CN108717116A - A kind of lymphocyte Photobiology sensor and its method for sensing based on optofluidic capillary microcavity - Google Patents
A kind of lymphocyte Photobiology sensor and its method for sensing based on optofluidic capillary microcavity Download PDFInfo
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- CN108717116A CN108717116A CN201810521335.6A CN201810521335A CN108717116A CN 108717116 A CN108717116 A CN 108717116A CN 201810521335 A CN201810521335 A CN 201810521335A CN 108717116 A CN108717116 A CN 108717116A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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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
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
Abstract
Present invention is disclosed a kind of lymphocyte Photobiology sensor and its method for sensing based on optofluidic capillary microcavity, the sensor includes frequency swept laser, capillary microcavity-micro-nano fiber coupling unit for carrying out sensing testing to cell solution, photodetector and feedback control system, frequency swept laser, capillary microcavity-micro-nano fiber coupling unit, photodetector and feedback control system are of coupled connections by fiber fuse between each other, feedback control system is electrically connected with photodetector and frequency swept laser respectively, capillary microcavity-micro-nano fiber coupling unit is mutually perpendicular to be coupled to form by micro-nano fiber and capillary microcavity.The sensor is using micro volume, heightQThe capillary microcavity of value is as lymphocyte sensing unit, by the control and interaction of light in microcavity and microfluid, realizes with highly sensitive, quick detection, unmarked, compact-sized, integrated level is high, Photobiology lymphocyte at low cost sensing.
Description
Technical field
The present invention relates to a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity and its sensing sides
Method can be used for sensor technical field.
Background technology
It was found that and quantization AIDS virus ability for doctor seek therapeutic effect to greatest extent be it is vital,
And it is exactly to observe the quantity of CD4+ lymphocytes to realize a kind of method of this target.The CD4+ cells of one healthy normal person
Number is in 1200/ μ L, and with the intensification of AIDS gradient of infection, this number can simultaneously decline, and be examined when dropping to 200/ μ L
Break as AIDS.
Currently, the counting of CD4+ lymphocytes can accurately be realized by flow cytometer.The work of these instruments
Principle is by being counted with fluorescence antibody label CD4+ receptors and pair fluorescence signal therefore generated.But while streaming is thin
The counting of born of the same parents' instrument is very accurate, they also have dependent on fluorescent marker, equipment cost is high, maintenance requirement is high, detection time is long
Etc. limitations.
Invention content
The purpose of the present invention is exactly to be proposed a kind of based on light stream hair control to solve the above-mentioned problems in the prior art
The lymphocyte Photobiology sensor and its method for sensing of tubule microcavity.
The purpose of the present invention will be achieved by the following technical programs：A kind of lymph based on optofluidic capillary microcavity
Cell biological optical sensor, including frequency swept laser, capillary microcavity-micro-nano for carrying out sensing testing to cell solution
Optic fiber coupling unit, photodetector and feedback control system, the frequency swept laser, capillary microcavity-micro-nano fiber coupling
Unit, photodetector and feedback control system are of coupled connections by fiber fuse between each other, the feedback control system point
It is not electrically connected with photodetector and frequency swept laser, the capillary microcavity-micro-nano fiber coupling unit is by micro-nano fiber
It is mutually perpendicular to be coupled to form with capillary microcavity, the frequency swept laser sends out laser and enters micro-nano fiber from the end of micro-nano fiber
Area is bored, capillary microcavity is coupled by evanscent field, excites Whispering-gallery-mode in capillary microcavity to resonate, Whispering-gallery-mode light
With the cell solution inside microcavity specific biological optics interaction occurs for field, passes through the light for detecting the output of the micro-nano fiber other end
Strong to demodulate tested lymphocyte Solution Cell concentration information, the feedback control system passes through electric connection and controls sweeping laser
The output wavelength and intensity of device, while also control photodetector detection is by another output of micro-nano fiber after capillary microcavity
The luminous intensity at end, the light realized the control to the optical wavelength and luminous power of frequency swept laser and measure micro-nano fiber output end
It is compared feedback op at specific wavelength of light with input light laser intensity by force, obtains the echo wall die with multiple transmission peaks
Formula resonance spectrum.
Preferably, the wavelength of the frequency swept laser is tunable.
Preferably, the micro-nano fiber is made of single mode optical fiber by drawing cone machine fused biconical taper.
Preferably, the capillary microcavity is prepared by hollow quartz capillary optical fiber progress fused biconical taper.
Preferably, the micro-nano fiber is close proximity on capillary microcavity, the axis of the micro-nano fiber and capillary microcavity
Line keeps antarafacial vertical.
Preferably, the capillary microcavity is high symmetrical hollow cylinder shape structure.
Preferably, only meet Whispering-gallery-mode resonance condition resonance wavelength can be generated in capillary microcavity it is humorous
It shakes, the resonance wavelength for meeting Whispering-gallery-mode resonance condition is determined by following formula：
The π of λ=2 rneff/m
Wherein r is resonant cavity radius, neffIt is the effective refractive index that resonant optical mode passes through, m is integer.
Preferably, resonant cycle period of the light wave in capillary microcavity determines have by the quality factor q of capillary microcavity
Imitate action length LeffIt is given by with quality factor q relationship：
Leff=Q the π of λ/2 neff。
Present invention further teaches a kind of sensings of the lymphocyte Photobiology sensor based on optofluidic capillary microcavity
Method includes the following steps：
S1：Clean microcavity；
It is passed through deionized water inside to capillary microcavity, to being cleaned inside capillary microcavity；
S2：Acid cleaning；
To being passed through dust technology inside the capillary microcavity after the cleaning of S1 steps, and liquid is sealed in capillary microcavity
Stand, after be alternately passed through with deionized water and alcohol, by washes clean in capillary microcavity；
S3：It is hydroxy activated；
To being passed through dense H in the capillary microcavity after S2 steps are washed2SO4Liquid is sealed in capillary by hydrogen peroxide solution
Stand in pipe microcavity, ensure that the hydroxyl in capillary microcavity inner wall surface fully activates, after will be washed in capillary microcavity
Totally, capillary microcavity inner hollow is then kept；
S4：3- aminopropyl triethoxysilane solution is passed through in capillary microcavity and is stood, is washed with deionized water and alcohol
It washs, removes the silane compound of non-covalent bonding in capillary microcavity；
S5：The PBS solution of the antibody containing CD4+ is passed through in capillary microcavity and is stood so that CD4+ antibody is cultivated to silanization
Good capillary microcavity inner wall surface, after, it is passed through alcohol and deionized water successively into capillary microcavity, cleans capillary
Inside microcavity；
S6：1XCD4+T cell PBS solutions to be measured are passed through capillary microcavity, record the Whispering-gallery-mode of different time
Resonance spectrum, until CD4+T cells are completely combined with antibody；
S7：It is passed through deionized water to the capillary microcavity after S6 step process to clean with PBS solution, be passed through again later
The PBS solution of 10XCD4+T cells records the echo wall die resonance spectrum of different time, until CD4+T cells are tied completely with antibody
It closes, echo wall die resonance spectrum no longer drifts about.
Preferably, in S2 steps, to being passed through a concentration of 5% dilute nitre inside the capillary microcavity after the cleaning of S1 steps
Acid；In S6 steps, CD4+T cells are 30~40 minutes with the time that antibody is completely combined.
The advantages of technical solution of the present invention, is mainly reflected in：The sensor is using micro volume, the capillary microcavity of high q-factor
As lymphocyte sensing unit, by the control and interaction of light in microcavity and microfluid, realize with highly sensitive, quick
Detection, unmarked, compact-sized, integrated level is high, Photobiology lymphocyte at low cost sensing.This method passes through to all -fiber
The mode of coupling excites and detects the Whispering-gallery-mode resonance spectrum in optical microcavity, under the means without any fluorescent marker,
Realize the detection to cell concentration in conjunction with optofluidic/microflow control technique, have all -fiber, it is quick, unmarked, inexpensive, can weigh
The characteristics of repetition measurement tries.The Photobiology sensor that the present invention is realized has in the pre- diagnosing and treating for solving the problems, such as AIDS
Potentially, huge application value.
Description of the drawings
Fig. 1 is optical sensor system structural schematic diagram of the present invention.
Fig. 2 is the pictorial diagram of CD4+T lymphocytes sensor of the present invention.
Fig. 3 is that optical sensor cross-sectional view of the present invention and light field transmit schematic diagram.
Fig. 4 is the non-functionalization of microcavity inner wall surface of the present invention, each leads into water, phosphate buffered saline solution, 1XCD4+T cells
The Whispering-gallery-mode resonance spectrum tested after PBS solution, 10XCD4+T cell PBS solutions.
Fig. 5 is that microcavity endolymph cell of the present invention generates biologic specificity interaction, i.e. CD4+T tested cells antigen and CD
The interaction process schematic of+4 antibody.
Fig. 6 is that echo wall die resonance Frequency bias changes over time situation during the present invention is antibody functionalized.
Fig. 7 is after microcavity inner wall surface of the present invention is implanted into specific receptor, to be surveyed after 1 × CD4+T cell liquid is passed through in microcavity
The Whispering-gallery-mode resonance spectrum for the different time that must be obtained.
Fig. 8 is that the wave length shift of Whispering-gallery-mode resonance spectrum of the present invention changes with time situation, and wave length shift is about
10pm。
Fig. 9 is that microcavity inner wall surface of the present invention is implanted into after CD4+ antibody, is passed through into microcavity containing 10 × CD4+T cells
PBS solution after different time test obtain Whispering-gallery-mode resonance spectrum.
Figure 10 is that the wave length shift of Whispering-gallery-mode resonance spectrum of the present invention changes with time situation, and wave length shift is about
14pm。
Specific implementation mode
The purpose of the present invention, advantage and feature, by by the non-limitative illustration of preferred embodiment below carry out diagram and
It explains.These embodiments are only the prominent examples using technical solution of the present invention, it is all take equivalent replacement or equivalent transformation and
The technical solution of formation, all falls within the scope of protection of present invention.
Present invention is disclosed a kind of lymphocyte Photobiology sensors based on optofluidic capillary microcavity, such as Fig. 1 institutes
Show, including frequency swept laser 1, for cell solution carry out sensing testing capillary microcavity-micro-nano fiber coupling unit 2,
Photodetector 3 and feedback control system 4, the frequency swept laser 1, capillary microcavity-micro-nano fiber coupling unit 2, photoelectricity
Detector 3 and feedback control system 4 are of coupled connections by fiber fuse between each other, the feedback control system 4 respectively with light
Electric explorer 3 and frequency swept laser 1 are electrically connected, and the wavelength of the frequency swept laser is tunable, and the capillary microcavity is
High symmetrical hollow cylinder shape structure.
Sensing testing, the capillary microcavity-are carried out to cell solution using capillary microcavity-micro-nano fiber coupling unit
Micro-nano fiber coupling unit 2 is mutually perpendicular to be coupled to form by micro-nano fiber 21 and capillary microcavity 22, and the frequency swept laser 1 is sent out
Go out laser and enter micro-nano fiber cone area from the end of micro-nano fiber, capillary microcavity is coupled by evanscent field, excites capillary
Whispering-gallery-mode resonates in microcavity, and with the cell solution inside microcavity specific biological optics interaction occurs for Whispering-gallery-mode light field
With, tested lymphocyte Solution Cell concentration information is demodulated by detecting the light intensity of micro-nano fiber other end output, it is described anti-
Present output wavelength and intensity that control system controls frequency swept laser by electric connection, while also control photodetector detection
The luminous intensity of another output end of micro-nano fiber after capillary microcavity realizes optical wavelength and luminous power to frequency swept laser
Control and light intensity that micro-nano fiber output end measures is compared feedback with laser intensity is inputted at specific wavelength of light
Operation obtains the Whispering-gallery-mode resonance spectrum with multiple transmission peaks.
For excitation Whispering-gallery-mode resonance, micro-nano fiber and capillary microcavity are vertical coupled, and Fig. 2 (a) is with hollow tube
Thin-walled column symmetry microcavity-conical fiber cross section pictorial diagram of road structure；Fig. 2 (b) is to be checked to be passed through in thin-walled column symmetry microcavity
Pictorial diagram is coupled after sample with conical fiber, shown in the two relative position such as Fig. 2 (a), it is micro- that micro-nano fiber is close proximity to capillary
On chamber, the two central axes keep antarafacial vertical, which can make microcavity after being passed through tested cell sample liquid, such as Fig. 2 (b) institutes
Show, the couple state still to keep relative stability with micro-nano fiber, to improve coupling efficiency, increases intracavitary distribution of light intensity, obtain Q
It is worth higher, the deeper Whispering-gallery-mode resonance spectrum of transmission peaks, ensures sensitivity and the stability of sensor.
The micro-nano fiber, by drawing cone machine fused biconical taper to be made, bores a diameter of 2-3 μm of area, institute by single mode optical fiber
It states capillary microcavity to be prepared by hollow quartz capillary optical fiber progress fused biconical taper, outer diameter is 90 μm, and 2-3 μm of wall thickness should
Capillary microcavity has the characteristics that high symmetry, thin-walled, volume are small.
Fig. 3 is the cross-sectional view and light field transmission schematic diagram of the technical program lymphocyte Photobiology sensor.
Light field is coupled to from micro-nano fiber cone area in capillary thin-walled microcavity in the form of evanscent field in micro-nano fiber cone area, due to total reflection
Effect, the light for meeting the specific wavelength of condition of resonance form Whispering-gallery-mode resonance in Microsphere Cavities, in optical field distribution such as Fig. 2
Shown in 10- Whispering-gallery-mode optical field distributions, most of light energy distribution near the internal wall surface regions of capillary microcavity,
And there is minimum mode volume, therefore the interaction of light and measured object is very strong, and highly sensitive sensing may be implemented.Work as microcavity
In when being passed through different samples, Whispering-gallery-mode resonance spectrum can because microcavity inner refractive index changes and to the sample of various concentration
Product generate different degrees of Frequency bias.
Resonance can be generated in capillary microcavity by only meeting the resonance wavelength of Whispering-gallery-mode resonance condition, be met
The resonance wavelength of Whispering-gallery-mode resonance condition is determined by following formula：
The π of λ=2 rneff/m
Wherein r is resonant cavity radius, neffIt is the effective refractive index that resonant optical mode passes through, m is integer.
Resonant cycle period of the light wave in capillary microcavity determine by the quality factor q of capillary microcavity, useful effect
Length LeffIt is given by with quality factor q relationship：
Leff=Q the π of λ/2 neff。
Resonance can be generated in capillary microcavity by only meeting the resonance wavelength of Whispering-gallery-mode resonance condition, be met
The resonance wavelength of Whispering-gallery-mode resonance condition is determined by following formula：
The π of λ=2 rneff/m。
Wherein r is resonant cavity radius, neffIt is the effective refractive index that resonant optical mode passes through, m is integer.Due to echo
Wall mode resonance light field has longer time photon lifetime, the Photobiology interaction between light field and tested lymphocyte solution
It is greatly increased with length and time.Wherein, interaction length depends on light in the microcavity determined by the quality factor q of microcavity
Wave cycle period determined, effective interaction length LeffIt is given by with quality factor q relationship：
Leff=Q the π of λ/2 neff
By taking the capillary microcavity and laser light source that the technical program uses as an example, quality factor q 106, effective refractive index
neff=1.45, when wavelength X=1.5 μm, effective interaction length is up to 15cm or more.
The lymphocyte Photobiology sensor is used for biological test for by optical device, surface has been carried out to microcavity
Functionalization is to improve specific interaction significance of the microcavity in testing lymphocyte solution processes.It is logical first in order to compare
It is surface-functionalized to the progress of microcavity inner wall to cross experiment test, by minute-pressure pump and microflow control technique, is passed through not into microcavity
With the variation characteristic of the Whispering-gallery-mode resonance spectrum of concentrations of cells solution.It is illustrated in figure 4 and each leads into water, phosphate-buffered salt
It is surveyed after (phosphate buffer saline, PBS) solution, 1XCD4+T cells PBS solution, 10XCD4+T cell PBS solutions
Obtained Whispering-gallery-mode resonance spectrum is tried, CD4+T cells are one kind of CD4+ lymphocytes, are measurand and antigen, right
The antibody of characteristic opposite sex interaction is wanted to be to determine in certain type of lymphocyte antigen and its progress test process.?
In the technical program, 1X, 10X concentration correspond to respectively 1000CD4+T cells/μm and 10000CD4+T cells/μm, similarly hereinafter.Inside
Lead to the CD4+T cell liquid of 1X and 10X in the microcavity of the non-functionalization of wall surface, spectrum has drifted about 6.8pm and 16pm respectively, this be because
It can cause variations in refractive index in microcavity for certain density cell solution, so as to cause the variation of Whispering-gallery-mode resonance spectrum.
Fig. 5 is that microcavity endolymph cell generates biologic specificity interaction, i.e. CD4+T tested cells antigen and CD+4 antibody
Interaction process schematic, 22 be capillary microcavity, 21 be micro-nano fiber, and 5 be CD4+T cellular antigens and 6 be CD4+ antibody.
CD4+ antibody is cultivated first to the good microcavity inner wall surface of silanization, then is passed through CD4+T cellular antigens by microflow control technique,
Antibody and anti-member will change microcavity inner wall thickness, so as to cause the drift of echo wall die resonance spectrum after the combination of microcavity inner wall surface
It moves, the amount of drift is directly proportional to detected CD4+T cell concentrations, realizes the measurement of lymphocyte quantity.
Realize that Photobiology sensing, microcavity have small with interaction by the control of light and microfluid in capillary microcavity
Diameter forms the totally-enclosed of lymphocyte solution, micro bearer path, realizes analyte channel in conjunction with microflow control technique
With the separation of detection channels, measuring stability is improved.
Present invention further teaches a kind of sensings of the lymphocyte Photobiology sensor based on optofluidic capillary microcavity
Method carries out hydroxy activated and silanization treatment to capillary microcavity inner wall surface, i.e., surface-functionalized, effectively to enhance microcavity
The specific biological optics interaction significance of Whispering-gallery-mode light field and lymphocyte solution near inner wall area, to improve
Sensing sensitivity.
This approach includes the following steps：
S1：It is passed through deionized water inside to capillary microcavity, to being cleaned inside capillary microcavity；
S2：To being passed through a concentration of 5% dust technology inside the capillary microcavity after the cleaning of S1 steps, and liquid is sealed up for safekeeping
In standing 30 minutes 2 hours in capillary microcavity, after be alternately passed through with deionized water and alcohol, by capillary microcavity wash-in
It washs clean；
S3：To being passed through dense H in the capillary microcavity after S2 steps are washed2SO4Liquid is sealed in by hydrogen peroxide solution
1 hour is stood in capillary microcavity, ensures that the hydroxyl in capillary microcavity inner wall surface fully activates, after capillary is micro-
Intracavitary washes clean then keeps capillary microcavity inner hollow, 40 DEG C of freeze-day with constant temperature；
S4：3- aminopropyl triethoxysilane solution is passed through in capillary microcavity, stands 30 minutes, with deionized water and
Ethanol wash removes the silane compound of non-covalent bonding in capillary microcavity；
S5：The PBS solution of the antibody containing CD4+ is passed through in capillary microcavity, stands 1 hour so that the cultivation of CD4+ antibody is arrived
The good capillary microcavity inner wall surface of silanization, after, it is passed through alcohol and deionized water successively into capillary microcavity, cleans
Inside capillary microcavity；
S6：1XCD4+T cell PBS solutions to be measured are passed through capillary microcavity, record the Whispering-gallery-mode of different time
Resonance spectrum specifically recorded a Whispering-gallery-mode resonance spectrum, until CD4+T cells are completely combined with antibody every 3 minutes；
In S6 steps, CD4+T cells are 30~40 minutes with the time that antibody is completely combined.
S7：It is passed through deionized water to the capillary microcavity after S6 step process to clean with PBS solution, be passed through again later
The PBS solution of 10XCD4+T cells records the echo wall die resonance spectrum of different time, specifically, primary every three minutes records
Echo wall die resonance spectrum, until CD4+T cells are completely combined with antibody, echo wall die resonance spectrum no longer drifts about.
After implementing above-mentioned S5 steps, i.e., Fig. 6 is：The PBS solution of the antibody containing CD4+ is passed through time that test in microcavity obtains
Sound wall mode resonance Frequency bias changes over time situation, and within the certain effect time, antibody is attached to the interior inner surface of microcavity, by
It is thickeied in wall thickness, also there is a phenomenon where drift about for Whispering-gallery-mode resonance spectrum.
Fig. 7 is to implement above-mentioned S6 steps, and different time is surveyed after the PBS solution containing 1 × CD4+T cells is passed through into microcavity
The Whispering-gallery-mode resonance spectrum obtained is tried, within the certain effect time, CD4+T cell antigens and CD4+ antibody cells combine, and return
Sound wall mode resonance spectrum is drifted about, and is tended towards stability after 30 minutes.Fig. 8 is the wave length shift of Whispering-gallery-mode resonance spectrum
Change with time situation, and wave length shift about 10pm, i.e. sensitivity reach 10pm/ (1.66 × 10-15mol/L/L)。
Fig. 9 is to implement above-mentioned S7 steps, and different time after the PBS solution containing 10 × CD4+T cells is passed through into microcavity
The Whispering-gallery-mode resonance spectrum obtained is tested, after certain reaction time, CD4+T cell antigens and CD4+ antibody cells combine,
Whispering-gallery-mode resonance spectrum drifts about, and tends towards stability after 20 minutes.Figure 10 is the wavelength of Whispering-gallery-mode resonance spectrum
Drift changes with time situation, and wave length shift about 14pm, i.e. sensitivity reach 14pm/ (1.66 × 10-14Mol/L), and
And realize the detection of unmarked CD4+T lymphocytes.
On the one hand the sensor utilizes micro-nano fiber and echo in the evanscent field coupling process excitation microcavity of capillary microcavity
Wall mode resonance, Whispering-gallery-mode resonance effects enhances microcavity inner wall area, and nearby light field and the lymphocyte inside microcavity are molten
The intensity of specific biological optics interaction occurs for liquid, can be quick, highly sensitive by the variation of Whispering-gallery-mode resonance spectrum
Demodulation is tested lymphocyte characteristic, and interaction process time is short and is not necessarily to any fluorescent marker process.On the other hand, capillary
Microcavity has minute diameter, and by combining microflow control technique in test process, the totally-enclosed for foring lymphocyte solution is micro
Bearer path realizes analyte channel and detection channels and separates, realizes to the micro, high stability of lymphocyte solution
Photobiology is tested.The micro-nano fiber and capillary microcavity that the sensor uses have all -fiber, compact-sized, preparation is simple etc.
Feature.Therefore, the present invention is detected with high sensitivity, quickly, unmarked, compact-sized, integrated level is high, at low cost, technique is simple
The advantages that single.
Still there are many embodiment, all technical sides formed using equivalents or equivalent transformation by the present invention
Case is within the scope of the present invention.
Claims (10)
1. a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity, it is characterised in that：Swash including frequency sweep
Light device, capillary microcavity-micro-nano fiber coupling unit, photodetector and feedback for carrying out sensing testing to cell solution
Control system, the frequency swept laser, capillary microcavity-micro-nano fiber coupling unit, photodetector and feedback control system
It is of coupled connections between each other by fiber fuse, the feedback control system is electrical with photodetector and frequency swept laser respectively
Connection, the capillary microcavity-micro-nano fiber coupling unit are mutually perpendicular to be coupled to form by micro-nano fiber and capillary microcavity, institute
State frequency swept laser send out laser from one end of micro-nano fiber enter micro-nano fiber bore area, capillary is coupled by evanscent field
Microcavity excites Whispering-gallery-mode in capillary microcavity to resonate, and Whispering-gallery-mode light field occurs special with the cell solution inside microcavity
Anisotropic Photobiology interaction demodulates tested lymphocyte Solution Cell by detecting the light intensity of micro-nano fiber other end output
Concentration information, the feedback control system control the output wavelength and intensity of frequency swept laser by electric connection, while also controlling
Photodetector detection processed is realized by the luminous intensity of another output end of micro-nano fiber after capillary microcavity to frequency swept laser
Optical wavelength and luminous power control and the light intensity that measures micro-nano fiber output end with input light laser intensity in specific light
It is compared feedback op at wavelength, obtains the Whispering-gallery-mode resonance spectrum with multiple transmission peaks.
2. a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity according to claim 1,
It is characterized in that：The wavelength of the frequency swept laser is tunable.
3. a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity according to claim 1,
It is characterized in that：The micro-nano fiber is by single mode optical fiber by drawing cone machine fused biconical taper to be made.
4. a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity according to claim 1,
It is characterized in that：The capillary microcavity carries out fused biconical taper by hollow quartz capillary optical fiber and is prepared.
5. a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity according to claim 1,
It is characterized in that：The micro-nano fiber is close proximity on capillary microcavity, and the central axes of the micro-nano fiber and capillary microcavity are kept
Antarafacial is vertical.
6. a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity according to claim 1,
It is characterized in that：The capillary microcavity is high symmetrical hollow cylinder shape structure.
7. a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity according to claim 1,
It is characterized in that：Resonance can be generated in capillary microcavity by only meeting the resonance wavelength of Whispering-gallery-mode resonance condition, full
The resonance wavelength of sufficient Whispering-gallery-mode resonance condition is determined by following formula：
The π of λ=2 rneff/m
Wherein r is resonant cavity radius, neffIt is the effective refractive index that resonant optical mode passes through, m is integer.
8. a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity according to claim 1,
It is characterized in that：Resonant cycle period of the light wave in capillary microcavity determine by the quality factor q of capillary microcavity, useful effect
Length LeffIt is given by with quality factor q relationship：
Leff=Q the π of λ/2 neff。
9. a kind of method for sensing of the lymphocyte Photobiology sensor based on optofluidic capillary microcavity, it is characterised in that：
Include the following steps：
S1：Clean microcavity；
It is passed through deionized water inside to capillary microcavity, to being cleaned inside capillary microcavity；
S2：Acid cleaning；
To being passed through dust technology inside the capillary microcavity after the cleaning of S1 steps, and liquid is sealed in quiet in capillary microcavity
Set, after be alternately passed through with deionized water and alcohol, by washes clean in capillary microcavity；
S3：It is hydroxy activated；
To being passed through dense H in the capillary microcavity after S2 steps are washed2SO4It is micro- to be sealed in capillary by hydrogen peroxide solution for liquid
Intracavitary is stood, and ensures that the hydroxyl in capillary microcavity inner wall surface fully activates, after by washes clean in capillary microcavity,
Then keep capillary microcavity inner hollow；
S4：3- aminopropyl triethoxysilane solution is passed through in capillary microcavity and is stood, with deionized water and ethanol wash, is gone
Except the silane compound of non-covalent bonding in capillary microcavity；
S5：The PBS solution of the antibody containing CD4+ is passed through in capillary microcavity and is stood so that it is good to silanization that CD4+ antibody is cultivated
Capillary microcavity inner wall surface, after, it is passed through alcohol and deionized water successively into capillary microcavity, cleans capillary microcavity
It is internal；
S6：1XCD4+T cell PBS solutions to be measured are passed through capillary microcavity, record the Whispering-gallery-mode resonance of different time
Spectrum, until CD4+T cells are completely combined with antibody；
S7：It is passed through deionized water to the capillary microcavity after S6 step process to clean with PBS solution, is passed through 10XCD4 again later
The PBS solution of+T cell records the echo wall die resonance spectrum of different time, until CD4+T cells are completely combined with antibody, echo
Wall mould resonance spectrum no longer drifts about.
10. a kind of lymphocyte Photobiology sensor based on optofluidic capillary microcavity according to claim 9
Method for sensing, it is characterised in that：In S2 steps, to being passed through a concentration of 5% inside the capillary microcavity after the cleaning of S1 steps
Dust technology；In S6 steps, CD4+T cells are 30~40 minutes with the time that antibody is completely combined.
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