CN1198135C - Biochip tester - Google Patents

Biochip tester Download PDF

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Publication number
CN1198135C
CN1198135C CN 00106437 CN00106437A CN1198135C CN 1198135 C CN1198135 C CN 1198135C CN 00106437 CN00106437 CN 00106437 CN 00106437 A CN00106437 A CN 00106437A CN 1198135 C CN1198135 C CN 1198135C
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bio
test device
order
chip test
spectroscope
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CN1317692A (en
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朱朝居
黄得瑞
杨子平
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Industrial Technology Research Institute ITRI
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Industrial Technology Research Institute ITRI
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Abstract

The present invention relates to a biochip tester which comprises an optical source, a holographic optical element, a spectroscope, an object lens, a filter plate and a signal detector. The holographic optical element is coupled with the optical source and divides a light beam into a zero-order light beam and a first-order light beam, and the first-order light beam deviates to the outside of the zero-order light beam. The spectroscope is coupled with the holographic optical element and guides the light beam to the object lens. The light beam penetrates through the object lens and is led to the biochip, the first-order light beam is reflected by the object lens and obliquely irradiates the biochip, and then the biochip generates fluorescence. The reflected zero-order light beam and the fluorescence are filtered by the filter plate coupled with the spectroscope after passing through the object lens and the spectroscope, and then the reflected zero-order light beam and the fluorescence are received by the signal detector coupled with the spectroscope.

Description

Bio-chip test device
Technical field
The present invention relates to a kind of pick-up unit, particularly relate to a kind of bio-chip test device.
Background technology
Biochip (Bio-Chip) has been widely used in the screening of sampling, after object sampling to be measured, sample is contacted with detecting unit in the biochip, and with the light beam irradiates biochip, be used optical detection apparatus again, the biochip of having taken a sample is carried out screening, can tell whether have special component in the sample.
At present, bio-chip test device adopts external light source, and makes light beam that light source the sends mode irradiating biological chip with oblique incidence.Detecting unit and the generation of the special component in sample biochemical reaction when biochip, again after the light beam irradiates of specific wavelength, the detecting unit of biochip can send fluorescent, obtains the fluorescent signal by pick-up unit then, to differentiate in the sample whether have special component.
Please refer to Fig. 1, what it illustrated is a kind of structural representation of existing bio-chip test device.The existing pick-up unit of this kind is made up of with computer 110 object lens 100, slit (Slit) 102, filter plate (Filter) 104, photomultiplier (Photo-Multiplier Tube) 106, electronic filter (Electronic Filter) 108.
As shown in Figure 1, light beam sends from argon laser (Argon Ion Laser) 150, after the scioptics 140, spends the incident angle oblique incidences to biochip 130 with 45, and biochip 130 is because of producing reaction with special component, so can send fluorescent 120 after light beam irradiates.By the fluorescent 120 that biochip 130 sends, the object lens 100 in the device focus on slit 102 after testing, and are being converted to electronic signal by being filtered by filter plate 104 after the slit 102, being received by photomultiplier 106.This electronic signal, is transferred into computer 110 and is handled after electronic filter 108 filters by photomultiplier 106 outputs.
Above-mentioned bio-chip test device must cooperate external light source to use, and its structure is complicated, volume is big, adjustment is difficult for, and all is to be set up in medical center or other similar units with fixed form usually so plant bio-chip test device.So when detecting on a large scale, the medical center is sent in the sampling that must will collect back to just can carry out screening.
Summary of the invention
The object of the present invention is to provide a kind of bio-chip test device, light source and receiving unit are combined in the same pick-up unit, the compact overall structureization of system can be made it easy to portably use, become portable bio-chip test device, can produce in batches.And the cooperation holography (as) optical element (Holographic Optical Element, HOE) utilization, can make light beam with suitable angle oblique incidence to biochip, improve biochip and absorb the efficient that energy produces fluorescent, thereby raising detection efficiency, can carry out in a large number and detection fast, also comparatively simple for the adjustment of system.Moreover, utilize by the biochip beam reflected, servocontrol (Servo) is carried out in the position of biochip, make system's adjustment robotization, can improve screening efficient, carry out in a large number, detect fast.
The object of the present invention is achieved like this, and a kind of bio-chip test device promptly is provided, and wherein comprises at least: a light source, in order to send a light beam; One holographic optical elements (HOE), couple with this light source optics, in order to receive the light beam that sends by this light source, this light beam is divided into a zero-order beam and a single order light beam, the direct of travel of this zero-order beam is remained unchanged, and make the direct of travel of this single order light beam be partial to the outside of this zero-order beam direct of travel; One spectroscope couples with this holographic optical elements (HOE) optics, and and this light source lay respectively at the different both sides of this holographic optical elements (HOE), in order to direct of travel deflection with this zero-order beam and this single order light beam; One object lens, couple with this spectroscope optics, with this zero-order beam and this single order beam direction one biological chip, and make this single order light beam with an incident angle oblique incidence to this biochip, wherein this incident angle is the angle by the incident ray of the surface of this biochip and this single order light beam; One filter plate couples with this spectroscope optics, and lays respectively at this spectroscopical different both sides with these object lens, after the fluorescent that this biochip sends passes through these object lens and this spectroscope, is filtered by this filter plate; An and signal detector, couple with this filter plate optics, and and this spectroscope lay respectively at the different both sides of this filter plate, in order to receive fluorescent by this filter plate, wherein this zero-order beam is received in order to produce by this signal detector and focuses on and follow the rail signal, and this single order light beam makes chip send fluorescent to be received by this signal detector.
The present invention also provides a kind of bio-chip test device, wherein comprises at least: a light source, in order to send a light beam; One holographic optical elements (HOE), couple with this light source optics, in order to receive the light beam that sends by this light source, this light beam is divided into a zero-order beam and a single order light beam, the direct of travel of this zero-order beam is remained unchanged, and make the direct of travel of this single order light beam be partial to the outside of this zero-order beam direct of travel; One spectroscope couples with this holographic optical elements (HOE) optics, and and this light source lay respectively at the different both sides of this holographic optical elements (HOE), in order to receive zero-order beam and this single order light beam from this holographic optical elements (HOE); One object lens, couple with this spectroscope optics, and and this holographic optical elements (HOE) lay respectively at this spectroscopical different both sides, will be by this spectroscopical zero-order beam and this single order beam direction one biological chip, and make this single order light beam with an incident angle oblique incidence to this biochip, wherein this incident angle is the angle by the incident ray of the surface of this biochip and this single order light beam; One filter plate couples with this spectroscope optics, after the fluorescent that this biochip sends passes through these object lens and this spectroscope, is filtered by this filter plate; An and signal detector, couple with this filter plate optics, and and this spectroscope lay respectively at the different both sides of this filter plate, in order to receive fluorescent by this filter plate, wherein this zero-order beam is received in order to produce by this signal detector and focuses on and follow the rail signal, and this single order light beam makes chip send fluorescent to be received by this signal detector.
The present invention also provides a kind of bio-chip test device, wherein comprises at least: a light source, in order to send a light beam; One holographic optical elements (HOE), couple with this light source optics, in order to receive the light beam that sends by this light source, this light beam is divided into a zero-order beam and a single order light beam, and the direct of travel of this zero-order beam is remained unchanged, and make the direct of travel of this single order light beam be partial to the outside of the direct of travel of this zero-order beam; One first spectroscope couples with this holographic optical elements (HOE) optics, and and this light source lay respectively at the different both sides of this holographic optical elements (HOE), in order to direct of travel deflection with this zero-order beam and this single order light beam; One object lens, couple with this first spectroscope optics, with this zero-order beam and this single order beam direction one biological chip, and make this single order light beam with an incident angle oblique incidence to this biochip, wherein this incident angle is the angle by the incident ray of the surface of this biochip and this single order light beam; One second spectroscope, couple with this first spectroscope optics, and lay respectively at this first spectroscopical different both sides, after this zero-order beam is reflected by this biochip with these object lens, behind these object lens and this first spectroscope, by of the direct of travel deflection of this second spectroscope with this zero-order beam; One servo-detector couples with this second spectroscope optics, in order to receive the zero-order beam by this second spectroscope deflection, servocontrol is carried out in the position of this biochip; One filter plate couples with this second spectroscope optics, and lays respectively at this second spectroscopical different both sides with this first spectroscope, and the fluorescent that this biochip sends is filtered by this filter plate by behind these object lens, this first spectroscope and second spectroscope; An and signal detector, couple with this filter plate optics, and and this second spectroscope lay respectively at the different both sides of this filter plate, in order to receive fluorescent by this filter plate, wherein this zero-order beam is received in order to produce by this signal detector and focuses on and follow the rail signal, and this single order light beam makes chip send fluorescent to be received by this signal detector.
Description of drawings
Below in conjunction with accompanying drawing, describe embodiments of the invention in detail, wherein:
Fig. 1 is a kind of structural representation of existing bio-chip test device;
Fig. 2 A and 2B are according to the first embodiment of the present invention, the structural representation of different bio-chip test devices;
Fig. 3 is the first embodiment of the present invention, the synoptic diagram of a kind of holographic optical elements (HOE) that bio-chip test device adopted;
Fig. 4 is according to the second embodiment of the present invention, the structural representation of another bio-chip test device.
Embodiment
The detection principle of biochip mainly is that with the light beam irradiates biochip, the product of reaction can absorb the energy of light beam and send fluorescent after the detecting unit of special component in the testing sample and biochip produces biochemical reaction.Use has the light beam irradiates biochip of specific wavelength, and the wavelength of the fluorescent that it produced can depart from the incident light wavelength, (the fluorescent wavelength that it sent is about 540 nanometers for Nanometer, green glow irradiating biological chip nm) for example to use wavelength to be about 532 nanometers.But bio-chip test device detection of biological chip sends fluorescent, promptly detects whether produce the fluorescent with specific wavelength, so its principle of work and CD player are similar.
Please refer to Fig. 2 A, it is according to the first embodiment of the present invention, a kind of bio-chip test device, the synoptic diagram of its structure.Shown in Fig. 2 A, comprise among the bio-chip test device 200a have light source 202a, holographic optical elements (HOE) 204a, spectroscope (Beam Splitter, BS) 206a, object lens 208a, filter plate 210a and signal detector 212a etc.Biochip 230a can be carried by chip microscope carrier (Holder) 214a; and chip microscope carrier 214a can adjust its position by other mechanisms (not being shown among the figure); and available cover glass (Cover Glass) 216a covers biochip 230a; protecting it not contaminated, and the thickness of cover glass 216a is about 0.1 millimeter (Millimeter.mm) to 1.2 millimeters.
In the bio-chip test device 200a of Fig. 2 A, light source 202a comprises LASER Light Source etc. in order to produce light beam irradiates biochip 230a, for example is the LASER Light Source that optical source wavelength is about 400 nanometer to 600 nanometers.Holographic optical elements (HOE) 204a couples with light source 202a optics, in order to receive the light beam 220a that is sent by light source 202a.Make light beam 220a produce diffraction phenomena (Diffraction) with holographic optical elements (HOE) 204a, and zeroth order/single order diffraction is arranged, light beam 220a is divided into zeroth order (Zero Order) light beam 222a and single order (First Order) light beam 224a.Wherein zero-order beam 222a advances along the direction of elementary beam 220a, and promptly the direct of travel of zero-order beam 222a remains unchanged; And deviation can take place in the angle of single order light beam 224a, and its direct of travel can be partial to the outside of the direct of travel of zero-order beam 222a.
Spectroscope 206a couples with holographic optical elements (HOE) 204a optics, and spectroscope 206a and light source 202a lay respectively at the different both sides of holographic optical elements (HOE) 204a, zero-order beam 222a and single order light beam 224a then by spectroscope 206a with its direct of travel deflection.Object lens 208a and spectroscope 206a optics couple, and between biochip 230a and spectroscope 206a, in order to zero-order beam 222a and single order light beam 224a guiding biochip 230a with spectroscope 206a deviation, and make single order light beam 224a with specific incident angle 218a oblique incidence to biochip 230a, 230a scans detection to biochip.Make light beam with oblique incidence mode irradiating biological chip, can improve the efficient that biochip sends fluorescent, the scope of incident angle 218a is about 30 degree to 50 degree, and preferable incident angle 218a is about 45 degree.(Numerical Aperture NA) be about 0.4 to 0.6, and object lens 208a comprises spherical lens, cylindrical lens etc. to the numerical aperture of object lens 208a.Use cylindrical lens can produce oval spot, with scanning detection of biological chip as object lens.
Filter plate 210a among Fig. 2 A couples with spectroscope 206a optics, and filter plate 210a and object lens 208a and biochip 230a lay respectively at the different both sides of spectroscope 206a, signal detector 212a couples with filter plate 210a optics, and signal detector 212a and spectroscope 206a lay respectively at the different both sides of filter plate 210a.Wherein filter plate 210a can carry out filtering to the light wave of specific wavelength, and with the light wave filtering of its commplementary wave length, and the optical wavelength scope of penetrable filter plate 210a approximates the fluorescent wavelength that biochip 230a is sent.Comprise photodetector (Photo Detector) etc. in order to the fluorescent signal detector 212a that receives by filter plate 210a.
Light beam 220a by light source 202a sends is divided into zero-order beam 222a and single order light beam 224a through holographic optical elements (HOE) 204a, by spectroscope 206a guiding object lens 208a, is radiated at then on the biochip 230a again.Wherein the direction of zero-order beam 222a can not depart from optical axis, single order light beam 224a can depart from optical axis before entering object lens 208a, and the outside of deflection optical axis, after object lens 208a refraction, to biochip 230a, make it send fluorescent 226a with incident angle 218a oblique incidence.And the fluorescent 226a that sends through the zero-order beam 222a and the biochip 230a of biochip 230a reflection, can advance along the forward of biochip 230a, behind object lens 208a and spectroscope 206a, by being signal detector 212a reception after the filter plate 210a filtration and handling.Wherein zero-order beam 222a is reflected onto signal detector (sensor) 212a, can focus on and follow the rail signal in order to produce, and carries out necessary servocontrol with comparison biochip 230a.Whether receive fluorescent by signal detector 212a, can whether contain special component in the judgement sample from biochip 230a.
Holographic optical elements (HOE) 204a among Fig. 2 A comprises circular symmetry holographic optical elements (HOE) (CircularHOE).Please refer to Fig. 3, what it illustrated promptly is according to preferred embodiment of the present invention, a kind of bio-chip test device, the wherein synoptic diagram of a kind of holographic optical elements (HOE) that is adopted.As shown in Figure 3, in circular symmetry holographic optical elements (HOE) 300, has the striped 302 that disposes in the concentric circles mode, the spacing of these stripeds 302 is radially outwards increased gradually by the center of circle, be that near the fringe spacing in circular symmetry holographic optical elements (HOE) 300 centers of circle is closeer, thinner in the fringe spacing of circular symmetry holographic optical elements (HOE) 300 peripheral edge portions.
Please refer to Fig. 2 B, what it illustrated is according to the first embodiment of the present invention, another kind of bio-chip test device, the synoptic diagram of its structure.In the bio-chip test device of Fig. 2 B and Fig. 2 A, each composed component is all identical, but its relative position is different.Shown in Fig. 2 B, bio-chip test device 200a among bio-chip test device 200b and Fig. 2 A is similar, wherein also comprise have light source 202b, holographic optical elements (HOE) 204b, spectroscope 206b, object lens 208b, filter plate 210b and signal detector 212b etc.With Fig. 2 category-A seemingly; biochip 230b can be carried by chip microscope carrier 214b; and chip microscope carrier 214b can adjust its position by other mechanisms (not being shown among the figure); and available cover glass 216b covers biochip 230b; protecting it not contaminated, and the thickness of cover glass 216b is about 0.1 millimeter to 1.2 millimeters.
Light source 202b among the bio-chip test device 200b comprises LASER Light Source etc. in order to produce light beam irradiates biochip 230b, for example is the LASER Light Source that optical source wavelength is about 400 nanometer to 600 nanometers.And holographic optical elements (HOE) 204b and light source 202b optics couple, to receive the light beam 220b that light source 202b sends.Holographic optical elements (HOE) 204b makes light beam 220b produce diffraction phenomena, and light beam 220b is divided into zero-order beam 222b and single order light beam 224b.Wherein zero-order beam 222b can not be partial to; Single order light beam 224b direct of travel then can be partial to the outside of the direct of travel of zero-order beam 222b.
Spectroscope 206b and holographic optical elements (HOE) 204b optics couple, and light source 202b and light microscopic 206b lay respectively at the different both sides of holographic optical elements (HOE) 204b, object lens 208b and spectroscope 206b optics couple, and between biochip 230b and spectroscope 206b, in order to zero-order beam 222b and single order light beam 224b guiding biochip 230b that will be by spectroscope 206b, and make single order light beam 224b with specific incident angle 218b oblique incidence to biochip 230b.And the scope of incident angle 218b is about 30 degree to 50 degree, and preferable incident angle 218b is about 45 degree.The numerical aperture of object lens 208b is about 0.4 to 0.6, and object lens 208b comprises spherical lens, cylindrical lens etc.Use cylindrical lens can produce oval spot, with scanning detection of biological chip as object lens.
Filter plate 210b among Fig. 2 B couples with spectroscope 206b optics, and signal detector 212b couples with filter plate 210b optics, and lays respectively at the different both sides of filter plate 210b with spectroscope 206b.Light beam 220b by light source 202b sends is divided into zero-order beam 222b and single order light beam 224b through holographic optical elements (HOE) 204b, behind spectroscope 206b and object lens 208b, is radiated on the biochip 230b.Wherein the direction of zero-order beam 222b can not depart from optical axis, single order light beam 224b can depart from optical axis before entering object lens 208b, and the outside of deflection optical axis, after object lens 208b refraction, to biochip 230b, make it send fluorescent 226b with incident angle 218b oblique incidence.And the fluorescent 226b that sends through the zero-order beam 222b and the biochip 230b of biochip 230b reflection, can advance along the forward of biochip 230b, behind object lens 208b,, receive and handle for signal detector 212b after filter plate 210b filters its direct of travel deflection and the filter plate 210b that leads by spectroscope 206b.
Wherein filter plate 210b can carry out filtering to the light wave of specific wavelength, and with the light wave filtering of its commplementary wave length, the optical wavelength scope of penetrable filter plate 210b approximates the fluorescent wavelength that biochip 230b is sent.Signal detector 212b comprises photodetector etc., and holographic optical elements (HOE) 206b is identical with holographic optical elements (HOE) 206a among Fig. 2 A, comprises the circular symmetry holographic optical elements (HOE), as shown in Figure 3.Zero-order beam 222b is reflected onto signal detector 212b, can focus on and follow the rail signal in order to produce, and with this biochip 230b be carried out necessary servocontrol.From signal detector 212b screening signal, but whether contain special component in the judgement sample.
Please refer to Fig. 4, what it illustrated is according to the second embodiment of the present invention, another bio-chip test device, the synoptic diagram of its structure.As shown in Figure 4, comprise in the bio-chip test device 400 have light source 402, holographic optical elements (HOE) 404, the first spectroscope 406a, the second spectroscope 406b, object lens 408, filter plate 410, servo-detector 414 and signal detector 412 etc.
Similar with first embodiment; biochip 430 can be carried by chip microscope carrier 414; and chip microscope carrier 416 can be adjusted its position by other mechanisms (not being shown among the figure); and available cover glass 418 covers biochip 430; to protect it not contaminated, the thickness of cover glass 418 is about 0.1 millimeter to 1.2 millimeters.
As shown in Figure 4, identical with first embodiment, in the bio-chip test device 400, light source 402 is in order to produce light beam irradiates biochip 430, to comprise LASER Light Source etc., for example is the LASER Light Source that optical source wavelength is about 400 nanometer to 600 nanometers.Holographic optical elements (HOE) 404 couples with light source 402 optics, to receive the light beam 420 that light source 402 sends, comprise the circular symmetry holographic optical elements (HOE), as shown in Figure 3, holographic optical elements (HOE) 404 can make light beam 420 produce diffraction phenomena, and light beam 420 is divided into zero-order beam 422 and single order light beam 424.Wherein zero-order beam 422 can be advanced and is not partial to along the direction of elementary beam 420, the direct of travel outside that single order light beam 424 can deflection zero-order beam 422.
The first spectroscope 406a among Fig. 4 connects with holographic optical elements (HOE) 404 optocouplers, and lays respectively at the different both sides of holographic optical elements (HOE) 404 with light source 402,424 of zero-order beam 422 and single order light beams by the first spectroscope 406a with its direct of travel deflection.The object lens 408 and the first spectroscope 406a optics couple, and between the biochip 430 and the first spectroscope 406a, in order to zero-order beam 422 and single order light beam 424 guiding biochips 430 with the first spectroscope 406a deviation, and make single order light beam 424 with specific incident angle 428 oblique incidences to biochip 430, biochip 430 is scanned detection.The scope of incident angle 428 is about 30 degree to 50 degree, and preferable incident angle 428 is about 45 degree.The numerical aperture of object lens 408 is about 0.4 to 0.6, and object lens 408 comprise spherical lens, cylindrical lens etc.Use cylindrical lens can produce oval spot, with scanning detection of biological chip as object lens.
The second spectroscope 406b among Fig. 4 and the first spectroscope 406a optics couple, and lay respectively at the different both sides of the first spectroscope 406a with object lens 408.Servo-detector 414 couples with the second spectroscope 406b optics respectively with filter plate 410, the filter plate 410 and the first spectroscope 406a lay respectively at the different both sides of the second spectroscope 406b, signal detector 412 is to couple with filter plate 410 optics, and lays respectively at different two of filter plate 410 with the second spectroscope 406b.Wherein filter plate 410 can carry out filtering to the light wave of specific wavelength, and with the light wave filtering of its commplementary wave length, the optical wavelength scope of penetrable filter plate 410 approximates the fluorescent wavelength that biochip 430 is sent.Signal detector 412 comprises photodetector etc., and servo-detector 414 is similar with signal detector 412, also comprises photodetector etc.
Light beam 420 by light source 402 sends is divided into zero-order beam 422 and single order light beam 424 through holographic optics part 404, through first spectroscope 406b deflection and by behind the object lens 408, is radiated on the biochip 430.Wherein zero-order beam 422 can not depart from optical axis, and single order light beam 424 can be partial to the outside of optical axis before entering object lens 408, after object lens 408 refractions, to biochip 430, makes it send fluorescent 426 with incident angle 428 oblique incidences.And the fluorescent 426 that sends through the zero-order beam 422 of biochip 430 reflection and biochip 430, can advance along the forward of biochip 430a, behind the object lens mirror 408 and first spectroscope 406, by the second spectroscope 406b with part light guiding servo-detector 414, focus on and follow the rail signal in order to produce, biochip 430 is carried out necessary servocontrol with this.By the light of the second spectroscope 406b, filter back signal detector 412 through filter plate 410 and receive and processing, whether contain special component through screening in judgement sample.
By the invention described above preferred embodiment as can be known, use bio-chip test device of the present invention, light source and receiving unit can be combined into one, make the one-piece construction of system simplify, be easy to carry, and can use the method for making of CD player read/write head, reduce its cost of manufacture, to produce in a large number.Moreover bio-chip test device of the present invention can increase the fluorescent efficient of biochip, thereby improves detection efficiency, can carry out in a large number and detection fast, and is also comparatively simple for the adjustment of system.In addition, utilize the chip beam reflected, servocontrol is carried out in its position,, can improve screening efficient system's adjustment robotization.
In sum, a kind of bio-chip test device provided by the invention wherein has light source, holographic optical elements (HOE), spectroscope, object lens, filter plate and signal detector.Holographic optical elements (HOE) and light source couple, and the light beam that light source can be sent is divided into zero-order beam and single order light beam, and zero-order beam can be partial to, and the single order light beam then can be partial to the outside of zero-order beam.Spectroscope and holographic optical elements (HOE) couple, with zeroth order and single order beam direction object lens.Light beam is by the object lens biochip that leads, and wherein the single order light beam is reflected by object lens, to biochip, makes it send fluorescent with specific incident angle oblique incidence.By the zero-order beam of chip reflection and the fluorescent that sends thereof, behind object lens, spectroscope, filter by the filter plate that couples with spectroscope, and received by signal detector.Received zero-order beam can be carried out servocontrol to chip in order to produce focusing and to follow the rail signal, and from signal detector screening fluorescent signal, but whether contain special component in the judgement sample.
In addition, the another kind of bio-chip test device that the present invention proposes wherein has light source, holographic optical elements (HOE), first spectroscope, second spectroscope, object lens, filter plate, servo-detector and signal detector.Holographic optical elements (HOE) and light source couple, and the light beam that light source can be sent is divided into zero-order beam and single order light beam, and zero-order beam can be partial to, and the single order light beam can be partial to the outside of zero-order beam.First spectroscope and holographic optical elements (HOE) couple, with zeroth order and single order beam direction object lens.Light beam is by the object lens biochip that leads, and wherein the single order light beam is reflected by object lens, to biochip, makes it send fluorescent with specific incident angle oblique incidence.By the zero-order beam of chip reflection and the fluorescent that sends thereof, behind object lens, first spectroscope, after the second spectroscope beam split that couples with first spectroscope, with part light guiding servo-detector.Servo-detector with second spectroscope couples receives the light beam from second spectroscope guiding, can carry out servocontrol to chip in order to produce focusing and to follow the rail signal.After filtering by filter plate by second spectroscopical light, received by signal detector again,, whether contained special component in the judgement sample with screening fluorescent signal.
Though disclosed the present invention in conjunction with above preferred embodiment; yet it is not in order to limit the present invention; any those skilled in the art; without departing from the spirit and scope of the present invention; should be used for a variety of modifications and variations, so protection scope of the present invention should be with being as the criterion that claim was defined.

Claims (46)

1. bio-chip test device wherein comprises at least:
One light source is in order to send a light beam;
One holographic optical elements (HOE), couple with this light source optics, in order to receive this light beam that sends by this light source, this light beam is divided into a zero-order beam and a single order light beam, the direct of travel of this zero-order beam is remained unchanged, and make the direct of travel of this single order light beam be partial to the outside of this zero-order beam direct of travel;
One spectroscope couples with this holographic optical elements (HOE) optics, and and this light source lay respectively at the different both sides of this holographic optical elements (HOE), in order to direct of travel deflection with this zero-order beam and this single order light beam;
One object lens, couple with this spectroscope optics, with this zero-order beam and this single order beam direction one biological chip, and make this single order light beam with an incident angle oblique incidence to this biochip, wherein this incident angle is the angle by the incident ray of the surface of this biochip and this single order light beam;
One filter plate couples with this spectroscope optics, and lays respectively at this spectroscopical different both sides with these object lens, after the fluorescent that this biochip sends passes through these object lens and this spectroscope, is filtered by this filter plate; And
One signal detector, couple with this filter plate optics, and and this spectroscope lay respectively at the different both sides of this filter plate, in order to receive fluorescent by this filter plate, wherein this zero-order beam is received in order to produce by this signal detector and focuses on and follow the rail signal, and this single order light beam makes chip send fluorescent to be received by this signal detector.
2. bio-chip test device as claimed in claim 1, wherein this light source comprises LASER Light Source.
3. bio-chip test device as claimed in claim 1, wherein this optical source wavelength is about 400 nanometer to 600 nanometers.
4. bio-chip test device as claimed in claim 1, wherein this holographic optical elements (HOE) comprises the circular symmetry holographic optical elements (HOE).
5. bio-chip test device as claimed in claim 4, wherein this circular symmetry holographic optical elements (HOE) has a plurality of circular symmetry stripeds, and the interval of this each circular symmetry striped is outwards cumulative by the center of circle of this circular symmetry holographic optical elements (HOE).
6. bio-chip test device as claimed in claim 1, wherein the numerical aperture of these object lens is about 0.4 to 0.6.
7. bio-chip test device as claimed in claim 1, wherein these object lens comprise spherical lens.
8. bio-chip test device as claimed in claim 1, wherein these object lens comprise lens pillar.
9. bio-chip test device as claimed in claim 1, wherein this incident angle is about 30 degree to 50 degree.
10. bio-chip test device as claimed in claim 9, wherein this incident angle is about 45 degree.
11. bio-chip test device as claimed in claim 1, wherein this filter plate has one and penetrates wavelength coverage, approximates the fluorescent wavelength that this biochip sends.
12. bio-chip test device as claimed in claim 1, wherein this biochip is positioned on the chip microscope carrier.
13. bio-chip test device as claimed in claim 12, wherein this biochip is covered with a cover glass.
14. bio-chip test device as claimed in claim 13, wherein the thickness of this cover glass is about 0.1 millimeter to 1.2 millimeters.
15. bio-chip test device as claimed in claim 1, wherein this signal detector comprises photodetector.
16. a bio-chip test device wherein comprises at least:
One light source is in order to send a light beam;
One holographic optical elements (HOE), couple with this light source optics, in order to receive the light beam that sends by this light source, this light beam is divided into a zero-order beam and a single order light beam, the direct of travel of this zero-order beam is remained unchanged, and make the direct of travel of this single order light beam be partial to the outside of this zero-order beam direct of travel;
One spectroscope couples with this holographic optical elements (HOE) optics, and and this light source lay respectively at the different both sides of this holographic optical elements (HOE), in order to receive zero-order beam and this single order light beam from this holographic optical elements (HOE);
One object lens, couple with this spectroscope optics, and and this holographic optical elements (HOE) lay respectively at this spectroscopical different both sides, will be by this spectroscopical zero-order beam and this single order beam direction one biological chip, and make this single order light beam with an incident angle oblique incidence to this biochip, wherein incident angle is the angle by the incident ray of the surface of this biochip and this single order light beam;
One filter plate couples with this spectroscope optics, after the fluorescent that this biochip sends passes through these object lens and this spectroscope, is filtered by this filter plate; And
One signal detector, couple with this filter plate optics, and and this spectroscope lay respectively at the different both sides of this filter plate, in order to receive fluorescent by this filter plate, wherein this zero-order beam is received in order to produce by this signal detector and focuses on and follow the rail signal, and this single order light beam makes chip send fluorescent to be received by this signal detector.
17. bio-chip test device as claimed in claim 16, wherein this light source comprises LASER Light Source.
18. bio-chip test device as claimed in claim 16, wherein this optical source wavelength is about 400 nanometer to 600 nanometers.
19. bio-chip test device as claimed in claim 16, wherein this holographic optical elements (HOE) comprises the circular symmetry holographic optical elements (HOE).
20. bio-chip test device as claimed in claim 19, wherein this circular symmetry holographic optical elements (HOE) has a plurality of circular symmetry stripeds, and the interval of this each circular symmetry striped is outwards cumulative by the center of circle of this circular symmetry holographic optical elements (HOE).
21. bio-chip test device as claimed in claim 16, wherein the numerical aperture of these object lens is about 0.4 to 0.6.
22. bio-chip test device as claimed in claim 16, wherein these object lens comprise spherical lens.
23. bio-chip test device as claimed in claim 16, wherein these object lens comprise lens pillar.
24. bio-chip test device as claimed in claim 16, wherein this incident angle is about 30 degree to 50 degree.
25. bio-chip test device as claimed in claim 24, wherein this incident angle is about 45 degree.
26. bio-chip test device as claimed in claim 16, wherein this filter plate has one and penetrates wavelength coverage, approximates the fluorescent wavelength that this biochip sends.
27. bio-chip test device as claimed in claim 16, wherein this biochip is positioned on the chip microscope carrier.
28. bio-chip test device as claimed in claim 27, wherein this biochip is covered with a cover glass.
29. bio-chip test device as claimed in claim 28, wherein the thickness of this cover glass is about 0.1 millimeter to 1.2 millimeters.
30. bio-chip test device as claimed in claim 16, wherein this signal detector comprises photodetector.
31. a bio-chip test device wherein comprises at least:
One light source is in order to send a light beam;
One holographic optical elements (HOE), couple with this light source optics, in order to receive the light beam that sends by this light source, this light beam is divided into a zero-order beam and a single order light beam, and the direct of travel of this zero-order beam is remained unchanged, and make the direct of travel of this single order light beam be partial to the outside of the direct of travel of this zero-order beam;
One first spectroscope couples with this holographic optical elements (HOE) optics, and and this light source lay respectively at the different both sides of this holographic optical elements (HOE), in order to direct of travel deflection with this zero-order beam and this single order light beam;
One object lens, couple with this first spectroscope optics, with this zero-order beam and this single order beam direction one biological chip, and make this single order light beam with an incident angle oblique incidence to this biochip, wherein this incident angle is the angle by the incident ray of the surface of this biochip and this single order light beam;
One second spectroscope, couple with this first spectroscope optics, and lay respectively at this first spectroscopical different both sides, after this zero-order beam is reflected by this biochip with these object lens, behind these object lens and this first spectroscope, by of the direct of travel deflection of this second spectroscope with this zero-order beam;
One servo-detector couples with this second spectroscope optics, in order to receive the zero-order beam by this second spectroscope deflection, servocontrol is carried out in the position of this biochip;
One filter plate couples with this second spectroscope optics, and lays respectively at this second spectroscopical different both sides with this first spectroscope, and the fluorescent that this biochip sends is filtered by this filter plate by behind these object lens, this first spectroscope and second spectroscope; And
One signal detector, couple with this filter plate optics, and and this second spectroscope lay respectively at the different both sides of this filter plate, in order to receive fluorescent by this filter plate, wherein this zero-order beam is received in order to produce by this signal detector and focuses on and follow the rail signal, and this single order light beam makes chip send fluorescent to be received by this signal detector.
32. bio-chip test device as claimed in claim 31, wherein this light source comprises LASER Light Source.
33. bio-chip test device as claimed in claim 31, wherein this optical source wavelength is about 400 nanometer to 600 nanometers.
34. bio-chip test device as claimed in claim 31, wherein this holographic optical elements (HOE) comprises the circular symmetry holographic optical elements (HOE).
35. bio-chip test device as claimed in claim 34, wherein this circular symmetry holographic optical elements (HOE) has a plurality of circular symmetry stripeds, and the interval of this each circular symmetry striped is outwards cumulative by the center of circle of this circular symmetry holographic optical elements (HOE).
36. bio-chip test device as claimed in claim 31, wherein the numerical aperture of these object lens is about 0.4 to 0.6.
37. bio-chip test device as claimed in claim 31, wherein these object lens comprise spherical lens.
38. bio-chip test device as claimed in claim 31, wherein these object lens comprise lens pillar.
39. bio-chip test device as claimed in claim 31, wherein this incident angle is about 30 degree to 50 degree.
40. bio-chip test device as claimed in claim 39, wherein this incident angle is about 45 degree.
41. bio-chip test device as claimed in claim 31, wherein this filter plate has one and penetrates wavelength coverage, approximates the fluorescent wavelength that this biochip sends.
42. bio-chip test device as claimed in claim 31, wherein this biochip is positioned on the chip microscope carrier.
43. bio-chip test device as claimed in claim 42, wherein this biochip is covered with a cover glass.
44. bio-chip test device as claimed in claim 43, wherein the thickness of this cover glass is about 0.1 millimeter to 1.2 millimeters.
45. bio-chip test device as claimed in claim 31, wherein this signal detector comprises photodetector.
46. bio-chip test device as claimed in claim 31, wherein this servo-detector comprises photodetector.
CN 00106437 2000-04-10 2000-04-10 Biochip tester Expired - Fee Related CN1198135C (en)

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CN1255671C (en) * 2002-08-02 2006-05-10 上海数康生物科技有限公司 Multiple-marknig-object biological chip signal analyzing systems
CN100381810C (en) * 2003-12-19 2008-04-16 财团法人工业技术研究院 Fluorometric auxiliary detection device
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JP2011038922A (en) * 2009-08-12 2011-02-24 Sony Corp Light detection chip, and light detection device using the same
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