Wearable Nanofiber-based Microfluidic Sensor And Its Application In Sweat Analysis

Sweat contains plentiful biomarkers（metabolites,proteins,hormones and electrolytes）relevant to physiological state,continuous detection of biomarkers in sweat is of great significance for monitoring daily health status and for early disease diagnosis.Wearable sweat senses represent an emerging technique and have begun unlocking new insights for personal daily exercise detection,physiological state monitoring and disease diagnosis,due to its portability,in situ,non-invasive and real-time.However,there are still some challenges to be solved in wearable sweat sensors:1)The stability and accuracy of these wearable devices are often limited due to sweat contamination during sampling,asymmetrical sweat delivery over sensor surface,cross-talk between different sensors,the mixture of old and new sweat,and unstable colorimetric reagent fixation;2)Sweat accumulation,poorly flexible and breathable substrates will affect wearing comfort;3)Most reported wearable devices require expensive instruments,specialized laboratory conditions and cumbersome fabrication processes;4)As the fabrication process involves integration of different materials,multiple functional layers and different sensing components,incorporating multimodal sensors,sweat collection devices and other devices into one wearable device still confronts notable challenges.To solve the problems mentioned above,this thesis focused on the in situ sweat analysis and performed in-depth research.In this thesis,the nanofibers were selected as the research object and different kinds of nanofiber-based sensors were constructed.This thesis focused on designing in situ sweat collection devices and integrated sensors,improving their performance and expanding their application.It combined wearable technique and microfluidic technique,with the help of simple and low-cost electrospinning and direct ink writing,to develop different types of nanofiber-based wearable sweat sensors.The main research contents in this work are presented as follows.A flexible electrochemical sensor was constructed to real-time and in situ monitoring of sweat cortisol by utilizing the porous and flexible of nanofiber membranes and the specific recognition mechanism of molecularly imprinted polymers for template molecules.Firstly,polyimide/sodium dodecyl sulfate nanofiber films were introduced as the supporting substrate for deposition of polydimethylsiloxane walls to construct nanofiber-based microfluidic chips.The nanofiber-based microfluidic chip was fabricated by electrospinning and direct ink writing,which could spontaneously capture and route sweat.Secondly,screen-printed flexible electrodes worked as sensor substrates,and carbon nanofiber membranes decorated with gold nanoparticles served as sensitization materials.Molecularly imprinted polymers for specific recognition of cortisol and Prussian blue nanoparticles as a“built-in”redox probe were modified on the surface of screen-printed flexible electrodes by electro-polymerization.Finally,by integrating nanofiber-based microfluidic chips,flexible sensors and flexible circuit boards,in situ,wireless and real-time measurement of sweat cortisol could be realized.The sensor demonstrated a wide detection range of 1.0 nmol/L～1.0μmol/L as well as low detection limit（0.35 nmol/L,S/N=3）,excellent selectivity,stability and reproducibility.Besides,on-body applicability of the sensor was also validated by real-time monitoring of healthy volunteers’sweat cortisol during morning and evening exercise.A flexible colorimetric sensor was presented for the real-time monitoring of glucose,Ca²⁺and Zn²⁺in sweat by utilizing the directional water transfer property of Janus membranes.Firstly,Janus nanofiber membranes were prepared by electrospinning hydrophobic polyurethane and hydrophilic polyacrylonitrile/silica,and a Janus nanofiber membrane-based chip was prepared by using Janus membranes as the substrate.Based on the advantages of the Janus membrane,the chip can transport sweat from the hydrophobic layer to the hydrophilic layer,which could realize the rapid evaporation of sweat and solve the problems of sweat accumulation and poor wearing comfort.Secondly,electrospinning was used to encapsulate colorimetric reagents into nanofibers to prepare functional nanofiber membranes,improving the stability of reagents immobilization.In addition,in terms of glucose detection,to solve the problems of poor long-term use stability,harsh use conditions and difficult recovery of natural enzymes,copper-hemin metal organic framework nanomaterials with excellent peroxidase performance were prepared.Finally,the functional nanofiber membrane and the Janus nanofiber membrane-based microfluidic chip were assembled to complete the simultaneous detection of glucose,Ca²⁺and Zn²⁺in sweat.Subsequently,the changes of the three substances in the body of volunteers before and after diet were successfully monitored,which verified the reliability of the sensor.A flexible dual-mode sensor was fabricated for the simultaneous monitoring of glucose,lactate,p H,Cl^-and urea by integrating a microfluidic network,an electrochemical sensing array and a colorimetric sensing array.Firstly,a nanofiber-based microfluidic network with a multi-layer structure was prepared by electrospinning and direct ink writing,which can spontaneously transport sweat to the detection area of different layers.Secondly,dual-mode sensing arrays were embedded into nanofiber-based microfluidic networks,and each sensing unit was located into an independent chamber,which reduces the crosstalk between sensing units.Meanwhile,the nanofiber membranes served as the substrate for constructing the dual-mode sensing array,which improves the flexibility of the device.Finally,the integration of electrochemical sensing arrays,colorimetric sensing arrays,nanofiber-based microfluidic networks and wireless electronics enables wireless,in situ,dual-mode,and simultaneous monitoring of five substances（glucose,lactate,p H,Cl^-and urea）.The sensor can meet the actual detection requirements of these five substances in sweat in terms of detection range,detection limit,anti-interference and stability.Human studies demonstrate that the proposed system can mount firmly on human skin during physical exercise and provide continuous,multimodal information associated with sweat chemistry.In summary,a variety of nanofiber-based wearable sweat sensors were constructed in this thesis,and their sensing performance was explored to realize in situ,reliable and real-time monitoring of multiple components of sweat.This work provides a new strategy for designing and fabricating a reliable,low-cost,diverse and integrated wearable sweat sensing system.The constructed wearable sweat sensor has shown promising applications in motion detection,health monitoring and disease diagnosis.