CN102680452A - Dual-detection biochemical sensing detector integrated with optofluidics - Google Patents
Dual-detection biochemical sensing detector integrated with optofluidics Download PDFInfo
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- CN102680452A CN102680452A CN2012101487398A CN201210148739A CN102680452A CN 102680452 A CN102680452 A CN 102680452A CN 2012101487398 A CN2012101487398 A CN 2012101487398A CN 201210148739 A CN201210148739 A CN 201210148739A CN 102680452 A CN102680452 A CN 102680452A
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/55—Specular reflectivity
- G01N21/552—Attenuated total reflection
- G01N21/553—Attenuated total reflection and using surface plasmons
- G01N21/554—Attenuated total reflection and using surface plasmons detecting the surface plasmon resonance of nanostructured metals, e.g. localised surface plasmon resonance
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/65—Raman scattering
- G01N21/658—Raman scattering enhancement Raman, e.g. surface plasmons
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Abstract
The invention discloses a dual-detection biochemical sensing detector integrated with optofluidics. The dual-detection biochemical sensing detector comprises a light source system, a light path reshaping system, a sensing chip, a three-dimensional control system, a surface-enhanced Raman SERS (Surface Enhanced Raman Scattering) detection system, a local surface plasma resonance LSPR (Localised Surface Plasmon Resonance) detection system and an automatic sampling control system. According to the sensing chip disclosed by the invention, two optical detection means of the LSPR and SERS are simultaneously adopted and are combined with microfluidics to form a novel microfluidics optical sensing chip; the application of traditional LSPR or SERS is extended by the technology; the sensing chip based on a double plasma structure has great attraction for biochemistry detection based on a liquid sample; and the research and application of the microfluidics optical sensing system are accelerated. The sample is detected by using two complementary modes of the LSPR and SERS; and the combination of the LSPR and SERS analytic technologies on the same substrate is realized.
Description
Technical field
The invention belongs to the biochemical sensitive detection range, relate to a kind of two biochemical sensitive detectors of surveying of SERS-local surface plasma resonance of integrated micro-fluidic optics.
Background technology
The micro-fluidic optical plasma is that microfluid, photonics and plasma are integrated; It is a new research direction that progressively forms in recent years; The achievement in research of plasma optics forefront is applied in this field, so the micro-fluidic optical plasma can produce infinite many new application in fields such as biology, chemistry, biological chemistry, medical science, engineerings.Plasma has unique physical attribute, and the optical property of local nanoscale can strengthen light and the matter interaction with free electron.One of them important application just is based on the biology sensor of plasma.Have a wide range of applications and clear and definite industrialization prospect at medical science, health, food, environmental science.
At present mainly utilize the micro-fluidic optical biochemical analysis or the sensing of optical properties to have: refractive index detects, fluoroscopic examination, and the surface increases Raman scattering and detects optical acquisition and optical control.The label-free biochemical detection method is developed rapidly; Particularly based on local surface plasma resonance LSPR sensing technology; Particularly in the process of surveying unimolecule and metal nanoparticle surface combination, the variation of local surface plasma resonance LSPR spectrum and SERS SERS " fingerprint " spectrum are important means.When unimolecule combined with the metal surface, the analysis of LSPR spectrum change can be controlled; And this moment, the detectable identification molecule of SERS also obtains the orientation of metal surface absorbing molecules.Yet the generation of SERS is by the laser excitation of single wavelength, and LSPR is excited by white light source, therefore, because excitation source is different, detects so these two kinds of detection meanss can not realize in-situ synchronization.
Summary of the invention
In order to solve the deficiency in traditional single measuring technology LSPR or the SERS technology; Utilize local surface plasma resonance LSRP technology, microflow control technique and micro-nano process technology; Realize high sensitivity, exempt from the nano-array bio-chemical detector of mark; And utilize LSPR detectable biomolecule cohesive process, judge the molecule of institute's absorption with the SERS technology.
The object of the present invention is to provide a kind of two biochemical sensitive detectors of surveying of SERS-local surface plasma resonance of integrated micro-fluidic optics.
Two biochemical sensitive detector of surveying of the present invention comprises: light-source system, light path orthopedic systems, sensing chip, three-dimensional control system, surface-enhanced Raman SERS detection system, local surface plasma resonance LSPR detection system; And auto injection control system; Wherein, sensing chip is installed on the three-dimensional control system; The auto injection control system is to the sensing chip injected sample; By light-source system laser or white light source are provided; Impinge perpendicularly on sensing chip through the light path orthopedic systems; Get into the SERS detection system through the sensing chip laser light reflected, and carry out corresponding SERS data processing and analysis; Get into the LSPR detection system from the white light of sensing chip projection, and carry out corresponding LSPR data processing and analysis.
Light-source system comprises: light source; Be installed in the switching device on the light source; Be connected in order to the power controller of control light source power with light source.Thereby light-source system can provide the laser of the single wavelength that excites SERS and the white light that excites LSPR through switching device.
The white light source that light source adopts is a kind of in LED, Halogen lamp LED, sodium vapor lamp and the mercury lamp, and its spectral range is between 200 ~ 2000nm.
Sensing chip is fixed in the three-dimensional control system, can realize three-dimensional accurate moving, and its precision can reach 10 microns.
The SERS detection system comprises: the SERS detecting devices; The data that the SERS detecting devices obtains are sent to computing machine No. one, by being arranged on a SERS data acquisition and the process software in the computing machine data are analyzed.
The LSPR detection system comprises: the LSPR detector; The LSPR detector is collected signal, transfers to spectrometer; The data that spectrometer obtains are sent to computing machine No. two, by being arranged on No. two LSPR data acquisition and the process softwares in the computing machine data are analyzed.
The auto injection control system comprises the above syringe pump of two-way, can parameter be set sequencing, thereby realizes sample is accurately controlled.
Sensing chip comprises the sensing chip unit of K*L display, and the sensing chip unit comprises: substrate and be bonded together with it last slice; Constitute import, outlet and the microcavity of microchannel in being formed on slice; Be formed on the substrate and be in the nano particle of the m*n array in the microcavity; Wherein, m, n, K and L are natural number.
The range of size of sensing chip unit is between tens microns to several microns.To between the hundreds of nanometer, the spacing range between the nano particle arrives between the hundreds of nanometer in tens nanometers the range of size of nano particle in tens nanometers.
Nano particle is precious metal particles such as gold or silver, is shaped as a kind of in sphere, elliposoidal, nano-seam and the nano-pore.The material of substrate is a kind of in the transparent materials such as K9 glass, quartz glass, dimethione PDMS, polymetylmethacrylate, polystyrene PS.Last slice material is dimethione PDMS or polymetylmethacrylate.
To between tens microlitres, its shape can be sphere or cube to the volume range of microcavity at several microlitres.The width range of microchannel is between 10 microns to 200 microns, and depth range is between 50 microns to 200 microns.
Sensing chip of the present invention adopts LSPR and two kinds of optical detection means of SERS simultaneously; And combine with microflow control technique and to have formed novel micro-fluidic optical sensing chip; This technology is for having expanded the application of traditional LSPR or SERS; This sensing chip based on the double plasma structure has very big attractive force in the biochemistry detection based on fluid sample, will accelerate the research and development and the application of micro-fluidic optical sensor-based system.Utilize two kinds of complement mode test sample of LSPR and SERS, in same substrate, realize the combination of LSPR and SERS analytical technology.
Advantage of the present invention:
(1) device structure simple, need not that mark can carry out directly, the equipment of real-time detection;
(2) realized the mutual supplement with each other's advantages of SERS and LSPR;
(3) can realize hyperchannel, high flux, parallel detection, improve the efficient of surveying;
(4) easy to operate, intelligent degree is high;
(5) sampling system has high precision, manageable characteristics;
(6) multiple-unit, array structure;
(7) adopt nanofabrication technique cheaply, can realize large tracts of land processing;
(8) combine with microflow control technique, realize the integrated of micro-fluidic optical sensor-based system.
Description of drawings
Fig. 1 is two structural representation of surveying the biochemical sensitive detector of the present invention;
Fig. 2 is the structural representation of sensing chip of the present invention;
Fig. 3 is the LSPR test result in the embodiments of the invention;
Fig. 4 is the SERS test result in the embodiments of the invention.
Embodiment
Below in conjunction with accompanying drawing, do further to describe in detail through the specific embodiment specific embodiments of the invention.
As shown in Figure 1, two biochemical sensitive detectors of surveying of the present invention comprise: light-source system 1, light path orthopedic systems 2, sensing chip 3, three-dimensional control system 4, surface-enhanced Raman SERS detection system 5, local surface plasma resonance LSPR detection system 6; And auto injection control system 7; Wherein, sensing chip 3 is installed on the three-dimensional control system 4; Auto injection control system 7 is to sensing chip 3 injected sample; By light-source system 1 laser or white light source are provided; Impinge perpendicularly on sensing chip 3 through light path orthopedic systems 2; Get into SERS detection system 5 through sensing chip 3 laser light reflected, and carry out corresponding SERS data processing and analysis; Get into LSPR detection system 6 from the white light of sensing chip 3 transmissions, and carry out corresponding LSPR data processing and analysis.
Laser source wavelength is 488nm, 632.8nm and 850nm in the light-source system 1.
As shown in Figure 2, sensing chip of the present invention comprises the sensing chip unit of K*L display, and the sensing chip unit comprises: substrate 31 and be bonded together with it last slice 32; Be formed on 32 interior import, outlet 33 and a microcavity 34 that constitute microchannel; Be formed on the substrate and be in the nano particle 35 of the m*n array in the microcavity; Wherein, m, n, K and L are natural number.
Present embodiment utilizes the SERS of a kind of integrated micro-fluidic optics of the present invention--and the two biochemical sensitive detectors of surveying of-local surface plasma resonance are used to detect the several samples of different refractivity.The SERS detection system of being selected for use in the SERS test is the HR800SERS detecting devices of HORIBAJOBIN YVON company, and light source is the HeNe laser instrument, and its power is 20mW, and wavelength is 632.8nm.Light source in the LSPR test in the selected light-source system is that spectral range is at 200 ~ 1100nm; Electric current 500mA, voltage 12VDC, the Halogen lamp LED that output power is 6.5 watts; 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 fixed on the three-dimensional high-precision fixed mount as the gold nano structure sensing unit of substrate.Spectrometer is selected the QE65000 type spectroanalysis instrument of Ocean Optics company for use; Behind the light transmission chip; Collect signal by detector; Surveyed by the spectrometer 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 the LSPR specimen is: air, NaCl (20%), glycerine.It is as shown in Figure 3 to handle the data result that obtains through analysis software; Because the refractive index of air NaCl (20%), three kinds of specimen of glycerine is respectively 1,1.3684 and 1.473; Because of specimen refractive index difference; The peaked position of the LSPR extinction spectra that obtains through this testing of equipment is respectively at 533.52nm, 577.97nm and 587.37nm, and refractive index increases, and red shift has taken place corresponding spectral line.The SERS specimen is: rhodamine R6G, and it is as shown in Figure 4 to handle the data result obtain through analysis software, and the wave number of its characteristic peak is respectively 1197,1277,1366,1509 and 1647cm
-1
It should be noted that at last; The purpose of publicizing and implementing mode is to help further to understand the present invention; But it will be appreciated by those skilled in the art that: in the spirit and scope that do not break away from the present invention and appended claim, various replacements and to revise all be possible.Therefore, the present invention should not be limited to the disclosed content of embodiment, and the scope that the present invention requires to protect is as the criterion with the scope that claims define.
Claims (9)
1. survey the biochemical sensitive detector for one kind pair; It is characterized in that said sensing detection appearance comprises: light-source system (1), light path orthopedic systems (2), sensing chip (3), three-dimensional control system (4), surface-enhanced Raman SERS detection system (5), local surface plasma resonance LSPR detection system (6); And auto injection control system (7); Wherein, sensing chip (3) is installed on the three-dimensional control system (4); Auto injection control system (7) is to sensing chip (3) injected sample; By light-source system (1) laser or white light source are provided; Impinge perpendicularly on sensing chip (3) through light path orthopedic systems (2); Get into SERS detection system (5) through sensing chip (3) laser light reflected, and carry out corresponding SERS data processing and analysis; Get into LSPR detection system (6) from the white light of sensing chip transmission, and carry out corresponding LSPR data processing and analysis.
2. sensing detection appearance as claimed in claim 1 is characterized in that said light-source system comprises: light source; Be installed in the switching device on the light source; Be connected in order to the power controller of control light source power with light source.
3. sensing detection appearance as claimed in claim 2 is characterized in that, the white light source that said light source adopts is a kind of in LED, Halogen lamp LED, sodium vapor lamp and the mercury lamp, and its spectral range is between 200 ~ 2000nm.
4. sensing detection appearance as claimed in claim 1 is characterized in that, said sensing chip comprises the sensing chip unit of K*L display, and the sensing chip unit comprises: substrate (31) and last slice (32) that are bonded together with it; Be formed on the import, outlet (33) and the microcavity (34) that constitute microchannel in slice (32); Be formed on the substrate and be in the nano particle (35) of the m*n array in the microcavity; Wherein, m, n, K and L are natural number.
5. sensing detection appearance as claimed in claim 1 is characterized in that, said SERS detection system comprises: the SERS detecting devices; The data that the SERS detecting devices obtains are sent to computing machine No. one, by being arranged on a SERS data acquisition and the process software in the computing machine data are analyzed.
6. sensing detection appearance as claimed in claim 1 is characterized in that, said LSPR detection system comprises: the LSPR detector; The LSPR detector is collected signal, transfers to spectrometer; The data that spectrometer obtains are sent to computing machine No. two, by being arranged on No. two LSPR data acquisition and the process softwares in the computing machine data are analyzed.
7. sensing detection appearance as claimed in claim 1 is characterized in that, said auto injection control system comprises the above syringe pump of two-way, through sequencing parameter is set, and sample is accurately controlled.
8. sensing detection appearance as claimed in claim 4 is characterized in that said nano particle is precious metal particles such as gold or silver, is shaped as a kind of in sphere, elliposoidal, nano slit and the nano-pore.
9. sensing detection appearance as claimed in claim 4 is characterized in that, between tens microlitres, its shape can be sphere or cube to the volume range of said microcavity at several microlitres.
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103033497A (en) * | 2012-12-25 | 2013-04-10 | 吉林大学 | Microfluidic chip analyzer applying raman spectrum for detection |
| CN103149193A (en) * | 2013-02-25 | 2013-06-12 | 重庆大学 | Light-stream control system based on gold-nanoparticle modified carbon nanotube array surface enhanced Raman scattering |
| CN103674902A (en) * | 2013-12-12 | 2014-03-26 | 中国科学院半导体研究所 | LSPR (Localized Surface Plasmon Resonance) portable biochemical detector based on mobile phone platform |
| 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 |
| CN104597035A (en) * | 2015-02-04 | 2015-05-06 | 吉林大学 | Method for detecting potassium ions by using SERS technology |
| 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 |
| CN108152249A (en) * | 2017-12-22 | 2018-06-12 | 太原理工大学 | Detect the optical biosensor and method of DNA mismatch in free fluid |
| CN109323977A (en) * | 2018-08-23 | 2019-02-12 | 中山大学 | A kind of blood count-haemocyte parting detector and preparation method thereof simultaneously |
| CN110244050A (en) * | 2019-06-11 | 2019-09-17 | 中央民族大学 | A kind of cell cracking original position optical sensing detection chip and its preparation and application |
| CN111795950A (en) * | 2019-04-03 | 2020-10-20 | 梅克文斯股份公司 | Biosensor platform and method for simultaneous, multiplex, ultrasensitive and high-throughput optical detection of biomarkers |
| CN112955731A (en) * | 2018-09-06 | 2021-06-11 | 尼科亚生命科学股份有限公司 | Plasmon Resonance (PR) systems and instruments, Digital Microfluidic (DMF) cartridges, and methods for analyte analysis using Localized Surface Plasmon Resonance (LSPR) |
| CN115096871A (en) * | 2022-07-22 | 2022-09-23 | 香港科技大学深圳研究院 | Detection device applied to multichannel SERS micro-fluidic chip |
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Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103033497A (en) * | 2012-12-25 | 2013-04-10 | 吉林大学 | Microfluidic chip analyzer applying raman spectrum for detection |
| CN103033497B (en) * | 2012-12-25 | 2014-10-15 | 吉林大学 | Microfluidic chip analyzer applying raman spectrum for detection |
| CN103149193A (en) * | 2013-02-25 | 2013-06-12 | 重庆大学 | Light-stream control system based on gold-nanoparticle modified carbon nanotube array surface enhanced Raman scattering |
| CN103149193B (en) * | 2013-02-25 | 2015-05-20 | 重庆大学 | Light-stream control system based on gold-nanoparticle modified carbon nanotube array surface enhanced Raman scattering |
| CN103674902A (en) * | 2013-12-12 | 2014-03-26 | 中国科学院半导体研究所 | LSPR (Localized Surface Plasmon Resonance) portable biochemical detector based on mobile phone platform |
| 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 |
| CN104597035A (en) * | 2015-02-04 | 2015-05-06 | 吉林大学 | Method for detecting potassium ions by using SERS technology |
| 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 |
| CN108152249A (en) * | 2017-12-22 | 2018-06-12 | 太原理工大学 | Detect the optical biosensor and method of DNA mismatch in free fluid |
| CN108152249B (en) * | 2017-12-22 | 2021-03-26 | 太原理工大学 | Optical biosensor and method for detecting DNA mismatch in free liquid |
| CN109323977A (en) * | 2018-08-23 | 2019-02-12 | 中山大学 | A kind of blood count-haemocyte parting detector and preparation method thereof simultaneously |
| CN112955731A (en) * | 2018-09-06 | 2021-06-11 | 尼科亚生命科学股份有限公司 | Plasmon Resonance (PR) systems and instruments, Digital Microfluidic (DMF) cartridges, and methods for analyte analysis using Localized Surface Plasmon Resonance (LSPR) |
| CN111795950A (en) * | 2019-04-03 | 2020-10-20 | 梅克文斯股份公司 | Biosensor platform and method for simultaneous, multiplex, ultrasensitive and high-throughput optical detection of biomarkers |
| CN110244050A (en) * | 2019-06-11 | 2019-09-17 | 中央民族大学 | A kind of cell cracking original position optical sensing detection chip and its preparation and application |
| CN115096871A (en) * | 2022-07-22 | 2022-09-23 | 香港科技大学深圳研究院 | Detection device applied to multichannel SERS micro-fluidic chip |
| CN115096871B (en) * | 2022-07-22 | 2022-12-23 | 香港科技大学深圳研究院 | Detection device applied to multichannel SERS micro-fluidic chip |
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Application publication date: 20120919 |