The Sensing Mechanism And Experimental Study Of Biochemical And Physiological Sensors Based On Micro/Nanofiber

The sensors with ability to distinguish biochemical molecules and monitor physiological parameters have acquired paramount importance in numerous fields such as medical diagnosis,health monitoring,pathological research and so on.Optical fiber sensors are well known by their advantages of compatct size,high sensitivity,multiplexing detection capability and immunity to electromagnetic interference,which has been applied to detect or monitor various analytes and physiological parameters in the past decade.Compared with the standard optical fiber,microfiber has diameter ranging from hundreds of nanometers to tens of micrometers.The reduced diameter results in large fractional evanescent field of microfiber to penetrate into environment,which allows the direct interaction between light and surroundings.The unique superiority of micro/nano fiber(MNF)makes it a better platform for detecting biochemical molecules and monitoring physiological parameters.In order to meet the requirements of detecting biological substances such as glucose,E.coli and DNA,as well as the requirements of monitoring physiological parameters such as heart rate,pulse and blood pressure,we studied the mode coupling theory of biconical microfiber and single end microfiber and the selective sensing mechanism when they were applied into the measurement of biochemical physiological parameters.Simulations and experiments were executed as well.The main research content includes:Firstly,the glucose sensor based on glucose oxidase(GOD)-immobilized biconical microfiber was proposed.Considering that the detection of glucose was based on the sensing of surrounding refractive index(RI)variation caused by the enzymatic reaction of glucose,the refractive index sensing characteristics of bioconical microfiber mode interferometer was investigated in detail.The analysis result indicated that the biconical microfiber interferometer had an ultrahigh RI sensitivity near the diserpersing turning point,which offered theoretical basis for the design and fabrication of glucose sensor.The method of surface functionalization of microfiber using GOD was researched,through which the glucose senor was manufactured successfully.The proposed glucose sensor was test in the samples with different glucose concentration.The results showed a high sensitivity of 1.74nm/(mg/ml)with selectivity,which was 5.8 times of other fiber-based glucose sensors.The practical utility of reported sensor was also proved by accurately detecting glucose content in animal serum samples.Secondly,the E.coli sensor based on T4 bacteriophage-immobilized biconical microfiber was proposed.For E.coli detection,the spectral change was not only influenced by the variation of surrounding RI but also by the thicknenss viriation of coating caused by the bonding of E.coli bacteria.Therefore,a new theoretical model was built to explain this sensing mechanism.In this model,the E.coli bonded on the microfiber surface was equivalent to a layer of biological substance and its influence to the performance was simulated using Comsol Multiphysics.The simulation results offered the reference for the design and fabrication of microfiber-based E.coli sensor.Additionally,the effect of proposed E.coli sensor was measured through immersing the T4 bacteriaphage-immobilized microfiber into the samples with different E.coli concentration.By tracking the spectral change of bioconical microfiber mode interferometer,a minimum detectable concentration of 10~3cfu/ml and a faster response time of 7mins were realized.Thirdly,a single end microfiber interferometer was designed to simplify the structure and improve convenience of biconical microfiber.The spectral characteristics of single end microfiber interferometer was investigated.The degree of asymmetry(DOA)of taper was defined and its influence to the spectrum extinction ratio of microfiber was demonstrated in theory.The analysis results showed that the symmetrical single-cone microfiber interferometer has the same sensitivity and higher spectral extinction ratio than the non-strictly symmetric biconical microfiber interferometer.In addition,a two-step method of"stretch and fracture"for fabricating single end microfiber interferometer was proposed based on the theory of brittle fracture.The experimental results showed that the extinction ratio of the single-cone interferometer reaches 10d B.Forthly,a DNA sensor based on single stranded DNA(ss DNA)-immobilized single end microfiber interferometer was proposed.The ss DNA with specific sequences,which was also called probe ss DNA,was bonded on the microfiber surface to recognize its complementary ss DNA molecules.In order to improve the packaging of single end microfiber-based DNA sensor,a microdevice was designed and fabricated to protect the microfiber based on soft lithography and microfluidic techniques.The detection processes of DNA hybridization in various concentration of target DNA solutions were monitored in real-time and the experimental results presented a minimum detectable concentration of 10p M with good repeatability.Additionally,the detection specificity is also investigated by immersing the microfiber probe into the non-complementary ss DNA solutions.The observed spectral variation indicated that the proposed DNA sensor had a good selectivity.Finally,flexible pulse sensor based on single end microfiber was proposed.The sensing mechanism of micro-deformation based on power coupling was investigated as well.In order to detect the weak vibration signal,the sensitization mechanism of Polydimethylsiloxane(PDMS)package structure was analyzed,and the flexible fiber pulse wave sensor was successfully prepared.Through measuring the power variation of reflected light caused by the arteriopalmus,the pulse waveform with high precision was recovered.Furthermore,according to the relationship model between Pulse transit time(PTT)and blood pressure,Systolic blood pressure(SBP)and Diastolic blood pressure(DBP)of human body were measured.In particular,seven samples were tested and the measurement results were compared with the data of commercial sphygmomanometer.The experimental results showed that the measurement error of proposed sensor was less than 8mm/Hg,which met the error requirements of the Association for the Advancement of Medical Instrumentation(AAMI)for commercial sphygmomanometer.