CN106507801B - Full-automatic spatial cell biological study experiment porch - Google Patents

Full-automatic spatial cell biological study experiment porch Download PDF

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Publication number
CN106507801B
CN106507801B CN200410029062.1A CN200410029062A CN106507801B CN 106507801 B CN106507801 B CN 106507801B CN 200410029062 A CN200410029062 A CN 200410029062A CN 106507801 B CN106507801 B CN 106507801B
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cell culture
module
cell
submodule
shell
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谭映军
李莹辉
于建茹
聂捷琳
戴钟铨
丁柏
张晓铀
熊江辉
杨芬
万玉民
毕蕾
叶东明
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China Astronaut Research and Training Center
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China Astronaut Research and Training Center
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Abstract

A kind of full-automatic spatial cell biological study experiment porch, it is characterized in that it by structurally and functionally distinguish completely self-contained module composition.According to different requirement of experiment, it at least may include 26 samples and seven modules, realize the functions such as the culture of cell is compareed with process, on-line checking, image record, temperature control, gravity, parameter monitoring, parameter show respectively.This device applied range, high degree of automation, operation and maintenance are convenient, the dynamic-change information of cell cultivation process can be realized continuously, real-time online tracking and monitoring and record, directly perceivedization display and ground monitoring.

Description

Full-automatic spatial cell biological study experiment porch
Technical field is the present invention relates to a kind of cell experiment platform, more particularly, to a kind of full-automatic spatial cell Biological study experiment porch.
The full-automatic spatial cell biological study experiment porch of background technology will be applied to retrievable satellite, airship With the spacecraft such as space shuttle there is provided cells survival optimal under the conditions of Space Special Environment, growth with Experiment condition, sets up progress spatial cell molecular biology and aerospace medicine research under the conditions of Space Special Environment Solid technology platform.The platform can be automatically performed by preset program under unmanned subsidiary conditions and all preset in fact Test content;Simultaneously provided with artificial interference interface, it is allowed to intervened during the in-orbit experiment of spacefarer, to obtain More research informations, improve the effective utilization of full-automatic spatial cell biological study experiment porch.
At present, numerous studies have been carried out in this area both at home and abroad, some relevant devices are also have developed.Due to These equipment all serve a certain particular studies target, thus inevitably with one in function and structure A little limitations and deficiency.Foreign countries are disclosed this kind equipment and reported with U.S. NASA disclosed in No. N94-25672 Equipment is representative.The equipment is microbial cultivation device, and this device is mainly used in carrying out microorganism in space The culture of culture, suspension growth cell etc..Agent structure point:Test block, centrifugation area, liquid changing device, figure As six parts such as system, sensor, communications.
The major experimental area of microbial cultivation device is the 40 independent culturing room being distributed in a ring compositions.Each Culturing room is cylinder, and a diameter of 1.2cm, high 5cm, each culture building volume are 3ml.Culturing room is by one The individual serum cap with reusable film, transparent plastic cylinder, elastoplast bag and pellicle composition. Whole culturing room is sealing.The film that culturing room covers can be carried out by liquid transfer needle pierces liquid transfer, Supplement operation;Transparent column part can be utilized for image record in culturing room;Elastoplast bag can be in training Nutrient solution is stretched when passing in and out culturing room, culturing room is always at full up state;Culturing room is divided into gas by pellicle Liquid two parts.This compact conformation of culturing room, but whole culturing room is without transparent plane, so can not see Form, the structure of Object of Development are examined, turbidity can only be recorded in the form of luminous flux to determine that experimental subjects increases Grow situation.
Centrifugation area is that a diameter of 15.2cm centrifugal hoop is constituted, and its rotating speed is 108.5rpm, and speed error is 2rpm can realize 0.89g~1.11g acceleration, but the culturing room in centrifugation area changes liquid and needs to stop in centrifuge Under, the shortcoming so operated is that experimental subjects will be acted on repeatedly by microgravity, thus the stringency of experiment contrast It is affected.
In microbial cultivation device, the transfer of nutrient solution is main by 3 motors and transfer head by one The mechanical arm of composition is realized.These three motors are used for realizing that the three-dimensional of liquid transfer head is mobile, so as to reach The purpose of nutrient solution supplement and transfer is carried out to each culturing room.Transfer head first will during liquid transfer operation The film that culturing room covers is pierced through, then by pump driving nutrient solution flowing.This mode of operation has higher pollution Probability, is all that first transfer syringe needle is pierced into culturing room, after the completion of operation again when being filled to each culturing room Transfer head is extracted.The operating process that this thorn one is pulled out destroys the sealing of culturing room to a certain extent, Add the chance that experimental subjects is contaminated, and the mutual pollution being likely to result between culturing room, effective sample This number is so as to be affected.This another deficiency for changing liquid mode is exactly that make use of film to carry out separating experiment object With the mode of nutrient solution, experimental subjects can be caused to block the situation of seperation film when shifting nutrient solution, so that Liquid transfer efficiency is reduced, and nutrient solution transfer is insufficient, and is likely to result in experimental subjects damage.
Image recording system is made up of microscope, camera and camera.Camera and camera are connected to aobvious In the output of micro mirror, microscopical output can be output on camera or camera by changing selection, its The signal of middle video camera can pass ground back.
There are temperature, illumination, gravity, vibration and radiation sensor on microbial cultivation device, for monitoring ring Border condition.The monitoring of wherein pH value is the method with indicator.This method can only substantially determine pH value Scope, it is difficult to accurately determine pH value.For changing to environment acid-base value, very sensitive cell and microorganism come Say, this mensuration mode is partially thick.Meanwhile, not to dissolved oxygen level in nutrient solution in microbial cultivation device The sensor being measured, this cannot just reflect the important parameter of experimental subjects growing state, in the later stage point Also an important indicator has just been lacked in analysis.
In device from the data that sensor is obtained it is in-orbit when magnetic recording.The maximum deficiency of this recording mode Magnetizing mediums may be destroyed by being that volume is big, record unstable, extraneous magnetic field, and then influence the reading of data.
Weak point present in said apparatus have impact on the use of device to a certain extent.
The content of the invention purpose of the present invention be under the specific condition of space cellular and molecular level carry out aerospace medicine Cytology research provides a kind of full-automatic spatial cell biological study platform.It can not only overcome existing well There is the deficiency of device, and there is high degree of automation, have a wide range of application, be easy to operation and maintenance, can connect The feature such as continuous monitoring in real time, display directly perceived and digitlization storage, comparative study be rigorous.
The technological approaches taken is:Structure type is modular construction, each module not only in structure each other It is independent, and be also functionally separate.Such structure type can meet the reality of space application, Effectively improve the operability and maintainability of platform in-orbit period.The present invention include shell, eight modules, Image record group and convection fan composition, eight big modules are respectively cell culture and processing, on-line checking, figure As record, temperature control, gravity control, parameter monitoring, parameter are shown and automatic control module;To ensure Resistance to shock space full-automatic cell biological study experiment porch employs symmetrical structure, all modules with Installed based on experiment porch shell.Image records experimental group and gravity and lighting module is arranged in experiment porch The heart, is coupled by Rotatable base with shell;Image recording module and temperature control modules are arranged on shell knot On structure axis, pass through respective firm banking and cage connection respectively;Cell culture utilizes tool with processing submodule The mounting seat for having symmetrical structure is symmetrically distributed in the outside of experiment porch division center;Mounting seat uses vibration isolator It is fixed on experiment porch base;Heat-insulation layer is filled between experiment porch shell and vibration isolator;Convection current wind Fan and parameter monitoring module are arranged on experiment porch corner, and parameter display module is set in experiment porch front panel On.
Described cell culture is made up of with processing module 18 completely self-contained cell culture submodules, each Individual submodule can under control system driving follow procedure setting it is autonomous complete cell-stimulating, culture, processing, The experimental implementation such as fixed, these functions are by thin included in the totally enclosed stream of cell culture submodule plus the type that declines Born of the same parents' culture is realized in loop.The loop includes silicon rubber nutrient solution storage bag, a miniature multidirectional sample-adding Pump, fixer storage bag, reagent bag, a cell culture chamber, a waste liquid collecting bag and 2-8 Section silicone rubber tube composition.Above-mentioned miniature multidirectional sample-adding pump by 6-10mm miniature cocurrent electromotors, one 6-10mm miniature reducers, main shaft, commutator and I types and II types filling head composition, multidirectional sample-adding pump main shaft I types filling head, commutator and II type filling heads are installed successively after a fixed seat.
Cell culture submodule and its cell culture chamber are being mounted with that lid after submodule lower cover with fixing on submodule , will be whole after being sprung into by an elongated insertion part in the lock hole under culture submodule on lid in module mounting seat Individual cell culture submodule is locked in mounting seat, when experiment porch is subjected to rocket launching judder and return When time receiving high acceleration impacts, cell culture submodule will not be backing out from mounting seat.After experiment terminates, Pull bar ring is depressed, then the pull bar compression spring in draw-bar seat, submodule will be cultivated by Draw bar lock by the pull bar tip Elongated insertion part draws the lock hole on lid under culture submodule, so as to take out cell culture submodule.
On-line checking module is made up of measuring cell, sensing element, lead-out wire and parameter memory.Sensitive member Part is bumped into the cell culture plane (can partly be grown on sensing element) of cell culture chamber, when cell is micro- heavy When occurring physiological change under the influence of power, the signal that measuring cell is just gathered imports parameter through lead-out wire and stored In device.
Gravity to lighting module by a vibration isolation base, a micro-stepping stepper motor, 4 cell culture submodules and its All reservation, a shaft coupling composition.Gravity is to lighting module based on vibration isolation mounts.This structure avoids this Module is interfered with other intermodules.Micro-stepping stepper motor on vibration isolation mounts passes through shaft coupling With fixed bottom plate connecting, cell culture submodule is just installed on which floor plate.
Automatic control module is main to be made up of single-chip microcomputer and Darlington switch, the rotating speed of precise control motor, profit The three-dimensional isolation system constituted with rigidity Flat-plate-type vibration isolators such as 10-30 low deadweights, the three-dimensionals of low intrinsic frequency On base, external environment condition and this intermodule reciprocal influence are alleviated.Gravity can install 4 to lighting module Individual cell culture submodule.The complete of continuous stream plus formula culture cell can be completed by having in each submodule Experimental loop.
Image recording module differs camera lens, low illumination and high resolution minisize pick-up head, energy-conserving light source by high magnification numbe With scanner-recorder composition.Image recording module is arranged on focusing sliding bottom, microlens and miniature height After precision camera is combined, it is fastened on by fixing screws in integrative protection shell, it is outer by protection The adjustment of focal length is realized in the movement of shell;Guard shield realizes that micro-stepping is moved by Focussing screw mandrel, focal length Screw mandrel front end is adjusted by joining installed in focusing sliding bottom focusing front apron and focusing backboard with focusing handwheel Connect, when adjusting focusing handwheel, it will drive the rotation of Focussing screw mandrel, and drive integrative protection shell In microlens and miniature high-precision camera along focusing sliding bottom slide, so as to realize the adjustment of focal length.
During Space Experiments platform utonomous working, the visual field of image record can be set by ground, when there is spacefarer More apparent images can be obtained during operation, more effective informations also can be just extracted from image.Image is remembered Information is stored and transmitted in digitized form by record module, eliminates the disadvantage of magnetizing mediums banking system.
Parameter monitoring module is by temperature sensor, pressure sensor, microgravity sensor, pH sensors, molten Lambda sensor is constituted.PH value detection uses high-precision semisolid neutral film pH and passed in parameter monitoring module Sensor, measurement accuracy is high.The measurement of dissolved oxygen concentration is used with high stability in cell culture environment Dissolved oxygen electrode.
The display module of full-automatic spatial cell biological study experiment porch is under MCU driving, by liquid crystal Screen shows each state parameter of monitoring, makes each parameter more directly perceived.
Described automatic control module ensures the automatic realization of above-mentioned each functions of modules.
This seven big function is combined, and is formed of the invention powerful and comprehensive comprehensive function, specific skill Art effect is described as follows:
(1) present invention may include that (sample size can be expanded according to experiment demand for 26 and more than 26 samples Fill);
(2) realize that full-automatic resting state cell-stimulating, stream plus formula cell culture, addition are stimulated, cell is fixed;
(3) can physiological change of the real time on-line nondestructive detection cell in whole experiment process;
(4) just high magnification numbe micromirror is whole to cellular morphology and structure change progress image record for profit;
(5) requirement of the cell normal growth to temperature conditionss is met using active temperature control system;
(6) it can realize automatically including temperature, oxyty, pH value, Level of Microgravity, supply voltage, pressure Deng the record of experiment porch working status parameter and cell growth ambient parameter;
(7) real-time gravity (1G or more than 1G) control experiment group is provided, effectively differentiates microgravity to experiment pair The influence of elephant;
(8) the real-time display function of parameter is provided, reference is provided for artificial dry and experiment.
Figure of description Fig. 1 is overall structure diagram of the invention.Wherein 1-1- experiment porch shell,
1-2- heat-insulation layers, 1-3- vibration isolators, 1-4- convection fans, 1-5- mounting seats, 1-6- cell culture Module, 1-7- images record experimental group, 1-8- temperature control modules, 1-9- miniature images logging modle, 1-10- gravity is with reference to module, 1-11- parameter monitorings module, 1-12- display modules.
Fig. 2 is cell culture sub-modular structure figure.Wherein 2-a is that book module side view, 2-b are book Module overlooking structure figure.2-1- media to cell culture modules mounting seat, 2-2- culture modules lower cover, 2-3- cultures Lid, 2-5- cell culture chambers, 2-6- elongated insertion parts, 2-7- locking in module bodies, 2-4- culture modules The tip, 2-8- lock hooks, 2-9- pull bars, 2-10- springs, 2-11- draw-bar seats, 2-12- pull bar rings.
Fig. 3 is experimental loop flow chart.
Fig. 4 is miniature multidirectional sample-adding pump figure.Wherein 4-1- micropumps fixed seat, 4-2- DC micromotors, The miniature all-metal reduction boxes of 4-3-, 4-4- main shafts, 4-5-I types filling head, 4-6- commutators, 4-7-II Type filling head.
Fig. 5 is on-line checking function structure chart.Wherein 5-1- lead-out wires, 5-2- protecting seats, 5-3- measurements Element, 5-4- sensing elements, 5-5- cell culture chambers, 5-6- cell culture submodules.
Fig. 6 is that gravity compares function structure chart.Wherein 6-a be module side view, 6-b be module top view, 6-1- cell culture submodule, 6-2- shaft couplings, 6-3- bases, 6-4- stepper motors, 6-5- fix bottom Plate.
Fig. 7 is image recording module block diagram.
Fig. 8 is image recording module main structure chart.Wherein bottom is slided in 8-1- microlens, 8-2- focusing Seat, 8-3- Focussings screw mandrel, 8-4- focusing front apron, 8-5- focusing backboard, 8-6- focusing hands Wheel, 8-7- fixing screws, 8-8- miniature high-precisions camera, 8-9- guard shields.
Fig. 9 is control circuit block diagram.
Figure 10 is program flow diagram.
Embodiment uses for the space full-automatic cell biological study experiment porch shown in guarantee resistance to shock Fig. 1 Symmetrical structure.Image records experimental group 1-7 and gravity and is arranged on experiment porch center to lighting module 1-10, Image recording module 1-9 and temperature control modules 1-8 is arranged on axis;Cell culture submodule 1-6 is utilized Mounting seat 1-5 with symmetrical structure is symmetrically distributed in the outside of experiment porch division center;Mounting seat 1-5 is adopted It is fixed on vibration isolator 1-3 on experiment porch base;Filled out between experiment porch shell 1-1 and vibration isolator 1-3 Heat-insulation layer 1-2 is filled;Convection fan 1-4 and parameter monitoring module 1-11 is arranged on experiment porch corner, and joins Number display module 1-12 is arranged on experiment porch front panel.
The space full-automatic cell biological study experiment porch of the present invention is first preheated before work, temperature control Module 1-8 makes environment temperature in experiment porch reach after 36.0 ± 0.5 DEG C of scopes of setting, from inside to outside successively Cell culture submodule 1-6 is installed, experiment porch enters holding state.It is micro- heavy after experiment porch transmitting is entered the orbit Force snesor detects triggering experiment porch after microgravity environment and enters working condition.Parameter monitoring module 1-11 Detect and store experiment porch state parameter, gravity enters working condition to lighting module 1-10, compares gravity Cell experiences 1G simulated gravities in group, and image recording module 1-9 automatic recording charts are as cell in record group 1-7 State before activation, each cell culture submodule 1-6, which enters in working condition, active activation cell culture chamber, to stop Dormancy cell, makes it into normal growth stage;After cell convalescence, each cell culture submodule 1-6 to Being introduced in cell culture chamber stimulates or medicine, and experiment enters the normal experimental stage;In the normal experimental stage, Line detection module detects that cell physiological changes in real time, cell record module 1-9 whole process record cellular morphology and knot Structure changes, parameter monitoring module 1-11 monitoring cell growth ambient parameters and experiment porch working status parameter, Parameter display module shows each major parameter in real time;After normal experiment terminates, media to cell culture modules is trained to cell Support room and add fixer, fixed cell;Cell culture submodule is changed, proceeds next round experiment;It is real Test after all terminating, experiment porch is shut down with gravity to lighting module 1-10, image recording module 1-9 stops work Make, temperature control modules 1-8 is stopped, the wholly off work of order of experiment porch power-off.
Cell culture submodule block main body 2-3 and cell culture chamber 2-5 shown in Fig. 2 is being mounted with to cover in module It is fixed on after 2-4 and module lower cover 2-2 on module mounting seat 2-1, elongated insertion part springs into culture module lower cover 2-2 On lock hole in, whole media to cell culture modules is locked on mounting seat 2-1.Fire is subjected in experiment porch Judder is with when high acceleration impacts when reclaiming when arrow is launched, and said structure can ensure that media to cell culture modules not Can be backing out from mounting seat.After experiment terminates, pull bar ring 2-12, the then drawing in draw-bar seat 2-11 are depressed Bar 2-9 compression spring 2-10, are drawn by Draw bar lock 2-8 by pull bar tip 2-7 by module elongated insertion part 2-6 is cultivated Go out to cultivate the lock hole on module lower cover 2-2, so as to take out media to cell culture modules.
Fig. 3 be cell culture submodule in it is totally-enclosed stream plus formula cell culture loop flow chart, the loop by Nutrient solution storage bag, miniature multidirectional sample-adding pump are fixer storage bag, medicine (or reagent) storage bag, thin Born of the same parents culturing room, waste liquid collecting bag and 4 sections of silicone rubber tube compositions.
8mm6V DC micromotors 4-2 and miniature all-metal are slowed down in miniature multidirectional sample-adding pump shown in Fig. 4 Case 4-3 combinations are lower to reach 1024: 1 high speed reducing ratio;Main shaft 4-4 after micropump fixed seat 4-1 successively I type filling heads 4-5, commutator 4-6 and II type filling head 4-7 are installed.In different experiments stage, commutator 4-6 drives different filling head work, so as to realize that multi-pipeline automatically switches.
In the present invention, cell culture is normally given birth to processing module major function for cell under space condition Long and propagation provide necessary to nutrition and dissolved oxygen, and can automatic sequence perform to the activation of cell, culture, The sequence of operations such as processing and fixation.Cell culture is with processing module by 18 completely self-contained submodule groups Into.Each submodule can under control system driving by the autonomous completion activation of program of setting, culture, The experimental implementation such as processing, fixed.Each submodule can complete the totally-enclosed of aforesaid operations including a whole set of and decline Type cell experiment loop.After the aircraft of carried experiment platform is entered the orbit, the experiment of microgravity sensor-triggered is flat Bench control system enters mode of operation, and experiment porch enters working condition, and miniature multidirectional sample-adding pump is trained to cell Supporting filling cell activator in room makes cell enter normal growth vegetative state from resting state, in normal growth (it can be set during propagation by different cells and different experiments requirement), experimental loop is automatically to culturing room In cell take the training method that continuous stream adds, i.e. fresh medium multidirectional sample-adding pump driving under with specific Flow velocity continuously flow in cell culture chamber, with ensure cell normal growth propagation during enriched Nutrition and sufficient dissolved oxygen.During normal experiment, experiment porch can be trained by different experiments purpose to cell Support and different medicine or stimulation are added in room (being added in such as cells into cardiomyocytes culturing room improves heart collecting moving function Medicine, the medicine etc. for preventing that bone calcium from losing is added into osteoblasts cultivation room).Terminate in Space Experiments Afterwards, experiment porch in real time into cell culture chamber inject fixer (be fixed liquid whether can empirically require into Row setting), cell is maintained structure and form during Space Experiments, it is to avoid cell is in aircraft recovery stage Influenceed again by various mechanics factors, it is ensured that the Space Experiments sample of recovery has Impersonal authenticity.
Because different modules is being structurally and functionally completely self-contained, therefore experiment porch can be different Different cell is cultivated in module or different processing is carried out to cell (once mounting can cultivate 26 kinds or more Different cell or the different cell processing modes for carrying out up to 26 kinds and its more than 26 kinds simultaneously).In space flight Member cooperation under, reset by simply changing submodule and program, experiment porch just can repeat experiment or Carry out other types of spatial cell research experiment.The foundation of modular construction and artificial interference interface enters one Step has embodied its huge superiority, is amplified sample quantity and opens up Guangping platform in-orbit period experiment type Key effect has been arrived, the efficiency of experiment porch is improved again.
Microscale experiment loop in submodule be it is totally enclosed, it is various need fill liquid reagents by with it Drive and flowed in silicon rubber pipeline without the multidirectional sample-adding pump that directly contacts, any step of experimentation is equal It is not related to inside experimental loop, this just farthest eliminates the contaminated possibility of sample in experimentation Property, improve the success rate of Space Experiments.
Fig. 5 shows the basic structure of on-line checking interface module, and sensing element 5-4 is bumped into cell culture chamber 5-5 cell culture plane, part cell will be grown on sensing element 5-4, when this part cell is due to micro- The influence of gravity environment condition, the signal that measuring cell 5-3 is gathered when its physiology changes is by lead-out wire 5-1 is imported in parameter storage device.
On-line checking interface module carries out space reality during can realizing Space Experiments using cell sensor system The real-time detection tested.Cell sensor can pass through cell solution variations in refractive index, soda acid under different experimental conditions The different physiological changes of the information continuous monitoring such as degree and inorganic ion concentration and analysis cell, coordinate flexible design Detection scheme, can obtain a large amount of traditional " fixation-recovery-Ground analysis " modes can not provide Real time information, research microgravity etc. factor can realize the screening of protection medicine to the influencing mechanism of cell With pharmacological research, the experimental result that each space flight experiment is obtained is greatly increased, this cell experiment is improved and puts down The analyzing and processing performance of platform.Different signal transductions are for example added by liquid ingress system and intervene reagent, can Influencing mechanism of the factors such as microgravity to cell is studied with real-time quantitative;By recording microgravity and 1G controls Under the conditions of response of the cell to same signal Signal Transduction Pathways activator, microgravity can be compared different cells are believed The influence of number transduction pathway;Add medicine (such as Quercetin) to be studied, then can be with this kind of medicine of preliminary assessment Action effect, and the information such as signal transduction pathway of its effect is obtained, so as to realize the screening of protection medicine With pharmacological research etc..
Fig. 6 shows basic structure of the gravity to lighting module.6-a is module side view, and 6-b overlooks for module Figure, wherein gravity is to lighting module based on vibration isolation mounts 6-3, and this structure avoids the module and other modules Between interfere;Micro-stepping stepper motor 6-4 on vibration isolation mounts 6-3 is by shaft coupling 6-2 with consolidating Determine base plate 6-5 connections, cell culture submodule 6-1 is mounted directly on which floor plate.
Gravity is to provide 1G control groups to the major function of lighting module.Such experimental design can be tied in the later stage Fruit effectively rejects other space environment factors (such as radiation) and transmitting landing when analyzing and processing when mechanics factor Influence, makes microgravity more prominent to impact cell.
Gravity switchs the automatic control system for setting up stepper motor to lighting module using Single-chip Controlling Darlington, The rotating speed of precise control motor, so as to be met the control group G values of requirement of experiment.Using it is multiple it is low deadweight, The three-dimensional isolation system of the rigidity such as three-dimensional of low intrinsic frequency Flat-plate-type vibration isolator composition is arranged on base 6-3, Alleviate external environment condition and this intermodule reciprocal influence.Gravity can install 4 samples (i.e. 4 to lighting module Individual cell culture submodule, control group sample number can be expanded by different experiments requirement).Due to each The full experiment loop of continuous stream plus formula culture cell can be completed by all having in submodule, and cell is during testing Change liquid or other processes without shutting down, it is to avoid cell is influenceed by microgravity upon activation.
The block diagram of image recording module is shown, figure includes in Fig. 7:It is illumination, experimental subjects, micro- Type camera lens, low-light camera head and image memory board.
Fig. 8 shows that image recording module is installed in focusing sliding bottom in the agent structure of image recording module On 8-2, after microlens 8-1 and miniature high-precision camera 8-8 are combined, by fixing screws 8-7 It is fastened in integrative protection shell 8-9, the adjustment of focal length is realized by guard shield 8-9 movement; Guard shield 8-9 realizes that micro-stepping is moved by Focussing screw mandrel 8-3, and Focussing screw mandrel 8-3 front ends lead to Cross the focusing front apron 8-4 and focusing backboard 8-5 and focusing handwheel 8-6 installed in focusing sliding bottom 8-2 Connection, when adjusting focusing handwheel 8-6, it will drive Focussing screw mandrel 8-3 rotations, and drive one Change the microlens 8-1 and miniature high-precision camera 8-8 edges focusing sliding bottom 8-2 in guard shield 8-9 Slide, so as to realize the adjustment of focal length.
In order to more preferably understand the dynamic process of cell form and structure change during Space Experiments, see in real time The newest change of cell is examined, image record mould is introduced in full-automatic spatial cell biological study experiment porch Block.The module differs camera lens, low illumination and high resolution minisize pick-up head, energy-conserving light source and image by high magnification numbe Logger is constituted.After platform is entered the orbit, energy-conserving light source is opened, high magnification numbe difference camera lens and high resolution micro Camera composition records preceding pole start recording cellular morphology and structure in image, and recorded signal is stored in image In logger.The dynamic of image recording module whole record cellular prion protein change during Space Experiments Information, is that ground experiment interpretation of result and experimentation reproduce and provide image document.The information root of module record According to requiring to pass ground back in real time or be stored in the image reservoir carried.
When Space Experiments platform is in automatic mode, the visual field of image record is set by ground.In space flight , also just can be from by simple visual field map function with regard to more apparent images can be obtained under the auxiliary of member More effective informations are extracted in image.Image recording module can install 4 samples, and (sample number can be tested factually It is required that being expanded).
Image information is digitized transmission and stored by image recording module, eliminates magnetizing mediums banking system The hidden danger of presence.
Parameter detection module is responsible for Space Experiments working platform state parameter and cell culture environment state parameter Measurement and storage.Monitored parameters include temperature, pressure, supply voltage, micro- heavy, pH, oxyty Deng.PH value detection uses high-precision semisolid neutral film pH sensors.Measurement accuracy can be controlled for a long time In ± 0.1pH scopes, measurement result directly passes ground back or deposit is carried in memory.Cell culture environment is The monitoring of oxygen concentration, cell growth change is more comprehensive under the conditions of making understanding Space Experiments.Dissolved oxygen concentration Measurement uses the high stability dissolved oxygen electrode that has, and it can be in the very first time by dissolved oxygen in cell culture The change in concentration of gas is embodied, and most direct foundation is provided to carry out Experiment intervention.
The display module of full-automatic spatial cell biological study experiment porch is under MCU driving, by liquid crystal Screen shows each state parameter of monitoring, makes each parameter more directly perceived.
Fig. 9 shows the control circuit block diagram of the present invention.
Figure 10 shows present procedure flow chart.
According to platform feature requirement and circuit theory diagrams, system software controls content bag acquisition parameter, control electricity Machine and video recorder action, and automatically shut power off.Therefore, perform software it is main by clock read-write program, Sample and storage program, the program module composition such as signal inquiry, Serial output program.
Singlechip clock frequency 6MHz, the μ s of instruction cycle 2.Real-time clock (RTC) device X1228 addresses are 1101111, E2PROM devices X24C04 (1) address is that 1010000, X24C04 (2) address code is 1010010. Input-output equipment is a notebook computer, is connected by serial communication interface, serial port communication baud rate 1200BPS。
Single-chip processor i/o mouthful distribution:
P0.0-- real-time clock (RTC) serial time clock lines
P0.1-- real-time clock (RTC) serial bidirectional data lines
P0.2-- acceleration signal test points
P0.3-- hand switches
P0.4-- video recording lamps
P0.5--EEPROM write lines
P0.6--EEPROM serial time clock lines
P0.7--EEPROM serial bidirectional data lines
P1.0-- power-offs are controlled
The rewinding of P1.1-- video cameras is controlled
P1.2-- video cameras play control
P1.4-- camera power supplies open control
P1.5-- video cameras tape transport/pause control
P1.6-- video camera tape transports start control
P1.7-- video cameras stop (closing power supply) control
P2.0, P2.1-- sampling are selected all
P2.3-- video recorder status inquiries
P2.7-- input end of motor
P3.0 (RXD) -- external microcomputer serial ports TXD ends (by level translator MAX232)
P3.1 (TXD) -- external microcomputer serial ports RXD ends (by level translator MAX232)
P3.2-- interrupt INT O, the step-by-step counting converted for V-F (rear along triggering).
V/F is converted:1000 pulse/V are produced by device LM33l, single-chip microcomputer INTO ends are input to, by fixed When device 0 in mode 2 interrupt modes produce 500 microsecond when base, external interrupt 0 is in edging trigger mode to defeated Enter pulse to be counted, according to the umber of pulse in 0.1 second, calculated rate F, calculating simulation voltage V.
Timer 1 is the Baud rate generator that serial ports is exported.
The input-output equipment of the present invention is a notebook computer, the purpose is to be easy to the debugging of system, and on ground Observing system working result when interview is tested.In order to avoid there is excessive lead, notebook computer is by serially receiving Hair device MAX232 is connected with system.By monitoring programme, system parameter setting, thermodynamic state verification and result are realized The functions such as output.The monitoring software of system mainly includes:Real-time clock time setting, video recorder control, system Status checkout, record output, the demonstration of system general reset, system operatio etc..
Experimental record output exports real year, month, day and the hour tested at that time every time, makes experimental result more Comprehensively, it is more directly perceived.Experimental record output format is:
" during order /day month year temperature power supplys "
If system electrification detects and do not connect notebook, i.e., operated by the default value of real-time master slave system.In real time Clock default value (is made) for 24 hours when being time (starting the time) 1 day 0 January in 2003.
Space Experiments platform realizes structure aeromedicine cell well under the cooperation of above-mentioned seven big modules The function of experiment porch is learned, reliable guarantee is provided to carry out aerospace medicine research in cellular and molecular level. Compared with domestic and international existing relevant device, the invention has the advantages that:
1. unique modular construction enables Space Experiments platform according to the requirement of different experiments in function and sample Building block system assembling is carried out in this quantity, the application of the platform is expanded significantly;Meanwhile, modular construction is more Beneficial to the operation and maintenance under space condition, the operating efficiency of spacefarer is improved.
2. it is completely independent in structure function, the submodule with intact cell culture experiment loop and uniqueness Assembling caliper type combining structure, can meet the particularity requirement of correlation space cytology research, enhance the pin of experiment To property and purpose, the utilization rate of space resources is improved.
3. brand-new cell sensor on-line monitoring interface module, can be with advanced spatial cell on-line checking system System is connected, and realizes the change of continuous monitoring and analysis cell under the effect of different stimulated factor, can be passed The real time information that " fixation-recovery-Ground analysis " mode of system can not be provided, improves spatial cell real Test the On-line Control and analyzing and processing performance of platform.
4. the variable synchronous gravity real-time contrast group of sample size, can exclude transmitting vibrations, overload etc. other The influence of environmental factor, strengthens the objectivity and science of the influence experiment of microgravity.
5. the all-the-way tracking that the image recording module of fine definition realizes experimentation is real there is provided space The real-time dynamic information of the change such as cellular morphology, structure, overcomes the "black box" in Space Experiments during testing Obstacle, make experimentation intuitively visual, the extreme enrichment effective information amount to obtain of experimental study.
6. the important parameter of reflection experiment porch working condition and cell culture environment can pass through parameter monitoring mould Block is recorded in real time in the digital memory more more reliable than magnetizing mediums;Or pass through aircraft data transmission platform; Realize that the ground of Space Experiments is monitored in real time.
7. display module selectively shows each parameter this just makes the work of experiment porch in real time State, cell culture environment and experimentation progress directly perceivedization, foundation is provided for artificial intervention experiment.

Claims (1)

1. a kind of full-automatic spatial cell biological study experiment porch, including shell, eight modules, image records Group and convection fan composition, eight modules be respectively cell culture with processing, on-line checking, image record, Temperature control, gravity control, parameter monitoring, parameter show and automatic control module that eight modules are in shell In installation employ symmetrical structure, all modules are installed based on shell;Image record experimental group and Gravity is arranged on experiment porch center to lighting module, is coupled respectively by Rotatable base with shell;Image is remembered Record module and temperature control modules are arranged on shell mechanism axis, pass through firm banking and cage connection;Carefully Born of the same parents cultivate utilizes the mounting seat with symmetrical structure to be symmetrically distributed in the outer of housing center structure with processing submodule Side;Mounting seat is fixed on experiment porch base using vibration isolator;Filled between platform shell and vibration isolator There is heat-insulation layer;Convection fan and parameter monitoring module are arranged on shell corner, before parameter display module is set in On plate;
Described cell culture is made up of with processing module 18 completely self-contained cell culture submodules, each Individual submodule autonomous under automatic control module driving can complete cell-stimulating, culture, processing, fixation etc. There are a totally enclosed stream plus the type cell culture loop that declines in experimental implementation, each cell culture submodule The loop includes a silicon rubber nutrient solution storage bag, miniature multidirectional sample-adding pump, a fixer storage Bag, reagent bag, a cell culture chamber, a waste liquid collecting bag and 2-8 sections of silicone rubber tubes are constituted, micro- The multidirectional sample-adding pump of type by 6-10mm miniature cocurrent electromotors, 6-10mm miniature reducers, a main shaft, change Constituted to device and I types and II types filling head, multidirectional sample-adding pump main shaft is installed I types after a fixed seat and added successively Head, commutator and II type filling heads, cell culture submodule are being provided with submodule under lid and submodule Gai Hou, the mounting seat of cell culture submodule springs into the locking under culture submodule on lid by an elongated insertion part Kong Zhonghou, whole cell culture submodule is locked in mounting seat;
Described on-line checking module is made up of measuring cell, sensing element, lead-out wire and parameter memory: Sensing element is bumped into the cell culture plane of cell culture chamber;
Described gravity is to lighting module by a vibration isolation base, micro-stepping stepper motor, 4 cell culture submodules In block and its fixed seat, a shaft coupling composition, 4 cell culture submodules and cell culture and processing module Submodule is identical, and gravity is arranged on shell to lighting module by vibration isolation mounts, and micro-stepping stepper motor passes through connection Axle device couples with fixed seat, and cell culture submodule is fixed on base plate;Automatic control module is main by monolithic Machine and Darlington switch composition, the rotating speed of precise control motor utilize 10-30 low deadweight, low intrinsic frequency The three-dimensional isolation system of the rigidity Flat-plate-type vibration isolator such as three-dimensional composition be arranged on base, gravity is to lighting module 4 cell culture submodules can be installed;
Described image recording module differs camera lens, low illumination and high resolution minisize pick-up head, section by high magnification numbe Can light source and scanner-recorder composition, image recording module be arranged on focusing sliding bottom on, microlens and Miniature high-precision camera is combined and is fastened on by fixing screws in integrative protection shell, by anti- The adjustment of the mobile meter Shi Xian focal lengths of shell is protected, guard shield realizes that micro-stepping is moved by Focussing screw mandrel, Focussing screw mandrel front end passes through installed in focusing sliding bottom focusing front apron and focusing backboard and focusing hand Wheel connection, when adjusting focusing handwheel, it will drive the rotation of Focussing screw mandrel, and drive integrative protection Microlens and miniature high-precision camera in shell are slided along focusing sliding bottom, so as to realize focal length Adjustment;
Described parameter monitoring module is sensed by temperature sensor, pressure sensor, microgravity sensor, pH PH value detection uses high-precision semisolid neutral film in device, dissolved oxygen sensor composition, parameter monitoring module The measurement of dissolved oxygen concentration uses the dissolved oxygen electricity with high stability in pH sensors, cell culture environment Pole;Described parameter display module is shown each state parameter of monitoring by liquid crystal display under MCU driving Out;
Described automatic control module ensures the automatic realization of above-mentioned each functions of modules.
CN200410029062.1A 2004-05-12 2004-05-12 Full-automatic spatial cell biological study experiment porch Expired - Lifetime CN106507801B (en)

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CN107739713A (en) * 2017-10-13 2018-02-27 中国科学院上海技术物理研究所 It is a kind of to change liquid system suitable for what spatial cell was cultivated automatically
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CN107739713A (en) * 2017-10-13 2018-02-27 中国科学院上海技术物理研究所 It is a kind of to change liquid system suitable for what spatial cell was cultivated automatically
CN108611270A (en) * 2018-05-08 2018-10-02 中国科学院力学研究所 A kind of spatial cell biomechanics experiment system
CN109012767A (en) * 2018-07-31 2018-12-18 吉林大学 A kind of medicine sampling test device under space environment
CN109632280A (en) * 2018-12-29 2019-04-16 湖北航天技术研究院总体设计所 A kind of vibration isolator test device
CN109788066A (en) * 2019-01-30 2019-05-21 北京金科汇智科技有限公司 A kind of material tests test process record system and method based on image
CN110132692B (en) * 2019-05-27 2021-09-28 福州迈新生物技术开发有限公司 Method for reducing specimen sample and consumable material loss of pathological staining system
CN110132692A (en) * 2019-05-27 2019-08-16 福州迈新生物技术开发有限公司 Method for reducing specimen sample and consumable material loss of pathological staining system
CN110791427A (en) * 2019-10-25 2020-02-14 上海东富龙医疗装备有限公司 General cell processing total station system
CN114456938A (en) * 2022-03-02 2022-05-10 蓝莲(杭州)生物科技有限公司 Rolling cell culture instrument
CN114735251A (en) * 2022-03-28 2022-07-12 逆火(太仓)空间技术有限公司 Space microgravity biological experiment payload device, method and system
CN116478808A (en) * 2023-06-21 2023-07-25 长沙迈迪克智能科技有限公司 Pipetting robot, control method and storage medium
CN116478808B (en) * 2023-06-21 2023-09-19 长沙迈迪克智能科技有限公司 Pipetting robot, control method and storage medium
CN117853850A (en) * 2024-03-07 2024-04-09 威海紫光科技园有限公司 Detection and evaluation system and method for NK cell cultivation process

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