CN208430181U - The control system of bioreactor culture parameter - Google Patents

Abstract

The utility model discloses the control systems of bioreactor culture parameter, including main control unit, sub-control unit, pallet and cell culture bags；The main control unit, which is used to receive the parameter information of user setting and controls each sub-control unit according to parameter information, executes corresponding operating；The sub-control unit includes temperature control unit, liquid control unit, gas control unit and shakes control unit.Temperature control unit, liquid control unit, gas control unit are controlled respectively by a main control unit and shake control unit, existing disposable bioreactor is different from system architecture and structure type, and every height control unit belongs to a kind of closed-loop control, so that whole system control precision is high, control stability is good, and system response is fast.

Description

The control system of bioreactor culture parameter

Technical field

The utility model relates to bio-medical technology fields, in particular to a kind of control system of bioreactor culture parameter System.

Background technique

Disposable bioreactor can be divided into wave, stirring-type and rail mounted life according to the difference of motion mode and platform Object reactor, system architecture, structure type, control mode of different types of disposable bioreactor etc. are also not quite similar. Such as in terms of the control of the temperature parameter on stirring-type disposable bioreactor, tank body external sheath heating jacket, heating Circulation constant temperature water in collet is heated or is freezed to jacket water (J.W.) using heat exchanger in cyclic process, by directly controlling collet Circulating water temperature constitutes the principle of similar water bath with thermostatic control, the temperature electrode in culture tank or bag to indirectly control pot temperature Temperature sensor data information, temperature data information send control unit to, and control unit regulates and controls heating folder according to this information again Heated condition in set or water jacket.Although this temperature control mode can regulate and control temperature, due to being to combine thermostatted water The mode of bath, there are temperature regulation speed it is slow, the defect of regulating effect difference.It is for example reacted again in the wave disposable biological of GE In terms of the control of cell culture parameter on device, first by providing the size of cell culture bags or the weight of cell culture bags Or the information about cell culture state after the received information of control unit, then controls temperature, pH, DO etc. to control unit Cell culture parameter.Although this control mode automation is high, its cell culture parameter depends on the size of cell culture bags Or weight or the information about cell culture state, these information belong to the information limited, are not easy to manual modification And operation, it can not be by being manually entered control of the control instruction realization to culture parameters.Such as rail mounted disposable biological is anti-again In terms of the control for answering the gas parameter on device, the culture vessel of disposable plastic material surrounds center axis rotation first, in liquid It is centrally formed whirlpool, oscillation liquid forms film in reactor wall, by controlling the flow and flow rate of oxygen, to keep top empty Between oxygen be fused to film, then this film is combined with liquid phase main body rapidly, and then passes through surface ventilation and quickly mixed It closes and stronger oxygen conveying capacity is provided.This control mode can also have that gas mixing is uneven, control is not accurate. The control mode of above-mentioned each bioreactor culture parameter, respectively there is a superiority and inferiority, and generally existing structure is complicated and control logic is chaotic Defect, easily lead to that maintenance is difficult, be also not necessarily all suitable for the bioreactor of cell culture pocket type, cell culture environment It can not stablize and be precisely controlled.

Utility model content

The purpose of the utility model is to overcome existing bioreactor, control system, structure is complicated, control logic confusion Problem provides a kind of control system of bioreactor culture parameter.

To achieve the above object, the control system of bioreactor culture parameter designed by the utility model, including support Disk, the cell culture bags set on the pallet upper end, shaking for driving pallet centering type to be vortexed set on the pallet lower end Agitating device, the heating device between the pallet and cell culture bags, for acquiring the cell culture bags temperature Central temperature probe, the first peristaltic pump, weighing sensor, the culture medium storage container being placed on the weighing sensor, more It a gas bomb, the gas ratio valve set on gas bomb output end, the gas mixer that is connected to gas ratio valve and sets In gas mixer inside or the density of carbon dioxide gas sensor of output end；The mixed gas of the gas mixer Outlet is connected to the cell culture bags；The liquid inlet of first peristaltic pump is connected to culture medium storage container, and first is compacted The liquid outlet of dynamic pump is connected to the cell culture bags；The heating device and central temperature probe are connected to cell culture bags Surface；It further include the control unit being electrically connected with above-mentioned each electronic component.

Further, the agitating device includes driving motor and is set in driving motor output shaft with certain inclination angle The eccentric shaft of degree；Eccentric shaft upper end is connect with pallet lower end center, and eccentric shaft outer cover is equipped with elastic spacing one, the elasticity Locating part upper end is connect with pallet, the shell or driving motor cage connection of lower end and agitating device.

Preferably, the heating device is equipped with the heating device temp probe for acquiring the heating device temperature； The heating device temp probe is electrically connected with the control unit.

Still further, the control system further includes popping one's head in for acquiring the environment temperature of environment temperature；The environment Temp probe is electrically connected with the control unit.

Further, the control system further includes for monitoring agitating device waving angle/speed/positional angle Degree/speed/positional sensor；The angle/speed/positional sensor is electrically connected with the control unit.

Preferably, the control system further includes the second peristaltic pump for pumping out liquid in the cell culture bags； Second peristaltic pump is electrically connected with the control unit.

Optionally, the control system further includes multiple gas flowmeters, and each gas ratio valve corresponds at least one gas Flowmeter body；The gas flowmeter input terminal is connected to the gas ratio valve output end, gas flowmeter output end and gas The connection of body mixing arrangement input terminal.

Further, the gas ratio valve includes carbon dioxide ratio valve, nitrogen ratios valve, oxygen proportion valve and air Proportioning valve；The gas flowmeter includes carbon dioxide stream meter, nitrogen stream meter, oxygen flow meter and air flow meter；Institute Stating gas bomb includes carbon dioxide steel cylinder, nitrogen cylinder, air steel cylinder and oxygen bottle.

Preferably, the control system further includes gas filter system and the gas filtration for wrapping up gas filter system Device heating device；Gas filter system include pneumatic filter, set on described pneumatic filter one end air inlet pipe, be set to it is described The escape pipe of the pneumatic filter other end and the gas stop valve on the escape pipe；Pneumatic filter heating device includes Shell and the heating sheet being disposed in the housing；The top and bottom of the shell are equipped with the pipeline for holding the gas filter system The through-hole passed through, when gas filter system is placed in shell, shell is in full closeding state；The heating sheet by power supply line with External power supply electrical connection.By using by the totally enclosed structure type of gas filter system, i.e. shell not only encases gas filtration Device, but also air inlet pipe, escape pipe and gas stop valve are encased, the difference of gas temperature inside and outside gas filter system is reduced, Make gas that can not occur condensing phenomenon in entire gas filter system, not only ensure that the smooth discharge of steam in gas, and And the phenomenon that preventing low temperature low velocity gas to generate condensed water in gas filter system again, it ensure that pneumatic filter is normal Using function, the use environment of disposable bioreactor has also been widened.

The beneficial effects of the utility model are: passing through heating device, heating device temp probe and central temperature probe Effect, can real-time control heating device heated condition (starting heating, stop heating, continuous heating), realize to cell culture The real-time monitoring and control of final feedback temperature in bag；By the effect of the first peristaltic pump and weighing sensor, so that being pumped into thin The culture medium amount of being pumped into born of the same parents' culture bag can be effectively precisely controlled, and can carry out active control to cell culture environment；Pass through gas The effect of mixing arrangement and density of carbon dioxide gas sensor not only accelerates the exchange speed of mixed gas in cell culture bags Rate improves dissolved oxygen rate and carbon dioxide solubility rate in culture solution, and can fast, accurately reach parameter set by user Value, is greatly saved regulating time, can also receive user in real time to flow, concentration and gaseous species while system work The modification of parameter simultaneously responds rapidly；By the effect of agitating device, cell culture bags can be made to carry out eccentric rotary, to make Its internal culture cell carries out centering type vortex, and cell can be quickly sufficiently mixed；By a control unit respectively to heating Temperature, the culture medium amount of being pumped into, mixed gas concentration and shake speed or waving angle are controlled, in system architecture and structure shape Existing disposable bioreactor is different from formula, whole system controls precision height, and control stability is good, and system response is fast.

Detailed description of the invention

Fig. 1 is a kind of structural schematic diagram of embodiment of the utility model control system.

Fig. 2 is the main control unit of another embodiment of the utility model control system and the structural block diagram of son control unit.

Fig. 3 is the structural block diagram of temperature control unit in Fig. 2.

Fig. 4 is the partial structural diagram of Fig. 3.

Fig. 5 is the structural block diagram of liquid control unit in Fig. 2.

Fig. 6 is the structural schematic diagram of liquid control unit in Fig. 5.

Fig. 7 is the structural block diagram of gas control unit in Fig. 2.

Fig. 8 is the structural block diagram that control unit is shaken in Fig. 2.

Fig. 9 is the structural schematic diagram of agitating device in Fig. 8.

Figure 10 is the structural schematic diagram when pneumatic filter heating device of the utility model control system uses.

Figure 11 is the structural schematic diagram after the pneumatic filter heating device in Figure 10 is split.

In figure, 1. main control units；1.1. operating system；1.1.1. input system；1.1.2. operation interface；1.2. center control Device processed；2. sub-control unit；3. temperature control unit；3.1. temperature control modules；3.2. heating device controller；3.3. center Temp probe；3.4. heating device；3.5. heating device temp probe；3.6. environment temperature is popped one's head in；4. liquid control unit； 4.1. the first peristaltic pump；4.2. weighing sensor；4.3. the second peristaltic pump；4.4. culture medium storage container；5. gas control is single Member；5.1. Gas Control Module；5.2. gas bomb；5.3. gas ratio valve；5.4. gas mixer；5.5. carbon dioxide Gas concentration sensor；5.6. gas flowmeter；6. shaking control unit；6.1. control module is shaken；6.2. agitating device； 6.2.1. driving motor；6.2.2. eccentric shaft；6.2.3. elastic spacing one；6.3. angle/speed/positional sensor；7. pallet； 8. cell culture bags；9. gas filter system；9.1. pneumatic filter；9.2. air inlet pipe；9.3. escape pipe；9.4. gas ends Valve；10. pneumatic filter heating device；10.1. shell；10.2. heating sheet；10.3. bracket；10.4. rotating mechanism.

Specific embodiment

The utility model is described in further detail below in conjunction with the drawings and specific embodiments.

Embodiment 1

The control system of bioreactor culture parameter as shown in Figure 1, including pallet 7, the cell set on 7 upper end of pallet Culture bag 8, the agitating device 6.2 shaken for driving pallet 7 centering type to be vortexed set on 7 lower end of pallet are set to pallet 7 and thin Heating device 3.4 between born of the same parents' culture bag 8, the central temperature probe 3.3, first for acquiring 8 temperature of cell culture bags are wriggled Pump 4.1, the culture medium storage container 4.4 being placed on weighing sensor 4.2, multiple gas bombs 5.2, is set weighing sensor 4.2 In the gas ratio valve 5.3 of 5.2 output end of gas bomb, the gas mixer 5.4 that is connected to gas ratio valve 5.3 and it is set to The density of carbon dioxide gas sensor 5.5 of 5.4 inside of gas mixer or output end；The mixing of gas mixer 5.4 Gas vent is connected to cell culture bags 8；The liquid inlet of first peristaltic pump 4.1 is connected to culture medium storage container 4.4, and first The liquid outlet of peristaltic pump 4.1 is connected to cell culture bags 8；Heating device 3.4 and central temperature probe 3.3 are connected to cell training Support 8 surface of bag；It further include that the control unit that is electrically connected with above-mentioned each electronic component is not shown).

Agitating device 6.2 includes driving motor 6.2.1 and is set on driving motor 6.2.1 output shaft with certain inclination angle The eccentric shaft 6.2.2 of degree；The upper end eccentric shaft 6.2.2 is connect with 7 lower end center of pallet, and eccentric shaft 6.2.2 outer cover is equipped with bullet Property locating part 6.2.3, the upper end elastic spacing one 6.2.3 connect with pallet 7, the shell or driving electricity of lower end and agitating device 6.2 Machine 6.2.1 cage connection.

Heating device is equipped with the heating device temp probe 3.5 for acquiring 3.4 temperature of heating device；Heating device temperature Degree probe 3.5 is electrically connected with control unit.Control system further includes the environment temperature probe 3.6 for acquiring environment temperature；Ring Border temp probe 3.6 is electrically connected with control unit.

Control system further includes passing for monitoring 6.2 waving angles of agitating device/speed/positional angle/speed/positional Sensor (not shown)；Angle/speed/positional sensor is electrically connected with control unit.Control system further includes for training cell Support the second peristaltic pump 4.3 that liquid pumps out in bag 8；Second peristaltic pump 4.3 is electrically connected with control unit.Control system further includes more A gas flowmeter 5.6, at least one corresponding gas flowmeter 5.6 of each gas ratio valve 5.3；Gas flowmeter 5.6 inputs End is connected to 5.3 output end of gas ratio valve, and 5.6 output end of gas flowmeter is connected to 5.4 input terminal of gas mixer.Gas Body proportioning valve 5.3 includes carbon dioxide ratio valve, nitrogen ratios valve, oxygen proportion valve and AIR Proportional valve；Gas flowmeter 5.6 Including carbon dioxide stream meter, nitrogen stream meter, oxygen flow meter and air flow meter；Gas bomb 5.2 includes carbon dioxide Steel cylinder, nitrogen cylinder, air steel cylinder and oxygen bottle.

Embodiment 2

The control system of bioreactor culture parameter as shown in Fig. 2~11, including control unit, pallet 7 and cell Culture bag 8；Control unit includes main control unit 1 and sub-control unit 2；

Main control unit 1 is used to receive the parameter information of user setting and controls each sub-control unit 2 according to parameter information and holds Row corresponding operating；Sub-control unit 2 includes temperature control unit 3, liquid control unit 4, gas control unit 5 and shakes control Unit 6；

Temperature control unit 3 controls heating device 3.4 to the interior cell culture containing cell mixture according to parameter information Bag 8 is heated, and the heated condition for the temperature data adjustment heating device 3.4 for acquiring and feeding back in real time according to temp probe；

Liquid control unit 4 controls peristaltic pump according to parameter information and is pumped into the culture medium amount of being pumped into cell culture bags 8, and According to the amount of being pumped into for 4.4 weight data of the culture medium storage container adjustment peristaltic pump that weighing sensor 4.2 is acquired and fed back in real time；

Gas control unit 5 according to parameter information control enter cell culture bags 8 in carbon dioxide in gas mixture it is dense Degree, and the concentration is adjusted according to 5.5 feedback data of density of carbon dioxide gas sensor in real time；

Control unit 6 is shaken to be started or stoped according to parameter information control agitating device 6.2；Agitating device 6.2 is for driving The dynamic pallet 7 for carrying cell culture bags 8 carries out eccentric rotary.

Main control unit 1 includes operating system 1.1 and is connect with operating system 1.1 by RS485 bus or wireless telecommunications Central controller 1.2；Operating system 1.1 includes the parameter information for receiving user setting and parameter information is sent to center The input system 1.1.1 of controller 1.2 and the operation for being used to show and be arranged parameter information being electrically connected with input system 1.1.1 Interface 1.1.2 (can be the combination of touch screen displays or display and operation keyboard).

Parameter information includes temperature parameter information, liquid parameter information, gas parameter information and shakes parameter information；Temperature Parameter information includes the temperature information that need to be heated and maintain；Liquid parameter information includes the flow velocity and flow information of liquid；Gas Parameter information includes the type, concentration and flow information of gas；Shaking parameter information includes angle, speed and the position letter shaken Breath.

Temperature control unit 3 as shown in Figure 3,4 includes the temperature control modules with 1.2 communication connection of central controller 3.1, be electrically connected with temperature control modules 3.1 heating device controller 3.2 and central temperature probe 3.3 and with heating device control The heating device 3.4 that device 3.2 processed is electrically connected；Central temperature probe 3.3 is for acquiring 8 temperature of cell culture bags, and by acquisition Central temperature data real-time transmission is to temperature control modules 3.1；It is carried out between central controller 1.2 and temperature control modules 3.1 Real-Time Signal Transfer；Central temperature data judgement are compared with temperature parameter information and obtain center temperature by central controller 1.2 Central temperature comparison result signal is simultaneously fed back to temperature control modules 3.1 by degree comparison result signal；Temperature control modules 3.1 will Central temperature comparison result signal is sent to heating device controller 3.2；Heating device controller 3.2 is compared according to central temperature The heated condition of consequential signal control heating device 3.4.Believed by heating device controller 3.2 according to central temperature comparison result Number control heating device 3.4 heated condition, it is unstable to solve the problems, such as that existing bioreactor temperature controls, passes through center Acquisition 8 temperature of cell culture bags, the heated condition of real-time control heating device 3.4 (start heating, stop temp probe 3.3 in real time Only heating, continuous heating), realize the real-time monitoring and control to feedback temperature final in cell culture bags 8.

Temperature control unit 3 further includes being electrically connected with temperature control modules 3.1 for acquiring 3.4 temperature of heating device Heating device temp probe 3.5；Heating device temp probe 3.5 controls the heating temperature data real-time transmission of acquisition to temperature Module 3.1；Heating temperature data judgement are compared with temperature parameter information and show that heating temperature compares by central controller 1.2 Heating temperature comparison result signal is simultaneously fed back to temperature control modules 3.1 by consequential signal；Temperature control modules 3.1 will heat temperature Degree comparison result signal is sent to heating device controller 3.2；Heating device controller 3.2 is believed according to heating temperature comparison result Number control heating device 3.4 heated condition.The temperature of heating device 3.4 can be acquired in real time by heating device temp probe 3.5 Degree is realized to the real-time monitoring and control for initially entering temperature in cell culture bags 8, avoids heating device 3.4 from crossing thermal damage thin Cell in born of the same parents' culture bag 8.

Temperature control unit 3 further includes the environment temperature probe 3.6 being electrically connected with temperature control modules 3.1；Environment temperature The ambient temperature data information of acquisition is sent to central controller 1.2, center control through temperature control modules 3.1 by probe 3.6 Ambient temperature data information is fed back to the operation interface 1.1.2 of operating system 1.1 by device 1.2.User can pass through operation interface 1.1.2 it checks real time environment temperature information, external temperature environment, such as the temperature of air-conditioning is adjusted by ambient temperature data information Degree.It can effectively avoid that ambient temperature is too high or too low to impact cell culture by environment temperature probe 3.6.

The cell culture bags 8 of this system are placed on pallet 7 (or on bioreactor shaking table)；Heating device 3.4 is placed in support On disk 7 and cell culture bags 8 are placed on heating device 3.4, and heating device 3.4 is made to be connected to 8 lower end outer wall of cell culture bags simultaneously The cell mixture in cell culture bags 8 is transferred heat to by way of contact heating.Central temperature probe 3.3 is set as It is connected to 8 outer wall of cell culture bags, for example pallet 7 is fixed in 3.3 lower ends of central temperature probe, upper end passes through heating device 3.4 The temperature sense part of rear center's temp probe 3.3 is connected to cell culture bags 8.Environment temperature probe 3.6 can be directly arranged in support On disk 7 and its induction part is placed in air back to heating device 3.4 and/or cell culture bags 8.Heating device temp probe 3.5 induction part can directly be connected to heating device 3.4 or heating device temp probe 3.5 is placed directly within heating device 3.4 It is interior.User is by 1.1 input temp parameter information of operating system, such as the temperature for needing to heat, the temperature, the highest that need to maintain Temperature, minimum temperature etc., system will be heated to cell culture required temperature automatically, and temperature is not too high or too low.

The control section of the temperature control unit 3 of this control system is actually a kind of closed-loop control system.Wherein, it operates System 1.1 is preferably 7 operating system 1.1 of Windows, and central controller 1.2 is preferably MCU central controller 1.2；Temperature control Molding block 3.1 is preferably embedded temperature control modules 3.1 comprising the pid algorithm based on ARM chip development platform；Such as Using increment type PID algorithm, formula is as follows:

U (k)=kp × error (k)+λ × ki ∑ error (j)+kd (error (k)-error (k-1))

Wherein u (k) is the controlling value at k moment, and error (k) is the relative error at k moment, and kp is proportionality coefficient, and ki is product Divide coefficient, kd is differential coefficient, and λ is subsection integral variation coefficient.The value of λ changes with the absolute value of relative error and is changed, When the absolute value of relative error is bigger, i.e., when measured value deviation setting value is bigger, λ takes smaller value, on the contrary, λ takes the larger value.

When the temperature that center temp probe 3.3 acquires is less than 20 DEG C, λ=1.0

When the temperature that center temp probe 3.3 acquires is less than 35 DEG C, λ=0.9

When the temperature that center temp probe 3.3 acquires is less than 40 DEG C, λ=0.6

DB type electric hot plate or the HTL-500/400/300EX type nanometer heating plate of NanoHeat can be selected in heating device 3.4； The SWK-XCXB type temperature controller or internal exploitation embedded control panel of prosperous sincerity can be selected in heating device controller 3.2； The RTD-809 type surface temperature probe of U.S. omega can be selected in central temperature probe 3.3 and heating device temp probe 3.5；Ring The P-L-1/10-1/4-6-1/8-P-3 type temperature sensor of omega can be selected in border temp probe 3.6.

The control routine of the temperature control unit 3 of this control system is as follows:

Liquid control unit 4 as shown in Figure 5,6 includes that first connect respectively with 1.2 electric signal of central controller wriggles Pump 4.1 and weighing sensor 4.2；First peristaltic pump 4.1 is for culture medium to be pumped into cell culture bags 8；Weighing sensor 4.2 The weight of real-time monitoring culture medium storage container 4.4, and by weight information Real-time Feedback to central controller 1.2；Center control The culture medium amount of being pumped into of the first peristaltic pump of real time correction 4.1 according to weight information of device 1.2.

Liquid control unit 4 further includes the second peristaltic pump 4.3 for pumping out liquid in cell culture bags 8；Second is compacted Dynamic pump 4.3 is connect with 1.2 electric signal of central controller.

This control mode is actually also a kind of closed-loop control, since the first peristaltic pump 4.1 oneself can not realize closed loop Control, the amount of being pumped into has deviation, it is therefore desirable to increase weighing sensor 4.2 to be corrected, thus the first peristaltic pump 4.1 with Weighing sensor 4.2 realizes closed-loop control under cooperating.

If 4.4 initial weight of culture medium storage container being placed on weighing sensor 4.2 is W1, as culture medium is by the One peristaltic pump 4.1 is pumped into cell culture bags 8, and 4.4 weight of culture medium storage container on weighing sensor 4.2 becomes W2, center It is W3 that 1.2 calculation processing of controller, which show that culture medium storage container 4.4 reduces weight, and W3=W1-W2, W3 can be indirectly by Internal processes obtain；If the liquid parameter information (flow velocity and flow information of liquid) of operation interface 1.1.2 setting is W4, that is, use The weight for needing to be pumped into the culture medium in cell culture bags 8 of family setting is W4, and W4 data-signal is transmitted through central controller 1.2 To the first peristaltic pump 4.1, the first peristaltic pump 4.1 executes this order, starts to be pumped into culture medium in cell culture bags 8；It pumps at this time The culture medium actual weight entered in cell culture bags 8 is W5, and a certain amount of culture medium can be remained in pipeline, weight W6, W6 can be by W6=3.14 (D/2)²× L is obtained, and wherein D is liquid line internal diameter, and L is liquid line length.

When the first peristaltic pump 4.1 works a period of time, when so that the reduction weight W3 that weighing sensor 4.2 claims being equal to W4, Actually entering the culture medium weight W5 also almost (the residual W6 of pipeline) in cell culture bags 8 can be only achieved the weight value of W4； Therefore, central controller 1.2 controls the first peristaltic pump 4.1 and works on, so that being pumped into cell culture bags 8 when W3=W6 The value of culture medium actual weight W5 will be closer to the practically necessary value W4 of cell culture；And this state, need weighing sensor 4.2 are uploaded to weight information central controller 1.2 in real time, make central controller 1.2 convenient for the first peristaltic pump 4.1 of control in time Closing.

It should be noted that the first peristaltic pump 4.3 and the second peristaltic pump 4.3 are preferably Watson-Marlow 114FD OEM peristaltic pump or Lange T300-S51/FG15-13-B type peristaltic pump.Weighing sensor 4.2 is preferably single-point type sensor, Electronic balance can be directlyed adopt to weigh to culture medium storage container 4.4；Wherein, plum Teller-can be used in single-point type sensor Hold in the palm benefit MT1022- aluminum single-point type sensor；If directlying adopt electronic balance, using the serial ports based on RS485 communications protocol It is connect with MCU central controller 1.2, then treasure perseverance BN-V8-3000+R type electronic balance can be selected or other meet precision on the market Electronic balance.

In addition, the control routine of liquid control unit 4 is as follows:

Gas control unit 5 as shown in Figure 7 include with the Gas Control Module 5.1 of 1.2 communication connection of central controller, Multiple gas bombs 5.2, set on 5.2 output end of gas bomb and the gas ratio valve that is electrically connected with Gas Control Module 5.1 5.3, the gas mixer 5.4 that is connected to gas ratio valve 5.3 and set on the two of 5.4 inside of gas mixer or output end Carbon oxide gas concentration sensor 5.5；The output end of gas mixer 5.4 is connected to cell culture bags 8；Carbon dioxide gas Concentration sensor 5.5 is by density of carbon dioxide gas information Real-time Feedback to Gas Control Module 5.1；Gas Control Module 5.1 The opening-closing size of each gas ratio valve 5.3 is controlled according to parameter information, and is fed back according to density of carbon dioxide gas sensor 5.5 Data information adjusts the opening-closing size of each gas ratio valve 5.3.

Gas control unit 5 further includes multiple gas flowmeters 5.6, at least one corresponding gas of each gas ratio valve 5.3 Flowmeter body 5.6；5.6 input terminal of gas flowmeter is connected to 5.3 output end of gas ratio valve, 5.6 output end of gas flowmeter It is connected to 5.4 input terminal of gas mixer.

Gas ratio valve 5.3 includes carbon dioxide ratio valve, nitrogen ratios valve, oxygen proportion valve and AIR Proportional valve；Gas Flowmeter body 5.6 includes carbon dioxide stream meter, nitrogen stream meter, oxygen flow meter and air flow meter；Gas bomb 5.2 wraps Include carbon dioxide steel cylinder, nitrogen cylinder, air steel cylinder and oxygen bottle.

Gas Control Module 5.1 is dense by the carbon dioxide gas of 5.5 real-time monitoring of density of carbon dioxide gas sensor It spends information dynamic regulation gas ratio valve 5.3 (carbon dioxide ratio valve, nitrogen ratios valve, oxygen proportion valve and AIR Proportional valve) Opening size, be allowed in proportion enter gas mixer 5.4, the mixture through gas mixer 5.4, then pass through dioxy Change carbon gas concentration sensor 5.5, density of carbon dioxide gas sensor 5.5 feeds back to Gas Control Module for data are acquired again 5.1, Gas Control Module 5.1 is judged according to feedback data information and readjusts the aperture of each gas ratio valve 5.3 Size, until reaching the concentration (5%) of required carbon dioxide.Central controller 1.2 passes through built-in pid algorithm, quick, essence True reaches parameter value set by user, and regulating time is greatly saved, and can also receive in real time while system work User is to the modification of flow, concentration and gas species parameter and responds rapidly；Such as, user is received while work to repair Mixed gas total flow F after changing calculates tested gas outflow magnitude F1=after being tested the instruction of gas concentration C first F/(100/C)；Carrier gas output stream magnitude F2=F1 × (100/C-1) is directly adjusted by regulating gas proportioning valve 5.3 and is arrived this Flow.

The control routine of gas control unit 5 are as follows:

Shake control unit 6 as shown in Figure 8,9 includes the shake control module with 1.2 communication connection of central controller 6.1 and with shake the agitating device 6.2 that is electrically connected of control module 6.1 and for monitor 6.2 waving angles of agitating device/speed/ The angle of position/speed/positional sensor 6.3.By shaking the effect of control unit 6, cell culture bags 8 can be made to carry out bias Rotation, so that its internal culture cell be made to carry out centering type vortex, cell can be quickly sufficiently mixed.

Specifically, agitating device 6.2 may include shell, driving motor 6.2.1 (output shaft is vertical shape) and be set to driving With the eccentric shaft 6.2.2 of certain tilt angle on motor 6.2.1 output shaft；The upper end eccentric shaft 6.2.2 can connect with 7 center of pallet It connects, and the elastic spacing one 6.2.3 of bellows etc, the upper end elastic spacing one 6.2.3 can be arranged with outside eccentric shaft 6.2.2 It is connect with pallet 7, the shell or driving motor 6.2.1 cage connection of lower end and agitating device 6.2.Operating system 1.1, which receives, to be used The shake parameter information of family setting, the information such as speed, angle, position including selected shake, these information are total by RS485 Line is sent to central controller 1.2, and central controller 1.2 gives the speed of shake and angle information transfer to shake control module 6.1 and start command is issued, shakes speed and angle that control module 6.1 issues signal adjustment agitating device 6.2, agitating device 6.2 start to shake and drive pallet 7, and pallet 7 drives the cell in cell culture bags 8 to carry out centering type vortex and shakes, Jin Erman The demand that sertoli cell mixes；Angular transducer, velocity sensor and position sensor are by the angle monitored, speed and position simultaneously Confidence breath is fed back to again shakes control module 6.1, shakes the speed that control module 6.1 can based on the feedback signal to agitating device 6.2 Degree and angle are adjusted.When the sending of operating system 1.1 is ceased and desisted order, agitating device 6.2 will be controlled by shaking control module 6.1 Shake speed so that agitating device 6.2 is stopped at fixed position by the feedback information of velocity sensor and position sensor.

Shake the control routine of control unit 6 are as follows:

The control system as shown in Figure 10,11 further includes gas filter system 9 and the gas for wrapping up gas filter system 9 Body filter heating device 10；Gas filter system 9 includes pneumatic filter 9.1, the air inlet set on 9.1 one end of pneumatic filter Pipe 9.2, the gas stop valve 9.4 set on the escape pipe 9.3 of 9.1 other end of pneumatic filter and on escape pipe 9.3；Gas Filter heating device 10 includes shell 10.1 and the heating sheet 10.2 in shell 10.1；The top and bottom of shell 10.1 Equipped with the through-hole that the pipeline for holding gas filter system 9 passes through, when gas filter system 9 is placed in shell 10.1, shell 10.1 In full closeding state；Heating sheet 10.2 is electrically connected by power supply line with external power supply.It is sealed entirely by using by gas filter system 9 The structure type closed, i.e. shell 10.1 not only encase pneumatic filter 9.1, but also encase air inlet pipe 9.2, escape pipe 9.3 and Gas stop valve 9.4 reduces the difference of gas temperature inside and outside gas filter system 9, makes gas can not be in entire gas filtration Occur condensation phenomenon in system 9, not only ensure that the smooth discharge of steam in gas, and low temperature low velocity gas is prevented to exist again The phenomenon that condensed water is generated in gas filter system 9 ensure that pneumatic filter 9.1 normally using function, has also widened one The use environment of secondary property bioreactor.

In addition, pneumatic filter heating device 10 further includes on shell 10.1 for adjusting the bracket of its height 10.3；Bracket 10.3 is connect by rotating mechanism 10.4 with shell 10.1；Heating sheet 10.2 passes through power supply line and external power supply electricity Connection.Shell 10.1 may include abutting against and detachable left shell portion and right shell body portion；Bracket 10.3 and rotating mechanism 10.4 There are two each, one of bracket 10.3 is connect by a rotating mechanism 10.4 with left shell portion, another bracket 10.3 is logical Another rotating mechanism 10.4 is crossed to connect with right shell body portion.Heating sheet 10.2 at least there are two, be set to corresponding pneumatic filter 9.1 10.1 inner wall of shell of position, heating sheet 10.2 are preferably silica-gel electrothermic silk heating sheet 10.2.

Rotating mechanism 10.4 includes two shafts and two knobs；Shaft is equipped with external screw thread, and shaft one end and shell 10.1 is fixed, and the shaft other end is set to 10.1 outside of shell and is cooperated by external screw thread and knob thread；End cap on bracket 10.3 If or hook is located in shaft and is flexibly connected with shaft.The bearing surface in left shell portion and right shell body portion is equipped with the buckle mutually fastened Part.By the effect of fastener, make left shell portion and right shell body portion that can quickly split and splice merging, use is more convenient, and ties Structure is simple, at low cost.

By the effect of temperature control unit, can real-time control heating device heated condition (starting heating, stop plus Heat, continuous heating), realize the real-time monitoring and control to feedback temperature final in cell culture bags；Pass through liquid control unit Effect can be to cell culture so that the culture medium storage container amount of being pumped into being pumped into cell culture bags can be effectively precisely controlled Environment carries out active control；By the effect of gas control unit, the exchange of mixed gas in cell culture bags is not only accelerated Rate improves dissolved oxygen rate and carbon dioxide solubility rate in culture solution；And it can fast, accurately reach ginseng set by user Regulating time is greatly saved in numerical value, can also receive user in real time to flow, concentration and gas kind while system work The modification of class parameter simultaneously responds rapidly；By the effect of shake control unit, cell culture bags can be made to carry out eccentric rotary, To make its internal culture cell carry out centering type vortex, cell can be quickly sufficiently mixed；Distinguished by a main control unit It controls temperature control unit, liquid control unit, gas control unit and shakes control unit, in system architecture and structure type On be different from existing disposable bioreactor, and every height control unit belongs to a kind of closed-loop control, so that whole system It is high to control precision, control stability is good, and system response is fast.

Claims (9)

1. a kind of control system of bioreactor culture parameter, it is characterised in that: including pallet (7), be set to the pallet (7) The cell culture bags (8) of upper end, the shake shaken for driving pallet (7) centering type to be vortexed for being set to the pallet (7) lower end Device (6.2) is set to heating device (3.4) between the pallet (7) and cell culture bags (8), for acquiring the cell The central temperature probe (3.3) of culture bag (8) temperature, weighing sensor (4.2), is placed in the weighing at the first peristaltic pump (4.1) Culture medium storage container (4.4), multiple gas bombs (5.2) on sensor (4.2) are set to gas bomb (5.2) output end Gas ratio valve (5.3), the gas mixer (5.4) that is connected to gas ratio valve (5.3) and be set to gas mixer (5.4) internal or output end density of carbon dioxide gas sensor (5.5)；The gaseous mixture of the gas mixer (5.4) Body outlet is connected to the cell culture bags (8)；The liquid inlet of first peristaltic pump (4.1) and culture medium storage container (4.4) it is connected to, the liquid outlet of the first peristaltic pump (4.1) is connected to the cell culture bags (8)；The heating device (3.4) Cell culture bags (8) surface is connected to central temperature probe (3.3)；It further include the control being electrically connected with above-mentioned each electronic component Unit processed.

2. the control system of bioreactor culture parameter according to claim 1, it is characterised in that: the agitating device (6.2) include driving motor (6.2.1) and there is the eccentric shaft of certain tilt angle on driving motor (6.2.1) output shaft (6.2.2)；The eccentric shaft upper end (6.2.2) is connect with pallet (7) lower end center, and eccentric shaft (6.2.2) outer cover is equipped with elasticity Locating part (6.2.3), the elastic spacing one upper end (6.2.3) are connect with pallet (7), the shell of lower end and agitating device (6.2) Body or driving motor (6.2.1) cage connection.

3. the control system of bioreactor culture parameter according to claim 1, it is characterised in that: the heating device It is equipped with the heating device temp probe (3.5) for acquiring the heating device (3.4) temperature；The heating device temperature is visited Head (3.5) is electrically connected with the control unit.

4. the control system of bioreactor culture parameter according to claim 1, it is characterised in that: the control system It further include popping one's head in (3.6) for acquiring the environment temperature of environment temperature；The environment temperature probe (3.6) and described control unit Electrical connection.

5. the control system of bioreactor culture parameter according to claim 1, it is characterised in that: the control system It further include for monitoring the angle of agitating device (6.2) waving angle/speed/positional/speed/positional sensor (6.3)；It is described Angle/speed/positional sensor (6.3) is electrically connected with the control unit.

6. the control system of bioreactor culture parameter according to claim 1, it is characterised in that: the control system It further include the second peristaltic pump (4.3) for pumping out the cell culture bags (8) interior liquid；Second peristaltic pump (4.3) It is electrically connected with the control unit.

7. the control system of bioreactor culture parameter according to claim 1, it is characterised in that: the control system It further include multiple gas flowmeters (5.6), at least one corresponding gas flowmeter (5.6) of each gas ratio valve (5.3)；It is described Gas flowmeter (5.6) input terminal is connected to gas ratio valve (5.3) output end, gas flowmeter (5.6) output end with The connection of gas mixer (5.4) input terminal.

8. the control system of bioreactor culture parameter according to claim 7, it is characterised in that: the gas ratio Valve (5.3) includes carbon dioxide ratio valve, nitrogen ratios valve, oxygen proportion valve and AIR Proportional valve；The gas flowmeter It (5.6) include carbon dioxide stream meter, nitrogen stream meter, oxygen flow meter and air flow meter；Gas bomb (5.2) packet Include carbon dioxide steel cylinder, nitrogen cylinder, air steel cylinder and oxygen bottle.

9. the control system of bioreactor culture parameter according to claim 1, it is characterised in that: the control system It further include gas filter system (9) and the pneumatic filter heating device (10) for wrapping up gas filter system (9)；Gas mistake Filter system (9) includes pneumatic filter (9.1), the air inlet pipe (9.2) for being set to the pneumatic filter (9.1) one end, is set to institute The gas stop valve (9.4) stating the escape pipe (9.3) of pneumatic filter (9.1) other end and being set on the escape pipe (9.3)； Pneumatic filter heating device (10) includes shell (10.1) and the heating sheet (10.2) in the shell (10.1)；It is described The top and bottom of shell (10.1), which are equipped with, holds the through-hole that the pipeline of the gas filter system (9) passes through, when gas filtration system System (9) be placed in shell (10.1) it is interior when, shell (10.1) be in full closeding state；The heating sheet (10.2) is by power supply line and outside Portion's power electric connection.