CN102827758A - Cell microscopic observation monitor in cell factory - Google Patents
Cell microscopic observation monitor in cell factory Download PDFInfo
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- CN102827758A CN102827758A CN2012103568830A CN201210356883A CN102827758A CN 102827758 A CN102827758 A CN 102827758A CN 2012103568830 A CN2012103568830 A CN 2012103568830A CN 201210356883 A CN201210356883 A CN 201210356883A CN 102827758 A CN102827758 A CN 102827758A
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Abstract
The invention relates to a cell microscopic observation monitor in a cell factory, belonging to the technical field of bioengineering. The cell microscopic observation monitor is characterized in that a stepping motor is used to control a sample introduction driving system, so that cell culture dishes can simultaneously enter an illuminating system part and an imaging system part of the monitor; an LED (light-emitting diode) lamp is used as the illuminating system to illuminate the cell culture dishes, and cells are imaged on a CCD (charge-coupled device) through a microscopic lens with a long working distance; and cell images obtained after CCD imaging are subjected to image amplification processing through an image acquisition card and an image processing apparatus so as to obtain relatively perfect images, and the images are presented on a PC (personal computer) display. The cell microscopic observation monitor is quick and convenient to operate and low in cost, realizes automatic operation, and uses a cell factory microscopic monitoring system with a long working distance to realize the quick observation monitoring of cells in the multi-layer culture dishes in the cell factory. The cell microscopic observation monitor is widely used for cell real-time monitoring in the field of biopharmaceutical industry.
Description
Technical field
The invention belongs to technical field of bioengineering, relate to a kind of improvement of cell cultures Monitoring techniques.
Background technology
In recent years; Along with development of science and technology; Particularly cell cultures is in the fast development of field of biological pharmacy; Cell factory is a kind of mass cell culture vessel of widespread use, is made up of the multilayer petridish, thereby constantly occurs to the various microsurgical instruments that cell factory carries out monitoring observation; Yet can only carry out Real Time Observation monitoring to single petridish, at present domestic for cell factory multi-layer cellular petridish large scale culturing carry out real-time, low-cost, micro-Monitoring systems that robotization is easy report not also.Modern bio-pharmaceuticals and production of vaccine enterprise need badly a kind of fast, the cell real-time monitoring instrument and the monitoring method of low cost, robotization, easy operation.
Summary of the invention
The objective of the invention is: cell micro observation monitor in a kind of cell factory is provided, and it can be fast, low cost, robotization, easy operation, the pair cell of using long working distance are monitored in real time.
Technical scheme of the present invention is: by step motor control sample introduction drive system; Make Tissue Culture Dish get into the illumination and the imaging system part of instrument simultaneously; Then; Thrown light on as lighting system pair cell petridish by high precision cold light source LED lamp, the long working distance microlens through oblique below is imaged on the CDD at rear then; Carried out obtaining comparatively perfect image after zoom is handled through image pick-up card, image processing equipment by the cell image after the CCD imaging, image is presented on the PC indicating meter, and cell image can be handled or print at the enterprising line data of indicating meter.
Drive system comprises parts such as worktable, ball-screw, line slideway.Wherein move fore-and-aft direction, realize the comprehensive observation monitoring of petridish with this by horizontal screw lead, guide rail control petridish mounting table; Vertically leading screw, guide rail then are connected an end of optical system, and the vertical shifting up and down of control camera lens and cold light source is used for realizing observing fast simultaneously cell condition of living organism in a plurality of petridish of monitoring.
By PC end input movable signal, the control step motor carries out regularity and moves, and stepper-motor is connected the bottom of petridish mounting table, and the rotation that drives the petridish mounting table reaches moves, and realizes the complete observation monitoring of the various piece of enchylema in the petridish with this.
Image processing system partly is made up of CCD camera, image pick-up card, VDU, PC computingmachine, stamping machine etc.CCD receives the light from micro imaging system, is imaged on the CCD, through 1391 VGA image pick-up cards the image that obtains is carried out outputing on the computer video indicating meter after the acquisition process.
The invention has the beneficial effects as follows: fast, low cost, robotization, easy operation, use the micro-Monitoring systems of cell factory of long working distance, realize that the quick observation of the cell in the cell factory multilayer petridish is monitored.The cell that is widely used in the bio-pharmaceuticals industry field is monitored in real time.
Description of drawings
Fig. 1 is the apparatus structure schematic diagram;
Fig. 2 is a sample introduction drive system schematic diagram;
Fig. 3 is the system schematic diagram;
Fig. 4 is the lighting system schematic diagram;
Fig. 5 is the micro imaging system schematic diagram;
Wherein Fig. 5 a is a low power objective micro imaging system schematic diagram; Fig. 5 b is a high power objective micro imaging system schematic diagram;
Fig. 6 is the image processing system schematic diagram.
Fig. 7 is that the cell factory biomass cells is observed the monitor structure iron.
Embodiment
Embodiment 1
As shown in Figure 7, the 1st, VDU, 2 people are machine interactive systems, the 3rd, lighting source, the 4th, microlens, the 5th, worktable, the 6th, cell factory, the 7th, cell factory mounting table, the 8th, ball-screw, the 9th, line slideway.
Like Fig. 1, be the apparatus structure schematic diagram.The sample introduction drive system is got into the illumination and the imaging system part of instrument by the step motor control Tissue Culture Dish; Tissue Culture Dish is thrown light on as lighting system pair cell petridish by high precision cold light source LED lamp after getting into; Tissue Culture Dish is imaged on the CDD at rear through the long working distance microlens of oblique below after by light illumination; Carried out obtaining comparatively perfect image after zoom is handled through image pick-up card, image processing equipment by the cell image after the CCD imaging, image is presented on the PC indicating meter, and cell image can be handled or print at the enterprising line data of indicating meter.
Fig. 2 is a sample introduction drive system schematic diagram, and drive system comprises parts such as worktable, ball-screw, line slideway.Wherein move fore-and-aft direction, realize the comprehensive observation monitoring of petridish with this by horizontal screw lead, guide rail control petridish mounting table; Vertically leading screw, guide rail then are connected an end of optical system, and the vertical shifting up and down of control camera lens and cold light source is used for realizing observing fast simultaneously cell condition of living organism in a plurality of petridish of monitoring.
Fig. 3 is the system schematic diagram, and the petridish system comprises parts such as petridish mounting table, stepper-motor.By PC end input movable signal, the control step motor carries out regularity and moves, and stepper-motor is connected the bottom of petridish mounting table, and the rotation that drives the petridish mounting table reaches moves, and realizes the complete observation monitoring of the various piece of enchylema in the petridish with this.
Fig. 4 is the lighting system schematic diagram, and the light source of native system adopts the LED cold light source.1 expression illumination cold light source among the figure, the illumination that light source sends is mapped on the petridish 2, makes can evenly throw light on the petridish, and light is imaged on the VDU 4 by micro imaging system 3 through behind the petridish.
Cold light source is in the process of electric energy conversion luminous energy, by the effect of electrical principles and phosphor powder, only produces the heat energy of very small amount, more electric energy is converted to the light source of luminous energy.The characteristics of cold light source are almost all to be converted into visible light to other energy, the light of other wavelength seldom, and incandescence is just different, except visible light is arranged, also has a large amount of infrared lights, quite a few Conversion of energy has been a infrared light that illumination not have to contribute.When object was luminous, its temperature was high unlike envrionment temperature, can guarantee cell activity like this.
Fig. 5 is the micro imaging system schematic diagram.Microscopic system comprises two object lens, and a is a low power objective, and enlargement ratio is 4X, operating distance 140mm, and resolving power 3um adopts 1/3CCD.Effect is that pair cell liquid carries out scan full hard disk after petridish gets into viewing area, can reach roughly the effect of cell condition of living organism observation totally; B is a high power objective, and enlargement ratio is 10X, operating distance 140mm, and resolving power 3um adopts 1/2CCD.In the time of after utilizing scanning lens to observe overall cell live body, need examining monitoring, can adopt these object lens to carry out the part and amplify observation once more certain part cell live body.
Fig. 6 is the image processing system schematic diagram.Partly form by CCD camera, image pick-up card, VDU, PC computingmachine, stamping machine etc.CCD receives the light from micro imaging system, is imaged on the CCD, through 1391 VGA image pick-up cards the image that obtains is carried out outputing on the computer video indicating meter after the acquisition process.The image processing software that utilizes autonomous design can print, function such as cell number calculating when observing monitoring cell condition of living organism.
The operating process of 1 instrument
Preheating is 5 minutes after the start, examine cell factory 6 is placed on prepares to observe monitoring on the petridish mounting table 7.At first, through human-computer interaction system 2, the operator imports corresponding information, through the leading screw 8 of step motor control directions X, the position that guide rail 9 moves to the petridish group 6 that places suitable observation.Secondly, regulate lighting system 3 and micro imaging system 4, find the operating distance and work illuminance that are fit to observation through step motor control Y direction leading screw 8, guide rail 9; After finishing, adjusting needs in the visual field, to find a cell image place the most clearly through manual fine-tuning.Then, utilize CCD camera and VDU 1 to seek the cell condition of living organism image of required observation and inspection, also can carry out the part to image as required simultaneously and amplify, dwindle, dyeing, number calculates, independent research functions such as image print.At last, move up and down quick, the accurately observation monitoring that can realize,, can realize overall observation is monitored through rotational translation to petridish mounting table 7 to multi-layered cell factory through the Y direction of controlling micro imaging system 4.
2 cell factories with 40 layers of petridish are that example is monitored
At first connect instrument power source, preheating 5-8 minute, whole observation observation process need carry out under gnotobasis, to guarantee the good growing environment of cell.The operator needs petridish to be observed is placed on the petridish mounting table; After machine starts fully; Through the man-machine interactive system operator with input control information; Information is sent to stepper-motor after the PC end is handled, moved by step motor control horizontal direction guide rail drive cell factory mounting table to reach monitoring location to be observed.At this moment, the operator needs manual fine-tuning lighting system, micro imaging system, in the visual field, finds comparatively clear, complete cell image.
In observation process, relate to two groups of microlens, be respectively applied for the low power lens of overall observation monitoring and the high power camera lens that local detail is observed monitoring.Low power lens adopts five-spot to observe, and promptly move horizontally petridish the preliminary observation monitoring is carried out in five positions of Qi Sijiao and center, thereby preliminary growing state to overall cell has certain understanding; The high power camera lens adopts optics and digital two-stage to amplify, and observes monitoring to local detail in the petridish, better understands the cell growing state.The operator can carry out true-time operation through image processing system pair cell image when observing, like editor, preservation, printing etc.
Claims (4)
1. cell micro observation monitor in the cell factory; It is characterized in that: by step motor control sample introduction drive system; Make Tissue Culture Dish get into the illumination and the imaging system part of instrument simultaneously; Throw light on as lighting system pair cell petridish by high precision cold light source LED lamp, be imaged on the CDD at rear through the long working distance microlens tiltedly; Carried out obtaining comparatively perfect image after zoom is handled through image pick-up card, image processing equipment by the cell image after the CCD imaging, image is presented on the PC indicating meter, and cell image can be handled or print at the enterprising line data of indicating meter.
2. cell micro observation monitor in a kind of cell factory as claimed in claim 1 is characterized in that: moved fore-and-aft direction by horizontal screw lead, guide rail control petridish mounting table, realize the comprehensive observation monitoring of petridish with this; Vertically leading screw, guide rail then are connected an end of optical system, and the vertical shifting up and down of control camera lens and cold light source is used for realizing observing fast simultaneously cell condition of living organism in a plurality of petridish of monitoring.
3. cell micro observation monitor in a kind of cell factory as claimed in claim 1 is characterized in that: stepper-motor is connected the bottom of petridish mounting table, and the rotation that drives the petridish mounting table reaches moves.
4. cell micro observation monitor in a kind of cell factory as claimed in claim 1; It is characterized in that: CCD receives the light from micro imaging system; Be imaged on the CCD, the image that obtains carried out outputing on the computer video indicating meter after the acquisition process through image pick-up card.
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Cited By (10)
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CN107356500A (en) * | 2017-07-10 | 2017-11-17 | 珠海珠玻电子材料有限公司 | The infiltration system safety testing device and its method of testing of glass fabric |
CN108398103A (en) * | 2018-04-28 | 2018-08-14 | 北京大学 | A kind of high speed high throughput biological sample Morphology observation system |
CN109355177A (en) * | 2018-11-29 | 2019-02-19 | 苏州度奕星科技有限公司 | A kind of living cells monitoring device |
CN110184187A (en) * | 2019-07-08 | 2019-08-30 | 无锡瑞生医疗科技有限公司 | The online scope of minicell culture |
CN110305782A (en) * | 2019-07-15 | 2019-10-08 | 长春理工大学 | The optical axis spatial attitude of cell fermentation tank microscopic monitoring system adjusts device |
CN110715606A (en) * | 2019-11-18 | 2020-01-21 | 长春理工大学 | Cell factory bioreactor layer height dynamic calibration method based on region detection |
CN110747115A (en) * | 2019-11-19 | 2020-02-04 | 长春理工大学 | Micro-photoelectric monitoring system for bioreactor of cell factory |
CN112680345A (en) * | 2020-12-30 | 2021-04-20 | 木乃石达 | Biological cell is cultivated with observation case that has cycle recording function |
CN113388500A (en) * | 2021-06-01 | 2021-09-14 | 南京大学 | Cell culture monitoring system and method capable of being used under microgravity |
CN114149917A (en) * | 2021-11-15 | 2022-03-08 | 安徽骆华生物科技有限公司 | Integrated living cell workstation |
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Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
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CN107356500A (en) * | 2017-07-10 | 2017-11-17 | 珠海珠玻电子材料有限公司 | The infiltration system safety testing device and its method of testing of glass fabric |
CN108398103B (en) * | 2018-04-28 | 2023-11-10 | 北京大学 | High-speed high-flux biological sample form detection system |
CN108398103A (en) * | 2018-04-28 | 2018-08-14 | 北京大学 | A kind of high speed high throughput biological sample Morphology observation system |
CN109355177A (en) * | 2018-11-29 | 2019-02-19 | 苏州度奕星科技有限公司 | A kind of living cells monitoring device |
CN110184187A (en) * | 2019-07-08 | 2019-08-30 | 无锡瑞生医疗科技有限公司 | The online scope of minicell culture |
CN110305782A (en) * | 2019-07-15 | 2019-10-08 | 长春理工大学 | The optical axis spatial attitude of cell fermentation tank microscopic monitoring system adjusts device |
CN110305782B (en) * | 2019-07-15 | 2024-02-20 | 长春理工大学 | Optical axis space posture adjusting device of microscopic monitoring system of cell fermentation tank |
CN110715606A (en) * | 2019-11-18 | 2020-01-21 | 长春理工大学 | Cell factory bioreactor layer height dynamic calibration method based on region detection |
CN110715606B (en) * | 2019-11-18 | 2021-03-12 | 长春理工大学 | Cell factory bioreactor layer height dynamic calibration method based on region detection |
CN110747115A (en) * | 2019-11-19 | 2020-02-04 | 长春理工大学 | Micro-photoelectric monitoring system for bioreactor of cell factory |
CN112680345A (en) * | 2020-12-30 | 2021-04-20 | 木乃石达 | Biological cell is cultivated with observation case that has cycle recording function |
CN113388500A (en) * | 2021-06-01 | 2021-09-14 | 南京大学 | Cell culture monitoring system and method capable of being used under microgravity |
CN113388500B (en) * | 2021-06-01 | 2024-03-12 | 南京大学 | Cell culture monitoring system and method applicable to microgravity |
CN114149917A (en) * | 2021-11-15 | 2022-03-08 | 安徽骆华生物科技有限公司 | Integrated living cell workstation |
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