Rewarming device and control method thereof

By designing a cell retempering device containing a spiral ring-shaped curved delivery pipeline and an intelligent temperature control device, the problems of slow retempering speed, local overheating and pollution in the prior art are solved, and a fast, uniform and clean cell retempering effect is achieved.

CN113122442BActive Publication Date: 2025-04-25SHANGHAI HORIZON MEDICAL SCI CO LTD
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Patent Information

Application Number
CN201911407176.8
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2019-12-31
Publication Date
2025-04-25
Estimated Expiration
2039-12-31

AI Technical Summary

Technical Problem

The existing cell retempering methods have problems such as small temperature difference, slow retempering speed, local overheating, uneven heating, and artificial retempering pollution and inconvenient operation.

Method used

A retempering device including a support device, a spiral ring-shaped curved conveying pipeline, a sleeve, a heating wire and an intelligent temperature control device is designed. By controlling the preset temperature range and heating wire, rapid and uniform cell retempering is achieved.

Benefits of technology

The device can quickly and cleanly re-heat cells, reduce the damage to cells by recrystallization, avoid local overheating and uneven heating problems, and improve the stability and reliability of the operation.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention provides a rewarming device for cells after freezing, wherein the cells are frozen in a cryopreservation tube, and comprises a support device, a delivery pipeline, a sleeve, a heating wire, and an intelligent temperature control device. The support device fixedly supports the delivery pipeline; the delivery pipeline is arranged in a spiral ring shape along the longitudinal axis of the support device; the heating wire is arranged in at least two sections, and the heating wire is arranged between the sleeve and the outer tube wall of the delivery pipeline; the intelligent temperature control device couples the at least two sections of the heating wire, and controls the temperature heated by the at least two sections of the heating wire according to at least two preset temperature intervals; the cryopreservation tube is transported from the input port of the delivery pipeline to the output port. The present invention also provides a control method for a rewarming device, and the rewarming device and the control method thereof of the present invention can reduce the damage to cells caused by recrystallization during rapid rewarming of cells.
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Description

Technical Field

[0001] The present invention belongs to the field of medical devices, and in particular relates to a rewarming device for cells after freezing and a control method of the rewarming device. Background Art

[0002] Cryopreservation is an important means of cell preservation, and the rewarming speed determines the final state of the cells. When stored at low temperatures, cells must go through two processes: cooling and warming from room temperature to low temperature (usually -196°C), and then recovering from low temperature to the physiological state. They are more likely to face a series of damage threats caused by freezing twice. Among them, improper rewarming conditions during the rewarming process will cause recrystallization. Therefore, avoiding the formation and growth of ice crystals inside and outside cells is one of the most important factors for the success of cryopreservation. At present, in the cryopreservation stage, vitrification methods or programmed nucleation methods are used to reduce the damage of ice crystals to cells during cryopreservation.

[0003] In the existing thawing method, the warming process of the embryo from low temperature to the physiological state mainly involves taking the cryopreservation tube containing the cells out of liquid nitrogen and placing it directly in a 37°C water bath and shaking it back and forth rapidly until all the ice crystals disappear. However, a problem that this method easily leads to is that due to the small temperature difference, the thawing speed is not fast enough. When the temperature exceeds 37°C, due to the heat capacity of the material, it is easy to cause local overheating and uneven heating, resulting in overheating. At the same time, if the cryopreservation tube is not sealed strictly, the bacteria in the water bath water may also cause the cells that have just been thawed to be contaminated. In addition, the manual shaking process increases the pollution of artificial thawing and the inconvenience of operation.

[0004] In view of this, it is necessary to provide a cell rewarming device after freezing that is fast, clean, and can reduce cell damage during rewarming. Summary of the invention

[0005] In order to overcome the defects of the prior art, the object of the present invention is to provide a cell rewarming device after freezing and a control method thereof which is fast, clean and can reduce damage to the cells during rewarming after freezing.

[0006] To achieve the above-mentioned purpose, the technical solution adopted by the present invention is as follows: One aspect of the present invention provides a thawing device for thawing cells after freezing, wherein the cells are frozen in a cryopreservation tube, and comprises a supporting device, a conveying pipe, a sleeve, a heating wire, and an intelligent temperature control device, wherein the supporting device fixedly supports the conveying pipe; the conveying pipe is arranged in a spiral ring shape along the longitudinal axis of the supporting device; the sleeve is wrapped around the outer tube wall of the conveying pipe; the heating wire is provided with at least two sections, and the heating wire is provided between the sleeve and the outer tube wall of the conveying pipe, and surrounds the outer tube wall of the conveying pipe; the intelligent temperature control device couples the at least two sections of the heating wire to control the heating temperature of the at least two sections of the heating wire according to at least two preset temperature ranges; the cryopreservation tube is conveyed from the input port of the conveying pipe to the output port.

[0007] In a preferred embodiment of the present invention, the rewarming device further comprises a conveying device, wherein the conveying device is connected to an input port of the conveying pipeline, and the conveying device conveys the cryotube from the input port to the output port.

[0008] Preferably, the delivery device includes a jet pump, a jet control valve and a jet pipe; wherein one end of the jet pipe is connected to the input port of the delivery pipeline, the other end of the jet pipe is connected to the jet pump, and the jet control valve is arranged on the jet pipe to control the jet of the jet pipe. Preferably, the rewarming device also includes a special pipe joint, one end of which is connected to the jet pipe and the other end is connected to the input port of the delivery pipeline; a piston switch is arranged on the outer surface of the special pipe joint.

[0009] Preferably, the rewarming device further comprises a collecting device, the collecting device being connected to the output port of the delivery pipeline. More preferably, the collecting device is provided with an air release channel, the air release channel releases air when the air injection pipe injects air.

[0010] In another preferred embodiment of the present invention, the delivery pipeline is arranged in at least two levels of spiral annular bending from the lower part to the upper part or from the upper part to the lower part along the longitudinal axis of the support device. Preferably, the delivery pipeline is arranged in three levels of spiral annular bending from the lower part to the upper part or from the upper part to the lower part along the longitudinal axis of the support device, and the heating wire is arranged in three sections; the intelligent temperature control device is respectively coupled to the three sections of heating wire to control the heating temperature of the three sections of heating wire according to the three preset temperature intervals.

[0011] Preferably, at least one heat-insulating ring is provided between adjacent heating wires, and the heat-insulating ring surrounds the outer wall of the conveying pipeline and the inner wall of the sleeve.

[0012] Preferably, at least two temperature sensors are provided in the intelligent temperature control device, the number of the temperature sensors corresponds to the number of segments of the preset temperature interval, and the intelligent temperature control device is coupled to the heating wires respectively through the temperature sensors.

[0013] Preferably, the temperature sensor is a thermocouple, which passes through the sleeve to detect the temperature of the hollow inner cavity of the conveying pipe surrounded by the corresponding coupled heating wire.

[0014] Preferably, the jet intensity of the jet pipe is adjusted according to the heating rate of the hollow inner cavity of the conveying pipeline.

[0015] Preferably, the diameter of the hollow inner cavity of the delivery pipeline is larger than the outer diameter of the cryopreservation tube.

[0016] Preferably, the inner tube wall of the delivery pipe is provided with rifling, which is protruded from the inner tube wall of the delivery pipe toward the inner cavity.

[0017] Preferably, the supporting device is a cylindrical or cylindrical base.

[0018] Another aspect of the present invention provides a control method of the rewarming device, which is used for rewarming cells after freezing, comprising the following steps: the intelligent temperature control device presets at least two temperature intervals; wherein the temperature of the temperature interval is preset according to the following parameters: n-1 ,t n Indicates the time it takes for the cryopreservation tube to pass through at least two stages of transport pipelines, ...T n-1 , T n represents the temperature of the at least two-stage transport pipeline, ...T' n-1 , T' n represents the temperature of the cryopreservation tube leaving the at least two-stage transport pipeline, T'0 represents the initial temperature of the cryopreservation tube, α represents the convection heat transfer coefficient in the transport pipeline, C is the specific heat capacity, m is the mass of the cryopreservation tube, A is the total surface area of ​​the cryopreservation tube, ...L n-1 , L n represents the length of the at least two-stage delivery pipeline, the moving speed of the cryopreservation tube in the delivery pipeline is v, n is a positive integer, t n With T' n Satisfies the following system of equations:

[0019] as well as

[0020] The intelligent temperature control device is based on the at least two preset temperature intervals T n-1 , T nControl the temperature of the at least two heating wires; the cryopreservation tube passes through at least two temperature intervals T from the input port of the delivery pipeline n-1 , T n is transported to the output port. When the cryopreservation tube passes through the temperature range T n-1 After that, the temperature becomes T' n-1 When the cryopreservation tube passes through the temperature interval T n After that, the temperature becomes T' n ; where T' n-1 <T’ n =37℃.

[0021] The cell rewarming device and rewarming control method after freezing of the present invention solve the problems of overheating caused by small temperature difference, slow rewarming speed, local overheating, uneven heating, and pollution and inconvenience in operation caused by artificial rewarming. The rewarming device of the present invention can quickly and cleanly rewarm frozen cells, and can effectively reduce the damage of recrystallization to cells during rapid rewarming of cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] After reading the specific embodiments of the present invention with reference to the accompanying drawings, readers will have a clearer understanding of various aspects of the present invention.

[0023] Figure 1 It is a partial structural schematic diagram of a rewarming device according to a preferred embodiment of the present invention;

[0024] Figure 2 It is a schematic structural diagram of a rewarming device according to another preferred embodiment of the present invention;

[0025] Figure 3 A schematic diagram of the structure of a special pipe joint of the rewarming device of the present invention; and

[0026] Figure 4 It is a schematic diagram of the partial structure of a rewarming device in another preferred embodiment of the present invention.

[0027] The labels are as follows:

[0028] 10: conveying pipeline, 11: rifling, 12: supporting device, 13: casing, 14: insulation ring, 20: temperature sensor (thermocouple), 21: heating wire, 22: first temperature sensor, 24: second temperature sensor, 26: third temperature sensor, 213: first heating wire, 215: second heating wire, 217: third heating wire, 30: intelligent temperature control device, 400: conveying device, 40: jet pump, 41: jet control valve, 42: jet tube, 50: special pipe joint, 51: freezing tube, 52: piston switch, 60: ordinary pipe joint, 61: conveying hose, 70: collecting device with open end, 71: venting channel, 72: unpacking valve. DETAILED DESCRIPTION

[0029] In order to make the technical content disclosed in this application more detailed and complete, reference may be made to the accompanying drawings and the following specific embodiments of the present invention. However, it should be understood by those skilled in the art that the embodiments provided below are not intended to limit the scope of the present invention. In addition, the accompanying drawings are only schematically illustrated and are not drawn according to their original size.

[0030] The specific implementation modes of various aspects of the present invention are further described in detail below with reference to the accompanying drawings.

[0031] See also Figure 1 A schematic diagram of the partial structure of a rewarming device according to a preferred embodiment of the present invention, Figure 2 Another preferred structural schematic diagram of a cell rewarming device after freezing is shown. In this embodiment, the cells are frozen in a cryopreservation tube 51, and the cell rewarming device after freezing includes a delivery pipe 10, a support device 12, a sleeve 13, a heating wire 21, and an intelligent temperature control device 30, wherein the support device 12 fixedly supports the delivery pipe 10; the delivery pipe 10 is arranged in a spiral annular shape from the bottom to the top or from the bottom to the top along the longitudinal axis of the support device 12, and has an input port and an output port, a hollow inner cavity, and inner and outer tube walls; the sleeve 13 is wrapped around the outer tube wall of the delivery pipe 10, and has inner and outer walls; the heating wire 21 is arranged between the inner wall of the sleeve 13 and the outer tube wall of the delivery pipe 10, and surrounds the outer tube wall of the delivery pipe 10; the intelligent temperature control device 30 is coupled to the heating wire 21 to control the temperature of the heating wire 21 according to the temperature range preset by the intelligent temperature control device 30; the cryopreservation tube 51 is transported from the input port of the delivery pipe to the output port.

[0032] In this embodiment, the support device 12 is a cylindrical or cylindrical base, which is used to fix and support the delivery pipe 10. Preferably, in this embodiment, part or most of the delivery pipe 10 is embedded in the cylindrical or cylindrical base, integrated with the base, and is a through hollow pipe. In other embodiments of the present invention, the delivery pipe 10 can also be completely embedded in the base, or the base is not required, and only one fixed support point is needed to fix and support the delivery pipe 10.

[0033] In this embodiment, the delivery pipe 10 is made of a material having thermal conductivity, such as metal, and has smooth inner and outer pipe walls. The input port of the delivery pipe 10 is located at the lower end of the delivery pipe 10, and the output port of the delivery pipe 10 is located at the upper top of the delivery pipe 10. Those skilled in the art should understand that the description of the material of the delivery pipe 10 and the position of each component in this embodiment is only to schematically illustrate the structure and performance of the delivery pipe 10, and should not be understood as a limitation on the material of the delivery pipe 10 and the position of each component.

[0034] In this embodiment, the diameter of the hollow inner cavity of the delivery pipe 10 is larger than the outer diameter of the cryotube 51, and is used to accommodate the cryotube 51. In other embodiments of the present invention, the hollow inner cavity of the delivery pipe 10 may also be provided with rifling 11, which is protruded from the inner wall of the delivery pipe 10 toward the inner cavity and fits with the cryotube 51, so that the cryotube 51 can rotate in the hollow inner cavity of the delivery pipe 10.

[0035] In the present embodiment, the conveying pipe 10 is arranged in at least two levels of spiral annular bends from the bottom to the top, or from the top to the bottom, along the longitudinal axis of the support device 12; the heating wire 21 is arranged in at least two sections corresponding to the conveying pipe 10 arranged in two levels of spiral annular bends, respectively arranged between the outer pipe wall of the conveying pipe 10 of each level of spiral annular bend and the inner wall of the sleeve 13, and respectively surrounded by the outer pipe wall of each level of the conveying pipe 10; the intelligent temperature control device 30 is respectively coupled to the at least two sections of heating wire 21 to control the heating temperature of the at least two sections of heating wire 21 according to at least two temperature intervals preset by the intelligent temperature control device 30. In other embodiments of the present invention, the conveying pipe 10 can be arranged in three or more levels of spiral annular bends from the bottom to the top or from the top to the bottom according to actual needs, which will not be repeated here for the sake of simplicity.

[0036] Specifically, see Figure 4In another preferred embodiment of the present invention, the conveying pipeline 10 is arranged in a three-level spiral annular bend from the bottom to the top or from the top to the bottom along the longitudinal axis of the supporting device 12. For the sake of simplicity, in this embodiment, the first, second and third level spiral annular bends are referred to from the bottom to the top respectively; the heating wire 21 is provided with three sections, namely the first heating wire 213, the second heating wire 215 and the third heating wire 217. The first heating wire 213 is arranged between the outer tube wall of the first-level spiral annular bend conveying pipeline 10 and the inner wall of the casing 13, and surrounds the outer tube wall of the first-level conveying pipeline 10; the second heating wire 215 is arranged between the outer tube wall of the second-level spiral annular bend conveying pipeline 10 and the inner wall of the casing 13, and surrounds the outer tube wall of the second-level conveying pipeline 10; the third heating wire 217 is arranged between the outer tube wall of the third-level spiral annular bend conveying pipeline 10 and the inner wall of the casing 13, and surrounds the outer tube wall of the third-level conveying pipeline 10.

[0037] In this embodiment, the intelligent temperature control device 30 is coupled to the first, second and third heating wires 213, 215 and 217 respectively, so as to control the temperatures heated by the three sections of heating wires 213, 215 and 217 respectively according to the three temperature intervals preset by the intelligent temperature control device. Specifically, the intelligent temperature control device 30 is preset with a number of temperature intervals and temperature sensors 20 corresponding to the number of spiral annular bending stages of the conveying pipeline 10, and the intelligent temperature control device 30 is coupled to the heating wires 213, 215 and 217 respectively through the temperature sensors 20. More specifically, if the spiral annular bending level of the conveying pipeline 10 is set to three, then the temperature sensors 20 are set to three, including a first temperature sensor 22, a second temperature sensor 24 and a third temperature sensor 26. The first temperature sensor 22 is coupled to the first heating wire 213, and the intelligent temperature control device 30 detects the temperature of the inner cavity of the first-level conveying pipeline 10 through the first temperature sensor 22 and controls the heating temperature of the first heating wire 213; the second temperature sensor 24 is coupled to the second heating wire 215, and the intelligent temperature control device 30 detects the temperature of the inner cavity of the second-level conveying pipeline 10 through the second temperature sensor 24 and controls the heating temperature of the second heating wire 215; the third temperature sensor 26 is coupled to the third heating wire 217, and the intelligent temperature control device 30 detects the temperature of the inner cavity of the third-level conveying pipeline 10 through the third temperature sensor 26 and controls the heating temperature of the third heating wire 213. When the first to third heating wires 213, 215 and 217 are heated according to the three preset temperature ranges respectively, the temperature of the hollow inner cavity of the first to third stage conveying pipes 10 will also increase accordingly, so that the freezing tube 51 accommodated and moving in the hollow inner cavity of the conveying pipe 10 can be gradually heated up.

[0038] Preferably, in this embodiment, the temperature sensor 20 and its first temperature sensor 22, second temperature sensor 24 and third temperature sensor 26 are all thermocouples, which pass through the sleeve 13 respectively to detect the temperature of the hollow inner cavity of the first, second and third conveying pipes 10 surrounded by the first to third heating wires 213, 215 and 217 to which they are coupled. For example, in practical applications, the three temperature intervals of the intelligent temperature control device 30 can be defined as high temperature, medium-high temperature and medium-low temperature, respectively, with parameters of 100°C-80°C, 80°C-60°C, and 60°C-37°C, respectively, the first heating wire 213 is set to high temperature, the second heating wire 215 is set to medium-high temperature, and the third heating wire 217 is set to medium-low temperature. When the first temperature sensor 22, the second temperature sensor 24 and the third temperature sensor 26 respectively detect that the temperature of the hollow inner cavity of the first, second and third conveying pipes 10 reaches the specific temperature of the corresponding temperature interval, it is determined that the temperature is relatively stable. Of course, the specific temperature parameter setting range can be set according to actual needs, and this embodiment does not limit this.

[0039] Continue reading Figure 1 and Figure 2 In another preferred embodiment of the present invention, the rewarming device further comprises a conveying device 400 ; the conveying device 400 is connected to the input port of the conveying pipeline 10 , and conveys the cryotube 51 from the input port to the output port of the conveying pipeline through the hollow inner cavity of the conveying pipeline 10 .

[0040] In a more preferred embodiment, the conveying device 400 is a pneumatic conveying device, which is mainly used to inject gas or draw vacuum to make the cryopreservation tube 51 move passively, and includes a jet pump 40, a jet control valve 41 and a jet pipe 42; wherein, one end of the jet pipe 42 is connected to the input port of the conveying pipeline 10, and the other end of the jet pipe 42 is connected to the jet pump 40, and the jet control valve 41 is arranged on the jet pipe 42 to control the jet of the jet pipe 42. In this embodiment, the jet intensity of the jet pipe 42 of the conveying device 400 is adjusted according to the heating rate of the hollow inner cavity temperature of the conveying pipeline 10. In other embodiments of the invention, the jet intensity of the jet pipe 42 of the conveying device 400 can be adjusted according to different parameters according to actual needs.

[0041] See also Figure 3, which is a schematic diagram of a special pipe joint structure in another preferred embodiment of the present invention, in this embodiment, the cell rewarming device after freezing further includes a special pipe joint 50, one end of which is connected to one end of the jet pipe 42, and the other end is connected to the input port of the delivery pipe 10, so that one end of the jet pipe 42 is connected to the input port of the delivery pipe through the special pipe joint 50; a piston switch 52 with a hatch is provided on the outer surface of the special pipe joint 50. In this embodiment, the special pipe joint 50 is a special pipe interface, which is an L-shaped or arc-shaped pipe, one end of which can be connected to the jet pipe 42, and the other end can be seamlessly connected to the input port at the bottom of the delivery pipe 10. When the piston switch 52 with a hatch on the outer surface of the special pipe joint 50 is opened, the hatch can be opened to put in the cryotube 51 taken out of liquid nitrogen.

[0042] In a preferred embodiment of the present invention, at least one insulation ring 14 is provided between each adjacent section of the heating wire 213, 215, 217. The insulation rings 14 are respectively surrounded by the outer tube wall of each stage of the conveying pipeline 10, and are arranged between the outer tube wall of each stage of the spirally curved conveying pipeline 10 and the inner wall of the sleeve 13, so as to prevent the temperature conduction of the heating wire between adjacent sections, and further prevent the temperature conduction of the hollow inner cavity of the conveying pipeline 10 between different levels.

[0043] See also Figure 2 In a preferred embodiment of the present invention, the cell rewarming device after freezing further comprises a collecting device 70 with an open end, and the collecting device 70 with an open end is connected to the output port of the delivery pipe 10 to accommodate the cryotube 51 output from the output port. The collecting device 70 with an open end is provided with a deflation channel 71 and a box opening valve 72; the deflation channel 71 can deflate when the jet pipe 42 of the pneumatic delivery device 400 jets, and the box opening valve 72 can be opened or closed. When the box opening valve 72 is opened, the rewarmed cryotube 51 can be conveniently and cleanly taken out.

[0044] In this embodiment, the cell rewarming device after freezing also includes a common pipe joint 60 and a delivery hose 61, and the collection device 70 with an open end is connected to the output port of the delivery pipeline 10 with the common pipe joint 60 through the delivery hose 61. Specifically, one end of the common pipe joint 60 is connected to the output port of the delivery pipeline 10, and the other end is connected to one end of the delivery hose 61; the other end of the delivery hose 61 is connected to the open end of the collection device 70 with an open end, thereby, the collection device 70 with an open end is connected to the output port of the delivery pipeline 10 with the common pipe joint 60 through the delivery hose 61. In this embodiment, the material of the delivery hose 61 is preferably soft, bendable, and pressure-resistant, such as silicone, polymer flexible material, etc. Among them, the common pipe joint 60 is usually not provided with a hatch for discharging. The special pipe joint 50 is usually provided with a hatch for loading the cryopreservation tube 51. The delivery pipeline 10 includes heating, and the delivery hose 61 has no heating function and serves as a connection.

[0045] A preferred embodiment of the present invention further provides a control method of the rewarming device, which is used for rewarming cells after freezing, comprising the following steps:

[0046] The intelligent temperature control device is preset with at least two temperature intervals; wherein the temperature of the temperature interval is preset according to the following parameters: n-1 ,t n Indicates the time it takes for the cryopreservation tube to pass through at least two stages of transport pipelines, ...T n-1 , T n represents the temperature of the at least two-stage transport pipeline, ...T' n-1 , T' n represents the temperature of the cryopreservation tube leaving the at least two-stage transport pipeline, T'0 represents the initial temperature of the cryopreservation tube, α represents the convection heat transfer coefficient in the transport pipeline, C is the specific heat capacity, m is the mass of the cryopreservation tube, A is the total surface area of ​​the cryopreservation tube, ...L n-1 , L n represents the length of the at least two-stage delivery pipeline, the moving speed of the cryopreservation tube in the delivery pipeline is v, n is a positive integer, t n With T' n Satisfies the following system of equations:

[0047] as well as

[0048] The intelligent temperature control device is based on the at least two preset temperature intervals T n-1 , T n Controlling the heating temperature of the at least two sections of heating wires;

[0049] The cryopreservation tube passes through at least two temperature intervals T from the input port of the delivery pipeline. n-1 、T n is transported to the output port. When the cryopreservation tube passes through the temperature range T n-1 After that, the temperature becomes T' n-1 When the cryopreservation tube passes through the temperature interval T n After that, the temperature becomes T' n ; where T' n-1 <T’ n =37℃.

[0050] The following is an illustrative description of the process steps of a control method of a most preferred cell rewarming device after freezing of the present invention. Those skilled in the art should understand that this example is only for illustrating the optimal workflow steps and methods of the cell rewarming device after freezing, and other workflow steps and methods that reduce or add some components do not depart from the scope of the present invention.

[0051] This preferred embodiment is explained by taking the setting of three-stage temperature gradient as an example. In this preferred embodiment, the intelligent temperature control device 30 is turned on and receives preset instructions for the temperature range, wherein the temperature is preset according to the following parameters: the temperature of each stage of the delivery pipeline 10 is determined by the required heating time, t1, t2, and t3 respectively represent the time taken to pass through each stage of the delivery pipeline 10, T1, T2, and T3 respectively represent the temperature of each stage of the delivery pipeline 10, the temperature of the cryopreservation tube 51 leaving the delivery pipeline 10 at each stage is T'1, T'2, and T'3 respectively, T'0 represents the initial temperature of the cryopreservation tube 51, α represents the convection heat transfer coefficient in the pipeline, C is the specific heat capacity, m is the mass of the cryopreservation tube, A is the total surface area of ​​the cryopreservation tube 51, and the length of each stage of the delivery pipeline 10 is represented by L1, L2, and L 3. Since the suction or jet speed of the conveying device 400 is constant, the movement speed of the cryopreservation tube in the channel is v, and the temperatures T'1, T'2, and T'3 of each section satisfy the following equations:

[0052]

[0053]

[0054]

[0055]

[0056]

[0057]

[0058] Among them, T' 1< T' 2< T'3 = 37°C.

[0059] In this embodiment, T1, T2, and T3 are defined as high temperature, medium-high temperature, and medium-low temperature or the first temperature interval, the second temperature interval, and the third temperature interval, respectively, and the parameters are 100°C-80°C, 80°C-60°C, and 60°C-37°C, respectively.

[0060] The intelligent temperature control device controls the temperature of the three heating wires according to the preset three temperature intervals T1, T2, and T3. Accordingly, the first heating wire 213 is used to achieve heating to T1 = 100°C-80°C, the second heating wire 215 is used to achieve heating to T2 = 80°C-60°C, and the third heating wire 217 is used to achieve heating to T3 = 60°C-37°C. When the first temperature sensor 22, the second temperature sensor 24, and the third temperature sensor 26 respectively detect that the temperature of the hollow inner cavity of the first-level, second-level, and third-level conveying pipelines 10 reaches the specific temperature of the corresponding temperature interval, it is determined that the temperature is relatively stable.

[0061] When the first to third heating wires 213-217 heat the hollow inner cavities of the first to third level delivery pipes 10 respectively, the piston switch 52 with the hatch of the special pipe joint 50 is opened, the hatch is opened, and the cryopreservation tube 51 enters the special pipe joint 50 from the hatch, and the jet pipe 42 of the delivery device 400 is sprayed into the hollow inner cavity of the delivery pipe 10 through the jet pump 40. The jet intensity of the jet pipe 42 is adjusted according to the heating rate of the hollow inner cavity of the delivery pipe 10 and is controlled by the jet control valve 41. In this embodiment, when the jet control valve 41 controls the jet pipe 42 to spray into the hollow inner cavity of the delivery pipe 10 at a certain speed, the deflation channel 71 of the collection device 70 with an open end can deflate when the jet pipe 42 of the pneumatic delivery device 400 sprays, so as to ensure that the movement of the cryopreservation tube 51 in the hollow inner cavity of the delivery pipe 10 is not affected by the air pressure.

[0062] The cryopreservation tube 51 passes through the three hollow cavities of the delivery pipe 10 in three temperature ranges, namely, 100°C-80°C, 80°C-60°C, and 60°C-37°C, through the special pipe joint 50; when passing through the first-stage delivery pipe 10 in the T1 high temperature range, due to the large temperature difference, the cells will quickly heat up, and the temperature T'1 will rise from -196°C to about -80°C; when passing through the second-stage delivery pipe 10 in the T2 medium and high temperature range, due to the large temperature difference, the cells will also quickly heat up, and the temperature T'2 will rise from about -80°C to about 20°C; when passing through the third-stage delivery pipe 10 in the T3 medium and low temperature range, due to the temperature difference, the cells will also quickly heat up, and the temperature T'3 will rise from about 20°C to about 37°C, that is, T' 1< T' 2<T'3 = 37°C. The cryotube 51 moves at a constant speed in the hollow inner cavity of the delivery pipe 10 under the pneumatic conveying action of the jet pump 40. Controlling the power of the jet pump 40 can control the movement rate of the cryotube 51 in the delivery pipe 10. In this process, due to the presence of the rifling 11 in the hollow inner cavity of the delivery pipe 10, the cryotube 51 can rotate in the delivery pipe 10, so that the cryotube 51 is heated evenly and local overheating is avoided. The cryotube 51 will heat up rapidly during the process of passing through the three temperature zones of the three-stage delivery pipe 10. When the cryotube 51 reaches the output port of the delivery pipe 10, the ice crystals in the cryotube 51 have melted into liquid, the ice crystals disappear, and the temperature of the cryotube 51 is close to room temperature.

[0063] After that, the cryopreservation tube 51 passes through the common pipe joint 60 and the delivery hose 61, reaches the collection device 70 with an open end and is contained therein, and the opening valve 72 of the collection device 70 is usually in a closed state. When necessary, the opening valve 72 of the collection device 70 is opened to conveniently and cleanly take out the thawed cryopreservation tube 51. This process completes the rapid and uniform heating process of the cryopreservation tube 51, which can effectively overcome the uncertainty of the cells in the vibration of the cryopreservation tube in the water bath and the slow heating process in the traditional heating process.

[0064] The rewarming device and rewarming control method of cells after freezing of the present invention solve the uncertainty of cells in the vibrating cryopreservation tube in the water bath during the cell heating process under the traditional method, the problem of over-temperature caused by small temperature difference and slow rewarming speed, or local overheating and uneven heating during the manual rewarming operation, as well as the pollution and inconvenience of operation caused by manual rewarming. At the same time, the rewarming device of the present invention can quickly and cleanly rewarm frozen cells, and can effectively reduce the damage of recrystallization to cells during rapid cell rewarming, and has stability and reliability.

[0065] Obviously, the above embodiments of the present invention are only examples for clearly explaining the present invention, and are not intended to limit the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. The embodiments of the present invention cannot exhaust all implementation methods. All obvious changes or modifications derived from the technical solutions of the present invention are still within the scope of protection of the present invention. All documents mentioned in the present invention are cited as references in this application, just as if a document is cited as a reference alone.

Claims

1. A rewarming device for rewarming frozen cells, wherein the cells are frozen in cryopreservation tubes, characterized in that: It includes a supporting device, a conveying pipeline, a sleeve, a heating wire, and an intelligent temperature control device, wherein the supporting device fixedly supports the conveying pipeline; the conveying pipeline is arranged in a spiral annular shape along the longitudinal axis of the supporting device; The sleeve is wrapped around the outer wall of the conveying pipeline; The heating wire is provided with at least two sections, and the heating wire is provided between the sleeve and the outer tube wall of the conveying pipe, and surrounds the outer tube wall of the conveying pipe; The intelligent temperature control device is coupled to at least two sections of the heating wire to control the temperature of the at least two sections of the heating wire according to at least two preset temperature intervals; The cryotube is transported from the input port of the transport pipeline to the output port; The rewarming device further comprises a conveying device, the conveying device is connected to the input port of the conveying pipeline, and the conveying device conveys the cryopreservation tube from the input port to the output port; The conveying device includes a jet pump, a jet control valve and a jet pipe; wherein one end of the jet pipe is connected to the input port of the conveying pipeline, the other end of the jet pipe is connected to the jet pump, and the jet control valve is arranged on the jet pipe to control the jet of the jet pipe.

2. The rewarming device according to claim 1, characterized in that: The rewarming device also includes a special pipe joint, one end of which is connected to the jet pipe, and the other end is connected to the input port of the delivery pipeline; a piston switch is provided on the outer surface of the special pipe joint.

3. The rewarming device according to claim 2, characterized in that: The rewarming device further comprises a collecting device, and the collecting device is connected to the output port of the conveying pipeline.

4. The rewarming device according to claim 3, characterized in that: The collecting device is provided with an air release channel, and the air release channel releases air when the air injection pipe injects air.

5. The rewarming device according to claim 1, characterized in that: The conveying pipeline is arranged along the longitudinal axis of the supporting device in at least two levels of spiral annular bending from the lower part to the upper part or from the upper part to the lower part.

6. The rewarming device according to claim 1, characterized in that: The conveying pipeline is arranged in a three-level spiral ring bend from the bottom to the top or from the top to the bottom along the longitudinal axis of the supporting device, and the heating wire is arranged in three sections; the intelligent temperature control device is respectively coupled to the three sections of the heating wire to control the heating temperature of the three sections of the heating wire according to the preset three temperature ranges.

7. The rewarming device according to claim 1, characterized in that: At least one heat-insulating ring is arranged between adjacent heating wires, and the heat-insulating ring surrounds the outer wall of the conveying pipeline and the inner wall of the sleeve.

8. The rewarming device according to claim 1, characterized in that: At least two temperature sensors are arranged in the intelligent temperature control device, the number of the temperature sensors corresponds to the number of segments of the preset temperature interval, and the intelligent temperature control device is coupled to the heating wires respectively through the temperature sensors.

9. The rewarming device according to claim 8, characterized in that: The temperature sensor is a thermocouple, which passes through the sleeve to detect the temperature of the hollow inner cavity of the conveying pipe surrounded by the corresponding coupled heating wire.

10. The rewarming device according to claim 8, characterized in that: The jet intensity of the jet pipe is adjusted according to the heating rate of the hollow inner cavity of the conveying pipeline.

11. The rewarming device according to claim 1, characterized in that: The diameter of the hollow inner cavity of the delivery pipeline is larger than the outer diameter of the freezing tube.

12. The rewarming device according to claim 9, characterized in that: The inner tube wall of the delivery pipe is provided with rifling, which is protruded from the inner tube wall of the delivery pipe toward the inner cavity.

13. The rewarming device according to claim 1, characterized in that: The supporting device is a cylindrical or cylindrical base.

14. A control method for a rewarming device according to any one of claims 1 to 13, used for rewarming cells after freezing, characterized in that: The following steps are involved: The intelligent temperature control device is preset with at least two temperature intervals; wherein the temperature of the temperature interval is preset according to the following parameters: n-1、 t n It indicates the time taken by the cryopreservation tube to pass through at least two stages of transport pipelines, ... T n-1 , T n represents the temperature of the at least two-stage transport pipeline, ...T' n-1 , T' n represents the temperature of the cryopreservation tube leaving the at least two-stage transport pipeline, T'0 represents the initial temperature of the cryopreservation tube, α represents the convection heat transfer coefficient in the transport pipeline, C represents the specific heat capacity, m represents the mass of the cryopreservation tube, A represents the total surface area of ​​the cryopreservation tube, ...L n-1 , L n represents the length of the at least two-stage delivery pipeline, the moving speed of the cryopreservation tube in the delivery pipeline is v, n is a positive integer, t n With T' n Satisfies the following system of equations: ;as well as ; The intelligent temperature control device is based on the at least two preset temperature intervals T n-1 , T n Controlling the heating temperature of at least two sections of the heating wire; The cryopreservation tube passes through at least two temperature intervals T from the input port of the delivery pipeline. n-1 、T n is transported to the output port. When the cryopreservation tube passes through the temperature range T n-1 After that, the temperature becomes T' n-1 When the cryopreservation tube passes through the temperature interval T n After that, the temperature becomes T' n ; where T' n-1< T' n =37℃.

Citation Information

Patent Citations

  • Reheating device

    CN212077059U