CN208520876U - A kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor - Google Patents

A kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor Download PDF

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Publication number
CN208520876U
CN208520876U CN201820613394.1U CN201820613394U CN208520876U CN 208520876 U CN208520876 U CN 208520876U CN 201820613394 U CN201820613394 U CN 201820613394U CN 208520876 U CN208520876 U CN 208520876U
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fiber
interference
type micro
nano fiber
bragg grating
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孙丹丹
李吴璇
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Shanxi University
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Shanxi University
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Abstract

The utility model relates to optical fibre bio technical fields, in particular to optical fiber biosensor field.A kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor, it is made of the interference-type micro-nano fiber device 1 and fiber bragg grating device 2 that form cascaded structure over the same fiber, interference-type micro-nano fiber device 1 is processed to obtain by heat sealing machine to optical fiber fused tapering, 1 central waist diameter of interference-type micro-nano fiber device is 10 μm, length is 3mm, and two end cone section lengths are 2mm;Fiber bragg grating device 2 be the fiber bragg grating that 1070.49nm is length 3mm in the period.The utility model is by forming interference and optical grating construction over the same fiber, it can be achieved that many reference amounts detect.

Description

A kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor
Technical field
The utility model relates to optical fibre bio technical fields, in particular to optical fiber biosensor field.
Background technique
Breast cancer (breast cancer) has become current one of the most common malignant tumors in women, is the third-largest common Cancer, it is considered to be patient itself and family are given all to human health and the biggish malignant tumour of life threat in the whole world at present Great pain is caused, a large amount of social resources and wealth are also occupied, becomes the public health problem got worse.For This, the researcher of national governments and various fields has put into a large amount of manpower and material resources, on breast cancer research field It has breakthrough.The early diagnosis of breast cancer is mostly important, early treatment is found its object is to early, to mitigate patient suffering and essence Mind, financial burden.Biomarker for cancer is typically found in body fluid such as blood, serum, urine and tumour cell.It measures certain The content of marker can contribute to determine certain form of presence or progress cancer.HER2 is a kind of good life of document record Object marker, the patient with breast cancer of about 25%-30% with HER2 overexpression.In markers for breast cancer detection method often Fluorescent marker or dye marker are used, high sensitivity even single molecules level can be provided.However, still remaining cost Height, program complexity and label influence the challenge such as biomolecule nature.Therefore, with intelligence and it is miniaturized as showing for feature It is to promote " accuracy " and " realizability " that non-damaging approach early-stage breast cancer diagnoses to mention for optical fibre bio medicine sensing technology For powerful measure.
By feat of being constantly progressive in recent years, optical fiber sensing technology from initial physical quantity gradually penetrate into life, The fields such as chemistry, medicine detection, embody superior biomedical detection performance, for example, compact structure flexibly, low cost, can be remote Journey detection, electromagnetism interference, reusable, bio-compatibility, high sensitivity, response quickly etc..As a kind of promising optical fiber Senser element, interference-type micro-nano fiber sensor, which provides stronger evanescent wave, can complete highly sensitive detection, however usually exist There are Temperature cross-over sensitivity in bio-sensing measurement, detection accuracy is influenced.Therefore, while in actual monitored system examine in real time It surveys tumor markers concentration and temperature is most important.
Summary of the invention
The technical problem to be solved by the utility model is to the shortcomings that how overcoming the prior art and deficiency, construct one kind High sensitivity, high specific, it is label-free, easy, can physical examination survey micromation optical fiber biosensor.
The technical scheme adopted by the utility model is a kind of label-free interference-type micro-nano fiber markers for breast cancer is immune Biosensor, by formed over the same fiber cascaded structure interference-type micro-nano fiber device 1 and 2 groups of fiber bragg grating device At interference-type micro-nano fiber device 1 is processed to obtain by heat sealing machine to optical fiber fused tapering, in interference-type micro-nano fiber device 1 Between waist diameter be 10 μm, length 3mm, two end cone section lengths be 2mm;It is 1070.49nm that fiber bragg grating device 2, which is the period, It is the fiber bragg grating of length 3mm.A kind of immune bio-sensing of label-free interference-type micro-nano fiber markers for breast cancer Device is made of two detection units of parallel-connection structure, and the both ends of two detection units are all connected on detection device, the first detection Unit 4 is made of the interference-type micro-nano fiber device 1 and fiber bragg grating device 2 for forming cascaded structure on an optical fiber 3, the second inspection It is micro- by the interference-type micro-nano fiber device 1, fiber bragg grating device 2, interference-type for forming cascaded structure on an optical fiber 3 to survey unit 5 Nano fiber device 1, fiber bragg grating device 2 form, and interference-type micro-nano fiber device 1 processes optical fiber fused tapering by heat sealing machine It obtains, 1 central waist diameter of interference-type micro-nano fiber device is 10 μm, length 3mm, and two end cone section lengths are 2mm;Optical fiber light Gate device 2 be the fiber bragg grating that 1070.49nm is length 3mm in the period.
As a kind of preferred embodiment: optical fiber is the silica fibre that diameter is 125 μm.
Since the big evanscent field characteristic of interference-type micro-nano fiber device provides the variation of sensing external environment with sensitivity.It is dry Relating to type micro-nano fiber device 1, uniformly region and two tapering transition zones with a tight waist are constituted by mid diameter, a tapering transition The basic mode and high-order mode of region excitation couple, due to basic mode and high-order in regional spread with a tight waist with another tapering transition zone Mould transmission coefficient is different, 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 interference-type micro-nano fiber device sensing external environment is
For dispersion factor, it is generally negative value for silica fibre, embodies refringence and wavelength Between relationship.△ n is basic mode HE11And HE12The refringence of high-order mode.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).
Meanwhile the temperature-responsive formula of interference-type micro-nano fiber device is
Wherein α=0.55 × 10-6For the thermal expansion coefficient of quartz glass, βsi=dnsi/ dT=6 × 10-6For quartz glass Thermo-optical coeffecient.By calculating it is found that refringence is with quartzy refractive index nsiIncrease and reduce, and Section 2 in bracket Value is -1.04 × 10-4.In view of abbe number Γ is negative value, therefore interference fringe is drifted about as temperature increases to shortwave.Using Finite element software calculates, and in wavelength 1520nm, abbe number Γ is -0.91, and temperature-responsive sensitivity is 17.3pm/ DEG C.It is comprehensive On, interference-type micro-nano fiber device has high sensitivity to the refractive index of external environment, can be used for breast cancer tumour marker The detection of concentration, but the temperature-responsive of interference-type micro-nano fiber device can interfere the monitoring result of biological sample, this is just needed System temperature is measured, the influence of temperature in real-time monitoring bio-sensing.
And the work of fiber-optic grating sensor part is in basic mode mode, it is insensitive to the variations in refractive index of external environment, but its It is able to respond temperature change, temperature sensitivity formula is
Wherein α=0.55 × 10-6For the thermal expansion coefficient of quartz glass, βsi=dnsi/ dT=6 × 10-6For quartz glass Thermo-optical coeffecient, it is consistent with the above.Obtaining fiber-optic grating sensor part can be used as scale of thermometer devise a stratagem use.Therefore, this patent Fiber-optic grating sensor part is introduced into one entirety of composition in interference-type micro-nano fiber biosensor, while monitoring tumour mark Will object concentration and system temperature.
The beneficial effects of the utility model are: (1) the utility model by forming interference and grating over the same fiber Structure can monitor tumor markers concentration and system temperature, it is seen that the structure of the utility model optical fiber biosensor simultaneously It is compact, realize many reference amounts detection;The diameter of the utility model optical fiber biosensor is micron or nanometer scale, therefore this reality It is very small and exquisite with novel sensor structure.(2) optical fiber biosensor of the utility model simplifies program flow without label Journey solves the problems such as operation is strongly professional, at high cost, background signal is strong.The sound of bio-molecular interaction can be monitored in real time It answers, assessment rapidly can be made to analyte, and can regenerate reusable.(3) optical fibre bio of the utility model 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 utility model structure diagram.
Specific embodiment
(only see first detection unit 4) as shown in Figure 1, a kind of label-free interference-type micro-nano fiber markers for breast cancer is immune Biosensor, including interference-type micro-nano fiber device 1 and fiber bragg grating device 2, by making interference-type on an optical fiber 3 Micro-nano fiber device 1 and fiber bragg grating device 2 form cascade fibre optical sensor;It can be seen that the optical fiber biosensor of the present embodiment Composed structure and preparation process it is all very simple.
Wherein interference-type micro-nano fiber device 1 is to process to obtain by heat sealing machine fused biconical taper by 125 μm of silica fibres.Light Fine grating device 2 is that the mode of 193nm excimer laser combination phase mask plate realizes production, then uses fused biconical taper method Realize the preparation of interference-type micro-nano fiber device, thus piece optical fiber two sensors of series connection of realization, therefore the optical fiber of the present embodiment The structure of sensor is very small and exquisite.
Wherein the central waist diameter of interference-type micro-nano fiber device 1 of the invention is 10 μm, length 3mm, two end cones Section length is 2mm;Fiber bragg grating device 2 is the fiber bragg grating of length 3mm.
Wherein the interference-type micro-nano fiber device 1 of the present embodiment has big evanscent field characteristic, sensing external environment refraction The sensitivity of rate is strong, refractive index sensitivity 2400nm/RIU, and 2 pairs of fiber bragg grating device extraneous ambient refractive index change not It is sensitive.Interference-type micro-nano fiber device 1 and fiber bragg grating device 2 have certain response to temperature.So cascaded optical fiber senses Device is in biological testing process, and fiber bragg grating device 2, which can be used as the scale of thermometer and devise a stratagem, carrys out real-time monitoring system temperature, and interference-type Micro-nano fiber device 1 can the highly sensitive response for detecting bio-molecular interaction.
Surface-functionalized processing is carried out to cascaded optical fiber senser element using covalent bonding method in this example, it is same to cross Piranha Solution (H2SO4/H2O2=7:3, volume ratio) optical fiber surface can be made with hydroxyl (- OH), connect later with silane coupling A PTES It connects, and has NH2- group on APTES molecule, can be connect with the aldehyde radical (- CHO) of glutaraldehyde one end, and glutaraldehyde molecules The aldehyde radical of the other end and the breast cancer tumour marker HER2 antibody (10 μ g/mL of concentration) of modification NH2- group combine.Rear class Connection fiber optic sensing device can be used for monitoring the response of breast cancer tumour HER2 marker.Fibre optical sensor is supervised in real time in this example The real-time output light spectrogram of breast cancer tumour marker concentration (10ng/mL) and system temperature variation are surveyed, figure lower section is interference-type The enlarged drawing of micro-nano fiber device monitor tumor markers.Tumor markers concentration (the 10ng/ out of available in figure 60min The interference peaks of interference-type micro-nano fiber device 1 are drifted about to the right 1.4nm when mL), and response is very fast in period 10min;And optical fiber The peak value of grating 2 is constant to monitor that temperature changes very little in whole process, so this example cascade fibre optical sensor can be simultaneously Realize the real time monitoring function of tumor markers concentration and system temperature.
Embodiment 2
2 difference from Example 1 of the present embodiment is, using can two parallel-connection structures detection unit, the first detection Unit 4 is same as Example 1, the series connection of 5 equal two the 4th detection units 4 of second detection unit, the knot of two detection units Fruit compares and analyzes, and the sensitivity of detection can be improved.

Claims (4)

1. a kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor, it is characterised in that: by same Interference-type micro-nano fiber device (1) and fiber bragg grating device (2) composition, the interference-type that cascaded structure is formed on root optical fiber (3) are micro- Nano fiber device (1) is processed to obtain by heat sealing machine to optical fiber fused tapering, and interference-type micro-nano fiber device (1) central waist is straight Diameter is 10 μm, length 3mm, and two end cone section lengths are 2mm;Fiber bragg grating device (2) be 1070.49nm in the period be length The fiber bragg grating of 3mm.
2. a kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor according to claim 1, It is characterized by: optical fiber (3) is the silica fibre that diameter is 125 μm.
3. a kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor, it is characterised in that: by and be coupled Two detection units of structure are constituted, and the both ends of two detection units are all connected on detection device, and first detection unit (4) is by one The interference-type micro-nano fiber device (1) and fiber bragg grating device (2) composition of cascaded structure, the second detection are formed on root optical fiber (3) Unit (5) is by forming the interference-type micro-nano fiber device (1) of cascaded structure, fiber bragg grating device (2), doing on an optical fiber (3) Type micro-nano fiber device (1), fiber bragg grating device (2) composition are related to, interference-type micro-nano fiber device (1) is by heat sealing machine to optical fiber Fused biconical taper is processed to obtain, and interference-type micro-nano fiber device (1) central waist diameter is 10 μm, length 3mm, the two end cone heads of district Degree is 2mm;Fiber bragg grating device (2) be the fiber bragg grating that 1070.49nm is length 3mm in the period.
4. a kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor according to claim 3, It is characterized by: optical fiber (3) is the silica fibre that diameter is 125 μm.
CN201820613394.1U 2018-04-27 2018-04-27 A kind of label-free interference-type micro-nano fiber markers for breast cancer immunity biosensor Expired - Fee Related CN208520876U (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CN114371137A (en) * 2022-01-12 2022-04-19 厦门大学 Mark-free tumor marker detection system and method based on micro-nano structure optical chip

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CN114371137A (en) * 2022-01-12 2022-04-19 厦门大学 Mark-free tumor marker detection system and method based on micro-nano structure optical chip

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