CN108387505A - A kind of multifunctional light tweezers system and method based on micro-fluidic chip - Google Patents
A kind of multifunctional light tweezers system and method based on micro-fluidic chip Download PDFInfo
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Abstract
The invention discloses a kind of multifunctional light tweezers system and method based on micro-fluidic chip, the system include：Micro-fluidic chip particle sampling system, number system, signal detection system and optical tweezer separation system；Micro-fluidic chip particle sampling system, for making particle pass through micro-fluidic chip one by one along certain path by fluid dynamics focusing；When particle is by detecting count block, signal detection system is realized the luminous signal of particle and the multi-parameter of forward-scattering signal while being characterized by Feebleness Light Signal Examining technology, realizes the detection of particle, and counted to particle number by number system；When particle sorts area by capture, according to the testing result of particle, the sorting function of particle is realized into horizontal deflection to particular kind of particle by optical tweezer separation system.Apparatus of the present invention are compact-sized, easily realize that miniaturization, this method have many advantages, such as that high sensitivity, analyze speed are fast, high-throughput, selectivity is good, amount of samples is few, strong antijamming capability.
Description
Technical field
The present invention relates to Microfluid based Lab on a chip, the micro- manipulation technology of optical tweezer, nanophotonics and biomedical detections
Equal interleaving techniques field more particularly to a kind of multifunctional light tweezers system and method based on micro-fluidic chip.
Background technology
Common cell sorting method has cell sieve separating method, centrifugal classification method, laser induced fluorescence separating method and magnetic point
Select method.The flow cytometry generally use laser-Induced Fluorescence Detection of commercialization in conjunction with the method that dielectrophoretic force sorts, and is based on
Traditional cell sorting method can be generalized to the realization of microflow control technique level by the flow cytometry of micro-fluidic chip, using outer
Sorting is realized in the effect of power, micro-fluidic to fully demonstrate such as dielectrophoresis sorting, magnetic-adsorption, luminous power sorting harmony power sorting
Chip size is small, efficient, integrated level is high, analyze speed is fast, lower-price characteristic.
The concept of optical tweezer was proposed by American scientist Ashkin in 1970 earliest, by the gauss laser of a branch of high concentration
Sufficiently strong ligh trap gradient force is generated in focal point, the particle of micron or even nano-scale is captured and manipulated.Optical tweezer skill
Art uses contactless remote control operating mode, without processing micro- operating element, and will not generate mechanical damage to being steered cell,
Thus become the most common means that in micro-fluidic chip unicellular or other particles are carried out with optical control.
Up-conversion luminescence nanomaterial can absorb two or more lower energy photons and radiate a high-energy photon, typically will
Near infrared light is converted to visible light.It has many advantages, such as biomarker probe, such as：Hypotoxicity, high chemical stability,
Excellent photostability, narrow emission, the luminescent lifetime of length and high s/n ratio etc.；In addition, near-infrared laser is as its exciting light
Source brings many advantages, such as：Deeper smooth penetration depth, it is almost not damaged to biological tissue, without background fluorescence etc..
Suspension array technique based on microballoon refers to being immobilized on to be made on microsphere supported by antibody or other biological molecule to catch
Obtain microballoon, be then in different substance to be checked in the capture microballoon specific recognition detection architecture of suspended state, finally with report
It accuses antibody or hybridization or immune response occurs for biomolecule, form interlayer structure.By detecting the report molecule on single microballoon
Signal such as fluorescence, radioactivity, chemiluminescence etc. quantify the concentration of detection object.Pass through the size coding of microballoon, fluorescence
Coding etc. detects while capable of realizing multiple analytes, which is highly suitable for the detection of micro-example.
Based on micro-fluidic chip and upper conversion nano labelling technique, structure optical tweezer sorting system has in fields such as bioanalysis
Extraordinary application potential, can be to the various biomolecules such as nucleic acid, protein in complex sample (such as whole serum, whole plasm)
Deng or the determinands such as virion carry out highly sensitive detection, and to circulating tumor cell (CTCs) in tumor patient blood sample into
Row detection, sorting and parting, a kind of new analysis is provided for the early diagnosis of cancer, curative effect evaluation and cancer metastasis Mechanism Study
Technology.
Invention content
The technical problem to be solved in the present invention is for the defects in the prior art, to provide a kind of based on micro-fluidic chip
Multifunctional light tweezers system and method.
The technical solution adopted by the present invention to solve the technical problems is：
The present invention provides a kind of multifunctional light tweezers system based on micro-fluidic chip, which includes：Micro-fluidic chip is micro-
Grain sampling system, number system, signal detection system and optical tweezer separation system；Wherein：
Micro-fluidic chip particle sampling system, for making particle pass through one by one along certain path by fluid dynamics focusing
Micro-fluidic chip is preset with detection count block and capture sorting area on micro-fluidic chip；
When particle is by detecting count block, signal detection system realizes the hair of particle by Feebleness Light Signal Examining technology
The multi-parameter of optical signal and forward-scattering signal characterizes simultaneously, realizes the detection of particle, and by number system to particle number
Amount is counted；
When particle sorts area by capture, according to the testing result of particle, by optical tweezer separation system to particular kind of
Particle realizes the sorting function of particle into horizontal deflection.
Further, micro-fluidic chip of the invention is provided with 3 roads and flows into end and 3 road outflow ends, detects count block and catches
Obtain the position that sorting area is arranged between inflow end and outflow end；Wherein：
3 roads flow into end, and both sides are sheath stream, and centre is the sample flow of particle；Sample flow flows into detection meter simultaneously with sheath stream
Number area and capture sorting area, the sheath stream of both sides are used to ensure the particle that sample flow is individually arranged in intermediate formation, particle surrounding quilt
Sheath stream surrounds；
In 3 road outflow ends, centre is the outflow end (waste fluid channel) of sample flow, and both sides are collection channel；Pass through optical tweezer point
Optical tweezer deflection occurs for the particle of choosing, is flowed out by collection channel.
Further, the system of the invention further includes light-source system, and light-source system includes LED light source and laser light source；
Wherein：
LED light source generates White LED light, as the instruction light source of particle after lens focus, indicates light source from miniflow
It is irradiated above control chip particle sampling system；
Laser light source generates near-infrared laser, and by adjustable polarization type attenuator, unpolarized near-infrared laser is decomposed
At the different polarised light of two beams, including P light and S light, and the energy ratio of two beam laser is arbitrarily adjusted, two beam polarization lasers are from miniflow
It is irradiated below control chip particle sampling system.
Further, in two beam polarization lasers of the invention, S light is modulated by acousto-optic modulator, acousto-optic modulator
The modulation of intensity and deflection angle for being carried out at the same time laser；The focal beam spot of P light and S light is located on micro-fluidic chip
Upstream and downstream, be used separately as excitation light source and capture light source；S light is focused by object lens again by beam-expanding system and forms light
Trap, ligh trap is for capturing particle.
Further, the wavelength of near infrared laser of the invention is 808nm, 980nm or 1064nm.
Further, signal detection system of the invention includes multiple photomultiplier PMT and an InGaAs detector,
It is respectively used to up-conversion luminescence and the forward-scattering signal of detection of particles, it is logical to increase up-conversion luminescence signal detection as needed
Road number builds multichannel detection system.
The present invention provides a kind of multi-functional optical tweezer method based on micro-fluidic chip, includes the following steps：
Step 1：Up-conversion fluorescence probe is coupled to microparticle surfaces, single microparticle suspending liquid of formation injects micro-fluidic core
In the channel of piece particle sampling system, sample flow is set to be sorted in single file by detecting count block and capture according to flow focusing principle
Area；
Step 2：Start near infrared laser, the laser after object lens focus will be non-by adjustable polarization type attenuator
The near-infrared laser of polarization resolves into the different polarised light of two beams, including P light and S light；Pass through camera or video camera observation adjustment P
The position of light and S light, and laser power size is adjusted, so that upstream of the P light in channel is acted on particle, excites up-conversion luminescence
Signal, S light form ligh trap in downstream；
Step 3：Optical tweezer point is carried out according to up-conversion luminescence signal and forward-scattering signal intensity instruction acousto-optic modulator
Being turned on or off for system is selected, target particle is made to be entered collection channel by ligh trap active force, is not affected by the micro- of ligh trap force effect
Grain then enters waste fluid channel, to carry out real-time counting, quantitative analysis and sorting to target particle.
Further, probe of the invention is up-conversion nano material.
Further, the target particle type being detected of the invention includes：Cell, cell excretion body, and using micro-
Nucleic acid, albumen, virus, small molecule and the metal ion of ball enrichment.
Further, the target particle type sort of the invention is finely ground particles, including cell or microballoon.
The beneficial effect comprise that：The multifunctional light tweezers system and method based on micro-fluidic chip of the present invention,
It has the following advantages：
1, the present invention mutually ties Microfluid based Lab on a chip, up-conversion label biological sample with multifunctional light tweezers system
It closes, proposes that a kind of novel analysis and detection device, the device can carry out a variety of determinands to analyze and detach in real time.
2, the present invention is small to the damage of biological sample using the up-conversion luminescence nanomaterial of small particle as label probe.
3, it realizes sorting while the multifunctional light tweezers system that the present invention is built can be detected sample, has very high
Detect the accuracy of flux and sorting.
4, single beam laser is divided into P light and S light by the present invention, avoids using twin-laser, and be easy to adjust two beams respectively
The intensity of light, simplifies device, reduces cost.
5, the present invention is by simple White-light LED illumination light source instruction light source as sample simultaneously.
6, apparatus of the present invention using near-infrared laser due to realizing that excitation up-conversion nano material shines, and only laser is poly-
There is strong up-conversion luminescence signal in burnt focal point, and it is dry to overcome the autofluorescence for being difficult to overcome in conventional fluorescent detection method
It disturbs, therefore when analysis of this method for complex sample system, improves the anti-interference ability of method.In addition, laser and particle
The forward-scattering signal of effect can accurately judge the appearance of particle through spectroscope.The combination of physical signal and chemical signal
Analysis, is convenient for accurate follow-up separation.
7, apparatus of the present invention are detected weaker near-infrared scattered light signal by InGaAs devices, by photomultiplier
Up-conversion luminescence signal is detected.Two kinds of detectors all have high s/n ratio, high sensitivity and fast response time etc. excellent
Point.
8, apparatus of the present invention are convenient for quick positioning chip channel detection area by camera (video camera) field of view.
9, when the present invention is used for the detection of biological sample, have the characteristics that high-throughput, low background, high sensitivity.
Description of the drawings
Present invention will be further explained below with reference to the attached drawings and examples, in attached drawing：
Fig. 1 apparatus of the present invention structural schematic diagrams；
Fig. 2 floor layouts；
Fig. 3 tumor-marker substance markers up-conversion nano material schematic diagrames；
Fig. 4 cell marking up-conversion nano material schematic diagrames.
Specific implementation mode
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to the accompanying drawings and embodiments, right
The present invention is further elaborated.It should be appreciated that described herein, specific examples are only used to explain the present invention, not
For limiting the present invention.
In a specific embodiment of the present invention, it is based on up-conversion luminescence nanomaterial labels targets target micro-fluidic chip meter
Microfluid based Lab on a chip, up-conversion luminescence nanomaterial are marked biological target by number, detection and the multifunctional light tweezers system sorted
Mark is combined structure multifunctional light tweezers system, using acousto-optic modulator to capture laser into horizontal deflection, to realize collection counting, inspection
It surveys and sorts in the system of one, and the various biomolecules being applicable in complex sample (such as whole serum, whole plasm)
In the highly sensitive detection of such as nucleic acid, the protein or virion determinand and side such as the sorting of tumour cell and diagnosis
Face.
In order to achieve the above object, the multi-functional optical tweezer of counting, detection and sorting of the invention based on micro-fluidic chip
System, including micro-fluidic chip particle (cell, microballoon etc.) sampling system, forward scattering photometry number system, up-conversion luminescence letter
Number detecting system, optical tweezer deflect separation system.White LED light source is after lens focus as the instruction light source of particle.By close red
The laser that outer laser is sent out is divided into the different polarization state light of two beams, instead vertically into adjustable polarization type attenuator (VPBS)
It is S light to penetrate light, is P light through light, and P light enters second adjustable polarization type attenuator after lens group, speculum, reflects simultaneously
S light enter second adjustable polarization type attenuator through acousto-optic modulator (AOM) and lens group, two-beam is all through speculum at this time
With enter pupil after 20 times of object lens after two colo(u)r filters, and after being focused by object lens, P light realizes the up-conversion luminescence excitation of particle, claims
To detect laser, detection laser beam suitably adjusts beam diameter by lens group, it is made finally to be focused in microchannel by object lens
Spot diameter is 15-20 microns, and S light is focused by object lens forms ligh trap for capturing sample particle.P light actions are preceding on particle
Enter polarization spectroscope after the reflection of two colo(u)r filters after being collected to scattered light signal by condenser, then by InGaAs detectors
Detection, up-conversion luminescence signal is then returned and is detected by photomultiplier (PMT) through two colo(u)r filters, by signal detection system
(DAQ data collecting cards) combines up-conversion luminescence signal and forward-scattering signal, judges that this is micro- with while counting in detection
Whether grain is target particle, and optical tweezer deflection reaches collection channel, and the particle for being not affected by ligh trap force effect then enters waste fluid channel, from
And it realizes and counts, detect and sort in the system of one.
Using adjustable polarization type attenuator, non-polarized light is divided into two beam polarization state lights, the laser energy that can decay is to reality
Power needed for border, can also be according to the light detection scattered signal of polarization state.Adjustable polarization type attenuator half-wave plate and polarization point
Two kinds of optical element compositions of light microscopic, there are two half-wave plate in adjustable polarization type attenuator, the half-wave plate of incidence side, which rises to adjust, to be divided
The effect of beam ratio, outgoing side's half-wave plate play a part of to adjust outgoing light polarization direction.If the polarization direction of outgoing side meets need
It wants, then the half-wave plate of the side of outgoing can omit and not have to.When a branch of non-polarized light vertical incidence, spectroscope can be divided into two
Beam polarised light, polarization state is orthogonal, and reflected light is S light, is P light through light.The energy ratio and incident light of S light and P light it is inclined
The direction that shakes is related, therefore the polarization direction for changing incident light can change the energy ratio of P light and S light.
The S light separated by spectroscope is modulated by acousto-optic modulator, and acousto-optic modulator can be carried out at the same time the strong of laser
The modulation of degree and deflection angle.
The S light formed to same near-infrared laser beam beam splitting is different with the effect of P light.The focal beam spot of P light and S light is distinguished
Upstream and downstream in microchannel is used separately as excitation light source and capture light source.S light initially enters acousto-optic modulator, so
It is expanded by lens group, and is focused by object lens and form ligh trap.
The near infrared laser is suitable for the excitation of up-conversion luminescence signal, wavelength 808nm, 980nm or 1064nm.
The design of micro-fluidic chip channel is mainly based upon flow focusing sample, and sample particle is made to pass through detection zone one by one.
Sample particle is marked by up-conversion nano material, near-infrared laser excitation and detection, the light injury to biological sample
It is small.
Detection detects up-conversion luminescence by photomultiplier with counting module and InGaAs detectors detect forward scattering light,
CCD (or CMOS) camera (video camera) is used for imaging.
Acousto-optic modulator can modulate laser intensity and direction, form the optical tweezer of actively manipulation.
Signal detection system is made of the data collecting card and software of multichannel.
The multifunctional light tweezers system of counting, detection and sorting based on micro-fluidic chip realizes detection, sorting biological target
Method, be as follows：
Up-conversion fluorescence probe is coupled to microparticle surfaces by step 1, and individual particle suspension injection micro-fluidic chip is led to
In road, make sample in single file by presetting detection zone according to flow focusing principle；
Step 2 starts near infrared laser, and the laser after object lens focus adjusts laser power size, and P light is in upstream
It is acted on particle, it is ensured that excitation up-conversion luminescence signal；S light forms ligh trap in downstream；
Step 3 carries out optical tweezer according to up-conversion luminescence signal and forward-scattering signal intensity instruction acousto-optic modulator
It being turned on or off, target particle is made to enter collection channel, the particle for being not affected by ligh trap force effect then enters waste fluid channel, to
Carry out real-time counting, quantitative analysis and the sorting to target particle.
Apparatus of the present invention are by white LED light source as the instruction light source of sample particle after lens focus.It is by wavelength
The collimated mirror of laser that 980nm semiconductor near infrared light fibre lasers are sent out is vertically into adjustable polarization type attenuator
(VPBS), it is divided into two beam polarization state lights, reflected light is S light, is P light through light, and P light enters second after lens group and speculum
A adjustable polarization type attenuator, while the S light reflected enters second adjustable offset after lens group expands again through acousto-optic modulator
Formula of shaking attenuator, at this time two-beam all after speculum and two colo(u)r filters enter 20 × object lens after pupil, after being focused by object lens, P
Up-conversion luminescence of the light for cell excites, and referred to as detects laser, detection laser beam suitably adjusts beam diameter by lens group, makes
It is 15-20 μm that it finally focuses on the spot diameter in microchannel by object lens, and S light is focused by object lens forms ligh trap for capturing sample
Product particle.For P light actions on particle, scattered light signal enters polarization spectro after being collected by condenser after the reflection of two colo(u)r filters
Then mirror is detected by InGaAs detectors, up-conversion luminescence signal, which is then returned, to be examined through two colo(u)r filters by photomultiplier (PMT)
It surveys, by signal detection system combination up-conversion luminescence signal and forward-scattering signal, judges while detection is with counting micro-
Whether grain is target, and optical tweezer deflection reaches collection channel, and the particle for being not affected by ligh trap force effect then enters waste fluid channel, to real
It now counts, detect with sorting in the system of one.
The present invention marks determinand using up-conversion nano material, and the up-conversion luminescence material of different emission may be used
Material is marked, to realize the high throughput of a variety of particles while detect.It is waited for by scattering light and the realization of up-conversion luminescence signal
Survey the identification of object.
Sample particle is focused on picoliters rank by the present invention in such a way that fluid dynamics in micro-fluidic chip focus
Detection zone designs the separation that different determinands are realized in different sorting channels.
The present invention realizes the high-throughput sorting pattern of actively manipulation using acousto-optic modulator AOM.
Embodiment is set forth below to be described further detection proposed by the present invention with method for separating.
Embodiment 1
The detection of tumor markers AFP AFP and Carcinoembryonic Antigen CEA
By the different size of microballoon (3 microns and 5 microns) of surface modification carboxylic group, distinguished by two-site sandwich method
AFP and CEA antigens are enriched with, using up-conversion as marker material.
The first step prepares and coding microball is immunized.It is micro- to first pass through EDC/NHS reaction activation for the microballoon for taking surface carboxyl groups to modify
Then the carboxyl of ball surface is coupled AFP and CEA monoclonal antibodies, obtains immune microsphere respectively at room temperature.
Second step, transition probe in preparation.The amido modified up-conversion of SMCC activating surfaces, then covalent coupling is another
A kind of AFP and CEA monoclonal antibodies.
Third walks, and is enriched with tumor markers respectively.Antigen method is captured with double site one-step method, i.e., is added respectively in centrifuge tube
Enter a certain amount of above-mentioned various sizes of immune coding microball mixture, upper conversion nano probe and AFP and CEA antigens.No
Immune microsphere with size corresponds to the different antigen of enrichment, obtains coding microball compound.
4th step is injected above-mentioned coding microball compound in micro-fluidic chip by syringe pump, in the work of sheath fluid folder stream
In single file by detection zone under, near-infrared 980nm laser excitations generate up-conversion luminescence signal and scattered light signal, by photoelectricity
Multiplier tube PMT collects up-conversion luminescence signal, and InGaAs detectors collect forward-scattering signal.
5th step, quantitative analysis.The intensity for measuring the microballoon of a certain number of various concentration series standard samples makes mark
Directrix curve measures a certain number of unknown sample microballoons, and quantitative analysis is carried out using calibration curve method.
Embodiment 2
Sorting/parting of breast cancer cell
According to breast cancer cell (such as：Breast cancer cell MCF-7, SK-BR-3 and MDA-MB- of three kinds of different cell lines
453) parting is different, using green with red two kinds of up-conversion luminescence nanomaterials to the epithelial cell adhesion molecule on its surface
(EpCAM) and human epidermal growth factor receptor-2 (HER2) carries out double labeling, antibody and up-conversion nano material be coupled again with
It waits for that antigentic specificity combination forms " target cell-antigen-antibody-goes up conversion particles " compound on target cell in test sample, then passes through light
Tweezer screening enrichment.It is as follows：
The first step：Transition probe in preparation.The upper conversion of two kinds of amido modified different emissions of SMCC activating surfaces
Nano material, then two kinds of antibody of covalent coupling respectively, then " target cell-antigen-antibody-above turns with waiting for that target cell is formed in test sample
Change nano-particle " compound.
Second step：It will wait in test sample injection micro-fluidic chip channel, and make cell in single file by detection zone through flow focusing,
Near-infrared 980nm laser generates forward scattering light and up-conversion luminescence signal with cytosis, and scattered light signal is double for counting
Channel luminous signal intensity for judging cellularity, send after processing instruction by acousto-optic modulator AOM to capture laser into
Target cell is deflected to sorting channel by row modulation to decide whether to open optical tweezer.Detection up-conversion luminescence signal moment,
Optical tweezer laser is closed, and when green is notable (MCF-7), optical tweezer captures the cell and short distance moves to right, simultaneously
It closes laser and discharges cell, the result is that cell is brought into right channel；(SK-BR-3), laser optical tweezer when danger signal is notable
It captures the cell and short distance moves to left, laser release cell is simultaneously closed off, the result is that cell is brought into left channel；Red, green letter
When number very weak (MDA-MB-453), cell will continue to straight ahead and enter intermediate channel.
Embodiment 3
The detection and sorting of bacterium
The anti-medicine of secondary antibody selected marker being coupled according to monoclonal antibody TEM-1 beta-lactamases and up-conversion nano material
Bacterium counts total bacterium in conjunction with forward-scattering signal, recycles optical tweezer sorting enrichment.It is as follows：
The first step：Bacterium marks.Bacterium is successively green with monoclonal antibody TEM-1 beta-lactamases, covalent coupling secondary antibody
Up-conversion luminescent material is incubated.
Second step：It is sent out by upper conversion by forward scattering light to total bacterial count similar to second step in example 2
Optical signal determines whether anti-medicine bacterium.
It should be understood that for those of ordinary skills, it can be modified or changed according to the above description,
And all these modifications and variations should all belong to the protection domain of appended claims of the present invention.
Claims (8)
1. a kind of multifunctional light tweezers system based on micro-fluidic chip, which is characterized in that the system includes：Micro-fluidic chip particle
Sampling system, number system, signal detection system and optical tweezer separation system；Wherein：
Micro-fluidic chip particle sampling system, for making particle pass through miniflow one by one along certain path by fluid dynamics focusing
Chip is controlled, detection count block and capture sorting area are preset on micro-fluidic chip；
When particle is by detecting count block, signal detection system realizes the luminous letter of particle by Feebleness Light Signal Examining technology
Number and the multi-parameter of forward-scattering signal characterize simultaneously, realize the detection of particle, and by number system to particle number into
Row statistics；
When particle sorts area by capture, according to the testing result of particle, by optical tweezer separation system to particular kind of particle
Into horizontal deflection, the sorting function of particle is realized.
2. the multifunctional light tweezers system according to claim 1 based on micro-fluidic chip, which is characterized in that micro-fluidic chip
It is provided with 3 roads and flows into end and 3 road outflow ends, detect the position that count block and capture sorting area are arranged between inflow end and outflow end
It sets；Wherein：
3 roads flow into end, and both sides are sheath stream, and centre is the sample flow of particle；Sample flow flows into detection count block simultaneously with sheath stream
Area is sorted with capture, the sheath stream of both sides is used to ensure the particle that sample flow is individually arranged in intermediate formation, and particle surrounding is by sheath stream
It surrounds；
In 3 road outflow ends, centre is the outflow end of the waste fluid channel of sample flow, and both sides are collection channel；It is sorted by optical tweezer
Optical tweezer deflection occurs for particle, is flowed out by collection channel.
3. the multifunctional light tweezers system according to claim 1 based on micro-fluidic chip, which is characterized in that pass through adjustable offset
Unpolarized near-infrared laser is resolved into the different polarised light of two beams, including S light and P light by formula of shaking attenuator, and is arbitrarily adjusted
The energy ratio of two beam laser.It is used to be carried out at the same time S light the modulation of intensity and deflection angle by acousto-optic modulator；P light and S light
Focal beam spot be located at the upstream and downstream on micro-fluidic chip, be used separately as excitation light source and capture light source；S light leads to again
Beam-expanding system is crossed, and is focused by object lens and forms ligh trap, ligh trap is for capturing particle.
4. the multifunctional light tweezers system according to claim 1 based on micro-fluidic chip, which is characterized in that signal detection system
System includes multiple photomultiplier PMT and an InGaAs detector, is respectively used to up-conversion luminescence and the forward direction of detection of particles
Scattered light signal increases up-conversion luminescence signal detection port number as needed, builds multichannel detection system.
5. a method of using the multifunctional light tweezers system described in claim 1 based on micro-fluidic chip, which is characterized in that
Include the following steps：
Step 1：Up-conversion fluorescence probe is coupled to microparticle surfaces, single microparticle suspending liquid injection micro-fluidic chip of formation is micro-
In the channel of grain sampling system, make sample flow in single file by detecting count block and capture sorting area according to flow focusing principle；
Step 2：Start near infrared laser, the laser after object lens focus will be unpolarized by adjustable polarization type attenuator
Near-infrared laser resolve into the different polarised light of two beams, including P light and S light；By camera or video camera observation adjustment P light and
The position of S light, and laser power size is adjusted, so that upstream of the P light in channel is acted on particle, excitation up-conversion luminescence letter
Number, S light forms ligh trap in downstream；
Step 3：Optical tweezer sorting system is carried out according to up-conversion luminescence signal and forward-scattering signal intensity instruction acousto-optic modulator
Being turned on or off for system, makes target particle be entered collection channel by ligh trap active force, is not affected by the particle of ligh trap force effect then
Into waste fluid channel, to carry out real-time counting, quantitative analysis and sorting to target particle.
6. the multifunctional light tweezers system according to claim 5 based on micro-fluidic chip, which is characterized in that probe be upper turn
Change nano material.
7. the multifunctional light tweezers system according to claim 5 based on micro-fluidic chip, which is characterized in that be detected
Target particle type includes：Cell, cell excretion body, and nucleic acid, albumen, virus, small molecule and metal using microballoon enrichment
Ion.
8. the multifunctional light tweezers system according to claim 5 based on micro-fluidic chip, which is characterized in that sorted
Target particle type is finely ground particles, including cell or microballoon.
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