CN103115901A - 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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- CN103115901A CN103115901A CN2013100254770A CN201310025477A CN103115901A CN 103115901 A CN103115901 A CN 103115901A CN 2013100254770 A CN2013100254770 A CN 2013100254770A CN 201310025477 A CN201310025477 A CN 201310025477A CN 103115901 A CN103115901 A CN 103115901A
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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 the biological chip testing technology field, be specifically related to a kind of device based on resonant light scattering detection of biological chip.
Background technology
biochip (Microarray) is a new and high technology that developed rapidly in life science in recent years, it mainly refers to by micro-processing technology in the chemistry of micro-organisms system that only has the solid chip surface construction of several square centimeters, to realize DNA, protein, the biological samples such as cell fast, accurately with high-throughout detection, its cardinal principle is to adopt chemistry or physical method, a large amount of probes are solidified surface in holder, then according to the affinity interaction between biomolecule, base pairing effect as nucleic acid molecules, the combination of antigen-antibody waits reacts, again reaction signal is detected analysis, can obtain the relevant information of this sample.Because this technology can be fixed in a large amount of probes on holder simultaneously, so once just can detect analysis to a large amount of biomolecule, have high automation, high-throughout characteristics, along with the development of biochip technology, biological chip testing technology is also had higher requirement.
At present, detection for biochip mainly contains dual mode, a kind of mode is to detect by fluorescent method, this detection mode needs fluorescence molecule to carry out mark to biochip, because the fluorescence molecule intrinsic brightness is limited, optical quenching and photobleaching phenomenon easily occur, larger on the testing result impact; Another kind of detection mode is by biochip scanner, biochip to be detected, this detection mode exists the defective that ground unrest is higher, detection sensitivity is on the low side, testing result is produced serious influence, and therefore research and development have high sensitivity, high-resolution bio-chip test device is significant for the development biochip technology.
Summary of the invention
Too high and sensitivity problem on the low side, the invention provides a kind of device based on resonant light scattering detection of biological chip for the background noise that solves existing biochip scanner detection of biological chip existence.
The present invention is that the technical scheme that adopts of technical solution problem is as follows:
Based on the device of resonant light scattering detection of biological chip, this device comprises that light source drive, optical fiber, excitation source, coupled lens group, biochip objective table, photoelectric sensor, host computer, motion platform and multi-axle motor drive;
described light source drive is controlled excitation source and is produced exciting light, exciting light exports the coupled lens group to and it is carried out beam shaping by optical fiber, exciting light after shaping is incident on the biochip objective table, exciting light with incident angle greater than the angle of critical angle by the incident of biochip side, sample on biochip is subject to the rear generation resonant light scattering of exciting of exciting light, resonance light scattering to the external radiation specific wavelength, resonance light scattering is incident in photoelectric sensor, light signal is converted to electric signal, host computer receives the electric signal after conversion and by the upper computer software in host computer, it is carried out collection analysis, obtain scan image, upper computer software is controlled multi-axle motor and is driven operation and actuation movement platform movement, driving simultaneously the biochip objective table moves, whole point sample zone to biochip is scanned.
Described motion platform mainly is comprised of three straight-line displacement platforms.
Described biochip surface is placed with sample, and sample is subject to the rear generation resonant light scattering of exciting of exciting light, to the scattered light of external radiation specific wavelength.
Described upper computer software comprises: image acquisition, scan control, camera control, guide rail are controlled, scan-data analysis and data reset control.
Inventive principle: the present invention is based on resonant light scattering detection principle and comes the detection of biological chip, resonant light scattering (Resonance Light-Scattering, RLS) be a kind of have high sensitivity and research method optionally, it has utilized metal nanoparticle can produce the principle of strong scattered light in the white light excitation source, namely when excitation wavelength drops on the absorption band of molecule, electronics in molecule is due to the 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 the 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 can effectively improve the sensitivity of signal to noise ratio (S/N ratio) and detection.Simultaneously, the resonant light scattering detection technique uses white light as detection light source, and equipment is simple, and is cheap, and testing cost declines to a great extent.
waveguide (Waveguide) is a kind of device for microwave or visible light wave transmissions, wherein use optical fiber 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 waveguide and propagates in limited area on every side, when light beam during by optically denser medium incident optically thinner medium, incident angle that and if only if is during greater than critical angle, light signal generation total reflection, utilize optical waveguide this principle of limited area emittance towards periphery, with biochip as optical waveguide, exciting light by the biochip edge greater than critical angle incident, propagate in the total reflection mode at biochip up and down inside surface, the advantage of optical waveguide mode of excitation is to excite selectivity strong, namely only excite the chromophore that is positioned at biochip surface, utilization ratio of optical energy is high and the system background noise is low.
The invention has the beneficial effects as follows: the present invention utilizes the resonant light scattering principle, with exciting light by the biochip edge greater than critical angle incident, propagate in the total reflection mode at biochip up and down inside surface, optical waveguide excites by using, dynamic scan and data splicing, realized detecting efficiently, fast and accurately biochip, when the present invention detects, reappearance is strong and have very high sensitivity, effectively reduce ground unrest and improved the light signal utilization factor, simultaneously with advantage cheaply.
Description of drawings
Fig. 1 is the structural representation of the device based on resonant light scattering detection of biological chip of the present invention:
Fig. 2 is the process schematic diagram 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 of biological chip of the present invention biochip to be scanned the result schematic diagram that obtains;
Fig. 5 is the result contrast schematic diagram that utilizes the present invention to detect and utilize existing biochip scanner detection of biological chip, Fig. 5 a is for using device of the present invention biochip to be scanned the image that obtains, and Fig. 5 b is for using the commercialization scanner biochip to be scanned the image that obtains.
In figure: 1, light source drive, 2, excitation source, 3, optical fiber, 4, coupled lens group, 5, the 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, the data control that resets.
Embodiment
Below in conjunction with accompanying drawing, the present invention is described in further detail.
As shown in Figure 1, device based on resonant light scattering detection of biological chip of the present invention mainly drives 9 by 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 and forms.
As shown in Figure 3, interface for upper computer software, comprise: image acquisition 12, scan control 13, camera control 14, guide rail control 15, scan-data analysis 16 and data reset and control 17, and upper computer software is used for the information that demonstration, analysis and preservation collect, and finally forms scan image.
The concrete testing process of the device based on resonant light scattering detection of biological chip of the present invention is as follows:
use at least one metal nanoparticle to carry out mark on the body substrate of biochip 10, the biochip 10 for preparing is placed on biochip objective table 5, control by upper computer software that multi-axle motor drives 9 operations and actuation movement platform 8 moves, motion platform 8 moves drive biochip objective table 5 and moves, whole point sample zone to biochip 10 is scanned, obtain the scan image of biochip 10 as shown in Figure 4, in image, the sampling point of mark is clear, background becomes black, illustrate that the data background noise that obtains based on the device scanning of resonant light scattering detection of biological chip of the present invention is low, signal intensity is strong.
Biochip 10 to above-mentioned preparation uses name to be called SpotWare
TMThe biochip scanner scanning of Colorimetric Microarray Scanner, scanning result as shown in Figure 5, wherein, Fig. 5 a is for using device of the present invention to scan the image that obtains, and Fig. 5 b is for using biochip scanner to scan the image that obtains, as can be seen from Figure 5, identical biochip 10 is scanned, the data background noise that device scanning of the present invention obtains is lower, and signal intensity is stronger, has improved detection resolution and sensitivity.
Claims (4)
1. based on the device of resonant light scattering detection of biological chip, it is characterized in that, this device comprises that 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 drive (9);
described light source drive (1) is controlled excitation source (2) and is produced exciting light, exciting light exports coupled lens group (4) to and it is carried out beam shaping by optical fiber (3), exciting light after shaping is incident on biochip objective table (5), exciting light with incident angle greater than the angle of critical angle by biochip (10) side incident, sample (11) on biochip (10) is subject to the rear generation resonant light scattering of exciting of exciting light, resonance light scattering to the external radiation specific wavelength, resonance light scattering is incident in photoelectric sensor (6), light signal is converted to electric signal, host computer (7) receives the electric signal after conversion and by the upper computer software in host computer (7), it is carried out collection analysis, obtain scan image, upper computer software is controlled multi-axle motor driving (9) operation and actuation movement platform (8) moves, drive simultaneously biochip objective table (5) mobile, whole point sample zone to biochip (10) is scanned.
2. the device based on resonant light scattering detection of biological chip according to claim 1, is characterized in that, described motion platform (8) mainly is comprised of three straight-line displacement platforms.
3. the device based on resonant light scattering detection of biological chip according to claim 1, it is characterized in that, described biochip (10) surface is placed with sample (11), and sample (11) is subject to the rear generation resonant light scattering of exciting of exciting light, to the scattered light of external radiation specific wavelength.
4. the device based on resonant light scattering detection of biological chip 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 are controlled the control (17) that resets of (15), scan-data analysis (16) and data.
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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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| CN103926222A (en) * | 2014-04-15 | 2014-07-16 | 中国科学院长春应用化学研究所 | Miniaturized low-power-consumption biochip detection device |
| CN106769866A (en) * | 2016-12-28 | 2017-05-31 | 吉林大学 | A kind of biochip objective table |
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| CN103115901B (en) | 2015-05-20 |
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