CN103115901B - Device for detecting biological chips based on resonance light scattering - Google Patents
Device for detecting biological chips based on resonance light scattering Download PDFInfo
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- CN103115901B CN103115901B CN201310025477.0A CN201310025477A CN103115901B CN 103115901 B CN103115901 B CN 103115901B CN 201310025477 A CN201310025477 A CN 201310025477A CN 103115901 B CN103115901 B CN 103115901B
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Abstract
The invention discloses a device for detecting biological chips based on resonance light scattering, which comprises a light source driver, an optical fiber, an excitation light source, a coupling lens group, a biological chip objective table, a photoelectric sensor, an upper computer, a motion platform and a multi-axle motor drive, wherein the light source driver controls the excitation light source to generate excitation light; the excitation light is outputted to the coupling lens group through the optical fiber, subjected to beam shaping, and transmitted to the biological chip objective table, and the excitation light is transmitted from the side edge of a biological chip under the condition that an angle of incidence is greater than a critical angle; a sample after being excited by the excitation light produces resonance light scattering, and radiates resonance scattering light with a specific wavelength outwards; the resonance scattering light is transmitted to the inside of the photoelectric sensor; the upper computer receives converted electric signals and carries out acquisition and analysis on the converted electric signals through software of the upper computer, thereby obtaining scanning images; and the software of the upper computer controls the multi-axle motor drive to operate and drives the motion platform to move, in such a way, the biological chip objective table is driven to move, so that the whole point sample area of the biological chip is scanned. The device disclosed by the invention is low in background noises and high in detection sensitivity.
Description
Technical field
The present invention relates to biological chip testing technology field, be specifically related to a kind of device detecting biochip based on resonant light scattering.
Background technology
Biochip (Microarray) is the new and high technology developed rapidly in life science in recent years, it mainly refers to by micro-processing technology in the chemistry of micro-organisms system of solid chip surface construction only having several square centimeters, to realize DNA, protein, the biological samples such as cell quick, accurately with high-throughout detection, its cardinal principle adopts chemistry or physical method, a large amount of probe is solidified the surface in holder, then according to the affinity interaction between biomolecule, as the base pairing effect of nucleic acid molecules, the combinations of antigen-antibody etc. are reacted, carry out detection to reaction signal again to analyze, the relevant information of this sample can be obtained.Because a large amount of probes can be fixed on holder by this technology simultaneously, analyze so once just detection can be carried out to a large amount of biomolecule, there is high automation, high-throughout feature, along with the development of biochip technology, higher requirement be it is also proposed to biological chip testing technology.
At present, detection for biochip mainly contains two kinds of modes, a kind of mode is detected by fluorescent method, this detection mode needs fluorescence molecule to mark biochip, because fluorescence molecule intrinsic brightness is limited, easy generation optical quenching and photobleaching phenomenon are larger on testing result impact; Another kind of detection mode is detected biochip by biochip scanner, this detection mode also exists the defect that ground unrest is higher, detection sensitivity is on the low side, produce serious influence to testing result, therefore research and development have high sensitivity, high-resolution bio-chip test device is significant for development biochip technology.
Summary of the invention
Detecting the problem that background noise is too high and sensitivity is on the low side of biochip existence in order to solve existing biochip scanner, the invention provides a kind of device detecting biochip based on resonant light scattering.
The technical scheme that the present invention adopts for technical solution problem is as follows:
Detect the device of biochip based on resonant light scattering, this device comprises light source drive, optical fiber, excitation source, coupled lens group, biochip objective table, photoelectric sensor, host computer, motion platform and multi-axle motor and drives;
Described light source drive controls excitation source and produces exciting light, exciting light exports coupled lens group to by optical fiber and carries out beam shaping to it, exciting light after shaping is incident on biochip objective table, exciting light is greater than critical angle angle with incident angle is incident by biochip side, what the sample on biochip was subject to exciting light excites rear generation resonant light scattering, to the resonance light scattering of external radiation specific wavelength, resonance light scattering is incident in photoelectric sensor, light signal is converted to electric signal, electric signal after host computer receives conversion also carries out collection analysis by the upper computer software in host computer to it, obtain scan image, upper computer software controls multi-axle motor and drives operation and actuation movement platform movement, drive biochip objective table to move simultaneously, the whole spotted area of biochip is scanned.
Described motion platform forms primarily of three straight-line displacement platforms.
Described biochip surface is placed with sample, and what sample was subject to exciting light excites rear generation resonant light scattering, to the scattered light of external radiation specific wavelength.
Described upper computer software comprises: the control of image acquisition, scan control, camera control, guide rail, scan-data analysis and data reset control.
Inventive principle: the present invention detects biochip based on resonant light scattering Cleaning Principle, resonant light scattering (Resonance Light-Scattering, RLS) be that one has high sensitivity and optionally research method, which utilizes the principle that metal nanoparticle can produce strong scattered light in white light excitation source, namely when excitation wavelength drops on the absorption band of molecule, electronics in molecule is due to energy level transition effect, give off extremely strong scattered light to all directions, this phenomenon is called as resonant light scattering.
It is a kind of dark field detection mode that resonant light scattering detects, excitation source light does not directly enter detecting device visual field, the photon that detecting device is collected only comes from the scattered light of metal nanoparticle, noise comes from the dark current noise of detecting device, therefore effectively can improve the sensitivity of signal to noise ratio (S/N ratio) and detection.Meanwhile, resonant light scattering detection technique uses white light as detection light source, and equipment is simple, and cheap, testing cost declines to a great extent.
Waveguide (Waveguide) is a kind of device for microwave or visible light wave transmissions, optical fiber is wherein used to be widely used in the middle of network insertion and digital communication as the optical waveguide (Optical/light Waveguide) of transmission medium, between difference folding look rate medium, because electromagnetic total reflection makes light wave be confined to propagate in waveguide and surrounding limited area thereof, when light beam optically thinner medium incident by optically denser medium, when incident angle that and if only if is greater than critical angle, light signal is totally reflected, utilize optical waveguide this principle of limited area emittance towards periphery, using biochip as optical waveguide, exciting light is greater than critical angle incidence by biochip edge, propagate in total reflection mode at the upper and lower inside surface of biochip, the advantage of optical waveguide mode of excitation excites selectivity strong, namely the chromophore being positioned at biochip surface is only excited, utilization ratio of optical energy is high and system background noise is low.
The invention has the beneficial effects as follows: the present invention utilizes resonant light scattering principle, exciting light is greater than critical angle incidence by biochip edge, propagate in total reflection mode at the upper and lower inside surface of biochip, by use optical waveguide excite, dynamic scan and data splicing, achieve to biochip efficient, detect fast and accurately, when the present invention detects, reappearance is strong and have very high sensitivity, effectively reduce ground unrest and improve light signal utilization factor, simultaneously with the advantage of low cost.
Accompanying drawing explanation
Fig. 1 is the structural representation detecting the device of biochip based on resonant light scattering of the present invention:
Fig. 2 is the process schematic that exciting light is converted to resonance light scattering;
Fig. 3 is upper computer software interface schematic diagram;
Fig. 4 utilizes the device based on resonant light scattering detection biochip of the present invention biochip to be scanned to the result schematic diagram obtained;
Fig. 5 utilizes the present invention to detect and utilizes existing biochip scanner to detect the Comparative result schematic diagram of biochip, Fig. 5 a uses device of the present invention biochip to be scanned to the image obtained, and Fig. 5 b uses commercialization scanner biochip to be scanned to the image obtained.
In figure: 1, light source drive, 2, excitation source, 3, optical fiber, 4, coupled lens group, 5, biochip objective table, 6, photoelectric sensor, 7, host computer, 8, motion platform, 9, multi-axle motor drives, 10, biochip, 11, sample, 12, image acquisition, 13, scan control, 14, camera control, 15, guide rail controls, 16, scan-data analysis, 17, data reset control.
Embodiment
Below in conjunction with accompanying drawing, the present invention is described in further detail.
As shown in Figure 1, the device detecting biochip based on resonant light scattering of the present invention, drives 9 compositions primarily of light source drive 1, excitation source 2, optical fiber 3, coupled lens group 4, biochip objective table 5, photoelectric sensor 6, host computer 7, motion platform 8 and multi-axle motor.
Light source drive 1 produces exciting light for controlling excitation source 2, makes the power continuously adjustabe of excitation source 2; Excitation source 2 is for generation of the exciting light of excitation resonance light scattering; Exciting light exports coupled lens group 4 to by optical fiber 3, and coupled lens group 4 carries out beam shaping to it, and the exciting light after shaping is incident on biochip objective table 5; As shown in Figure 2, sample 11 is evenly distributed on biochip 10 surface, then biochip 10 is placed on biochip objective table 5, exciting light after beam shaping is greater than critical angle angle with incident angle is incident from biochip 10 side, carry out multiple total reflection in biochip 10 upper and lower surface, now, what sample 11 was subject to exciting light excites rear generation resonant light scattering, to the resonance light scattering of external radiation specific wavelength, resonance light scattering is incident in photoelectric sensor 6; Photoelectric sensor 6 pairs of resonance light scatterings carry out opto-electronic conversion, and light signal is converted to electric signal, are exported to by this electric signal in host computer 7; Upper computer software in host computer 7 gathers the electric signal from photoelectric sensor 6, analyze and obtain the scan image of sample 11.
Host computer 7 drives 9 to be connected by the general-purpose interface of self with multi-axle motor, upper computer software controls the operation that multi-axle motor drives 9, multi-axle motor drives 9 to be connected by cable with motion platform 8, for the movement of controlled motion platform 8, motion platform 8 is for controlling the movement of biochip objective table 5, different moving displacement platforms can be selected as required, in present embodiment, use three straight-line displacement platforms to realize.
As shown in Figure 3, for the interface of upper computer software, comprise: 16 and data reset control 17 are analyzed in image acquisition 12, scan control 13, camera control 14, guide rail control 15, scan-data, and upper computer software for showing, analyzing and preserve the information collected, and finally forms scan image.
The concrete testing process of the device based on resonant light scattering detection biochip of the present invention is as follows:
The body substrate of biochip 10 use at least one metal nanoparticle to mark, the biochip 10 prepared is placed on biochip objective table 5, drive 9 to run also actuation movement platform 8 by upper computer software control multi-axle motor to move, motion platform 8 moves and drives biochip objective table 5 to move, the whole spotted area of biochip 10 is scanned, obtain the scan image of biochip 10 as shown in Figure 4, the sampling point marked in image is clear, background becomes black, illustrate that the device based on resonant light scattering detection biochip of the present invention scans the data background noise obtained low, signal intensity is strong.
Name is used to be called SpotWare to the biochip 10 of above-mentioned preparation
tMthe biochip scanner scanning of Colorimetric Microarray Scanner, scanning result as shown in Figure 5, wherein, Fig. 5 a uses device of the present invention to carry out scanning the image obtained, and Fig. 5 b uses biochip scanner to carry out scanning the image obtained, as can be seen from Figure 5, identical biochip 10 is scanned, it is lower that device of the present invention scans the data background noise obtained, and signal intensity is stronger, improves detection resolution and sensitivity.
Claims (3)
1. the device of biochip is detected based on resonant light scattering, it is characterized in that, this device comprises light source drive (1), optical fiber (3), excitation source (2), coupled lens group (4), biochip objective table (5), photoelectric sensor (6), host computer (7), motion platform (8) and multi-axle motor and drives (9);
Described light source drive (1) controls excitation source (2) and produces exciting light, exciting light is exported to coupled lens group (4) by optical fiber (3) and is carried out beam shaping to it, exciting light after shaping is incident on biochip objective table (5), exciting light is greater than critical angle angle with incident angle is incident by biochip (10) side, using biochip (10) as optical waveguide, exciting light is greater than critical angle incidence by biochip (10) edge, propagate in total reflection mode at the upper and lower inside surface of biochip (10), sample (11) under the effect of the energy of optical waveguide limited area radiation towards periphery to the resonance light scattering of external radiation specific wavelength, resonance light scattering is incident in photoelectric sensor (6), light signal is converted to electric signal, electric signal after host computer (7) receives conversion also carries out collection analysis by the upper computer software in host computer (7) to it, obtain scan image, upper computer software controls multi-axle motor driving (9) operation and actuation movement platform (8) is mobile, drive biochip objective table (5) mobile simultaneously, the whole spotted area of biochip (10) is scanned.
2. the device detecting biochip based on resonant light scattering according to claim 1, it is characterized in that, described motion platform (8) forms primarily of three straight-line displacement platforms.
3. the device detecting biochip based on resonant light scattering according to claim 1, it is characterized in that, described upper computer software comprises: image acquisition (12), scan control (13), camera control (14), guide rail control (15), scan-data analysis (16) and data reset and control (17).
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| CN201310025477.0A CN103115901B (en) | 2013-01-23 | 2013-01-23 | Device for detecting biological chips based on resonance light scattering |
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| CN201310025477.0A CN103115901B (en) | 2013-01-23 | 2013-01-23 | Device for detecting biological chips based on resonance light scattering |
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| CN103926222B (en) * | 2014-04-15 | 2016-04-20 | 中国科学院长春应用化学研究所 | A kind of bio-chip test device of miniaturization low-power consumption |
| CN106769866A (en) * | 2016-12-28 | 2017-05-31 | 吉林大学 | A kind of biochip objective table |
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