CN1715881A - A kind of integrated form micro-fluidic chip control and analysis platform - Google Patents
A kind of integrated form micro-fluidic chip control and analysis platform Download PDFInfo
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- CN1715881A CN1715881A CN 200410020885 CN200410020885A CN1715881A CN 1715881 A CN1715881 A CN 1715881A CN 200410020885 CN200410020885 CN 200410020885 CN 200410020885 A CN200410020885 A CN 200410020885A CN 1715881 A CN1715881 A CN 1715881A
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Abstract
A kind of integrated form micro-fluidic chip control of the present invention and analysis platform mainly comprise laser-Induced Fluorescence Detection and ccd image monitoring optical module, eight electrode dc high-voltage source modules, program control three-dimensional platform, precise injection pump module and control circuit module.Wherein optical module is according to the burnt principle design of copolymerization, and the transmitted wave optical filter adapts to different dyes and requires conveniently replaced; PMT and ccd video camera are an angle of 90 degrees to be placed, and the light intensity that enters both is distributed by saturating anti-spectroscope.The present invention has laser-Induced Fluorescence Detection and chip channel ccd image monitoring two big functions simultaneously; Power module and precise injection pump module can satisfy the chip microfluidic control requirement of difference in functionality and different integrated levels; The present invention adopts wholly computer controlled, can realize the voltage of setting, PMT response signal and each electrode of microchannel automatic focus, each electrode program output voltage and syringe pump flow velocity under the CCD monitoring and the real-time monitoring of current value etc. by Control Software.
Description
Technical field:
The present invention relates to the instrument development technology in micro-fluidic chip field, a kind of integrated form micro-fluidic chip control and analysis platform are provided especially.
Background technology:
The micro-fluidic chip technology is the hot subject of present analysis chemistry and biochemical field.So-called micro-fluidic chip technology, be meant specimen preparation related in the fields such as biological and chemical, biological with chemical reaction, separate, basic operation unit such as detection is integrated or be integrated into substantially on more than one square centimeters the chip, in order to finishing different biological or chemical courses of reaction, and a kind of technology that its product is analyzed.
The present age, the developing history of analytical chemistry showed that a kind of analytical technology will make a breakthrough, and depended on the development and the commercialization of analytical instrument to a great extent.Early stage in the micro-fluidic chip technical development, chip capillary cataphoresis is its mainstream technology, adapts with it, and the exploitation of micro-fluidic chip instrument is also based on the chip electrophoresis instrument.
Visible commercialization instrument only has two kinds on the Chinese market: the one, and by the microfluidic tool kit that Canadian micralyne company produces, another kind is the bioanalyzer 2100 that Agilent company produces.The former excitation wavelength is 532nm, and four electrodes are only arranged, and the naked eyes hand focuses on, and no current shows, no channel monitoring function, and software is simple, can not store more experimental data, can not carry out subsequent treatment such as calculated by peak area to spectrogram.The latter's chip, electrode and kit are fixed mode, can not adjust, and are not suitable for basic pilot study.
Through fast development about ten years, the micro-fluidic chip technology has broken through nascent chip manufacture technical bottleneck, has presented at present functionalization, integrated developing state.Except the chip electrophoresis technology of comparative maturity, handle (filtration, Solid-Phase Extraction etc.), cellular incubation and functional units such as screening, Micropump and little valve and all on micro-fluidic chip, tentatively realize such as online biochemical reaction (as PCR), on-line sample.In order to support this functionalization, the research of integrated micro-fluidic chip, be necessary to develop the control of integrated form micro-fluidic chip and the analytical equipment that are different from simple chip electrophoresis instrument.
Summary of the invention:
For adaptive functionsization, integrated micro-fluidic chip are studied, the invention provides a kind of integrated form micro-fluidic chip control and analysis platform, the present invention has laser-Induced Fluorescence Detection and chip channel ccd image monitoring two big functions simultaneously, and can carry out the related application and the experimental study of micro-fluidic chip easily, use operating process very convenient.
Integrated form micro-fluidic chip control of the present invention and analysis platform, according to the burnt principle design of copolymerization, it mainly is made of laser-Induced Fluorescence Detection and ccd image monitoring optical module (1), eight electrode dc high-voltage source modules (2), control circuit module (3), program control three-dimensional platform (4), precise injection pump module (5) and Control Software; It is characterized in that:
Laser-Induced Fluorescence Detection and ccd image monitoring optical module (1) adopt the burnt principle work of copolymerization, and it is fixed on the two-dimensional stage; The sequencing of on light path, arranging during according to each parts real work, it mainly is made up of laser instrument (101), dichronic mirror (103), focusing objective len (104), saturating anti-spectroscope (105), photomultiplier PMT (109), ccd video camera (110);
Wherein: photomultiplier PMT (109) is an angle of 90 degrees with ccd video camera (110) and places, and the light intensity that enters both is distributed by 90/10 saturating anti-spectroscope (105).
Integrated form micro-fluidic chip control of the present invention and analysis platform, it is characterized in that: in laser-Induced Fluorescence Detection and the ccd image monitoring optical module (1), the sequencing of arranging on light path during according to each parts real work, exciting light optical filter (102) are placed between laser instrument (101) and the dichronic mirror (103).The effect of exciting light optical filter is the parasitic light in the light that sent of elimination laser instrument, if selected laser optical source quality is enough good, and then also can be without the exciting light optical filter.
Integrated form micro-fluidic chip control of the present invention and analysis platform, it is characterized in that: in laser-Induced Fluorescence Detection and the ccd image monitoring optical module (1), the sequencing of arranging on light path during according to each parts real work, emission light optical filter (106) is between saturating anti-spectroscope (105) and photomultiplier PMT (109).The effect of emission light optical filter (106) is the elimination background stray light, makes useful fluorescence not be subjected to excessive the influence, with monitoring and the imaging purpose that reaches expection.
Integrated form micro-fluidic chip control of the present invention and analysis platform, it is characterized in that: in laser-Induced Fluorescence Detection and ccd image monitoring optical module (1), the sequencing of arranging on light path during according to each parts real work, lens (107) and pin hole (108) are placed between emission light optical filter (106) and the photomultiplier PMT (109).The effect of lens (107) is that the fluorescence that sees through emission light optical filter is focused on processing, and the effect of pin hole (108) is to select a tuftlet light after lens (107) focus on to enter photomultiplier PMT (111) to detect.
Light path part principle of work of the present invention is summarized as follows:
The laser beam that semiconductor solid state laser (101) sends is reflected by dichronic mirror (103) behind exciting light optical filter (106) elimination veiling glare, focus on the microchannel of chip (101) by focusing objective len (102) again, thereby excite the fluorescent material in the microchannel to produce fluorescence, the fluorescence that sends is collected through same focusing objective len (102), see through dichronic mirror (103) back and be divided into two bundles by saturating anti-spectroscope (105), permeation parts focuses on the back with lens (105) and enters photomultiplier PMT (111) detection by pin hole (108) again through emission light optical filter (104) elimination background stray light; Realize the image monitoring function if desired; open the red light (effect is protection photomultiplier PMT) on chip (101) top earlier; the same line focus object lens of chip microchannel image (102) are collected, and see through dichronic mirror (103) back and enter ccd video camera (110) target surface imaging by the reflection of 90/10 saturating anti-spectroscope (105).The characteristics of this light path are easy accent simple in structure, can be in the light path coupling that need not to realize under the manual situation about switching laser-Induced Fluorescence Detection and ccd image monitoring.
Integrated form micro-fluidic chip control of the present invention and analysis platform is characterized in that:
Program control three-dimensional platform (4) is made up of two parts, and wherein a part connects firmly with whole laser-Induced Fluorescence Detection and ccd image monitoring optical module (1), and another part is equipped with experiment chip operation platform; In three dimensions, can realize the interactive matching relationship of any relative position between these two parts of program control three-dimensional platform (4).So-called interactive coupling has to make the two can form relative position relation arbitrarily on three dimensions.
Integrated form micro-fluidic chip control of the present invention and analysis platform is characterized in that:
Program control three-dimensional platform (4) is driven by three precision stepper motor, the moving up and down of one of them control chip operating platform, and the horizontal two-dimensions of two whole laser-Induced Fluorescence Detection of control and ccd image monitoring optical module (1) move in addition.
Program control three-dimensional platform (4) utilizes Control Software to pass through control circuit module (3) under the ccd image monitoring and realizes the automatic focus of chip microchannel is located with accurate.
Integrated form micro-fluidic chip control of the present invention and analysis platform, it is characterized in that: precise injection pump module (5) is made up of one or more micro-injection pump, is connected with chip by connecting line and interface arrangement.
Integrated form micro-fluidic chip control of the present invention and analysis platform, it is characterized in that: emission light optical filter (106) can be extracted replacing easily out, adapts with the fluorescent dye with different emission.
Eight electrode dc high-voltage source modules (2) of the present invention are made of four identical hardboards; Include two high-voltage power modules, four high-voltage relays, a slice single-chip microcomputer and supporting voltage control circuit, voltage and current acquisition circuit on the every hardboard; Each electrode all has three kinds of states: output, suspension and ground connection.
Control circuit module of the present invention (3) comprises high voltage control and collection plate, three-dimensional platform control panel, syringe pump control panel, PMT signal acquiring board and ccd image capture card;
Wherein, high voltage control and collection plate are responsible for high pressure output and are set and gather in real time each electrode output voltage and electric current with relay status, moving of three-dimensional platform plate control three-dimensional platform, the syringe pump control panel is responsible for the syringe pump state and flow velocity is set, the PMT signal acquiring board is responsible for PMT signals collecting and digital-to-analog conversion, and the ccd image capture card is finished ccd image signals collecting and output.
The present invention carries out whole process control by Control Software to complete machine, carries out data communication by COM+ port and control circuit system;
Control Software Borland C
++Write and form, the effect of software is: each electrode output voltage and relay status are set; Moving of control three-dimensional platform; The state and the flow velocity of control syringe pump; The voltage and current value that shows each electrode in real time; Show the PMT signal graph in real time; Spectrogram amplifies and preserves; Spectrogram peak height, peak area and transit time calculating etc.
The invention provides a kind of integrated form micro-fluidic chip control and analysis platform, it has following major advantage:
1) laser-Induced Fluorescence Detection and ccd image monitoring optical module (1) has laser-Induced Fluorescence Detection and chip channel ccd image monitoring two big functions simultaneously, and need not to carry out the light path switching, and two big functions can realize simultaneously, use operating process very convenient;
2) in the associating driver module that eight electrode dc high-voltage source modules (2) and precise injection pump module (5) are formed, eight built-in electrode dc high-voltage origin systems can satisfy the chip microfluidic control requirement of most of driven, and, can adopt external two syringe pumps and corresponding interface device to drive for being not suitable for electrically driven (operated) fluid;
3) under the ccd image monitoring, utilize program control three-dimensional platform can realize the automatic focus of chip microchannel is located with accurate;
4) employing is wholly computer controlled, and Control Software can show the voltage and the current value of PMT acquired signal and each electrode in real time, can also carry out subsequent treatment to spectrogram.
Description of drawings:
The whole principle of compositionality synoptic diagram of Fig. 1;
Fig. 2 light path synoptic diagram;
Fig. 3 software workflow schematic diagram.
Embodiment:
Description of drawings:
Fig. 1: main frame top is the chip operation platform, and the preceding bottom of main frame is an optical module, and the main frame rear portion is high-voltage power module and control circuit, and syringe pump is external;
Fig. 2: solid line is represented laser, and dotted line is represented fluorescence, and central square frame is a whole light path box.
The control of present embodiment integrated form micro-fluidic chip is formed (as accompanying drawing 1) by three parts in appearance with analysis platform: main frame, precise injection pump and computing machine.Main frame top is the chip operation platform, comprises electrode suppor, chip platform etc.; The preceding bottom of main frame is optical system and three-dimensional platform; The main frame rear portion is high-voltage power module and control circuit module, comprises hardboard, three-dimensional platform control panel and PMT signal acquiring board.Syringe pump is connected with chip by teflon pipe and specific interface arrangement.Main frame and syringe pump carry out communication by COM+ port and computing machine respectively and are connected.
During concrete operations, at first chip level is placed on the chip platform, selects suitable type of drive (apply voltage or adopt syringe pump) according to functional requirement; Open laser and illuminating lamp then,, under the CCD monitoring, carry out chip microchannel focusing and check point location by moving of software control three-dimensional platform; Each electrode output voltage and syringe pump flow velocity then are set in software; Open photomultiplier PMT at last, PMT response curve and each electrode output voltage and electric current are monitored in the beginning data acquisition in real time; After finishing, collection can amplify and preservation, subsequent treatment such as peak height, peak area and transit time calculating spectrogram.
Claims (8)
1, a kind of integrated form micro-fluidic chip control and analysis platform are mainly monitored optical module (1), eight electrode dc high-voltage source modules (2), control circuit module (3), program control three-dimensional platform (4), precise injection pump module (5) formation by laser-Induced Fluorescence Detection and ccd image; It is characterized in that:
Laser-Induced Fluorescence Detection and ccd image monitoring optical module (1) are fixed on the two-dimensional stage; The sequencing of on light path, arranging during according to each parts real work, it mainly is made up of laser instrument (101), dichronic mirror (103), focusing objective len (104), saturating anti-spectroscope (105), photomultiplier PMT (109), ccd video camera (110);
Wherein: photomultiplier PMT (109) is an angle of 90 degrees with ccd video camera (110) and places, and the light intensity that enters both is distributed by 90/10 saturating anti-spectroscope (105).
2, according to described integrated form micro-fluidic chip control of claim 1 and analysis platform, it is characterized in that: in laser-Induced Fluorescence Detection and the ccd image monitoring optical module (1), the sequencing of arranging on light path during according to each parts real work, exciting light optical filter (102) are placed between laser instrument (101) and the dichronic mirror (103).
3, according to described integrated form micro-fluidic chip control of claim 1 and analysis platform, it is characterized in that: in laser-Induced Fluorescence Detection and the ccd image monitoring optical module (1), the sequencing of arranging on light path during according to each parts real work, emission light optical filter (106) is between saturating anti-spectroscope (105) and photomultiplier PMT (109).
4, according to claim 1 or 3 described integrated form micro-fluidic chip control and analysis platforms, it is characterized in that: in laser-Induced Fluorescence Detection and ccd image monitoring optical module (1), the sequencing of arranging on light path during according to each parts real work, lens (107) and pin hole (108) are placed between emission light optical filter (106) and the photomultiplier PMT (109).
5, according to described integrated form micro-fluidic chip control of claim 1 and analysis platform, it is characterized in that:
Program control three-dimensional platform (4) is made up of two parts, and wherein a part connects firmly with whole laser-Induced Fluorescence Detection and ccd image monitoring optical module (1), and another part is equipped with experiment chip operation platform; In three dimensions, can realize the interactive matching relationship of any relative position between these two parts of program control three-dimensional platform (4).
6, according to claim 1 or 5 described integrated form micro-fluidic chip control and analysis platforms, it is characterized in that:
Program control three-dimensional platform (4) is driven by three precision stepper motor, the moving up and down of one of them control chip operating platform, and the horizontal two-dimensions of two whole laser-Induced Fluorescence Detection of control and ccd image monitoring optical module (1) move in addition.
7, according to described integrated form micro-fluidic chip control of claim 1 and analysis platform, it is characterized in that: precise injection pump module (5) is made up of one or more micro-injection pump, is connected with chip by connecting line and interface arrangement.
8, according to described integrated form micro-fluidic chip control of claim 1 and analysis platform, it is characterized in that: emission light optical filter (106) adapts with the fluorescent dye of different emission.
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