WO2022062977A1 - 一种细胞自动离心清洗换液方法及装置 - Google Patents

一种细胞自动离心清洗换液方法及装置 Download PDF

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WO2022062977A1
WO2022062977A1 PCT/CN2021/118377 CN2021118377W WO2022062977A1 WO 2022062977 A1 WO2022062977 A1 WO 2022062977A1 CN 2021118377 W CN2021118377 W CN 2021118377W WO 2022062977 A1 WO2022062977 A1 WO 2022062977A1
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cup
information
centrifuge
centrifugal
cell volume
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PCT/CN2021/118377
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English (en)
French (fr)
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郭霄亮
姚嘉林
商院芳
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深圳赛桥生物创新技术有限公司
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Priority to JP2023518456A priority Critical patent/JP2023542370A/ja
Priority to US18/028,217 priority patent/US20230374441A1/en
Priority to EP21871348.5A priority patent/EP4206314A1/en
Publication of WO2022062977A1 publication Critical patent/WO2022062977A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C12M33/10—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus by centrifugation ; Cyclones
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04—Cell isolation or sorting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B13/00—Control arrangements specially designed for centrifuges; Programme control of centrifuges
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/44—Means for regulation, monitoring, measurement or control, e.g. flow regulation of volume or liquid level
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48—Automatic or computerized control
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/02—Separating microorganisms from the culture medium; Concentration of biomass
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/10—Separation or concentration of fermentation products

Definitions

  • the invention relates to the technical field of cell culture, in particular to a method and device for automatic centrifugal cleaning and liquid exchange of cells.
  • cell culture In the field of cell biology research and life science research, cell culture is the most basic link.
  • Cell culture is a culture process in which cells are grown and valued for "various purposes" by using nutrients, etc. in an artificial environment.
  • the centrifugal separation device In the process of cell culture, the centrifugal separation device is an effective method to realize the solid-liquid separation of cell culture. It can be used for cleaning and liquid exchange of cell culture. It is a high-frequency operation in cell experiments.
  • manual centrifugation is often inefficient, with high manual participation, and it is easy to intervene in some unnecessary impurities to contaminate the culture medium, which cannot guarantee the culture environment of cells. Therefore, automatic cytocentrifugation devices have great development prospects.
  • Embodiments of the present invention provide a method and device for automatic centrifugation, cleaning, and liquid exchange of cells, which are used to solve the technical problems raised in the above-mentioned background art, or at least partially solve the technical problems raised in the above-mentioned background art.
  • an embodiment of the present invention provides a method for automatic centrifugation, cleaning and liquid exchange of cells, including:
  • the spin-down processing of the centrifuge cup is performed in combination with the cell volume and the information of the centrifuge cup.
  • the centrifugal cup information includes: cup length information, cup height information and cup radius information;
  • cup length information is the distance from the outer wall of the centrifugal cup to the exit position of the centrifugal device
  • cup height information is the height of the centrifugal cup
  • cup radius information is the radius of the centrifugal cup.
  • the steps of performing the spin-down processing of the centrifuge cup in combination with the cell volume and the centrifuge cup information specifically include:
  • the centrifuge device calculate the spin down speed of the centrifuge cup according to the cell volume, the cup length information and the cup radius information, so as to perform centrifugation according to the spin down speed of the centrifuge cup Cup spin down.
  • the step of performing the spin-down processing of the centrifuge cup in combination with the cell volume and the centrifuge cup information specifically further includes:
  • the centrifugal cup deceleration speed is calculated according to the cup length information and the cup radius information, so as to perform the centrifugal cup deceleration process according to the centrifugal cup deceleration speed.
  • the step of performing the spin-down processing of the centrifuge cup in combination with the cell volume and the centrifuge cup information specifically further includes:
  • the centrifuge device calculate the spin down speed of the centrifuge cup according to the cell volume, the cup length information, the cup radius information and the centrifuge cup height, so as to The speed of the cup is reduced to perform the centrifugal cup speed-down treatment.
  • an embodiment of the present invention provides an automatic centrifugal cleaning and liquid exchange device for cells, including:
  • the acquisition module is used to acquire the cell volume and the critical value information of the centrifugal device after the centrifugation device is stable;
  • the speed-down and liquid-exchange module is used to perform the spin-down processing of the centrifuge cup in combination with the cell volume and the information of the centrifuge cup according to the magnitude relationship between the cell volume and the information of the critical value of the centrifuge device.
  • the centrifugal cup information includes: cup length information, cup height information and cup radius information;
  • cup length information is the distance from the outer wall of the centrifugal cup to the exit position of the centrifugal device
  • cup height information is the height of the centrifugal cup
  • cup radius information is the radius of the centrifugal cup.
  • an embodiment of the present invention provides an electronic device, including a memory, a processor, and a computer program stored in the memory and running on the processor, the processor implementing the program as described in the first aspect when the processor executes the program Describe the steps of the method of automatic centrifugation, washing and medium exchange of cells.
  • an embodiment of the present invention provides a non-transitory computer-readable storage medium on which a computer program is stored, and when the computer program is executed by a processor, realizes the automatic centrifugal cleaning and fluid replacement method for cells according to the first aspect. step.
  • the embodiment of the present invention provides a method and device for automatic centrifugal cleaning and liquid exchange of cells.
  • the extraction volume is changed by rotating at a reduced speed, and the speed of rotation is adjusted according to the relationship between the cell volume and the critical value information of the centrifugal device. In this way, the optimal effect of cleaning and changing the medium for cells of different volumes can be realized, and the automatic centrifugation of the cells for cleaning and changing the medium can be realized.
  • FIG. 1 is a schematic flowchart of the method for automatic centrifugation, cleaning and liquid exchange of cells described in an embodiment of the present invention
  • FIG. 2 is a schematic diagram of a centrifuge device with a cell volume smaller than a critical value according to an embodiment of the present invention
  • FIG. 3 is a schematic diagram of a centrifuge device with a cell volume equal to a critical value according to an embodiment of the present invention
  • FIG. 4 is a schematic diagram of a centrifuge device with a cell volume greater than a critical value according to an embodiment of the present invention
  • FIG. 5 is a schematic diagram of the automatic centrifugation and cleaning of cells according to an embodiment of the present invention.
  • FIG. 6 is a schematic diagram of the automatic centrifugal cleaning and liquid exchange according to another embodiment of the present invention.
  • FIG. 7 is a diagram illustrating the relationship between the remaining liquid volume and the rotational speed by reducing the centrifugal rotational speed described in another embodiment of the present invention.
  • FIG. 8 is a schematic diagram of an automatic centrifugation, washing and liquid changing device for cells according to an embodiment of the present invention.
  • FIG. 9 is a schematic structural diagram of an electronic device according to an embodiment of the present invention.
  • FIG. 1 is a schematic flowchart of the method for automatic centrifugation, cleaning and liquid exchange of cells described in an embodiment of the present invention, as shown in FIG. 1 , including:
  • Step S1 after the centrifugation device is stable after centrifugation, obtain cell volume and critical value information of the centrifuge device;
  • centrifugation is first performed at an acceleration of 200 g or more for more than 1 min, and cells or other organisms are centrifuged to the axial outer wall of the centrifuge cup.
  • the centrifugation is stable, extract the solution as much as possible so that the interface of the solution is equivalent to the outlet, and then slowly reduce the rotation speed.
  • the cell volume described in the embodiment of the present invention can be measured and obtained in advance before centrifugation, or it can be calculated specifically.
  • the calculation method of the cell volume is as follows:
  • V cell ⁇ SLR
  • the cell volume algorithm is as follows:
  • V cell ⁇ HR(T+L)
  • V cell refers to the cell volume
  • L refers to the cup length information
  • R refers to the cup radius information
  • S refers to the height of the cells in the centrifuge cup
  • H the centrifuge cup height
  • Step S2 according to the size relationship between the cell volume and the information about the critical value of the centrifuge device, and combining the cell volume and the information of the centrifuge cup, the spin-down processing of the centrifuge cup is performed.
  • the cell volume is greater than the critical value information of the centrifugal device
  • the cell volume is smaller than the critical value information of the centrifugal device
  • the cell volume is equal to the critical value information of the centrifugal device.
  • the centrifugal cup is processed by reducing the speed, so as to ensure the maximum capture rate and high liquid exchange rate for cell samples of different volumes within the fixed parameters of the centrifugal cup.
  • the extraction volume is changed by decelerating rotation, and the rotation deceleration is adjusted according to the relationship between the cell volume and the critical value information of the centrifuge device, so as to realize the optimal cleaning and liquid exchange effect of cells of different volumes. Realize the automatic centrifugation of cells to wash and change the medium.
  • the centrifugal cup information includes: cup length information, cup height information and cup radius information;
  • cup length information L is the distance from the outer wall of the centrifugal cup to the exit position of the centrifugal device
  • cup height information H is the height of the centrifugal cup
  • cup radius information R is the radius of the centrifugal cup.
  • the steps of performing the spin-down processing of the centrifuge cup in combination with the cell volume and the centrifuge cup information specifically include:
  • the centrifuge device calculate the spin down speed of the centrifuge cup according to the cell volume, the cup length information and the cup radius information, so as to perform centrifugation according to the spin down speed of the centrifuge cup Cup deceleration treatment;
  • FIG. 2 is a schematic diagram of a centrifuge device with a cell volume less than a critical value according to an embodiment of the present invention, as shown in FIG.
  • the position from the outside of the outer wall of the cup to the outlet is L
  • the radius of the centrifuge cup is R
  • the height of the centrifuge cup is H.
  • V cell ⁇ SLR
  • the step of carrying out the spin-down processing of the centrifuge cup in combination with the cell volume and the centrifuge cup information specifically also includes:
  • the calculation of the deceleration speed of the centrifugal cup is as follows.
  • the position from the outside of the outer wall to the outlet is L
  • the radius of the centrifuge cup is R
  • the height of the centrifuge cup is H.
  • V cell ⁇ HLR
  • the height of the cell in the centrifuge cup is the height H of the centrifuge cup.
  • the recommended speed is ⁇ .
  • V cell refers to the cell volume
  • L refers to the cup length information
  • R refers to the cup radius information
  • ⁇ refers to the centrifugal cup deceleration speed
  • the step of performing the spin-down processing of the centrifuge cup in combination with the cell volume and the centrifuge cup information specifically further includes:
  • the centrifugal cup deceleration speed is calculated as: Schematic diagram of the centrifugal device, as shown in Figure 4, the position from the outside of the outer wall of the cup to the outlet described in the embodiment of the present invention is L, the radius of the centrifugal cup is R, and the height of the centrifugal cup is H.
  • V cell ⁇ HLR
  • the height of the cells in the centrifuge cup is S
  • the trapezoidal stacking surface formed by the centrifuged cells
  • the length of the trapezoid top is T
  • the centrifuge cup reduces the speed the recommended rotation speed is ⁇ .
  • V cell ⁇ HR(T+L)
  • the extraction volume is changed by decelerating rotation, and the rotation deceleration is adjusted according to the relationship between the cell volume and the critical value information of the centrifuge device, so as to realize the optimal cleaning and liquid exchange effect of cells of different volumes. Realize the automatic centrifugation of cells to wash and change the medium.
  • FIG. 5 is a schematic diagram of the automatic centrifugal cleaning and liquid exchange of cells according to an embodiment of the present invention
  • FIG. 6 is a schematic diagram of the automatic centrifugal cleaning and liquid exchange according to another embodiment of the present invention.
  • step 1 First, centrifuge with an acceleration of 200 g or more for more than 1 min, and cells or other organisms will be centrifuged to the axial outer wall of the centrifuge cup. An outlet is provided at a certain distance from the outer wall of the cup, and the size of the distance can be set to a distance corresponding to the maximum volume of processed cell samples.
  • Step 2 When the centrifugation is stable, extract the solution as much as possible so that the interface of the solution is equivalent to the outlet, and then slowly reduce the rotation speed. with decreasing speed. The liquid interface changes.
  • Step 3 Finally, all the waste liquid is withdrawn, leaving the cells after centrifugation.
  • Figure 7 is a graph showing the relationship between the remaining liquid volume and the rotation speed by reducing the centrifugal speed described in another embodiment of the present invention. As shown in Figure 7, for the cytocentrifugation, we achieved 95% of the cell medium exchange, and the cell capture rate reached more than 95%, and the cell activity remained basically unchanged.
  • FIG. 8 is a schematic diagram of an automatic centrifugal cleaning and liquid exchange device for cells according to an embodiment of the present invention. As shown in FIG. 8 , it includes: an acquisition module 810 and a deceleration liquid exchange module 820 ; wherein, the acquisition module 810 is used for centrifugation stabilization in the centrifugal device Then, obtain the cell volume and the information of the critical value of the centrifuge device; wherein, the speed-down and liquid-exchange module 820 is used to perform the spin-down processing of the centrifuge cup in combination with the cell volume and the information of the centrifuge cup according to the size relationship between the cell volume and the information of the critical value of the centrifuge device .
  • the centrifugal cup information includes: cup length information, cup height information and cup radius information;
  • cup length information is the distance from the outer wall of the centrifugal cup to the exit position of the centrifugal device
  • cup height information is the height of the centrifugal cup
  • cup radius information is the radius of the centrifugal cup.
  • the extraction volume is changed by decelerating rotation, and the rotation deceleration is adjusted according to the relationship between the cell volume and the critical value information of the centrifuge device, so as to realize the optimal cleaning and liquid exchange effect of cells of different volumes. Realize the automatic centrifugation of cells to wash and change the medium.
  • FIG. 9 is a schematic structural diagram of an electronic device according to an embodiment of the present invention.
  • the electronic device may include: a processor (processor) 910, a communications interface (Communications Interface) 920, a memory (memory) 930, and a communication The bus 940, wherein the processor 910, the communication interface 920, and the memory 930 complete the communication with each other through the communication bus 940.
  • processor processor
  • Communications Interface Communications Interface
  • memory memory
  • the bus 940 wherein the processor 910, the communication interface 920, and the memory 930 complete the communication with each other through the communication bus 940.
  • the processor 910 can call the logic instructions in the memory 930 to perform the following method: after the centrifugation device is centrifuged and stabilized, obtain the cell volume and the critical value information of the centrifugal device; according to the size relationship between the cell volume and the critical value information of the centrifugal device, combine Cell volume and beaker information for beaker spin down.
  • the above-mentioned logic instructions in the memory 930 can be implemented in the form of software functional units and can be stored in a computer-readable storage medium when sold or used as an independent product.
  • the technical solution of the present invention can be embodied in the form of a software product in essence, or the part that contributes to the prior art or the part of the technical solution.
  • the computer software product is stored in a storage medium, including Several instructions are used to cause a computer device (which may be a personal computer, a server, or a network device, etc.) to execute all or part of the steps of the methods described in the various embodiments of the present invention.
  • the aforementioned storage medium includes: U disk, mobile hard disk, Read-Only Memory (ROM, Read-Only Memory), Random Access Memory (RAM, Random Access Memory), magnetic disk or optical disk and other media that can store program codes .
  • An embodiment of the present invention discloses a computer program product, where the computer program product includes a computer program stored on a non-transitory computer-readable storage medium, the computer program includes program instructions, and when the program instructions are executed by a computer,
  • the computer can execute the methods provided by the above method embodiments, for example, including: after the centrifugation device is centrifuged and stabilized, acquiring cell volume and information on the critical value of the centrifuge device; Volume and beaker information for beaker spin-down processing.
  • Embodiments of the present invention provide a non-transitory computer-readable storage medium, where the non-transitory computer-readable storage medium stores server instructions, and the computer instructions cause a computer to execute the methods provided in the foregoing embodiments, for example, including: centrifuging a centrifuge device After stabilization, the cell volume and the centrifuge device critical value information are obtained; according to the magnitude relationship between the cell volume and the centrifuge device critical value information, the centrifuge cup deceleration process is performed in combination with the cell volume and the centrifuge cup information.
  • the device embodiments described above are only illustrative, wherein the units described as separate components may or may not be physically separated, and the components displayed as units may or may not be physical units, that is, they may be located in One place, or it can be distributed over multiple network elements. Some or all of the modules may be selected according to actual needs to achieve the purpose of the solution in this embodiment. Those of ordinary skill in the art can understand and implement it without creative effort.
  • each embodiment can be implemented by means of software plus a necessary general hardware platform, and certainly can also be implemented by hardware.
  • the above-mentioned technical solutions can be embodied in the form of software products in essence or the parts that make contributions to the prior art, and the computer software products can be stored in computer-readable storage media, such as ROM/RAM, magnetic A disc, an optical disc, etc., including several instructions for causing a computer device (which may be a personal computer, a server, or a network device, etc.) to perform the methods described in various embodiments or parts of the embodiments.

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Abstract

一种细胞自动离心清洗换液方法及装置，该方法包括：在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理。通过降速旋转来实现抽取体积改变，并根据所述细胞体积和离心装置临界值信息的大小关系，来调整旋转降速，进而可以实现不同体积细胞最优的清洗换液效果，保证在固定的离心杯参数中最大限度的对不同体积细胞样本获得高捕获率、高换液率，实现细胞自动离心清洗换液。

Description

一种细胞自动离心清洗换液方法及装置 技术领域
本发明涉及细胞培养技术领域，尤其涉及一种细胞自动离心清洗换液方法及装置。
背景技术
在细胞生物学研究领域和生命科学研究领域中，细胞培养是最基本的环节。细胞培养是把细胞在人工环境下，利用营养物质等，将其繁育增值，并用于“各种目的”的培养过程。在细胞培养过程中，离心分离装置是实现细胞培养物的固液分离的有效方法，可用于细胞培养的清洗和换液，在细胞实验中是一个高频的操作。然而手动的离心换液操作往往效率较低，人工参与度较高，很容易介入一些不必要的杂质污染培养液，无法保证细胞的培养环境，因此自动细胞离心装置具有很大的发展前景。
在一些自动细胞离心装置中，细胞在离心力的作用下会被离心到离心容器的轴向外壁上，如果想实现自动化液体的抽取，必须在合适的轴向位置上设置有液体自动输出口，此时离心设备的速度对离心效果有着重要的影响。
因此如何控制自动细胞离心装置，从而更好的实现自动化液体的抽取已经成为业界亟待解决的问题。
发明内容
本发明实施例提供一种细胞自动离心清洗换液方法及装置，用以解决上述背景技术中提出的技术问题，或至少部分解决上述背景技术 中提出的技术问题。
第一方面，本发明实施例提供一种细胞自动离心清洗换液方法，包括：
在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；
根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理。
更具体的，所述离心杯信息包括：杯长信息、杯高信息和杯半径信息；
其中，所述杯长信息为离心杯外壁到离心装置出口位置的距离；
其中，所述杯高信息为离心杯的高度；
其中，所述杯半径信息为离心杯的半径。
更具体的，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理的步骤具体包括：
在所述细胞体积小于离心装置临界值信息的情况时，根据所述细胞体积、所述杯长信息和所述杯半径信息计算离心杯降速转速，以根据所述离心杯降速转速进行离心杯降速处理。
更具体的，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理的步骤具体还包括：
在所述细胞体积等于离心装置临界值信息的情况时，根据所述杯长信息和所述杯半径信息计算离心杯降速转速，以根据所述离心杯降速转速进行离心杯降速处理。
更具体的，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理的步骤具体还包括：
在所述细胞体积大于离心装置临界值信息的情况时，根据所述细胞体积、所述杯长信息、所述杯半径信息和所述离心杯高度计算离心杯降速转速，以根据所述离心杯降速转速进行离心杯降速处理。
第二方面，本发明实施例提供一种细胞自动离心清洗换液装置， 包括：
获取模块，用于在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；
降速换液模块，用于根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理。
更具体的，所述离心杯信息包括：杯长信息、杯高信息和杯半径信息；
其中，所述杯长信息为离心杯外壁到离心装置出口位置的距离；
其中，所述杯高信息为离心杯的高度；
其中，所述杯半径信息为离心杯的半径。
第三方面，本发明实施例提供一种电子设备，包括存储器、处理器及存储在存储器上并可在处理器上运行的计算机程序，所述处理器执行所述程序时实现如第一方面所述细胞自动离心清洗换液方法的步骤。
第四方面，本发明实施例提供一种非暂态计算机可读存储介质，其上存储有计算机程序，该计算机程序被处理器执行时实现如第一方面所述细胞自动离心清洗换液方法的步骤。
本发明实施例提供的一种细胞自动离心清洗换液方法及装置，通过降速旋转来实现抽取体积改变，并根据所述细胞体积和离心装置临界值信息的大小关系，来调整旋转降速，进而可以实现不同体积细胞最优的清洗换液效果，实现细胞自动离心清洗换液。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作一简单地介绍，显而易见地，下面描述中的附图是本发明的一些实施例，对于本领域普 通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为本发明一实施例中所描述的细胞自动离心清洗换液方法流程示意图；
图2为本发明一实施例所描述的细胞的体积小于临界值的离心装置示意图；
图3为本发明一实施例所描述的细胞的体积等于临界值的离心装置示意图；
图4为本发明一实施例所描述的细胞的体积大于临界值的离心装置示意图；
图5为本发明一实施例所描述的细胞自动离心清洗换液工作示意图；
图6为本发明另一实施例所描述的自动离心清洗换液工作示意图；
图7为本发明另一实施例中所描述的减小离心转速来摸索剩余液体体积与转速关系图；
图8为本发明一实施例所描述细胞自动离心清洗换液装置示意图；
图9为本发明一实施例所描述的电子设备结构示意图。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚，下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
图1为本发明一实施例中所描述的细胞自动离心清洗换液方法流程示意图，如图1所示，包括：
步骤S1，在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；
具体的，在离心装置离心稳定前，首先用200g以上的加速度进行离心1min以上，细胞或者其他生物体会被离心到离心杯子的轴向外壁。当离心稳定后，尽可能抽取溶液，使得溶液的界面与出口相当，此时缓慢的降低旋转速度。
本发明实施例中所描述的离心装置临界值信息V cell临界＝πHLR。
本发明实施例中所描述的细胞体积可以预先在进行离心前进行测量获取，也可以具体计算，细胞体积的计算方法具体为：
当细胞体积小于临界值V cell＝πHLR，细胞在离心杯中的高度为S
V cell＝πSLR
当细胞体积大于临界值V cell＝πHLR，细胞在离心杯中的高度为S，离心后的细胞形成的梯形堆积面，此时细胞体积算法方法为：
V cell＝πHR(T+L)
其中，V cell是指细胞体积，L是指杯长信息，R是指杯半径信息，S是指细胞在离心杯中的高度，离心杯高度为H。
步骤S2，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理。
具体的，根据所述细胞体积和离心装置临界值信息的大小关系，分为，细胞体积大于离心装置临界值信息、细胞体积小于离心装置临界值信息和细胞体积等于离心装置临界值信息这三种情况，确定不同的离心杯降速转速计算方法，最终得到离心杯降速信息，进行离心杯降速处理。
本发明实施例中是通过对离心杯降速处理，以保证在固定的离心 杯参数中最大限度的对不同体积细胞样本获得高捕获率、高换液率。
本发明实施例通过降速旋转来实现抽取体积改变，并根据所述细胞体积和离心装置临界值信息的大小关系，来调整旋转降速，进而可以实现不同体积细胞最优的清洗换液效果，实现细胞自动离心清洗换液。
在上述实施例的基础上，所述离心杯信息包括：杯长信息、杯高信息和杯半径信息；
其中，所述杯长信息L为离心杯外壁到离心装置出口位置的距离；
其中，所述杯高信息H为离心杯的高度；
其中，所述杯半径信息R为离心杯的半径。
更具体的，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理的步骤具体包括：
在所述细胞体积小于离心装置临界值信息的情况时，根据所述细胞体积、所述杯长信息和所述杯半径信息计算离心杯降速转速，以根据所述离心杯降速转速进行离心杯降速处理；
根据所述细胞体积、所述杯长信息和所述杯半径信息计算离心杯降速转速具体为，图2为本发明一实施例所描述的细胞的体积小于临界值的离心装置示意图，如图2所示，杯子外壁外部到出口位置为L，离心杯的半径为R，离心杯高度为H，当细胞体积小于临界值V cell＝πHLR，细胞在离心杯中的高度为S，离心杯降低速度时，建议转速为ω，
V cell＝πSLR
Figure PCTCN2021118377-appb-000001
Figure PCTCN2021118377-appb-000002
在上述实施例的基础上，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理的步 骤具体还包括：
在所述细胞体积等于离心装置临界值信息的情况时，根据所述杯长信息和所述杯半径信息计算离心杯降速转速，以根据所述离心杯降速转速进行离心杯降速处理；
根据所述杯长信息和所述杯半径信息计算离心杯降速转速具体为，图3为本发明一实施例所描述的细胞的体积等于临界值的离心装置示意图，如图3所示，杯子外壁外部到出口位置为L，离心杯的半径为R，离心杯高度为H，当细胞体积处于一个临界值V cell＝πHLR，细胞在离心杯中的高度即为离心杯的高度H，离心杯降低速度时，建议转速为ω。
Figure PCTCN2021118377-appb-000003
Figure PCTCN2021118377-appb-000004
其中，V cell是指细胞体积，L是指杯长信息，R是指杯半径信息，ω是指离心杯降速转速。
在上述实施例的基础上，更具体的，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理的步骤具体还包括：
在所述细胞体积大于离心装置临界值信息的情况时，根据所述细胞体积、所述杯长信息、所述杯半径信息和所述离心杯高度计算离心杯降速转速计算离心杯降速转速，以根据所述离心杯降速转速进行离心杯降速处理；
根据所述细胞体积、所述杯长信息、所述杯半径信息和所述离心杯高度计算离心杯降速转速具体为，图4为本发明一实施例所描述的细胞的体积大于临界值的离心装置示意图，如图4所示，本发明实施例中所描述的杯子外壁外部到出口位置为L，离心杯的半径为R，离心杯高度为H，当细胞体积大于临界值V cell＝πHLR，细胞在离心 杯中的高度为S，离心后的细胞形成的梯形堆积面，梯形顶长为T，离心杯降低速度时，建议转速为ω。
V cell＝πHR(T+L)
Figure PCTCN2021118377-appb-000005
Figure PCTCN2021118377-appb-000006
本发明实施例通过降速旋转来实现抽取体积改变，并根据所述细胞体积和离心装置临界值信息的大小关系，来调整旋转降速，进而可以实现不同体积细胞最优的清洗换液效果，实现细胞自动离心清洗换液。
在本发明另一实施例中，图5为本发明一实施例所描述的细胞自动离心清洗换液工作示意图，图6为本发明另一实施例所描述的自动离心清洗换液工作示意图，如图5和图6所示，步骤1：首先用200g以上的加速度进行离心1min以上，细胞或者其他生物体会被离心到离心杯子的轴向外壁。在距离杯子外壁外部一定的距离设置有出口，距离的大小可以设定为最大处理细胞样本的体积对应的距离。步骤2：当离心稳定后，尽可能抽取溶液，使得溶液的界面与出口相当，此时缓慢的降低旋转速度。随着速度的降低。液体界面会发生变化。步骤3：最后将废液全部抽出，留下离心后的细胞。
图7为本发明另一实施例中所描述的减小离心转速来摸索剩余液体体积与转速关系图，如图7所示，对于细胞离心我们实现了95％的细胞换液，细胞捕获率达到95％以上，且细胞活性基本维持不变。
图8为本发明一实施例所描述细胞自动离心清洗换液装置示意图，如图8所示，包括：获取模块810和降速换液模块820；其中，获取模块810用于在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；其中，降速换液模块820用于根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯 降速处理。
更具体的，所述离心杯信息包括：杯长信息、杯高信息和杯半径信息；
其中，所述杯长信息为离心杯外壁到离心装置出口位置的距离；
其中，所述杯高信息为离心杯的高度；
其中，所述杯半径信息为离心杯的半径。
本发明实施例提供的装置是用于执行上述各方法实施例的，具体流程和详细内容请参照上述实施例，此处不再赘述。
本发明实施例通过降速旋转来实现抽取体积改变，并根据所述细胞体积和离心装置临界值信息的大小关系，来调整旋转降速，进而可以实现不同体积细胞最优的清洗换液效果，实现细胞自动离心清洗换液。
图9为本发明一实施例所描述的电子设备结构示意图，如图9所示，该电子设备可以包括：处理器(processor)910、通信接口(Communications Interface)920、存储器(memory)930和通信总线940，其中，处理器910，通信接口920，存储器930通过通信总线940完成相互间的通信。处理器910可以调用存储器930中的逻辑指令，以执行如下方法：在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理。
此外，上述的存储器930中的逻辑指令可以通过软件功能单元的形式实现并作为独立的产品销售或使用时，可以存储在一个计算机可读取存储介质中。基于这样的理解，本发明的技术方案本质上或者说对现有技术做出贡献的部分或者该技术方案的部分可以以软件产品的形式体现出来，该计算机软件产品存储在一个存储介质中，包括若干指令用以使得一台计算机设备(可以是个人计算机，服务器，或者网络设备等)执行本发明各个实施例所述方法的全部或部分步骤。而 前述的存储介质包括：U盘、移动硬盘、只读存储器(ROM，Read-Only Memory)、随机存取存储器(RAM，Random Access Memory)、磁碟或者光盘等各种可以存储程序代码的介质。
本发明实施例公开一种计算机程序产品，所述计算机程序产品包括存储在非暂态计算机可读存储介质上的计算机程序，所述计算机程序包括程序指令，当所述程序指令被计算机执行时，计算机能够执行上述各方法实施例所提供的方法，例如包括：在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理。
本发明实施例提供一种非暂态计算机可读存储介质，该非暂态计算机可读存储介质存储服务器指令，该计算机指令使计算机执行上述各实施例提供的方法，例如包括：在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理。
以上所描述的装置实施例仅仅是示意性的，其中所述作为分离部件说明的单元可以是或者也可以不是物理上分开的，作为单元显示的部件可以是或者也可以不是物理单元，即可以位于一个地方，或者也可以分布到多个网络单元上。可以根据实际的需要选择其中的部分或者全部模块来实现本实施例方案的目的。本领域普通技术人员在不付出创造性的劳动的情况下，即可以理解并实施。
通过以上的实施方式的描述，本领域的技术人员可以清楚地了解到各实施方式可借助软件加必需的通用硬件平台的方式来实现，当然也可以通过硬件。基于这样的理解，上述技术方案本质上或者说对现有技术做出贡献的部分可以以软件产品的形式体现出来，该计算机软件产品可以存储在计算机可读存储介质中，如ROM/RAM、磁碟、光盘等，包括若干指令用以使得一台计算机设备(可以是个人计算机， 服务器，或者网络设备等)执行各个实施例或者实施例的某些部分所述的方法。
最后应说明的是：以上实施例仅用以说明本发明的技术方案，而非对其限制；尽管参照前述实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的精神和范围。

Claims (9)

  1. 一种细胞自动离心清洗换液方法，其特征在于，包括：
    在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；
    根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理。
  2. 根据权利要求1所述细胞自动离心清洗换液方法，其特征在于，所述离心杯信息包括：杯长信息、杯高信息和杯半径信息；
    其中，所述杯长信息为离心杯外壁到离心装置出口位置的距离；
    其中，所述杯高信息为离心杯的高度；
    其中，所述杯半径信息为离心杯的半径。
  3. 根据权利要求2所述细胞自动离心清洗换液方法，其特征在于，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理的步骤具体包括：
    在所述细胞体积小于离心装置临界值信息的情况时，根据所述细胞体积、所述杯长信息和所述杯半径信息计算离心杯降速转速，以根据所述离心杯降速转速进行离心杯降速处理。
  4. 根据权利要求2所述细胞自动离心清洗换液方法，其特征在于，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理的步骤具体还包括：
    在所述细胞体积等于离心装置临界值信息的情况时，根据所述杯长信息和所述杯半径信息计算离心杯降速转速，以根据所述离心杯降速转速进行离心杯降速处理。
  5. 根据权利要求2所述细胞自动离心清洗换液方法，其特征在于，根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理的步骤具体还包括：
    在所述细胞体积大于离心装置临界值信息的情况时，根据所述细胞体积、所述杯长信息、所述杯半径信息和所述离心杯高度计算离心 杯降速转速，以根据所述离心杯降速转速进行离心杯降速处理。
  6. 一种细胞自动离心清洗换液装置，其特征在于，包括：
    获取模块，用于在离心装置离心稳定后，获取细胞体积和离心装置临界值信息；
    降速换液模块，用于根据所述细胞体积和离心装置临界值信息的大小关系，结合细胞体积和离心杯信息进行离心杯降速处理。
  7. 根据权利要求6所述细胞自动离心清洗换液装置，其特征在于，所述离心杯信息包括：杯长信息、杯高信息和杯半径信息；
    其中，所述杯长信息为离心杯外壁到离心装置出口位置的距离；
    其中，所述杯高信息为离心杯的高度；
    其中，所述杯半径信息为离心杯的半径。
  8. 一种电子设备，包括存储器、处理器及存储在存储器上并可在处理器上运行的计算机程序，其特征在于，所述处理器执行所述程序时实现如权利要求1至6任一项所述细胞自动离心清洗换液方法的步骤。
  9. 一种非暂态计算机可读存储介质，其上存储有计算机程序，其特征在于，该计算机程序被处理器执行时实现如权利要求1至6任一项所述细胞自动离心清洗换液方法的步骤。
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