CN1815186A - Multifunction chip-detecting apparatus - Google Patents
Multifunction chip-detecting apparatus Download PDFInfo
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- CN1815186A CN1815186A CN 200610024484 CN200610024484A CN1815186A CN 1815186 A CN1815186 A CN 1815186A CN 200610024484 CN200610024484 CN 200610024484 CN 200610024484 A CN200610024484 A CN 200610024484A CN 1815186 A CN1815186 A CN 1815186A
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Abstract
Multifunction chip inspection unit includes one frame, platform for holding chip, light path detecting module, light path inversion mechanism and control interface system. Said detecting light path in photoelectric detection module is located above chip platform, when reflection mirror of light path switch is in light path, array chip co-focusing scanning, miniflow control chip laser-induced fluorescence, and array chip CCD scanning can be completed. Said invention has wide applicability, flexible detecting light path regulation and data processing completed by computer.
Description
Technical field
The present invention relates to the biochip of life science, medical science, analytical chemistry, particularly a kind of multifunction chip-detecting apparatus, this device possess micro-fluidic chip laser-Induced Fluorescence Detection, array chip laser confocal scanning, array chip CCD simultaneously and scan three kinds of functions.
Background technology
Biochip is the product that has characteristics of the times in recent years in the high-technology field, belongs to molecular biology, physics and microelectronic comprehensive crossing domain.Biochip is widely used in fields such as life science, medical science, environmental monitoring, food industry, scientific research, biology sensor, various biochemical reaction process in these fields are carried out integrated, thereby realize bioactivators such as biomacromolecule, protein, microorganism are carried out the test and the analysis of efficient quick.
The laser-Induced Fluorescence Detection device has the micro-fluidic chip analyzer that Canadian Albert company produces, the 2100 type biological analysers that human relations company in Anji produces etc., and its ultimate principle is that the laser that laser instrument produces becomes approximate monochromatic light through an optical filter; This monochromatic light shines in the microchannel of chip through object lens then through semi-transparent semi-reflecting lens; Ducted fluorescent material inspires the fluorescence of certain wavelength after obtaining energy under the irradiation of laser.Then, excited fluorescent is passed through object lens, semi-transparent semi-reflecting lens again, and transmission is after optical filter filters out the light of non-excitation wavelength, and exciting light is collected by photomultiplier through diaphragm again, after amplifying light signal is transformed into electric signal, by Computer Processing.
Laser scanning confocal micro-scope is a kind of novel analytical instrument that the eighties is come out, because characteristics such as its high resolving power, high sensitivity and high power, on molecular level, can do multiple functional measurement and analysis, become the important tool of analysis, laser scanning confocal micro-scope is to dispose LASER Light Source, scanister, conjugation focalizer and detection system and the novel microscope that forms on the microscope basis.Product is mainly from the Bio-Rad and the Meridian company of the U.S., the Zeiss and the Leica company of Germany.
The array chip ccd scanner is with respect to the laser co-focusing chip scanner, and is relatively simple for structure.Biochip excites the fluorescence that produces down at the monochromatic light after exciting the spike interference filter optical filtering, and the spike interference filter before the CCD camera lens is caught by pick-up lens and is imaged on the CCD chip.Picture signal directly is transferred on the image card by the CCD camera, is directly handled by computing machine.CCD can only read an image under the excitation wavelength at every turn, for the chip of multicolor fluorescence dye marker, needs to change optical filter and excitation source, because the CCD chip scanner reads entire chip simultaneously, does not therefore need the moving chip platform.
The instrument of above-mentioned functions refers to only possess single function, in order to realize different chip operations, often needs to buy simultaneously these instruments.
Summary of the invention
The objective of the invention is in order to overcome above-mentioned shortcoming of the prior art, the invention provides a kind of multifunction chip-detecting apparatus, it should possess carries out confocal scanning, CCD scanning and three kinds of functions of laser-Induced Fluorescence Detection to array chip, has the characteristics of a tractor serves several purposes.
Technical scheme of the present invention is as follows:
A kind of multifunction chip-detecting apparatus comprises a frame and chip platform, and it also comprises:
1. detect the light path module, be one to fixedly install the module that detects light path, its light path is constructed as follows: a light source, the working direction of sending light beam along this light source with optical axis set gradually first optical filter and semi-transparent semi-reflecting lens, this semi-transparent semi-reflecting lens and the placement at 45 of above-mentioned light beam, folded light beam direction at this semi-transparent semi-reflecting lens is object lens, see through the described chip platform of this objective lens beam-pointing, see through described semi-transparent semi-reflecting lens by chip laser light reflected fluorescent light beam, in this transmitted light direction is change-over switch and the ccd detector with catoptron, is second optical filter successively on the reflected light path of described light path change-over switch, lens, diaphragm and photomultiplier;
2. light path invert mechanism, this light path invert mechanism is fixed on the described frame, by outer shaft, interior axle, annular arm and interior axle are formed with the fixed mechanism of outer shaft, described annular arm is fixed on an end of described interior axle, should in axle other end level and be set in coaxially in the bearing of horizontal cavity of described outer shaft, described annular arm is fixed described detection light path module, also be provided with fixed mechanism between axle and the outer shaft in described, under manual situation, axle can slide by along continuous straight runs in the inner chamber of outer shaft in described, again can be around 360 ° of rotations of transverse axis, drive annular arm and detect the light path module around described chip platform rotation, aim at the chip of chip platform when thing border group after, described interior axle is locked by described fixed mechanism with the relative position of outer shaft;
3. control interface system: the output of described photomultiplier is through filtering circuit, amplifying circuit, modulus converter A/D, to single-chip microcomputer; The instruction of the gain of the control photomultiplier that computing machine sends sends to photomultiplier through single-chip microcomputer and the 4th digital to analog converter D/A; Described ccd detector links to each other with computing machine through image pick-up card; Single-chip microcomputer links to each other with computing machine through the RS232 interface; The instruction of the control chip platform motion that computing machine sends sends to X-axis motor, the y-axis motor of controlling platform motion, the motion of chip for driving platform through the first digital to analog converter D/A and the second digital to analog converter D/A respectively through single-chip microcomputer; The instruction of the adjustment objective lens focal length that computing machine sends sends to the focusing motor through single-chip microcomputer through the 3rd digital to analog converter D/A, to adjust the focal length of objective lens.
Described light source is made up of white light source and LASER Light Source with optical axis, and described LASER Light Source can be changed as required, so that select suitable operation wavelength.
All optical elements of described detection light path module all are placed in the corresponding draw-in groove, and this draw-in groove has the loading and unloading member of respective optical element.
Described objective lens and its support are by being threaded, by focusing Electric Machine Control screw thread rotation, to regulate the focal length of objective lens.
Described light path change-over switch is toggle switch or the parallel movable switch of pivoting.
The aperture of the diaphragm of described diaphragm has adjusting mechanism.
The mobile accuracy of described chip platform is better than 100 μ m.
Described computing machine has the data acquisition process program.
The wave filter of the photomultiplier output signal in the described Photoelectric Detection module adopts the Order RC low-pass filter.
The fixed mechanism of described light path invert mechanism be one by outer shaft penetrate in the axle puller bolt.
Technique effect of the present invention:
LASER Light Source among the present invention in the Photoelectric Detection module can be changed, and selectes according to the needed optical maser wavelength of earnest to be measured, and the wavelength usable range of apparatus of the present invention is broader, uses flexibly;
Among the present invention in the detection light path of Photoelectric Detection module all optical mirror slips all be placed in the corresponding draw-in groove, can change at any time as required, adjustable positions has improved the Device Testing dirigibility;
The focal length of described objective lens is adjustable; The aperture of diaphragm is adjustable, and the fine setting scope is 2 μ m～28 μ m;
Detection light path in the described Photoelectric Detection module is above chip platform, and the catoptron of described light path change-over switch can be finished the confocal scanning of array chip in light path the time;
Detection light path in the described Photoelectric Detection module is below chip platform the time, and the catoptron of described light path change-over switch can be finished the laser-Induced Fluorescence Detection of micro-fluidic chip in light path the time;
Detection light path in the described Photoelectric Detection module is above chip platform, and the catoptron of described light path change-over switch can be finished the CCD scanning of array chip when shifting out light path;
The present invention is applied widely, and it is flexible to detect the light path adjustment, and data processing is finished automatically by computing machine.
Description of drawings
Fig. 1 detects the light path principle block diagram of light path module for apparatus of the present invention;
Fig. 2 is the computer control interface synoptic diagram of apparatus of the present invention;
Fig. 3 is the middle light path invert mechanism synoptic diagram of apparatus of the present invention;
Among the figure:
1-detects the light path module; The 101-light source; 102-first optical filter;
The 103-semi-transparent semi-reflecting lens; The 104-objective lens; 105-light path change-over switch; 106-second optical filter;
The 107-lens; The 108-diaphragm; The 109-photomultiplier; The 110-CCD detector;
11-light path invert mechanism; The 111-fixed mechanism; The 112-outer shaft;
Axle in the 113-; 114-annular arm;
The 2-filtering circuit; The 3-amplifying circuit;
The 4-computing machine; The 41-image pick-up card; The 42-RS232 interface;
The 5-converter; The 51-first digital to analog converter D/A; The 52-second digital to analog converter D/A;
53-the 3rd digital to analog converter D/A; 54-the 4th digital to analog converter D/A;
The 55-modulus converter A/D;
The 6-drive motor; The 61-X spindle motor; The 62-Y spindle motor; The 63-motor of focusing;
The 7-chip platform; The 8-biochip; The 9-single-chip microcomputer.
Embodiment
The invention will be further described below in conjunction with accompanying drawing, but should not limit protection scope of the present invention with this.
As shown in Figure 1 to Figure 3, the present invention is a kind of multifunction chip-detecting apparatus, and its formation comprises:
One frame and confession chip platform 7 also comprise:
1. detect light path module 1 (as shown in Figure 1), be one to fixedly install the template that detects light path, its light path is constructed as follows: a light source 101, the working direction of sending light beam along this light source 101 with optical axis set gradually first optical filter 102 and semi-transparent semi-reflecting lens 103, this semi-transparent semi-reflecting lens 103 and the placement at 45 of above-mentioned light beam, folded light beam direction at this semi-transparent semi-reflecting lens 103 is an objective lens 104, see through the described chip platform 7 of beam-pointing of this objective lens 104, fluorescent light beam by chip 8 reflections sees through described semi-transparent semi-reflecting lens 103, in this transmitted light direction is light path change-over switch 105 and the ccd detector 110 with catoptron, is second optical filter 106 successively on the reflected light path of described light path change-over switch 105, lens 107, diaphragm 108 and photomultiplier 109;
2. light path invert mechanism 11 (as shown in Figure 3), this light path invert mechanism 11 is fixed on the described frame, by outer shaft 112, interior axle 113, annular arm 114 and interior axle 113 are formed with the fixed mechanism 111 of outer shaft 112, described annular arm 114 is fixed on an end of described interior axle 113, should in axle other end level of 113 and being set in coaxially in the bearing of horizontal cavity of described outer shaft 112, described annular arm 114 fixing described detection light path modules 1, also be provided with fixed mechanism 111 between axle 113 and the outer shaft 112 in described, under manual situation, axle 113 can slide by along continuous straight runs in the inner chamber of outer shaft 112 in described, again can be around 360 ° of rotations of transverse axis, drive annular arm 114 and detect light path module 1 around described chip platform 7 rotations, after thing border group 104 was aimed at the chip of chip platform 7, described interior axle 113 was locked by described fixed mechanism 111 with the relative position of outer shaft 112;
3. control interface system (as shown in Figure 2): the output of described photomultiplier 109 is through filtering circuit 2, amplifying circuit 3, modulus converter A/D 55, to single-chip microcomputer 9; The instruction of the gain of the control photomultiplier 109 that computing machine 4 sends sends to photomultiplier 109 through single-chip microcomputer 9 and the 4th digital to analog converter D/A54; Described ccd detector 110 links to each other with computing machine 4 through image pick-up card 41; Single-chip microcomputer 9 links to each other with computing machine 4 through RS232 interface 42; The instruction of control chip platform 7 motions that computing machine 4 sends sends to X-axis motor 61, the y-axis motor 62 that control platform 7 moves, the motion of chip for driving platform 7 through the first digital to analog converter D/A51 and the second digital to analog converter D/A52 respectively through single-chip microcomputer 9; The instruction of adjustment objective lens 104 focal lengths that computing machine 4 sends sends to focusing motor 63 through single-chip microcomputer 9 through the 3rd digital to analog converter D/A53, to adjust the focal length of objective lens 104.
Described light source 101 is made up of white light source and LASER Light Source with optical axis, and described LASER Light Source can be changed as required, so that select suitable operation wavelength.
All optical elements of described detection light path module 1 all are placed in the corresponding draw-in groove, and this draw-in groove has the loading and unloading member of respective optical element.
Described objective lens 104 and its support are by being threaded, by focusing Electric Machine Control screw thread rotation, to regulate the focal length of objective lens.
The light path change-over switch 105 of the catoptron in the described Photoelectric Detection module 1 is toggle switch or the parallel movable switch of pivoting.
The aperture of the diaphragm of described diaphragm 108 has adjusting mechanism.
The mobile accuracy of described chip platform 7 is better than 100 μ m.
Described computing machine 4 has the data acquisition process program; Described single-chip microcomputer 9 is the 89C51 single-chip microcomputer.
The wave filter 2 of described photomultiplier 109 output signals adopts the Order RC low-pass filter.
The fixed mechanism 11 of described light path invert mechanism 11 be one penetrate by outer shaft 112 in axle 113 puller bolt.
Apparatus of the present invention have three kinds of functions:
1. the laser-Induced Fluorescence Detection of micro-fluidic chip, its program is as follows:
1. adjust each component of the detection light path module 1 in the multifunction chip-detecting apparatus of the present invention as required;
2. manually the position of described detection light path module 1 is placed the below of chip platform 7;
3. send the instruction of regulating photomultiplier 109 gains by computing machine 4, send single-chip microcomputer 9, regulate the gain of photomultiplier through the 4th digital to analog converter 54 through RS232 interface 42;
4. the catoptron with light path change-over switch 105 resets, the LASER Light Source of light source 101 is sent the laser of specific wavelength, be radiated at the microchannel of the micro-control stream chip 8 that is arranged on the chip platform 7 successively through objective lens 104 through first optical filter 102, semi-transparent semi-reflecting lens 103 and reflection, material in this microchannel produces fluorescence under the effect of exciting light.This fluorescence is successively through objective lens 104, semi-transparent semi-reflecting lens 103 and 105 reflections of light path change-over switch, filter through second optical filter 106 then, eliminate the outer parasitic light of fluorescence, fluorescence is again through lens 107, diaphragm 108, receive by photomultiplier 109, the electric signal that produces is after filtering circuit 2 filtering, amplify through amplifying circuit 10, amplifying signal is converted to through analog to digital converter 55 and sends into computing machine 4 by RS232 interface 42 after digital signal send single-chip microcomputer 89C519 to handle, computing machine 4 service data acquisition process programs are finished the fluoroscopic examination for the treatment of microchannel in the micrometer control stream chip 8.
2. the laser confocal scanning of array chip, its program is as follows:
1. adjust each component of the detection light path module 1 in the multifunction chip-detecting apparatus of the present invention as required;
2. the position that manually will detect light path module 1 places the top of chip platform 7;
3. send the instruction of regulating photomultiplier 109 gains by computing machine 4, send single-chip microcomputer 89C519, regulate the gain of photomultiplier 109 through the 4th digital to analog converter 54 through RS232 interface 42;
4. the reflective mirror of light path change-over switch 105 resets;
5. according to the specification of array chip, computing machine 4 sends control chip platform 7 along the moving speed of X, y-axis shift and the instruction of distance, after RS232 interface 42 is sent into single-chip microcomputer (89C51) 9 processing, through first digital to analog converter 51 and second digital to analog converter 52, produce pulse signal control X, Y-axis motor servo driver, drive the motion of X, Y-axis servomotor, by 62 chip for driving platforms, 7 motions of chip platform 7 travel mechanisms.
6. in the moving process of chip platform 7, the LASER Light Source of light source 101 is sent the laser of specific wavelength, through first optical filter 102, semi-transparent semi-reflecting lens 103 and reflection are radiated at the array chip 8 that is positioned on the chip platform 7 through objective lens 104, material in this array chip is under the effect of exciting light, produce fluorescence, this fluorescence is through objective lens 104, semi-transparent semi-reflecting lens 103, the mirror reflects of light path change-over switch 105, filter through second optical filter 106, eliminate the outer parasitic light of fluorescence, fluorescence is again through lens 107, diaphragm 108, received by photomultiplier 109, the electric signal of generation is behind filtering circuit 2 and amplifying circuit 10, and amplifying signal is converted to through analog to digital converter 55 and sends into computing machine 4 by RS232 interface 42 after digital signal send single-chip microcomputer (89C51) 9 to handle, computing machine 4 service data acquisition process programs are finished the laser confocal scanning to array chip to be measured.
3. the CCD of array chip scanning
1. adjust each component of the detection light path module 1 in the multifunction chip-detecting apparatus of the present invention as required;
2. the position that manually will detect light path module 1 places the top of chip platform 7;
3. the light path change-over switch is shifted out reflective mirror 105;
4. the LASER Light Source of light source 101 is sent the laser of specific wavelength, shine the array chip 8 that is positioned on the chip platform 7 through first optical filter 102, semi-transparent semi-reflecting lens 103 reflections through objective lens 104, material in this array chip is under the effect of exciting light, produce fluorescence, this fluorescence is through objective lens 104, semi-transparent semi-reflecting lens 103, receive by CCD110 by the light path change-over switch, send into computing machine 4 by image pick-up card 41, computing machine 4 service data acquisition process programs are finished the CCD scanning to array chip to be measured.
From the above, apparatus of the present invention provide a kind of multifunction chip-detecting apparatus, and it possesses carries out confocal scanning, CCD scanning and three kinds of functions of laser-Induced Fluorescence Detection to array chip, has the characteristics of a tractor serves several purposes.
Claims (10)
1. a multifunction chip-detecting apparatus comprises a frame and the chip platform of placing for chip (7), it is characterized in that also comprising:
1. detect light path module (1), be one to fixedly install the module that detects light path, its light path is constructed as follows: a light source (101), the working direction of sending light beam along this light source (101) with optical axis set gradually first optical filter (102) and semi-transparent semi-reflecting lens (103), this semi-transparent semi-reflecting lens (103) and the placement at 45 of above-mentioned light beam, folded light beam direction at this semi-transparent semi-reflecting lens (103) is objective lens (104), see through the described chip platform of this objective lens (104) beam-pointing (7), fluorescent light beam by the chip reflection sees through described semi-transparent semi-reflecting lens (103), in this transmitted light direction is light path change-over switch (105) and the ccd detector (110) with catoptron, is second optical filter (106) successively on the reflected light path of described light path change-over switch (105), lens (107), diaphragm (108) and photomultiplier (109);
2. light path invert mechanism (11), this light path invert mechanism (11) is fixed on the described frame, by outer shaft (112), interior axle (113), annular arm (114) and interior axle (113) are formed with the fixed mechanism (111) of outer shaft (112), described annular arm (114) is fixed on an end of described interior axle (113), should in axle (113) other end level and be set in coaxially in the bearing of horizontal cavity of described outer shaft (112), described annular arm (114) is fixed described detection light path module (1), also be provided with fixed mechanism (111) between axle (113) and the outer shaft (112) in described, under manual situation, axle (113) along continuous straight runs in the inner chamber of outer shaft (112) slides in described, or around 360 ° of rotations of transverse axis, drive annular arm (114) and detect light path module (1) around described chip platform (7) rotation, aim at the chip of chip platform (7) when thing border group (104) after, described interior axle (113) is locked by described fixed mechanism (111) with the relative position of outer shaft (112);
3. control interface system: the output of described photomultiplier (109) is through filtering circuit (2), amplifying circuit (3), modulus converter A/D (55), to single-chip microcomputer (9); The instruction of the gain of the control photomultiplier (109) that computing machine (4) sends sends to photomultiplier (109) through single-chip microcomputer (9) and the 4th digital to analog converter D/A (54); Described ccd detector (110) links to each other with computing machine (4) through image pick-up card (41); Single-chip microcomputer (9) links to each other with computing machine (4) through RS232 interface (42); The instruction of control chip platform (7) motion that computing machine (4) sends sends to X-axis servomotor (61), the Y-axis servomotor (62) that control chip platform (7) moves, the motion of chip for driving platform (7) through the first digital to analog converter D/A (51) and the second digital to analog converter D/A (52) respectively through single-chip microcomputer (9); The instruction of adjustment objective lens (104) focal length that computing machine (4) sends sends to focusing servomotor (63) through single-chip microcomputer (9) through the 3rd digital to analog converter D/A (53), to adjust the focal length of objective lens (104).
2. multifunction chip-detecting apparatus according to claim 1 is characterized in that described light source (101) is made up of white light source and LASER Light Source with optical axis, and described LASER Light Source can be changed as required, so that select suitable operation wavelength.
3. multifunction chip-detecting apparatus according to claim 1 is characterized in that all optical elements of described detection light path module (1) all are placed in the corresponding draw-in groove, and this draw-in groove has the loading and unloading member of respective optical element.
4. multifunction chip-detecting apparatus according to claim 1 is characterized in that described objective lens (104) and its support are by being threaded, by focusing servomotor (63) control screw thread rotation, to regulate the focal length of objective lens (104).
5. multifunction chip-detecting apparatus according to claim 1, the light path change-over switch (105) that it is characterized in that described catoptron is the element with logical light and reflected light function, it is toggle switch or the parallel movable switch of pivoting.
6. multifunction chip-detecting apparatus according to claim 1 is characterized in that the aperture of the diaphragm of described diaphragm (108) has adjusting mechanism.
7. multifunction chip-detecting apparatus according to claim 1 is characterized in that the mobile accuracy of described chip platform (7) is better than 100 μ m.
8. multifunction chip-detecting apparatus according to claim 1 is characterized in that described computing machine (4) has the data acquisition process program.
9. multifunction chip-detecting apparatus according to claim 1 is characterized in that the filtering circuit (2) of described photomultiplier (109) output signal adopts the Order RC low-pass filter.
10. according to each described multifunction chip-detecting apparatus of claim 1 to 9, the fixed mechanism (111) that it is characterized in that described light path invert mechanism (11) is one to penetrate the puller bolt of interior axle (113) by outer shaft (112).
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| CNB2006100244849A CN100427923C (en) | 2006-03-08 | 2006-03-08 | Multifunction chip-detecting apparatus |
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| CNB2006100244849A CN100427923C (en) | 2006-03-08 | 2006-03-08 | Multifunction chip-detecting apparatus |
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| CN1815186A true CN1815186A (en) | 2006-08-09 |
| CN100427923C CN100427923C (en) | 2008-10-22 |
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| CN1987430B (en) * | 2006-12-20 | 2011-01-12 | 东华大学 | Integrated multifunction chip instrument |
| CN101493424B (en) * | 2008-01-23 | 2012-06-20 | 政美仪器有限公司 | Small chip surface detecting system in bearing disk and method thereof |
| CN102830224A (en) * | 2012-08-28 | 2012-12-19 | 天津市先石光学技术有限公司 | Optical path switching mechanism for homogeneous luminescent immunodetection |
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| US6407395B1 (en) * | 2000-02-29 | 2002-06-18 | The University Of Chicago | Portable biochip scanner device |
| CN1176367C (en) * | 2002-01-11 | 2004-11-17 | 清华大学 | Automatic focus regulator for laser cofocal scanner |
| FR2848669B1 (en) * | 2002-12-12 | 2005-09-02 | Commissariat Energie Atomique | METHOD FOR MEASURING A QUANTITY OF PHOTONS PROPORTIONAL TO THE QUANTITY OF PHOTONS RECEIVED BY THE OBJECT AND ASSOCIATED DEVICE |
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| WO2021103250A1 (en) * | 2019-11-27 | 2021-06-03 | Zhongke Jingyuan Electron Limited, Beijing (CN) | Electron beam detection apparatus for semiconductor device and electron beam detection assembly |
| US11703467B2 (en) | 2019-11-27 | 2023-07-18 | Zhongke Jingyuan Electron Limited, Beijing | Electron beam detection apparatus for semiconductor device and electron beam detection assembly |
| CN113483657A (en) * | 2021-05-26 | 2021-10-08 | 广州万孚倍特生物技术有限公司 | Data acquisition method, detection turntable, device, computer equipment and storage medium |
| CN115015286A (en) * | 2022-06-13 | 2022-09-06 | 中大智能科技股份有限公司 | Chip detection method and system based on machine vision |
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