CN2551994Y - Scanner for biogene chip - Google Patents

Scanner for biogene chip Download PDF

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Publication number
CN2551994Y
CN2551994Y CN02264877U CN02264877U CN2551994Y CN 2551994 Y CN2551994 Y CN 2551994Y CN 02264877 U CN02264877 U CN 02264877U CN 02264877 U CN02264877 U CN 02264877U CN 2551994 Y CN2551994 Y CN 2551994Y
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CN
China
Prior art keywords
laser
chip
catoptron
biogene
light source
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Expired - Fee Related
Application number
CN02264877U
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Chinese (zh)
Inventor
王文奎
刘敏
胡企铨
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Shanghai Institute of Optics and Fine Mechanics of CAS
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Shanghai Institute of Optics and Fine Mechanics of CAS
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Priority to CN02264877U priority Critical patent/CN2551994Y/en
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    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The utility model relates to a scanner for a biogene chip, which is suitable to be used for detecting hepatitis A and B pathogen after the crossing of the fluorescence marked biogene. The scanner includes two laser sources with different wave length. The laser beam emitted by the laser sources changes into a ling shape thin light beam through a ling shape shaper so as to permeate a narrow gap on a narrow gap reflecting mirror and emit to a standby biogene chip which is positioned on a movable platform. The light beam emitted back from the standby biogene chip passes through an imaging system and then the laser beam of the laser sources is filtered by a filter; and then the fluorescent signal of the standby biogene chip is assembled on the photosensitive face of a photoelectric charge coupler. The output of the photoelectric charge coupler is inputted into a computer through a data acquisition card so as to carry out data treatment. Compared with the prior art, the utility model has the use functions of simplified scanning manner, increased scanning scope and enlarged scanning device.

Description

The scanister of biological gene chip
Technical field:
The utility model relates to a kind of scanister of biological gene chip, is mainly used in the detection behind the fluorescently-labeled biological gene chip hybridization; Equally also can be used for the detection of pathogen such as first and second livers.
Background technology:
For with fluorescently-labeled biological gene chip, the detection after the hybridization need be with special genetic chip scanister.Special-purpose at present genetic chip scanister roughly is divided into two classes:
One class is to use laser excitation, based on the gene chip detecting system of doing detecting element with photomultiplier (PMT-photomultiplier tube).Another kind of is to add the optical filter illumination with the high brightness continuous light source to excite, based on the gene chip detecting system of doing detecting element with charge-coupled image sensor (CCD-charge-coupled devices).The background technology of these two kinds of different systems is summarized as follows:
The laser-based that with the photomultiplier is detecting element is because of the chip scanning device, laser beam with a branch of definite wavelength when detecting genetic chip collimates via lens combination and the synthetic beam-expanding system of spike interference filter, through the dichroscope reflection, by object lens focusing, deexcitation is placed on the biochip of crossing with fluorescence labeling on the mechanical scanner that uses step motor again.The fluorescence that produces after fluorescent material is excited is collected through object lens, by mirror reflects, filters by narrow band pass filter behind dichroscope, and again by lens focus, process diaphragm elimination parasitic light is delivered to photomultiplier.Photomultiplier is converted to electric signal with light signal, and the electric signal after the conversion converts analog quantity to digital quantity through analog to digital conversion again and delivers to computing machine through signal amplifier.Computing machine is handled the data of delivering to, analyze through special data processing software, can draw the various information of the chip under test that comprises image.Because the single beam laser of its use fixed wave length focuses on and scans excited sample, therefore needs the motion of laser beam or objective chip, makes laser sweep to the entire chip sample.In order to guarantee that imaging is clear and laser focusing is accurate, object lens need have the automatic focusing controller.The laser-based that with the photomultiplier is detecting element need expend the long time because of the chip scanning device detects genetic chip at every turn, therefore laser instrument is had special requirement.Require the output of laser instrument to have very high beam quality, long-term stability and extremely low noise.Be characterized in that scan image has very high resolution.
With the charge-coupled device is the genetic chip scanister of detecting element, generally has intermediate resolution, and it is detecting element with the charge-coupled device; Adopt the high power xenon lamp to make high brightness continuous agitation light source; Change excitation wavelength by the conversion optical filter; In order to make genetic chip be excited illumination evenly, often need to adopt beam-averaging device; Image-forming objective lens then will be after filtration the imaging signal of the genetic chip of mating plate deliver to imaging on the pixel of charge-coupled device.This genetic chip scanister once can get the larger area imaging region.But, the imaging area of the charge-coupled device digital camera of best performance has only 16 * 12mm (pixel is 10 * 10 μ m) at present, as will (the standard area be 1 " * 3 ", and 25 * 75mm or 26 * 76mm) imagings then need to adopt expensive large-size array charge-coupled device to entire chip.Or with several charge-coupled device element splicings, or the motion chip is with the image mosaic of gained.Certainly, also can downscaled images, to be cost then to reduce chip scanning resolution and precision.Its volume, power consumption are all bigger.
In addition, above-mentioned technology formerly also has some common shortcomings: detected object (chip) or excitation laser beam will be done the translation motion of XY both direction just can finish the detection task, so chip scanner will have the motion of two dimension; The image of gained all needs computer data to handle the back splicing, and all very high to the positioning accuracy request of motion precision and motion, and it is complicated that the process of controlled motion also becomes; Entire chip scanning needs the long time of cost, thereby efficient is lower; The cost of complete machine is somewhat expensive etc.
Summary of the invention:
In order to overcome above-mentioned two kinds of shortcomings of technology formerly, the utility model provides the scanister of biological gene chip as shown in Figure 1.
Scanister of the present utility model comprises:
The mobile platform 14 of putting biological gene chip 15 to be measured is arranged, the light beam that fires back by biological gene chip 15 to be measured through 13 reflections of slit catoptron after, be mapped on the photoelectrical coupler 8 after the mating plate 11 after filtration, the output of photoelectrical coupler 8 is connected on the computing machine 7 through data collecting card 9 again; Unequal first LASER Light Source 2 of wavelength and second LASER Light Source 16 are arranged, by of the reflection of first LASER Light Source, 2 emitted laser bundles through penetration mirror 18, by second LASER Light Source, 16 emitted laser bundles through the reflection of the 3rd catoptron 17 after, after seeing through penetration mirror 18, two laser is all again through the reflection of first catoptron 1, see through shaping lens 3, reflected into into linear reshaper 4 by second catoptron 5, the slit that sees through on the slit catoptron 13 through the light beam after the shaping is mapped on the biological gene chip 15 to be measured; On the light path between slit catoptron 13 and the optical filter 11, be equipped with imaging system 12; Computing machine 7 links to each other with optical filter 11 by first controller 6, and computing machine 7 links to each other with mobile platform 14 by second controller 10.As shown in Figure 1.
As mentioned above, the utility model replaces traditional microcobjective with imaging system 12; Use two bundle laser (laser beam of sending by first the LASER Light Source 2 or laser beam of sending by second LASER Light Source 16) to excite the biological gene chip 15 to be measured that is positioned on the mobile platform 14 respectively, use fluorescent dye Cy3 on the biological gene chip 15 to be measured TMAnd Cy5 TMThe sample of mark can send fluorescence under the exciting of respective wavelength laser (as being respectively 532nm and 650nm).The utility model scanister can excite two kinds of fluorescent dye (Cy3 TMAnd Cy5 TM), (combination that this linear reshaper 4 is aspheric surface cylindrical mirror or aspheric surface cylindrical mirror) becomes the even fine rule of a high brightness through linear reshaper 4 for laser beam of being sent by first LASER Light Source 2 or the laser beam sent by second LASER Light Source 16, the fine rule beam excitation with the fluorescence signal that produces after the sample (on biological gene chip 15 to be measured) of fluorochrome label by the catoptron 13 that has slit after again by imaging system 12, image space place in imaging system 12 is placed with photoelectrical coupler 8, photoelectrical coupler 8 changes the light signal of receiving into electric signal, deliver in the computing machine 7 through data (A/D) capture card 9, moving of biological gene chip 15 finished by second controller 10.First controller 6 drives a rotating mechanism and changes spike interference filter 11.Above-mentioned imaging system 12 is actually an image-forming objective lens or camera lens.
In Fig. 1, mobile platform 14 is driven along the to-and-fro movement of one dimension direction by computer-controlled second controller 10, the linear laser light beam of the high brightness of linear reshaper 4 shapings of process and the direction of motion of mobile platform 14 are orthogonal, the size that is imaged on picture on photoelectrical coupler 8 photosurfaces can be controlled easily by the position of adjusting the imaging lens in the imaging system 12, thereby the resolution of the scanister of biological gene chip can be controlled.Can select different optical filter 11 to reach the purpose of removing noise according to the LASER Light Source difference.Optical filter is changed and is finished or changed by manual way by first controller 6.
Below be the course of work of the scanister of this biological gene chip:
After first LASER Light Source 2 gives off laser beam, after the reflection through the penetration mirror 18 and first catoptron 1, after reflecting through second catoptron 5 again after 3 shapings of light beam process shaping lens, light beam is through becoming the uniform linear beam of a branch of high brightness behind the linear reshaper 4, and this light beam impinges upon on the biological gene chip 15 to be measured that is placed on the mobile platform 14 after passing slit on the slit catoptron 13 that has slit.The fluorescence signal that produces through reaction on this biological gene chip 15 to be measured is excited out, together with the laser signal one that is reflected reflection all around in the same way, most reflector laser reflexes in the imaging system 12 by slit catoptron 13, is imaged onto on the photoelectrical coupler 8.Owing to wherein be mixed with laser, so need spike interference filter 11 to come filtering laser.The fluorescence signal that removes laser after filtration is imaged on the photosurface of linear array photoelectrical coupler 8 at last.The output of photoelectrical coupler 8 is passed through data (A/D) capture card 9 to computing machine 7.Computing machine 7 carries out data processing with the electric signal of collecting.Moving by second controller 10 of mobile platform 14 finished by computing machine 7 controls.
When 16 work of second LASER Light Source, the laser beam that it sends is through 17 reflections of the 3rd catoptron, see through through penetration mirror 18 again, 1 reflection of first catoptron, shaping lens 3 shapings, 5 reflections of second catoptron, through becoming the very high laser beam of a beam brightness after the linear reshaper 4, this light beam passes deexcitation behind the slit on the slit catoptron 13 and is placed on biological gene chip 15 to be measured on the mobile platform 14, the fluorescence signal that inspires and laser light reflected through 13 reflections of slit catoptron after through imaging system 12 imagings, for the filtering laser signal, the spike interference filter 11 that will place filtering second excitation source equally comes the filtering laser signal.Be replaced with and the corresponding optical filter 11 of second LASER Light Source, 16 emission of lasering beam wavelength by computing machine 7 controls first controller 6.The fluorescence signal that removes laser beam after filtration finally is imaged on the photosurface of photoelectrical coupler 8.Photoelectrical coupler 8 is input to computing machine 7 enterprising line data by data (A/D) capture card 9 and handles.
Compare with technology formerly, unequal two LASER Light Source 2,16 of wavelength are arranged in the scanister of the present utility model, slit catoptron 13 and the highly sensitive photoelectrical coupler 8 and the penetration mirror 18 of linear reshaper 4 and band slit are arranged, and laser beam is through being pressed into the uniform linear laser bundle of a high brightness behind the linear reshaper 4.This linear laser bundle is when exciting biological gene chip 15 to be measured, only need make mobile platform 14 move the scanning that to finish the biological gene chip along the one dimension direction, this have only the scanister of one dimension mobile device to simplify scan mode, also saved sweep time simultaneously, can also reach the effect that strengthens sweep limit by the mobile platform 14 of selecting big stroke in addition.Different object distances can obtain different scanning resolutions and scanning accuracy with image distance in the imaging system 12 by selecting.And use two LASER Light Source 2,16 respectively, and can measure two kinds of different fluorescent dyes, a scanister can be finished the measurement of two kinds of biological gene chips 15 to be measured.Enlarged functions of use.
Description of drawings:
Fig. 1 is the structural representation of the scanister of biological gene chip of the present utility model.
Embodiment:
Be the structural representation of the scanister of the utility model biological gene chip as shown in Figure 1.Imaging system 12 is a camera lens in the utility model, focal distance f=85mm, and F2, Zhu's bit trade mark, the apparent field of its best image planes position is greater than the photoelectrical coupler 8 receiving plane sizes of linear array.Photoelectrical coupler 8 is linear arrays, and Toshiba produces has 2160 pixels, has very high sensitivity, and its Pixel Dimensions is 14 ì m * 14 ì m, and pixel center is apart from being 14 ì m.Wherein first LASER Light Source 2 is that output wavelength is the semiconductor laser of 650nm, and the about 10mW of output power is used to excite Cy5 TMFluorescent dye.Second LASER Light Source 16 is semiconductor pumped neodymium-doped yttrium-aluminum garnet (Nd:YAG) solid state laser (laser of frequency multiplication output 532nm wavelength), and the about 20mW of output power is used to excite Cy3 TMFluorescent dye, penetration mirror 18 is to 45 ° of incident total reflections of 650nm light, to 45 ° of incident full impregnateds of 532nm light mistake, first catoptron 1, second catoptron 5 and the 3rd catoptron 17 are the completely reflecting mirrors of aluminizing, be conversion light path usefulness, linear reshaper 4 is thinner employing of hot spot of the light beam that makes first LASER Light Source 2 and second LASER Light Source 16.When opening first LASER Light Source 2 or second LASER Light Source 16, select different optical filter 11 to come filtering laser signal (being equivalent to ground unrest this moment) by first controller 6; After laser beam that first LASER Light Source 2 or second LASER Light Source 16 are sent is shaped to a light pencil through linear reshaper 4 by the slit on the slit catoptron 13, can excite biological gene chip 15 to be measured to produce fluorescence signals when impinging upon the biological gene chip 15 to be measured that places on the mobile platform 14, the fluorescence signal that produces passes through imaging system 12 through slit catoptron 13 reflection backs, after optical filter 11 filters laser signal, received by linear array photoelectrical coupler 8, the fluorescence signal that linear array photoelectrical coupler 8 receives is delivered to computing machine 7 after being converted into electric signal, computing machine 7 will obtain the fluorescence signal of tested biological gene chip, send with corresponding information such as image or text.Second controller 10 is to be used for making the mobile platform 14 of placing biological gene chip 15 to be measured to move along the one dimension direction among Fig. 1.First controller 6 is used for selecting suitable spike interference filter 11 to come the light beam of filtering excitation source (first LASER Light Source 2 or second LASER Light Source 16) to make the background interference of the signal that obtained as far as possible little to reach.

Claims (1)

1. the scanister of a biological gene chip comprises:
<1〉mobile platform (14) of storing biological gene chip to be measured (15), the light beam that fires back by biological gene chip to be measured (15) through slit catoptron (13) reflection after, be mapped on the photoelectrical coupler (8) after the mating plate (11) after filtration, the output of photoelectrical coupler (8) is connected on the computing machine (7) through data collecting card (9) again;
It is characterized in that:
<2〉unequal first LASER Light Source of wavelength (2) and second LASER Light Source (16) are arranged, by of the reflection of first LASER Light Source (2) emitted laser bundle through penetration mirror (18), by second LASER Light Source (16) emitted laser bundle through after the 3rd catoptron (17) reflection, after seeing through penetration mirror (18), two laser is all again through the reflection of first catoptron (1), see through shaping lens (3), reflected into into linear reshaper (4) by second catoptron (5), the slit that sees through on the slit catoptron (13) through the light beam after the shaping is mapped on the biological gene chip to be measured (15);
<3〉on the light path between slit catoptron (13) and the optical filter (11), be equipped with imaging system (12);
<4〉computing machine (7) links to each other with optical filter (11) by first controller (6), and computing machine (7) links to each other with mobile platform (14) by second controller (10).
CN02264877U 2002-06-19 2002-06-19 Scanner for biogene chip Expired - Fee Related CN2551994Y (en)

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100417931C (en) * 2005-04-06 2008-09-10 博奥生物有限公司 Microarray chip detection system
CN101839860A (en) * 2010-07-01 2010-09-22 湖南科技大学 Multi-wave excitation device of laser Raman spectrometer
CN101813822B (en) * 2010-01-27 2012-05-16 深圳大学 Fluorescent three-dimensional nano-resolution imaging method with axial selectivity excitation and device thereof
CN104293648A (en) * 2014-09-29 2015-01-21 深圳市大族激光科技股份有限公司 Gene sequencing light-path system
CN105039147A (en) * 2015-06-03 2015-11-11 西安交通大学 Base fluorescence image capturing system device and method for high-flux genome sequencing
CN108828625A (en) * 2018-08-27 2018-11-16 安徽科创中光科技有限公司 The device and method of one seed sand formula theorem imaging laser radar inverting atmospheric visibility
CN110826352A (en) * 2018-08-10 2020-02-21 维蒂克影像国际无限责任公司 Long range bar code scanning by coherent light conversion
CN116718578A (en) * 2023-08-11 2023-09-08 深圳赛陆医疗科技有限公司 Super-resolution microscopic imaging system and imaging method

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100417931C (en) * 2005-04-06 2008-09-10 博奥生物有限公司 Microarray chip detection system
CN101813822B (en) * 2010-01-27 2012-05-16 深圳大学 Fluorescent three-dimensional nano-resolution imaging method with axial selectivity excitation and device thereof
CN101839860A (en) * 2010-07-01 2010-09-22 湖南科技大学 Multi-wave excitation device of laser Raman spectrometer
CN104293648A (en) * 2014-09-29 2015-01-21 深圳市大族激光科技股份有限公司 Gene sequencing light-path system
CN104293648B (en) * 2014-09-29 2016-08-24 大族激光科技产业集团股份有限公司 Gene sequencing light path system
CN105039147A (en) * 2015-06-03 2015-11-11 西安交通大学 Base fluorescence image capturing system device and method for high-flux genome sequencing
CN105039147B (en) * 2015-06-03 2016-05-04 西安交通大学 A kind of high flux gene sequencing base fluoroscopic image capture systems device and method
CN110826352A (en) * 2018-08-10 2020-02-21 维蒂克影像国际无限责任公司 Long range bar code scanning by coherent light conversion
CN108828625A (en) * 2018-08-27 2018-11-16 安徽科创中光科技有限公司 The device and method of one seed sand formula theorem imaging laser radar inverting atmospheric visibility
CN116718578A (en) * 2023-08-11 2023-09-08 深圳赛陆医疗科技有限公司 Super-resolution microscopic imaging system and imaging method
CN116718578B (en) * 2023-08-11 2023-10-27 深圳赛陆医疗科技有限公司 Super-resolution microscopic imaging system and imaging method

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