CN103897985A - Electronic control system for living single cell sorting - Google Patents

Electronic control system for living single cell sorting Download PDF

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CN103897985A
CN103897985A CN201210567603.0A CN201210567603A CN103897985A CN 103897985 A CN103897985 A CN 103897985A CN 201210567603 A CN201210567603 A CN 201210567603A CN 103897985 A CN103897985 A CN 103897985A
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sorting
single cell
cell sorting
module
living single
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CN103897985B (en
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任立辉
宁康
马波
徐健
黄巍
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Qingdao Institute of Bioenergy and Bioprocess Technology of CAS
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Qingdao Institute of Bioenergy and Bioprocess Technology of CAS
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • C12M23/16Microfluidic devices; Capillary tubes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48Automatic or computerized control

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Abstract

An electronic control system for living single cell sorting aims at the problems in exiting single cell sorting, such as deviation of time and precision, low efficiency and incapability of multi-channel simultaneous sorting, and solves the problem that existing cell sorting equipment is expensive, complex in structure, large in volume and not easy to popularize, and provides an electronic control system for living single cell sorting. The electronic control system for living single cell sorting includes main modules of a power supply, an industrial control board, a storage medium, a display screen, a channel control module, a sorting module, a solenoid valve and the software system. The system has the following characteristics: (1) a multi-channel pluggable sorting control module; (2) real-time living single cell sorting; and (3) an intelligent software system.

Description

Living single cell sorting electronic system
Technical field
Patent of the present invention relates to a kind of electronic system of can hyperchannel simultaneously Living single cell being carried out the software and hardware combining of sorting, is especially applicable to being applied in micro-fluidic chip, carrying out Living single cell cell sorting.
Background technology
Single cell analysis is significant to the research of major disease early diagnosis, treatment, drug screening and cell physiological, pathologic process, has become one of focus of research at present.Because cell is minimum, diameter is generally 5-500 μ m, and volume is at fL-nL, and component concentration few (fmol-zmol), of a great variety, makes manipulation and analyze difficulty very large.Therefore, carry out the research of unicellular level, the precondition that cell sorting necessitates.
Cell sorting is the necessary means of obtaining the target cell of character homogeneous from complex environment, and micro-fluidic chip system has the advantage of following uniqueness aspect unicellular sorting:
(1) passage of micro-fluidic chip micron-scale and typical single biomass cells size match, and are suitable for single celled introducing and manipulation;
(2) development of micro-fabrication technology, makes micro-fluidic chip by integrated to the multiple manipulations such as passage and Micropump, micro-valve, microelectrode, detector;
(3) microfluidic chip analysis speed is fast, separation efficiency is high, the consumption of sample and reagent is few, can realize the high throughput analysis of cell.
Therefore, on micro-fluidic chip, carrying out cell sorting is more and more subject to people's attention.Wherein, for the liquid-flow on chip carries out automatization control, the element such as pump, valve in meta system is introduced microchip systems, the i.e. micro-valve of Micropump by the micro-processing technology based on photoetching technique.They are core components of sample driving control unit, and Micropump is commonly used to actuating fluid, and micro-valve is commonly used to control the mobile direction of fluid.Therefore adopt the micro-valve of Micropump to carry out cell sorting and unicellular proximate analysis and can realize the automatization of high level very and integrated.
But, on the one hand, along with the raising of micro-fluidic chip complexity, typical patent has US2007/0071638, US7718127, EP2191895 etc., cause the micro-valve quantity of Micropump also to increase thereupon, because the micro-valve control ratio of many group Micropumps is more loaded down with trivial details, operate also relative complex, carrying out being easy to produce deviation in cell sorting process, thus inconvenience to some extent in actual applications.At present domestic also do not have special service in the monitoring instrument of the micro-valve of many groups Micropump.In other one side, present stage, commercial cell sorting instrument was flow cytometer (US8290625), be applied in hospital, scientific research institutions, but this equipment distinct disadvantage is expensive, and complex structure, bulky, be difficult for universal.
Therefore, current existing cell sorting system, all cannot realize the object of modularization, miniaturization, intellectuality, hyperchannel sorting simultaneously.
Summary of the invention
In order to realize hyperchannel, high efficiency sorting cells and to simplify the micro-valve control system of Micropump, solve existing flow cytometer expensive simultaneously, complex structure, bulky, be difficult for universal problem, the present invention is according to the feature of micro-fluidic chip and the micro-valve principle of work of Micropump and actual requirement, develop a Living single cell sorting electronic system instrument, this instrument module structure design, adopt the high device of integrated level, develop intelligentized software system simultaneously, can realize Living single cell sorting in real time automatically.
The technical solution used in the present invention is adopt pluggable module structure design and construct highly efficient, unified software platform (Fig. 1) thereon.Be characterized in that (1) hyperchannel can plug selection control module, voltage is adjustable.(2) real-time active somatic cell sorting function (3) intelligent software system.
(1) hyperchannel can plug selection control module
This hardware system adopts Modular Structure Design, is designed with altogether 9 selection control modules, in conjunction with sorting module, can carry out at most 144 passage cell sortings simultaneously.Wherein each passage can be realized the basic selection control operation such as switch, time delay.9 selection control modules can plug, and can increase as required or pull out selection control module.
Meanwhile, native system has designed VRM Voltage Regulator Module, regulating voltage size according to actual needs, and voltage variable range is 0-24V.Can realize the different effect of disparate modules service voltage simultaneously.
(2) real-time Living single cell sorting function
Cell sorting function is realized by selection control module, sorting module, micro-fluidic chip.The signals such as the acousto-optic-electric providing according to sorting module, judge that by respective logic real-time and selection control module communicates, thereby control the mobile passage of cell, reach flowing through unicellular object of carrying out sorting in micro-fluidic chip.
(3) intelligent software system
These software system adopt the INTERFACE DESIGN of hommization and good program frame to build, and make user's monitoring instrument (Fig. 2) eaily.After instrument starts, software system can be inserted selection control module number by automatic decision, adjust interface and relevant parameters according to module number.Then selection control module switch, time delay and voltage swing are set as required, and in real time with sorting module communication, obtain the sorting signals that sorting module provides, according to signal come to the stream of cells of control respective channel to.
Therefore this software platform depends on Living single cell sorting electronic system hardware platform, only cooperatively interacts and can bring into play the function of the unicellular sorting of high-performance.
The invention has the beneficial effects as follows, Living single cell sorting electronically controlled software system match with electronic system hardware platform, the time of the unicellular appearance of sorting and the bottleneck of precision upper variation of tolerance and inefficiency are overcome, and effectively realized the integrated and miniaturization of Controlling System, be easy to universal market.It is unicellular towards miniaturization, integrated, intelligent direction development that application of the present invention will be accelerated sorting, and then the research of speed-raising single cell analysis.
Brief description of the drawings
The hardware structure of Fig. 1, Living single cell sorting electronic system.Its major portion is: the first, Mini-ITX mainboard, adopt ultralow Consumption, and there is superpower performance and extended capability simultaneously.The second, selection control module, has designed 9 control modules, and can increase as required or pull out control module, has improved the practicality of instrument.The 3rd, sorting module, this module is in the signal detection of sound, optical, electrical signal, and sends message according to detected result to software system.The 4th, voltage adjustable module.Regulation output voltage swing according to actual needs, voltage range is 0-24V, thereby increases the range of application of instrument.
Fig. 2, Living single cell sorting electronic system software workflow.Its flow process key step is: first, and instrument initialize.After instrument starts, software system automatic decision inserts selection control module number, adjusts display interface and relevant parameters according to insert module quantity.Secondly, related work parameter is set.According to the equipment connecting in selection control module, output voltage size need to be set, and passage working order is carried out to parameter setting.Finally start to carry out cell sorting.Start according to actual needs power supply or timing power supply, the different sorting signalses such as the acousto-optic-electric providing according to sorting module and respective logic judge to be controlled magnetic valve, thereby the micro-valve of Micropump is controlled, reached the object of sorting cells, experiment finishes rear power-off shutdown.
Embodiment
In Fig. 1, Living single cell sorting electronic system hardware basic configuration is: the industrial control board that comprises pci bus and USB port, and internal memory is at least more than 1GB, and hard disk is at least more than 50G.
In Fig. 2, the software platform basic configuration of Living single cell sorting electronic system is: Windows XP operating system, and prepackage Living single cell sorting electronically controlled software system, software system are furnished with electronic edition operation instruction.
Reference
1.Karsten Kraiczek et al.Parallel processing microfluidic chip. U.S. Patent number: US, 2007/0071638
2.Reiner
Figure BSA00000829283500031
microfluidic chip. U.S. Patent number: US, 7718127.
3.Masataka Shinoda.Microparticle analysis device, microfluidic chip for microparticleanalysis, the and microparticle analysis method. European Union patent No.: EP, 2191895.
4.Charles S.Bay, Jeffrey W.Degeal et al.Flow cytometer sorter. U.S. Patent number: US, 8290625.

Claims (3)

1. the Living single cell sorting electronic system of a software and hardware combining, it is characterized in that: instrument comprises energy supply control module, sorting module, hyperchannel selection control module, industrial control board etc. and base software system thereon, can control selection control module number and adjust electric power output voltage by demand, judge that according to the different sorting signalses such as acousto-optic-electric and respective logic real-time and selection control module communicates, thereby control the mobile passage of cell, in conjunction with micro-fluidic chip, reach the single celled object of hyperchannel sorting simultaneously.
2. Living single cell sorting electronic system according to claim 1, it is characterized in that: instrument hardware system comprises power supply, industrial control board, storage media, display screen, passage control module, sorting module, magnetic valve etc., is a portable pluggable instrument.
3. Living single cell sorting electronic system according to claim 1, is characterized in that: instrument software system comprises the complete Living single cell sorting electronically controlled software of Living single cell sorting electronically controlled hardware system compatibility.These software system adopt the INTERFACE DESIGN of hommization and good program frame to build, and control sorting module and adjust electric power output voltage according to different sorting signalses and respective logic judgement, make user control eaily unicellular sorting.
CN201210567603.0A 2012-12-25 2012-12-25 living single cell sorting electronic control system Expired - Fee Related CN103897985B (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106148159A (en) * 2015-03-23 2016-11-23 西南大学 A kind of fast-growth microalgae algae plant height throughput screening systems and method
WO2019080905A1 (en) * 2017-10-25 2019-05-02 中国科学院青岛生物能源与过程研究所 Raman activated droplet sorting system and method
CN113664820A (en) * 2021-08-11 2021-11-19 华中科技大学 A micro-fluidic chip and software robot for software robot logic control

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005089944A2 (en) * 2004-03-17 2005-09-29 Goetzen Reiner Microfluidic chip
US20070071638A1 (en) * 2004-05-22 2007-03-29 Karsten Kraiczek Parallel processing microfluidic chip
CN101738357A (en) * 2008-11-19 2010-06-16 索尼株式会社 Microparticle analysis device, microfluidic chip for microparticle analysis, and microparticle analysis method
CN101743303A (en) * 2007-04-20 2010-06-16 赛路拉公司 Cell sorting system and methods
CN102019277A (en) * 2010-10-29 2011-04-20 北京惟馨雨生物科技有限公司 Sorter and sorting method for separating cells and particles
CN103298922A (en) * 2011-03-29 2013-09-11 南京新诺丹生物技术有限公司 Multifunctional bioreactor system and methods for cell sorting and culturing
CN103333799A (en) * 2013-07-09 2013-10-02 广州一代医药科技有限公司 Magnetic cell sorting apparatus based on nanoferritin adsorption

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005089944A2 (en) * 2004-03-17 2005-09-29 Goetzen Reiner Microfluidic chip
US20070071638A1 (en) * 2004-05-22 2007-03-29 Karsten Kraiczek Parallel processing microfluidic chip
CN101743303A (en) * 2007-04-20 2010-06-16 赛路拉公司 Cell sorting system and methods
CN101738357A (en) * 2008-11-19 2010-06-16 索尼株式会社 Microparticle analysis device, microfluidic chip for microparticle analysis, and microparticle analysis method
CN102019277A (en) * 2010-10-29 2011-04-20 北京惟馨雨生物科技有限公司 Sorter and sorting method for separating cells and particles
CN103298922A (en) * 2011-03-29 2013-09-11 南京新诺丹生物技术有限公司 Multifunctional bioreactor system and methods for cell sorting and culturing
CN103333799A (en) * 2013-07-09 2013-10-02 广州一代医药科技有限公司 Magnetic cell sorting apparatus based on nanoferritin adsorption

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106148159A (en) * 2015-03-23 2016-11-23 西南大学 A kind of fast-growth microalgae algae plant height throughput screening systems and method
WO2019080905A1 (en) * 2017-10-25 2019-05-02 中国科学院青岛生物能源与过程研究所 Raman activated droplet sorting system and method
CN113664820A (en) * 2021-08-11 2021-11-19 华中科技大学 A micro-fluidic chip and software robot for software robot logic control

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