GB2610116A - Method and apparatus for large-scale spheroid generation - Google Patents

Method and apparatus for large-scale spheroid generation Download PDF

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Publication number
GB2610116A
GB2610116A GB2217222.5A GB202217222A GB2610116A GB 2610116 A GB2610116 A GB 2610116A GB 202217222 A GB202217222 A GB 202217222A GB 2610116 A GB2610116 A GB 2610116A
Authority
GB
United Kingdom
Prior art keywords
nozzle
droplets
reservoir
temperature
vessel
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
GB2217222.5A
Other versions
GB202217222D0 (en
Inventor
Freyer James
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bennubio Inc
Original Assignee
Bennubio Inc
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 Bennubio Inc filed Critical Bennubio Inc
Publication of GB202217222D0 publication Critical patent/GB202217222D0/en
Publication of GB2610116A publication Critical patent/GB2610116A/en
Pending legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
    • B01J2/06—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a liquid medium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/18—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic using a vibrating apparatus
    • 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
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
    • 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
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668—Trapping microscopic beads
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1861—Means for temperature control using radiation
    • B01L2300/1866—Microwaves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1861—Means for temperature control using radiation
    • B01L2300/1872—Infrared light
    • 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

Abstract

Methods and apparatus for easily and reproducibly producing large numbers of uniform spheroids including spheroid co-cultures by combining vibrational droplet generation with one or more temperature-controlled transition zones.

Claims (20)

What is claimed is:
1. An apparatus for spheroid generation comprising: a reservoir configured to contain and suspend a population of cells of interest in a pre gel solution, the reservoir being in fluidic communication with a nozzle via a fluidic supply channel; vibratory means for vibrating the nozzle so as to produce droplets from the gel-solution; a vessel physically distanced from the nozzle and positioned to receive droplets produced by the nozzle; and a temperature-controlled zone between the distal end of the nozzle and the vessel.
2. The apparatus of claim 1 wherein the vibratory means is an acoustic transducer.
3. The apparatus of claim 1 further comprising a heating element that controls the temperature of the temperature-controlled zone.
4. The apparatus of claim 1 wherein the reservoir and fluidic supply channel are temperature controlled.
5. The apparatus of claim 4 further comprising a first cooling element that controls the temperature of the reservoir and/or the fluidic supply channel.
6. The apparatus of claim 1 wherein the vessel is temperature controlled.
7. The apparatus of claim 6 further comprising a heating element to control the temperature of the vessel.
8. The apparatus of claim 7 wherein the heating element that controls the vessel also controls the temperature of the temperature-controlled zone.
9. The apparatus of claim 1 wherein the nozzle is directed upwards to produce an upwardly directed spray of droplets.
10. The apparatus of claim 1 wherein the nozzle or the fluidic supply line is movable between at least two positions wherein in the first position the nozzle is directed upwards to produce an upwardly directed spray of droplets and in the second position the nozzle is directed downwards.
11. The apparatus of claim 6 wherein the vessel is movable so that it can be positioned to catch the droplets.
12. The apparatus of claim 1 further comprising a second reservoir in fluidic communication with the nozzle.
13. The apparatus of claim 12 wherein the second reservoir is temperature-controlled by the first or a second cooling element.
14. The apparatus of claim 1 further comprising a second reservoir in fluidic communication with a second nozzle.
15. The apparatus of claim 14 wherein the second nozzle is nested within the first nozzle.
16. A method of producing spheroids comprising: providing the apparatus of claim 1 ; suspending a population of cells of interest in a pre-gel solution in the reservoir; forming droplets by delivering the pre-gel solution to the nozzle such that droplets are expelled from the nozzle into a heating zone; heating the droplets in the heating zone so that they undergo gelation and form gelled droplets; collecting the gelled droplets in a stirred media containing vessel; and culturing the collected droplets to form spheroids.
17. The method of claim 16 wherein the droplets are expelled from the nozzle in an upward trajectory.
18. The method of claim 16 wherein the trajectory of the droplet as it travels between the terminal end of the nozzle and the vessel ensures that sufficient conditions will exist for the droplet to undergo gelation prior to contacting the media in the vessel.
19. The method of claim 16 wherein the apparatus comprises first and second reservoirs fluidly connected to the nozzle wherein the first and second reservoirs comprise first and second populations of cells of interest, respectively, such that the resulting spheroid comprises a mixed co-culture comprising both the first and second populations of cells of interest.
20. The method of claim 16 wherein the apparatus comprises a first reservoir fluidly connected to a first nozzle and a second reservoir fluidly connected to a second nozzle wherein the second nozzle is nested within the first nozzle; wherein the first reservoir contains a first population of cells of interest and the second reservoir contains a second population of cells of interest such that; the resulting spheroid contains a positional co-culture wherein the first population of cells surrounds the second population of cells.
GB2217222.5A 2020-02-18 2021-02-18 Method and apparatus for large-scale spheroid generation Pending GB2610116A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202062977874P 2020-02-18 2020-02-18
PCT/US2021/018453 WO2021168034A1 (en) 2020-02-18 2021-02-18 Method and apparatus for large-scale spheroid generation

Publications (2)

Publication Number Publication Date
GB202217222D0 GB202217222D0 (en) 2023-01-04
GB2610116A true GB2610116A (en) 2023-02-22

Family

ID=77391628

Family Applications (1)

Application Number Title Priority Date Filing Date
GB2217222.5A Pending GB2610116A (en) 2020-02-18 2021-02-18 Method and apparatus for large-scale spheroid generation

Country Status (2)

Country Link
GB (1) GB2610116A (en)
WO (1) WO2021168034A1 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1541739A (en) * 1967-08-28 1968-10-11 Cie Pour L Etude Et La Realisa Ultrasonic spraying of meltable or soluble liquids or solids
US20040121451A1 (en) * 2001-03-16 2004-06-24 Niko Moritz Treatment of sols, gels and mixtures thereof
US20100243753A1 (en) * 2007-06-22 2010-09-30 Arizona Board of Regents, a body corporate acting for and on behalf of Arizona State University Gas Dynamic Virtual Nozzle for Generation of Microscopic Droplet Streams
US20130274353A1 (en) * 2012-03-16 2013-10-17 The University Of Hong Kong System and method for generation of emulsions with low interfacial tension and measuring frequency vibrations in the system
US20190157060A1 (en) * 2017-11-22 2019-05-23 Labcyte, Inc. System and method for the acoustic loading of an analytical instrument using a continuous flow sampling probe

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1541739A (en) * 1967-08-28 1968-10-11 Cie Pour L Etude Et La Realisa Ultrasonic spraying of meltable or soluble liquids or solids
US20040121451A1 (en) * 2001-03-16 2004-06-24 Niko Moritz Treatment of sols, gels and mixtures thereof
US20100243753A1 (en) * 2007-06-22 2010-09-30 Arizona Board of Regents, a body corporate acting for and on behalf of Arizona State University Gas Dynamic Virtual Nozzle for Generation of Microscopic Droplet Streams
US20130274353A1 (en) * 2012-03-16 2013-10-17 The University Of Hong Kong System and method for generation of emulsions with low interfacial tension and measuring frequency vibrations in the system
US20190157060A1 (en) * 2017-11-22 2019-05-23 Labcyte, Inc. System and method for the acoustic loading of an analytical instrument using a continuous flow sampling probe

Also Published As

Publication number Publication date
GB202217222D0 (en) 2023-01-04
WO2021168034A1 (en) 2021-08-26

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