CN102735654A - Reflection-type local surface plasma resonance enhanced biochemical detector - Google Patents
Reflection-type local surface plasma resonance enhanced biochemical detector Download PDFInfo
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- CN102735654A CN102735654A CN2012102122979A CN201210212297A CN102735654A CN 102735654 A CN102735654 A CN 102735654A CN 2012102122979 A CN2012102122979 A CN 2012102122979A CN 201210212297 A CN201210212297 A CN 201210212297A CN 102735654 A CN102735654 A CN 102735654A
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Abstract
The invention discloses a reflection-type local surface plasma resonance enhanced biochemical detector, which comprises a light source system, an optical detection system, a data acquisition and treatment system, a metal nanostructured sensing array system and a microfluid sampling control system, wherein the light source system emits light, the light passes through the optical detection system and is vertically irradiated to the integrated micro fluidic metal nanostructured sensing chip in the metal nanostructured sensing array system, and a sample to be measured is injected in the integrated micro fluidic metal nanostructured sensing chip by the microfluid sampling control system; the incident light is irradiated to the sample to be measured and is reflected, the reflected light enters to the data acquisition and treatment system by the optical detection system, and the data acquisition and treatment are carried out by the data acquisition and treatment system. The detector has the advantages of simple structure, low cost, convenient carrying, multiple components and high flux for parallel detection. The detector can satisfy the biochemical detection requirements in the fields of medical science, health, food, environment and the like, and is convenient for popularization.
Description
Technical field
The present invention relates to biochemical sensitive detection technique field, relate in particular to a kind of reflective local surface plasma resonance (LSPR) and strengthen bio-chemical detector.
Background technology
Based on local surface plasma optical sensing and micro-fluidic Research of Integration is the forward position and the hot issue of present international micro-fluidic optical sensing technology, has a wide range of applications and clear and definite industrialization prospect at medical science, health, food, environmental science.
Tradition biochemical sensitive technology needs mark usually; Mainly use radioactive isotope, enzyme or fluorescence etc. as marker, poor stability and poor stability, simultaneously; System bulk is big, sensitivity is low, process is loaded down with trivial details, efficient is low, can not satisfy fast, the demand of sensitivity, special efficacy, high throughput testing.In recent years; The label-free biochemical detection method is developed rapidly; Surface plasma body resonant vibration (SPR) sensing technology particularly, its principle of work are to adopt prism-coupled to add that high precision angle scanning, intensity and phase-detection mode carry out acquisition of signal, the intermolecular interaction of monitoring bio in real time; Be widely used in fields such as proteomics, medicament research and development, clinical diagnosis, food security and environmental monitoring, and improved detection efficiency.
But traditional SPR analyser price is up to millions of, and the instrument volume is bigger; Complicacy, it is lower that refractive index detects dynamic range, and owing to receive the restriction of surface plasma excimer spread length; Spatial resolution is lower; Be difficult in and realize on the one chip that highdensity sensor array unit is integrated, reach the purpose of high flux sensing detection, can't realize popularization and application at all and satisfy the demand that the outfield is surveyed.Simultaneously, current chip can only be bought from Biacore company, costs an arm and a leg, and causes a lot of instrument utilization factors low, and resource is in idle state.
Along with micro-nano process technologies such as electron beam lithography develop rapidly; For this metalloid nanosensor unit processing is provided convenience; Particularly the development of nanometer embossing makes efficient batch making metal nano sensing unit become possibility, reduces the processing cost of metal Nano structure greatly.Simultaneously; The achievement in research of plasma optics and micro-nano fluid technique forefront is applied in the biochemical sensitive detection system field; Make micro-fluidic optical plasma sensor-based system can produce infinite many new application in fields such as biochemical sensitive detections, have that volume is little, in light weight, cost is low, anti-pollution, required sample and plurality of advantages such as reagent is few, high flux, many components, high precision.Particularly survey unimolecule in the adsorption process of metal surface; LSPR (Localized Surface Plasmon Resonance) spectrum change is used for confirming that molecule combines and course of reaction, and this haves laid a good foundation in the interaction on conformation, the behavior of molecule interface and character, molecule and the mark metal particle surface of biomolecule for LSPR undoubtedly.And combine with microfluid can be from rule, the generation of disease and the interaction of development, medicine and body etc. of molecular level research vital movement; This sensor-based system based on the local surface plasma integrated micro-fluidic can adopt the wavelength detection mode; Detecting light path is the coaxial light path of normal incidence; Simplified the sensor-based system structure like this; The required cost of the equipment that greatly reduces also helps the miniaturization and the reliability of equipment, and very big attractive force is arranged in biochemistry detection, will accelerate research and development and application based on plasma micro-fluidic optical sensor-based system.
Summary of the invention
The technical matters that (one) will solve
In view of this; Fundamental purpose of the present invention is to provide a kind of reflective local surface plasma sensor-based system, bio-sensing chip and job operation thereof, shortcomings such as traditional SPR biochemical sensitive technological system is complicated, cost is high, analysis time is long, temperature influence is obvious, sensitivity is low to solve, small throughput, sensing chip is expensive, the sample consumption is big.
(2) technical scheme
For achieving the above object; The invention provides a kind of reflective local surface plasma resonance reinforced biochemical detector; Comprise light-source system 1, optical detection system 2, data Collection & Processing System 3, metal Nano structure sensor array system 4 and microfluid sampling control system 5; Wherein: the light that this light-source system 1 sends is injected with testing sample by this microfluid sampling control system 5 through the integrated micro-fluidic metal Nano structure sensing chip of these optical detection system 2 vertical irradiations in this metal Nano structure sensor array system 4 in this integrated micro-fluidic metal Nano structure sensing chip; Incident illumination is reflected after being mapped to this testing sample, and reflected light gets into this data Collection & Processing System 3 through this optical detection system 2 again, carries out data acquisition and processing by this data Collection & Processing System 3.
In the such scheme; Said light-source system 1 is made up of light source, power controller and optical fiber coupling device; Wherein this power controller is controlled input voltage and then is played the luminous power of regulating light source; Make light source can send the broad-spectrum white-light of wavelength 200-2000nm, the broad-spectrum white-light that sends gets into this optical detection system 2 through this optical fiber coupling device.The light source that said light-source system 1 adopts is LED, Halogen lamp LED, sodium vapor lamp or mercury lamp, and its spectral range is at 200-2000nm.
In the such scheme; Said optical detection system 2 comprises optical fiber and lens; This optical fiber comprises six core diameter incident opticals and a core diameter mirror based fiber optica; Wherein this six core diameters incident optical and this core diameter mirror based fiber optica constitute seven core diameter incidents/reflective probe, and this core diameter mirror based fiber optica is positioned at the center of this seven core diameters incident/reflective probe, and this six core diameters incident optical is evenly distributed on around this core diameter mirror based fiber optica; These lens are positioned at the front end of this seven core diameters incident/reflective probe, are used to compile hot spot.Said seven core diameter incidents/reflective probe and said lens are positioned on the coaxial light path, adopt reflective detection.
In the such scheme; Said data Collection & Processing System 3 comprises interconnective spectrometer and computing machine; And data acquisition software and data processing software are installed on this computing machine; This spectrometer is gathered reflective spectrum and is sent to this computing machine, is installed on data acquisition software on this computing machine and this spectrometer is sent spectral signal carries out record, and utilize the data processing software that is installed on this computing machine that spectral signal is carried out data processing.
In the such scheme; Said metal Nano structure sensor array system 4 comprises microfluid passage, metal Nano structure sensing chip and chip set; This metal Nano structure sensing chip is encapsulated in and forms this integrated micro-fluidic metal Nano structure sensing chip in this microfluid passage, and this integrated micro-fluidic metal Nano structure sensing chip is fixed on this chip set.The base material of said metal Nano structure sensing chip is transparent or opaque material, on this base material, is processed with metal Nano structure.
In the such scheme, said microfluid sampling control system 5 is made up of the multichannel syringe pump, can parameter be set sequencing, thereby realizes the accurate control to sample; Said microfluid sampling control system 5 utilizes plastic catheter that this multichannel syringe pump is connected with this integrated micro-fluidic metal Nano structure sensing chip, and testing sample is injected in this integrated micro-fluidic metal Nano structure sensing chip through syringe pump.
In the such scheme, this reflective local surface plasma resonance reinforced biochemical detector is used for surveying virus, bacterium, protein or cancer markers.
(3) beneficial effect
The advantage that the present invention is compared with prior art had is:
(1) bio-chemical detector device structure of the present invention simple, need not that mark can carry out directly, the equipment of real-time detection;
(2) bio-chemical detector of the present invention adopts reflective detection, and it is highly sensitive;
(3) bio-chemical detector of the present invention can be realized hyperchannel, high flux, parallel detection, has improved the efficient of surveying:
(4) easy to operate, the intelligent degree of bio-chemical detector of the present invention is high;
(5) sampling system of bio-chemical detector of the present invention has high precision, characteristics easy to control;
(6) bio-chemical detector of the present invention also have simultaneously miniaturization, in light weight, advantage such as be easy to carry;
(7) bio-sensing chip of the present invention is multiple-unit, array structure;
(8) bio-sensing chip of the present invention is to combine with microflow control technique, realizes the integrated of micro-fluidic optical sensor-based system.
Description of drawings
Fig. 1 is the structural representation of low cost provided by the invention, the reflective local surface plasma resonance reinforced biochemical detector of high sensitivity;
Fig. 2 is the test process synoptic diagram of low cost provided by the invention, the reflective local surface plasma resonance reinforced biochemical detector of high sensitivity;
Fig. 3 is the test result in embodiment illustrated in fig. 21.
Embodiment
For making the object of the invention, technical scheme and advantage clearer, below in conjunction with specific embodiment, and with reference to accompanying drawing, to further explain of the present invention.
The invention provides a kind of reflective local surface plasma resonance reinforced biochemical detector; It is a kind of biochemical sensitive checkout equipment based on spectral analysis technique; Comprise light-source system 1, optical detection system 2, data Collection & Processing System 3, metal Nano structure sensor array system 4 and microfluid sampling control system 5; Wherein: the light that this light-source system 1 sends is injected with testing sample by this microfluid sampling control system 5 through the integrated micro-fluidic metal Nano structure sensing chip of these optical detection system 2 vertical irradiations in this metal Nano structure sensor array system 4 in this integrated micro-fluidic metal Nano structure sensing chip; Incident illumination is reflected after being mapped to this testing sample, and reflected light gets into this data Collection & Processing System 3 through this optical detection system 2 again, carries out data acquisition and processing by this data Collection & Processing System 3.
Wherein, Said light-source system 1 is made up of light source, power controller and optical fiber coupling device; Wherein this power controller is controlled input voltage and then is played the luminous power of regulating light source; Make light source can send the broad-spectrum white-light of wavelength 200-2000nm, the broad-spectrum white-light that sends gets into this optical detection system 2 through this optical fiber coupling device.The light source that said light-source system 1 adopts is LED, Halogen lamp LED, sodium vapor lamp or mercury lamp, and its spectral range is at 200-2000nm.
Said optical detection system 2 comprises optical fiber and lens; This optical fiber comprises six core diameter incident opticals and a core diameter mirror based fiber optica; Wherein this six core diameters incident optical constitutes seven core diameter incidents/reflective probe with this core diameter mirror based fiber optica; And this core diameter mirror based fiber optica is positioned at the center of this seven core diameters incident/reflective probe, and this six core diameters incident optical is evenly distributed on around this core diameter mirror based fiber optica; These lens are positioned at the front end of this seven core diameters incident/reflective probe, are used to compile hot spot.Said seven core diameter incidents/reflective probe and said lens are positioned on the coaxial light path, adopt reflective detection.
Said data Collection & Processing System 3 comprises interconnective spectrometer and computing machine; And data acquisition software and data processing software are installed on this computing machine; This spectrometer is gathered reflective spectrum and is sent to this computing machine; Be installed on data acquisition software on this computing machine and this spectrometer is sent spectral signal carry out record, and utilize the data processing software that is installed on this computing machine that spectral signal is carried out data processing.
Said metal Nano structure sensor array system 4 comprises microfluid passage, metal Nano structure sensing chip and chip set; This metal Nano structure sensing chip is encapsulated in and forms this integrated micro-fluidic metal Nano structure sensing chip in this microfluid passage, and this integrated micro-fluidic metal Nano structure sensing chip is fixed on this chip set.The base material of said metal Nano structure sensing chip is transparent or opaque material, on this base material, is processed with metal Nano structure.
Said microfluid sampling control system 5 is made up of the multichannel syringe pump, can parameter be set sequencing, thereby realizes the accurate control to sample; Said microfluid sampling control system 5 utilizes plastic catheter that this multichannel syringe pump is connected with this integrated micro-fluidic metal Nano structure sensing chip, and testing sample is injected in this integrated micro-fluidic metal Nano structure sensing chip through syringe pump.
This reflective local surface plasma resonance reinforced biochemical detector can be used for surveying virus, bacterium, protein or cancer markers etc.
Among Fig. 1, light-source system 1 is used to provide the broad-spectrum white-light light source of adjustable power; The light that white light source sends gets into optical detection system 2 (reflective probe and lens) through optical fiber coupling device; Then the light that sends of white light source by vertical irradiation to integrated micro-fluidic metal Nano structure sensing chip; Incident light is reflected by integrated micro-fluidic metal Nano structure sensing chip; Reflected light passes through the reflective probe of optical detection system again, and through the spectrometer of optical fiber entering data Collection & Processing System, spectrometer links to each other with the computing machine of data Collection & Processing System; This computing machine carries out data processing to the spectral signal of spectrometer input, and is presented on the computer screen.
Based on the structural representation of reflective local surface plasma resonance reinforced biochemical detector shown in Figure 1, Fig. 2 shows high sensitivity LSPR bio-chemical detector test process synoptic diagram of the present invention.Earlier the integrated micro-fluidic metal Nano structure sensing chip for preparing is installed on the sensing chip support; And be connected with the microfluid sampling control system; Open light source and data Collection & Processing System, regulate the parameter of light source power and spectral manipulation software, avoid data saturated.Then, close light source, gather the half-light spectrum; Open light source, gather reference spectra, utilize the microfluid sampling control system sample to be injected in the microcavity of integrated micro-fluidic metal Nano structure sensing chip again,, carry out the different spectrum test according to different specimen.At last, utilize data handling system analysis, processing half-light spectrum, reference spectra and the specimen spectrum of the least significant end of system, judge the corresponding characteristic that passes.
In a specific embodiment of the present invention, utilize the bio-chemical detector of the reflective local surface plasma resonance enhancing of the present invention, be used to detect the sample of different refractivity.Light source in the selected light-source system is that spectral range is at 200～1100nm; Electric current 500mA; Voltage 12VDC, output power: 6.5 watts Halogen lamp LED, through optical fiber and reflective probe (Ocean Optics; QR400-7-UV-VIS) the back outgoing beam is behind lens, and the employing quartz of rayed in sensor-based system is as the gold nano structure sensing unit of substrate.The integrated microfluidic sensing unit is fixed on the sensing chip fixed mount.Spectroscopic analysis system is selected the QE65000 type spectroanalysis instrument of Ocean Optics company for use; After light reflects through detection chip; Collect signal by a reflective probe; Surveyed by the spectroanalysis instrument of rear end, the data of being gathered are carried out data communication through USB2.0 interface and computer system again, and data processing software can comprise that user interface, detection, control and data processing and output show several functional modules.
The biochemical sensitive system that the integrated microfluidic sensing unit that utilization is processed and the present invention announce tests, and specimen is: air, NaCl (20%), glycerine.It is as shown in Figure 3 to handle the data result that obtains through analysis software.
Above-described specific embodiment; The object of the invention, technical scheme and beneficial effect have been carried out further explain, and institute it should be understood that the above is merely specific embodiment of the present invention; Be not limited to the present invention; All within spirit of the present invention and principle, any modification of being made, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. reflective local surface plasma resonance reinforced biochemical detector; It is characterized in that; Comprise light-source system (1), optical detection system (2), data Collection & Processing System (3), metal Nano structure sensor array system (4) and microfluid sampling control system (5), wherein:
The light that this light-source system (1) sends arrives the integrated micro-fluidic metal Nano structure sensing chip in this metal Nano structure sensor array system (4) through this optical detection system (2) vertical irradiation, in this integrated micro-fluidic metal Nano structure sensing chip, is injected with testing sample by this microfluid sampling control system (5); Incident illumination is reflected after being mapped to this testing sample, and reflected light gets into this data Collection & Processing System (3) through this optical detection system (2) again, carries out data acquisition and processing by this data Collection & Processing System (3).
2. reflective local surface plasma resonance reinforced biochemical detector according to claim 1; It is characterized in that; Said light-source system (1) is made up of light source, power controller and optical fiber coupling device; Wherein this power controller is controlled input voltage and then is played the luminous power of regulating light source, makes light source can send the broad-spectrum white-light of wavelength 200-2000nm, and the broad-spectrum white-light that sends gets into this optical detection system (2) through this optical fiber coupling device.
3. reflective local surface plasma resonance reinforced biochemical detector according to claim 2 is characterized in that, the light source that said light-source system (1) adopts is LED, Halogen lamp LED, sodium vapor lamp or mercury lamp, and its spectral range is at 200-2000nm.
4. reflective local surface plasma resonance reinforced biochemical detector according to claim 1; It is characterized in that; Said optical detection system (2) comprises optical fiber and lens; This optical fiber comprises six core diameter incident opticals and a core diameter mirror based fiber optica; Wherein this six core diameters incident optical and this core diameter mirror based fiber optica constitute seven core diameter incidents/reflective probe, and this core diameter mirror based fiber optica is positioned at the center of this seven core diameters incident/reflective probe, and this six core diameters incident optical is evenly distributed on around this core diameter mirror based fiber optica; These lens are positioned at the front end of this seven core diameters incident/reflective probe, are used to compile hot spot.
5. reflective local surface plasma resonance reinforced biochemical detector according to claim 4 is characterized in that, said seven core diameter incidents/reflective probe and said lens are positioned on the coaxial light path, adopt reflective detection.
6. reflective local surface plasma resonance reinforced biochemical detector according to claim 1; It is characterized in that; Said data Collection & Processing System (3) comprises interconnective spectrometer and computing machine; And data acquisition software and data processing software are installed on this computing machine; This spectrometer is gathered reflective spectrum and is sent to this computing machine, is installed on data acquisition software on this computing machine and this spectrometer is sent spectral signal carries out record, and utilize the data processing software that is installed on this computing machine that spectral signal is carried out data processing.
7. reflective local surface plasma resonance reinforced biochemical detector according to claim 1; It is characterized in that; Said metal Nano structure sensor array system (4) comprises microfluid passage, metal Nano structure sensing chip and chip set; This metal Nano structure sensing chip is encapsulated in and forms this integrated micro-fluidic metal Nano structure sensing chip in this microfluid passage, and this integrated micro-fluidic metal Nano structure sensing chip is fixed on this chip set.
8. reflective local surface plasma resonance reinforced biochemical detector according to claim 7; It is characterized in that; The base material of said metal Nano structure sensing chip is transparent or opaque material, on this base material, is processed with metal Nano structure.
9. reflective local surface plasma resonance reinforced biochemical detector according to claim 1; It is characterized in that; Said microfluid sampling control system (5) is made up of the multichannel syringe pump, can parameter be set sequencing, thereby realizes the accurate control to sample; Said microfluid sampling control system (5) utilizes plastic catheter that this multichannel syringe pump is connected with this integrated micro-fluidic metal Nano structure sensing chip, and testing sample is injected in this integrated micro-fluidic metal Nano structure sensing chip through syringe pump.
10. reflective local surface plasma resonance reinforced biochemical detector according to claim 1 is characterized in that, this reflective local surface plasma resonance reinforced biochemical detector is used for surveying virus, bacterium, protein or cancer markers.
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| CN102938964A (en) * | 2012-10-26 | 2013-02-20 | 山东东仪光电仪器有限公司 | Multichannel plasma light source |
| CN104076013A (en) * | 2013-07-03 | 2014-10-01 | 青岛派科森光电技术股份有限公司 | Offshore oil spill detection system and method based on LSPR (Localized Surface Plasmon Resonance) sensor |
| CN106596474A (en) * | 2016-12-05 | 2017-04-26 | 重庆三峡学院 | Three-channel SPR (surface plasma resonance) sensor based on seven-core optical fiber |
| CN108106994A (en) * | 2017-12-15 | 2018-06-01 | 中国科学院光电技术研究所 | A kind of scan-type local enhances biochemical sensitive device |
| CN108931503A (en) * | 2018-04-19 | 2018-12-04 | 中山大学 | A kind of multiple determination device based on local surface plasma resonance sensing |
| CN113295651A (en) * | 2021-05-19 | 2021-08-24 | 中央民族大学 | High-flux array scanning type LSPR sensing detection system based on MEMS galvanometer |
| CN113295652A (en) * | 2021-05-19 | 2021-08-24 | 中央民族大学 | High-flux array scanning type LSPR sensing detection system |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102938964A (en) * | 2012-10-26 | 2013-02-20 | 山东东仪光电仪器有限公司 | Multichannel plasma light source |
| CN102938964B (en) * | 2012-10-26 | 2016-03-30 | 山东东仪光电仪器有限公司 | Multichannel plasma light source |
| CN104076013A (en) * | 2013-07-03 | 2014-10-01 | 青岛派科森光电技术股份有限公司 | Offshore oil spill detection system and method based on LSPR (Localized Surface Plasmon Resonance) sensor |
| CN106596474A (en) * | 2016-12-05 | 2017-04-26 | 重庆三峡学院 | Three-channel SPR (surface plasma resonance) sensor based on seven-core optical fiber |
| CN106596474B (en) * | 2016-12-05 | 2020-11-06 | 重庆三峡学院 | Three-channel SPR sensor based on seven-core optical fiber |
| CN108106994A (en) * | 2017-12-15 | 2018-06-01 | 中国科学院光电技术研究所 | A kind of scan-type local enhances biochemical sensitive device |
| CN108931503A (en) * | 2018-04-19 | 2018-12-04 | 中山大学 | A kind of multiple determination device based on local surface plasma resonance sensing |
| CN113295651A (en) * | 2021-05-19 | 2021-08-24 | 中央民族大学 | High-flux array scanning type LSPR sensing detection system based on MEMS galvanometer |
| CN113295652A (en) * | 2021-05-19 | 2021-08-24 | 中央民族大学 | High-flux array scanning type LSPR sensing detection system |
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Application publication date: 20121017 |