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WO2018169284A1 - Bioreactor for in vitro proliferation of cells - Google Patents

Bioreactor for in vitro proliferation of cells Download PDF

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Publication number
WO2018169284A1
WO2018169284A1 PCT/KR2018/002943 KR2018002943W WO2018169284A1 WO 2018169284 A1 WO2018169284 A1 WO 2018169284A1 KR 2018002943 W KR2018002943 W KR 2018002943W WO 2018169284 A1 WO2018169284 A1 WO 2018169284A1
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WO
WIPO (PCT)
Prior art keywords
cells
bioreactor
pressure
unit
vitro proliferation
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Ceased
Application number
PCT/KR2018/002943
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French (fr)
Korean (ko)
Inventor
신정욱
강윤경
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Industry Academic Cooperation Foundation of Inje University
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Industry Academic Cooperation Foundation of Inje University
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Publication of WO2018169284A1 publication Critical patent/WO2018169284A1/en
Anticipated expiration legal-status Critical
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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
    • C12M21/00—Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
    • 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
    • C12M1/00—Apparatus for enzymology or microbiology
    • 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
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/14—Bags
    • 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
    • C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/16—Vibrating; Shaking; Tilting
    • 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
    • C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus
    • 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
    • C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus
    • C12M3/06—Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
    • 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
    • C12M41/40—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure

Definitions

  • the present invention relates to a bioreactor for in vitro proliferation of cells, and more particularly, to a bioreactor capable of in vitro proliferation of hematopoietic stem cells or cells having non-adherent properties obtained from a human body, and a storage unit for storing cells.
  • the present invention relates to a bioreactor for in vitro proliferation of cells that can easily proliferate hematopoietic stem cells or cells having non-adherent properties in vitro by maintaining an environment similar to the proliferation environment by applying pressure to the inside and stirring the same.
  • cord blood refers to the blood collected from the umbilical cord, which is connected to the mother's placenta and supplies nutrients and oxygen to the fetus.
  • Umbilical cord blood contains a large amount of hemopoietic stem cells that produce blood cells such as red blood cells, white blood cells, and platelets, which play an important role in maintaining the body's immune system and life. Therefore, as well as various refractory blood diseases, it is used as a valuable life resource to treat solid cancers such as breast cancer and various metabolic diseases, hereditary diseases and the like. It is commonly known as bone marrow transplant, but it is actually bone marrow hematopoietic stem cell transplant.
  • Cord blood hematopoietic stem cells may also be used in the same way, but have several advantages over bone marrow. Since hematopoietic stem cells in umbilical cord blood are immature than hematopoietic stem cells in bone marrow, cord blood hematopoietic stem cells should be transplanted when only four genetic factors are matched. This is a great advantage, since it is possible and there are fewer immunological side effects after transplantation. Umbilical cord blood is also easier to collect than bone marrow.
  • cord blood hematopoietic stem cells have less complications in transplants where the HLA genes do not match perfectly.
  • gene therapy such as its usefulness varies.
  • Hematopoietic stem cells are absolutely necessary for human survival and are usually present in the bone marrow or placenta and umbilical cord of babies.
  • cell therapy research using stem cells present in cord blood has been actively conducted, and thus the medical and social value of cord blood Is expected to spread dramatically.
  • hematopoietic stem cells are difficult to grow in vitro and difficult to maintain performance in vitro.
  • a portion of the blood bag is placed in a blood bag (bag) and then transplanted after storage for a certain period (about 72 hours).
  • Hematopoietic stem cells are unlikely to grow in vitro and difficult to maintain performance in vitro, unlike normal cells.
  • hematopoietic cells are not cells that attach and grow, but are also floating in the body and may be suspended at some positions. Therefore, in general, it is difficult to incubate by attaching in the culture plate, there was a problem that the performance is sharply reduced even if diarrhea culture.
  • the present invention to solve the above problems
  • a base portion coupled to one side of the stirring portion
  • a holder part installed vertically from one surface of the base part
  • a storage unit storing cells to be proliferated and mounted on one surface of the base unit; It provides a bioreactor for cell in vitro proliferation comprising; and a control unit for adjusting the pressure and release pressure into the reservoir.
  • the base portion of the plate-shaped plate may include a protrusion formed to project a plurality on one surface of the plate.
  • the holder portion is a pair of supports extending vertically spaced apart from each other from the plate; And a fastening portion connected between the pair of supports, wherein the height of the fastening portion is adjustable along the support.
  • the storage unit may be made of any one of a sealed pouch, a pack, and a blood bag which are generally used for blood storage.
  • the storage unit is characterized in that it comprises one tube tube generally connected to the outside.
  • control unit is connected to the storage and the pressure supply for applying pressure to the inside of the storage; And a pressure release unit connected to the pressure supply unit and releasing the pressure pressurized by the storage unit.
  • the pressure supply unit, the first tube tube one side is inserted into the storage;
  • a compressor connected to the other side of the first tube tube to apply pressure; It may include a filter unit located between the storage unit and the compressor and a solenoid valve positioned between the storage unit and the filter unit.
  • the pressure of the solenoid valve may be characterized in that 18Kpa to 22Kpa.
  • control unit may further include a control unit for automatically controlling the solenoid valve and the clamp.
  • control unit may be characterized in that the control to close the clamp when pressed to the storage unit.
  • control unit may be characterized in that the solenoid valve is closed and the clamp is opened when back pressure.
  • the storage unit for storing the hematopoietic stem cells collected from the human body by adding pressure to the storage unit for storing the hematopoietic stem cells collected from the human body and stirring the storage unit, it is possible to maintain in vitro proliferation and performance of the hematopoietic stem cells.
  • the storage portion is built up vertically or at a desired angle, so that the flow of gas and hematopoietic stem cells introduced into the storage portion Stirring can be done smoothly.
  • the reservoir by placing the reservoir on one surface of the base including a plurality of protrusions protruding on one surface of the plate, to prevent the reservoir from being separated from the base and at the same time the contact of the reservoir during stirring It gives the effect of fluctuating irregularly.
  • the solenoid valve is disposed between the first tube tube and the compressor to apply a constant hydrostatic pressure desired by the user to the reservoir, thereby maintaining the state of the hematopoietic stem cells in the reservoir for a predetermined period of time. You can.
  • FIG. 1 is a schematic perspective view of a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention.
  • Figure 2 is a side view showing a shape in which the storage unit of the present invention is installed obliquely.
  • FIG. 3 is a conceptual diagram showing the configuration of a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention.
  • 4 and 5 are conceptual views showing that the pressure is released and released to the reservoir.
  • Figure 6 is a schematic perspective view of a cell in vitro proliferation bioreactor according to another embodiment of the present invention.
  • FIG. 1 is a schematic perspective view of a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention
  • Figure 2 is a side view showing the shape inclined to install the storage unit of the present invention
  • Figure 3 according to an embodiment of the present invention 4 is a conceptual diagram showing the configuration of a bioreactor for in vitro proliferation of cells
  • FIG. 4 and FIG. 5 are conceptual views showing that pressure is released and released from the storage unit
  • FIG. It is a perspective view which shows the holder part with an addition.
  • the bioreactor for in vitro proliferation of cells includes a stirring part 100, a base part 200, a holder part 300, a storage part 400 and It includes an adjusting unit 500.
  • the present invention is supported by the stirring portion 100, the base portion 200 coupled to the upper portion of the stirring portion, the holder portion 300 is installed vertically from one surface of the base portion, the base is supported by the holder, It is mounted on one side of the unit, and includes a storage unit 400 for storing cells to be proliferated, such as hematopoietic stem cells collected from the human body and a control unit 500 connected to the storage unit for applying and releasing pressure into the storage unit.
  • a storage unit 400 for storing cells to be proliferated, such as hematopoietic stem cells collected from the human body
  • a control unit 500 connected to the storage unit for applying and releasing pressure into the storage unit.
  • FIGS. 1 to 2 a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention will be described in more detail with reference to FIGS. 1 to 2.
  • the stirring unit 100 is to create a uniform mixed state of two or more substances having different physical or chemical properties by using external mechanical energy, mixing while applying pressure to the hematopoietic stem cells stored in the storage unit 400 to be described later Device.
  • the stirring unit 100 may include a housing and may include a motor and a gear inside the housing (not shown).
  • the housing may be a driving unit moving up, down, left, and right by the above-described motor and gear. It may be configured (not shown).
  • the cells to proliferate in the bioreactor for in vitro proliferation of cells is not limited to 'hematopoietic stem cells', including hematopoietic stem cells or hematopoietic stem cells extracted from a patient or a donor and non-adherent It is possible to proliferate non-adherent cells.
  • the base unit 200 may be coupled to one side of the stirring unit 100 to move in response to the movement of the stirring unit 100.
  • the base part 200 is located above the stirring part 100, as shown in FIG. 1, and is coupled to the driving part formed on the upper part of the stirring part 100. That is, the base unit 200 may be moved in response to the movement of the driving unit moving up, down, left, and right as the base unit 200 is connected to the motor and gears and coupled to the driving unit.
  • the base 200 includes a plate 210 and the protrusion 220.
  • the plate 210 is formed in a flat plate shape and may have a constant thickness.
  • Protruding portion 220 may be formed to protrude a plurality on one surface of the plate (210).
  • the protrusions 210 may include a plurality of protrusions protruding in a hemispherical shape from an upper surface of the plate 210 at regular intervals.
  • the protrusion 210 prevents the storage 400 from slipping from the base part by friction of the protrusion even when the storage part 400 is mounted on the plate 210 and the stirring part 100 is stirred.
  • the protrusion 220 may apply an appropriate pressure to the hematopoietic stem cells stored in the storage unit 400 during the stirring movement of the stirring unit 100.
  • an uneven portion having a plurality of grooves formed at regular intervals may be formed on the upper surface of the base portion 200 (not shown).
  • Holder portion 300 is installed vertically from one surface of the base portion 200 is connected to the upper portion of the storage portion 400 to support the storage portion. That is, as shown in FIG. 1, the holder part 300 serves to vertically mount the storage part 400 on the upper surface of the base part 200, and for this purpose, the holder part 300 has a pair of supports. 310 and the fastening part 320.
  • the pair of supports 310 are installed to be vertically spaced apart from each other from the upper surface of the plate 210. More specifically, the pair of supports 310 has a sliding rail formed therein so that the fastening part 320 is inserted into and coupled to the rail, so that vertical movement can be performed smoothly in the vertical direction along the rail.
  • the fastening part 320 is connected between the pair of supports 310 to support the storage part 400. More specifically, the fastening part 320 is a rod-shaped extending in the longitudinal direction, and is made of a tong structure that is separated from side to side so that the upper portion of the storage unit 400 is fitted, it is connected to both sides of the pair of supports 310
  • the storage unit 400 serves to stand vertically.
  • the pair of supports 310 moves the fastening part 320 in the up and down direction according to the amount of proliferating cells stored in the storage part 400, so that the angle and the height of the storage part mounted on the base part can be adjusted. As shown in FIG. 2, the pair of supports 310 adjusts the height of the fastening part 320 so that the storage part 400 coupled with the fastening part 320 has a desired angle on one surface of the base part 200. It is possible to mount inclined by.
  • the storage unit 400 stores cells such as hematopoietic stem cells to be proliferated and is supported by a support and mounted on one surface of the base unit 200.
  • the storage unit 400 may be a blood bag generally used to contain blood, and may be made of any one of a sealed pouch, a pack, and a bag.
  • FIG. 3 is a conceptual diagram showing the configuration of a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention.
  • the adjusting unit 500 is connected to the storage 400 to control the application or release of pressure into the storage 400.
  • the adjusting unit 500 includes a pressure supply unit 510 and a pressure release unit 520.
  • the pressure supply part 510 is connected to the storage part 400 and applies pressure to the inside of the storage part 400.
  • the pressure supply unit 510 includes a first tube tube 511, a compressor 512, a filter unit 513, and a solenoid valve unit 514.
  • the first tube tube 511 is formed in a hollow shape, one side is inserted into the storage unit 400, and the other side is connected to the compressor 512 to apply pressure from the compressor to the storage unit 400. Play a role.
  • the compressor 512 is connected to the other side of the first tube tube to apply a pressure may be made of an air compressor structure.
  • the compressor 512 compresses ambient air to supply compressed air to the inside of the storage unit 400 through the first tube tube 511.
  • the filter unit 513 is disposed between the storage unit 400 and the compressor 512 to purify contaminants that may flow into the storage unit 400. More specifically, the filter unit 513 may be formed of a rectangular main body and a filter inserted into the main body (not shown).
  • the filter may include a pre-filter for filtering large dust, a deodorizing filter for removing odors in the air, and a candle. It is also possible to comprise a hepa filter for removing fine dust.
  • the main body is formed in a structure that is separated there is an advantage that the exchange of the filter is easy. As such, the filter unit 513 cleans compressed air generated from the compressor 512 and supplies clean air to the storage unit 400 to prevent contamination of hematopoietic stem cells.
  • the solenoid valve 514 is located between the storage unit 400 and the filter unit 513 serves to control the flow of pressure.
  • the pressure of the solenoid valve is preferably 18 Kpa (kilopascal) to 22 Kpa (kilopascal).
  • the 18 Kpa to 22 Kpa pressure is similar to the pressure blood receives in the bone marrow. Therefore, the solenoid valve 514 may maintain a constant pressure of 18Kpa to 22Kpa to maintain in vitro growth and performance of hematopoietic stem cells in the storage unit 400.
  • the pressure release unit 520 serves to release the pressure pressurized into the storage unit 400.
  • the pressure release part 520 includes a second tube tube 521 and a clamp 522.
  • the second tube tube 521 is connected to the first tube tube, the tube is separated from the first tube tube and may be formed in a hollow shape.
  • the second tube tube 521 is a tube separated from one side of the outer circumferential surface of the first tube tube connected to the storage unit 400, and is located between the storage unit 400 and the solenoid valve 514.
  • the clamp 522 is connected to the other side of the second tube tube 521 to apply or release pressure to the reservoir as the clamp is opened and closed.
  • the adjusting unit 500 including the pressure supply unit 510 and the pressure release unit 520 may further include a control unit 530.
  • the controller 530 may control the solenoid valve 514 and the clamp 522 to control supply of a constant pressure to the storage unit 400 and release of the supplied pressure.
  • the controller 530 controls to close the clamp 522 when the pressure is applied to the storage.
  • the controller 530 controls the solenoid valve 514 to close and the clamp 522 to open slowly when the pressure of the storage unit is back pressured.
  • FIG. 6 shows a bioreactor for in vitro proliferation of cells according to another embodiment of the present invention.
  • the bioreactor for in vitro proliferation of cells shown in FIG. 6 includes a holder part including an accommodating part and an inclined part in a base part.
  • the base part 200 ′ includes a plate 210 ′ having a flat plate shape and a partition wall 220 ′ extending vertically from a plate edge at a predetermined height.
  • the holder part 300 ' is mounted on the upper surface of the base part 200' and includes an accommodating part 310 'having a space for accommodating a storage part therein and an inclined part 320 inclined in one direction on a lower surface of the accommodating part. Contains').
  • the accommodating part 310 ′ is preferably opened at one side of the upper surface to accommodate the storage part 400.
  • the holder part 300 ' can be stably mounted in a state in which the storage part 400 is inclined to the base part 200', it is possible to maximize the stirring effect of the hematopoietic stem cells.

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Abstract

The present invention relates to a bioreactor for in vitro proliferation of cells, and the bioreactor for in vitro proliferation of cells comprises: a stirring part and a base part coupled to one side of the stirring part; a holder formed to be perpendicular to one surface of the base part; a storage part, which stores cells to be proliferated, including hematopoietic cells collected from a human body, and is mounted on one surface of the base part; and a pressure part and a control part for applying pressure to or releasing pressure from the interior of the storage part.

Description

세포 체외 증식을 위한 바이오리액터Bioreactor for In Vitro Proliferation of Cells

본 발명은 세포 체외 증식을 위한 바이오리액터에 관한 것으로, 보다 상세하게는 인체에서 채취한 조혈모세포 혹은 non-adherent 성질을 가진 세포를 체외 증식시킬 수 있는 바이오 리액터에 관한 것으로서, 세포를 저장하는 저장부 내부에 압력을 가함과 동시에 교반시킴으로써 체내 증식 환경과 유사한 환경을 유지하여 조혈모세포 혹은 non-adherent 성질을 가진 세포를 체외에서 용이하게 증식시킬 수 있는 세포 체외 증식을 위한 바이오리액터에 관한 것이다.The present invention relates to a bioreactor for in vitro proliferation of cells, and more particularly, to a bioreactor capable of in vitro proliferation of hematopoietic stem cells or cells having non-adherent properties obtained from a human body, and a storage unit for storing cells. The present invention relates to a bioreactor for in vitro proliferation of cells that can easily proliferate hematopoietic stem cells or cells having non-adherent properties in vitro by maintaining an environment similar to the proliferation environment by applying pressure to the inside and stirring the same.

일반적으로 제대혈(탯줄혈액, Cord Blood)은 모체의 태반과 연결되어 발육에 도움이 되는 영양분과 산소를 태아에게 공급하는 탯줄에서 채취한 혈액을 말한다. 제대혈에는 인체 내의 면역 체계와 생명을 유지하는데 중요한 역할을 하는 적혈구, 백혈구, 혈소판 등의 혈액세포를 생성하는 조혈모세포(造血母細胞, Hemopoietic Stem Cell)가 다량 함유되어 있어, 골수이식을 보완 혹은 대체하여 각종 난치성 혈액질환은 물론, 유방암 등과 같은 고형암 및 각종 대사성 질환, 유전성 질환 등을 치료할 수 있는 소중한 생명의 자원으로 활용되고 있다. 흔히 골수이식이라고 알려져 있는데 실은 골수 조혈모세포이식이다. In general, cord blood (cord blood) refers to the blood collected from the umbilical cord, which is connected to the mother's placenta and supplies nutrients and oxygen to the fetus. Umbilical cord blood contains a large amount of hemopoietic stem cells that produce blood cells such as red blood cells, white blood cells, and platelets, which play an important role in maintaining the body's immune system and life. Therefore, as well as various refractory blood diseases, it is used as a valuable life resource to treat solid cancers such as breast cancer and various metabolic diseases, hereditary diseases and the like. It is commonly known as bone marrow transplant, but it is actually bone marrow hematopoietic stem cell transplant.

제대혈의 조혈모세포 또한 똑같이 사용될 수 있으며, 오히려 골수에 비해 여러 가지 장점이 있다. 제대혈에 들어있는 조혈모세포는 골수에 들어있는 조혈모세포보다 미성숙하기 때문에, HLA(human leukocyte antigen) 유전자 6개가 다 일치해야 이식이 가능한 골수 조혈모세포에 비해 제대혈 조혈모세포는 4개의 유전인자만 맞으면 실제 이식이 가능하고, 이식수술 후 면역학적인 부작용이 훨씬 적다는 큰 장점이 있다. 또한 제대혈은 골수에 비해 쉽게 채취할 수 있다.Cord blood hematopoietic stem cells may also be used in the same way, but have several advantages over bone marrow. Since hematopoietic stem cells in umbilical cord blood are immature than hematopoietic stem cells in bone marrow, cord blood hematopoietic stem cells should be transplanted when only four genetic factors are matched. This is a great advantage, since it is possible and there are fewer immunological side effects after transplantation. Umbilical cord blood is also easier to collect than bone marrow.

이렇듯 제대혈 조혈모세포는 HLA 유전자가 완벽하게 일치하지 않는 이식에서도 합병증이 적고, 골수 속 조혈모세포에 비해 그 채취방법이나 조혈기능, 증폭능력이 뛰어나 골수를 대체할 자원으로 각광받고 있으며, 백혈병과 각종 암의 치료뿐 만 아니라 유전자요법 등 그 유용성이 다양하다.As such, cord blood hematopoietic stem cells have less complications in transplants where the HLA genes do not match perfectly. In addition to the treatment of gene therapy, such as its usefulness varies.

조혈모세포는 인간의 생존유지에 절대적으로 필요한 것이며 보통 골수나 아기의 태반과 탯줄에 존재한다. 또한 미래의학의 핵심축으로 부상하고 있는 재생의학(Regenerative Medicine) 분야에서도 제대혈내에 존재하는 줄기세포(Mesenchymal Stem Cell)를 활용한 세포치료(Cell Therapy) 연구가 활발히 이루어지고 있어 제대혈의 의학적, 사회적 가치는 비약적으로 확산될 것으로 전망된다.Hematopoietic stem cells are absolutely necessary for human survival and are usually present in the bone marrow or placenta and umbilical cord of babies. In addition, in the field of regenerative medicine, which is emerging as a core axis of future medicine, cell therapy research using stem cells present in cord blood has been actively conducted, and thus the medical and social value of cord blood Is expected to spread dramatically.

하지만, 조혈모세포는 일반 세포와는 달리 체외증식이 어렵고 체외에서 성능을 유지하기 어렵다. 즉, 현재 임상적으로 조혈모세포를 포함하는 혈액을 채취하게 되면 일정부분 걸러낸 후 혈액백(bag) 에 담아 단순히 이식전 일정기간(약 72시간 이내) 보관 후 이식한다. 조혈모세포는 일반 세포와 달리 체외증식이 어렵고 체외에서 성능을 유지하기 어렵기 때문이다. However, unlike normal cells, hematopoietic stem cells are difficult to grow in vitro and difficult to maintain performance in vitro. In other words, at present, when clinically collected blood containing hematopoietic stem cells is filtered, a portion of the blood bag is placed in a blood bag (bag) and then transplanted after storage for a certain period (about 72 hours). Hematopoietic stem cells are unlikely to grow in vitro and difficult to maintain performance in vitro, unlike normal cells.

이를 위해 종래 체외에서 다양한 chemical factors를 사용하였다. 또한, 조혈세포는 일반적인 세포와는 달리 부착하여 성장하는 세포가 아니고, 몸속에서 떠돌아다니기도 하고, 일부 어느 위치에 매달려 있기도 하다. 따라서, 일반적으로 culture plate에서 부착하여 배양하기 어렵고, 설사 배양하여도 그 성능이 급격히 저하되는 문제점이 있었다.To this end, various chemical factors have been used in vitro. Unlike hematopoietic cells, hematopoietic cells are not cells that attach and grow, but are also floating in the body and may be suspended at some positions. Therefore, in general, it is difficult to incubate by attaching in the culture plate, there was a problem that the performance is sharply reduced even if diarrhea culture.

본 발명은 상기와 같은 종래기술의 문제점을 해결하기 위하여 인체에서 채취한 조혈모세포를 저장하는 저장부 내부에 압력을 가함과 동시에 교반시킴으로써, 조혈모세포의 체외 증식 및 성능을 유지시키는 새로운 구조의 세포 체외 증식을 위한 바이오리액터를 제공하고자 한다.In order to solve the problems of the prior art as described above, by applying pressure to the inside of the storage unit for storing the hematopoietic stem cells collected from the human body and stirring at the same time, in vitro growth of the hematopoietic stem cells in vitro with a new structure to maintain performance It is intended to provide a bioreactor for propagation.

본 발명은 상기와 같은 과제를 해결하기 위하여The present invention to solve the above problems

교반부;Agitator;

상기 교반부의 일측에 결합되는 베이스부;A base portion coupled to one side of the stirring portion;

상기 베이스부의 일면으로부터 수직하게 설치되는 홀더부;A holder part installed vertically from one surface of the base part;

증식하고자 하는 세포를 저장하며, 상기 베이스부의 일면에 실장되는 저장부; 및 상기 저장부 내부로 압력을 가압과 해제를 조절하는 조절부;를 포함하는 세포 체외 증식을 위한 바이오리액터를 제공한다.A storage unit storing cells to be proliferated and mounted on one surface of the base unit; It provides a bioreactor for cell in vitro proliferation comprising; and a control unit for adjusting the pressure and release pressure into the reservoir.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 베이스부는 평판 형상의 플레이트; 및 상기 플레이트의 일면에 다수로 돌출 형성되는 돌기부를 포함할 수 있다.In the bioreactor for in vitro proliferation of cells according to an embodiment of the present invention, the base portion of the plate-shaped plate; And it may include a protrusion formed to project a plurality on one surface of the plate.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 홀더부는 상기 플레이트로부터 서로 이격되어 수직하게 연장되는 한 쌍의 지지대; 및 상기 한 쌍의 지지대 사이에 연결되는 체결부를 포함하고, 상기 체결부의 높이가 지지대를 따라 조절 가능한 것을 특징으로 할 수 있다.In the bioreactor for extracellular proliferation according to an embodiment of the present invention, the holder portion is a pair of supports extending vertically spaced apart from each other from the plate; And a fastening portion connected between the pair of supports, wherein the height of the fastening portion is adjustable along the support.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 저장부는, 일반적으로 혈액 저장을 위해 사용되는 밀폐형 파우치, 팩, 혈액백 중 어느 하나로 이루어지는 것을 특징으로 할 수 있다. 본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 저장부는, 일반적으로 외부와 연결되는 1개의 튜브관을 포함하는 것을 특징으로 한다. In the bioreactor for extracellular proliferation of cells according to an embodiment of the present invention, the storage unit may be made of any one of a sealed pouch, a pack, and a blood bag which are generally used for blood storage. In the bioreactor for in vitro proliferation of cells according to an embodiment of the present invention, the storage unit is characterized in that it comprises one tube tube generally connected to the outside.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 조절부는 상기 저장부와 연결되며 상기 저장부의 내부에 압력을 가하는 압력 공급부; 및 상기 압력 공급부에 연결되며 상기 저장부에 가압된 압력을 해제시키는 압력 해제부를 포함할 수 있다. In the bioreactor for extracellular proliferation of cells according to an embodiment of the present invention, the control unit is connected to the storage and the pressure supply for applying pressure to the inside of the storage; And a pressure release unit connected to the pressure supply unit and releasing the pressure pressurized by the storage unit.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 압력 공급부는, 일측이 상기 저장부의 내부에 삽입되는 제1 튜브관; 상기 제1 튜브관의 타측에 연결되어 압력을 가하는 압축기; 상기 저장부와 상기 압축기 사이에 위치하는 필터부 및 상기 저장부와 상기 필터부 사이에 위치하는 솔레노이드밸브를 포함할 수 있다.In the bioreactor for extracellular proliferation of cells according to an embodiment of the present invention, the pressure supply unit, the first tube tube one side is inserted into the storage; A compressor connected to the other side of the first tube tube to apply pressure; It may include a filter unit located between the storage unit and the compressor and a solenoid valve positioned between the storage unit and the filter unit.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 솔레노이드밸브의 압력은 18Kpa 내지 22Kpa인 것을 특징으로 할 수 있다.In the bioreactor for extracellular proliferation according to an embodiment of the present invention, the pressure of the solenoid valve may be characterized in that 18Kpa to 22Kpa.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 압력 해제부는, 상기 제1 튜브관과 연결되는 제2 튜브관; 상기 제2 튜브관의 일측에 연결되는 클램프를 포함할 수 있다.In the bioreactor for extracellular proliferation of cells according to an embodiment of the present invention, the pressure release portion, the second tube tube connected to the first tube tube; It may include a clamp connected to one side of the second tube tube.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 조절부는, 상기 솔레노이드밸브 및 상기 클램프를 자동 제어하는 제어부를 더 포함할 수 있다.In the bioreactor for extracellular proliferation according to an embodiment of the present invention, the control unit may further include a control unit for automatically controlling the solenoid valve and the clamp.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 제어부는, 저장부로 가압하는 경우 상기 클램프가 폐쇄되도록 제어 하는 것을 특징으로 할 수 있다.In the bioreactor for in vitro proliferation of cells according to an embodiment of the present invention, the control unit may be characterized in that the control to close the clamp when pressed to the storage unit.

본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에 있어서, 상기 제어부는, 배압하는 경우 상기 솔레노이드 밸브가 폐쇄되고, 상기 클램프가 개방되도록 제어 하는 것을 특징으로 할 수 있다.In the bioreactor for in vitro proliferation of cells according to an embodiment of the present invention, the control unit may be characterized in that the solenoid valve is closed and the clamp is opened when back pressure.

본 발명의 실시예에 따르면, 인체에서 채취한 조혈모세포를 저장하는 저장부 내부에 압력을 가함과 동시에 저장부를 교반시킴으로써, 조혈모세포의 체외 증식 및 성능을 유지시킬 수 있다.According to an embodiment of the present invention, by adding pressure to the storage unit for storing the hematopoietic stem cells collected from the human body and stirring the storage unit, it is possible to maintain in vitro proliferation and performance of the hematopoietic stem cells.

본 발명의 실시예에 따르면, 베이스부의 일면으로부터 수직하게 설치되는 지지부에 저장부의 상부와 연결되는 구조에 의해 저장부가 수직하게, 또는 원하는 각도로 세워짐으로써, 저장부 내부로 유입되는 기체와 조혈모세포의 교반이 원활하게 이루어 질 수 있다.According to an embodiment of the present invention, by the structure connected to the upper portion of the storage portion vertically installed from one surface of the base portion, the storage portion is built up vertically or at a desired angle, so that the flow of gas and hematopoietic stem cells introduced into the storage portion Stirring can be done smoothly.

본 발명의 실시예에 따르면, 플레이트의 일면에 다수로 돌출 형성되는 돌기부를 포함하는 베이스부의 일면에 저장부를 얹혀 놓음으로써, 저장부가 베이스부로부터 이탈되는 것을 방지함과 동시에 교반시 저장부의 접촉부위를 불일정하게 요동시키는 효과를 제공하게 된다.According to an embodiment of the present invention, by placing the reservoir on one surface of the base including a plurality of protrusions protruding on one surface of the plate, to prevent the reservoir from being separated from the base and at the same time the contact of the reservoir during stirring It gives the effect of fluctuating irregularly.

본 발명의 실시예에 따르면, 제 1 튜브관 및 압축기 사이에 솔레노이드 밸브가 배치되어 저장부에 사용자가 원하는 정수압력을 일정하게 가함으로써, 저장부 내부에 조혈모세포의 상태를 원하는 일정기간지속적으로 유지시킬 수 있다.According to an embodiment of the present invention, the solenoid valve is disposed between the first tube tube and the compressor to apply a constant hydrostatic pressure desired by the user to the reservoir, thereby maintaining the state of the hematopoietic stem cells in the reservoir for a predetermined period of time. You can.

도 1은 본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터의 개략적인 사시도이다.1 is a schematic perspective view of a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention.

도 2는 본 발명의 저장부를 경사지게 설치한 형상을 나타낸 측면도이다.Figure 2 is a side view showing a shape in which the storage unit of the present invention is installed obliquely.

도 3은 본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터의 구성을 나타낸 개념도이다.3 is a conceptual diagram showing the configuration of a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention.

도 4 및 도 5는 저장부에 압력이 가압과 해제되는 것을 나타낸 개념도이다.4 and 5 are conceptual views showing that the pressure is released and released to the reservoir.

도 6은 본 발명의 다른 실시예에 따른 세포 체외증식 바이오리액터의 개략적인 사시도이다.Figure 6 is a schematic perspective view of a cell in vitro proliferation bioreactor according to another embodiment of the present invention.

이하, 본 발명의 바람직한 실시예를 첨부된 도면들을 참조하여 상세히 설명한다. 우선 각 도면의 구성요소들에 참조부호를 부가함에 있어서, 동일한 구성요소들에 대해서는 비록 다른 도면상에 표시되더라도 가능한 한 동일한 부호를 가지도록 하고 있음에 유의해야 한다. 또한, 본 발명을 설명함에 있어, 관련된 공지 구성 또는 기능에 대한 구체적인 설명이 본 발명의 요지를 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명은 생략한다.Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. First of all, in adding reference numerals to the components of each drawing, it should be noted that the same reference numerals are used as much as possible even if displayed on different drawings. In addition, in describing the present invention, when it is determined that the detailed description of the related well-known configuration or function may obscure the gist of the present invention, the detailed description thereof will be omitted.

명세서 전체에서, 어떤 부분이 다른 부분과 "연결"되어 있다고 할 때, 이는 "직접적으로 연결"되어 있는 경우뿐 아니라, 그 중간에 다른 부재를 사이에 두고 "간접적으로 연결"되어 있는 경우도 포함한다. 또한, 어떤 부분이 어떤 구성요소를 "포함"한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성요소를 더 구비할 수 있다는 것을 의미한다.Throughout the specification, when a part is "connected" to another part, it includes not only "directly connected" but also "indirectly connected" with another member in between. . In addition, when a part is said to "include" a certain component, this means that unless otherwise stated, it may further include other components rather than excluding the other components.

도 1은 본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터의 개략적인 사시도이고, 도 2는 본 발명의 저장부를 경사지게 설치한 형상을 나타낸 측면도이고, 도 3은 본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터의 구성을 나타낸 개념도이고, 도 4 및 도 5는 저장부에 압력이 가압과 해제되는 것을 나타낸 개념도이고, 도 6은 본 발명의 응용에 따라 베이스부에 수용부 및 경사부가 포함된 홀더부를 나타낸 사시도이다.1 is a schematic perspective view of a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention, Figure 2 is a side view showing the shape inclined to install the storage unit of the present invention, Figure 3 according to an embodiment of the present invention 4 is a conceptual diagram showing the configuration of a bioreactor for in vitro proliferation of cells, and FIG. 4 and FIG. 5 are conceptual views showing that pressure is released and released from the storage unit, and FIG. It is a perspective view which shows the holder part with an addition.

도 1 및 도 2에 도시된 바와 같이, 본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터는 교반부(100), 베이스부(200), 홀더부(300), 저장부(400) 및 조절부(500)를 포함한다.As shown in FIG. 1 and FIG. 2, the bioreactor for in vitro proliferation of cells according to an embodiment of the present invention includes a stirring part 100, a base part 200, a holder part 300, a storage part 400 and It includes an adjusting unit 500.

보다 상세하게는, 본 발명은 교반부(100), 상기 교반부의 상부에 결합되는 베이스부(200), 베이스부의 일면으로부터 수직하게 설치되는 홀더부(300), 상기 홀더부에 의해 지지되고, 베이스부의 일면에 실장되며, 인체에서 채취된 조혈모세포 등 증식하려고 하는 세포를 저장하는 저장부(400) 및 저장부에 연결되어 저장부의 내부로 압력을 인가하고 해제하는 조절부(500)를 포함한다.More specifically, the present invention is supported by the stirring portion 100, the base portion 200 coupled to the upper portion of the stirring portion, the holder portion 300 is installed vertically from one surface of the base portion, the base is supported by the holder, It is mounted on one side of the unit, and includes a storage unit 400 for storing cells to be proliferated, such as hematopoietic stem cells collected from the human body and a control unit 500 connected to the storage unit for applying and releasing pressure into the storage unit.

이하 도 1 내지 도 2를 참조하여 본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터를 더욱 상세히 설명한다.Hereinafter, a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention will be described in more detail with reference to FIGS. 1 to 2.

교반부(100)는 물리적 또는 화학적 성질이 다른 2종 이상의 물질을 외부적인 기계 에너지를 사용하여 균일한 혼합 상태를 만드는 것으로, 후술하는 저장부(400)에 저장된 조혈모세포에 압력을 인가하면서 혼합시키는 장치이다. 이러한 교반부(100)는 하우징을 구비하고 하우징 내부에 모터 및 기어로 구성될 수 있다.(미도시) 또한, 하우징은 상부에 전술한 모터 및 기어에 의해 상,하,좌,우로 움직이는 구동부로 구성될 수 있다.(미도시). 또한, 하우징은 종래 당업자들이 사용하는 볼텍스 기기를 사용하는 것이 가능하다.Stirring unit 100 is to create a uniform mixed state of two or more substances having different physical or chemical properties by using external mechanical energy, mixing while applying pressure to the hematopoietic stem cells stored in the storage unit 400 to be described later Device. The stirring unit 100 may include a housing and may include a motor and a gear inside the housing (not shown). In addition, the housing may be a driving unit moving up, down, left, and right by the above-described motor and gear. It may be configured (not shown). In addition, it is possible to use a vortex device used by those skilled in the art for the housing.

또한, 본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터에서 증식시키는 세포는 '조혈모세포' 에 한정되지 않으며 조혈모세포 또는 환자나 공여자로부터 추출한 조혈모세포 및 관련 주변세포를 포함하여, 비 부착성 세포(non-adherent cells)를 증식시키는 것이 가능하다. In addition, the cells to proliferate in the bioreactor for in vitro proliferation of cells according to an embodiment of the present invention is not limited to 'hematopoietic stem cells', including hematopoietic stem cells or hematopoietic stem cells extracted from a patient or a donor and non-adherent It is possible to proliferate non-adherent cells.

베이스부(200)는 교반부(100)의 일측에 결합되어 교반부(100)의 움직임에 대응하여 움직일 수 있다. 보다 상세하게 베이스부(200)는 도 1에 도시된 바와 같이 교반부(100)의 상측에 위치하며, 교반부(100)의 상부에 형성된 구동부와 결합된다. 즉, 베이스부(200)는 하우징 내부에 모터 및 기어와 연결되어 구동부와 결합됨에 따라 상, 하, 좌, 우로 움직이는 구동부의 움직임에 대응하여 움직이는 것이 가능하다.The base unit 200 may be coupled to one side of the stirring unit 100 to move in response to the movement of the stirring unit 100. In more detail, the base part 200 is located above the stirring part 100, as shown in FIG. 1, and is coupled to the driving part formed on the upper part of the stirring part 100. That is, the base unit 200 may be moved in response to the movement of the driving unit moving up, down, left, and right as the base unit 200 is connected to the motor and gears and coupled to the driving unit.

또한, 베이스부(200)는 플레이트(210) 및 돌기부(220)를 포함한다. 플레이트(210)는 평판 형상으로 이루어지며, 일정한 두께를 가질 수 있다. 돌기부(220)는 플레이트(210)의 일면에 다수로 돌출 형성될 수 있다. 여기서 돌기부(210)는 도 1에 도시된 바와 같이, 일정한 간격으로 플레이트(210)의 상면으로부터 반구형상으로 돌출된 돌기가 다수로 이루어진다. 이러한 돌기부(210)는 저장부(400)가 플레이트(210)에 실장된 후, 교반부(100)가 교반되는 경우에도 돌기부의 마찰에 의하여 저장부(400)가 베이스부로부터 미끄러지는 것을 방지한다. 이러한 돌기부(220)는 교반부(100)의 교반 운동 시 저장부(400)에 저장된 조혈모세포에 적절한 압력을 인가할 수 있다. In addition, the base 200 includes a plate 210 and the protrusion 220. The plate 210 is formed in a flat plate shape and may have a constant thickness. Protruding portion 220 may be formed to protrude a plurality on one surface of the plate (210). As shown in FIG. 1, the protrusions 210 may include a plurality of protrusions protruding in a hemispherical shape from an upper surface of the plate 210 at regular intervals. The protrusion 210 prevents the storage 400 from slipping from the base part by friction of the protrusion even when the storage part 400 is mounted on the plate 210 and the stirring part 100 is stirred. . The protrusion 220 may apply an appropriate pressure to the hematopoietic stem cells stored in the storage unit 400 during the stirring movement of the stirring unit 100.

본 발명의 다른 일 실시예에 의한 세포 체외 증식을 위한 바이오리액터에서는 베이스부(200)의 상면에 다수의 홈을 일정간격으로 형성시킨 요철부가 형성될 수도 있다.(미도시)In the bioreactor for in vitro proliferation of cells according to another embodiment of the present invention, an uneven portion having a plurality of grooves formed at regular intervals may be formed on the upper surface of the base portion 200 (not shown).

본 발명에 따른 홀더부(300)는 베이스부(200)의 일면으로부터 수직하게 설치되어 저장부(400)의 상부와 연결되어 저장부를 지지한다. 즉, 도 1에 도시된 바와 같이 홀더부(300)는 베이스부(200)의 상면에 저장부(400)를 수직하게 세워서 실장하는 역할을 하며, 이를 위해 홀더부(300)는 한 쌍의 지지대(310) 및 체결부(320)를 포함한다.Holder portion 300 according to the present invention is installed vertically from one surface of the base portion 200 is connected to the upper portion of the storage portion 400 to support the storage portion. That is, as shown in FIG. 1, the holder part 300 serves to vertically mount the storage part 400 on the upper surface of the base part 200, and for this purpose, the holder part 300 has a pair of supports. 310 and the fastening part 320.

한 쌍의 지지대(310)는 플레이트(210)의 상면으로부터 서로 이격되어 수직하게 연장되어 설치된다. 보다 상세하게 한 쌍의 지지대(310)는 내부에 슬라이딩 레일이 형성되어 체결부(320)가 레일에 삽입 결합됨으로써, 레일을 따라 상하 방향으로 수직이동이 원활하게 이루어질 수 있다. The pair of supports 310 are installed to be vertically spaced apart from each other from the upper surface of the plate 210. More specifically, the pair of supports 310 has a sliding rail formed therein so that the fastening part 320 is inserted into and coupled to the rail, so that vertical movement can be performed smoothly in the vertical direction along the rail.

체결부(320)는 저장부(400)를 지지하도록 한 쌍의 지지대(310) 사이에 연결된다. 보다 상세하게 체결부(320)는 길이방향으로 연장되는 막대형상이며, 저장부(400)의 상부가 끼워지도록 좌우로 분리되는 집게구조로 이루어짐으로써, 한 쌍의 지지대(310)의 양측과 연결되어 저장부(400)가 수직하게 세워지도록 하는 역할을 한다.The fastening part 320 is connected between the pair of supports 310 to support the storage part 400. More specifically, the fastening part 320 is a rod-shaped extending in the longitudinal direction, and is made of a tong structure that is separated from side to side so that the upper portion of the storage unit 400 is fitted, it is connected to both sides of the pair of supports 310 The storage unit 400 serves to stand vertically.

한 쌍의 지지대(310)는 저장부(400)에 저장된 증식 세포의 양에 따라 체결부(320)를 상하 방향으로 이동시킴으로써, 저장부가베이스부에 실장되는 각도 및 높이를 조절하는 것이 가능하다. 도 2에 도시된 바와 같이, 한 쌍의 지지대(310)는 체결부(320)의 높이를 조절하여 체결부(320)와 결합된 저장부(400)를 베이스부(200)의 일면에 원하는 각도로 경사 실장하는 것이 가능하다.The pair of supports 310 moves the fastening part 320 in the up and down direction according to the amount of proliferating cells stored in the storage part 400, so that the angle and the height of the storage part mounted on the base part can be adjusted. As shown in FIG. 2, the pair of supports 310 adjusts the height of the fastening part 320 so that the storage part 400 coupled with the fastening part 320 has a desired angle on one surface of the base part 200. It is possible to mount inclined by.

저장부(400)는 증식하고자 하는 조혈모세포 등 세포를 저장하며, 지지대에 지지되어 베이스부(200)의 일면에 실장된다. 저장부(400)는 일반적으로 혈액을 담기 위해 사용되는 혈액백이 사용될 수 있으며, 밀폐형 파우치, 팩, 백 중 어느 하나로 이루어지는 것이 가능하다.The storage unit 400 stores cells such as hematopoietic stem cells to be proliferated and is supported by a support and mounted on one surface of the base unit 200. The storage unit 400 may be a blood bag generally used to contain blood, and may be made of any one of a sealed pouch, a pack, and a bag.

도 3은 본 발명의 실시예에 따른 세포 체외 증식을 위한 바이오리액터의 구성을 나타낸 개념도이다.3 is a conceptual diagram showing the configuration of a bioreactor for in vitro proliferation of cells according to an embodiment of the present invention.

도 3을 참조하면, 본 발명에 따른 조절부(500)는 저장부(400)에 연결되어 저장부(400)의 내부로 압력을 인가하거나 해제하는 것을 조절한다. Referring to FIG. 3, the adjusting unit 500 according to the present invention is connected to the storage 400 to control the application or release of pressure into the storage 400.

조절부(500)는 압력 공급부(510) 및 압력 해제부(520)를 포함한다. 압력 공급부(510)는 저장부(400)와 연결되며 저장부(400)의 내부에 압력을 인가한다. 이를 위해 압력 공급부(510)는 제1 튜브관(511), 압축기(512), 필터부(513) 및 솔레노이드밸부(514)를 포함한다.The adjusting unit 500 includes a pressure supply unit 510 and a pressure release unit 520. The pressure supply part 510 is connected to the storage part 400 and applies pressure to the inside of the storage part 400. To this end, the pressure supply unit 510 includes a first tube tube 511, a compressor 512, a filter unit 513, and a solenoid valve unit 514.

제1 튜브관(511)은 중공형으로 형성되어 일측이 저장부(400)의 내부에 삽입되고, 타측은 압축기(512)에 연결되어, 압축기로부터 저장부(400)의 내부로 압력을 인가하는 역할을 한다. The first tube tube 511 is formed in a hollow shape, one side is inserted into the storage unit 400, and the other side is connected to the compressor 512 to apply pressure from the compressor to the storage unit 400. Play a role.

압축기(512)는 제1 튜브관의 타측에 연결되어 압력을 가하는 것으로 에어 압축기 구조로 이루어질 수 있다. 이러한 압축기(512)는 주변 공기를 압축하여 압축한 공기를 제1 튜브관(511)을 통해 저장부(400)의 내부로 공급하는 역할을 한다.The compressor 512 is connected to the other side of the first tube tube to apply a pressure may be made of an air compressor structure. The compressor 512 compresses ambient air to supply compressed air to the inside of the storage unit 400 through the first tube tube 511.

필터부(513)는 저장부(400)와 압축기(512) 사이에 위치하여 저장부(400)로 유입될 수 있는 오염물질을 정화한다. 보다 상세하게 필터부(513)는 사각형상의 본체와 본체 내부에 삽입되는 필터로 이루어질 수 있다.(미도시) 여기서, 필터는 큰 먼지를 걸러주는 프리필터, 공기 중 냄새를 제거하는 탈취필터, 초 미세먼지를 제거하는 헤파필터로 구성되는 것도 가능하다. 또한 본체가 분리되는 구조로 형성되어 필터의 교환이 용이하다는 장점이 있다. 이와 같이 필터부(513)는 압축기(512)로부터 발생되는 압축공기를 정화하여 저장부(400)로 깨끗한 공기를 공급 하여 조혈모세포의 오염을 방지하는 역할을 한다.The filter unit 513 is disposed between the storage unit 400 and the compressor 512 to purify contaminants that may flow into the storage unit 400. More specifically, the filter unit 513 may be formed of a rectangular main body and a filter inserted into the main body (not shown). Here, the filter may include a pre-filter for filtering large dust, a deodorizing filter for removing odors in the air, and a candle. It is also possible to comprise a hepa filter for removing fine dust. In addition, the main body is formed in a structure that is separated there is an advantage that the exchange of the filter is easy. As such, the filter unit 513 cleans compressed air generated from the compressor 512 and supplies clean air to the storage unit 400 to prevent contamination of hematopoietic stem cells.

솔레노이드밸브(514)는 저장부(400)와 필터부(513)사이에 위치하며 압력의 흐름을 제어하는 역할을 한다. 또한, 솔레노이드밸브의 압력은 18Kpa(킬로파스칼) 내지 22Kpa(킬로파스칼)인 것이 바람직하다. 일례로, 18Kpa 내지 22Kpa 압력은 혈액이 골수에서 받는 압력과 유사하다. 따라서 솔레노이드밸브(514)는 18Kpa 내지 22Kpa의 압력을 일정하게 유지하도록 하여 저장부(400)의 내부에서 조혈모세포의 체외증식 및 성능을 유지시키는 것이 가능하다.The solenoid valve 514 is located between the storage unit 400 and the filter unit 513 serves to control the flow of pressure. In addition, the pressure of the solenoid valve is preferably 18 Kpa (kilopascal) to 22 Kpa (kilopascal). In one example, the 18 Kpa to 22 Kpa pressure is similar to the pressure blood receives in the bone marrow. Therefore, the solenoid valve 514 may maintain a constant pressure of 18Kpa to 22Kpa to maintain in vitro growth and performance of hematopoietic stem cells in the storage unit 400.

한편, 압력 해제부(520)는 저장부(400)의 내부로 가압된 압력을 해제 시키는 역할을 한다. 이를 위해 압력 해제부(520)는 제2 튜브관(521) 및 클램프(522)를 포함한다.On the other hand, the pressure release unit 520 serves to release the pressure pressurized into the storage unit 400. To this end, the pressure release part 520 includes a second tube tube 521 and a clamp 522.

제2 튜브관(521)은 제1 튜브관과 연결되고, 제 1 튜브관으로부터 분리되는 관이며 중공형으로 형성될 수 있다. 제2 튜브관(521)은 저장부(400)와 연결된 제1 튜브관의 외주면 일측으로부터 분리되는 관이며, 저장부(400)와 솔레노이드밸브(514) 사이에 위치한다.The second tube tube 521 is connected to the first tube tube, the tube is separated from the first tube tube and may be formed in a hollow shape. The second tube tube 521 is a tube separated from one side of the outer circumferential surface of the first tube tube connected to the storage unit 400, and is located between the storage unit 400 and the solenoid valve 514.

클램프(522)는 제2 튜브관(521)의 타측에 연결되어 클램프가 개방 폐쇄됨에 따라 저장부로 압력을 인가하거나 해제한다. The clamp 522 is connected to the other side of the second tube tube 521 to apply or release pressure to the reservoir as the clamp is opened and closed.

압력 공급부(510) 및 압력 해제부(520)를 포함하는 조절부(500)는 제어부(530)를 더 포함할 수 있다.The adjusting unit 500 including the pressure supply unit 510 and the pressure release unit 520 may further include a control unit 530.

제어부(530)는 솔레노이드밸브(514) 및 클램프(522)를 제어하여 저장부(400)에 일정한 압력을 공급 및 공급되는 압력을 해제시키는 것을 제어할 수 있다.The controller 530 may control the solenoid valve 514 and the clamp 522 to control supply of a constant pressure to the storage unit 400 and release of the supplied pressure.

도 4 및 도 5를 참조하면, 제어부(530)는 저장부로 압력을 가압하는 경우 클램프(522)를 폐쇄하도록 제어한다. 또한, 제어부(530)는 저장부의 압력을 배압하는 경우 솔레노이드밸브(514)가 폐쇄되고 클램프(522)가 서서히 열리도록 제어한다. 4 and 5, the controller 530 controls to close the clamp 522 when the pressure is applied to the storage. In addition, the controller 530 controls the solenoid valve 514 to close and the clamp 522 to open slowly when the pressure of the storage unit is back pressured.

도 6은 본 발명의 다른 실시예에 따른 세포 체외 증식을 위한 바이오리액터를 나타낸다. 6 shows a bioreactor for in vitro proliferation of cells according to another embodiment of the present invention.

도 6에 나타낸 세포 체외 증식을 위한 바이오리액터는 베이스부에 수용부 및 경사부가 포함된 홀더부를 포함한다. 도 6을 참조하면, 베이스부(200')는 평판 형상으로 이루어진 플레이트(210') 및 플레이트의 테두리로부터 수직하게 소정높이로 연장되는 격벽(220')을 포함한다.The bioreactor for in vitro proliferation of cells shown in FIG. 6 includes a holder part including an accommodating part and an inclined part in a base part. Referring to FIG. 6, the base part 200 ′ includes a plate 210 ′ having a flat plate shape and a partition wall 220 ′ extending vertically from a plate edge at a predetermined height.

홀더부(300')는 베이스부(200')의 상면에 실장되며 내부에 저장부를 수용할 수 있는 공간이 형성되는 수용부(310') 및 수용부의 하면에 일방향으로 경사를 이루는 경사부(320')를 포함한다. 여기서 수용부(310')는 저장부(400)를 수용하기 위해 상면 일측이 개방되는 것이 바람직하다.The holder part 300 'is mounted on the upper surface of the base part 200' and includes an accommodating part 310 'having a space for accommodating a storage part therein and an inclined part 320 inclined in one direction on a lower surface of the accommodating part. Contains'). Here, the accommodating part 310 ′ is preferably opened at one side of the upper surface to accommodate the storage part 400.

이러한 홀더부(300')는 저장부(400)가 베이스부(200')에 경사진 상태로 안정적으로 실장될수 있으므로 조혈모세포의 교반 효과를 극대화 시키는 것이 가능하다.Since the holder part 300 'can be stably mounted in a state in which the storage part 400 is inclined to the base part 200', it is possible to maximize the stirring effect of the hematopoietic stem cells.

전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예는 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. 예를 들어, 단일형으로 설명되어 있는 각 구성 요소는 분산되어 실시될 수도 있으며, 마찬가지로 분산된 것으로 설명되어 있는 구성 요소들도 결합된 형태로 실시될 수 있다.The foregoing description of the present invention is intended for illustration, and it will be understood by those skilled in the art that the present invention may be easily modified in other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined form.

본 발명의 범위는 후술하는 특허청구범위에 의하여 나타내어지며, 특허청구범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present invention is represented by the following claims, and it should be construed that all changes or modifications derived from the meaning and scope of the claims and their equivalents are included in the scope of the present invention.

(부호의 설명)(Explanation of the sign)

100 : 교반부100: stirring section

200, 200' : 베이스부200, 200 ': base part

210, 210' : 플레이트210, 210 ': plate

220 : 돌기부220: projection

220' : 격벽 220 ': bulkhead

300, 300' : 홀더부300, 300 ': Holder

310 : 한 쌍의 지지대310: pair of supports

310' : 수용부310 ': receiving part

320 : 체결부320: fastening part

320' : 경사부320 ': slope

400 : 저장부400: storage

500 : 조절부500: control unit

510 : 압력 공급부 510: pressure supply

511 : 제1 튜브관511: first tube tube

512 : 압축기512: Compressor

513 : 필터부513: filter unit

514 : 솔레노이드밸브514: solenoid valve

520 : 압력 해제부520: pressure release unit

521 : 제2 튜브관 521 a second tube tube

522 : 클램프522: clamp

530 : 제어부530: control unit

Claims (11)

교반부;Agitator; 상기 교반부의 일측에 결합되는 베이스부;A base portion coupled to one side of the stirring portion; 상기 베이스부의 일면으로부터 수직하게 설치되는 홀더부;A holder part installed vertically from one surface of the base part; 증식하고자 하는 세포를 저장하며, 상기 베이스부의 일면에 실장되는 저장부; 및A storage unit storing cells to be proliferated and mounted on one surface of the base unit; And 상기 저장부의 내부로 압력을 가압과 해제를 조절하는 조절부;를 포함하는Control unit for adjusting the pressure and release the pressure into the reservoir; 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 1 항에 있어서,The method of claim 1, 상기 베이스부는The base portion 평판 형상의 플레이트; 및Flat plate; And 상기 플레이트의 일면에 다수로 돌출 형성되는 돌기부;를 포함하는Includes; protrusions protruding in a plurality on one surface of the plate 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 1 항에 있어서,The method of claim 1, 상기 홀더부는The holder part 상기 플레이트로부터 서로 이격되어 수직하게 연장되는 한 쌍의 지지대; 및A pair of supports extending vertically apart from each other from the plate; And 상기 한 쌍의 지지대 사이에 연결되는 체결부;를 포함하고,Includes; fastening portion connected between the pair of supports, 상기 체결부의 높이가 지지대를 따라 조절 가능한 것인 The height of the fastening portion is adjustable along the support 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 1 항에 있어서,The method of claim 1, 상기 저장부는The storage unit 밀폐형 파우치, 팩, 백 중 어느 하나로 이루어지는 것을 특징으로 하는It is made of any one of a sealed pouch, pack, bag 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 1 항에 있어서,The method of claim 1, 상기 조절부는The control unit 상기 저장부와 연결되며 상기 저장부의 내부에 압력을 가하는 압력 공급부; 및A pressure supply unit connected to the storage unit and applying pressure to the inside of the storage unit; And 상기 압력 공급부에 연결되며 상기 저장부에 가압된 압력을 해제시키는 압력 해제부;를 포함하는And a pressure release unit connected to the pressure supply unit and releasing the pressure pressurized by the storage unit. 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 5 항에 있어서,The method of claim 5, wherein 상기 압력 공급부는The pressure supply unit 일측이 상기 저장부의 내부에 삽입되는 제1 튜브관;A first tube tube having one side inserted into the storage unit; 상기 제1 튜브관의 타측에 연결되어 압력을 가하는 압축기;A compressor connected to the other side of the first tube tube to apply pressure; 상기 저장부와 상기 압축기 사이에 위치하는 필터부 및A filter unit located between the storage unit and the compressor; 상기 저장부와 상기 필터부 사이에 위치하는 솔레노이드밸브;를 포함하는It includes; a solenoid valve located between the storage unit and the filter unit 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 6 항에 있어서,The method of claim 6, 상기 솔레노이드밸브의 압력은 18Kpa 내지 22Kpa인 것을 특징으로 하는The pressure of the solenoid valve is characterized in that 18Kpa to 22Kpa 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 5 항에 있어서,The method of claim 5, wherein 상기 압력 해제부는The pressure release portion 상기 제1 튜브관과 연결되는 제2 튜브관;A second tube tube connected with the first tube tube; 상기 제2 튜브관의 일측에 연결되는 클램프;를 포함하는It includes; a clamp connected to one side of the second tube tube 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 5 항에 있어서,The method of claim 5, wherein 상기 조절부는The control unit 상기 솔레노이드밸브 및 상기 클램프를 제어하는 제어부;를 더 포함하는And a control unit for controlling the solenoid valve and the clamp. 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 9 항에 있어서,The method of claim 9, 상기 제어부는The control unit 상기 저장부로 압력을 인가하는 경우 상기 클램프가 폐쇄되도록 제어 하는 것을 특징으로 하는When the pressure is applied to the reservoir characterized in that the control to close the clamp 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells. 제 9 항에 있어서,The method of claim 9, 상기 제어부는The control unit 상기 저장부의 압력을 배압하는 경우 상기 솔레노이드밸브가 폐쇄되고, 상기 클램프가 개방되도록 제어 하는 것을 특징으로 하는The solenoid valve is closed when the pressure of the storage unit back pressure, and the clamp is controlled to open. 세포 체외 증식을 위한 바이오리액터.Bioreactor for in vitro proliferation of cells.
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