WO2023048701A1 - Commandes de gouttelettes microfluidiques - Google Patents

Commandes de gouttelettes microfluidiques Download PDF

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Publication number
WO2023048701A1
WO2023048701A1 PCT/US2021/051416 US2021051416W WO2023048701A1 WO 2023048701 A1 WO2023048701 A1 WO 2023048701A1 US 2021051416 W US2021051416 W US 2021051416W WO 2023048701 A1 WO2023048701 A1 WO 2023048701A1
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WO
WIPO (PCT)
Prior art keywords
droplet
valve
dmf
board
oil
Prior art date
Application number
PCT/US2021/051416
Other languages
English (en)
Inventor
Michael W. Cumbie
Viktor Shkolnikov
Original Assignee
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.)
Filing date
Publication date
Application filed by Hewlett-Packard Development Company, L.P. filed Critical Hewlett-Packard Development Company, L.P.
Priority to PCT/US2021/051416 priority Critical patent/WO2023048701A1/fr
Publication of WO2023048701A1 publication Critical patent/WO2023048701A1/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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
    • 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
    • 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
    • B01L2400/049—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics vacuum

Definitions

  • a biological/chemical workflow may include single cell analysis, including single cell sequencing and associated library preparation. Such workflows may generate a large number of droplets (e.g., greater than 10,000) to serve as micro-reactors. The droplets can be manipulated and analyzed to perform the workflows.
  • FIG. 1 illustrates a block diagram of a top view of an example apparatus of the present disclosure
  • FIG. 2 illustrates a more detailed block diagram of an example apparatus of the present disclosure
  • FIG. 3 illustrates a top-view of an example flow field generated by the apparatus of the present disclosure
  • FIG. 4 illustrates a cross-sectional side view of a droplet in the apparatus near an injection port and an aspiration port
  • FIG. 5 illustrates a cross-sectional side view of the droplet in the apparatus being collected by the aspiration port
  • FIG. 6 illustrates a top view of a sequence of movements of a droplet within the apparatus of the present disclosure
  • FIG. 7 illustrates a block diagram of another example apparatus with feedback controls of the present disclosure
  • FIG. 8 illustrates a block diagram of another example apparatus with a single pressure controller of the present disclosure
  • FIG. 9 illustrates a block diagram of another example apparatus with a recirculating oil system of the present disclosure
  • FIG. 10 illustrates a block diagram of another example apparatus with multiple input droplet lines and/or multiple droplet collection lines of the present disclosure.
  • Examples described herein provide a microfluidic droplet control interface.
  • Many biological/chemical workflows benefit from having a large number of reactions occurring in parallel.
  • An example of a biological/chemical workflow may include single cell analysis, including single cell sequencing and associated library preparation.
  • Such workflows may generate a large number of droplets (e.g., greater than 10,000) to serve as micro-reactors. The droplets can be manipulated and analyzed to perform the workflows.
  • DMF digital microfluidic
  • the size of the DMF board may be increased. However, increasing the size of the DMF board would be undesirable, as this would increase the footprint of the DMF device. Thus, providing a system that can continuously move droplets on and off the DMF board at a through-put in a well-organized manner would increase the performance and efficiency of droplet operations by the DMF board.
  • the present disclosure provides a modified DMF device that provides continuous droplet control.
  • the droplets may be transported within an immiscible mixture with a carrier fluid.
  • the DMF device may have a collection region that includes an injection port and an aspiration port.
  • the injection port may provide the carrier fluid.
  • the droplet may be moved to the collection region on the DMF board to be mixed with the carrier fluid.
  • the droplet in the carrier fluid may be collected by the aspiration port.
  • the droplets may be collected in a known order within a collection line of the aspiration port to be dispensed in a desired manner.
  • droplets on the DMF board can be removed and/or added in a continuous manner at a high throughput to increase the number of workflows that may be performed.
  • the droplets may be moved in a known order and dispensed one droplet at a time in a known order into a desired destination.
  • FIG. 1 illustrates a block diagram of a top view of an example apparatus 100 of the present disclosure.
  • the apparatus 100 may include a digital microfluidics (DMF) board 102.
  • the DMF board 102 may include a collection region 104 that includes an injection port 106 and an aspiration port 108.
  • a droplet 110 may be manipulated by the DMF board 102 to move into the collection region 104. Although a single droplet 110 is illustrated in FIG. 1 , it should be noted that a plurality of droplets 110 may be located and/or manipulated by the DMF board 102 simultaneously.
  • the droplet 110 may contain analytes or compounds within a fluid.
  • the analytes or compounds may be mixed with other analytes or compounds within the fluid for analysis.
  • the droplet 110 may provide a mini-reactor for the reaction to occur, as described above.
  • the DMF board 102 may include a plurality of ports 114i to 114 n (hereinafter also referred to individually as a port 114 or collectively as ports 114).
  • a droplet 110 may be injected into the DMF board 102 to be manipulated by the DMF board 102.
  • the DMF board 102 may be an enclosed structure that includes a substrate with a plurality of electrodes 1161 to 116 m (hereinafter also referred to individually as an electrode 116 or collectively as electrodes 116) formed on the substrate.
  • a droplet 110 may be manipulated by selectively applying a voltage to desired electrodes 116.
  • the DMF board 102 may be able to move the droplet 110 to any desired location on DMF board 102, merge the droplet 110 with another droplet, split the droplet 110, and so forth, by applying a voltage in a desired sequence across the electrodes 116.
  • the injection port 106 may provide a continuous supply of a carrier fluid 112 within the collection region 104.
  • the droplet 110 may be mixed with the carrier fluid 112 in an immiscible mixture to be collected by the aspiration port 108.
  • the carrier fluid 112 may be any type of fluid that is immiscible with the droplet 110.
  • the carrier fluid 112 may be oil.
  • the DMF board 102 may also have a separate supply of carrier fluid (not shown) that is used to manipulate the droplet 110.
  • the aspiration port 108 may collect a series of droplets 110 in a desired order.
  • the sequence of the droplets 110 may be tracked within a collection line (shown in FIG. 2 and discussed below) and dispensed into a desired location.
  • the apparatus 100 of the present disclosure provides a way to collect droplets 110 off of the DMF board 102 and to allow the DMF board 102 to have a higher throughput for processing/manipulation of droplets 110.
  • the collection region 104 is illustrated at a particular location on the DMF board 102, it should be noted that the collection region 104 may be located anywhere on the grid of electrodes 116.
  • the size or area (e.g., a length x a width) of the collection region 104 may be a function of a variety of different parameters.
  • the size of the collection region 104 may be a function of a size of the droplets 110, a size of the DMF board 102, an amount of vacuum that is pulled by the aspiration port 108, and the like.
  • the amount of vacuum that is pulled by the aspiration port 108 may be controlled to match the desired area for the collection region 104.
  • the amount of vacuum that is generated may be sufficient to work within a defined boundary of the collection region 104, as discussed in further details below.
  • the larger the amount of vacuum that is pulled the larger the area of the collection region 104 may be.
  • the smaller the amount of vacuum that is pulled the smaller the area of the collection region 104 may be.
  • the carrier fluid 112 may be kept within the collection region 104 by the corresponding amount of vacuum that is pulled by the aspiration port 108.
  • the apparatus 100 may include a plurality of injection ports 106.
  • multiple injection ports 106 may be used to manipulate a shape of the carrier fluid 112 within the collection region 104.
  • the multiple injection ports 106 may be used to create a desired shape of the carrier fluid 112 within the collection region 104.
  • FIG. 2 illustrates a more detailed block diagram of an apparatus 200 of the present disclosure.
  • the apparatus 200 includes the DMF board 102, the injection port 106, and the aspiration port 108 of the apparatus 100 illustrated in FIG. 1 and described above.
  • the injection port 106 may be coupled to an oil reservoir 202.
  • the oil reservoir 202 may be located upstream from the injection port 106.
  • a pressure controller 204 may be communicatively coupled to the oil reservoir 202.
  • the pressure controller 204 may monitor a pressure inside of the DMF board 102.
  • the pressure controller 204 may adjust a flow rate of the carrier fluid or oil injected into the DMF board 102 to maintain a constant pressure or a desired pressure level.
  • the pressure controller 204 may be coupled to a flow meter or a flow valve (not shown) located between the oil reservoir 202 and the injection port 106.
  • the aspiration port 108 may be coupled to a valve 210.
  • the valve 210 may also be coupled to a collection line 212 and a second oil reservoir 206.
  • the oil reservoir 206 may be coupled downstream from the aspiration port 108.
  • a second pressure controller 208 may be coupled to the oil reservoir 206.
  • the pressure controller 208 may control an amount of carrier fluid or oil that is released into the carrier line 212 to maintain a constant pressure in the carrier line 212.
  • a flow meter or a flow valve (not shown) may be located between the valve 210 and the oil reservoir 206 to control the flow of the oil from the oil reservoir 206 via control signals from the pressure controller 208.
  • a second valve 214 may be coupled to the carrier line 212 downstream from the first valve 210.
  • the valve 214 may be coupled to a vacuum or vacuum generator 218 and a dispensing port 216.
  • the vacuum 218 may generate a vacuum or air flow to suck droplets 110 mixed with the carrier fluid 112 one droplet at a time into the aspiration port 108 within the collection region 104.
  • the amount of vacuum that is generated by the vacuum 218 may determine a size of the collection region 104.
  • the boundaries of the collection region 104 may also be controlled by the amount of vacuum that is generated.
  • the boundaries of the collection region 104 should be defined to prevent a droplet 110 from being collected by the aspiration port 108 when outside of the collection region 104. Said another way, the boundaries of the collection region 104 may be defined so as to not disturb a droplet 110 on an electrode 116 located outside of the collection region 104.
  • FIG. 3 illustrates an example flow field 300 that can be created by a controlled amount of vacuum.
  • the flow field 300 may define the boundaries or size of the collection region 104.
  • FIG. 3 illustrates arrows 302 to show how the carrier fluid 112 flows within the collection region 104.
  • arrows 304 illustrate how the oil provided by the DMF board 102 flows within the collection region 104.
  • the size of the collection region 104 may be increased as the size of the flow field 300 would be increased. For example, more vacuum would pull more oil of the DMF board 102 from a larger distance.
  • the size of the collection region 104 may be decreased as the size of the flow field 300 would be decreased. For example, less vacuum would pull less oil of the DMF board 102 in from a smaller distance.
  • a droplet sensor 222 may be coupled to an end of the dispensing port 216.
  • the droplet sensor 222 may be an optical sensor or an image sensor that can monitor the dispensing port 216.
  • the droplet sensor 222 may provide a signal or image to provide confirmation that a droplet 110 in the dispensing port 216 was dispensed to a dispensing location 220.
  • the droplet sensor 222 may also provide confirmation that the correct number of droplets 110 was dispensed into the dispensing location 220.
  • the dispensing location 220 may be any type of receptacle to receive the droplet 110.
  • the examples herein illustrate the dispensing location 220 as a two-dimensional well on a movable stage.
  • the stage may move a desired well that is to receive the droplet 110 below the dispensing port 216.
  • the dispensing location 220 may be another DMF board 102, a reactor, another type of collection plate or well, and the like.
  • the valves 210 and 214 may be controlled to switch between a collection operation to collect the droplet 110 from the DMF board 102 and a dispensing operation to dispense the droplet 110 into the dispensing location 220.
  • a first combination of valve positions of the valves 210 and 214 may allow the aspiration port 108 to collect the droplet 110 from the collection region 104.
  • the valve 210 may block flow from the oil reservoir 206 and allow flow from the aspiration port 108 to the collection line 212.
  • the valve 214 may block flow to the dispensing port 216 and allow flow from the collection line 212 to the vacuum 218.
  • the vacuum 218 may generate a vacuum that flows from the aspiration port 108, through the valve 210, through the collection line 212, and the valve 214.
  • valves 210 and 214 may be controlled to be moved into a second combination of valve positions.
  • the valve 210 may be controlled to block flow from the aspiration port 108 and allow oil from the oil reservoir 206 to flow through the valve 210.
  • the valve 214 may be controlled to block flow from the vacuum 218 and allow flow to the dispensing port 216.
  • the oil from the oil reservoir 206 may be used to push the droplets 110 in the collection line 212 and out of the dispensing port 216 one droplet at a time.
  • FIGs. 4 and 5 illustrate a cross-sectional view of the droplet 110 near the injection port 106 and the aspiration port 108 of the DMF board 102.
  • the DMF board 102 may be an enclosed system.
  • the injection port 106 and the aspiration port 108 may be integrally formed as part of the enclosed system of the DMF board 102.
  • the DMF board 102 may include openings to receive separate injection and aspiration lines that are inserted into the openings of the DMF board 102 to form the injection port 106 and the aspiration port 108.
  • the injection port 106 may provide a continuous supply of a carrier fluid 112.
  • the droplet 110 may be manipulated to move near the collection region 104 of the DMF board 102. As shown in FIG. 4, the droplet 110 may be moved near the injection port 106 and the aspiration port 108.
  • FIG. 5 illustrates how the droplet 110 may be collected by the aspiration port 108.
  • the aspiration port 108 may collect the droplet 110 mixed with the carrier fluid 112.
  • the diameter of the aspiration port 108 and the amount of vacuum may be selected to reduce an amount of shear applied to the droplet 110.
  • the diameter of the aspiration port 108 and the amount of vacuum may be selected to ensure that the droplet does not break up or burst when being collected by the aspiration port 108.
  • the droplet 110i may be manipulated to move closer to the collection region 104. For example, a voltage may be applied to select electrodes 116 to attract the droplet 110i to the charged electrodes. The droplet 110 may be moved as the voltage is applied to a sequence of electrodes 116 towards the collection region 104.
  • the droplet 110i may enter the collection region 104.
  • the droplet 110i may be mixed with the carrier fluid 112.
  • the carrier fluid 112 may be immiscible with the fluid of the droplet 110i .
  • a mixture of the carrier fluid 112 and the droplet 110i may be collected by the aspiration port 108 as illustrated by an arrow 602.
  • FIGs. 7-10 illustrate different examples and/or variations of the apparatus 100 and 200.
  • FIG. 7 illustrates an example apparatus 700 with a feedback control.
  • the apparatus 700 may include the DMF board 102 with the injection port 106 and aspiration port 108, as illustrated in FIG. 1.
  • the apparatus 700 may include an oil reservoir 702 and pressure controller 704 upstream from the injection port 106.
  • the apparatus may also include an oil reservoir 706, a pressure controller 708, and a vacuum 718 downstream from the aspiration port 108.
  • a valve 710 and a valve 714 may be located on opposite ends of a collection line 712 to control the flow between the aspiration port 108, the oil reservoir 706, the vacuum 718, and a dispensing port 716, as described above.
  • the droplets 110 may be dispensed out of the dispensing port 716 into a dispensing location 720.
  • the apparatus 700 may include a sensor 730 and a proportional integral derivative (PI D) controller 732.
  • the sensor 730 may be a pressure sensor or an optical sensor.
  • the sensor 730 may be used to monitor the flow field (e.g., the flow field 300 illustrated in FIG. 3) within the collection region 104.
  • the flow field may be monitored based on a pressure value with a pressure sensor or based on an appearance of the flow field with an optical sensor.
  • the PID controller 732 may be communicatively coupled to a flow meter (FM) 734 and a flow meter (FM) 736.
  • the flow meter 734 may be located between the oil reservoir 702 and the injection port 106.
  • the flow meter 736 may be located between the valve 710 and the aspiration port 108.
  • the PID controller 732 may control the flow meter 734 and the flow meter 736 based on feedback collected from the sensor 730. For example, if the pressure is too low or too high, the PID controller 732 may control the flow meter 734 and/or the flow meter 736 to adjust the pressure of the collection region 104.
  • the PID controller 732 may control the flow meter 734 and/or the flow meter 736 to adjust the shape of the flow field in the collection region 104.
  • a tracer dye may be injected into the carrier fluid 112 to track a shape of the flow field within the collection region 104.
  • FIG. 8 illustrates an example apparatus 800 with a single pressure controller 804.
  • the apparatus 800 may include the DMF board 102 with the injection port 106 and aspiration port 108, as illustrated in FIG. 1.
  • the apparatus 800 may include an oil reservoir 802 and pressure controller 804 upstream from the injection port 106.
  • the apparatus may also include a vacuum 818 downstream from the aspiration port 108.
  • a valve 810 and a valve 814 may be located on opposite ends of a collection line 812 to control the flow between the aspiration port 108, the vacuum 818, and a dispensing port 816, as described above.
  • the droplets 110 may be dispensed out of the dispensing port 816 and into a dispensing location 820.
  • the apparatus 800 may include a single oil reservoir 802 and a single pressure controller 804.
  • An additional valve 806 may be located between the oil reservoir 802, the injection port 106, and the valve 810.
  • the valve 806 may be controlled to direct carrier fluid 112 (e.g., oil) from the oil reservoir 802 to the injection port 106 or to the carrier line 812.
  • the valve 806 may be controlled to block flow toward the valve 810 and allow the carrier fluid 112 to be delivered to the injection port 106.
  • the valves 810 and 814 may be controlled to allow flow from the aspiration port 108 through the collection line 812 and to the vacuum 818.
  • the valve 810 may be positioned to block flow from the valve 806.
  • the valve 814 may be positioned to block flow to the dispensing port 816.
  • the valve 806 may be controlled to allow the carrier fluid 112 to flow towards the valve 810.
  • the valve 810 may be positioned to block flow from the aspiration port 108 and allow the carrier fluid 112 to pass through the valve 810 towards the carrier line 812.
  • the valve 814 may be positioned to block flow from the vacuum 818 and to allow flow towards the dispensing port 816.
  • the carrier fluid 112 from the oil reservoir 802 may be used to push the droplet 110 through the collection line 812 and out of the dispensing port 816.
  • FIG. 9 illustrates an example apparatus 900 with a recirculating oil system of the present disclosure.
  • the apparatus 900 may include the DMF board 102 with the injection port 106 and aspiration port 108, as illustrated in FIG. 1.
  • the apparatus 900 may include an oil reservoir 902 and pressure controller (e.g., pump 904) upstream from the injection port 106.
  • a valve 910 and a valve 914 may be located on opposite ends of a collection line 912 to control the flow between the aspiration port 108 and a dispensing port 916, as described above.
  • the droplets 110 may be dispensed out of the dispensing port 916 into a dispensing location 920.
  • the apparatus 900 may include a single oil reservoir 902 and a valve 906.
  • the valve 906 may control the flow of the carrier fluid 112 from the oil reservoir 902 towards the injection port 106 or towards the collection line 912.
  • the apparatus 900 may include a recirculating oil system that includes a damper, filter, and air separator 918, and the pump 904. For example, some of the excess carrier fluid 112 or oil may be collected by the recirculating oil system to be reused in the oil reservoir 902. The damper, filter, and air separator 918 may filter the used carrier fluid 112 and remove air from the carrier fluid 112. The carrier fluid 112 may then be returned to the oil reservoir 902 via the pump 904.
  • the pump 904 may be any type of positive displacement pump.
  • the pump 904 may be a peristaltic pump. It should be noted that although a particular location of the pump 904 is illustrated in FIG. 9, the pump 904 may be positioned in other locations. For example, the pump 904 may also be located between the aspiration port 108 and the valve 910.
  • FIG. 10 illustrates an example apparatus 1000 with multiple input droplet lines and/or multiple collection lines.
  • the apparatus 1000 may include the DMF board 102 with the injection port 106 and aspiration port 108, as illustrated in FIG. 1.
  • the apparatus 1000 may include an oil reservoir 1002 and pressure controller 1004 upstream from the injection port 106.
  • the apparatus may also include an oil reservoir 1006, a pressure controller 1008, and a vacuum 1018 downstream from the aspiration port 108.
  • a valve 1010 and a valve 1014 may be located on opposite ends of a plurality of collection lines 1012i to 1012 n (hereinafter also referred to individually as a collection line 1012 or collectively as collection lines 1012) to control the flow between the aspiration port 108, the oil reservoir 1006, the vacuum 1018, and a dispensing port 1016, as described above.
  • the droplets 110 may be dispensed out of the dispensing port 1016 and into a dispensing location 1020
  • the apparatus 1000 may include a plurality of input droplet lines 1030i to 1030 m (hereinafter also referred to individually as an input droplet line 1030 or collectively as input droplet lines 1030).
  • the plurality of input droplet lines 1030 may include droplets in the carrier fluid 112 from another reactor or another apparatus 100, 200, 700, 800, 900, or 1000 located upstream from the apparatus 1000 illustrate in FIG. 10.
  • a valve 1032 may be located between the input droplet lines 1030, the oil reservoir 1002, and the injection port 106.
  • the injection port 106 may also be referred to as a droplet injection port 106 in the apparatus 1000, as the droplet injection port 106 may also inject droplets from the input droplet lines 1030 as well as the carrier fluid 112 into the DMF board 102.
  • the valve 1032 may be controlled to select a flow between the oil reservoir or one of the input droplet lines 1030 and the injection port 106.
  • the valve 1032 may be positioned to allow carrier fluid 112 to flow from the oil reservoir 1002 towards the injection port 106.
  • the valve 1032 may then be positioned to allow input droplet line 1030i to be selected to dispense a droplet in the input droplet line 1030i onto the DMF board 102 via the injection port 106.
  • selected droplets may then be merged with the droplet 110 in the collection region 104.
  • the merged droplets may then be collected by the aspiration port 108 for further manipulation or analysis.
  • the apparatus 1000 may also have a plurality of collection lines 1012i to 1012 n .
  • the valves 1010 and 1014 may be controlled to select a particular collection line 1012 when a droplet 110 is collected from the DMF board 102.
  • droplets 110 may be collected from the DMF board 102 into one of the collection lines 1012i to 1012 n .
  • the valves 1010 and 1014 may also be controlled to select one of the collection lines 1012i to 1012 n to dispense a desired droplet 110 into the dispensing location 1020 via the dispensing port 1016.
  • the valve 1014 may be positioned to select a droplet from the collection line 1012i .
  • the valve 1014 may be positioned to select a droplet from the collection line 1012 n , and so forth.
  • the multiple collection lines 1012 may provide for further control of the manner in which the droplets 110 are to be organized and dispensed.
  • the present disclosure provides various examples of an apparatus that can provide a high throughput of droplets for processing and/or manipulation on a DMF board.
  • the various examples of the apparatuses illustrated in FIGs. 1 , 2, and 7-10 may be combined.
  • the feedback control of the apparatus 700 may be added to the apparatus 200, 800, 900, or 1000.
  • the feedback control of the apparatus 700 and the recirculating oil system of the apparatus 900 may be combined into the apparatus 1000.
  • the apparatus 1000 may include multiple droplet input lines, but a single collection line.
  • the present disclosure is intended to provide various examples that can be combined in any fashion.

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  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

Selon des mises en œuvre données à titre d'exemple, l'invention concerne un appareil. L'appareil comprend une plaque microfluidique numérique (DMF), un orifice d'injection, et un orifice d'aspiration. La plaque DMF est destinée à manipuler une gouttelette. La plaque DMF comprend une région de collecte. L'orifice d'injection est situé au-dessus de la région de collecte pour fournir une alimentation continue d'un fluide porteur. La gouttelette est non miscible dans le fluide porteur. L'orifice d'aspiration est situé adjacent à l'orifice d'injection et situé au-dessus de la région de collecte pour collecter la gouttelette et le fluide porteur.
PCT/US2021/051416 2021-09-22 2021-09-22 Commandes de gouttelettes microfluidiques WO2023048701A1 (fr)

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Citations (3)

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Publication number Priority date Publication date Assignee Title
WO2013159117A1 (fr) * 2012-04-20 2013-10-24 SlipChip, LLC Dispositifs fluidiques et systèmes pour préparation d'échantillons ou analyse autonome
WO2019086286A1 (fr) * 2017-11-06 2019-05-09 Sartorius Stedim Biotech Gmbh Module de filtrage et procédé pour la détection de micro-organismes
EP3708256A1 (fr) * 2015-04-22 2020-09-16 Stilla Technologies Procédé d'amorçage sans contact permettant de charger une solution dans un dispositif microfluidique et système associé

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013159117A1 (fr) * 2012-04-20 2013-10-24 SlipChip, LLC Dispositifs fluidiques et systèmes pour préparation d'échantillons ou analyse autonome
EP3708256A1 (fr) * 2015-04-22 2020-09-16 Stilla Technologies Procédé d'amorçage sans contact permettant de charger une solution dans un dispositif microfluidique et système associé
WO2019086286A1 (fr) * 2017-11-06 2019-05-09 Sartorius Stedim Biotech Gmbh Module de filtrage et procédé pour la détection de micro-organismes

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