WO1987002122A1 - Procede et appareil de rechauffage et de refroidissement d'eprouvettes - Google Patents

Procede et appareil de rechauffage et de refroidissement d'eprouvettes Download PDF

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Publication number
WO1987002122A1
WO1987002122A1 PCT/AU1986/000278 AU8600278W WO8702122A1 WO 1987002122 A1 WO1987002122 A1 WO 1987002122A1 AU 8600278 W AU8600278 W AU 8600278W WO 8702122 A1 WO8702122 A1 WO 8702122A1
Authority
WO
WIPO (PCT)
Prior art keywords
specimen
cooling
warming
carriage
chamber
Prior art date
Application number
PCT/AU1986/000278
Other languages
English (en)
Inventor
John Andrew Beilby
Yianni Attikouzel
Original Assignee
John Andrew Beilby
Yianni Attikouzel
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 John Andrew Beilby, Yianni Attikouzel filed Critical John Andrew Beilby
Publication of WO1987002122A1 publication Critical patent/WO1987002122A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/54—Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0236—Mechanical aspects
    • A01N1/0242—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
    • A01N1/0252—Temperature controlling refrigerating apparatus, i.e. devices used to actively control the temperature of a designated internal volume, e.g. refrigerators, freeze-drying apparatus or liquid nitrogen baths
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0278—Physical preservation processes
    • A01N1/0284—Temperature processes, i.e. using a designated change in temperature over time
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F25—REFRIGERATION OR COOLING; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS; MANUFACTURE OR STORAGE OF ICE; LIQUEFACTION SOLIDIFICATION OF GASES
    • F25D—REFRIGERATORS; COLD ROOMS; ICE-BOXES; COOLING OR FREEZING APPARATUS NOT OTHERWISE PROVIDED FOR
    • F25D3/00—Devices using other cold materials; Devices using cold-storage bodies
    • F25D3/10—Devices using other cold materials; Devices using cold-storage bodies using liquefied gases, e.g. liquid air
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/42—Low-temperature sample treatment, e.g. cryofixation

Definitions

  • the present invention relates to a specimen cooling and warming apparatus and method particularly envisaged for use in cooling specimens to a state of freezing and warming frozen specimens to room temperature.
  • cooling specimens to a frozen state has been effected by placing the specimens into a fully enclosed chamber and gradually reducing the temperature therein. Temperature reduction to low temperatures is conveniently achieved using liquid nitrogen. Introduction of the liquid nitrogen is performed by a pump mechanism. A complex control system is required to monitor the temperature in the chamber and regulate the pump mechanism to achieve a desired cooling rate and substan ⁇ tially uniform temperature throughout the chamber. Once the specimens are frozen they are transferred to a long term storage container.
  • a less common cooling and warming apparatus comprises a relatively large chamber supplied with liquid nitrogen and having a substantially uniform temperature through ⁇ out and a smaller container arranged to be located in it.
  • the smaller container is provided with a heating means and arranged to store the specimen.
  • a control system is provided to operate the heating means in order to allow cooling and warming of the specimen.
  • Such apparatus are relatively inexpensive and of low complexity but are also of low accuracy and are prone to overheat or even cook the specimen (in the case of a biological specimen) .
  • the present invention provides a specimen cooling and warming apparatus employing a temperature gradient for use in cooling and warming specimens.
  • a specimen cooling and warming apparatus characterised in that it comprises a chamber having a base and one or more walls thereabout and having a moveable carriage located in it, the carriage being arranged to carry a specimen, a cooling means to form a temperature gradient in the chamber and a control means to move the carriage through the temperature gradient.
  • a method of cooling and warming a specimen characterised in that it comprises - 3 -
  • relatively warm temperatures are those about room temperature and relatively cold temperatures are those between -100°C to -200°C.
  • Figure 1 is an upper perspective view of a specimen cooling and warming apparatus according to the present invention
  • Figure 2 is a functional block diagramme of a control means of the specimen cooling and warming apparatus; and Figure 3 is a control circuit diagramm of a control algorithm of the control means of Figure 2. DESCRIPTION OF THE INVENTION
  • FIG. 1 there is shown a specimen cooling and warming apparatus 10 comprising a chamber 12 conven ⁇ iently formed from 4 walls 14 and a base bounded by the walls 14.
  • the walls 14 and the base may be made with a stainless steel outer covering and an inner insulation layer.
  • the insulation may conveniently be polystyrene or polyurethane.
  • the chamber 12 also comprises a lid 16 hinged atop one of the walls 14 and disposed to close off the chamber 12 so that turbulance in air outside the chamber is less likely to produce turbulance inside the chamber 12.
  • the chamber 12 also comprises a carriage 18 located within its confines.
  • the carriage 18 is conveniently in the form of a tray 20 having two swing pivots 22.
  • the swing pivots 22 each receive a first arm 24 fixed to a rotatable rod 26. Rotation of the rod 26 produces an angular displacement of the first forms 24 and a corres ⁇ ponding raising or lowering of the tray 20.
  • the tray 20 is made of material having low thermal mass. It is envisaged that the tray 20 could therefor be made substantially of plastics materials.
  • the rod 26 also conveniently has fixed to it two second arms 28 disposed to rotate with the rod 26.
  • the second arms 28 are arranged to raise the lid 16 when the carriage 18 is in a raised condition, as shown in Figure 1.
  • the second arms 28 are not fixed to the lid 16 but are arranged to slidingly engage with the lid. When the carriage 18 is lowered the second arms 28 are angularly displaced and lower the lid 16. Once the lid 16 comes into contact with tops of the walls 14 the second arms 28 continue to rotate downwardly.
  • the specimen cooling and warming apparatus 10 also comprises a drive mechanism 30 which is configured to rotate the rod 26 and hence the first and second arms 24 and 28. It is intended that the drive mechanism 30 comprise a stepper motor connected to receive electrical impulses to cause it to accordingly rotate an output shaft connected to a speed reduction gear box (not shown) and hence to the rod 2 ⁇ .
  • the specimen cooling and warming apparatus 10 also comprises a cooling means.
  • the cooling means is conveniently in the form of a volume of relatively cold liquid stored within the chamber 12.
  • the store of relatively cold liquid may be a store of liquid nitrogen 32 which has a temperature of about -196°C.
  • the store of liquid 32 produces a temperature gradient inside the chamber -12. The temperature gradient varies from about -196°C adjacent the store of liquid 32 to about room temperature adjacent the lid 16.
  • the chamber 12 comprises means providing greater inailation effect toward the base and lesser insulation effect toward the lid 16 so as to aid in maintaining the temperature gradient.
  • the thickness of the insulation in the walls 14 could be varied from relatively thick toward the base to relatively thin toward the lid 16.
  • the walls 14 could comprise ventilation means adjacent the lid 16 to allow escape of nitrogen vapour but whilst reducing the chance of external air flows causing turbulance within the chamber, which turbulance could otherwise disturb the temperature gradient. It is preferred to establish a linearity in the temperature gradient.
  • the specimen cooling and warming apparatus 10 also comprises a control means 40 as shown in Figure 2.
  • the control means 40 comprises a temperature sensor 42 arranged to be in contact with the specimen. It is intended that the temperature sensor 42 be in the form of a thermistor and be located within the specimen. It has been found preferable to use thermistors since they display reproducable resistance/temperature characteristics which can be readily characterised and display a relatively high sensitivity as compared with thermocouples. It has been found most desirable, especially with biological specimens such as semen, to place the temp ⁇ erature sensor 42 inside the specimen since during freezing the temperature of the specimens may not precisely match the temperature of the tray 20.
  • the control means 40 also comprises a sample and hold circuit 44 connected to the temperature sensor 42 and configured to periodically sample a voltage appearing across the resistance of the thermistor.
  • An analogue to digital converter (A/D) 46 is provided to convert the sampled thermister voltage measurement from an analogue value to a digital value.
  • a measurement converter 48 is connected to the A/D converter 46 is configured with information regarding the resistance/temperature characteristics of the thermistor.
  • the measurement converter 48 thereby converts the digitized voltage into an absolute temp ⁇ erature in degrees celcius for example.
  • the absolute temperature reading may be stored by a data logger 50 for later use and experimentation in developing optimum cooling and warming rates for various specimens.
  • the control means 40 also comprises a control algorithm means 52 as detailed in Figure 3.
  • the control algorithm means 52 has an input C from the measurement converter 48 and an input R from a cooling/warming., rate means 54 and an output U to a position controller 56 arranged to send electrical pulses to the drive mechanism 30.
  • the control algorithm means 52 comprises means for proportional and differential control of the angular position of the rod 26 dependent upon the measured temperature of the specimen.
  • the cooling/warming rate means 54 comprises a keyboard 58 ( Figure 1) configured to allow entry of data corres ⁇ ponding to desired cooling and warming rates.
  • the data may include the rate in terms of temperature per unit time at which cooling and warming is to take place and the absolute temperature at whcih such rate is to commence or cease.
  • the data may also include a time period for which the temperature is to be maintained constant.
  • the control algorthm means interprets the data from the cooling/warming rate means 54 and activates the position controller 56 accordingly.
  • cooling and warming rates could be in the range from 0.1 to 20°C/minute although it is estimated that slower rates could be used. It has been found that faster cooling rates may be used once the specimen is frozen. It has also been found that at freezing a latent heat of fusion is released and may increase the temperature of the specimen by 5 to 10°C. Accordingly, the control means 40 is preferably configured to disregard such changes.
  • the specimen cooling and warming apparatus 10 is employed to cool to freezing a specimen to be subse ⁇ quently stored in a long term cold storage flask or to warm from a frozen state a specimen removed from such a flask.
  • the apparatus 10 is then supplied with a store of the liquid 32 to establish the temperature gradient. Then the temperature sensor 42 is placed in contact with the sample and both are placed on the tray.
  • the control algorithm means 52 sets the position controller 56 to send electrical pulses to the drive mechanism 30 to rotate the rod 36 to angularly displace the first and second arms 24 and 14 and hence lower the tray 20.
  • the sample and hold circuit 44 measures the temperature of the specimen -with the thermistor and the A/D converter 46 and the measurement converter 48 convert the sample into an absolute temperature reading which is then recorded by the data logger 50.
  • the control means 40 varies or maintains the rate of lowering of the tray 20. When the measured temperature reaches a certain value the rate of lowering may be altered as directed by the cooling/warming rate means 54.
  • any number of cooling and warming rates could be used, although 3 to 5 different rates are considered to be most likely.
  • the rates of cooling shown in Table 1 may be used to freeze semen: Table 1 possible cooling rates for semen . RATE BREAK TEMPERATURE .
  • the break temperature is the temperature at which the rate of cooling is altered to the next rate.
  • a display means 60 display the temperature of the specimen.
  • the control means 40 may be directed by the operator to lower the carriage 18, under manual control, into the store of liquid 32 to reduce the specimen to the temperature of the liquid 32.
  • the the carriage 18 may be manually raised as described hereinabove and the lid 16 opened, the specimen removed and placed in a long term storage flask.
  • the reverse procedure is used to warm to room temper ⁇ ature a frozen specimen.
  • the apparatus 10 is then ready for cooling and warming of the specimens. Since the temperature gradient in the chamber 12 is substantially maintained during cooling and warming procedures the apparatus 10 is virtually immediately ready for further such procedures. Consequently, the apparatus 10 of the present invention has been found to be relatively efficient and speedy in performing multiples of such procedures. It is to be noted that prior art apparatus have gener ⁇ ally not considered the desirability of .controlled warming of frozen specimens.
  • the rates of cooling and warming generally decided to be used depend inter alia on the thermal mass of the specimen.
  • the apparatus 10 has been found to consume liquid nitrogen at rates substantially less than prior art apparatus.
  • the apparatus 10 by virtue of its low complexity and a small demand on electrical power may be used whilst in transport. Such use is particularly impor- tant in collecting animal semen specimens from farms.
  • the provision of the data logger 50 is expected to aid in experimentation in evaluating the effect of cooling and warming rates on particular specimens and to produce optimum rates. Modifications and variations such as would be .apparent to a skilled addressee are deemed within the scope of the present invention.
  • a screw thread type drive mechanism could be used to raise and lower the carriage 18.
  • the cooling/warming rate means 54 could be provided with predefined series of cooling and warming rates.

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  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Thermal Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Dentistry (AREA)
  • Zoology (AREA)
  • Clinical Laboratory Science (AREA)
  • Mechanical Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Combustion & Propulsion (AREA)
  • General Engineering & Computer Science (AREA)

Abstract

L'appareil ci-décrit comprend une chambre (12) pourvue d'un couvercle (16) et d'un gradient thermique. Un chariot (18) commandé par un organe de commande (40) et un mécanisme d'entraînement (10) se déplace à travers le gradient thermique à des vitesses désirées pour parvenir à des vitesses désirées de refroidissement pour congeler des éprouvettes y compris des éprouvettes biologiques ou de réchauffement pour réchauffer les éprouvettes congelées.
PCT/AU1986/000278 1985-09-26 1986-09-26 Procede et appareil de rechauffage et de refroidissement d'eprouvettes WO1987002122A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPH2620 1985-09-26
AU262085 1985-09-26

Publications (1)

Publication Number Publication Date
WO1987002122A1 true WO1987002122A1 (fr) 1987-04-09

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Application Number Title Priority Date Filing Date
PCT/AU1986/000278 WO1987002122A1 (fr) 1985-09-26 1986-09-26 Procede et appareil de rechauffage et de refroidissement d'eprouvettes

Country Status (2)

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EP (1) EP0238558A1 (fr)
WO (1) WO1987002122A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0290722A2 (fr) * 1987-05-15 1988-11-17 Limitek Oy Incubateur à gradient de température
EP0299521A2 (fr) * 1987-07-15 1989-01-18 Fuji Photo Film Co., Ltd. Appareil d'analyses biochimiques
EP0363143A2 (fr) * 1988-10-06 1990-04-11 Coy Corporation Appareil de régulation de température
WO1990005947A1 (fr) * 1988-11-17 1990-05-31 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Thermostat
WO2001049574A3 (fr) * 2000-01-04 2002-03-28 Thermokeep Ltd Appareil et procede de regulation de temperature
DE20117661U1 (de) * 2001-10-29 2003-03-13 Mwg Biotech Ag Thermocyclervorrichtung
CN110108532A (zh) * 2019-05-17 2019-08-09 中国科学院理化技术研究所 高低温处理设备
WO2022142061A1 (fr) * 2020-12-28 2022-07-07 生物岛实验室 Puce de congélation, système de congélation et système et procédé de test d'échantillon
WO2022142062A1 (fr) * 2020-12-28 2022-07-07 生物岛实验室 Puce de réfrigération, système de réfrigération et système et procédé de test d'échantillon
US20220236002A1 (en) * 2021-01-22 2022-07-28 Alpha International Health Solution Limited Ultra-low temperature storage and dispensing system
US11608221B2 (en) 2018-06-15 2023-03-21 Cold Chain Technologies, Llc Shipping system for storing and/or transporting temperature-sensitive materials
US11634266B2 (en) 2019-01-17 2023-04-25 Cold Chain Technologies, Llc Thermally insulated shipping system for parcel-sized payload

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3080725A (en) * 1960-08-11 1963-03-12 Union Carbide Corp Method and apparatus for controlled rate cooling and warming of biological substances
US3092974A (en) * 1960-07-21 1963-06-11 Union Carbide Corp Method and apparatus for controlled freezing of biologicals
US3494140A (en) * 1967-10-17 1970-02-10 Integral Process Syst Inc Liquid nitrogen flash freezing
US3613386A (en) * 1970-03-23 1971-10-19 Air Prod & Chem Cryogenic freezer control
US3891477A (en) * 1971-09-09 1975-06-24 Mangrove Enterprise Inc Material treatment by cryogenic cooling
US3916640A (en) * 1974-06-10 1975-11-04 Ivan Rasovich Portable cryogenic fluid immersion-type freezer
US4306425A (en) * 1979-11-03 1981-12-22 C. Reichert Optische Werke Ag Device for the cryo-substitution of small biological objects for microscopic research, especially electron microscopic investigations
AU1287483A (en) * 1982-03-26 1983-09-29 Dean W. Schilling Grydgenic device and method
AU2303484A (en) * 1983-01-14 1984-07-19 Hoxan Corp. Freezing biological materials using a chamber with two separate heat xfr bodies

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3092974A (en) * 1960-07-21 1963-06-11 Union Carbide Corp Method and apparatus for controlled freezing of biologicals
US3080725A (en) * 1960-08-11 1963-03-12 Union Carbide Corp Method and apparatus for controlled rate cooling and warming of biological substances
US3494140A (en) * 1967-10-17 1970-02-10 Integral Process Syst Inc Liquid nitrogen flash freezing
US3613386A (en) * 1970-03-23 1971-10-19 Air Prod & Chem Cryogenic freezer control
US3891477A (en) * 1971-09-09 1975-06-24 Mangrove Enterprise Inc Material treatment by cryogenic cooling
US3916640A (en) * 1974-06-10 1975-11-04 Ivan Rasovich Portable cryogenic fluid immersion-type freezer
US4306425A (en) * 1979-11-03 1981-12-22 C. Reichert Optische Werke Ag Device for the cryo-substitution of small biological objects for microscopic research, especially electron microscopic investigations
AU1287483A (en) * 1982-03-26 1983-09-29 Dean W. Schilling Grydgenic device and method
AU2303484A (en) * 1983-01-14 1984-07-19 Hoxan Corp. Freezing biological materials using a chamber with two separate heat xfr bodies

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0290722A3 (fr) * 1987-05-15 1989-07-12 Limitek Oy Incubateur à gradient de température
EP0290722A2 (fr) * 1987-05-15 1988-11-17 Limitek Oy Incubateur à gradient de température
EP0299521A2 (fr) * 1987-07-15 1989-01-18 Fuji Photo Film Co., Ltd. Appareil d'analyses biochimiques
EP0299521A3 (en) * 1987-07-15 1989-11-15 Fuji Photo Film Co Ltd Biochemical analysis apparatus and refrigerator for the same
US5004582A (en) * 1987-07-15 1991-04-02 Fuji Photo Film Co., Ltd. Biochemical analysis apparatus
EP0363143A3 (fr) * 1988-10-06 1991-05-29 Coy Corporation Appareil de régulation de température
EP0363143A2 (fr) * 1988-10-06 1990-04-11 Coy Corporation Appareil de régulation de température
US5224536A (en) * 1988-11-17 1993-07-06 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Thermostatting device
WO1990005947A1 (fr) * 1988-11-17 1990-05-31 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Thermostat
WO2001049574A3 (fr) * 2000-01-04 2002-03-28 Thermokeep Ltd Appareil et procede de regulation de temperature
DE20117661U1 (de) * 2001-10-29 2003-03-13 Mwg Biotech Ag Thermocyclervorrichtung
US11608221B2 (en) 2018-06-15 2023-03-21 Cold Chain Technologies, Llc Shipping system for storing and/or transporting temperature-sensitive materials
US11634266B2 (en) 2019-01-17 2023-04-25 Cold Chain Technologies, Llc Thermally insulated shipping system for parcel-sized payload
CN110108532A (zh) * 2019-05-17 2019-08-09 中国科学院理化技术研究所 高低温处理设备
CN110108532B (zh) * 2019-05-17 2024-04-19 中国科学院理化技术研究所 高低温处理设备
WO2022142061A1 (fr) * 2020-12-28 2022-07-07 生物岛实验室 Puce de congélation, système de congélation et système et procédé de test d'échantillon
WO2022142062A1 (fr) * 2020-12-28 2022-07-07 生物岛实验室 Puce de réfrigération, système de réfrigération et système et procédé de test d'échantillon
US20220236002A1 (en) * 2021-01-22 2022-07-28 Alpha International Health Solution Limited Ultra-low temperature storage and dispensing system

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