CN110132896A - The micro optical fiber biosensor of markers for breast cancer in a kind of quick detection serum - Google Patents
The micro optical fiber biosensor of markers for breast cancer in a kind of quick detection serum Download PDFInfo
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- CN110132896A CN110132896A CN201910373463.5A CN201910373463A CN110132896A CN 110132896 A CN110132896 A CN 110132896A CN 201910373463 A CN201910373463 A CN 201910373463A CN 110132896 A CN110132896 A CN 110132896A
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- breast cancer
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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
- G01N21/45—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
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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
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57415—Specifically defined cancers of breast
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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
- G01N21/45—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
- G01N2021/458—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods using interferential sensor, e.g. sensor fibre, possibly on optical waveguide
Abstract
The present invention relates to a kind of fibre-optical sensing device, the micro optical fiber biosensor of markers for breast cancer, the antibody including micro-nano fiber interferometer, biological functional film and markers for breast cancer in a kind of quick detection serum;The micro optical fiber biosensor is to immerse after the antibody of markers for breast cancer is fixed containing in markers for breast cancer (HER2) sample liquid, and light source is opened so that light is input to micro optical fiber biosensor, utilize the characteristic that micro-nano fiber interferometer surface evanescent wave is highly sensitive to environmental change, the antibody specificity of markers for breast cancer (HER2) and markers for breast cancer is combined and causes sensor surface variations in refractive index, to quickly detect the concentration of markers for breast cancer in serum (HER2).
Description
Technical field
The present invention relates to a kind of fibre-optical sensing device, the optical fiber of markers for breast cancer in especially a kind of quickly detection serum
Method for sensing belongs to optical fiber biosensor field.
Background technique
Breast cancer is the third-largest common cancer, it has also become threatens the kinds of tumor of women's health.The morbidity of global breast cancer
Rate is constantly in ascendant trend, all causes great pain to patient and family, therefore the death rate for reducing breast cancer is to work as
The significant problem of preceding society's urgent need to resolve.This just needs early to find early treatment to breast cancer early-stage cases, to reduce patient's pain
Bitter and raising survival rate.Such as blood in the body fluid of pre-cancer patient, serum will appear Tumor biomarkers in urine etc.
Overexpression, as long as can contribute to determine certain form of presence or progress cancer to the detection of breast cancer marker object content.
It is well known that HER2 is good biomarker, the patient with breast cancer of about 25%-30% with HER2 overexpression.
Fluorescent marker or dye marker are commonly used in markers for breast cancer detection, provide high sensitivity even single molecules level in this way,
But there are the defects of at high cost, program complexity and label influence biomolecule nature.Therefore, developmental research is a kind of fast
The mini optical fibre sensor of markers for breast cancer in speed detection serum, promotes the " accurate of non-damaging approach early-stage breast cancer diagnosis
Property " and " realizability ".
Summary of the invention
The technical problems to be solved by the present invention are: the shortcomings that how overcoming the above-mentioned prior art and deficiency, construct one kind
The micro optical fiber biosensor of markers for breast cancer in serum is quickly detected, which uses the conduct of micro-nano fiber interferometer
The interface of evanescent wave detection, and effective carrier of the modification recognition component as specific detection on the surface.The present invention is not only
It is label-free, inexpensive, and using optical fiber probe feature small in size, it can be achieved that quickly detecting biomarker in serum.
The technical scheme adopted by the invention is that: a kind of mini optical fibre biology quickly detecting markers for breast cancer in serum
Sensor, the antibody including micro-nano fiber interferometer, biological functional film and markers for breast cancer;The micro-nano fiber interferometer
Structure is made of micro-nano fiber transition region and homogeneity range;The biological functional film is to connect optical fiber and cream by covalent bond effect
Gland cancer antibody has function served as bridge;The antibody of the markers for breast cancer is fixed as identification molecule by biological functional film
Onto optical fiber surface;The micro optical fiber biosensor is to immerse to contain mammary gland after the antibody of markers for breast cancer is fixed
In carcinoma marker (HER2) sample liquid, and light source is opened so that light is input to micro optical fiber biosensor, utilizes micro-nano light
The fine interferometer surface evanescent wave characteristic highly sensitive to environmental change, to markers for breast cancer (HER2) and markers for breast cancer
Antibody specificity, which combines, causes sensor surface variations in refractive index, to quickly detect markers for breast cancer in serum (HER2)
Concentration.
Further, the micro-nano fiber interferometer is by drawing light-sensitive optical fibre by thermal-flame.
Further, the homogeneity range diameter of the micro-nano fiber interferometer is 5-7 μm.
Further, the light source is the wideband light source of 1250-1650nm wave band.
Since the big evanscent field characteristic of micro-nano fiber interferometer provides the variation of sensing external environment with sensitivity.Micro-nano light
By mid diameter, uniformly region and two tapering transition zones with a tight waist are constituted fine interferometer, what a tapering transition zone excited
Basic mode and high-order mode couple, due to basic mode and high-order mode transmission coefficient in regional spread with a tight waist with another tapering transition zone
Difference just forms interference fringe in the case where meeting interference condition.Interference overall strength be
IcoAnd IclRespectively the first basic mode HE11With the second basic mode HE12The intensity of high-order mode.φ be two interference patterns it
Between phase difference.
The sensitivity formula of micro-nano fiber interferometer sensing external environment is
For dispersion factor, it is generally negative value for silica fibre, embodies refringence and wavelength
Between relationship.Δ n is basic mode HE11With high-order mode HE12Refringence.It is rolled in bracket dependent on external environment on the right side of equal sign
Penetrate the variation of rate.External environment refractive index nexWhen increase, usual HE12Compare HE11Effective refractive index have bigger increment, thereforeBy formula (2) push away with external environment refractive index increase, wavelength can occur red shift (to long wave direction float
It moves).To sum up, micro-nano fiber interferometer has high sensitivity to the refractive index of external environment, can be used for breast cancer tumour mark
The detection of object concentration.
The beneficial effects of the present invention are: single cone micro-nano fiber is formed interference structure as pickup probe by (1) present invention, lead to
It crosses covalent bond effect and breast cancer antibody is fixed on optical fiber surface, and then the markers for breast cancer specificity knot different from serum
It closes, therefore can be to slowdown monitoring tumor markers concentration fast in serum, it is seen that compact-sized, the reality of optical fiber biosensor of the present invention
Existing many reference amounts detection;The diameter of optical fiber biosensor of the present invention is micron or nanometer scale, therefore sensor of the invention
Structure is very small and exquisite.(2) optical fiber biosensor of the invention simplifies program circuit without label, and it is professional to solve operation
By force, at high cost, the problems such as background signal is strong.The response of bio-molecular interaction can be monitored in real time, can rapidly to point
Analysis object makes assessment, and can regenerate reusable.(3) optical fiber biosensor of the invention is passed with traditional electrochemistry
Sensor is compared, the advantage with electromagnetism interference, therefore can realize the real time monitor in vivo of markers for breast cancer.(4) of the invention
Using the evanescent wave at the micro-nano fiber interferometer interface characteristic sensitive to extraneous environmental change, by observing fiber optic interferometric peak position
Variation obtains markers for breast cancer concentration information, and high sensitivity reaches 0.11nm/ (ng/mL).(5) optical fibre bio of the invention passes
Sensor, which is gathered around, to have broad application prospects, such as other early diagnosis of cancer such as lung cancer tumor marker.
Detailed description of the invention
Fig. 1 is the principle of the invention and structural schematic diagram;
The output spectrum of fibre optical sensor Fig. 2 of the invention fast slowdown monitoring difference tumor markers concentration when immersing in serum
Figure.
Interference peaks wavelength change when Fig. 3 is fibre optical sensor of the invention fast slowdown monitoring serum tumor marker concentration
Figure.
Specific embodiment
As shown in Figure 1, a kind of micro optical fiber biosensor for quickly detecting markers for breast cancer in serum, including micro-nano
The antibody 3 of fibre optic interferometer 1, biological functional film 2 and markers for breast cancer, by being fabricated to bio-sensing on an optical fiber
Probe, it is seen that the composed structure and preparation process of the optical fiber biosensor of the present embodiment are all very simple.
Wherein micro-nano fiber interferometer 1 is to process to obtain by flame fused biconical taper by light-sensitive optical fibre, preferred micro-nano light
Fine central waist diameter is 5 μm.Therefore the structure of the fibre optical sensor of the present embodiment is very small and exquisite.
Wherein biological functional film 2 connects optical fiber surface and breast cancer antibody by covalent bond effect, has intermediate bridge
Effect, is wrapped in the outer surface of micro-nano fiber interferometer 1.Surface is specifically carried out to fiber optic sensing device using covalent bonding method
Micro-nano fiber interferometer 1 is constituted U-typed structure and interferometer is made to become probe-type structure, used by functionalization, step 1
Centrifuge tube dispenses a small amount of biological solution, realizes in micro-nano fiber part fixed biologically functional film 2;Step 2 does micro-nano fiber
Interferometer 1 the concentrated sulfuric acid and hydrogen peroxide by volume 7:3 with soaking at room temperature 30 minutes in solution, optical fiber surface can be made with hydroxyl
Base;Micro-nano fiber interferometer 1 is put into the 5% 3- aminopropyl triethoxysilicane using dehydrated alcohol as solvent by step 3 again
Alkane (3-aminopropyl-triethoxysilane (APTES)) solution is dipped into 15 minutes;It is soaked into 2.5% glutaraldehyde
(glutaraldehyde) solution room temperature 30 minutes, the solution is by phosphate buffered saline buffer (phosphate
Buffered saline buffer (PBS, pH=7.4)) it is concentration needed for solvent burden ratio goes out;Step 4 again does micro-nano fiber
Interferometer 1 be immersed in concentration be 10 μ g/mL breast cancer tumour marker HER2 antibody-solutions 3, room temperature 1 hour.
The micro-nano fiber interferometer 1 of the present embodiment have big evanscent field characteristic, sensing external environment refractive index it is sensitive
Strong, the refractive index sensitivity 1867nm/RIU of property.It is highly sensitive to environmental change using micro-nano fiber interferometer surface evanescent wave
Characteristic, the antibody specificity of markers for breast cancer (HER2) and markers for breast cancer is combined and causes sensor surface refractive index
Variation, to quickly detect the concentration of markers for breast cancer in serum (HER2).
When such as Fig. 2 being fibre optical sensor of the invention in fast slowdown monitoring serum various concentration tumor markers output spectrum
Figure.Because the specific binding of antigen-antibody so that the wavelength of sensing surface evanescent wave interference peaks with markers for breast cancer (HER2)
Concentration variation.Experimentation is to reach fast compared with Electrochemical Detection and fluorescence detection at interval of one concentration of measurement in 15 minutes
The effect of speed detection.Fig. 3 is in concentration 2ng/mL to 15ng/mL concentration range, with markers for breast cancer (HER2) concentration
Increase, linear rule is presented in interference peaks wavelength change, and relationship may be expressed as:
Δ λ (nm)=0.11c (ng/mL) -0.11
Wherein, Δ λ is the wave length shift of interference peaks, and c is the concentration of markers for breast cancer (HER2).
Therefore, interference peaks change in location through the invention obtains markers for breast cancer concentration information, high sensitivity
Up to 0.11nm/ (ng/mL).
Claims (5)
1. the micro optical fiber biosensor of markers for breast cancer in a kind of quickly detection serum, it is characterised in that: including micro-nano
The antibody of fibre optic interferometer, biological functional film and markers for breast cancer;The micro-nano fiber interferometer structure is by micro-nano fiber
Transition region and homogeneity range composition;The biological functional film is to connect optical fiber and breast cancer antibody by covalent bond effect, is had
Function served as bridge;The antibody of the markers for breast cancer is fixed on optical fiber surface by biological functional film;The miniature light
Fine biosensor is being immersed containing in markers for breast cancer sample liquid, and light is input to micro optical fiber biosensor, and utilization is micro-
The nano fiber interferometer surface evanescent wave characteristic highly sensitive to environmental change, resists markers for breast cancer and markers for breast cancer
Body specific binding causes sensor surface variations in refractive index, to quickly detect the concentration of markers for breast cancer in serum.
2. the micro optical fiber biosensor of markers for breast cancer in a kind of quickly detection serum according to claim 1,
It is characterized by: micro-nano fiber interferometer is made by flame fused biconical taper light-sensitive optical fibre.
3. the micro optical fiber biosensor of markers for breast cancer in a kind of quickly detection serum according to claim 1,
It is characterized by: the central waist diameter of preferred micro-nano fiber interferometer is 5-7 μm.
4. the micro optical fiber biosensor of markers for breast cancer in a kind of quickly detection serum according to claim 1,
It is characterized by: carrying out surface biological functionalization to fiber optic sensing device using covalent bonding method, there is spy as bridge connection
Anisotropic identification molecule breast cancer antibody.
5. the micro optical fiber biosensor of markers for breast cancer in a kind of quickly detection serum according to claim 1,
It is characterized by:, as markers for breast cancer concentration increases, interfering spike in concentration 2ng/mL to 15ng/mL concentration range
Linear rule is presented in long variation, and relationship may be expressed as:
Wherein,For the wave length shift of interference peaks, c is the concentration of markers for breast cancer.
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Cited By (4)
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CN112680503A (en) * | 2020-12-31 | 2021-04-20 | 中国科学院长春光学精密机械与物理研究所 | Biosensor for nucleic acid detection and preparation method thereof |
CN113189052A (en) * | 2021-04-14 | 2021-07-30 | 暨南大学 | Acid phosphatase optical fiber biosensor and preparation method and application thereof |
CN113466145A (en) * | 2021-06-15 | 2021-10-01 | 山西大学 | Micro-nano optical fiber sensor for in-situ loading and releasing of medicine and preparation method thereof |
CN113504222A (en) * | 2021-05-26 | 2021-10-15 | 南京品傲光电科技有限公司 | Multi-biological-component sensing system of cascade m-FBG array and rapid detection method of multi-biological components |
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