the droplet phase fluid may be dispersed in the continuous phase fluid which acts as a carrier for the droplet phase and to flow the droplet phase fluid through a microfluidic path of the DMF device to drive chemical processing operations on the droplet phase fluid.
  • a continuous phase fluid includes and/or refers to a fluid that flows through portions of the DMF device and which carries solid and/or fluid particles.
  • a droplet phase fluid includes and/or refers to a fluid that, when dispersed in the continuous phase fluid, forms fluid packets and/or fluid droplets of the droplet phase fluid as emulsified fluid.
  • chemical processing operations are performed on and/or using the droplet phase fluid.
  • a sample and/or reagents may be delivered in the droplet phase fluid, and the DMF device may be used to perform chemical processing thereon.
  • chemical components of the droplet phase fluid may partition into the interface of the continuous phase fluid and the droplet phase fluid.
  • Multiphase flows may include a moving interface, at which a chemical component in one phase interacts with a chemical component in another phase.
  • the dynamics of this interface determines the behavior of the fluid flow.
  • a continuous phase fluid may carry a droplet phase fluid including a protein sample having proteins with hydrophobic domains. The proteins with hydrophobic domains may partition at the interface of the droplet phase fluid and the continuous phase fluid, which may be caused by van der Waals force interactions with the components.
  • the partition of components of the droplet phase fluid may impact the performance of the DMF device. For example, once the components have partitioned, the components may denature and may not participate in the chemical processing operation designed to occur in the DMF device, which may result in incomplete chemical processing operations. Even if the components do not denature, the partitioning of the components reduces the effectiveness of the components in participating in chemical processing.
  • fluids with a greater density than water may be used as the continuous phase fluid and may prevent or mitigate partitioning of components of the droplet phase fluid into the interface due to the density of the fluids.
  • dense continuous phase fluids cause the droplet phase fluid to float to the ceiling of the DMF device, with respect to gravity, which may prevent use of or make it difficult to use well regions to insert the droplet phase fluid to the DMF device.
  • the mechanism for causing fluid flow may be located on the floor of the DMF device, with respect to gravity and for manufacturing purposes, and may generate an electric field to cause the fluid flow. As the mechanism for causing fluid flow is located on the floor of the DMF device, and the droplet phase fluid floats to the ceiling, the electric field may be unable to reach the droplet phase fluid in a well region at a sufficient level to cause fluid flow.
  • Examples of the present disclosure are directed to a DMF device that has a well region coupled to a primary chamber, with at least one of the well region and the primary chamber containing a continuous phase fluid that is denser than a droplet phase fluid to prevent or mitigate partitioning of components of the droplet phase fluid.
  • the droplet phase fluid may be inserted into the DMF device at the well region and is carried through a microfluidic path.
  • Use of a well region may allow for processing greater volumes of droplet phase fluids, as compared to DMF devices without well regions, and which may allow for parallel chemical processing.
  • Electrodes may be disposed proximal to the well region to move the droplet phase fluid through the continuous phase fluid and along the well region to the primary chamber.
  • individual fluid droplets of the droplet phase fluid may be separated from each other, with the continuous phase fluid being interposed between, and/or generally surrounding, the fluid droplets of the droplet phase fluid.
  • the movement of the droplet phase fluid within and through the DMF device may be accompanied by, and/or supported via, similar movement of the continuous phase fluid.
  • both the well region and the primary chamber are filled with the continuous phase fluid that is denser than the droplet phase fluid.
  • the primary chamber is filled with the continuous phase fluid that is denser than the droplet phase fluid and the well region is filled with another continuous phase fluid that is less dense than the droplet phase fluid.
  • the well region is sized to contain more fluid than the primary chamber, allowing for the DMF device to operate on larger amounts of fluids.
  • the denser continuous phase fluid provides an interface that is more resistant to components within the droplet phase fluid collecting at the interface or partitioning into the continuous phase fluid as compared to a less dense fluid.
  • the droplet phase fluid is either not exposed to a less dense continuous phase fluid or the exposure is minimized by using different continuous phase fluids, which may prevent or mitigate component partitioning into the interface.
  • the continuous phase fluid carries the droplet phase fluid.
  • the continuous phase fluid which may be referred to as being in a continuous phase, may be an inert fluid filler, such an oil or other inert fluid.
  • the continuous phase fluid may include a fluorinated oil.
  • the continuous phase fluid may include any fluid that is immiscible with the droplet phase fluid.
  • Chemical processing operations may be performed on and/or using the droplet phase fluid, when immersed in the continuous phase fluid, and which may sometimes be in the droplet phase.
  • the droplet phase fluid may comprise an aqueous solution including a sample and/or reagents, which may include solid or fluid particles.
  • the droplet phase fluid may transition to a droplet phase in which fluid droplets of the droplet phase fluid are formed from a volume of the droplet phase fluid via use of the continuous phase fluid and electrowetting forces, as further described herein.
  • the volume of the droplet phase fluid used to form a fluid droplet of the droplet phase fluid may be larger than the volume of the fluid droplet, and may be referred to as a fluid packet and/or a bulk phase.
  • the interface of the continuous phase fluid and the droplet phase fluid herein generally referred to as the “interface” for ease of reference, includes and/or refers to a boundary and/or surface contact between the continuous phase fluid and the droplet phase fluid.
  • the shape of the interface may be controlled by surface tension.
  • a surfactant may be contained in the continuous phase fluid and/or the droplet phase fluid, which may reduce a surface tension between continuous phase fluid and the droplet phase fluid by preventing fluid droplets of the droplet phase fluid from coalescing with each other.
  • a well includes and/or refers to a column capable of storing a volume of fluid that is larger than a volume of a fluid droplet of the droplet phase fluid.
  • the fluid droplet of the droplet phase fluid may include a volume of about 1 microliter (pL) or less, such as a volume of between about 0.1 pL and about 1 pL, about 0.25 pL and about 1 pL, about 0.5 pL and about 1 pL, about 0.5 pL and about 0.75 pL, about 0.25 pL and about 0.75 pL, or about 0.1 pL and about 0.5 pL, among other ranges.
  • the well may store a volume of fluid that includes more than one droplet of fluid, such as at least two fluid droplets of the droplet phase fluid.
  • a well may store a volume of fluid in a range between about 1 pL and about several milliliters (mL) of fluid.
  • the well may store a volume of fluid between about 1 pL and about 1 mL, about 1 pL and about 500 pL, about 1 pL and about 50 pL, about 1 pL and about 10 pL, or about 1 pL and about 5 pL, among other volume ranges.
  • a well region includes and/or refers to a region of the DMF device including a well.
  • a chamber includes and/or refers to an enclosed and/or semi-enclosed region of the DMF device, which may be formed of an etched or micromachined portion (e.g., negative space forming a conduit in a substrate or substrates) and which may be used to perform chemical processing on fluids therein.
  • a channel includes and/or refers to a path through which a fluid or semi-fluid may pass, which may allow for transport of volumes of fluid on the order of pL, nanoliters, picoliters, or femtoliters.
  • [0017JA fluid droplet of the droplet phase fluid refers to and/or includes a discrete portion of fluid (e.g., a liquid), which may be surrounded by the continuous phase fluid.
  • a fluid droplet of the droplet phase fluid an immiscible fluid, such as an aqueous solution, is surrounded by an oil phase.
  • a fluid packet of the droplet phase fluid includes and/or refers to a volume of fluid that is larger than a fluid droplet of the droplet phase fluid.
  • a DMF device comprising a housing that defines a microfluidic path including a well region including a plurality of electrodes supported by the housing, a primary chamber fluidically coupled to the well region, and a continuous phase fluid disposed within the primary chamber.
  • the continuous phase fluid having a first density that is greater than a second density of a droplet phase fluid.
  • the DMF device further comprises a fluidic inlet fluidically coupled to the well region to input the droplet phase fluid to the DMF device.
  • the plurality of electrodes include transparent electrodes that are to actuate to move the droplet phase fluid along a portion of the microfluidic path associated with the well region and to form fluid droplets from the droplet phase fluid.
  • the DMF device further includes a fluid actuator disposed proximal to the primary chamber to actuate to move fluid droplets of the droplet phase fluid along a portion of the microfluidic path associated with the primary chamber.
  • the continuous phase fluid is further disposed within the well region and is immiscible with the droplet phase fluid
  • the plurality of electrodes include actuating electrodes disposed proximal to a ceiling surface of the DMF device with respect to a direction of gravity.
  • the DMF device further includes a second continuous phase fluid disposed within the well region, wherein the second continuous phase fluid has a third density that is less than the second density of the droplet phase fluid and the plurality of electrodes include actuating electrodes disposed proximal to a floor surface of the DMF device with respect to a direction of gravity.
  • the continuous phase fluid includes an oil fluid and the droplet phase fluid includes an aqueous fluid.
  • the DMF device further includes circuitry supported by the housing and communicatively coupled to the plurality of electrodes to actuate the plurality of electrodes and, in response, to cause application of electrowetting forces on the droplet phase fluid within the well region to drive the droplet phase fluid to the primary chamber as fluid droplets of the droplet phase fluid.
  • the DMF device further includes a plurality of well regions fluidically coupled to the primary chamber, wherein the plurality of well regions including the well region, and a plurality of fluidic inlets fluidically coupled to the plurality of well regions, wherein the plurality of fluidic inlets including the fluidic inlet.
  • the DMF device includes a housing that defines a microfluidic path including a well region and a primary chamber, a plurality of electrodes supported by the housing and disposed proximal to the well region, a first continuous phase fluid disposed within the primary chamber, wherein the first continuous phase fluid has a first density that is greater than a second density of a droplet phase fluid, a second continuous phase fluid disposed within the well region, and a fluidic inlet fluidically coupled to the well region to input the droplet phase fluid to the DMF device.
  • the circuitry is communicatively coupled to the plurality of electrodes to selective actuate the plurality of electrodes and, in response, to cause application of electrowetting forces on the droplet phase fluid to drive the droplet phase fluid along the microfluidic path from the well region and to the primary chamber in a droplet phase.
  • the first continuous phase fluid and the second continuous phase fluid are the same type of fluorinated oil fluid.
  • the plurality of electrodes include a plurality of actuating electrodes and a ground electrode disposed along the microfluidic path.
  • the housing includes a transparent lid and the fluidic inlet is disposed on and through the transparent lid, and the DMF device further includes a fluid actuator disposed proximal to the primary chamber.
  • An example method comprises inputting a droplet phase fluid into a DMF device via a fluidic inlet of the DMF device, wherein the fluidic inlet is fluidically coupled to a well region of the DMF device that is filled with a continuous phase fluid with a first density that is greater than a second density of the droplet phase fluid, and sequentially actuating a plurality of electrodes disposed proximal to the well region and a fluid actuator disposed proximal to a primary chamber of the DMF device.
  • the method comprises flowing the droplet phase fluid toward the primary chamber from the well region, forming fluid droplets from the droplet phase fluid while flowing the droplet phase fluid into the primary chamber, and flowing the fluid droplets of the droplet phase fluid along the primary chamber.
  • the method can further include allowing the droplet phase fluid to migrate toward a ceiling surface of the DMF device with respect to a direction of gravity.
  • the method can further include filling the DMF device with the continuous phase fluid via the fluidic inlet, wherein the continuous phase fluid is filled within the well region and the primary chamber.
  • FIG. 1 illustrates an example DMF device, in accordance with examples of the present disclosure.
  • an example DMF device 100 comprises a housing 102 that defines a microfluidic path 105 including a well region 104, a primary chamber 108, and a continuous phase fluid 110.
  • the housing 102 may include a first substrate and a second substrate, with the well region 104 and the primary chamber 108, among other components, formed by and/or between the substrates as etched or micromachined portions.
  • the etched or micromachined portions forming the well region 104, the primary chamber 108, and optionally additional chambers, wells, and/or channels may be a height in the range of about 10 micrometers (pm) to about 2 millimeters (mm).
  • the well region 104, the primary chamber 108, and optionally other chambers and channels may be formed by etching or micromachining processes in a substrate to form the various etched or micromachined portions. Accordingly, the well regions, chambers, and/or channels may be defined by surfaces fabricated in the substrate of the DMF device 100.
  • the well region 104 includes a plurality of electrodes 106 supported by the housing 102.
  • the plurality of electrodes 106 may be disposed proximal to a portion of the microfluidic path 105.
  • the electrodes 106 are positioned along and/or exposed to the well region 104.
  • Proximal as used herein (e.g., proximal to the portion of the microfluidic path 105, the well region 104, and/or the primary chamber 108), includes and/or refers to being disposed within or in line with a portion of the DMF device 100, such as being positioned along, above, below, and/or exposed to the portion of the DMF device 100.
  • the plurality of electrodes 106 are to actuate to move a droplet phase fluid along a (first) portion of microfluidic path 105 associated with the well region 104 and to form fluid droplets from the droplet phase fluid.
  • Example electrodes include transparent electrodes, ring electrodes, linear electrodes, almost continuous electrodes, ground electrodes, and/or actuating electrodes, among others.
  • the plurality of electrodes 106 may be the same size or different sizes.
  • the electrodes may be formed of a conductive material, such as metal, conductive polymers, indium tin oxide (ITO), transparent conductive oxides, carbon nanotube, among other material.
  • a transparent electrode includes and/or refers to an electrode that is transparent or semi-transparent. Use of transparent electrodes, along with a transparent lid, as further described below, may allow for a user to visually view fluid flow within the DMF device 100 while chemical operations are being performed by the DMF device 100 and/or to verify proper fluid processing is occurring.
  • a ring electrode includes and/or refers to an electrode which is annulus shaped. In some examples, the ring electrode(s) may be shaped to extend around a portion of the DMF device 100, such as a portion of the well region 104 or primary chamber 108.
  • a linear electrode includes and/or refers to an electrode which extends in a straight line and for a sub-portion of the DMF device 100.
  • a plurality of linear electrodes may be placed in an array along the portion of the DMF device 100 (e.g., a portion of the well region 104), and may provide greater control of fluid flow, as compared to an almost continuous electrode, due to known electrode positions and localized resolution.
  • An almost continuous electrode includes and/or refers to an electrode which extends along a portion of the DMF device 100, such as along the floor surface or ceiling surface of a well region 104 or a primary chamber 108 (e.g., see electrode 206- 8 and 216-1 of FIG. 2B).
  • An almost continuous electrode may reduce manufacturing costs, as compared to an array of linear electrodes.
  • a ground electrode includes and/or refers to an electrode that provides or establishes a connection to ground.
  • An actuating electrode includes and/or refers to an electrode that is actuated (e.g., a voltage is applied thereto by coupled circuitry), and in response, generates an electric field based on a differential between the actuating electrode (e.g., the applied voltage) and ground.
  • ground may be provided by a ground electrode, and in other examples, ground is provided by the fluid within the DMF device 100.
  • use of a ground electrode may provide greater control of fluid flow and/or formation of a fluid droplet of the droplet phase fluid as compared to use of fluid (e.g., the continuous phase fluid and/or droplet phase fluid) as ground. Using fluid as ground may reduce manufacturing costs.
  • the plurality of electrodes 106 include transparent electrodes which may allow for optical monitoring of operation of the DMF device 100 and/or the plurality of electrodes 106.
  • the droplet phase fluid may form a fluid packet, which comprises a finite number of separate fluid droplets of the droplet phase fluid which may be moved together within the well region 104.
  • the electrodes 106 may form fluid droplets of the droplet phase fluid from the fluid packet, as further described herein.
  • the droplet phase fluid may be inserted to the well region 104 via a pipette or other object containing a volume of the droplet phase fluid and that is inserted into the fluidic inlet 112 and which forms the fluid packet of the droplet phase fluid.
  • the droplet phase fluid may be generated by mixing a sample and/or reagents, which may be in solid or fluid form, with an aqueous fluid or other fluid with the second density and that is immiscible with the continuous phase fluid 110.
  • the fluid droplets of the droplet phase fluid may be formed using the plurality of electrodes 106.
  • electrowetting forces generated by the electrodes 106 may be used to split a fluid packet into fluid droplets of the droplet phase fluid.
  • the electrowetting forces are generated by applying an electric field via the electrodes 106, and which cause individual fluid droplets of the droplet phase fluid to pull off from the fluid packet.
  • the electric field may cause a change in conductivity and permittivity at the interface between the droplet phase fluid and the continuous phase fluid 110 and produces an electric force on the interface.
  • the electric force may cause stress on the interface, which may be referred to as a Maxwell stress, or when integrated over the area of the interface, this may be referred to as the Maxwell force.
  • the fluid droplet of the droplet phase fluid is broken off from the fluid packet of the droplet phase fluid.
  • the droplet phase fluid 214-1 , 214-2 as a fluid packet 214-1 , may be pulled into a shape that contains a neck 221 , and then pulled further by the electrowetting forces, with the neck 221 breaking off to form a fluid droplet 214-2 of the droplet phase fluid 214-1 , 214-2.
  • At least two of the electrodes 206-1 , 206-2, 206-3, 206-4, 206-5, 206-6 of the well region 204 may provide electrowetting forces on the fluid packet 214-1 of the droplet phase fluid 214-1 , 214-2 to form the neck 221 and break off the neck 221 to form the fluid droplet 214-2 of the droplet phase fluid 214-1 , 214-2 that is smaller than the fluid packet 214-1.
  • the plurality of electrodes 206-1 , 206-2, 206-3, 206-4, 206-5, 206-6 may include a first electrode next to a second electrode, where the first electrode is larger than the second electrode (not illustrated by FIG. 2B), which may be used to pull off the fluid droplet 214-2 of the droplet phase fluid 214-1 , 214-2 from the fluid packet 214-1 using electrowetting forces.
  • the primary chamber 108 is coupled to the well region 104.
  • the primary chamber 108 includes and/or refers to a chamber in which at least a portion of the chemical processing operations are performed in.
  • a continuous phase fluid 110 is disposed within the primary chamber 108.
  • the continuous phase fluid 110 has a first density that is greater than a second density of the droplet phase fluid.
  • the continuous phase fluid 110 may include an inert fluid filler, such as an oil fluid.
  • the continuous phase fluid 110 includes an oil fluid and the droplet phase fluid includes an aqueous fluid. Examples are not so limited and the continuous phase fluid 110 can include any fluid that is immiscible with the droplet phase fluid and is denser than the droplet phase fluid.
  • the continuous phase fluid 110 includes a fluorinated oil, such as FC-40 or FC-3283.
  • Non-limiting examples of the continuous phase fluid 110 include FC-40, FC-43, FC-77, fluorophoroheptane (FC-84), FC-3283, perfluoro-n-octane, perfluorodecalin, perfluorophenanthrene, perfluorohexyloctane, octofluoropropane, decafluorobutane, perfluoropentane, perfluorohexane, perfluorooctane, decafluoropentane, perfluoro(2-methyl-3- pentaone), perfluoro- 15-crown-5-ether, bis-(perfluorobutyl) ethane, perfluorobutyl tetrahydrofuran, bi-perfluorohexyl ethane, perfluoro-n-hexane, perfluorooctyl bromide, perfluorotributylamine, perfluorotripent
  • the continuous phase fluid 110 may have a density of between about 1.1 and about 3.0 grams/centimeter 3 (g/cm 3 ), about 1.2 and about 3.0 g/cm 3 , about 1 .3 and about 3.0 g/cm 3 , about 1 .3 and about 2.8 g/cm 3 , about 1 .3 and about 2.6 g/cm 3 , about 1 .3 and about 2.4 g/cm 3 , about 1 .3 and about 2.2 g/cm 3 , about 1 .3 and about 2.0 g/cm 3 , about 1 .3 and about 1 .9 g/cm 3 , about 1 .3 and about 1 .8 g/cm 3 , about 1 .3 and about 1 .7 g/cm 3 , or about 1 .3 and about 1 .6 g/cm 3 , among other ranges.
  • g/cm 3 grams/centimeter 3
  • g/cm 3 grams
  • the continuous phase fluid 110 may have a molecular weight of between about 100 g/mole (mol) and about 900 g/mol, about 100 g/mol and about 850 g/mol, about 100 g/mol and about 800 g/mol, about 100 g/mol and about 750 g/mol, about 100 g/mol and about 700 g/mol, about 100 g/mol and about 650 g/mol, about 150 g/mol and about 600 g/mol, about 150 g/mol and about 500 g/mol, about 150 g/mol and about 850 g/mol, about 200 g/mol and about 850 g/mol, about 250 g/mol and about 850 g/mol, about 300 g/mol and about 800 g/mol, or about 400 g/mol and about 700 g/mol, among other values.
  • the continuous phase fluid 110 may have a boiling point of between about -40 degrees Celsius (°C) and about 200 °C, about 30 °C and about 200 °C, about 50 °C and about 200 °C, about 100 °C and about 200 °C, about 125 °C and about 200 °C, about 150 °C and about 200 °C, about 30 °C and about 150 °C, about 30 °C and about 125 °C, or about 30 °C and about 100 °C, among other values.
  • °C degrees Celsius
  • the DMF device 200 may further include a fluid actuator 218 disposed proximal to the primary chamber 208.
  • a fluid actuator includes and/or refers to circuitry and/or a physical structure that causes movement of fluid.
  • the fluid actuator 218 may be used to provide fluid flow within the primary chamber 208.
  • the fluid actuator 218 may actuate to move the fluid droplets of the droplet phase fluid along a (second) portion of the microfluidic path associated with the primary chamber 208.
  • Example fluid actuators include a (second) plurality of electrodes, a fluidic pump, a magnetostrictive element, an ultrasound source, mechanical/impact driven membrane actuators, and magneto-restrictive drive actuators, among others.
  • example fluidic pumps include a piezo-electric pump and a resistor, such as a thermal inkjet resistor (TIJ).
  • TIJ thermal inkjet resistor
  • fluid droplets of the droplet phase fluid formed by the plurality of electrodes 206-1 , 206-2, 206-3, 206-4, 206-5, 206-6 may be further reduced in size while in the primary chamber 208.
  • the fluid actuator 218 may generate a flow of the continuous phase fluid 210 within the primary chamber 208 that is used to form the fluid droplets of the droplet phase fluid.
  • the flow may include a cross-flow, an angleflow, or a co-flow with respect to the flow of the droplet phase fluid caused by the plurality of electrodes 206-1 , 206-2, 206-3, 206-4, 206-5, 206-6 or flow caused by another fluid actuator disposed within the primary chamber 208, which causes the fluid droplets of the droplet phase fluid to split in two as the two fluid flows intersect.
  • the well region 204 may include a well 213 having a first dimension D1 that is greater than a second dimension D2 of the primary chamber 208.
  • the first and second dimensions D1 , D2 may include a height, a width, a diameter, and/or a volume.
  • the first and second dimensions D1 , D2 include a first height and a second height
  • the well region 204 further includes a taper portion 215 that transitions from the first height proximal to the well 213 toward the second height at a fluidic connection between the well region 204 and the primary chamber 208.
  • a taper portion 215 includes and/or refers to a portion of the well region 204 that reduces in size from a first end 207 to a second end 211.
  • the taper portion 215 may assist in providing greater control of formation and/or flow of fluid droplets of the droplet phase fluid as compared to a well region 204 that is the same dimension throughout (e.g., D1) by preventing or mitigating fluid droplets of the droplet phase fluid from being trapped by a ceiling corner of the well region 204.
  • the well region 204 may be sized to contain greater amounts of fluid than the primary chamber 208.
  • the well region 204 may hold volumes of between 1-50 pL, although examples are not so limited.
  • the DMF device 100 further includes a fluidic inlet 112 fluidically coupled to the well region 104 to input the droplet phase fluid to the DMF device 100.
  • the fluidic inlet 112 may include an inlet port, e.g., an aperture, that is fluidically coupled to a channel that fluidically couples to the well region 104.
  • a volume of the droplet phase fluid may be input to the inlet port and flows along the channel to the well region 104.
  • a pipette or other fluid source may be used to input the droplet phase fluid to the fluidic inlet 112.
  • the well region 104 may further include a continuous phase fluid disposed therein, which may include the continuous phase fluid 110 or another fluid.
  • the continuous phase fluid 110 may be further disposed within the well region 104.
  • the plurality of electrodes 506-1 , 506-2, 506-3, 506-4 of the well region 504 may include actuating electrodes disposed proximal to a ceiling surface 517 of the DMF device 500 with respect to a direction of gravity.
  • a ceiling surface includes and/or refers to a top or overhead surface of the well region and/or primary chamber with respect to gravity.
  • a floor surface includes and/or refers to a bottom or lower surface of the well region and/or primary chamber with respect to gravity.
  • a second continuous phase fluid which is different than the continuous phase fluid 110, is disposed within the well region 104.
  • the second continuous phase fluid may have a third density that is less than the second density of the droplet phase fluid.
  • the continuous phase fluid 110 and/or the second continuous phase fluid are immiscible with the droplet phase fluid.
  • Examples of the second continuous phase fluid may include silicon oil.
  • the plurality of electrodes 606-1 , 606-2, 606-3 of the well region 604 may include actuating electrodes disposed proximal to a floor surface 619 of the DMF device 660 with respect to a direction of gravity.
  • the actuating electrodes are disposed proximal to the floor surface 619 and the second continuous phase fluid 610-2 is less dense than the droplet phase fluid 614-1 , 614-2, upon inserting the droplet phase fluid 614-1 , 614-2 into the well region 604, the droplet phase fluid 614-1 , 614-2 migrates down and/or toward the actuating electrodes.
  • the housing 202-1 , 202-2 may include a first substrate 202-1 and a second substrate 202-2.
  • the first substrate 202-1 and second substrate 202-2 may be manufactured with one as the top substrate, e.g., the first substrate 202-1 , and the other as the bottom substrate, e.g., the second substrate 202-2.
  • the top substrate may include a transparent lid, and, in other examples, both the top and bottom substrates include a transparent lid.
  • the ceiling surface 217 and floor surface 219 may be associated with one of the first substrate 202-1 (e.g., top) and second substrate 202-2 (e.g., bottom) of the DMF device 200.
  • the first substrate 202-1 is associated with the ceiling surface 217 and the second substrate 202-2 is associated with the floor surface 219.
  • the housing may be flipped upside-down during operation, and the first substrate 202-1 is associated with the floor surface and the second substrate 202-2 is associated with the ceiling surface.
  • ceiling surface and floor surface are with respect to gravity, with the floor surface being in the direction of gravity and the ceiling surface being in the opposite direction of gravity.
  • the DMF device 300 may include circuitry 320 supported by the housing 302-1 , 302- 2.
  • the circuitry 320 may be communicatively coupled to the plurality of electrodes 306-1 , 306-2, 306-3, 306-4 to actuate the plurality of electrodes 306- 1 , 306-2, 306-3, 306-4 and, in response, to cause application of electrowetting forces on the droplet phase fluid within the well region 304 to drive the droplet phase fluid to the primary chamber 308 as fluid droplets of the droplet phase fluid.
  • the plurality of electrodes 306-1 , 306-2, 306-3, 306-4 may be actuated to provide electrowetting forces on fluids within or proximal to the microfluidic path 305 and to draw the fluids along the microfluidic path 305.
  • Examples are not limited to the circuitry 320 being supported by the housing 302-1 , 302-2, and, in some examples, the circuitry 320 may be external to the housing 302-1 , 302-2 and/or the DMF device 300.
  • the DMF device 100 may include additional well regions and fluidic inlets, as further illustrated by FIGs. 7B-7C.
  • the DMF device 100 may include a plurality of well regions fluidically coupled to the primary chamber 108, wherein the plurality of well regions include the well region 104, and a plurality of fluidic inlets fluidically coupled to the plurality of well regions, wherein the plurality of fluidic inlets include the fluidic inlet 112.
  • the DMF device 100 may include between 1 and 96 well regions, 8 and 96 well regions, 8 and 16 well regions, 96 well regions, 8 well regions, and 16 well regions, as well as coupled fluidic inlets and other variations.
  • FIGs. 2A-2C illustrate different example DMF devices, in accordance with examples of the present disclosure.
  • Each of the DMF device 200, 201 , 203 of FIGs. 2A-2C may comprise at least some of substantially the same features and attributes as DMF device 100 of FIG. 1 , as shown by the similar numbering.
  • each DMF device 200, 201 , 203 includes a housing formed by a first substrate 202-1 and a second substrate 202-2, a well region 204 including a plurality of electrodes 206-1 , 206-2, 206-3, 206-4, 206-5, 206-6 (herein generally referred to as “the electrodes 206” for ease of reference), a primary chamber 208 filled with a continuous phase fluid 210, and a fluidic inlet 212.
  • the DMF devices 200, 201 , 203 include a lid and the fluidic inlet 212 is disposed in and through the lid. The common features and attributes are not repeated for ease of reference.
  • the plurality of electrodes 206 may be disposed within the microfluidic path in a variety of different arrangements and include different types and numbers of electrodes. Examples are not limited to the number of electrodes illustrated by the DMF device 200, 201 , 203 (as well as any of the DMF devices) and may include more or less electrodes.
  • the DMF device 200 includes the plurality of electrodes 206 disposed in the well region 204 that include a plurality of actuating electrodes 206-1 , 206-2, 206-3, 206-4, 206-5 and a ground electrode 206-6.
  • the actuating electrodes 206-1 , 206-2, 206-3, 206-4, 206-5 may be disposed on or within the first substrate 202-1 and the ground electrode 206-6 may be disposed on or within the second substrate 202-2.
  • 3, 206-4, 206-5 may allow for greater control of fluid flow and/or formation of fluid droplets of the droplet phase fluid as compared to using fluid (e.g., the continuous phase fluid and/or droplet phase fluid) as ground.
  • fluid e.g., the continuous phase fluid and/or droplet phase fluid
  • 206-5 may go to ground. In some instances, without the use of the ground electrode 206-6, a stray charge may accumulate in the DMF device 200, which produces an electric field and causes forces on fluid therein.
  • the plurality of actuating electrodes 206-1 , 206-2, 206-3, 206-4, 206-5 may be arranged in an array, which may be used to provide localized resolution of the electric field used to provide fluid flow and droplet formation of the droplet phase fluid.
  • the well region 204 may include a well 213 and a taper portion 215.
  • the well 213 may have a first height D1 and the primary chamber 208 may have a second height D2.
  • the taper portion 215 may transition from the first height D1 to the second height D2 at a fluidic connection between the well region 204 and the primary chamber 208.
  • the first height D1 may be between about 300 pm and about 2 mm
  • the second height D2 may be between about 30 pm and 400 pm.
  • D1 may be between about 700 pm and about 2 mm, about 1 mm and about 2 mm, about 700 pm and about 1 mm, or about 300 pm and about 1 mm, among other ranges.
  • D2 may be between about 100 pm and about 400 pm, about 150 pm and about 400 pm, about 30 pm and about 300 pm, about 30 pm and about 200 pm, or about 30 pm and about 150 pm, among other ranges.
  • a portion of the actuating electrodes 206-1 , 206-2, 206-3, 206-4, 206-5 may be located on the taper portion 215.
  • the fluid flow within the primary chamber 208 may be provided by a variety of sources, such as via electrowetting, pumps, magnetic sources, and gravity, among other sources.
  • the primary chamber 208 may include a fluid actuator 218.
  • the fluid actuator 218 may be disposed on or proximal to the first substrate 202-1 and/or the second substrate 202-2.
  • Example fluid actuators include a fluidic pump, a plurality of electrodes used to provide electrowetting forces (e.g., similar to the plurality of electrodes 206), a magnetostrictive element, an ultrasound source, mechanical/impact driven membrane actuators, and magneto-restrictive drive actuators, among others.
  • a fluidic pump may comprise a piezoelectric-based pump.
  • a piezoelectric-based pump may include a pump assembly comprising a piezoelectric element combined with a pair of one-way valves to promote oneway directional flow through the pump and primary chamber 208 to which the pump is in fluid communication.
  • the fluidic pump include TIJ resistors.
  • Activation of the TIJ resistor may create the flow of fluid by firing drops of fluid from the primary chamber 208 and/or creating a vapor bubble.
  • the DMF device 200 may perform a variety of different operations on the fluid by driving the fluid along the microfluidic path and through the primary chamber 208. [0063]ln some examples, the well region 204 and the primary chamber 208 may be filled with the continuous phase fluid 210 which is denser than the droplet phase fluid.
  • the droplet phase fluid may migrate toward the actuating electrodes 206-1 , 206-2, 206-3, 206-4, 206-5 and a ceiling surface 217 of the DMF device 200 associated with the first substrate 202-1 .
  • the electrodes 206 may be actuated, via coupled circuitry, to move the droplet phase fluid toward the primary chamber 208.
  • the fluid actuator 218 may be actuated to provide a flow of the continuous phase fluid 210 disposed within the primary chamber 208.
  • the fluid droplets of the droplet phase fluid are formed by the actuating electrodes 206-1 , 206-2, 206-3, 206-4, 206-5, as previously described.
  • ground electrode 206-6 as a single electrode (e.g., an almost continuous electrode), examples are not so limited.
  • a plurality of ground electrodes may be disposed on or within the second substrate 202-2. In other examples, all electrodes are actuating, and no ground electrodes are used. In some examples, at different points in time, respective electrodes of the plurality 206 may be floating or set at ground, such as when the respective electrodes are not being used to draw the fluid along the microfluidic path.
  • the primary chamber 208 may include a second plurality of electrodes 216-1 , 216-2, 216-3, herein generally referred to as “the second plurality of electrodes 216” for ease of reference.
  • the second plurality of electrodes 216 may include a plurality of actuating electrodes 216-2, 216-3 and a ground electrode 216-1.
  • the actuating electrodes 216-2, 216-3 are disposed proximal to the first substrate 202-1 and a ground electrode 216-1 is disposed proximal to the second substrate 202-2.
  • actuating electrodes 216-2, 216-3 may disposed proximal to the second substrate 202-2 and the ground electrode 216-1 disposed proximal to the first substrate 202-1 and/or the DMF device 201 may not include the ground electrode 216-1.
  • the droplet phase fluid 214-1 , 214-2 migrates toward the actuating electrodes 206- 1 , 206-2, 206-3, 206-4, 206-5 and a ceiling surface 217 of the DMF device 201 associated with the first substrate 202-1 .
  • the electrodes 206 may be actuated, via coupled circuitry, to move the droplet phase fluid 214-1 , 214-2 toward the primary chamber 208 as fluid droplets of the droplet phase fluid 214-1 , 214-2.
  • the second plurality of electrodes 216 may be actuated to provide a flow of the continuous phase fluid 210 disposed within the primary chamber 208 and movement of the fluid droplets of the droplet phase fluid 214-1 , 214-2 along the primary chamber 208.
  • the primary chamber 208 is filled with the continuous phase fluid 210-1 and the well region 204 is filled with a second continuous phase fluid 210-2.
  • the second continuous phase fluid 210-2 has a third density that is less than the second density of the droplet phase fluid 214-1 , 214-2.
  • the droplet phase fluid 214- 1 , 214-2 migrates in the direction of gravity and toward a floor surface 219 of the DMF device 203 associated with the second substrate 202-2.
  • the DMF device 203 may be operated by flipping the DMF device 203 such that the first substrate 202-1 with the actuating electrodes 206-1 , 206- 2, 206-3, 206-4, 206-5 is associated with a floor surface of the DMF device 203.
  • the actuating electrodes 206-1 , 206- 2, 206-3, 206-4, 206-5 may be disposed on or proximal to the second substrate 202-2 and the ground electrode 206-6 may be disposed on or proximal to the first substrate 202-1.
  • the electrodes 206, 216 may have a variety of different arrangements and sizes.
  • the electrodes 206 within the well region 204 are smaller, larger, and/or the same size as the electrodes 216 of the primary chamber 208.
  • the electrodes 206, 216 may be arranged in linear arrays, two dimensional arrays, and/or may include ring electrodes, and interface devices may include more or less electrodes than illustrated.
  • Example DMF devices and/or apparatuses may include variations from that illustrated by FIGs. 1 and 2A-2C. As noted above, such variations may include but are not limited to the fluidic pumps and/or electrodes in the primary chamber, the number of fluidic inlets and/or well regions, the number of electrodes, and/or arrangement of electrodes, among others.
  • FIG. 3 illustrates an example apparatus including a DMF device and coupled circuitry, in accordance with examples of the present disclosure.
  • the DMF device 300 may comprise an example implementation of, or comprise at least some of substantially the same features and attributes as, any one of the examples DMF as described in association with at least FIGs. 1A-2C.
  • the DMF device 300 includes a housing 302-1 , 302-2 that defines a microfluidic path 305 including a well region 304 and a primary chamber 308, a plurality of electrodes 306-1 , 306-2, 306-3, 306-4 (herein generally referred to as “the electrodes 306” for ease of reference) supported by the housing 302-1 , 302-2 and disposed proximal to the well region 304, and a fluidic inlet 312 fluid ical ly coupled to the well region 304 to input a droplet phase fluid to the DMF device 300.
  • the plurality of electrodes 306 may include actuating electrodes and a ground electrode(s) disposed along the microfluidic path 305, although examples are not so limited. The details of the common features and attributes are not repeated for ease of reference.
  • a first continuous phase fluid 310-1 is disposed within the primary chamber 308 and a second continuous phase fluid 310-2 is disposed within the well region 304.
  • the first continuous phase fluid 310-1 has a first density that is greater than a second density of the droplet phase fluid.
  • the second continuous phase fluid 310-2 is the same type of fluid as the first continuous phase fluid 310-1 .
  • the first continuous phase fluid 310-1 and the second continuous phase fluid 310-2 may be the same type of oil fluid, such as a fluorinated oil.
  • the second continuous phase fluid 310-2 is different than the first continuous phase fluid 310-1.
  • the second continuous phase fluid 310-2 may have a third density that is less than the second density of the droplet phase fluid.
  • the first continuous phase fluid 310-1 and the second continuous phase fluid 310-2 each include an oil fluid and the droplet phase fluid includes an aqueous fluid. Examples are not so limited and the continuous phase fluids 310-1 , 310-2 can include any fluid that is immiscible with the droplet phase fluid.
  • the DMF device 300 includes a fluid actuator 318 disposed proximal to the primary chamber 308.
  • the fluid actuator 318 may include a plurality of electrodes to provide electrowetting forces or a fluidic pump, as previously described.
  • the housing 302-1 , 302-2 may include a lid and the fluidic inlet 312 is disposed on and through the lid, and the fluid actuator 318 is disposed proximal to the primary chamber 308.
  • the lid may be a transparent lid, in some examples.
  • the lid may be transparent and the electrodes may be transparent.
  • a transparent lid and/or electrodes may allow for viewing of fluid flow and/or chemical operations within the DMF device 300 by a user, which may be used to visually verify the DMF device 300 is functioning properly.
  • the apparatus 325 further includes circuitry 320.
  • the circuitry 320 is communicatively coupled to the plurality of electrodes 306 to selectively actuate the plurality of electrodes 306 and, in response, to cause application of electrowetting forces on the droplet phase fluid to drive the droplet phase fluid along the microfluidic path 305 from the well region 304 and to the primary chamber 308 in a droplet phase.
  • the circuitry 320 is further communicatively coupled to the fluid actuator 318 to actuate the fluid actuator 318 to flow the fluid droplets of the droplet phase fluid along a portion of the primary chamber 308.
  • the circuitry 320 is coupled to or forms part of the DMF device 300, and may track and/or control operation of the plurality of electrodes 306 and the fluid actuator 318. Such operations may comprise activation or actuation, deactivation, and other settings, such as setting to ground or floating and timings associated with the same.
  • the circuitry 320 may coordinate operations of the DMF device 300 including the flow of fluid and/or electrowetting-caused manipulation of fluid droplets of the droplet phase fluid within the DMF device 300, such as moving, merging, and/or splitting, respectively. Such manipulation may include causing fluid droplets of the droplet phase fluid to move along the microfluidic path 305 within the DMF device 300.
  • the various examples operations of the circuitry 320 may be operated interdependently and/or in coordination with each other, in at least some examples.
  • FIG. 4 illustrates an example method for flowing a droplet phase fluid within a well region and a primary chamber of a DMF device, in accordance with examples of the present disclosure.
  • the method 430 may be implemented using any of the above or below-described DMF devices and apparatuses.
  • the method 430 includes inputting a droplet phase fluid into a DMF device via a fluidic inlet of the DMF device, wherein the fluidic inlet is fluidically coupled to a well region of the DMF device that is filled with a continuous phase fluid with a first density that is greater than a second density of the droplet phase fluid.
  • the method 430 includes sequentially actuating a plurality of electrodes disposed proximal to the well region.
  • the method 430 includes, in response to the sequential actuation, flowing the droplet phase fluid toward the primary chamber from the well region, forming fluid droplets from the droplet phase fluid while flowing the droplet phase fluid into the primary chamber, and flowing the fluid droplets of the droplet phase fluid along the primary chamber.
  • the method 430 further includes allowing the droplet phase fluid to migrate toward a ceiling surface of the DMF device with respect to a direction of gravity.
  • the droplet phase fluid moves toward the ceiling surface via a buoyancy force.
  • a buoyancy force includes and/or refers to a force exerted on the droplet phase fluid that is in an opposite direction of gravity, e.g., toward the ceiling surface of the DMF device, and that opposes the weight of the droplet phase fluid immersed in the continuous phase fluid. As the droplet phase fluid has a density less than the continuous phase fluid, the buoyancy force is greater than gravity and causes the droplet phase fluid to move toward the ceiling surface.
  • the buoyancy force may be less than gravity and which causes the droplet phase fluid to move in the direction of gravity and toward the floor surface.
  • the droplet phase fluid may be allowed to migrate toward the ceiling surface prior to and/or concurrently with the sequential actuation.
  • the method 430 may further include filling the DMF device with the continuous phase fluid via the fluidic inlet, wherein the continuous phase fluid is filled within the well region and the primary chamber.
  • the DMF device may be flipped prior to filling the DMF device with the continuous phase fluid and/or inserting the droplet phase fluid.
  • Examples are not limited to methods as described by FIG. 4 and in some examples may include the use of multiple continuous phase fluids.
  • other methods may be directed to forming or manufacturing a DMF device and/or an apparatus as described herein.
  • An example method of manufacturing may include forming a housing defining a microfluidic path including the well region coupled to a fluidic inlet and the primary chamber and to support a plurality of electrodes and/or a fluid actuator disposed along the microfluidic path to move a droplet phase fluid along the microfluidic path and disposing the plurality of electrodes and/or a fluid actuator along the microfluidic path.
  • the method may further include including positioning circuitry for support by the housing for actuating the plurality of electrodes and/or the fluid actuator.
  • a housing may formed of a plurality of different materials which are in layers, e.g., layers of substrates, in a stack.
  • the different material layers may include a first (transparent) substrate material (e.g., top) layer and a second substrate material (e.g., bottom) layer, with etched or micromachined portions between that form the well region and the primary chamber, among other components.
  • At least one of the substrate layers may have electrodes formed thereon.
  • the first (transparent) substrate material and the second substrate layer may have a low energy coating (e.g., a polytetrafluoroethylene (PTFE), such as TeflonTM, fluorosilane, a polyamide, such as Kapton® FN, fluoroalkylsilane, 1 H,1 H,2H,2H- Perfluorodecyltriethoxysilane, trichloro(1 H,1 H,2H,2H-perfluorooctyl)silane)) proximal to and/or in contact with the chambers, wells, and/or channels of the DMF device and the electrodes, and/or a dielectric coating (e.g., a polyimide, such as Kapton®, Ethylene tetrafluoroethylene (ETFE), paralyne, alumina, silica, silicon nitride, aluminum nitride, aluminum oxide) proximal and/or in contact
  • a low energy coating includes and/or refers to a layer formed of a material having surface free energy less than 30 milliNewton/meter (mN/m).
  • the low energy coating may have a free energy of 20 mN/m, and/or may provide a contact angle hysteresis of less than about 10 degrees.
  • the stack may additionally include a planarization layer with a thickness that is proportional to the electrodes, which may be formed of SU-8, paralyne, Polydimethylsiloxane (PDMS), acrylates, among other materials.
  • the planarization layer may have a thickness between the same thickness as the electrodes (e.g., in well region and/or primary chamber) to plus 100 percent of the thickness of the electrodes (e.g., two times the thickness of the electrodes). In some examples, the planarization layer has a thickness of between the same thickness as the electrodes and plus 10 percent of the thickness of the electrodes, or the same thickness of the electrodes and plus 50 percent of the thickness of the electrodes, among other ranges.
  • the continuous phase fluid(s) e.g., an inert filler fluid
  • the chambers, wells, and/or channels may be a height in the range of about 10 pm to about 2 mm.
  • the various electrodes may be a length of about 40 pm to about 3 mm.
  • the low energy coating is formed of PTFE.
  • the dielectric coating may be formed of a polyimide (e.g., Kapton®) for ease of deposition.
  • the dielectric coating may be formed of silicon nitride.
  • the planarization layer may be formed of the same material as the dielectric coating, such as a polyimide, and which may reduce the number of fabrication steps.
  • the stack may include a low energy coating formed of PTFE, a dielectric coating formed of a polyimide (e.g., Kapton®), and a planarization layer formed of the polyimide (e.g., Kapton®).
  • control the flow of fluid within the well region and/or the primary chamber of any of the described DMF devices may be provided via ion emitters of the DMF device, instead of and/or by the electrodes of the well region.
  • a charge applicator may be brought into charging relation to a plate of the DMF device, whereby the charge applicator is to apply (e.g., deposit) charges onto the plate to cause an electric field which induces electrowetting movement of fluid within and through the DMF device.
  • the charge applicator is an addressable airborne charge depositing unit which may be brought into charging relation to the plate of the DMF device to deposit airborne charges onto the plate.
  • the charge applicator may be brought into releasable contact with, and charging relation to, the plate.
  • the charge applicator may generate and apply the charges having a first polarity and/or an opposite second polarity, depending on whether the charge applicator is to build charges on anisotropic decoupling layer of the DMF device or is to neutralize charges.
  • the first polarity may be positive or negative depending on the particular goals, while the second polarity is the opposite of the first polarity.
  • example DMF may omit the electrodes, which would otherwise be used to cause microfluidic operations such as moving, merging, and/or splitting droplets within the DMF device.
  • Charge refers to and/or ions (+/-) or free electrons.
  • FIGs. 5A-5E illustrate further example DMF devices, in accordance with examples of the present disclosure.
  • Each of the example DMF devices 500, 545, 551 , 553 of FIGs. 5A-5E comprise an example implementation of, or comprise at least some of substantially the same features and attributes as, any one of the example DMF devices as described in association with at least FIGs. 1A-3, as shown by the similar numbering with example variations described herein.
  • 5A- 5E include a housing formed by substrates 502-1 , 502-2, a well region 504, a primary chamber 508, a plurality of electrodes 506-1 , 506-2, 506-3, 506-4 (herein generally referred to as “the electrodes 506” for ease of reference), a fluid actuator 518, and a fluidic inlet 512.
  • the electrodes 506 for ease of reference
  • the fluid actuator 518 for ease of reference
  • a fluidic inlet 512 The details of the common features and attributes are not repeated for ease of reference.
  • a DMF device 500 may include a plurality of electrodes 506 that include actuating electrodes disposed on a second substrate 502-2.
  • the first substrate 502-1 may include a lid and may be transparent.
  • the continuous phase fluid 510 is disposed within both the well region 504 and the primary chamber 508.
  • the fluidic inlet 512 may include an inlet port 540 fluidically coupled to a channel 542 that fluidically couples to the well region 504.
  • the channel 542 is a convex-shaped channel, such as being U-shaped. The convex shaped channel may mitigate or prevent fluid from exiting out of the fluidic inlet 512 unintentionally.
  • the DMF device 500 may be flipped upside-down, such that the second substrate 502-2 is facing up and the first substrate 502-1 is facing down. While upside-down, the DMF device 500 may be filled with the continuous phase fluid 510.
  • the continuous phase fluid 510 may be inserted using a pipette 541 and/or robotics. After filling with the continuous phase fluid 510, a volume of the droplet phase fluid 514-1 , 514-2 may be inserted into the DMF via a pipette 541 , migrates toward the ceiling surface 517 associated with the second substrate 502-2, and forms a fluid packet 514-1 proximal to the ceiling surface 517.
  • the floor surface 519 may be associated with the first substrate 502-1 , in such examples.
  • the fluid packet 514-1 may flow toward the primary chamber 508 by the plurality of electrodes 506.
  • the plurality of electrodes 506 may be used to generate electrowetting forces on the fluid packet 514-1 to cause the movement of the fluid packet 514-1.
  • the fluid packet 514-1 may be moved within and through the well region 504 via principles of electrowetting movement, such as but not limited to electrowetting-on-dielectric (EWOD) movement.
  • EWOD electrowetting-on-dielectric
  • the plurality of electrodes 506 provide an electric field within the well region 504 and/or onto the fluid, and due to a charge of the droplet phase fluid, the droplet phase fluid is directed along the microfluidic path.
  • the plurality of electrodes 506 may be sequentially actuated to draw the fluid packet 514-1 along the microfluidic path toward the primary chamber 508 and to form fluid droplets of the droplet phase fluid 514-1 , 541-2, such as the illustrated fluid droplet 514-2 of the droplet phase fluid 514-1 , 541-2.
  • Driving fluid flow using the electrodes 506 may provide instantaneous or near instantaneous response and may utilize existing control source.
  • the fluid actuator 518 may actuate to drive fluid flow within the primary chamber 508.
  • the DMF device 545 of FIG. 5B may comprise substantially the same features and attributes as the DMF device 500 of FIG. 5A, with the addition of an anisotropic decoupling layer 546.
  • the anisotropic decoupling layer 546 may be disposed between the second substrate 502-2 containing the electrodes 506. Any of the above described device and/or substrates may include an anisotropic decoupling layer 546.
  • the anisotropic decoupling layer 546 may decouple the working areas of the DMF device 545 (e.g., the well region 504 and primary chamber 508) from electronics of the DMF device 545, such as the plurality of electrodes 506 and/or the fluid actuator 518.
  • the decoupling may allow for the working areas of the of the DMF device 545, which contain fluids, to be inexpensive and consumable.
  • the anisotropic decoupling layer 546 may be formed of metal microparticles or nanoparticles aligned to form chains in one direction and encased in a polymer matrix (e.g., polymethylacrylate).
  • the DMF device 551 of FIG. 5C may comprise substantially the same features and attributes as the DMF device 500 of FIG. 5A, with a fluidic inlet 512 that is differently shaped.
  • the fluidic inlet 512 is rectangular shaped and includes a channel 542 fluidically coupled to the well region 504.
  • the rectangular shape of the fluidic inlet 512 may allow for greater ease of use of robotics to fill the DMF device 551 with fluids, as compared to the shape of the fluidic inlet 512 illustrated by FIG. 5A.
  • the DMF device 551 of FIG. 5C may be used with a specialized pipette 543 which includes a loading tip 555 that is arranged at an angle with respect to the elongate portion 557 of the pipette 543.
  • the specialized pipette 543 may provide further efficiencies for robotics to be used to fill the DMF device 551 with fluids.
  • a DMF device 553 may include electrodes 506-1 , 506-2, 506-3, 516-1 , 516-2, 516-3, 516-4, 526-5, 516- 6, herein generally referred to as “the electrodes 506, 516”, that are disposed on or proximal to both substrates 502-1 , 502-2.
  • an etched or micromachined portion e.g., negative space form
  • the well region 504 may be attached to the first substrate 502-1 and is formed by a third substrate 502-3 which may be a lid.
  • a lid may be formed on both sides of the DMF device 553.
  • the DMF device 553 may be filled with the continuous phase fluid 510 by flipping the DMF device 553 upside-down, such that the fluidic inlet 512 is facing up. After filling with the continuous phase fluid 510, the DMF device 553 is flipped back, such that the first substrate 502-1 is on top, and then the droplet phase fluid 514-1 , 514-2 is inserted via the fluidic inlet 512. Surface tension may hold the meniscus 552 against gravity.
  • the droplet phase fluid 514-1 , 514-2 migrates toward a first plurality of electrodes 506-1 , 506-2, 506-3 disposed proximal to the well region 504 and forms a fluid packet 514-1 , and which are actuated to drive the fluid packet 514-1 toward the primary chamber 508 and to form the fluid droplet 514-2 of the droplet phase fluid 514-1 , 514-2.
  • a second plurality of electrodes 516-1 , 516-2, 516-3, 516-4, 516-5, 516-6 which may include the first plurality of electrodes 506-1 , 506-2, 506-3, may drive flow of fluid within the primary chamber 508, such as driving the flow the fluid droplets of the droplet phase fluid 514-1 , 514-2 along the primary chamber 508, as previously described.
  • the DMF device 553 may include multiple floor surfaces 519-1 , 519-2 and ceiling surfaces 517-1 , 517-2.
  • a first floor surface 519-1 may be associated with the third substrate 502-3 in the well region 504 and a second floor surface 519-2 may be associated with the first substrate 502-1 in the primary chamber 508.
  • a first ceiling surface 517-1 may be associated with the first substrate 502-1 in the well region 504 and a second ceiling surface 517-2 may be associated with the second substrate 502-2 in the primary chamber 508.
  • Examples DMF device and apparatuses including a DMF device are not limited to the variations illustrated by FIGs. 5A-5E. In various examples, the different variations and features illustrated by the devices may be combined in different combinations. In any of the above described examples, the DMF device(s) may draw fluid back into the well regions using the electrodes and/or fluid actuators.
  • FIGs. 6A-6B illustrate example DMF devices with two different continuous phase fluids, in accordance with examples of the present disclosure.
  • Each of the example DMF devices 660, 670 of FIGs. 6A-6B comprise an example implementation of, or comprise at least some of substantially the same features and attributes as, any one of the example DMF devices as described in association with at least FIGs. 1 A-5E, as shown by the similar numbering and with variations described herein.
  • 6A-6B include a housing formed by substrates 602-1 , 602-2, a well region 604, a primary chamber 608, a first plurality of electrodes 606-1 , 606-2, 606-3, 606-4 (herein generally referred to as “the first plurality of electrodes 606” for ease of reference), a fluid actuator formed of a second plurality of electrodes 616-1 , 616-2, 616-3, 616-4, 616-5, 616-6 (herein generally referred to as “the second plurality of electrodes 616” for ease of reference), and a fluidic inlet 612.
  • the details of the common features and attributes are not repeated for ease of reference.
  • the DMF devices 660, 670 may be filled with the continuous phase fluids 610-1 , 610-2 without flipping the DMF devices 660, 670 upside-down due to the less dense second continuous phase fluid 610-2 and which may allow for greater automation for filling the devices 660, 670 as compared to flipping the devices.
  • the DMF devices 660, 670 may include inlets which are rectangular shaped which, as previously described, may allow for greater use of using robotics.
  • a first continuous phase fluid 610-1 may be disposed within the primary chamber 608 and a second continuous phase fluid 610-2, which is different than the first continuous phase fluid 610-1 , may be disposed within the well region 604.
  • the first continuous phase fluid 610-1 may have a first density that is greater than a second density of the droplet phase fluid 614-1 , 614-2.
  • the second continuous phase fluid 610-2 may have a third density that is less than the second density of the droplet phase fluid 614-1 , 614-2.
  • the fluidic inlet 612 may be formed on and through a lid on the first substrate 602-1 .
  • the first continuous phase fluid 610-1 may be first inserted into the DMF devices 660, 670, followed by the second continuous phase fluid 610-2, and then the droplet phase fluid 614-1 , 614-2.
  • the droplet phase fluid 614-1 , 614-2 may migrate down toward the floor surface 619 associated with the second substrate 602-2 because the droplet phase fluid 614-1 , 614-2 is denser than the second continuous phase fluid 610- 2.
  • the first plurality of electrodes 606 are disposed on or proximal to the second substrate 602-2 and are actuated to drive flow of the droplet phase fluid 614-1 , 614-2, which may form a fluid packet 614-1 , toward the primary chamber 608 and to form fluid droplets of the droplet phase fluid 614-1 , 614-2, as illustrated by the fluid droplet 614-2 of the droplet phase fluid 614-1 , 614-2.
  • the second plurality of electrodes 616 may be used to flow the fluid droplets of the droplet phase fluid 614-1 , 614-2 along the primary chamber 608, as previously described. As the droplet phase fluid 614-1 , 614-2 has limited and/or minimal exposure to the second continuous phase fluid 610-2, partitioning of components into the interface may be mitigated.
  • the first plurality of electrodes 606 and the second plurality of electrodes 616 may be disposed on the same substrate, e.g., second substrate 602-2.
  • the first plurality of electrodes 606 and the second plurality of electrodes 616 may be disposed on the different substrates 602-1 , 602-2.
  • the fluid droplet 614-2 of the droplet phase fluid 614-1 , 614-2 is allowed to migrate toward the ceiling surface 617 of the DMF device 670.
  • FIGS. 7A-7C illustrate different views of example DMF devices, in accordance with examples of the present disclosure.
  • Each of the example DMF devices 700, 701 , 703 of FIGs. 7A-7C comprise an example implementation of, or comprise at least some of substantially the same features and attributes as, any one of the example DMF devices as described in association with at least FIGs. 1A-3 and 5A-6B, as shown by the similar numbering. The details of the common features and attributes are not repeated for ease of reference.
  • FIG. 7 A illustrates a three-dimensional view of a DMF device 700.
  • the DMF device 700 includes a housing formed by substrates 702-1 , 702-2, a well region 704, a primary chamber 708, and a fluidic inlet 512.
  • a plurality of electrodes are disposed on the first substrate 702-1 and/or the second substrate 702-2 proximal to the well region 704 and a fluid actuator is disposed on the first substrate 702-1 and/or the second substrate 702-2 proximal to the primary chamber 708.
  • the fluidic inlet 712 is disposed on and through the first substrate 702-1 , which may include a lid, as previously described.
  • example DMF devices 701 , 703 may include a plurality of fluidic inlets 712-1 , 712-2, 712-3, 712-4, 712-5, 712-6, 712-7, 712-8, 712-9, herein generally referred to as “the fluidic inlets 712”.
  • Each of the fluidic inlets 712 may be fluidically coupled to a different well region, with each of the different well regions being fluidically coupled to the primary chamber (not illustrated).
  • the fluidic inlets 712 may be disposed on the edges of the primary chamber.
  • the fluidic inlets 712 may be disposed anywhere with respect to the primary chamber.
  • the well regions may be formed as shown by the DMF device 553 of FIG. 5E.
  • DMF devices 701 , 703 may include between 1 and 96 fluidic inputs and well regions.
  • Circuitry such as the circuitry 320 of FIG. 3, may include a processor and a memory. Circuitry may comprise a processor and associated memories, and optionally communication circuitry. Example circuitry includes a processor electrically coupled to, and in communication with, memory to generate control signals to direct operation of a DMF device, as well as the particular portions, components, operations, instructions, and/or methods, as described herein. Example control signals include instructions stored in memory to direct and manage microfluidic operations.
  • the circuitry may be referred to as being programmed to perform the above-identified actions, functions, etc.
  • the circuitry In response to or based on commands received and/or via machine readable instructions, the circuitry generates control signals as described above.
  • the circuitry may be embodied in a general purpose computing device and/or incorporated into or associated with at least some of the example DMF devices, as well as the particular portions, components, electrodes, fluid actuators, operations, instructions, and/or methods, etc. as described herein.
  • Processor includes and/or refers to a presently developed or future developed processor that executes machine readable instructions contained in a memory or that includes circuitry to perform computations. Execution of the machine readable instructions, such as those provided via memory of the circuitry, may cause the processor to perform the above-identified actions, such as circuitry to implement operations via the various examples.
  • the machine readable instructions may be loaded in a random access memory (RAM) for execution by the processor from their stored location in a read only memory (ROM), a mass storage device, or some other persistent storage (e.g., non- transitory tangible medium or non-volatile tangible medium), as represented by memory.
  • the machine readable instructions may include a sequence of instructions, a processor-executable machine learning model, or the like.
  • memory comprises a computer readable tangible medium providing non-volatile storage of the machine readable instructions executable by a processor of circuitry.
  • the machine readable tangible medium may be referred to as, and/or comprise at least a portion of, a computer program product.
  • hard wired circuitry may be used in place of or in combination with machine readable instructions to implement the functions described.
  • circuitry may be embodied as part of at least one application-specific integrated circuit (ASIC), at least one field- programmable gate array (FPGA), and/or the like.
  • ASIC application-specific integrated circuit
  • FPGA field- programmable gate array
  • the circuitry not limited to any specific combination of hardware circuitry and machine readable instructions, nor limited to any particular source for the machine readable instructions executed by the circuitry.
  • the circuitry may be implemented within or by a stand-alone device, such as a microprocessor.
  • the circuitry may be partially implemented in interface devices and partially implemented in a computing resource separate from, and independent of, the example interface devices but in communication with the example interface devices.
  • the circuitry may be implemented via a server accessible via the cloud and/or other network pathways.
  • the circuitry may be distributed or apportioned among multiple devices or resources
  • the droplet phase fluid may include a sample fluid and/or reagents.
  • the droplet phase fluid may include an aqueous solution or fluid containing a sample, in solid or fluid form, and/or reagents.
  • a sample fluid refers to and/or any material, collected from a subject, such as biologic material.
  • Example samples include, but are not limited to, whole blood, blood plasma, and other body fluids, as well as tissue cell cultures obtained from humans, plants, or animals.
  • Such samples may contain any viral or cellular material, including all prokaryotic or eukaryotic cells, viruses, bacteriophages, mycoplasmas, protoplasts, and organelles.
  • Such biological material may comprise all types of mammalian and non-mammalian animal cells, plant cells, algae including blue-green algae, fungi, bacteria, protozoa, etc.
  • samples include whole blood and blood-derived products such as plasma, serum and buffy coat, urine, feces, cerebrospinal fluid or any other body fluids, tissues, cell cultures, cell suspensions, etc.
  • Other samples include fluids containing functionalized beads to which a portion of a biologic sample or other particles are attached.
  • Sample fluids may contain an analyte of interest, such as a substance (e.g., molecule, particle, protein, nucleic acid, antigen) of interest for a chemical process or test.

Abstract

Un exemple de dispositif microfluidique numérique (DMF) comprend un boîtier et une entrée fluidique. Le boîtier délimite une voie microfluidique comprenant une région de puits, une chambre primaire et un fluide en phase continue. La région du puits comprend une pluralité d'électrodes reposant sur le boîtier. La chambre primaire est couplée fluidiquement à la région du puits, et le fluide en phase continue est disposé dans la chambre primaire, le fluide en phase continue possédant une première densité supérieure à une seconde densité d'un fluide en phase de gouttelettes. L'entrée fluidique est couplée à la région du puits pour introduire le fluide en phase de gouttelettes dans le dispositif DMF.
PCT/US2022/013992 2022-01-27 2022-01-27 Dispositifs microfluidiques numériques à fluides en phase continue WO2023146521A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016197103A1 (fr) * 2015-06-05 2016-12-08 Miroculus Inc. Appareils et procédés microfluidiques numériques à matrice d'air destinés à limiter l'évaporation et l'encrassement de surface
WO2018067872A1 (fr) * 2016-10-05 2018-04-12 Abbott Laboratories Dispositifs et procédés d'analyse d'échantillon
WO2018187476A1 (fr) * 2017-04-04 2018-10-11 Miroculus Inc. Appareils microfluidiques numériques et procédés de manipulation et de traitement de gouttelettes encapsulées
US20200188920A1 (en) * 2017-06-20 2020-06-18 10X Genomics, Inc. Methods and systems for improved droplet stabilization

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016197103A1 (fr) * 2015-06-05 2016-12-08 Miroculus Inc. Appareils et procédés microfluidiques numériques à matrice d'air destinés à limiter l'évaporation et l'encrassement de surface
WO2018067872A1 (fr) * 2016-10-05 2018-04-12 Abbott Laboratories Dispositifs et procédés d'analyse d'échantillon
WO2018187476A1 (fr) * 2017-04-04 2018-10-11 Miroculus Inc. Appareils microfluidiques numériques et procédés de manipulation et de traitement de gouttelettes encapsulées
US20200188920A1 (en) * 2017-06-20 2020-06-18 10X Genomics, Inc. Methods and systems for improved droplet stabilization

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