CN1435794A - Bio-chip fluorescent detection scanning device with light filter rotary disk - Google Patents
Bio-chip fluorescent detection scanning device with light filter rotary disk Download PDFInfo
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- CN1435794A CN1435794A CN 02112625 CN02112625A CN1435794A CN 1435794 A CN1435794 A CN 1435794A CN 02112625 CN02112625 CN 02112625 CN 02112625 A CN02112625 A CN 02112625A CN 1435794 A CN1435794 A CN 1435794A
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Abstract
A scanner with filter turn-table for the 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, it passes through the central through hole of a hollow perflector and a focusing lens to be focused to a dot on biochip. Multiple 2D fluorescence images of biochip can be obtained by the 2D movement of said X-Y platform. Its advantages are compact structure, high scan speed, small size, light weight, low cost and high correctness.
Description
Technical field;
The present invention relates to a kind of harvester of the biological chip fluorescent picture with filter wheel, 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 is accurately and reliably with the bio-chip fluorescent detection scanning device of filter wheel.
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 is housed successively, hollow total reflective mirror 4, laser condensing lens 7, laser beam ECDC light prism 3 reaches 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 9,10 on platform 9 and platform are equipped with guide rail 11, on the fluorescence receiving light path, Cy3 optical filter 14, Cy5 optical filter 12 is fixed on the rotating disk 13, rotation by rotating disk 13 makes Cy3 optical filter 14 or the Cy5 optical filter 12 corresponding with green glow solid state laser 1 and red light semiconductor laser 2 enter the fluorescence receiving light path, except that optical filter, two fluorescence receiving light paths are shared, respectively through confocal mirror 15, project behind the pin hole 16 on the photomultiplier 17.Confocal mirror 15, pin hole 16, photomultiplier 17 are installed on the support 6 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 optical filters.Owing to adopted two laser instruments, therefore except that optical filter, two fluorescence receiving light paths are shared in the present invention, 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 reflexed on the fluorescence receiving light path by hollow total reflective mirror 4 behind laser condensing lens 7 collimations, and two fluorescence receiving light paths are shared except that optical filter 14,12.Cy3 optical filter 14, Cy5 optical filter 12 are installed on the rotating disk 13, and rotating disk 13 is installed on the turning axle of motor 18, and motor 18 is installed on the support 6.Rotation by rotating disk 13 makes Cy3 optical filter 14, the Cy5 optical filter 12 corresponding with green glow solid state laser 1 and red light semiconductor laser 2 enter fluorescence receiving light path (when laser instrument 1 or laser instrument 2 work).Fluorescence through confocal mirror 15, projects behind the pin hole 16 on the photomultiplier 17 behind optical filter 14 or 12.Confocal mirror 15, pin hole 16, photomultiplier 17 are installed on the support 6 successively.This structure arrangement of the present invention can be realized reading one by one two or more fluorescent material images on two or more biochips.
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 scans to detect one or more biochips.Two kinds of fluorescent material images on the biochip read one by one.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 bands greater than 98%.When the present invention works, have only one to open in two laser instruments, in Dui Ying Cy3 optical filter 14 or the Cy5 optical filter 12 enters the fluorescence receiving light path with it.When green glow solid state laser 1 is opened, the Cy3 fluorescent dye image on the detection of biological chip 8, at this moment Cy3 optical filter 14 enters the fluorescence receiving light path.Reflect next Cy3 fluorescence through Cy3 optical filter 14 from hollow total reflective mirror 4, behind confocal mirror 15, the pin hole 16, convert the electric signal that is directly proportional with the fluorescence flux to by photomultiplier 17.When red light semiconductor laser 2 is opened, the Cy5 fluorescent dye image on the detection of biological chip 8, at this moment Cy5 optical filter 12 enters the fluorescence receiving light path.Cy5 fluorescence Cy5 optical filter 12 from 4 reflections of hollow total reflective mirror come behind confocal mirror 15, the pin hole 16, is converted to the electric signal that is directly proportional with the fluorescence flux by photomultiplier 17.The focal length of confocal mirror 15 is 32mm, and the clear aperture of pin hole 16 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 20 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 Shu Xianhou incides the same point on the biochip, and a plurality of biochips are placed on the platform, namely can be together Time scanning detects a plurality of biochips; 2, signal to noise ratio height, the detection sensitivity height. Because this device laser swashs Luminous road separates with the fluorescence reception light path, avoids easily the laser excitation light beam to enter the fluorescence reception light path, and is big Reduced greatly noise; 3, image processing method just, the degree of accuracy height of testing result. A plurality of laser in this device Incidence point overlap, so various fluoroscopic images are carried out correlation analysis and data are processed the result who obtains Real; 4, simple in structure, compact, realize high-velocity scanning easily. Remove biochip at the X-platform On do outside the two dimensional motion, all the other parts are all motionless, the load on the platform is little, can use low in energy consumption, The X-Y platform that volume is little is realized rapid scanning; 5, volume is little, and is in light weight, and cost is low, is convenient to promote Use. This device has adopted solid state laser and the semiconductor laser of low-power consumption.
Claims (6)
1, a kind of bio-chip fluorescent detection scanning device with filter wheel 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; Optical filter (14), (12) are fixed on the rotating disk (13), rotation by rotating disk (13) makes optical filter (14) or (12) corresponding with green glow solid state laser (1) and red light semiconductor laser (2) enter the fluorescence receiving light path, except that optical filter, two fluorescence receiving light paths are shared, respectively behind confocal mirror (15), pin hole (16), project on the photomultiplier (17), confocal mirror (15), pin hole (16), photomultiplier (17) are installed on the support (6) successively.
2, the bio-chip fluorescent detection scanning device of band filter wheel according to claim 1, it is characterized in that described light-combining prism (3) is the above cone prism in a two sides or two sides, conical surface becomes same locking angle with its exit facet, and the α angle is 0-45 °.
3, the bio-chip fluorescent detection scanning device of band filter wheel 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, the bio-chip fluorescent detection scanning device of band filter wheel 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 optical filters.
5, the bio-chip fluorescent detection scanning device of band filter wheel according to claim 1 is characterized in that it is 4-6mm that described hollow total reflective mirror (4) is gone up central through hole (5) diameter.
6, the bio-chip fluorescent detection scanning device of band filter wheel according to claim 1, the clear aperture that it is characterized in that described pin hole (16) are φ 80-φ 120 μ m.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02112625 CN1435794A (en) | 2002-01-30 | 2002-01-30 | Bio-chip fluorescent detection scanning device with light filter rotary disk |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02112625 CN1435794A (en) | 2002-01-30 | 2002-01-30 | Bio-chip fluorescent detection scanning device with light filter rotary disk |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100390575C (en) * | 2005-11-03 | 2008-05-28 | 中国科学院半导体研究所 | Structure for expanding operation wavelength of cut off filter, and method of application |
| CN101256255B (en) * | 2008-03-21 | 2010-10-13 | 北京理工大学 | System for joining light path of multiplex laser |
| CN101936904A (en) * | 2010-08-31 | 2011-01-05 | 上海交通大学 | Portable fluorescence tomography detection system |
| CN102147365A (en) * | 2010-12-22 | 2011-08-10 | 中国科学院上海微系统与信息技术研究所 | Handheld bioluminescent detector and detection method |
| CN102159936A (en) * | 2008-09-18 | 2011-08-17 | 株式会社岛津制作所 | Fluorescent image detector and method for detecting fluorescent image |
| CN107817227A (en) * | 2016-09-12 | 2018-03-20 | 台达电子国际（新加坡）私人有限公司 | Fluorescence detection device |
-
2002
- 2002-01-30 CN CN 02112625 patent/CN1435794A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100390575C (en) * | 2005-11-03 | 2008-05-28 | 中国科学院半导体研究所 | Structure for expanding operation wavelength of cut off filter, and method of application |
| CN101256255B (en) * | 2008-03-21 | 2010-10-13 | 北京理工大学 | System for joining light path of multiplex laser |
| CN102159936A (en) * | 2008-09-18 | 2011-08-17 | 株式会社岛津制作所 | Fluorescent image detector and method for detecting fluorescent image |
| CN101936904A (en) * | 2010-08-31 | 2011-01-05 | 上海交通大学 | Portable fluorescence tomography detection system |
| CN102147365A (en) * | 2010-12-22 | 2011-08-10 | 中国科学院上海微系统与信息技术研究所 | Handheld bioluminescent detector and detection method |
| CN107817227A (en) * | 2016-09-12 | 2018-03-20 | 台达电子国际（新加坡）私人有限公司 | Fluorescence detection device |
| CN107817227B (en) * | 2016-09-12 | 2020-08-28 | 台达电子国际（新加坡）私人有限公司 | Fluorescence detection device |
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