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 PDF

Info

Publication number
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
Authority
CN
China
Prior art keywords
breast cancer
markers
micro
optical fiber
biosensor
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201910373463.5A
Other languages
Chinese (zh)
Inventor
孙丹丹
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanxi University
Original Assignee
Shanxi University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shanxi University filed Critical Shanxi University
Priority to CN201910373463.5A priority Critical patent/CN110132896A/en
Publication of CN110132896A publication Critical patent/CN110132896A/en
Pending legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41Refractivity; Phase-affecting properties, e.g. optical path length
    • G01N21/45Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • G01N33/57415Specifically defined cancers of breast
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41Refractivity; Phase-affecting properties, e.g. optical path length
    • G01N21/45Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
    • G01N2021/458Refractivity; 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

The micro optical fiber biosensor of markers for breast cancer in a kind of quick detection serum
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.
CN201910373463.5A 2019-05-06 2019-05-06 The micro optical fiber biosensor of markers for breast cancer in a kind of quick detection serum Pending CN110132896A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910373463.5A CN110132896A (en) 2019-05-06 2019-05-06 The micro optical fiber biosensor of markers for breast cancer in a kind of quick detection serum

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910373463.5A CN110132896A (en) 2019-05-06 2019-05-06 The micro optical fiber biosensor of markers for breast cancer in a kind of quick detection serum

Publications (1)

Publication Number Publication Date
CN110132896A true CN110132896A (en) 2019-08-16

Family

ID=67576380

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910373463.5A Pending CN110132896A (en) 2019-05-06 2019-05-06 The micro optical fiber biosensor of markers for breast cancer in a kind of quick detection serum

Country Status (1)

Country Link
CN (1) CN110132896A (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1354791A (en) * 1999-04-02 2002-06-19 科里克萨有限公司 Compositions for treatment and diagnosis of breast cancer and methods for their use
CN1443239A (en) * 2000-05-24 2003-09-17 科里克萨有限公司 Compositions and methods for therapy and diagnosis of breast cancer
CN101118216A (en) * 2007-09-07 2008-02-06 中国科学院长春光学精密机械与物理研究所 Optical fibre biological detecting probe, manufacturing method and use thereof
JP4445596B2 (en) * 1997-10-14 2010-04-07 バイエル・シエリング・フアーマ・アクチエンゲゼルシヤフト Optical measuring device for detecting luminescence or fluorescence signals
CN106290896A (en) * 2016-07-27 2017-01-04 东北师范大学 A kind of photonic crystal fiber immunosensor and application thereof
CN109060727A (en) * 2018-08-22 2018-12-21 东北大学 A kind of double channel optical fiber surface plasmon resonance biosensor
EP3465206A1 (en) * 2016-06-06 2019-04-10 Medizinische Universität Wien Method for the detection of an IgM antibody specific for a flavivirus in a sample

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4445596B2 (en) * 1997-10-14 2010-04-07 バイエル・シエリング・フアーマ・アクチエンゲゼルシヤフト Optical measuring device for detecting luminescence or fluorescence signals
CN1354791A (en) * 1999-04-02 2002-06-19 科里克萨有限公司 Compositions for treatment and diagnosis of breast cancer and methods for their use
CN1443239A (en) * 2000-05-24 2003-09-17 科里克萨有限公司 Compositions and methods for therapy and diagnosis of breast cancer
CN101118216A (en) * 2007-09-07 2008-02-06 中国科学院长春光学精密机械与物理研究所 Optical fibre biological detecting probe, manufacturing method and use thereof
EP3465206A1 (en) * 2016-06-06 2019-04-10 Medizinische Universität Wien Method for the detection of an IgM antibody specific for a flavivirus in a sample
CN106290896A (en) * 2016-07-27 2017-01-04 东北师范大学 A kind of photonic crystal fiber immunosensor and application thereof
CN109060727A (en) * 2018-08-22 2018-12-21 东北大学 A kind of double channel optical fiber surface plasmon resonance biosensor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
孙丹丹: "光栅型与干涉型微纳光纤生物传感器", 《中国博士学位论文全文数据库 医药卫生科技辑》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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
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

Similar Documents

Publication Publication Date Title
CN110132896A (en) The micro optical fiber biosensor of markers for breast cancer in a kind of quick detection serum
Li et al. Immobilized optical fiber microprobe for selective and high sensitive glucose detection
US8476007B2 (en) Optical fiber probe
Li et al. A SERS nano-tag-based fiber-optic strategy for in situ immunoassay in unprocessed whole blood
CN108613950A (en) Sensitizing type cytochrome c fibre-optical sensing device and method
KR100927655B1 (en) Bio detection sensor
CN108572141B (en) Composite enhanced optical fiber biosensor and method for detecting concentration of biological protein molecules
Sun et al. Non-enzymatic glucose detection based on phenylboronic acid modified optical fibers
Zhou et al. Universal quantum dot-based sandwich-like immunoassay strategy for rapid and ultrasensitive detection of small molecules using portable and reusable optofluidic nano-biosensing platform
CN109557051A (en) Sensitizing type microRNA fibre-optical sensing device and production, measurement method
CN201060167Y (en) Microstructure optical fibre sensing probe
Li et al. Gold/zinc oxide nanoparticles functionalized tapered SMF-MMF-SMF-based sensor probe for uric acid detection
Chen et al. High-Sensitivity Carcinoembryonic Antigen Detection Using Open Cavity Fabry-Perot Immunosensor Based on Vernier Effect
Cao et al. Point-of-care diagnosis of pre-eclampsia based on microfiber Bragg grating biosensor
CN109342716B (en) D-type optical fiber sensor based on single-mode-few-mode-single-mode structure
CN208520876U (en) A kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor
CN106442979A (en) Fast quantitative immunity test strip used for detecting four indicators of hepatic fibrosis
Matějec et al. Extrinsic fiber-optic sensor for detection of saliva pH
JP5234453B2 (en) Method for analyzing skin cathepsin, method for determining skin light stress, and kit therefor
Li et al. Label free hCG concentration biosensor based on suspension core fiber microfluidic technology
CN112268874A (en) Rapid ultra-sensitive sensing device based on optical fiber biochemical probe
CN113281271A (en) Biomedical detection system and method for micro-nano material modification
Hu et al. Magnetic microspheres enhanced peanut structure cascaded lasso shaped fiber laser biosensor for cancer marker-CEACAM5 detection in serum
Zhang et al. Dual-tapered optical fiber structure-based LSPR sensor for cholesterol detection
Amani et al. Smartphone-assisted quantitative colorimetric identification of thrombin based on peroxidase mimetic features of fibrinogen-gold nanozymes

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20190816