| Biosensor has great research significance and application value in the fields of biomedicine,clinical diagnosis,pharmaceutical analysis,food inspection,environment monitoring and bioterrorism defense,etc.Health care,food safety and environmental pollution problems have draw more and more attentions in 21 st century,so the development of new biosensor with high sensitivity,low cost,small portable size,fast response and easy operation is now a social urgent demand.Optical fiber sensor has been studied extensively and developed rapidly in biosensing during the recent 20 years,due to its advantages of small size,high sensitivity,immunity to electromagnetic interference,good biocompatibility and so on.Label-free optical fiber biosensor combines the optical fiber sensor with label-free biological detection method,and detects analyte according to the change of optical signal induced by biological reaction directly.It can cut out the labeling process,save time and cost,and provide in-situ,real-time and on-line detection of dynamic process of biological reaction.So the label-free optical fiber biosensor has great potential and application prospect.It has become a research hotspot in biosensing recently.However,label-free optical fiber biosensor is still in the stage of laboratory research overall at present.It's very tough but essential to improve the sensitivity,anti-interference capability,stability,repeatability and specificity of label-free optical fiber biosensor,when it faces the problems of external environment disturbance,low concentration of analyte,complex composition and so on in practical application.Optical fiber sensor itself has relatively high sensitivity,but it's usually easily affected by temperature or strain cross-sensitivity,so the anti-interference capability needs to be improved.The immobilization of bio-molecules recognition element on sensor surface is the key of biosensor fabrication.The density and activity of bio-molecules on sensor surface can directly affect the sensitivity,stability,detection range,specificity and repeatability of biosensor.Recently,the development of all kinds of new nanomaterials has brought about a new situation for building biosensing interface and improving detection performance.In this dissertation,an optical fiber Fabry-Perot(F-P)sensor based on hollow-core photonic crystal fiber(HCPCF)for label-free biosensing is mainly proposed and studied by theoretic analysis and experiments.The HCPCF-based optical fiber F-P sensor is act as a biosensing transducer,converting the refractive index or thickness change of bio-molecular layer immobilized on sensor end face induced by the biological reaction into the change of output interference spectrum.The sensor has advantages of small size and stable structure.Its probe structure and reflection-type detection mode make the use of the sensor more simple and flexible.The HCPCF-based optical fiber F-P sensor provides a new approach for biosensing.The use of novel carbon nanomaterial—graphene oxide for building biosensing interface is further proposed in this dissertation.The immobilization effect of biomolecules and detection performance of biosensor can be improved by the good biocompatibility and large specific surface area of graphene oxide.The main contents of this dissertation are as follows:(1)The output interference spectrum characteristic of the HCPCF-based optical fiber F-P sensor is analyzed theoretically based on Fresnel reflection principle and three beams interference model first.The effects of sensor structure parameters on the fringe contrast of interference spectrum are analyzed.Refractive index measurement is the basis of label-free optical fiber biosensor,so the refractive index response characteristic of the HCPCF-based optical fiber F-P sensor is analyzed theoretically.The simulation results show that the fringe contrast of interference spectrum decreases as the external refractive index increases,and the sensor shows a good linear response in a relatively large range of refractive index.The effects of sensor structure parameters on its refractive index sensitivity are further analyzed.Meanwhile,the temperature sensitivity characteristic of sensor is analyzed.Results show that the change of environment temperature leads to the shift of interference fringe wavelength,while it has almost no effect on the fringe contrast.Thus the HCPCF-based optical fiber F-P sensor can be applied to refractive index measurement and temperature detection simultaneously with negligible cross-sensitivity by demodulating the fringe contrast and wavelength of interference spectrum respectively.(2)The HCPCF-based optical fiber F-P sensor is fabricated by arc fusion splicing method,and the refractive index response characteristic of the fabricated sensor is analyzed experimentally using sucrose solutions of different concentration.Experimental results show that in the range of 1.33-1.44RIU(refractive index unit),the sensor shows good linearity and repeatability,and the refractive index sensitivity is about-136dB/RIU.Detection of yeast growth is conducted by the optical fiber F-P sensor according to the refractive index change of liquid culture during yeast growth.Results confirm the resolution capability of the sensor for detecting tiny change of external refractive index.In addition,a new SDI(spectrum differential integration)data analysis method is proposed to improve the accuracy of refractive index demodulation result.(3)A label-free optical fiber F-P immunosensor is proposed.The immunosensing is realized by the refractive index and thickness changes of the protein molecular film immobilized on sensor end face induced by the combination of antibody and antigen.First,four beams interference model for film-coated optical fiber F-P sensor is build,and the immunosensing principle is analyzed theoretically.In experiment,the sensor end face is modified with silanization and glutaraldehyde,and then immobilized with goat anti-rabbit IgG(immunoglobulin G)by covalent binding.And rabbit IgG is detected by the sensor.Experimental results vertify the feasibility of the proposed immunosensor preliminarily.(4)A graphene oxide coated optical fiber F-P label-free immunosensor is proposed.The immobilization effect of biomolecules on sensor end face and the detecting sensitivity of biosensor can be improved by the good biocompatibility and large specific surface area of graphene oxide.First,graphene oxide is coated on optical fiber end face by different methods,and the coated films are characterized by SEM(scanning electron microscope)and analyzed contrastively.Graphene oxide film is coated on the optical fiber F-P sensor end face and the interference spectrum of the sensor is simulated and analyzed.The effect of graphene oxide film thickness on the interference spectrum is analyzed theoretically.In immunosensing experiment,goat anti-rabbit IgG is immobilized on the graphene oxide coated sensor end face,and rabbit IgG is tested.Experimental results show that the interference spectrum of the graphene oxide coated sensor has more obvious changes with the antibody immobilization and antigen binding.The results vertify the immunosensor performance improvement by graphene oxide preliminarily.(5)An optical fiber F-P humidity sensor coated with chitosan film is fabricated as an extended research of optical fiber F-P sensor based on HCPCF for humidity measurement in the biomedical field and so on.According to the swell effect of chitosan when exposed to humid environment,the refractive index and thickness of chitosan film will change with humidity.By demodulating the changes of interference fringe contrast and wavelength,the relative humidity of environment is detected. |
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