CN102277298A - Culturing system of biological tissue engineering - Google Patents

Culturing system of biological tissue engineering Download PDF

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Publication number
CN102277298A
CN102277298A CN 201110185541 CN201110185541A CN102277298A CN 102277298 A CN102277298 A CN 102277298A CN 201110185541 CN201110185541 CN 201110185541 CN 201110185541 A CN201110185541 A CN 201110185541A CN 102277298 A CN102277298 A CN 102277298A
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Prior art keywords
control station
culture systems
microcomputer control
nutritive medium
gas
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CN 201110185541
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Chinese (zh)
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李卓权
吴志明
李胜蓝
蔡春苗
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    • 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
    • C12M21/00Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
    • 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
    • C12M37/00Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
    • 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
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • C12M41/14Incubators; Climatic chambers
    • 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
    • C12M41/48Automatic or computerized control
    • 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
    • C12M41/26Means for regulation, monitoring, measurement or control, e.g. flow regulation of pH

Abstract

The invention relates to a culturing system of biological tissue engineering. The culturing system provided by the invention comprises a culturing part and a control part. The culturing part comprises a culturing system (7), a power system (8), a gas exchanging system (11) and a nutrient solution exchanging system (10); the systems need to be installed in a sterile room (4); the control part comprises a main engine (5) of a microcomputer control station, an output line concentrator (6) and an input line concentrator (12). The main engine (5) of the microcomputer control station is used for controlling the work of each system of the control part through a connection circuit of the output line concentrator (6); and each system of the culturing part is used for feeding detection parameters back to the main engine (5) of the microcomputer control station through the connection circuit of the input line concentrator (12). The system provided by the invention is used for in-vitro tissue cultures and in-vitro organ cultures.

Description

A kind of bioengineered tissue culture systems
Technical field
The invention belongs to bioengineered tissue and cultivate equipment.For bioengineered tissue vitro tissue and organ culture provide simulation biological internal milieu, build physiological environments such as controlled biotic factor, pH, temperature, VITAMIN and mineral ion concentration.Can be used for external dynamic culturing cell and make up histoorgan.
Background technology
Multidisciplinary intersections such as biomedicine, biomaterial and automatization control are to the invention provides the theory and practice basis.Cell in vitro, histoorgan two-dimensional static or Three-Dimensional Dynamic are cultivated in biomedical research and production field widespread usage at present.Cell in vitro is cultivated, the histoorgan two-dimensional static is cultivated and is used for fundamental research more, and production application research is mainly artificial skin, cartilaginous tissue reparation etc. provides seed cell.Three-Dimensional Dynamic is cultivated and is mainly used in bio-reactor, produces the medicinal organism molecule.Along with the discipline development that biomaterial is learned, degradable, lifeless matter toxicity, biomaterial plastic, that have certain physical stress are developed successively, and small-scale production, as hydroxyapatite, chitosan, poly(lactic acid) etc.Automatization control provides theoretical and equipment support for the physiological environment of the accurately outer construction of control volume especially, comprises various automatic equipments.
Oncology studies is pointed out us: biological tissue's survival, the pipeline construction that nutrition is provided is the key that tissue survives.In order to address this problem, material scholar and biologist are in common constantly effort, and hope can provide enough fluid force for the space in the material, induce seed cell to form blood vessel when growing up to tissue, for follow-up transplanting reparation provides blood for path.
Comprehensive above-mentioned achievement in research, in conjunction with our research, the equipment of our invention can provide and form the needed different physics power of blood vessel, stimulates vascularization, and the size that can regulate physics power, the concentration of various biotic factors in the control nutritive medium.Under the acting in conjunction of physics power and various biotic factors, can form the tissue that size shape differs, the tissue that function differs.
Summary of the invention
The bioengineered tissue culture systems mainly is made up of five parts: culture systems, power system, gaseous interchange system, nutritive medium exchange system, microcomputer control station.Each part is independently finished self function, can also feed back to the microcomputer control station to self parameter, by the work of microcomputer control station regulator control system each several part, finishes organizational project jointly and cultivates task.
(1) culture systems comprises five parts: culture chamber, heating and cooling, sterilization, illumination and shooting, power supply.(1) can place common culture tank, cylinder culture tank, pipeline shunting dividing potential drop culture tank in the culture chamber, satisfy different tissue culture demands.(2) heating and cooling partly comprise warming module, refrigerating module, temperature detection instrument, guarantee that whole culture systems can add gentle cooling fast fast, and can be transferred to the microcomputer control station to real time temperature in the culture systems.(3) sterilising part is ozonizer/dry sterilization system, by ozone/xeothermic culture space is sterilized, and guarantees that environment is aseptic in the culture chamber.(4) illumination and camera part are for convenience when not opening culture systems, under the LED houselights by camera culture chamber in image send out in real time, promptly can be observed the situation of histoorgan cultivation at the microcomputer station.(5) supplying unit is expanded space for the repacking of culture chamber and improvement provide.
(2) power system comprises four parts: pump, pipeline, valve, hydrodynamicpressure are surveyed.(1) the pump part can provide two kinds of power-driven pumps: the one, and peristaltic pump, the one, reciprocation pump is for whole bioengineered tissue culture systems provides hydrodynamic force.(2) pipe section is made up of silicone tube, glass-tube glass and the stainless joint of different tube diameters, and is streamed by different branches, is the nutrition of cultured tissue conveyed, gas and meta-bolites, waste gas.(3) valve is a single-way flow restricting valve, is made up of silica gel, stainless steel or glass, and the nutritive medium flow direction meets experiment production design requirements in the safeguards system.(4) hydrodynamicpressure is surveyed, and instrument is installed on culture chamber, tubing system shunting, position, pump system front and back, in time to microcomputer control station feedback system fluid pressure changing conditions, provides parameter for adjusting power and separating liquid.
(3) the gaseous interchange system comprises three parts: gaseous interchange, gas concentration are surveyed, gas flow control.(1) gaseous interchange has the two kinds of patterns that can select: the one, and by the exchange of tubular fibre gas-liquid convection, the one, the liquid gas phase is by the film exchanging gas.In addition, system can also carry out histoorgan and cultivate directly for culture chamber provides needed gas on air fluid level.(2) the gas concentration probe portion comprises that oxygen concn is surveyed, gas concentration lwevel is surveyed, employing be up-to-date infrared detection head, the gas standard of collecting is transported to the microcomputer control station, provide parameter for system moves.(3) the gas flow control section can be according to the adjustment signal at microcomputer control station, the flow and the flow velocity of oxygen and carbonic acid gas input gaseous interchange instrument is moved, to keep in the total system oxygen and gas concentration lwevel in the gas-liquid phase material.
(4) the nutritive medium exchange system comprises three parts: dialysis, pH monitoring and urea monitoring.Can replace nutritional fluid composition in the system by dialysis apparatus, pH and urea monitor can prevent that pair cell organizes the objectionable impurities composition to pile up in the locking system.Be transported to the parameter at microcomputer control station by pH and urea monitor, can control, keep in the system nutrient composition and histoorgan is kept or growth conditions the best the dialysis apparatus working order.
(5) the microcomputer control station comprises three parts: signal collection, signal processing and adjustment signal output.(1) signal collection is mainly by following equipment induction: minisize pick-up head, temperature detecting head, hydrodynamicpressure detection instrument, oxygen detection head, carbonic acid gas detecting head, pH monitor, urea monitor etc.(2) signal processing is the core at microcomputer control station, comprises bioengineered tissue culture systems software, computer, signal input and output concentrator.(3) adjustment signal output is main by following equipment action: LED lamp, heating module, refrigerating module, pump, gas flow controller, dialysis apparatus etc.
Description of drawings
Fig. 1 bioengineered tissue culture systems mounting arrangement figure
Fig. 2 bioengineered tissue culture systems working portion
1 is passage room among the figure, and 2 is clean workplace, and 3 between the wind pouring, 4 is aseptic, and 5 is microcomputer control station host, and 6 is output wire collector, 7 is culture systems, 8 is power system, and 9 is culture chamber, and 10 is the nutritive medium exchange system, 11 is the gaseous interchange system, 12 are the input concentrator, and 13 is the histoorgan culturing bottle, and 14 is the temperature detection instrument, 15 is heating module/refrigerating module, 16 is the pH monitor, and 17 is the urea monitor, and 18 is oxygen detection head and carbonic acid gas detecting head, 19 is the hydrodynamicpressure detection instrument, 20 is single-way flow restricting valve, and 21 is minisize pick-up head, and 22 is the LED head light, 23 is gas flow controller, 24 is gas meter, and 25 is power supply, and 26 is ozonizer/dry sterilization system
Embodiment
The present invention is described in detail below in conjunction with the drawings and specific embodiments.
Embodiment one biological tissue's engineering culture systems mounting arrangement
A kind of bioengineered tissue culture systems, its mounting arrangement as shown in Figure 1, this mounting arrangement mainly contains culture systems 7, power system 8, gaseous interchange system 11, nutritive medium exchange system 10, microcomputer control station host 5.Wherein culture systems 7, power system 8, gaseous interchange system 11, nutritive medium exchange system 10 are installed in aseptic 4, the microcomputer control station is installed in the clean workplace 2, the staff enters and need change whole body formula barrier gown through passage room 1, enter aseptic 4 and need drench through wind between 3.When system's startup, in clean workplace 2, the staff sends signal by microcomputer control station host 5 operator's console software interfaces.Signal starts the warming module/refrigerating module of culture systems 7 and LED head light, the pump of power system 8, the gaseous interchange system 1 in the culture chamber 9 through output wire collector 6) gas flow controller, the dialysis apparatus of nutritive medium exchange system 10.In the course of the work, parameters such as intrasystem temperature, shooting, hydrodynamicpressure, gas concentration, pH value, urea concentration are sent to signal input concentrator 12 by each instrument, enter microcomputer control station host 5 then,, adjust each system device action as required by software system analysis.
Embodiment two histoorgans are cultivated
Utilizing the bioengineered tissue culture systems to carry out histoorgan cultivates, culturing process 2 is finished in aseptic, the culture systems that wherein relates to as shown in Figure 2, working process is described below: main pipe line in the aseptic silica gel tube short circuit culture chamber 9, in nutritive medium exchange system 10, inject nutritive medium, make in the circulating line of system and fill with nutritive medium.By microcomputer control station host 5 operation interfaces, start the ozonizer/dry sterilization system 26 and the heating module/refrigerating module 15 of culture systems 7, culture chamber 9 is sterilized and made wherein that temperature reaches 37 ℃.Insert histoorgan culturing bottle 13 in the culture chamber 9 and connect two ends nutritive medium input and manage, open both sides single-way flow restricting valve 20.Start the pump of power system 8, nutritive medium flows in the drive system; Start the gas flow controller 23 in the gaseous interchange system 11, regulate oxygen concn in the nutritive medium; The dialysis apparatus that starts in the nutritive medium exchange system 10 keeps the nutritive medium ingredient stability.Start-up temperature detecting head 14 feeds back to microcomputer control station host 5 to temperature parameter in the system simultaneously; Start hydrodynamicpressure detection instrument 19, histoorgan culturing bottle both sides hydrodynamicpressure parameter is fed back to microcomputer control station host 5; Start the gas meter 24 in the gaseous interchange system 11, the gas flow parameter that enters the gaseous interchange system is fed back to microcomputer control station host 5; Start oxygen detection head and carbonic acid gas detecting head 18, monitor nutritive medium oxygen and gas concentration lwevel in the pipeline, and these two parameters are fed back to microcomputer control station host 5; Start pH monitor 16 and urea monitor 17, nutritive medium pH value in the pipeline and urea concentration running parameter are fed back to microcomputer control station host 5; Start LED head light 22 and minisize pick-up head 21 in the culture chamber 9, graphic information in the histoorgan culturing bottle is sent to microcomputer control station host 5, wherein the light shading value is adjustable, and the camera shooting angle is also adjustable.According to each susceptor feedack, can be by microcomputer control station host 5 control heating module/refrigerating module 15, power system 8, gas flow controller 23, the 10 dialysis apparatus work of nutritive medium exchange system automatically; Also can pass through microcomputer control station host 5 operator's console Artificial Control.Need to expand electronics is installed, can be by power supply 25 power supplies.

Claims (3)

1. a bioengineered tissue culture systems is characterized in that, this system comprises cultivates part and control section.Cultivate part and comprise culture systems (7), power system (8), gaseous interchange system (11), nutritive medium exchange system (10); Control section comprises microcomputer control station host (5), output wire collector (6), input concentrator (12).The partly work of each system is cultivated by the control of output wire collector (6) connection line by microcomputer control station host (5), cultivates each system of part and by input concentrator (12) connection line detecting parameter is fed back to microcomputer control station host (5).Culture systems (7), power system (8), gaseous interchange system (11), nutritive medium exchange system (10) are installed in aseptic (4), and microcomputer control station host (5), output wire collector (6), input concentrator (12) are installed in the clean workplace (2).
2. a kind of bioengineered tissue culture systems according to claim 1 is characterized in that, described culture systems (7) shell is equipped with heating module/refrigerating module (15), temperature detection instrument (14), power supply (25); Described culture systems (7) inside is equipped with power system (8), nutritive medium exchange system (10), gaseous interchange system (11), culture chamber (9), and above-mentioned parts connect by silicone tube, glass or stainless joint; Histoorgan culturing bottle (13), LED head light (22), minisize pick-up head (21) and ozonizer/dry sterilization system (26) is housed in the described culture chamber (9); Described culture chamber (7) upstream and downstream is equipped with single-way flow restricting valve (20), hydrodynamicpressure detection instrument 19; Be provided with pH monitor (16), urea monitor (17) between described power system (8) and the nutritive medium exchange system (10); Be provided with oxygen detection head and carbonic acid gas detecting head (18) between described nutritive medium exchange system (10) and the gas exchange system (11); The external gas pipeline of described gaseous interchange system (11) is connected with gas meter (24), gas flow controller (23).
3. a kind of bioengineered tissue culture systems according to claim 2 is characterized in that the mouth of pipe of described silica gel pipeline is the clamping mouth, and interface is provided with sealing-ring.
CN 201110185541 2011-07-04 2011-07-04 Culturing system of biological tissue engineering Pending CN102277298A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102618442A (en) * 2012-04-06 2012-08-01 中国人民解放军第四军医大学 Artificial skin culture device and using method thereof
CN104750022A (en) * 2015-02-05 2015-07-01 西安交通大学 Tissue engineering and 3D printing meat tissue production processing system and method

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102618442A (en) * 2012-04-06 2012-08-01 中国人民解放军第四军医大学 Artificial skin culture device and using method thereof
CN104750022A (en) * 2015-02-05 2015-07-01 西安交通大学 Tissue engineering and 3D printing meat tissue production processing system and method

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Application publication date: 20111214