CN114796658A - Blood low-temperature storage bag and rapid and uniform cooling and rewarming method thereof - Google Patents
Blood low-temperature storage bag and rapid and uniform cooling and rewarming method thereof Download PDFInfo
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- CN114796658A CN114796658A CN202210440393.2A CN202210440393A CN114796658A CN 114796658 A CN114796658 A CN 114796658A CN 202210440393 A CN202210440393 A CN 202210440393A CN 114796658 A CN114796658 A CN 114796658A
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- 210000004369 blood Anatomy 0.000 title claims abstract description 102
- 239000008280 blood Substances 0.000 title claims abstract description 102
- 238000003860 storage Methods 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000001816 cooling Methods 0.000 title claims description 17
- 238000010899 nucleation Methods 0.000 claims abstract description 43
- 230000006911 nucleation Effects 0.000 claims abstract description 43
- 239000002184 metal Substances 0.000 claims abstract description 39
- 230000008569 process Effects 0.000 claims abstract description 23
- 238000001514 detection method Methods 0.000 claims abstract description 10
- 230000002093 peripheral effect Effects 0.000 claims abstract description 9
- 239000007788 liquid Substances 0.000 claims abstract description 7
- 238000004321 preservation Methods 0.000 claims description 21
- 238000005138 cryopreservation Methods 0.000 claims description 15
- 239000013078 crystal Substances 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 238000007789 sealing Methods 0.000 claims description 3
- 238000004781 supercooling Methods 0.000 claims description 3
- 239000000853 adhesive Substances 0.000 claims 1
- 230000001070 adhesive effect Effects 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 abstract description 9
- 238000007710 freezing Methods 0.000 abstract description 8
- 230000008014 freezing Effects 0.000 abstract description 8
- 210000000601 blood cell Anatomy 0.000 abstract description 6
- 230000001954 sterilising effect Effects 0.000 abstract description 6
- 238000004659 sterilization and disinfection Methods 0.000 abstract description 6
- 230000009286 beneficial effect Effects 0.000 abstract description 4
- 230000002349 favourable effect Effects 0.000 abstract 1
- 238000010791 quenching Methods 0.000 abstract 1
- 230000000171 quenching effect Effects 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 8
- 239000002344 surface layer Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229920000297 Rayon Polymers 0.000 description 2
- 239000010836 blood and blood product Substances 0.000 description 2
- 229940125691 blood product Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229920000915 polyvinyl chloride Polymers 0.000 description 2
- 239000004800 polyvinyl chloride Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002577 cryoprotective agent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000003761 preservation solution Substances 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 238000004017 vitrification Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/02—Blood transfusion apparatus
- A61M1/0272—Apparatus for treatment of blood or blood constituents prior to or for conservation, e.g. freezing, drying or centrifuging
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- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Engineering & Computer Science (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Abstract
The invention discloses a blood low-temperature storage bag and a method for uniformly freezing and quickly heating by magnetic heat, wherein the blood low-temperature storage bag comprises a storage bag body, a sterilization metal film is arranged in the storage bag body, a plurality of through holes are formed in the sterilization metal film, and the peripheral edge of the sterilization metal film is fixed with the peripheral edge of the storage bag body; the bottom of the storage bag is provided with a plurality of nucleation sites which are oppositely arranged, and the top of the storage bag is provided with a blood inlet, a blood detection channel and a blood outlet; the design of the metal nucleation site is beneficial to quenching nucleation operation in the freezing process, and the heterogeneous nucleation in the bag body is easy to reduce the freezing damage of blood cells; the metal film can realize rapid and uniform rewarming inside the bag body in a mode of exciting and heating by an alternating magnetic field; the inner porous structure is favorable for the flow of the melted liquid after rewarming; the good thermal conductivity of the metal film and the design of the sandwich structure obviously improve the temperature uniformity of different areas inside the whole large-volume blood bag in the freezing and rewarming processes.
Description
Technical Field
The invention relates to the field of medical instruments, in particular to a blood low-temperature storage bag and a rapid and uniform cooling and rewarming method thereof.
Background
The cryopreservation of blood can solve the fundamental problem of uneven distribution of blood resources in space and time at the present stage. In the aspect of storing blood at deep low temperature, the low-temperature protection solution and corresponding blood products (blood plasma, blood cells and the like) are mixed with each other and then are gradually cooled to-80 ℃ or-196 ℃ for long-term storage. At low temperatures, the quality of the blood product generally does not change significantly. The key to determining the quality of the product is the damage of the freezing process and the rewarming process. The traditional freezing process can face ice crystal damage, protective agent permeation damage and the like, and the rewarming process can be generated under the conditions of recrystallization and the like. Many experiments verify that the blood cells after being subjected to nucleation and storage have higher survival rate and better morphological structure, and if the operation of nucleation can be introduced in the storage process, the blood cells can be better stored by matching the cooling rate of the blood cells. The conventional blood low-temperature preservation consumable is generally made of a PVC (polyvinyl chloride) blood bag, the thermal conductivity of the blood bag is poor, nucleation is difficult to occur at a proper temperature (-5 to-10 ℃), and the large-capacity preservation volume has uneven temperature to a certain extent in the cooling process, so that a temperature field inside the whole volume has large difference, and the preservation of cells inside the blood is not facilitated.
Most of the rewarming devices available from Thawstar et al are rewarmed with external heating by raising the temperature of the external surface, but the external temperature rise must be limited to a reasonable temperature range, typically below 42 ℃, above which cell viability is severely impaired. The rewarming rate can be slightly increased to a certain extent by increasing the heating temperature of the water bath from 37 ℃ to 42 ℃, but the increasing degree is very small, so that the current situation that the rewarming rate is too slow in the external heating process cannot be fundamentally changed. On the other hand, the blood is generally preserved by 1-2 units (100-400 mL), and the volume is large, so that the external heating rewarming mode is difficult to conduct to the inside in time, and a certain time is needed for heat to diffuse on a large scale. Due to the limitation of the large volume, a larger temperature difference is formed in the process of rewarming, and the synchronous rewarming of the central area and the edge area of the structure cannot be realized. And because the rewarming rate of the central area is slower, the condition of ice crystal regrowth can occur in the rewarming process of the central area sample, further damage is caused to important cells in blood, and the quality of the blood after preservation is seriously reduced.
Disclosure of Invention
The invention aims to solve the problems and provides a blood low-temperature storage bag which comprises a storage bag body, wherein a heat conducting piece is arranged in the storage bag body, a plurality of nucleation sites are arranged at the bottom of the storage bag body by the heat conducting piece, and the nucleation sites and the heat conducting piece are integrally arranged; the top of the preservation bag is provided with a blood inlet, a blood detection channel and a blood outlet, and the blood inlet, the blood detection channel and the blood outlet are arranged opposite to the nuclear placement sites.
Further, the heat conducting piece is a metal film, the metal film is provided with a plurality of through holes, and the peripheral edge of the metal film is hermetically bonded with the peripheral edge of the storage bag through viscose and heat sealing technology.
Further, a plurality of the nucleation sites are arranged at equal intervals at the bottom of the preservation bag.
Furthermore, the thickness of the metal film is 0.2-1 mm.
A rapid and uniform cooling method using the blood low-temperature preservation bag comprises the following steps:
step 2: taking out the special storage bag, rapidly immersing the nucleation site in liquid nitrogen, and performing local supercooling to form a local nucleation site;
and step 3: placing the blood low-temperature preservation bag with the local nucleation points back into the program cooling instrument, keeping the initial nucleation temperature and balancing for 3-5 min;
and 4, step 4: the crystal nucleus growth process starts to occur in a local area inside the metal film, crystal nuclei are formed at multiple positions in the metal film, and then the crystal nuclei are uniformly distributed in the whole blood bag;
and 5: finally, the whole blood low-temperature preservation bag is cooled to-80 ℃ or-196 ℃ and stored for a long time.
Further, a rapid and uniform rewarming method using the blood cryopreservation bag as described above is characterized in that the inside and the outside of the blood cryopreservation bag are heated together by exciting the metal film and the convection water bath with an alternating magnetic field, respectively, to achieve rapid rewarming.
Compared with the prior art, the invention has the following beneficial effects:
1. through the good thermal conductivity of the metal film and the design of local nucleation sites, the heterogeneous nucleation probability can be improved, the successful realization of the nucleation operation is facilitated, more nucleation sites exist at the edge of the internal porous structure, more uniform nucleation in different areas is facilitated, and the uniformity of the internal crystallization process of the whole large-volume blood bag is greatly improved;
2. the metal film can realize large-volume rapid and uniform rewarming at a high speed, the internal porous structure of the metal film can facilitate flowing heat exchange of melted liquid in the rewarming process, and the large metal film structure can be used as a good heat conduction structure to ensure that the temperature field of the whole freezing system is heated more uniformly and rapidly.
Drawings
FIG. 1 is a bottom view of a blood cryopreservation bag according to the present invention;
FIG. 2 is a view showing the structure of the intermediate layer of the blood cryopreservation bag of the present invention;
FIG. 3 is a view showing the structure of the top layer of the blood cryopreservation bag of the present invention;
fig. 4 is a view showing the entire structure of the blood cryopreservation bag of the present invention.
In the figure, 1, the bottom layer; 2. an intermediate layer; 3. a surface layer; 4. a nuclear locus is placed; 5. a blood inlet; 6. a blood detection channel; 7. a bleeding outlet.
Detailed Description
While a blood cryopreservation bag and a method of rapidly cooling and warming the same according to the present invention will be described in more detail below with reference to schematic drawings, in which preferred embodiments of the present invention are shown, it will be appreciated that those skilled in the art can modify the invention described herein while still achieving the advantageous effects of the invention. Accordingly, the following description is to be construed as broadly as possible to those skilled in the art and not as limiting the invention.
In the description of the present invention, it should be noted that, for the terms of orientation, such as "central", "lateral", "longitudinal", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", etc., it indicates that the orientation and positional relationship shown in the drawings are based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, but does not indicate or imply that the device or element referred to must have a specific orientation, be constructed in a specific orientation, and be operated without limiting the specific scope of protection of the present invention.
As shown in fig. 1 to 4, a blood low-temperature storage bag comprises a storage bag body, a heat conducting member is arranged in the storage bag, the heat conducting member is a sterilized metal film, the thickness of the heat conducting member is 0.2 to 2mm, a blood inlet 5, a blood detection channel 6 and a blood outlet 7 are arranged at the edge of the top of the storage bag, a plurality of nucleation sites 4 are arranged at the bottom of the storage bag, the blood detection channel 6 stores a small amount of blood, the blood detection channel can extract a small amount of blood for detection before use, and the blood inlet 5 or the blood outlet 7 does not need to be opened, so that pollution is reduced; the plurality of nucleation sites 4 and the whole metal film structure are beneficial to the whole nucleation operation of the blood low-temperature storage bag, and the uniform cooling of the blood in the bag body is realized.
The storage bag adopts a sandwich layer design and is provided with a surface layer 3, a middle layer 2 and a bottom layer 1. The sterilized metal film is the middle layer 2. The peripheral edges of the surface layer 3, the middle layer 2 and the bottom layer 1 are sealed and bonded by viscose glue and heat sealing technology. Two solution chambers for storing blood are formed between the surface layer 3 and the middle layer 2 and between the bottom layer 1 and the middle layer 2, the whole sterilized metal film is covered with a plurality of through holes, and the blood in the two solution chambers can flow between the two solution chambers through the plurality of through holes.
As shown in FIGS. 1 and 4, in the present invention, the blood inlet 5, the blood detecting channel 6 and the blood outlet 7 are provided at the upper edge of the bottom sheet 1, and the blood inlet 5, the blood detecting channel 6 and the blood outlet 7 are provided at the same side.
Referring to fig. 2 and 4, it is worth mentioning that a plurality of nucleation sites 4 are integrally disposed on the sterilization metal film, and the plurality of nucleation sites 4 are disposed at the bottom of the sterilization metal film, and the peripheral edge of the sterilization metal film is fixed to the peripheral edges of the surface layer 3 and the bottom layer 1, so that the plurality of nucleation sites 4 are disposed at the bottom of the blood low-temperature storage bag, and the present invention is provided with 3 nucleation sites 4, and 3 nucleation sites 4 are disposed at the bottom of the storage bag at equal intervals.
The invention relates to a method for realizing rapid and uniform cooling through a nucleation site, which uses a blood low-temperature storage bag.
In the process of low-temperature preservation of blood, the whole blood bag needs to be gradually cooled to-80 ℃ or-196 ℃, the nucleation operation is carried out at minus 5 ℃ to-10 ℃, the external solution is pre-crystallized in advance, the concentration of the intracellular cryoprotectant is further improved, and the vitrification preservation of blood cells in the whole blood low-temperature preservation bag after cooling can be easily realized in the process of cooling. The specific mode of the process of pre-nucleating is that the whole blood low-temperature preservation bag is slowly cooled to-5 to-10 ℃ by a program cooling instrument, the blood low-temperature preservation bag is taken out, a plurality of nucleation sites 4 at the bottom of the bag body of the blood low-temperature preservation bag are quickly immersed in liquid nitrogen for local supercooling to form local nucleation sites, the program cooling instrument is continuously put back to be kept in the initial nucleation temperature balance for 3-5 min, and the balance process has the effect that the ice crystal form is more stable after the nucleation operation, so that the survival of cells in the subsequent further cooling process is facilitated. Next, the program cooling instrument continues to perform a cooling phase, in which a crystal nucleus growth process begins to occur in a local area of the inner metal film portion, and the crystal nucleus growth speed increases with the increase of the cooling rate. More crystal nuclei can be formed at the contact interface of the metal film and the solution and are uniformly distributed in the whole blood low-temperature preservation solution, so that the solution in the whole large-volume blood low-temperature preservation bag realizes more uniform nucleation, a great promotion effect is generated on the improvement of the temperature and the concentration uniformity inside the whole large-volume blood low-temperature preservation bag, and the whole large-volume blood low-temperature preservation bag can be stored for a long time after being cooled to-80 ℃ or-196 ℃.
For the method for rapidly and uniformly rewarming the blood low-temperature storage bag stored for a long time, the alternating magnetic field is used for exciting the metal film, and the most common method for heating the blood low-temperature storage bag in clinic at present is as follows: the blood low-temperature preservation bag is put into a water bath box for heating. When the water bath box is used for heating, the blood low-temperature storage bag with lower temperature is placed in a constant-temperature water bath with the temperature of about 37 ℃, at the moment, the problem of non-uniformity inside and outside in the rewarming process of different positions of the blood low-temperature storage bag exists, the area which is firstly contacted with the water bath outside melts firstly, so that the phenomenon of ice crystal regrowth appears when the blood rewarming of the central area is not in time, and the blood quality after rewarming is reduced. The blood low-temperature storage bag can utilize the alternating magnetic field of the excitation coil to excite the internal metal film to quickly generate heat, can realize large-volume quick and uniform rewarming with a larger speed by combining an external water bath rewarming mode, has a porous structure of the internal metal film which is beneficial to flowing heat exchange of melted liquid in the rewarming process, and has a large-sheet metal film structure which is also a good heat conduction structure, so that the temperature field of the whole freezing system can be more uniformly and quickly heated, and the blood quality is improved.
The above description is only a preferred embodiment of the present invention, and does not limit the present invention in any way. It will be understood by those skilled in the art that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (6)
1. A blood low-temperature storage bag is characterized by comprising a storage bag body, wherein a heat conducting piece is arranged inside the storage bag body, a plurality of nucleation sites are arranged at the bottom of the storage bag body by the heat conducting piece, and the nucleation sites and the heat conducting piece are integrally arranged; the top of the preservation bag is provided with a blood inlet, a blood detection channel and a blood outlet, and the blood inlet, the blood detection channel and the blood outlet are arranged opposite to the nuclear placement sites.
2. The blood cryopreservation bag of claim 1, wherein the heat conducting member is a metal film provided with a plurality of through holes, and the peripheral edge of the metal film is hermetically bonded to the peripheral edge of the bag body by an adhesive and a heat sealing technique.
3. The blood cryopreservation bag of claim 2, wherein two solution chambers are formed in the bag body through the metal film, the two solution chambers are respectively arranged on two sides of the metal film, and the metal film and the two solution chambers are arranged in a sandwich structure.
4. The blood cryopreservation bag of claim 3, wherein the metal film has a thickness of 0.2-2 mm.
5. A rapid and uniform cooling method using the blood cryopreservation bag according to any one of claims 1 to 4, comprising the steps of:
step 1, placing a blood low-temperature storage bag in a program cooling instrument, cooling to a target temperature range of-5 ℃ to-10 ℃ required by nucleation, wherein the blood low-temperature storage bag obtains a supercooled state required by the nucleation of a solution system;
step 2: taking out the blood low-temperature storage bag, quickly immersing the nucleation site in liquid nitrogen, and performing local supercooling to form a local nucleation site;
and step 3: placing the blood low-temperature preservation bag with the local nucleation points back into the program cooling instrument, keeping the initial nucleation temperature and balancing for 3-5 min;
and 4, step 4: after the balance isothermal stage is finished, continuing a cooling program, and starting a crystal nucleus growth process in a local area inside the metal film; crystal nuclei are formed at multiple positions in the metal film, so that the uniform ice crystal growth process is realized in the whole blood bag;
and 5: finally, the whole blood low-temperature storage bag is cooled to-80 ℃ or placed in liquid nitrogen to reach-196 ℃, and is stored for a long time.
6. A rapid and uniform rewarming method using the blood cryopreservation bag as claimed in any one of claims 1 to 4, wherein the interior and exterior of the blood cryopreservation bag are heated together by exciting the metal film and the convection water bath in the blood cryopreservation bag through the alternating magnetic field, thereby achieving rapid rewarming of the frozen state in the whole bag body.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210440393.2A CN114796658A (en) | 2022-04-25 | 2022-04-25 | Blood low-temperature storage bag and rapid and uniform cooling and rewarming method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210440393.2A CN114796658A (en) | 2022-04-25 | 2022-04-25 | Blood low-temperature storage bag and rapid and uniform cooling and rewarming method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114796658A true CN114796658A (en) | 2022-07-29 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210440393.2A Pending CN114796658A (en) | 2022-04-25 | 2022-04-25 | Blood low-temperature storage bag and rapid and uniform cooling and rewarming method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114796658A (en) |
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2022
- 2022-04-25 CN CN202210440393.2A patent/CN114796658A/en active Pending
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