WO2015143743A1 - 一种细胞培养与实验装置 - Google Patents

一种细胞培养与实验装置 Download PDF

Info

Publication number
WO2015143743A1
WO2015143743A1 PCT/CN2014/075210 CN2014075210W WO2015143743A1 WO 2015143743 A1 WO2015143743 A1 WO 2015143743A1 CN 2014075210 W CN2014075210 W CN 2014075210W WO 2015143743 A1 WO2015143743 A1 WO 2015143743A1
Authority
WO
WIPO (PCT)
Prior art keywords
compartment
central
culture
dispensing
distribution
Prior art date
Application number
PCT/CN2014/075210
Other languages
English (en)
French (fr)
Inventor
崔金明
曾诗杰
艾澈熙
黄建东
杜如虚
Original Assignee
广州中国科学院先进技术研究所
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 广州中国科学院先进技术研究所 filed Critical 广州中国科学院先进技术研究所
Priority to EP14887546.1A priority Critical patent/EP3124595B1/en
Priority to US14/434,661 priority patent/US20170130183A1/en
Publication of WO2015143743A1 publication Critical patent/WO2015143743A1/zh
Priority to US15/275,503 priority patent/US10407656B2/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/42Integrated assemblies, e.g. cassettes or cartridges
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/34Internal compartments or partitions
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/40Manifolds; Distribution pieces
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/04Filters; Permeable or porous membranes or plates, e.g. dialysis
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M35/00Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/02Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/36Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/46Means for regulation, monitoring, measurement or control, e.g. flow regulation of cellular or enzymatic activity or functionality, e.g. cell viability

Definitions

  • the invention relates to the field of biological and genetic engineering experimental devices, and in particular to a cell culture and experimental device.
  • Manipulating cells by chemical, electrical, or other physical means, such as introduction of genetic material such as plasmids or oligonucleotides;
  • the present invention provides a miniaturized cell culture and experimental device that can replace a human hand operation, can complete a variety of experimental projects, save time and labor, and avoid waste of experimental raw materials.
  • a cell culture and experimental device including a central distribution compartment, a culture compartment, a treatment compartment, a central distribution compartment and a culture compartment, and a central distribution compartment.
  • a conduit for inter-liquid transfer between the processing compartments a central dispensing compartment having a dispensing chamber and a piston movable back and forth within the dispensing chamber to change the working volume of the dispensing chamber, the central dispensing compartment being disposed at the bottom end of the dispensing chamber
  • the central distribution compartment, the culture compartment and the treatment compartment are separately arranged, and the central distribution compartment forms a plurality of installation surfaces which can be connected to the culture compartment or the processing compartment around the distribution valve, and the central distribution
  • the compartment is provided with a central pipe leading from the distribution valve to each mounting surface, and the distribution valve comprises a central cylindrical hole provided at the bottom end of the distribution chamber and a central valve core inserted into the central cylindrical hole and rotatable in the central cylindrical hole, the central valve A central flow passage is provided on the core, and the central flow passage can open the distribution chamber and any central conduit when the central spool is rotated.
  • the culture compartment comprises a culture chamber formed by a cylindrical outer wall and a plug provided at the front end of the outer wall, and a multi-directional valve disposed at the rear end of the outer wall, the plug is provided with a gas hole, and the multi-directional valve
  • the utility model comprises a first standard shape block which can be connected with the mounting surface and is provided with a cylindrical hole and a pipe, and a first valve core which is inserted into the cylindrical hole and can rotate in the cylindrical hole, and the first standard shape block is provided with a first connector,
  • the first valve core is provided with a first flow channel, and the first flow channel can conduct the first connector and the culture cavity through the pipeline when the first valve core rotates, or open the first connector and the distribution valve, or conduct the culture cavity And distribution valve.
  • the outer side of the outer wall is sleeved with a sleeve, and a cavity is formed between the sleeve and the outer wall, and the front and rear ends of the sleeve form an outlet and an inlet that are electrically connected to the cavity, and the cavity is provided with a spiral.
  • the partition wall forms a passage that surrounds the outer wall and connects the outlet and the inlet.
  • a spiral conduit is provided around the outer wall, and the inner diameter of the spiral conduit is smaller than the outer diameter of the culture chamber.
  • the processing compartment comprises an electrical processing compartment, the electrical processing compartment comprising a second standard shaped block provided with a pipe and connectable to the mounting surface, the middle of the second standard shaped block being in the middle of the pipe
  • Two electrodes are arranged on the side, and the outer ends of the two electrodes are provided with an electrical connector that can be connected to an external power source or a measuring device.
  • An insulating spacer is arranged between the two electrodes in the pipe, and the insulating spacer forms a control liquid flow. The protrusion of the pipe.
  • the processing compartment comprises a first filtering compartment
  • the first filtering compartment comprises a third standard shape block provided with a pipe and connectable to the mounting surface
  • the third standard shape block is provided
  • the pipe is divided into a front and a rear filter device
  • the filter device comprises a filter membrane and a porous member disposed on the rear side of the filter membrane
  • the third standard shape block comprises a front half portion and a rear half portion which can be assembled into one body, the front half and the rear portion
  • An inner cavity in which the filter device is placed is formed between the half portions, and the front half portion forms a spiral first guide groove at an end surface close to the filter film, and the first guide groove forms a first port for external liquid injection on the side of the front half portion.
  • the processing compartment comprises a second filtering compartment
  • the second filtering compartment comprises a fourth standard shape block provided with a pipe and connectable to the mounting surface, and the interior of the fourth standard shape block is formed
  • the filter inner cavity is connected to the filter cavity, and the end of the filter inner cavity is provided with a plug which is sealed and connected with the fourth standard shape block and has a built-in pipe.
  • the inner end of the plug has a fiber filter protruding into the filter cavity, the fourth standard
  • the side wall of the shaped block is provided with a second port that is in communication with the filtering lumen, and the second port is introduced tangentially into the filtering lumen.
  • the inner wall of the filtering inner cavity is provided with a spiral second guiding groove, and the second guiding groove is connected to the second port and disposed around the fiber filter.
  • the processing compartment comprises a cell density measuring compartment, the cell density measuring compartment comprising a fifth standard shape block provided with a pipe and connectable to the mounting surface, and the fifth standard shape block is provided with a lateral direction
  • the light channel penetrating the pipe is provided with a light source and a photosensitive element at both ends of the light channel, and a transparent waveguide element is disposed between the light source and the photosensitive element on both sides of the pipe.
  • the central distribution compartment is provided with a light channel transversely penetrating the distribution cavity, and the two ends of the light channel are respectively provided with a light source and a photosensitive element, and the light source and the photosensitive element are on both sides of the distribution cavity A transparent waveguide element is provided.
  • the present cell culture and experimental apparatus comprises at least one culture compartment, a central distribution compartment including a piston and a dispensing valve, at least one processing compartment, and a series of liquid transport between the compartments Pipeline.
  • the cells When used, the cells first grow in the culture compartment.
  • the cell suspension can be transferred from the culture compartment to the processing compartment by selecting a dispensing valve passage and moving the piston within the dispensing chamber. Further processing in the processing compartment includes optical density measurement, cell and culture separation, conductivity measurement, electrical conversion, temperature rise, temperature reduction, and electromagnetic radiation.
  • the present invention provides a miniaturized device integrating the central distribution compartment, the culture compartment and the processing compartment, thereby ensuring the completion of cell culture and various experimental items, and replacing the manual operation, saving Time and manpower, avoiding the waste of experimental raw materials, while reducing the exposure of experimental personnel to harmful substances.
  • FIG. 1 is a schematic view showing the basic structure of an embodiment of the present invention.
  • FIG. 2 is a schematic structural view of a distribution valve according to an embodiment of the present invention.
  • Figure 3 is a schematic view showing the structure of the valve core when it is turned to the position I in the embodiment of the present invention
  • Figure 4 is a schematic view showing the structure of the valve core when it is turned to position II in the embodiment of the present invention
  • Figure 5 is a schematic view showing the structure of the valve core when it is turned to position III in the embodiment of the present invention.
  • Figure 6 is a schematic view showing the structure of the valve core when it is turned to the position III' in the embodiment of the present invention.
  • Figure 7 is a schematic view showing the structure of the valve core when it is turned to the position IV in the embodiment of the present invention.
  • Figure 8 is a cross-sectional view taken along line A-A of Figure 1;
  • Figure 9 is a cross-sectional view taken along line B-B of Figure 8.
  • Figure 10 is a schematic view showing the structure of the outer wall surrounded by the spiral conduit in the embodiment of the present invention.
  • FIG. 11 is a schematic structural view of an electrical treatment compartment in an embodiment of the present invention.
  • Figure 12 is a cross-sectional view taken along line C-C of Figure 11;
  • Figure 13 is a schematic structural view of a first filter compartment in an embodiment of the present invention.
  • Figure 14 is a cross-sectional view taken along line D-D of Figure 13;
  • Figure 15 is a schematic view showing the explosion structure of the filtration compartment in the embodiment of the present invention.
  • Figure 16 is a schematic view showing the structure of a first embodiment of a second filter compartment in the present invention.
  • Figure 17 is a cross-sectional view taken along line E-E of Figure 16;
  • Figure 18 is a schematic view showing the structure of a second embodiment of the second filter compartment in the present invention.
  • Figure 19 is a schematic view showing the structure of a first embodiment of a cell density measuring compartment in the present invention.
  • Figure 20 is a schematic view showing the structure of a second embodiment of a cell density measuring compartment in the present invention.
  • Figure 21 is a schematic view showing the concept of using a general shape as a standard shape block in the present invention.
  • Figure 22 is a schematic view showing the structure of a composite processing compartment in the present invention.
  • the present invention provides a cell culture and experimental apparatus comprising a central distribution compartment 1, a culture compartment 2, a treatment compartment 3, a central distribution compartment 1 and a culture compartment 2, and a conduit 4 for liquid transfer between the central dispensing compartment 1 and the processing compartment 3, the central dispensing compartment 1 having a dispensing chamber 11 and a piston 12 movable back and forth within the dispensing chamber 11 to change the working volume of the dispensing chamber 11
  • a distribution valve 13 that controls the distribution chamber 11 to communicate with either of the conduits 4 is provided at the bottom end of the distribution chamber 11 in the central distribution compartment 1.
  • the central dispensing compartment 1, the culture compartment 2 and the processing compartment 3 are arranged separately, and the central dispensing compartment 1 forms three mounting faces around the dispensing valve 13 that connect the culture compartment 2 or the processing compartment 3.
  • the central distribution compartment 1 is provided with three central ducts 14 leading from the distribution valve 13 to the three mounting faces, the distribution valve 13 comprising a central cylindrical bore 131 provided at the bottom end of the dispensing chamber 11 and inserted into the central cylindrical bore 131 and
  • the central spool 132 is rotated in the central cylindrical bore 131.
  • the central spool 132 is provided with a central flow passage 133.
  • the central flow passage 133 can open the distribution chamber 11 and any central conduit 14 when the central spool 132 rotates.
  • the central spool 132 of the dispensing valve 13 has a projection 134 at one end and a retaining member 135 (such as a Seeger snap ring or coil spring) at the other end for securing the central spool 132 in a particular axial direction of the central cylindrical bore 131. on.
  • the fixing element 135 can also be used in place of the projection 134 for fixing the axial direction.
  • the central flow passage 133 on the central spool 132 can have a different shape.
  • the central flow passage 133 can pass through the central spool 132 for connecting the central conduits 14 that are opposite the ends; the central flow passage 133 is located at the outer periphery of the cylindrical spool 132 for connecting adjacent central conduits 14.
  • the angle between adjacent central ducts 14 is 90 degrees.
  • Two central elastic sealing members 136 are provided on the central spool 132 on both sides of the central flow passage 133 for preventing liquid from leaking along the long axis of the central spool 132.
  • FIG. 3 to 7 illustrate four working positions of the dispensing valve 13.
  • the central spool 132 When the central spool 132 is turned to position I, the culture compartment 2 is connected to the dispensing chamber 11.
  • the treatment compartment 3 communicates with the central conduit 14 below and can rely on an external pump to deliver liquid.
  • the central spool 132 When the central spool 132 is turned to position III, the culture compartment 2 is connected to the processing compartment 3, and the distribution chamber 11 is connected to the central duct 14 below. It should be noted that at position III, if it is not desired to connect the culture compartment 2 to the treatment compartment 3, position III can be changed to position III'. Since the dispensing chamber 11 is different in diameter from the central duct 14, the dispensing chamber 11 can be connected to the lower central duct 14 while the culture compartment 2 and the processing compartment 3 remain closed.
  • the piston 12 is inserted into the dispensing chamber 11 in the central dispensing compartment 1 and is movable back and forth.
  • the piston 12 is coupled to the linear drive (not shown) by the rigid member 121 and is coupled to the resilient member 122.
  • the elastic member 122 is attached to the front end of the rigid member 121 and is axially movable along the dispensing chamber 11. This design is commonly used in syringes and syringe pumps, and has three advantages for the device of the present invention:
  • the piston 12 can clean the inner wall while moving along the inner wall of the dispensing chamber 11. This self-cleaning feature eliminates the need for additional cleaning steps, so the same central dispensing compartment 1 can be used when handling various types of liquids;
  • dispensing valve 13 is directly connected to the dispensing chamber 11, which minimizes the amount of residual liquid between the dispensing chamber 11 and the dispensing valve 13 when performing different steps.
  • the culture compartment 2 includes a culture chamber 23 formed of a cylindrical outer wall 21 and a plug 22 provided at the front end of the outer wall 21, and a multi-directional valve 24 provided at the rear end of the outer wall 21, and the plug 22 is provided. There is a vent 221, and the plug 22 is sealed to the outer wall 21 by the second elastic sealing member 222.
  • the multi-way valve 24 and the distribution valve 13 are of similar design, including a first standard shape block 241 connectable to the mounting surface and provided with a cylindrical bore and conduit 4, and a first spool that is inserted into the cylindrical bore and rotatable within the cylindrical bore 242, the first standard shape block 241 is provided with a first connector 243, the first valve core 242 is provided with a first flow channel 244, the first flow channel 244 can isolate the culture cavity 23 when the first valve core 242 rotates, or The culture chamber 23 is in communication with the dispensing valve 13 or is connected to the first connector 243 via a conduit 4. If air is introduced into the culture chamber 23 from the first connector 243, the generated bubbles will supply oxygen to the cells in the culture chamber 23 while stirring and mixing the culture solution.
  • a sleeve 25 is formed on the outer side of the outer wall 21, and a cavity 26 is formed between the sleeve 25 and the outer wall 21.
  • the front and rear ends of the sleeve 25 form an outlet 251 which is electrically connected to the cavity 26. Entrance 252.
  • the formed cavity 26 can pass into a cooled or heated liquid that exits the cavity 26 through the outlet 251 and the inlet 252.
  • a spiral partition wall may be incorporated in the cavity 26 to form a passage around the outer wall 21 and connecting the outlet 251 and the inlet 252 to direct liquid flow (not shown).
  • FIG. 10 Another alternative to heating or cooling the culture chamber 23 is shown in Fig. 10: the outer wall 21 surrounded by the helical conduit 27, the heating or cooling liquid running inside the helical conduit 27.
  • the inner diameter of the helical conduit 27 is slightly smaller than the outer diameter of the culture chamber 23 such that the helical conduit 27 will abut the outer wall 21. When it is desired to remove the helical conduit 27, it is slightly relaxed to increase its inner diameter.
  • the treatment compartment 3 provided in the present invention includes an electrical treatment compartment, a filtration compartment, and a cell density measurement compartment.
  • the electrical processing compartment includes a second standard shape block 311 provided with a duct 4 and connectable to the mounting surface.
  • the middle portion of the second standard shape block 311 is disposed opposite to both sides of the duct 4.
  • Two electrodes 312, the outer ends of the two electrodes 312 are provided with an electrical connector 313 that can be connected to an external power source.
  • the second standard shape block 311 is made of an electrically insulating material, and the cell suspension can be treated under alternating current, direct current, or short instantaneous current or voltage.
  • the power source is connected to the electrode 312 through the electrical connector 313, and a certain volume of the cell suspension will be in an electric field between the two electrodes 312, continuously vibrating the cell suspension.
  • the frequency of the shock matches the flow rate of the cell suspension.
  • an insulating spacer 314 is provided between the two electrodes 312 in the duct 4, and the insulating spacer 314 forms a projection that controls the flow of liquid through the duct 4.
  • the filter compartment provided by the present invention comprises two designs of a first filter compartment and a second filter compartment.
  • the first filtering compartment includes a third standard shape block 321 provided with a pipe 4 and connectable to the mounting surface, and the third standard shape block 321 is provided with a pipe 4
  • the filter device of the front and rear stages includes a filter membrane 322 and a porous member 323 disposed on the rear side of the filter membrane 322.
  • the third standard shape block 321 includes a front half portion 324 and a rear half portion 325 that can be assembled into one body. An inner cavity in which the filter device is placed is formed between the front half 324 and the rear half 325.
  • the front half 324 forms a spiral first guide groove 326 at the end surface of the filter membrane 322.
  • the first guide groove 326 is formed on the side of the front half 324.
  • the cell suspension flows through the membrane 322 and the porous member 323 through the conduit 4, thereby depositing the cells on the residual liquid surface of the membrane 322.
  • the filter membrane 322 When the filter membrane 322 is replaced, it can be performed by disassembling the front half 324 and the rear half 325. After filtration, cell resuspension can be achieved in two ways:
  • Fresh liquid can be injected from the first port 327, and the spiral first channel 326 will direct fresh liquid to flow on the residual liquid surface of the filter membrane 322.
  • the first port 327 needs to be connected to the valve and remain closed during the filtration process. At this point the liquid in the cell suspension will pass through the filter membrane 322 and the cells will remain on the residual liquid surface of the filter membrane 322.
  • the second filter compartment includes a fourth standard shape block 331 provided with a duct 4 and connectable to the mounting surface.
  • the interior of the fourth standard shape block 331 forms a filter cavity 332 that is electrically connected to the duct 4.
  • the end of the filtering inner cavity 332 is provided with a plug 333 which is sealingly connected with the fourth standard shape block 331 and has a built-in pipe 4, and the inner end of the plug 333 is provided with a fiber filter 334 extending into the filtering inner cavity 332, the fourth standard
  • the side wall of the shape block 331 is provided with a second port 335 that is in communication with the filter lumen 332, and the second port 335 is introduced tangentially into the filter lumen 332.
  • the inner end of the plug 333 forms a cylindrical protrusion.
  • the fiber filter 334 is placed over the cylindrical projection and fixed by the resin and closed.
  • the plug 333 is integrally enclosed by the end of the filter lumen 332 by a resilient sealing element.
  • the cell suspension enters the filtration lumen 332 and flows along the outside of the fiber membrane 334.
  • the second filter compartment there are two ways to resuspend the cells outside the fiber filter 334: (1) fresh liquid is injected from the plug 333 and pressed back through the fiber filter 334; (2) fresh liquid from the second port The 335 enters the filtration lumen 332 tangentially to create a circulation that facilitates cell resuspension.
  • the inner wall of the filter inner chamber 332 is provided with a spiral second guide groove 336 which is connected to the second port 335 and surrounds the fiber filter.
  • Membrane 334 is provided.
  • the cell density measuring compartment includes a fifth standard shape block 341 provided with a duct 4 and connectable to the mounting surface, and the fifth standard shape block 341 is provided with an optical passage transversely penetrating the duct 4, two of the optical passages
  • the ends are respectively provided with a light source 342 and a photosensitive element 343, and a transparent waveguide element 344 is disposed between the light source 342 and the photosensitive element 343 on both sides of the pipe 4.
  • light emitted by the light source 342 (which may be used by the light emitting diode)
  • the transparent waveguide element 344 interacts with the cell suspension and is received by the other transparent waveguide element 344 to reach the photosensitive element 343 (phototransistor).
  • the cell density measurement of the cell suspension is then completed.
  • the cell density measuring compartment is integrally provided with the central dispensing compartment 1, i.e., a light channel transversely penetrating the dispensing chamber 11 is disposed on the central dispensing compartment 1 such that the light source 342 and the photosensitive element 343 are respectively located in the dispensing chamber.
  • a transparent waveguide member is disposed between the light source 342 and the photosensitive member 343 on both sides of the distribution chamber 11.
  • the present invention employs a standard shape block having a general shape 5 as a basis for the culture compartment 2, the central distribution compartment 1, and all the processing compartments 3.
  • the footprint of the culture compartment 2, the central dispensing compartment 1 and all of the processing compartments 3 can be considered as a multiple of this general shape 5, so that the culture compartment 2, the central distribution compartment 1 and all the processing compartments 3 are also easy to combine.
  • This design concept is reflected in Figure 21, and the general shape 5 is represented by a square.
  • the apparatus shown in Figure 21 comprises two culture compartments 2 and a central distribution compartment 1, a treatment compartment 3, and three valves.
  • the footprint of the central dispensing compartment 1 can be seen as three general shapes 5. In addition to this, the footprint of all compartments is equal to a common shape.
  • Figure 22 shows a composite processing compartment in which the electrical processing compartment and the first filtering compartment described above are combined in a standard shaped block.
  • the advantage of this combination is that the volume of the suspension of the conduit 4 is minimized.
  • the design of the universal shape 5 is matched.
  • matching holes 43 are provided in each compartment, which enable a perfect connection by means of a simple connector element 44, wherein the connector element 44 can be used with a simple cylindrical pin or flat key.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Sustainable Development (AREA)
  • Clinical Laboratory Science (AREA)
  • Analytical Chemistry (AREA)
  • Cell Biology (AREA)
  • Physics & Mathematics (AREA)
  • Electromagnetism (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

本发明公开了一种细胞培养与实验装置,用于生物和遗传工程实验装置领域,包括中央分配隔间、培养隔间、处理隔间、实现中央分配隔间与培养隔间之间以及中央分配隔间与处理隔间之间液体传送的管道,中央分配隔间内设有分配腔和可在分配腔内前后移动以改变分配腔的工作容积的活塞,中央分配隔间内在分配腔的底端设有控制分配腔与任一管道导通的分配阀。使用时,细胞在培养隔间内生长繁殖。通过分配阀以及在分配腔内移动活塞,细胞悬液可从培养隔间送到处理隔间。本发明通过上述设计,提供一种将中央分配隔间、培养隔间和处理隔间集于一体的小型化装置,使得在完成细胞培养和多种实验项目的同时,替代人手操作,节省时间和人力,避免实验原材料浪费。

Description

一种细胞培养与实验装置
技术领域
本发明用于生物和遗传工程实验装置领域,特别是涉及一种细胞培养与实验装置。
背景技术
在微生物学领域,尤其是生物工程和遗传工程等领域,研究人员利用培养的细胞进行实验操作以验证他们的理论与实验。这些基础的实验操作包括但不仅限于:
1.细胞培养,尤其是令细胞在一种或多种成分确定的液体培养基中繁殖;
2.测量细胞密度;
3.将细胞与液体培养基分离;
4.用新鲜液体将细胞重悬;
5.通过化学、电、或其它物理手段对细胞进行操作,例如引入质粒或寡核苷酸等遗传物质;
6.使用酒精或其它溶液将器械消毒灭菌;
7.用水清洗器械。
当前主流的实验流程,是依赖人手操作,小批量依次完成上述步骤。常使用的传统实验器械包括:试管、摇瓶、摇床、培养皿、比色皿、注射器、移液器、离心机、滤膜,等等。当进行多轮或多个样品的实验操作时,需要耗费大量的时间与人力。
尽管将传统器械组合成小型工厂并加入控制组件,亦能获得一定程度的自动化;但这一方案的缺陷在于,各个传统器械并非为组合而设计,相互规格不匹配,而且组合成的小型工厂对于传统的生物化学类实验室而言太大,所需的相对大量的细胞培养液也将造成实验原材料过于昂贵。
发明内容
为解决上述问题,本发明提供一种替代人手操作,能够完成多种实验项目,节省时间和人力,避免实验原材料浪费的小型化细胞培养与实验装置。
本发明解决其技术问题所采用的技术方案是:一种细胞培养与实验装置,包括中央分配隔间、培养隔间、处理隔间、实现中央分配隔间与培养隔间之间以及中央分配隔间与处理隔间之间液体传送的管道,中央分配隔间内设有分配腔和可在分配腔内前后移动以改变分配腔的工作容积的活塞,中央分配隔间内在分配腔的底端设有控制分配腔与任一管道导通的分配阀。
进一步作为本发明技术方案的改进,中央分配隔间、培养隔间和处理隔间分体设置,中央分配隔间围绕所述分配阀形成若干可连接培养隔间或处理隔间的安装面,中央分配隔间上设有由分配阀引至各安装面的中央管道,分配阀包括设在分配腔底端的中央圆柱孔和插入中央圆柱孔内并可在中央圆柱孔内转动的中央阀芯,中央阀芯上设有中央流道,中央流道在中央阀芯转动时可导通分配腔与任一中央管道。
进一步作为本发明技术方案的改进,培养隔间包括由圆筒形的外壁和设在外壁前端的塞子形成的培养腔,以及设于外壁后端的多向阀门,塞子上设有气孔,多向阀门包括可与安装面连接且设有圆柱孔和管道的第一标准形状块以及插入圆柱孔内且可在圆柱孔内转动的第一阀芯,第一标准形状块上设有第一连接器,第一阀芯上设有第一流道,第一流道在第一阀芯转动时可通过管道导通第一连接器和培养腔,或者导通第一连接器和分配阀,或者导通培养腔和分配阀。
进一步作为本发明技术方案的改进,外壁的外侧套装有袖筒,袖筒和外壁之间形成空腔,袖筒的前、后两端形成与空腔导通的出口和入口,空腔内设有螺旋状的隔墙以形成环绕外壁且连接出口和入口的通道。
进一步作为本发明技术方案的改进,围绕外壁设有螺旋状导管,螺旋状导管的内径小于培养腔的外径。
进一步作为本发明技术方案的改进,处理隔间包括电处理隔间,电处理隔间包括设有管道且可与安装面连接的第二标准形状块,第二标准形状块的中部在管道的两侧正对设有两个电极,两个电极的外端设有可与外部电源或测量器接通的电连接器,管道内在两个电极间设有绝缘隔片,绝缘隔片形成控制液体流过管道的凸起。
进一步作为本发明技术方案的改进,处理隔间包括第一过滤隔间,第一过滤隔间包括设有管道且可与安装面连接的第三标准形状块,第三标准形状块内设有将管道分为前、后两段的过滤装置,过滤装置包括滤膜和设于滤膜后侧的多孔构件,第三标准形状块包括可组装为一体的前半部和后半部,前半部和后半部间形成放置过滤装置的内腔,前半部在紧贴滤膜的端面形成螺旋形的第一导槽,第一导槽在前半部的侧面形成供外部液体注入的第一端口。
进一步作为本发明技术方案的改进,处理隔间包括第二过滤隔间,第二过滤隔间包括设有管道且可与安装面连接的第四标准形状块,第四标准形状块的内部形成与管道导通的过滤内腔,过滤内腔的末端设有与第四标准形状块密封连接且内置管道的堵头,堵头的内端设有伸入过滤内腔的纤维滤膜,第四标准形状块的侧壁设有与过滤内腔导通的第二端口,第二端口沿切向引入过滤内腔。
进一步作为本发明技术方案的改进,过滤内腔的内壁设有螺旋形的第二导槽,第二导槽与第二端口接通并围绕纤维滤膜设置。
进一步作为本发明技术方案的改进,处理隔间包括细胞密度测量隔间,细胞密度测量隔间包括设有管道且可与安装面连接的第五标准形状块,第五标准形状块上设有横向穿透管道的光通道,光通道的两端分别设有光源和光敏元件,光源和光敏元件之间在管道的两侧设有透明波导元件。
进一步作为本发明技术方案的改进,中央分配隔间上设有横向穿透分配腔的光通道,光通道的两端分别设有光源和光敏元件,光源和光敏元件之间在分配腔的两侧设有透明波导元件。
本发明的有益效果:本细胞培养与实验装置中,包含至少一个培养隔间,一个包括活塞与分配阀的中央分配隔间,至少一个处理隔间,和一系列用于隔间之间液体传送的管道。
使用时,细胞首先在培养隔间内生长繁殖。通过选择分配阀通路以及在分配腔内移动活塞,细胞悬液可从培养隔间传送到处理隔间。在处理隔间内进一步的完成包括光学密度测量、细胞与培养液分离、电导率测量、电转化、升温、降温和电磁辐射在内的处理操作。
本发明通过上述设计,提供了一种将中央分配隔间、培养隔间和处理隔间集于一体的小型化装置,保证能够完成细胞培养和多种实验项目的同时,替代了人手操作,节省了时间和人力,避免了实验原材料的浪费,同时减少实验人员暴露于有害物质的机会。
附图说明
下面结合附图对本发明作进一步说明:
图1是本发明实施例基本结构示意图;
图2是本发明实施例分配阀结构示意图;
图3是本发明实施例中阀芯转到位置I时结构示意图;
图4是本发明实施例中阀芯转到位置II时结构示意图;
图5是本发明实施例中阀芯转到位置III时结构示意图;
图6是本发明实施例中阀芯转到位置III’时结构示意图;
图7是本发明实施例中阀芯转到位置IV时结构示意图;
图8是图1中A-A处截面图;
图9是图8中B-B处截面图;
图10是本发明实施例中螺旋状导管围绕的外壁结构示意图;
图11是本发明实施例中电处理隔间结构示意图;
图12是图11中C-C处截面图;
图13是本发明实施例中第一过滤隔间结构示意图;
图14是是图13中D-D处截面图;
图15是本发明实施例中过滤隔间爆炸结构示意图;
图16是本发明中第二过滤隔间第一实施例结构示意图;
图17是是图16中E-E处截面图;
图18是本发明中第二过滤隔间第二实施例结构示意图;
图19是本发明中细胞密度测量隔间第一实施例结构示意图;
图20是本发明中细胞密度测量隔间第二实施例结构示意图;
图21是本发明中采用通用形状作为标准形状块的理念示意图;
图22是本发明中复合处理隔间结构示意图。
具体实施方式
参照图1~图22,本发明提供了一种细胞培养与实验装置,包括中央分配隔间1、培养隔间2、处理隔间3、实现中央分配隔间1与培养隔间2之间以及中央分配隔间1与处理隔间3之间液体传送的管道4,中央分配隔间1内设有分配腔11和可在分配腔11内前后移动以改变分配腔11的工作容积的活塞12,中央分配隔间1内在分配腔11的底端设有控制分配腔11与任一管道4导通的分配阀13。
参照图1,中央分配隔间1、培养隔间2和处理隔间3分体设置,中央分配隔间1围绕分配阀13形成三个可连接培养隔间2或处理隔间3的安装面,中央分配隔间1上设有由分配阀13引至三个安装面的三个中央管道14,分配阀13包括设在分配腔11底端的中央圆柱孔131和插入中央圆柱孔131内并可在中央圆柱孔131内转动的中央阀芯132,中央阀芯132上设有中央流道133,中央流道133在中央阀芯132转动时可导通分配腔11与任一中央管道14。
参照图2,分配阀13的中央阀芯132的一端有突起134,另一端有固定元件135(如Seeger卡环或盘簧),用于固定中央阀芯132在中央圆柱孔131的特定轴向上。显然,固定元件135也可以替代突起134,用于固定轴向。
中央阀芯132上的中央流道133可以有不同的形状。例如,中央流道133可以穿过中央阀芯132,用于连接两端正对的中央管道14;中央流道133位于圆柱形阀芯132的外周,用于连接相邻的中央管道14。在本实施例中,相邻的中央管道14之间的角度为90度。通过调节中央流道133的长度,可以适应小于或大于90度的夹角。
中央阀芯132上在中央流道133的两侧设有两个第一弹性密封元件136,用于防止液体沿着中央阀芯132的长轴泄漏。
图3~图7示意了分配阀13的四种工作位置。当中央阀芯132转到位置I时,培养隔间2与分配腔11相连。处理隔间3与下方的中央管道14相通,可依靠外部泵传送液体。
当中央阀芯132转到位置II时,分配腔11与处理隔间3相连,上方和下方的中央管道14则是关闭的。
当中央阀芯132转到位置III时,培养隔间2和处理隔间3相连,分配腔11和下方的中央管道14相连。应当注意在位置III时,若不希望培养隔间2和处理隔间3相连,可以将位置III换为位置III’。由于分配腔11与中央管道14的直径不同,可以让分配腔11和下方的中央管道14相连,同时培养隔间2和处理隔间3保持关闭。
当中央阀芯132转到位置IV时,中央管道14和分配腔11全部相互分隔,这可以用于装置的待机模式。
显然通过中央管道14的其它组合还可以获得其它不同特性的阀门。
本发明中,活塞12插入中央分配隔间1内的分配腔11中并可前后移动,活塞12由刚性部件121连接至线性驱动装置(图略),并连接有弹性部件122。弹性部件122附着在刚性部件121前端,并可沿分配腔11轴向运动。这种设计常用于注射器及注射泵,用于本发明装置有以下三个优点:
(i)活塞12沿着分配腔11的内壁运动的同时可清洁内壁。这种自我清洁特性免除了额外的清洗步骤,因而在处理各类液体时可以使用同一个中央分配隔间1;
(ii)可吸取或推送液体、含细胞的悬浮液、气体等等;
(iii)利用分配腔11的横截面积,活塞12的线性运动可轻松换算为体积、流量等。
此外,分配阀13直接连接于分配腔11,进行不同步骤时,这使得分配腔11和分配阀13之间残余的液体量减至最小。
参照图8、图9,培养隔间2包括由圆筒形的外壁21和设在外壁21前端的塞子22形成的培养腔23,以及设于外壁21后端的多向阀门24,塞子22上设有气孔221,塞子22利用第二弹性密封元件222而与外壁21密闭。多向阀门24与分配阀13采用类似设计,包括可与安装面连接且设有圆柱孔和管道4的第一标准形状块241以及插入圆柱孔内且可在圆柱孔内转动的第一阀芯242,第一标准形状块241上设有第一连接器243,第一阀芯242上设有第一流道244,第一流道244在第一阀芯242转动时可隔离培养腔23,或令培养腔23与分配阀13相通,又或者通过管道4与第一连接器243相连。若从第一连接器243向培养腔23内通入空气,产生的气泡将为培养腔23中的细胞提供氧气,同时搅拌混匀培养液。
为了控制细胞的代谢与生长速率,在外壁21的外侧套装有袖筒25,袖筒25和外壁21之间形成空腔26,袖筒25的前、后两端形成与空腔26导通的出口251和入口252。形成的空腔26可通入冷却或加热的液体,这些液体通过出口251和入口252出入空腔26。为了改善热传导,在空腔26中可装入螺旋状的隔墙以形成环绕外壁21且连接出口251和入口252的通道,以引导液体流动(图略)。
对培养腔23的加热或制冷的另一个方案如图10所示:由螺旋状导管27围绕的外壁21,加热或冷却液体在螺旋状导管27内部运行。螺旋状导管27的内径稍小于培养腔23的外径,这样螺旋状导管27将紧贴外壁21。当需要移除螺旋状导管27时,需将其稍微放松以增加其内径。
本发明中提供的处理隔间3包括电处理隔间、过滤隔间以及细胞密度测量隔间。其中,参照图11、图12,电处理隔间包括设有管道4且可与安装面连接的第二标准形状块311,第二标准形状块311的中部在管道4的两侧正对设有两个电极312,两个电极312的外端设有可与外部电源接通的电连接器313。具体的,第二标准形状块311由电绝缘材料制成,可将细胞悬浮液置于交流、直流、或短瞬电流或电压下处理。这可用于测量细胞悬浮液的电属性,或用于短暂改变细胞特性,如短瞬的高压脉冲可将质粒或寡核苷酸等大分子送入细胞(电转化)。使用时,电源通过电连接器313与电极312相接,一定微小体积的细胞悬浮液将处于两个电极312之间的电场,不断对细胞悬浮液进行电击。电击频率与细胞悬浮液的流速相匹配。为了避免两个电极312的意外接触,管道4内在两个电极312间设有绝缘隔片314,并且绝缘隔片314形成控制液体流过管道4的凸起。
本发明提供的过滤隔间包括第一过滤隔间和第二过滤隔间两种设计。具体的,参照图13、图14和图15,第一过滤隔间包括设有管道4且可与安装面连接的第三标准形状块321,第三标准形状块321内设有将管道4分为前、后两段的过滤装置,过滤装置包括滤膜322和设于滤膜322后侧的多孔构件323,第三标准形状块321包括可组装为一体的前半部324和后半部325,前半部324和后半部325间形成放置过滤装置的内腔,前半部324在紧贴滤膜322的端面形成螺旋形的第一导槽326,第一导槽326在前半部324的侧面形成供外部液体注入的第一端口327。使用时,细胞悬浮液经管道4流经滤膜322和多孔构件323,从而将细胞沉积在滤膜322的残余液面上。更换滤膜322时,可通过拆开前半部324和后半部325进行。过滤后,细胞的重悬可通过两种办法实现:
(i)新鲜液体可从滤膜322的反面反向压过滤膜322;
(ii)新鲜液体可从第一端口327注入,螺旋形的第一导槽326将引导新鲜液体在滤膜322的残余液面上流动。注意第一端口327需与阀门相连,并在过滤过程中保持关闭。此时细胞悬浮液中的液体将透过滤膜322,而细胞将留在滤膜322的残余液面上。
参照图16、图17,第二过滤隔间包括设有管道4且可与安装面连接的第四标准形状块331,第四标准形状块331的内部形成与管道4导通的过滤内腔332,过滤内腔332的末端设有与第四标准形状块331密封连接且内置管道4的堵头333,堵头333的内端设有伸入过滤内腔332的纤维滤膜334,第四标准形状块331的侧壁设有与过滤内腔332导通的第二端口335,第二端口335沿切向引入过滤内腔332。堵头333的内端形成圆柱状突起。纤维滤膜334套在圆柱状突起上,并由树脂固定并封闭。堵头333通过弹性密封元件整体封闭于过滤内腔332的末端。细胞悬浮液进入过滤内腔332,沿纤维滤膜334的外侧流动。通过将过滤内腔332设计成比纤维滤膜334的外径稍大,过滤内腔332与纤维滤膜334的间隔可以控制得很小。细胞沉积于纤维滤膜334外侧的同时,液体将透过纤维滤膜334并从堵头333的管道4流出。对于第二过滤隔间,有两个办法重悬纤维滤膜334外侧的细胞:(1)新鲜液体从堵头333注入并反向压过纤维滤膜334;(2)新鲜液体从第二端口335沿切向进入过滤内腔332,以产生环流有利于细胞重悬。
参照图18,作为进一步的改进,在第二过滤隔间中,过滤内腔332的内壁设有螺旋形的第二导槽336,第二导槽336与第二端口335接通并围绕纤维滤膜334设置。当重悬细胞时,新鲜液体将沿着呈螺旋形的第二导槽336流动并重悬细胞。同样,通过控制螺旋形第二导槽336的内径,它可以保持整个第二过滤隔间的微小体积。
参照图19,细胞密度测量隔间包括设有管道4且可与安装面连接的第五标准形状块341,第五标准形状块341上设有横向穿透管道4的光通道,光通道的两端分别设有光源342和光敏元件343,光源342和光敏元件343之间在管道4的两侧设有透明波导元件344。具体的,光源342(可用发光二极管)发射的光,经由透明波导元件344,与细胞悬液相互作用之后被另一透明波导元件344接收,到达光敏元件343(光电晶体管)。进而完成细胞悬浮液的细胞密度测量。
如图20所示,细胞密度测量隔间与中央分配隔间1一体设置,即在中央分配隔间1上设置横向穿透分配腔11的光通道,使得光源342和光敏元件343分别位于分配腔11的两侧的光通道内,光源342和光敏元件343之间在分配腔11的两侧设有透明波导元件。上述设计这不但减少了细胞密度测量时所需的液体量,也减少了所需的机械动作:一旦培养隔间2与中央分配隔间1建立起连接,细胞到达分配腔11后,细胞密度便可直接测量。此外,由于分配腔11具有更大的直径,因此被测量的细胞量更大,测量结果更准确。
为了让实验者能根据实验流程自由地选择隔间来安装装置,本发明中采用具有通用形状5的标准形状块作为基础应用于培养隔间2、中央分配隔间1和所有处理隔间3。培养隔间2、中央分配隔间1和所有处理隔间3的印迹都可看作是这个通用形状5的倍数,因此培养隔间2、中央分配隔间1和所有处理隔间3也易于组合成不同配置。图21所示反映了这一设计理念,通用形状5以正方形为代表。图21中所示的装置包含两个培养隔间2与中央分配隔间1,一个处理隔间3,及三个阀门。中央分配隔间1的印迹则可看作三个通用形状5。除此之外,所有隔间的印迹都等于一个通用形状。
图22所示为一复合处理隔间,由上文所描述的电处理隔间和第一过滤隔间组合在一个标准形状块中,这种组合的优点在于将管道4的悬液体积尽量缩小,同时吻合通用形状5的设计。
参照图1,为了连接两个相邻的隔间,不同隔间的管道4的外部出口将随着隔间自身边界对齐而对齐。在不同隔间管道4的外部出口周围留有凹槽41,在凹槽41内设置密封元件用于隔间之间管道4的密封,以防止液体在连接处泄漏。
为了保证两个相邻隔间完全对准,在各隔间上都设置了匹配孔洞43,它能通过简易的连接器元件44实现完美连接,其中连接器元件44可以使用简易的圆柱销或平键。
当然,本发明创造并不局限于上述实施方式,熟悉本领域的技术人员在不违背本发明精神的前提下还可作出等同变形或替换,这些等同的变型或替换均包含在本申请权利要求所限定的范围内。

Claims (11)

  1. 一种细胞培养与实验装置,其特征在于:包括中央分配隔间、培养隔间、处理隔间、实现中央分配隔间与培养隔间之间以及中央分配隔间与处理隔间之间液体传送的管道,所述中央分配隔间内设有分配腔和可在所述分配腔内前后移动以改变分配腔的工作容积的活塞,所述中央分配隔间内在分配腔的底端设有控制分配腔与任一所述管道导通的分配阀。
  2. 根据权利要求1所述的细胞培养与实验装置,其特征在于:所述中央分配隔间、培养隔间和处理隔间分体设置,所述中央分配隔间围绕所述分配阀形成若干可连接培养隔间或处理隔间的安装面,所述中央分配隔间上设有由分配阀引至各所述安装面的中央管道,所述分配阀包括设在分配腔底端的中央圆柱孔和插入所述中央圆柱孔内并可在中央圆柱孔内转动的中央阀芯,所述中央阀芯上设有中央流道,所述中央流道在中央阀芯转动时可导通分配腔与任一所述中央管道。
  3. 根据权利要求2所述的细胞培养与实验装置,其特征在于:所述培养隔间包括由圆筒形的外壁和设在外壁前端的塞子形成的培养腔,以及设于所述外壁后端的多向阀门,所述塞子上设有气孔,所述多向阀门包括可与所述安装面连接且设有圆柱孔和管道的第一标准形状块以及插入所述圆柱孔内且可在圆柱孔内转动的第一阀芯,所述第一标准形状块上设有第一连接器,所述第一阀芯上设有第一流道,所述第一流道在第一阀芯转动时可通过所述管道导通第一连接器和培养腔,或者导通第一连接器和分配阀,或者导通培养腔和分配阀。
  4. 根据权利要求3所述的细胞培养与实验装置,其特征在于:所述外壁的外侧套装有袖筒,所述袖筒和外壁之间形成空腔,袖筒的前、后两端形成与所述空腔导通的出口和入口,所述空腔内设有螺旋状的隔墙以形成环绕外壁且连接出口和入口的通道。
  5. 根据权利要求3所述的细胞培养与实验装置,其特征在于:围绕所述外壁设有螺旋状导管,所述螺旋状导管的内径小于培养腔的外径。
  6. 根据权利要求2所述的细胞培养与实验装置,其特征在于:所述处理隔间包括电处理隔间,所述电处理隔间包括设有管道且可与所述安装面连接的第二标准形状块,所述第二标准形状块的中部在管道的两侧正对设有两个电极,两个电极的外端设有可与外部电源或测量器接通的电连接器,管道内在两个电极间设有绝缘隔片,所述绝缘隔片形成控制液体流过管道的凸起。
  7. 根据权利要求2所述的细胞培养与实验装置,其特征在于:所述处理隔间包括第一过滤隔间,所述第一过滤隔间包括设有管道且可与所述安装面连接的第三标准形状块,所述第三标准形状块内设有将管道分为前、后两段的过滤装置,所述过滤装置包括滤膜和设于所述滤膜后侧的多孔构件,所述第三标准形状块包括可组装为一体的前半部和后半部,所述前半部和后半部间形成放置过滤装置的内腔,所述前半部在紧贴滤膜的端面形成螺旋形的第一导槽,所述第一导槽在前半部的侧面形成供外部液体注入的第一端口。
  8. 根据权利要求2所述的细胞培养与实验装置,其特征在于:所述处理隔间包括第二过滤隔间,所述第二过滤隔间包括设有管道且可与所述安装面连接的第四标准形状块,第四标准形状块的内部形成与管道导通的过滤内腔,过滤内腔的末端设有与第四标准形状块密封连接且内置管道的堵头,堵头的内端设有伸入所述过滤内腔的纤维滤膜,所述第四标准形状块的侧壁设有与过滤内腔导通的第二端口,所述第二端口沿切向引入过滤内腔。
  9. 根据权利要求8所述的细胞培养与实验装置,其特征在于:所述过滤内腔的内壁设有螺旋形的第二导槽,所述第二导槽与第二端口接通并围绕纤维滤膜设置。
  10. 根据权利要求2所述的细胞培养与实验装置,其特征在于:所述处理隔间包括细胞密度测量隔间,所述细胞密度测量隔间包括设有管道且可与所述安装面连接的第五标准形状块,第五标准形状块上设有横向穿透管道的光通道,光通道的两端分别设有光源和光敏元件,光源和光敏元件之间在管道的两侧设有透明波导元件。
  11. 根据权利要求1或2所述的细胞培养与实验装置,其特征在于:所述中央分配隔间上设有横向穿透分配腔的光通道,光通道的两端分别设有光源和光敏元件,光源和光敏元件之间在分配腔的两侧设有透明波导元件。
PCT/CN2014/075210 2014-03-25 2014-04-11 一种细胞培养与实验装置 WO2015143743A1 (zh)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP14887546.1A EP3124595B1 (en) 2014-03-25 2014-04-11 Apparatus for cell culture and experiment
US14/434,661 US20170130183A1 (en) 2014-03-25 2014-04-11 Device for Cell Culturing and Processing
US15/275,503 US10407656B2 (en) 2014-03-25 2016-09-26 Cell culture and experiment device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201410112722.6A CN103881911B (zh) 2014-03-25 2014-03-25 一种细胞培养与实验装置
CN201410112722.6 2014-03-25

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/275,503 Continuation US10407656B2 (en) 2014-03-25 2016-09-26 Cell culture and experiment device

Publications (1)

Publication Number Publication Date
WO2015143743A1 true WO2015143743A1 (zh) 2015-10-01

Family

ID=50951038

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2014/075210 WO2015143743A1 (zh) 2014-03-25 2014-04-11 一种细胞培养与实验装置

Country Status (4)

Country Link
US (2) US20170130183A1 (zh)
EP (1) EP3124595B1 (zh)
CN (1) CN103881911B (zh)
WO (1) WO2015143743A1 (zh)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103881911B (zh) * 2014-03-25 2015-09-09 广州中国科学院先进技术研究所 一种细胞培养与实验装置
DE102017125881B4 (de) * 2017-11-06 2019-06-19 Sartorius Stedim Biotech Gmbh Filtermodul und Verfahren zum Nachweis von Mirkoorganismen
CN109777733B (zh) * 2019-02-26 2022-02-01 中国人民解放军军事科学院军事医学研究院 微波生物效应照射装置
CN112625900B (zh) * 2020-12-17 2022-05-17 西安电子科技大学 倾斜波导谐振腔电磁辐照细胞实验装置
CN114672415B (zh) * 2022-04-08 2022-12-20 湖北明德健康科技有限公司 一种稀释装置

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002018902A1 (en) * 2000-08-25 2002-03-07 Cepheid Fluid control and processing system

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA784744B (en) * 1977-08-31 1979-08-29 C Jottier Apparatus for the treatment of fluids
WO1999042557A1 (en) * 1998-02-19 1999-08-26 Introtech Sperm analysis system
JP2004069395A (ja) * 2002-08-02 2004-03-04 Nec Corp マイクロチップ、マイクロチップの製造方法および成分検出方法
ES2208127B1 (es) * 2002-11-28 2005-09-01 Universitat Politecnica De Catalunya Sistema modular de multiples minibiorreactores automatizados para screenning multifuncional (hts) en biotecnologia.
US8900828B2 (en) * 2006-05-01 2014-12-02 Cepheid Methods and apparatus for sequential amplification reactions
US20080026451A1 (en) * 2006-06-15 2008-01-31 Braman Jeffrey C System for isolating biomolecules from a sample
US8876765B2 (en) * 2007-05-16 2014-11-04 Smiths Medical Asd, Inc. Pump module for use in a medical fluid dispensing system
US9115340B2 (en) * 2008-08-08 2015-08-25 Agency For Science Technology & Research Microfluidic continuous flow device
CN102378945B (zh) * 2008-12-23 2015-08-05 佐马美国有限公司 柔性制造系统
US9090863B2 (en) * 2010-05-17 2015-07-28 Pall Corporation System for seeding cells onto three dimensional scaffolds
CN103370409B (zh) * 2011-01-17 2017-05-10 学校法人东京女子医科大学 细胞培养处理系统以及细胞培养处理系统的模块连接方法
CN103881911B (zh) * 2014-03-25 2015-09-09 广州中国科学院先进技术研究所 一种细胞培养与实验装置

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002018902A1 (en) * 2000-08-25 2002-03-07 Cepheid Fluid control and processing system

Also Published As

Publication number Publication date
US20170009196A1 (en) 2017-01-12
CN103881911A (zh) 2014-06-25
EP3124595A1 (en) 2017-02-01
CN103881911B (zh) 2015-09-09
US10407656B2 (en) 2019-09-10
US20170130183A1 (en) 2017-05-11
EP3124595B1 (en) 2020-04-22
EP3124595A4 (en) 2017-11-15

Similar Documents

Publication Publication Date Title
WO2015143743A1 (zh) 一种细胞培养与实验装置
TWI806116B (zh) 多槽盤培養器、用於出入培養器之內部腔室之方法及培養系統
EP0232975A2 (en) Membrane cell culturing device
US20180298319A1 (en) Interconnections of multiple perfused engineered tissue constructs and microbioreactors, multi-microformulators and applications of the same
CA2407012A1 (en) Cell and tissue culture device with enhanced culture fluid flow
WO2016064757A1 (en) Modular microfluidic system for perfused cell culture
CN107400633A (zh) 中空纤维交换器及中空纤维交换式培养系统
US20210024866A1 (en) Microfluidic control
EP1585804A4 (en) SYSTEMS, APPARATUS AND METHOD FOR CELL CULTIVATION AND STORAGE
JP6857123B2 (ja) 細胞ベースの相互作用を調べるためのマイクロ流体プラットフォーム
US20220025308A1 (en) Tissue culture platform having multiple well chambers fluidically coupled via microfluidic channels and selector valves
CN113249215B (zh) 多腔室样品制备盒
CN112957829A (zh) 一种用于呼吸机的过滤装置
WO2022267247A9 (zh) 培养装置
JP2022516186A (ja) 細胞処理コンテナ、細胞処理システム、およびそれを使用する方法
US20130333178A1 (en) Serviceable bioreactor
JP2018502302A (ja) 疑似移動床クロマトグラフィー用弁マニホールド
WO2018097510A1 (ko) 생물반응용기
CN112958173B (zh) 一种微流控试剂盒
JP7297272B2 (ja) 細胞製造装置
CN206721192U (zh) 一种气混装置以及微生物实验器材
JP2023512310A (ja) モジュラー培養チャンバおよびウイルス不活化方法
RU185769U1 (ru) Многоканальный коннектор для подключения устройства подачи рабочей среды к микрофлюидному чипу
WO2023113186A1 (ko) 대상물 공급 장치
CN114917970B (zh) 一种微流控装置

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14887546

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

REEP Request for entry into the european phase

Ref document number: 2014887546

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2014887546

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 14434661

Country of ref document: US