WO2024081206A1 - Appareil et procédés de distribution de gouttelettes - Google Patents

Appareil et procédés de distribution de gouttelettes Download PDF

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Publication number
WO2024081206A1
WO2024081206A1 PCT/US2023/034777 US2023034777W WO2024081206A1 WO 2024081206 A1 WO2024081206 A1 WO 2024081206A1 US 2023034777 W US2023034777 W US 2023034777W WO 2024081206 A1 WO2024081206 A1 WO 2024081206A1
Authority
WO
WIPO (PCT)
Prior art keywords
tube
micrometers
dispenser
liquid
channel
Prior art date
Application number
PCT/US2023/034777
Other languages
English (en)
Inventor
Adam ABATE
Krzysztof LANGER
Original Assignee
Cz Biohub Sf, Llc
The Regents Of The Universtiy Of California
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 Cz Biohub Sf, Llc, The Regents Of The Universtiy Of California filed Critical Cz Biohub Sf, Llc
Publication of WO2024081206A1 publication Critical patent/WO2024081206A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10—Processes of additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10—Processes of additive manufacturing
    • B29C64/106—Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/307—Handling of material to be used in additive manufacturing

Definitions

  • Bioprinting can be used to spatially control the placement of cells in many applications including tissue engineering, organoids, stem cell research, and high-throughput screening.
  • an apparatus in accordance with a first implementation, includes a dispenser, a liquid source, and a pressure source.
  • the dispenser includes a tube having an outlet, a channel surrounding the tube, and a flow path coupling the channel and the outlet of the tube.
  • the liquid source to be coupled to the tube and to contain a liquid and the pressure source to be coupled to the channel.
  • the liquid is to flow from the liquid source through the tube and the pressure source is to flow gas through the channel to cause a droplet of the liquid to be dispensed from the outlet of the tube.
  • an apparatus in accordance with a second implementation, includes a dispenser having a tube having an outlet at a flow path and a membrane valve at least partially defining the flow path and actuatable to a first position and a second position.
  • the membrane valve being in the first position causes the flow path to have a first width and the membrane valve being in the second position causes the flow path to have a second width.
  • an apparatus and/or method may further comprise or include any one or more of the following:
  • the pressure source is to flow the gas at a substantially constant flow rate.
  • the channel and the tube are coaxial.
  • the tube includes a capillary.
  • the capillary includes a glass capillary.
  • the capillary includes a tip having the outlet.
  • the tube includes an optical fiber.
  • the tube includes a microfluidic channel.
  • the gas includes air.
  • the apparatus includes a sorting module having a charging electrode, a sorting electrode and a grounded waste channel.
  • the sorting module includes an insulator.
  • the apparatus includes a second dispenser and a mover.
  • the mover to carry the dispenser and the second dispenser.
  • the dispenser carries a first actuator and the second dispenser carries a second actuator.
  • the first actuator and the second actuator enable relative movement between the dispenser and the second dispenser.
  • the liquid includes an emulsion.
  • the dispenser includes a channel surrounding the tube and the flow path coupling the channel and the outlet of the tube.
  • the apparatus includes a pressure source to be coupled to the channel. The pressure source is to flow gas through the channel.
  • the first width is between about 60 micrometers and about 310 micrometers.
  • the second width is between about 60 micrometers and about 310 micrometers.
  • the first width is between about 60 micrometers and about 170 micrometers and the second width is between about 170 micrometers and about 310 micrometers.
  • the first width is between about 10 micrometers and about 5,000 micrometers.
  • the second width is between about 11 micrometers and about 10,000 micrometers.
  • the first width is between about 10 micrometers and about 170 micrometers and the second width is between about 170 micrometers and about 310 micrometers.
  • the apparatus includes a second membrane valve opposing the membrane valve and at least partially defining the flow path and actuatable to the first position and the second position.
  • the apparatus also includes a liquid source to be coupled to the tube and to contain a liquid.
  • the liquid is to flow from the liquid source through the tube.
  • the membrane valve being in the first position causes a first droplet of the liquid to be dispensed from the outlet of the tube and the membrane valve being in the second position causes a second droplet of the liquid to be dispensed from the outlet of the tube.
  • the first droplet having a first size and the second droplet having a second size.
  • the apparatus also includes a second dispenser coupled to the dispenser.
  • the dispenser includes a pair of channels on either side of the tube and the flow path coupling the channels and the outlet of the tube.
  • the apparatus includes a pressure source to be coupled to the channels. The pressure source is to flow gas through the channels.
  • FIG. 1 is a schematic diagram of a system in accordance with teachings of this disclosure.
  • FIG. 2 is a schematic diagram of another system in accordance with teachings of this disclosure.
  • FIG. 3 is a schematic diagram of another system in accordance with teachings of this disclosure.
  • FIG. 4 is a schematic diagram of another system in accordance with teachings of this disclosure.
  • FIG. 1 is a schematic diagram of a system 100 in accordance with teachings of this disclosure.
  • the system 100 can be used to dispense a liquid 102 such as a droplet 104 onto a substrate 106.
  • the system 100 may dispense 3,000 droplets in about one second in some implementations.
  • the liquid 102 may be referred to as a substance, may include cells, spheroids, organoids, glass or polymer beads, chemicals, biomolecules, and/or may be an emulsion.
  • the system 100 may be used for in-situ bioprinting in plastic surgery and/or in diabetes treatment of ulcers as examples.
  • the system 100 may be used for different applications, however.
  • the system 100 includes a dispenser 108, a liquid source 110, a pressure source 112, and a regulator 113.
  • the dispenser 108 may be referred to as a printhead.
  • the system also includes a sorting module 114, a mover 116, an actuator 118, and a controller 120.
  • the mover 116 may include and/or be implemented by a robotic arm and/or a liquid handling robot.
  • the regulator 113 may be used to regulate a flow of the gas from the pressure source 112 to the dispenser 108, for example.
  • the controller 120 is electrically and/or communicatively coupled to the dispenser 108, the liquid source 110, the regulator 113, the sorting module 114, the mover 116, and/or the actuator 118 to perform various functions as disclosed herein.
  • the dispenser 108 includes a tube 122 having an outlet 124 and a channel 126 surrounding the tube 122.
  • the dispenser 108 also includes a flow path 128 that couples the channel 126 and the outlet 124 of the tube 122.
  • the flow path 128 may be referred to as an air-liquid co-flow junction.
  • the approach of the channel 126 surrounding the tube 122 may be referred to as co-flow.
  • the liquid source 110 is shown coupled to the tube 122 and contains the liquid 102 and the pressure source 112 is coupled to the channel 126.
  • the liquid 102 flows from the liquid source 110 through the tube 122 in operation and the pressure source 112 flows gas through the channel 126 to cause the droplet 104 of the liquid 102 to be dispensed from the outlet 124 of the tube 122.
  • the pressure source 112 flows the gas at a substantially constant flow rate in some implementations.
  • the gas may be air. Other gases may prove suitable, however.
  • the channel 126 and the tube 122 are coaxial in the implementation shown.
  • the channel 126 may alternatively not surround and/or may not be coaxial with the tube 122.
  • the channel 126 may positioned on a side of the tube 122 and coupled to the flow path 128 in such implementations (see one of the channels of FIG. 4, for example).
  • the tube 122 may be a capillary 132 such as a glass capillary 134.
  • the capillary 132 has a tip 136 that includes the outlet 124.
  • the tube 122 may additionally or alternatively be an optical fiber 138 and/or a microfluidic channel 140.
  • the optical fiber 138 may be hollow in such implementations.
  • the sorting module 114 includes a charging electrode 142, a sorting electrode 144, and a grounded waste channel 146.
  • the charging electrode 142 may include a light source 147, optical fibers 148, and/or optical fibers 150.
  • the light source 147 may be a laser and/or a light-emitting diode(s) (LED). The LED may operate at a desired wavelength and/or be associated with a filter(s).
  • the optical fibers 148 and/or 150 may include a conductive coating that removes static charge from the cladding of the optical fibers.
  • the light source 147 is connected to optical fibers 148, the optical fibers 148 apply excitation energy from the light source 147 to the droplet 104 flowing through the flow path 128, and the optical fibers 150 collect a signal produced by the application of excitation energy 108 to the droplet 104.
  • the signal may be associated with an optical property of the droplet 104, for example.
  • the sorting electrode 144 can sort the droplet 104 based on the detection of the optical property.
  • the droplet 104 is deposited on the substrate 106 when the sorting electrode 144 is turned on and the droplet 104 is directed to the waste channel 146 when the sorting electrode 144 is turned off in some implementations.
  • the droplet 104 may alternatively be deposited on the substrate 106 when the sorting electrode 144 is turned off and the droplet 104 may be directed to the grounded waste channel 146 when the sorting electrode 144 is turned on in other implementations.
  • the waste channel 146 being grounded deters static charge buildup that may inadvertently defect the droplet 104 away from the waste channel 146.
  • the sorting module 114 includes an insulator 152 in the implementation shown.
  • the insulator 152 is shown on and/or around the sorting electrode 144.
  • the insulator 152 may deter electrical short circuits between the sorting electrode 114 and the grounded waste channel 146 and, thus, may increase the useful life of the sorting module 114.
  • the system 100 also includes a second dispenser 154 and the mover 116 that carries the dispenser 108 and the second dispenser 154.
  • the mover 116 moves the dispensers 108, 154 relative to the substrate 106 in operation to allow the droplets 104 to be dispensed on the substrate 106, for example.
  • the dispensers 108 and/or 154 can independently dispense droplets 104 or may dispense droplets 104 in parallel.
  • the second dispenser 154 is the same as the dispenser 108 in the implementation shown.
  • the system 100 may include any number of dispensers (e.g., 1 , 2, 3, 4, 5, 6, 7, 8...,12, .... 50), however.
  • the dispenser 108 carries the first actuator 118 and the second dispenser 154 carries a second actuator 156.
  • the actuator 118 and/or the second actuator 156 may be implemented by direct drive linear actuators, for example. Other types of actuators may be used, however.
  • the first actuator 118 and the second actuator 156 enable relative movement between the dispenser 108 and the second dispenser 154.
  • the actuator 118 may move the dispenser 108 in the x-direction relative the second dispenser 154 and/or the substrate 106 and/or the second actuator 156 may move the second dispenser 154 in the x- direction relative to the dispenser 108 and/or the substrate 106, for example.
  • the controller 120 includes a user interface 158, a communication interface 160, one or more processors 162, and a memory 164 storing instructions executable by the one or more processors 162 to perform various functions including the disclosed implementations.
  • the user interface 158, the communication interface 160, and the memory 164 are electrically and/or communicatively coupled to the one or more processors 162.
  • the user interface 158 is adapted to receive input from a user and to provide information to the user associated with the operation of the system 100 and/or a dispensing operation taking place.
  • the user interface 158 may include a touch screen, a display, a keyboard, a speaker(s), a mouse, a track ball, and/or a voice recognition system.
  • the touch screen and/or the display may display a graphical user interface (GUI).
  • GUI graphical user interface
  • the communication interface 160 is adapted to enable communication between the system 100 and a remote system(s) (e.g., computers) via a network(s).
  • the network(s) may include the Internet, an intranet, a local-area network (LAN), a wide-area network (WAN), a coaxial-cable network, a wireless network, a wired network, a satellite network, a digital subscriber line (DSL) network, a cellular network, a Bluetooth connection, a near field communication (NFC) connection, etc.
  • Some of the communications provided to the remote system may be associated with analysis results, imaging data, etc. generated or otherwise obtained by the system 100.
  • Some of the communications provided to the system 100 may be associated with droplet dispensing and/or a protocol(s) to be executed by the system 100.
  • the one or more processors 162 and/or the system 100 may include one or more of a processor-based system(s) or a microprocessor-based system(s).
  • the one or more processors 162 and/or the system 100 includes one or more of a programmable processor, a programmable controller, a microprocessor, a microcontroller, a graphics processing unit (GPU), a digital signal processor (DSP), a reduced-instruction set computer (RISC), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a field programmable logic device (FPLD), a logic circuit and/or another logic-based device executing various functions including the ones described herein.
  • a programmable processor a programmable controller, a microprocessor, a microcontroller, a graphics processing unit (GPU), a digital signal processor (DSP), a reduced-instruction set computer (RISC), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA),
  • the memory 164 can include one or more of a semiconductor memory, a magnetically readable memory, an optical memory, a hard disk drive (HDD), an optical storage drive, a solid-state storage device, a solid-state drive (SSD), a flash memory, a readonly memory (ROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), a random-access memory (RAM), a non-volatile RAM (NVRAM) memory, a compact disc (CD), a compact disc read-only memory (CD-ROM), a digital versatile disk (DVD), a Blu-ray disk, a redundant array of independent disks (RAID) system, a cache, and/or any other storage device or storage disk in which information is stored for any duration (e.g., permanently, temporarily, for extended periods of time, for buffering, for caching).
  • HDD hard disk drive
  • SSD solid-state drive
  • flash memory a readonly memory
  • ROM readonly memory
  • FIG. 2 is a schematic diagram of another system 200 in accordance with teachings of this disclosure.
  • the system 200 is similar to the system 100 of FIG. 1 .
  • the dispenser 108 of system 200 includes a membrane valve 202 however at least partially defines the flow path 128 and that is actuatable to a first position and a second position.
  • the membrane valve 202 may include an elastomeric material that is flexible between different positions based on the pressure applied, for example.
  • the membrane valve 202 of the dispenser 108 is shown in the first position and the membrane valve 202 of the second dispenser 154 is shown in the second position.
  • the membrane valve 202 being in the first position causes the flow path 128 to have a first width 204 and the membrane valve 202 being in the second position causes the flow path 128 to have a second width 206.
  • the membrane valve 202 changes a width of the flow path 128 in a droplet generating region 203 of the flow path 128.
  • the membrane valve 202 may also be positioned in a third position between the first position and the second position.
  • the membrane valve 202 may be dynamically adjusted to any number of positions to define different widths for the flow path 128 and, therefore, control a size of the droplets 108 being generated and dispensed as a result.
  • the first width 204 may between about 60 micrometers and about 310 micrometers and/or the second width 206 may be between about 60 micrometers and about 310 micrometers.
  • the first width 204 may alternatively be between about 60 micrometers and about 170 micrometers and/or the second width 206 may alternatively been between about 170 micrometers and about 310 micrometers.
  • the first width 204 may alternatively be between about 10 micrometers and about 5,000 micrometers and/or the second width 206 may be between about 11 micrometers and about 10,000 micrometers.
  • the first width 204 may alternatively be between about 10 micrometers and about 170 micrometers and/or the second width 206 is between about 170 micrometers and about 310 micrometers.
  • the membrane valve 202 being in the first position in operation causes a first droplet 210 of the liquid 102 to be dispensed from the outlet 124 of the tube 122 and the membrane valve 202 being in the second position causes a second droplet 212 of the liquid 102 to be dispensed from the outlet 124 of the tube 122.
  • the first droplet 210 has a first size and the second droplet 212 has a second size. The first size is larger than the second size as shown.
  • the membrane valve 202 dynamically adjusting the width of the flow path 128 allows the dispenser 108 to dynamically dispense droplets 104 of different sizes.
  • a valve 208 is coupled between the pressure source 112 and the membrane valve 202.
  • the valve 208 controls the flow of fluid to the membrane valve 202.
  • the fluid actuates the membrane valve 202 in operation.
  • the membrane valve 202 may be actuated using gas and/or a liquid such as hydraulic fluid.
  • the membrane valve 202 may be coupled to a liquid source instead of the pressure source 112 if liquid is used to actuate the membrane valve 202.
  • the dispenser 108 of the system 200 is also shown including a second membrane valve 214 that opposes the membrane valve 202.
  • the second membrane valve 214 at least partially defines the flow path 128 and is actuatable to the first position and the second position.
  • the second membrane valve 214 may alternatively be omitted.
  • FIG. 3 is a schematic diagram of a system 300 in accordance with teachings of this disclosure.
  • the system 300 is similar to the system 200 of FIG. 2.
  • the system 300 is shown including the dispenser 108 but not including the second dispenser 154.
  • FIG. 4 is a schematic diagram of a system 400 in accordance with teachings of this disclosure.
  • the system 400 is similar to the system 300 of FIG. 3.
  • the dispenser 108 of FIG. 4 does not include the channel 126 that surrounds the tube 122.
  • the dispenser 108 of FIG. 4 instead includes a pair of channels 402, 404 on either side of the tube 122.
  • the flow path 128 couples the channels 402, 404 and the outlet 124 of the tube 122.
  • the pressure source 112 is coupled to the channels 402, 404 and flows gas through the channels 126.
  • the approach of the channels 402, 404 being on either side of tube 122 may be referred to as flow focusing.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Physics & Mathematics (AREA)
  • Manufacturing & Machinery (AREA)
  • Mechanical Engineering (AREA)
  • Optics & Photonics (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne des procédés et un appareil de distribution de gouttelettes. Selon un mode de réalisation, un appareil comprend un distributeur, une source de liquide et une source de pression. Le distributeur comprend un tube présentant une sortie, un canal entourant le tube, un trajet d'écoulement couplant le canal et la sortie du tube. La source de liquide doit être couplée au tube et contenir un liquide et la source de pression doit être couplée au canal. Le liquide doit s'écouler de la source de liquide à travers le tube et la source de pression est destinée à faire circuler un gaz dans le canal pour amener une gouttelette du liquide à être distribuée à partir de la sortie du tube.
PCT/US2023/034777 2022-10-14 2023-10-10 Appareil et procédés de distribution de gouttelettes WO2024081206A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263416363P 2022-10-14 2022-10-14
US63/416,363 2022-10-14

Publications (1)

Publication Number Publication Date
WO2024081206A1 true WO2024081206A1 (fr) 2024-04-18

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180029055A1 (en) * 2015-02-20 2018-02-01 Ingeniatrics Tecnologias An apparatus and a method for generating droplets
US20180056288A1 (en) * 2014-10-22 2018-03-01 The Regents Of The University Of California High Definition Microdroplet Printer

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180056288A1 (en) * 2014-10-22 2018-03-01 The Regents Of The University Of California High Definition Microdroplet Printer
US20180029055A1 (en) * 2015-02-20 2018-02-01 Ingeniatrics Tecnologias An apparatus and a method for generating droplets

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
A. MOHAN: "A microfluidic flow analyzer with integrated lensed optical fibers", BIOMICROFLUIDICS, AIP, US, vol. 14, no. 5, 1 September 2020 (2020-09-01), US , XP093163612, ISSN: 1932-1058, DOI: 10.1063/5.0013250 *
MICHAEL V. SEFTON: "Microencapsulation of mammalian cells in a water‐insoluble polyacrylate by coextrustion and interfacial precipitation", BIOTECHNOLOGY AND BIOENGINEERING, JOHN WILEY, HOBOKEN, USA, vol. 29, no. 9, 20 June 1987 (1987-06-20), Hoboken, USA, pages 1135 - 1143, XP093163610, ISSN: 0006-3592, DOI: 10.1002/bit.260290914 *
SUCAMORI ET AL.: "Microencapsulation of pancreatic islets in a water insoluble polyacrylate", ASAIO JOURNAL, vol. 35, no. 4, 1 October 1989 (1989-10-01), pages 791 - 799, XP000095131 *

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