CN1435684A - Bio-chip fluorescent testing scanning device - Google Patents
Bio-chip fluorescent testing scanning device Download PDFInfo
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- CN1435684A CN1435684A CN 02112626 CN02112626A CN1435684A CN 1435684 A CN1435684 A CN 1435684A CN 02112626 CN02112626 CN 02112626 CN 02112626 A CN02112626 A CN 02112626A CN 1435684 A CN1435684 A CN 1435684A
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- laser
- fluorescence
- mirror
- light
- biochip
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Abstract
A scanner for fluorescence detection of biochip is composed of laser exciting light path, fluorescence receiving light path, X-Y platform for putting biochip on it, and supporter. After two laser beams are combined by a gathering prism and then come in a same light path, the combined beam passes through the central through holes of a hollow perflector and a focusing lens to be focused to a dot on biochip. The said both light pathes are separated by said perflector and fluorescence splitter. More 2D images of biochip can be obtained by the 2D movement of X-Y platform. Its advantages are compact structure, high scan speed, small size, light weight, low cost, high correctness and low power consumption.
Description
Technical field:
The present invention relates to a kind of harvester of biological chip fluorescent picture, the scanning that is used for fluoroscopic image on the biochip detects.
Technical background:
Before the present invention makes, in prior art, the Affymetrix of U.S. Affymetrix company
TMFluorescence biosensor chip pick-up unit (Thane Kreiner is published in " American laboratory " magazine, in March, 1996,39-43 page or leaf).This device is mainly by Ar
+Laser instrument, shutter, first deviation mirror, laser line optical filtering, dichronic mirror, second deviation mirror, focusing scanning head, chip set, laser intensity detector, filter set, achromatic lens, pin hole and photomultiplier are formed laser excitation light path and fluorescence receiving light path.
Its course of work is: Ar
+The laser beam that laser instrument sends is behind shutter, first deviation mirror and laser line optical filtering, and with the monochromatic light directed dichronic mirror, dichronic mirror is to the laser beam total reflection, and allows fluorescence see through.This light beam is reflexed to second deviation mirror by dichronic mirror, enters the focusing scanning head and is focused biochip surface on chip set through reflection.Excite down at incoming laser beam, the fluorescent material on the biochip will send fluorescence.The fluorescence line focus scanner head and second deviation mirror arrive dichronic mirror, and the saturating look dichronic mirror of fluorescence, filter set, achromatic lens, pin hole and photomultiplier finally are converted into the electric signal that is directly proportional with fluorescence intensity.The laser of being returned by biochip reflection and scattering is reflected back by dichronic mirror, can not arrive photomultiplier.In order to obtain the two-dimentional fluoroscopic image on the entire chip, the focusing scanning head need move horizontally, and chip set is then done vertical movement.The weak point of this device is: 1, volume is big, the power consumption height.Owing to adopted the extremely low Ar of electro-optical efficiency
+Laser instrument, its life-span is short, and volume is big, and thermal value is big, needs to force cooling, is unfavorable for the miniaturization of complete machine; And the manufacturing cost height is unfavorable for promoting the use of; 2, detection speed is slow, inefficiency.Owing to adopt a kind of laser instrument, so can only obtain a kind of image of fluorescent material; In order to obtain the fluoroscopic image of several fluorescent materials on the biochip, must use many scanning detection apparatus that adopt multiple corresponding laser instrument.And this device once can only detect the fluoroscopic image of an a kind of fluorescent material on the biochip.3, detection accuracy is poor.Owing to, must make focusing scanning head and chip set do orthogonal linear movement respectively, and the focusing scanning head separates with chip set in order to obtain the two-dimentional fluoroscopic image on the biochip.This motion is difficult to reach high stability with high-speed, and whole device easily produces problems such as imbalance and out of focus, thereby influences the accuracy of testing result.
Summary of the invention:
The objective of the invention is to overcome above-mentioned weak point, thereby for the biochip fluoroscopic examination provides that a kind of volume is little, cost is low, detection efficiency is high, testing result bio-chip fluorescent detection scanning device accurately and reliably.
Main solution of the present invention is achieved in that
The present invention mainly comprises the laser excitation light path, the platform of fluorescence receiving light path and placement biochip.On the laser excitation light path, green glow solid state laser 1 and red light semiconductor laser 2 are housed on the support 6, on green glow solid state laser 1 and red light semiconductor laser 2 emitted laser bundle working direction, light-combining prism 3, hollow total reflective mirror 4, laser condensing lens 7 are housed successively, laser beam ECDC light prism 3 arrives with after the light path, pass the through hole 5 at hollow total reflective mirror 4 centers, be focused on biochip 8 through laser beam behind the laser condensing lens 7, biochip 8 is installed on the platform 9, and 10 on platform 9 and platform are equipped with guide rail 11.On the fluorescence receiving light path, the fluorescence that biochip 8 sends is behind laser condensing lens 7 collimations, reflex to fluorescence dichronic mirror 16 by hollow total reflective mirror 4, fluorescence dichronic mirror 16 is contained on the support 6, is divided into two-way through fluorescence dichronic mirror 16 fluorescence light paths, after a route fluorescence dichronic mirror 16 reflections, through optical filter 15, confocal mirror 14, pin hole 13, arrive photomultiplier 12, optical filter 15, confocal mirror 14, pin hole 13, photomultiplier 12 is contained on the support 6 successively.After fluorescence dichronic mirror 16 is crossed by another Reuter,, arrive photomultiplier 20 at last through optical filter 17, confocal mirror 18, pin hole 19, optical filter 17, confocal mirror 18, pin hole 19, photomultiplier 20 is installed on the support 6 equally successively.
Description of drawings:
Fig. 1 is a structural representation of the present invention:
Embodiment:
Embodiment during following the present invention incites somebody to action in conjunction with the accompanying drawings is further described:
The present invention mainly is made up of laser excitation light path, fluorescence receiving light path and X-Y platform that a plurality of biochips can be installed.On the laser excitation light path, green glow solid state laser 1 is housed, red light semiconductor laser 2, light-combining prism 3, hollow total reflective mirror 4, laser condensing lens 7 on the support 6.Between green glow solid state laser 1, red light semiconductor laser 2 and hollow total reflective mirror 4, light-combining prism 3 is housed, between light-combining prism 3 and laser condensing lens 7, hollow total reflective mirror 4 is housed.On green glow solid state laser 1 and red light semiconductor laser 2 emitted laser bundle working direction, owing to be equipped with light-combining prism 3, hollow total reflective mirror 4, laser condensing lens 7, be parallel to each other behind the laser beam ECDC light prism 3 that sends by them and abut against together, pass the through hole 5 at hollow total reflective mirror 4 centers, the through hole 5 at hollow total reflective mirror 4 centers can allow two or more laser beam to pass, and making the fluorescence reflection, realization laser separates with fluorescence.Be focused same point on biochip 8 through two bundle laser behind the laser condensing lens 7, or the fixing consecutive point of relative position, realize that promptly the scanning of two light beam concurrents detects, and can detect one or detect two above biochips simultaneously.Two or more biochips place on the X-Y two-dimensional stage.X-Y platform is combined by directions X platform 9 and Y direction platform 10.Directions X platform 9 is installed on the Y direction platform 10, between platform 9 and the platform 10 guide rail 11 is housed.Directions X platform 9 is one and comes and goes scanning platform fast, Y direction platform 10 be one at a slow speed folk prescription to big stroke platform, directions X platform 9 is an inswept line on biochip 8, then Y direction platform 10 takes a step forward, the exercise group of two platforms is synthesized a two-dimensional scan campaign, realizes reading two-dimentional fluoroscopic image on the biochip 8.
Light-combining prism 3 recited above is the above cone prism in a two sides or two sides, conical surface becomes same locking angle with its exit facet, the locking angle angle is 0-45 °, it can with specific incident angle laser beam incident thereon to penetrate perpendicular to the exit facet direction, if there are two above laser beam to enter light-combining prism 3 from different conical surfaces with separately specific incident angle, then these laser beam reach the purpose of closing light with parallel outgoing.The optical axis of green glow solid state laser 1 and red light semiconductor laser 2 emitted laser bundles and the emergent light axis of light-combining prism 3 be angled θ respectively
1And θ
2Place, and θ
1=(n
1-1) α, θ
2=(n
2-1) α, n
1And n
2Be respectively the refractive index of green glow solid state laser 1 and red light semiconductor laser 2 wavelength place light-combining prisms 3, the rest may be inferred by analogy for it.If adopt plural laser instrument, then the number of the conical surface of light-combining prism 3 can be made with the laser instrument number and equated, scanning detects when can realize two above laser.The placement at 45 of the reflecting surface of hollow total reflective mirror 4 recited above and optical axis, the through hole 5 in the middle of it allows multiple laser beam to pass, and need not to do any special processing, thereby makes the invention compact conformation, is easy to make.
On the laser excitation light path, two or more laser instruments can be housed, correspondingly, need two or more fluorescence receiving light paths.In the present invention owing to adopted two laser instruments, so the fluorescence receiving light path also has two, and they receive corresponding fluorescence signal respectively.5 return by original optical path from biochip 8 laser light reflected bundles from through hole, do not enter the fluorescence receiving light path.The fluorescence that is sent by biochip 8 is behind laser condensing lens 7 collimations, reflex to fluorescence dichronic mirror 16 by hollow total reflective mirror 4, the fluorescence that two kinds of laser excitation goes out by fluorescence dichronic mirror 16 separately, reflected fluorescent light is through Cy5 optical filter 15, behind confocal mirror 14 and the pin hole 13, project on the photomultiplier 12, convert the electric signal that is directly proportional with fluorescence intensity at last to.Above-mentioned fluorescence dichronic mirror 16, optical filter 15, confocal mirror 14, pin hole 13, photomultiplier 12 are installed on the support 6 respectively successively.After fluorescence dichronic mirror 16 is crossed by another Reuter,, project at last on the photomultiplier 20, convert the electric signal that is directly proportional with fluorescence intensity at last to through Cy3 optical filter 17, confocal mirror 18, pin hole 19.Optical filter 17, confocal mirror 18, pin hole 19, photomultiplier 20 are installed on the support 6 too successively.This structure arrangement of the present invention reads when can carry out the fluoroscopic image of multiple fluorescent material to biochip 8.
Below of the present inventionly be described further for example:
Shown in Fig. 1 structure: this is a kind of device that adopts two kinds of laser instruments to scan the one or more biochips of detection simultaneously.The wavelength of green glow solid state laser 1 and red light semiconductor laser 2 is respectively 532nm and 635nm, and laser output power is respectively 10mW and 12mW, and the diameter of laser beam is 2mm, is used for two kinds of fluorescent materials on the detection of biological chip.Light-combining prism 3 adopts the manufacturing of K9 optical glass to form α=10 ° n
1=1.51904, n
2=1.51459.The optical axis included angle θ of the optical axis of green glow solid state laser 1 and red light semiconductor laser 2 and light-combining prism 3
1=5.1904 °, θ
2=5.4459 °, promptly two laser beam focus on same point on the biochip 8 through laser condensing lens 7.Focal distance f=the 12mm of laser condensing lens 7 is so laser facula is of a size of φ 10 μ m on the biochip.The diameter of the through hole 5 at hollow total reflective mirror 4 centers is 4-6mm, the reflecting surface plating broadband film that is all-trans, at the reflectivity of 570-750nm wave band greater than 98%.The total reflection of 16 pairs of 670-750nm wave bands of fluorescence dichronic mirror, to 570-620nm wave band total transmissivity, so it will reflect the fluorescence that the Cy5 dyestuff sends, and the fluorescence that transmission Cy3 dyestuff sends.The fluorescence that sends through two kinds of fluorescent materials of fluorescence dichronic mirror 16 reflection and transmission behind the pin hole 13,19, converts the electric signal that with fluorescence intensity be directly proportional by photomultiplier 12,20 through optical filter 15 and 17 separately, confocal mirror 14,18.The focal length of confocal mirror 14 is 32mm, and the clear aperture of pin hole 13 is φ 80-φ 120 μ m.
Placed three biochips to be measured on the X-Y platform, the sensing range of single biochip is 25.4mm * 66mm.The round frequency of directions X platform 9 is 10Hz, all gathers fluorescence signal in coming and going scanning process.Most preferred embodiment reaches 0.1 molecule/μ m to the detection sensitivity of above-mentioned two kinds of fluorescent materials
2, two kinds of fluoroscopic images of three biochips of acquisition promptly can get six fluoroscopic images altogether in 10 minutes.Above-mentioned described two kinds of fluorescent materials are respectively Cy3 and Cy5.
Compared with the prior art the present invention has the following advantages:
1, detection efficiency height. This device makes two or more laser owing to adopt light-combining prism Bundle incides the same point on the biochip simultaneously, and a plurality of biochips are placed on the platform, namely can be together Time scanning detects a plurality of biochips, and has a plurality of laser beams and scan simultaneously and detect a plurality of biochips Performance; 2, signal to noise ratio height, the detection sensitivity height. Because this device laser excitation light path and fluorescence reception light Separate on the road, avoids easily the laser excitation light beam to enter the fluorescence reception light path, greatly reduces noise; 3, figure Picture is processed convenient, the degree of accuracy height of testing result. The incidence point of a plurality of laser overlaps in this device, and institute is right Various fluoroscopic images carry out correlation analysis and data, and to process the result who obtains be real; 4, simple in structure, Compact, realize high-velocity scanning easily. Except biochip X-Y platform is made two dimensional motion, all the other Parts are all motionless, and the load on the platform is little, can use X-Y platform low in energy consumption, that volume is little real Existing rapid scanning; 5, volume is little, and is in light weight, and cost is low, easy to utilize. This device has adopted low The solid state laser of power consumption and semiconductor laser.
Claims (6)
1, a kind of bio-chip fluorescent detection scanning device comprises the laser excitation light path, the fluorescence receiving light path, support, it is characterized in that: on the laser excitation light path, green glow solid state laser (1) and red light semiconductor laser (2) are housed on the support (6), on green glow solid state laser (1) and red light semiconductor laser (2) emitted laser bundle working direction, light-combining prism (3) is housed successively, hollow total reflective mirror (4), laser condensing lens (7), laser beam ECDC light prism (3) arrives with after the light path, pass the through hole (5) at hollow total reflective mirror (4) center, be focused on biochip (8) through laser beam behind the laser condensing lens (7), biochip (8) is installed on the platform (9), between platform (9) and platform (10) guide rail (11) is housed; On the fluorescence receiving light path, the fluorescence that biochip (8) sends is behind laser condensing lens (7) collimation, reflex to fluorescence dichronic mirror (16) by hollow total reflective mirror (4), fluorescence dichronic mirror (16) is contained on the support (6), be divided into two-way through fluorescence dichronic mirror (16) fluorescence light path, after the reflection of one route fluorescence dichronic mirror (16), through optical filter (15), confocal mirror (14), pin hole (13), arrive photomultiplier (12), optical filter (15), confocal mirror (14), pin hole (13), photomultiplier (12) is contained on the support (6) successively, after fluorescence dichronic mirror (16) is crossed by another Reuter, through optical filter (17), confocal mirror (18), pin hole (19), arrive photomultiplier (20) at last, optical filter (17), confocal mirror (18), pin hole (19), photomultiplier (20) is installed on the support (6) successively.
2, bio-chip fluorescent detection scanning device according to claim 1 is characterized in that described light-combining prism (3) is the above cone prism in a two sides or two sides, and conical surface becomes same locking angle with its exit facet, and the α angle is 0-45 °.
3, bio-chip fluorescent detection scanning device according to claim 1 and 2 is characterized in that the optical axis of described green glow solid state laser (1), red light semiconductor laser (2) emitted laser bundle optical axis and light-combining prism (3) outgoing is distinguished angled θ
1And θ
2Place, and θ
1=(n
1-1) α, θ
2=(n
2-1) α, n
1And n
2It is respectively the refractive index of green (light) laser (1) and red light semiconductor laser (2) wavelength place light-combining prism (3).
4, bio-chip fluorescent detection scanning device according to claim 1 is characterized in that can being equipped with two or more laser instruments on the described laser excitation light path, correspondingly, needs two or more fluorescence receiving light paths.
5, bio-chip fluorescent detection scanning device according to claim 1 is characterized in that upward central through hole (5) of described hollow total reflective mirror (4), and its diameter is 4-6mm.
6, bio-chip fluorescent detection scanning device according to claim 1, the clear aperture that it is characterized in that described pin hole (13), (19) are φ 80-φ 120 μ m.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02112626 CN1435684A (en) | 2002-01-30 | 2002-01-30 | Bio-chip fluorescent testing scanning device |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02112626 CN1435684A (en) | 2002-01-30 | 2002-01-30 | Bio-chip fluorescent testing scanning device |
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|---|---|
| CN1435684A true CN1435684A (en) | 2003-08-13 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101361015B (en) * | 2005-11-23 | 2012-11-21 | 伊鲁米那股份有限公司 | Confocal imaging methods and apparatus |
| CN106248578A (en) * | 2016-08-24 | 2016-12-21 | 中国科学院光电技术研究所 | A kind of integrated form protein chip scanner |
| CN112326606A (en) * | 2020-09-11 | 2021-02-05 | 广州万孚生物技术股份有限公司 | In-vitro diagnosis and analysis system, optical detection device and motion disc module |
| CN113092424A (en) * | 2021-03-18 | 2021-07-09 | 上海医本医疗器械有限公司 | Novel high-flux biochip analyzer |
| CN113189102A (en) * | 2021-04-29 | 2021-07-30 | 中国工程物理研究院激光聚变研究中心 | Dual-wavelength dual-confocal laser microscopic measurement device and measurement method |
-
2002
- 2002-01-30 CN CN 02112626 patent/CN1435684A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101361015B (en) * | 2005-11-23 | 2012-11-21 | 伊鲁米那股份有限公司 | Confocal imaging methods and apparatus |
| CN106248578A (en) * | 2016-08-24 | 2016-12-21 | 中国科学院光电技术研究所 | A kind of integrated form protein chip scanner |
| CN112326606A (en) * | 2020-09-11 | 2021-02-05 | 广州万孚生物技术股份有限公司 | In-vitro diagnosis and analysis system, optical detection device and motion disc module |
| CN113092424A (en) * | 2021-03-18 | 2021-07-09 | 上海医本医疗器械有限公司 | Novel high-flux biochip analyzer |
| CN113189102A (en) * | 2021-04-29 | 2021-07-30 | 中国工程物理研究院激光聚变研究中心 | Dual-wavelength dual-confocal laser microscopic measurement device and measurement method |
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