WO2020122556A1 - Procédé et dispositif de simulation bioenvironnementale - Google Patents

Procédé et dispositif de simulation bioenvironnementale Download PDF

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Publication number
WO2020122556A1
WO2020122556A1 PCT/KR2019/017388 KR2019017388W WO2020122556A1 WO 2020122556 A1 WO2020122556 A1 WO 2020122556A1 KR 2019017388 W KR2019017388 W KR 2019017388W WO 2020122556 A1 WO2020122556 A1 WO 2020122556A1
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WO
WIPO (PCT)
Prior art keywords
unit
mounting
pressure
shear force
target cell
Prior art date
Application number
PCT/KR2019/017388
Other languages
English (en)
Korean (ko)
Inventor
양승희
김연수
김동기
이사람
김용철
유미연
김지은
Original Assignee
서울대학교산학협력단
서울대학교병원
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 서울대학교산학협력단, 서울대학교병원 filed Critical 서울대학교산학협력단
Priority to EP19894508.1A priority Critical patent/EP3896147A4/fr
Priority to US17/054,999 priority patent/US11530377B2/en
Priority claimed from KR1020190163783A external-priority patent/KR102371708B1/ko
Publication of WO2020122556A1 publication Critical patent/WO2020122556A1/fr

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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
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/04—Apparatus for enzymology or microbiology with gas introduction 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
    • 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
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/36—Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
    • 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
    • C12M1/42—Apparatus for the treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves

Definitions

  • the present invention relates to a bioenvironmental simulation device and method, and more particularly, to a bioenvironmental simulation device and method for providing pressure through a rotational force to a cell and shear force through a flow rate of a culture medium.
  • Hypertension refers to a chronic disease in which blood pressure is higher than the normal range. In general, for adults 18 years of age or older, high blood pressure is diagnosed when systolic blood pressure measured at rest is greater than or equal to 140 mmHg or diastolic blood pressure is greater than or equal to 90 mmHg.
  • Hypertension itself is mostly symptom-free, but it can show complications such as stroke, heart failure, retinopathy, coronary artery disease, renal failure, and peripheral vascular disease.
  • complications such as stroke, heart failure, retinopathy, coronary artery disease, renal failure, and peripheral vascular disease.
  • kidney damage caused by hypertension can lead to reduced glomerular function and extensive fibrosis of kidney tissue.
  • An aspect of the present invention provides a bioenvironmental simulation apparatus and method using rotational force and shear force to stably provide a constant pressure and flow rate to cells to be similar to the environment in vivo.
  • the bioenvironmental mimetic device includes at least one mounting unit on which cells to be measured are seated;
  • a rotation force applying unit for rotating the mounting unit so as to apply rotational force to the measurement target cell mounted on the mounting unit; It includes a culture medium flow device configured to flow the culture medium across the mounting unit, the culture medium flow device for flowing the culture medium to apply a shear force to the cells to be measured.
  • the at least one mounting unit has a first cell seating surface on which a first cell to be measured is seated on one surface of the separation membrane, and the first cell seating surface faces the first cell forming a first space through which the first culture medium passes.
  • Mounting unit As a second space having a second cell seating surface on which the second cell to be measured, which interacts with the first cell to be measured, is seated on the other surface of the separation membrane, the second cell seating surface faces and the second culture medium passes, And a second mounting portion forming a second space partitioned from the first space by the separator.
  • the first and second culture fluid may be configured to pass through the first and second spaces at independent flow rates.
  • the culture fluid flow device includes: a first supply unit circulating the first culture fluid passing through the first space; And a second supply unit circulating the second culture medium passing through the second space, the second supply unit operating independently of the first supply unit.
  • the first and second cell seating surfaces on which the first and second measurement target cells are disposed, respectively, are subjected to a pressure due to a combined force of gravity and rotational force generated by the rotational force applying unit in a first direction, and the culture fluid flows.
  • the shear force due to the flow of the first and second culture fluid by the device may be configured to be applied in a second direction perpendicular to the first direction.
  • the second mounting portion may be disposed outside in the first direction than the first mounting portion.
  • the at least one mounting unit includes: a first inlet and a first outlet connected to the first mounting unit and configured to allow the first culture medium to flow in and out of the first space;
  • the second inlet and the second outlet connected to the second mounting portion and configured to flow in and out of the second culture medium; including, the first inlet, the first outlet, the second inlet, and the second outlet are respectively the first , It may be disposed in the second direction with respect to the two mounting portion.
  • a pressure sensor for sensing the pressure in the mounting unit.
  • the first and second mounting portions one side of which faces the first and second spaces, and the other side of which is a transparent surface exposed to the outside, a permeable member that transmits air to the first and second spaces. can do.
  • the transmissive member may include polydimethylsiloxane (PDMS).
  • PDMS polydimethylsiloxane
  • the at least one mounting unit includes a plurality of mounting units radially disposed around the rotational force applying unit; and transmitting the rotational force of the rotating force applying unit to the plurality of mounting units, and rotating together with the plurality of mounting units. It may further include a unit mount;
  • the unit mount is a plurality of mount legs that are radially divided and disposed, and the plurality of mount units are respectively disposed, and a plurality of mount legs configured to vary angles with the ground according to the rotational force of the rotation force applying unit. can do.
  • the pressure and shear force satisfying the appropriate pressure condition and the appropriate shear force condition are applied to the measurement target cell based on the appropriate pressure condition and the appropriate shear force condition matched to the type of the target cell and the target cell type. It may further include a rotation force applying unit and a control unit for controlling the culture fluid flow device.
  • the appropriate pressure condition includes information on a relationship between the blood pressure of the body and the pressure applied to the measurement target cell in a condition in which the measurement target cell is present in the body, and the controller controls the Using information, a value of the actual pressure, which is the pressure applied to the measurement target cell, is calculated under the condition that the measurement target cell is present in the body having a blood pressure equal to the preset blood pressure setting value, and the pressure equal to the value of the actual pressure
  • the rotation force applying unit may be controlled to be applied to the measurement target cell.
  • the appropriate shear force condition includes information on a relationship between the blood flow of the body and the shear force applied to the measurement target cell in a condition in which the measurement target cell is present in the body, and the controller controls the within the appropriate shear force condition.
  • the value of the actual shear force which is the shear force applied to the cell to be measured under the condition that the target cell is present in the body having the blood pressure equal to the predetermined blood flow, calculates the shear force equal to the value of the actual shear force
  • the culture fluid flow device can be controlled to be applied to the cells to be measured.
  • the control unit calculates a speed of rotational movement of the mounting unit that satisfies the appropriate pressure condition and provides it to the rotation force applying unit, calculates a flow rate of the culture medium that satisfies the appropriate shear force condition, and provides it to the culture fluid flow device. Can be.
  • the appropriate pressure condition and the appropriate shear force condition may be determined based on the pressure and shear force within a range in which the cell to be measured can survive for a predetermined threshold time over a predetermined threshold probability.
  • a desired pressure and shear force can be applied to cells to be tested using centrifugal force generated by rotation and flow of a fluid.
  • centrifugal force and shear force as described above, it is possible to stably apply pressure to the cell without damaging the cell, and also has the advantage of being easy to operate and having high repeatability.
  • the present invention it is possible to identify the behavior and response of various cells inside the patient's body according to the blood pressure of the patient.
  • the results according to an embodiment of the present invention may be applied to drug development for the treatment of hypertension and analysis of the effectiveness of the drug, and ultimately to contribute to improving the health and quality of life of hypertensive patients.
  • FIG. 1 is a perspective view of a biological environment simulation apparatus according to an embodiment of the present invention.
  • FIG. 2 is a side view of a bioenvironmental simulation device according to an embodiment of the present invention.
  • Figure 3 is a perspective view of the device removed from the bio-environment simulation apparatus according to an embodiment of the present invention.
  • Figure 4 is a perspective view of a mounting unit and a pressure sensor of the bio-environment simulation apparatus according to an embodiment of the present invention.
  • Figure 5 is an exploded perspective view of the mounting unit and the pressure sensor of the bio-environment simulation apparatus according to an embodiment of the present invention.
  • FIG. 6 is a view showing a cross-section of the mounting unit of the bio-environment simulation apparatus according to an embodiment of the present invention and the flow of the culture medium.
  • FIG. 7 is a view showing a lower portion of the mounting unit of the bio-environment simulation apparatus according to an embodiment of the present invention.
  • FIG. 8 is a perspective view of a bioenvironment simulation apparatus according to another embodiment of the present invention.
  • first may be referred to as a second component without departing from the scope of the present invention, and similarly, the second component may be referred to as a first component.
  • the term “and/or” includes a combination of a plurality of related listed items or any one of a plurality of related listed items.
  • ⁇ unit may refer to a unit that processes at least one function or operation.
  • the terms may mean at least one process processed by at least one hardware, at least one software or processor stored in memory, such as a field-programmable gate array (FPGA)/application specific integrated circuit (ASIC). have.
  • FPGA field-programmable gate array
  • ASIC application specific integrated circuit
  • FIG. 1 is a perspective view of a bioenvironment simulation apparatus according to an embodiment of the present invention
  • FIG. 2 is a side view of a bioenvironment simulation apparatus according to an embodiment of the present invention
  • FIG. 3 is a bioenvironment simulation according to an embodiment of the present invention This is a perspective view of the device with the device cover removed.
  • the bioenvironmental simulation device 1 can reproduce the environment similar to the environment in the living body, thereby identifying the operation or response of various cells.
  • the bioenvironmental simulation device 1 may include a mounting unit 10, a rotation force applying unit 50, and a culture fluid flow device 60.
  • the cell to be measured may be mounted on the mounting unit 10.
  • the cells to be measured mounted on the mounting unit 10 may be provided with pressure and shear force through a rotational motion described later and a flow of the culture medium.
  • the mounting unit 10 includes a plurality of separate spaces that can be interacted with, and the plurality of spaces can be configured to flow a culture medium having a different type or flow rate.
  • At least one mounting unit 10 may be provided.
  • the bio-environment simulation apparatus 1 is arranged such that the six mounting units 10 are spaced apart from each other in the rotational direction around the rotational force applying unit 50, but the number is not limited. The specific configuration of the mounting unit 10 will be described later in detail.
  • the rotation force applying unit 50 is provided to rotate the mounting unit 10.
  • the rotation force applying unit 50 may apply a centripetal force to the mounting unit 10 so that the mounting unit 10 moves circularly along a circular orbit as shown in R of FIG. 1 around a central point.
  • the plurality of mounting units 10 may be configured to have the same rotation center and circular motion by the rotation force applying unit 50.
  • the rotational force applying unit 50 may include a power device such as a general motor.
  • the rotation force applying unit 50 rotates the mounting unit 10 to apply pressure to the cell to be measured in the first direction (see W1, FIG. 2 ), which is the combined direction of gravity and rotation force.
  • the culture fluid flow device 60 is provided to flow the culture fluid to the mounting unit 10.
  • the culture fluid flow device 60 may allow the culture fluid to flow across the mounting unit 10.
  • the culture fluid flow device 60 may flow the culture fluids of different types into the mounting unit 10, and may also flow culture fluids of different flow rates.
  • the culture fluid flow device 60 may allow the culture fluids to flow, to apply shear force to the cells to be measured seated on the mounting unit 10.
  • the culture fluid flow device 60 may include first and second culture fluid storage units 62a and 62b, a first supply unit 64a (see FIG. 3 ), and a second supply unit (not shown).
  • the culture fluid circulated to the mounting unit 10 may be stored in the first and second culture fluid storage units 62a and 62b, respectively.
  • the culture medium stored in the first and second culture medium storage units 62a and 62b may be defined as first and second culture medium, respectively.
  • the first and second culture fluids may be culture fluids of different types as necessary, or may be the same culture fluid.
  • the first supply unit 64a and the second supply unit are provided so that the first and second culture fluid stored in the first and second culture fluid storage units 62a and 62b flow through the mounting unit 10.
  • the first supply unit 64a is connected to the first culture medium storage unit 62a, and the second supply unit is provided to be connected to the second culture medium storage unit 62b.
  • the second supply unit may be symmetrically disposed on the other side of the first supply unit 64a.
  • the first supply unit 64a and the second supply unit may include a power device such as a pump.
  • the first and second supply units 64a may operate independently by the control unit. That is, the first supply unit 64a and the second supply unit (not shown) may operate to circulate the first and second culture fluids stored in the first and second culture fluid storage units 62a and 62b, respectively, with independent flow rates.
  • the bioenvironmental simulation device 1 may include circulation tubes 38a and 38b.
  • the circulation tubes 38a and 38b may include a first circulation tube 38a and a second circulation tube 38b.
  • the first circulation tube 38a may be provided to connect the first culture unit storage section 62a, the first supply unit 64a, and the first mounting unit 30 described later among the at least one mounting unit 10.
  • the second circulation tube 38b may be provided to connect the second culture part storage part 62b, the second supply part (not shown), and the second placement part 40 described later among at least one of the mounting units 10. .
  • the culture fluid flow device 60 may include a device cover 68.
  • the device cover 68 is provided to cover the first and second supply parts 64a so that the first and second supply parts 64a are not exposed to the outside, and the first and second culture fluid storage parts 62a and 62b are exposed to the outside. It is prepared.
  • the device cover 68 knows the amount of the culture medium in the concave portions 69a and the first and second culture liquid storage portions 62a and 62b, which are concavely formed such that the first and second culture liquid storage portions 62a and 62b are located. It may include a gauge check groove (69b) formed to be long in the longitudinal direction of the culture medium storage portion.
  • the bioenvironmental simulation device 1 may include a unit mount 70.
  • the unit mount 70 may be provided so that at least one mounting unit 10 is mounted.
  • the unit mount 70 is equipped with at least one mounting unit 10, and is provided to transmit the rotational force supplied from the rotational force applying unit 50 to each of the mounting units 10.
  • the unit mount 70 may be formed in the shape of a rotating body. In this embodiment, the unit mount 70 extends in the radial direction with respect to the rotational force applying unit 50 in consideration of rotational force and gravity, and may have a shape inclined in the direction of gravity.
  • the shape of the unit mount 70 is not limited. The unit mount 70 satisfies this if it is configured to connect the rotational force applying unit 50 and the mounting unit 10 so as to transmit the rotational force of the rotational force applying unit 50 to the mounting unit 10.
  • the unit mount 70 satisfies this if it is configured to support the mounting unit 10 in a state inclined at a predetermined angle with respect to the ground, considering the combined force of rotational force and gravity.
  • a plurality of mounting units 10 are mounted on one unit mount 70, but is not limited thereto.
  • the unit mounts 70 divided into a plurality are radially arranged, and each of the mounting units 10 may be mounted on a plurality of unit mounts 70 arranged radially.
  • the bioenvironmental simulation device 1 may include a hydraulic sensor (not shown), a pressure sensor 82a, and an acceleration sensor 82b.
  • a hydraulic sensor (not shown) is provided to sense the pressure due to the flow rate of the culture fluid flowing by the first and second supply units of the culture fluid flow device 60. By controlling the flow rate of the culture medium, as described later, the shear force applied to the cells to be measured can be adjusted.
  • the pressure sensor 82a and the acceleration sensor 82b are provided to sense the pressure and acceleration of the rotational force of the rotational force applying unit 50.
  • the pressure sensor 82a may be mounted to the mounting unit 10 through a sensor mounting hole 12c (see FIGS. 3 and 6) formed below the unit body 12 described later.
  • the results measured by the hydraulic sensor, the pressure sensor 82a, and the acceleration sensor 82b may be transmitted to the storage unit through wireless communication.
  • the result values transmitted to the storage unit may be output to the output unit 94 or transmitted to a user terminal through wireless communication.
  • FIG. 4 is a perspective view of a mounting unit and a pressure sensor of a bioenvironmental simulation device according to an embodiment of the present invention
  • FIG. 5 is an exploded perspective view of a mounting unit and a pressure sensor of a bioenvironmental simulation device according to an embodiment of the present invention.
  • 6 is a view showing a cross-section of the mounting unit of the bio-environment simulation apparatus according to an embodiment of the present invention and the flow of the culture medium
  • FIG. 7 shows a lower portion of the mounting unit of the bio-environment simulation apparatus according to an embodiment of the present invention It is one drawing.
  • the mounting unit 10 may include a unit body 12 having an opening 12a formed on one side and a body cover 14 that opens and closes the opening 12a.
  • a cell to be measured and a separation membrane 22 are disposed inside the unit body 12, and a space through which the culture medium can flow may be formed. Since the body cover 14 is coupled to the unit body 12, an inner space 12b may be formed therein.
  • the unit body 12 and the body cover 14 may include first and second transmission members 16a, 16b, and FIG. 6, respectively.
  • the first and second permeable members 16a and 16b may be configured such that the culture solution does not pass and air can pass therethrough.
  • the first and second permeable members 16a and 16b have their inner surfaces connected to the inner space 12b so that air passing through the first and second permeable members 16a and 16b flows into the inner space 12b. You can.
  • the first transmission member 16a may be exposed to the outside through a through hole (16d, see FIG. 7) formed in the lower portion of the unit body 12, the second transmission member 16b of the body cover 14 It can be exposed to the outside.
  • the cells to be measured can breathe through the air flowing in and out through the permeable members 16a and 16b, and the culture medium therein can be prevented from leaking to the outside.
  • the type of the transmissive members 16a, 16b is not limited.
  • the transmissive members 16a and 16b may include polydimethylsiloxane (PDMS).
  • PDMS polydimethylsiloxane
  • the transmission members 16a and 16b are illustrated as members having a predetermined thickness, but are not limited thereto.
  • the transmissive members 16a, 16b may be composed of at least one film.
  • the mounting unit 10 may include a separation member 20.
  • the separating member 20 is provided to divide the inner space 12b formed therein.
  • the separation member 20 may be provided to divide the inner space 12b into a first space 32 and a second space 42 as shown in FIG. 6.
  • the mounting unit 10 may include a first mounting portion 30 forming a first space 32 and a second mounting portion 40 forming a second space 42.
  • the first and second mounting portions 30 and 40 may be divided by the separation member 20.
  • the second mounting portion 40 may be disposed outside the first direction W1 with respect to the first mounting portion 30.
  • the first direction W1 may mean a combined force direction between rotational force and gravity.
  • the separation member 20 may include a separation membrane (membrane, 22).
  • One surface of the separator 22 may face the first space 32, and the other surface of the separator 22 may be configured to face the second space 42. That is, the first and second spaces 32 and 42 may be partitioned by the separation membrane 22.
  • the separator 22 may be formed on one surface and the other surface, and may include first and second cell seating surfaces 22a and 22b on which cells are seated. Cells may be seated on the first and second cell seating surfaces 22a and 22b of the separator 22, and may be configured to cause interaction. That is, the first cell to be measured disposed on the first cell seating surface 22a and the second cell to be measured disposed on the second cell seating surface 22b may interact through the separation membrane. Cells disposed on the first and second cell seating surfaces 22a and 22b may be the same cell or cells of different types. The first and second cell seating surfaces 22a and 22b may be disposed to face the first space 32 and the second space 42, respectively.
  • the first and second cell seating surfaces 22a and 22b may be one configuration of the first and second mounting portions 30 and 40, respectively.
  • the first and second target cells to be seated on the first and second cell seating surfaces 22a and 22b may be subjected to shear force in the flow direction of the first and second culture medium by the flow of the first and second culture medium, respectively.
  • the flow direction of the first and second culture fluid may be the second direction W2 perpendicular to the first direction W1.
  • the separation member 20 may include a separation membrane mounting member 24 formed along the periphery of the separation membrane 22 so that the separation membrane 22 can be mounted inside the unit body 12.
  • the separation membrane mounting member 24 has a separation membrane 22 disposed therein, and an outer surface thereof may be mounted on the inner surface of the unit body 12.
  • the mounting unit 10 may include a first inlet 34, a first outlet 36, a second inlet 44, and a second outlet 46.
  • the first inlet 34, the first outlet 36, the second inlet 44, and the second outlet 46 may be arranged in a second direction W2 perpendicular to the first direction W1. .
  • Shear force can be applied in two directions.
  • the inlets and outlets are disposed in the second direction, it is possible to minimize the offset of the pressure and shear force by the rotational force.
  • the first inlet 34 and the first outlet 36 may be provided to flow in and out of the first culture medium.
  • the first inlet 34 and the first outlet 36 may form a first flow passage 66a passing through the first space 32 together with the first mounting portion 30. Since the first inlet 34 and the first outlet 36 are disposed in the second direction W2, the first flow path 66a may also be formed in the second direction W2.
  • the first culture medium stored in the first culture medium storage unit 62a may be introduced into the first inlet 34 at a flow rate preset by the first supply unit 64a. The first culture medium flowing into the first inlet 34 moves along the first flow path 66a, exerts a shear force on the first measurement target cell and can be discharged to the first outlet 36.
  • the second inlet 44 and the second outlet 46 may be provided to allow the second culture medium to flow in and out.
  • the second inlet 44 and the second outlet 46 may form a second flow path 66b passing through the second space 42 together with the second mounting portion 40. Since the second inlet 44 and the second outlet 46 are disposed in the second direction W2, the second flow path 66b may also be formed in the second direction W2.
  • the second culture solution stored in the second culture solution storage part 62b may be introduced into the second inlet 44 at a predetermined flow rate by the second supply part 64b.
  • the second culture medium flowing into the second inlet 44 moves along the second flow path 66b, exerts shear force on the second measurement target cell, and can be discharged to the second outlet 46.
  • the control unit may control the speed at which the rotational force applying unit 50 rotates the rotating shaft, so as to adjust the pressure applied to the cells mounted on the mounting unit 10.
  • the control unit independently controls the flow rates of the first and second culture fluids discharged from the culture fluid flow device 60, to be applied to cells to be measured by the first and second culture fluids passing through the first and second spaces 32 and 42. Shear force can be controlled.
  • control unit based on the type of the cell, the appropriate pressure and the appropriate shear force conditions matched to the type of the cell, the pressure and shear force satisfying the appropriate pressure condition and the appropriate shear force condition to be applied to the cell Can be. That is, the control unit may calculate the speed of the circular motion of the mounting unit 10 that satisfies the appropriate pressure condition and provide it to the rotation force applying unit 50, and discharge the first and second culture fluid that satisfies the appropriate shear force condition. The speed can be calculated and provided to the culture fluid flow device 60.
  • the control unit may include a computing device such as a microprocessor.
  • the input unit 92 may receive necessary information such as the type of cell from a user of the bioenvironment simulation device 1.
  • the database (not shown) may store information necessary for the operation of the bioenvironmental simulation device 1 such as appropriate pressure conditions and proper shear force conditions determined for each cell type and stored according to each cell type.
  • the output unit 94 may provide the user with information necessary for the operation of the bioenvironment simulation apparatus 1 (for example, rotation speed of the mounting unit 10, flow rate information of the culture medium, etc.).
  • the input unit 92 and the output unit 94 may be provided to be exposed to the outside of the device body, and the control unit and the database may be provided inside the device body, respectively.
  • the input unit 92 may include a keypad for receiving input of more specific information from the user (eg, blood pressure setting value, blood flow rate, proper pressure condition to be stored in the database, proper shear force condition, etc.).
  • the output unit 94 may include a visual output device such as a display, or an acoustic output device such as a speaker.
  • the database may be implemented through a computer readable recording medium, and examples of such a computer readable recording medium include magnetic media such as hard disks, floppy disks, and magnetic tapes, and optical recording media such as CD-ROMs and DVDs. and hardware devices specially configured to store and execute program instructions such as (optical media), magneto-optical media (floptical disk), and flash memory (flash memory).
  • a computer readable recording medium include magnetic media such as hard disks, floppy disks, and magnetic tapes, and optical recording media such as CD-ROMs and DVDs.
  • hardware devices specially configured to store and execute program instructions such as (optical media), magneto-optical media (floptical disk), and flash memory (flash memory).
  • Proper pressure and proper shear force conditions stored in the database can be determined to include various information. For example, an appropriate pressure and an appropriate shear force condition may be determined based on pressure and shear force within a range in which a cell to be tested can survive for a predetermined threshold time over a predetermined threshold probability. This is because proper pressure and proper shear force conditions that ensure a survival rate above a certain level may be different for each cell. Based on the proper pressure and proper shear force conditions, the control unit may adjust the pressure and shear force within a range matched to the type of the test target cell input through the input unit 92 to be applied to the test target cell.
  • the control unit when the input unit 92 receives the blood pressure and blood flow rate set values from the user, the control unit is present in the body where the cells to be tested have blood pressure and blood flow rate equal to the blood pressure and blood flow rate set values.
  • the values of the actual pressure and the shear force which are the pressure and shear force applied to the cells under test, are calculated, and the rotation force application unit 50 and the culture solution are applied so that the pressure and shear forces equal to the values of the actual pressure and shear force are applied to the cells under test.
  • the flow device 60 can be controlled.
  • the control unit based on the entered information, the rotational speed and culture medium of the mounting unit 10 Will automatically determine the flow rate.
  • the cells to be measured are seated on the first and second cell seating surfaces 22a and 22b of the separation membrane 22 and the mounting unit 10 is mounted on the unit mount 70.
  • the mounting unit 10 can be rotated at a calculated circular motion speed, and the culture fluid can be controlled to circulate at the calculated flow rate.
  • the rotational force can be transmitted to the first and second cell seating surfaces 22a and 22b of the mounting unit 10 through the rotational force applying unit 50.
  • the first and second cell seating surfaces 22a and 22b of the mounting unit 10 may be rotated at a predetermined rotational speed.
  • the mounting unit 10 is circularly moved by the rotational force applying unit 50, so that pressure by the rotational force can be applied to the first and second cell seating surfaces 22a and 22b.
  • first and second culture fluid may pass through the first and second flow paths 66a and 66b having the first and second cell seating surfaces 22a and 22b at a predetermined flow rate. Through this, shear force can be applied to the cells to be measured seated on the first and second cell seating surfaces 22a and 22b.
  • Either one of the pressure due to rotation and the shear force caused by the first and second culture fluid may be applied to the cells to be measured first, or simultaneously.
  • the unit mount 170 may include a leg support portion 171 divided into a plurality, and a mount leg 172 rotatably provided on the leg support portion 171.
  • the plurality of leg support portions 171 are connected to the rotation force applying portion 50 and are provided to rotate about the rotation axis when the rotation force is generated by the rotation force applying portion 50.
  • the plurality of mount legs 172 may be rotatably coupled to the plurality of leg supports 171, respectively.
  • the plurality of mount legs 172 may be configured to be radially disposed from the rotation force applying unit 50.
  • Each of the mounting units 10 may be mounted to the plurality of mount legs 172 that are radially disposed with respect to the rotation force applying unit 50.
  • a plurality of mount legs 172 the direction of the combined force with gravity varies depending on the strength of the rotational force applied from the rotational force applying unit 50, and when the rotational force increases with the mounting unit 10, the angle formed with the ground is also small. It can be configured to spread. Through this configuration, it is possible to apply pressure in the direction perpendicular to the first and second cell seating surfaces 22a and 22b on which the cells arranged on the mounting unit 10 are seated.
  • the plurality of mount legs 172 may operate the mounting unit 10 up and down as shown in the R direction in FIG. 8 according to the magnitude of the rotational force generated by the rotational force applying unit 50.
  • the plurality of unit mounts 70 and the plurality of mounting units 10 gradually open parallel to the ground. That is, the mount leg 172 and the mounting unit 10 mounted on the mount leg 172 may be located at a higher position than when the rotational force is a constant speed.
  • the plurality of unit mounts 70 and the plurality of mounting units 10 gradually narrow in a direction perpendicular to the ground. That is, the mount leg 172 and the mounting unit 10 mounted to the mount leg 172 may be located below the rotational force when the constant speed.
  • the mount leg 172 is rotatably coupled to the leg support 171, and the leg support 171 has been described as being connected to the rotational force applying unit 50.
  • the present invention is not limited thereto, and the mount leg 172 may be directly and rotatably coupled to the rotation force applying unit 50. That is, if the mounting unit 10 is configured by the mount leg 172 to vary the angle with the ground according to the strength of the rotational force generated by the rotational force applying unit 50, this is satisfied.
  • a separate circulation tube is not illustrated in FIG. 8, like the circulation tubes in FIGS. 1 to 3 described above, a plurality of mounting units 10 may be connected, or may be connected to the culture fluid flow device 60.

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Abstract

Un dispositif de simulation bioenvironnementale de la présente invention comprend: au moins une unité de support sur laquelle des cellules à mesurer sont placées de manière stable; une partie d'application de force de rotation pour faire tourner l'unité de support de façon à appliquer une force de rotation aux cellules à mesurer, qui ont été placés de façon stable sur l'unité de support; et un dispositif d'écoulement de fluide de culture qui est configuré pour permettre à un fluide de culture de s'écouler à travers l'unité de support, et fait circuler le fluide de culture pour appliquer une force de cisaillement aux cellules à mesurer.
PCT/KR2019/017388 2018-12-10 2019-12-10 Procédé et dispositif de simulation bioenvironnementale WO2020122556A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP19894508.1A EP3896147A4 (fr) 2018-12-10 2019-12-10 Procédé et dispositif de simulation bioenvironnementale
US17/054,999 US11530377B2 (en) 2018-12-10 2019-12-10 Bioenvironmental simulation device and method

Applications Claiming Priority (4)

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US201862777502P 2018-12-10 2018-12-10
US62/777,502 2018-12-10
KR10-2019-0163783 2019-12-10
KR1020190163783A KR102371708B1 (ko) 2018-12-10 2019-12-10 생체환경모사장치 및 방법

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20100088297A (ko) * 2009-01-30 2010-08-09 한국과학기술원 세포배양 복합자극챔버와 이를 이용한 세포배양장치
KR20130120792A (ko) * 2012-04-26 2013-11-05 한국과학기술원 전단응력과 전기장 및 바닥의 강성조절이 가능한 미세유체 세포배양장치
JP2015073468A (ja) * 2013-10-08 2015-04-20 独立行政法人産業技術総合研究所 細胞培養装置および細胞培養方法
US9500642B2 (en) * 2012-04-18 2016-11-22 Hemoshear, Llc In vitro model for pathological or physiologic conditions
KR20180103692A (ko) * 2017-03-10 2018-09-19 서울대학교산학협력단 회전력을 이용한 생체 환경 모사 장치 및 방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20100088297A (ko) * 2009-01-30 2010-08-09 한국과학기술원 세포배양 복합자극챔버와 이를 이용한 세포배양장치
US9500642B2 (en) * 2012-04-18 2016-11-22 Hemoshear, Llc In vitro model for pathological or physiologic conditions
KR20130120792A (ko) * 2012-04-26 2013-11-05 한국과학기술원 전단응력과 전기장 및 바닥의 강성조절이 가능한 미세유체 세포배양장치
JP2015073468A (ja) * 2013-10-08 2015-04-20 独立行政法人産業技術総合研究所 細胞培養装置および細胞培養方法
KR20180103692A (ko) * 2017-03-10 2018-09-19 서울대학교산학협력단 회전력을 이용한 생체 환경 모사 장치 및 방법

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