Study On Flexible Electrochemical Sensors For Human Metabolite Detection

Human metabolic biomarkers are certain physiological and pathological processes,and the accurate detection of the concentration is important in prevention,diagnose and threatment of disease.Most human metabolite tests require patients to endure invasive procedures,such as blood draws or tissue biopsies,which undoubtedly cause pain to patirnts.For this reason,as opposed to invasive blood or tissue analysis,non-invasive wearable sensors can be an emerging health monitoring device to monitor human body health by analyzing the correlation between metabolites and disease states.The type of sensor not only reduces the harm caused by sampling,but also allows real-time monitoring of metabolites to enable the monitoring of human health status,timely detection of problems and reduction of medical costs.However,the composition of human metabolites is more complex.And it is important to investigate how to develop a high-performance,highly selective,portable,and easily integrated sensor for human metabolite monitoring in a complex monitoring environment.In this paper,pH and lactate sensors related to movement status,ascorbic acid sensors related to human metabolism,and ammonia flexible sensors closely related to kidney diseases were constructed,respectively.Then,the above sensors were integrated to design a multiplex wearable sensor,and the application of the sensors in human metabolic substance detection was explored.The main contents of this dissertation are as follows:The first part of this dissertation investigates polymer film-based flexible electrochemical sensors for pH and lactate detection,which contains the following two main studies:In view of the poor flexibility,portability and low sensitivity of pH and lactate sensors in sweat,the flexible pH and lactate sensors were prepared using polymer with good mechanical properties and high electrical conductivity as a sensitive layer.（1）Firstly,polyaniline（PANI）film was prepared at the air-water interface by interfacial synthesis.The film can be transferred directly to the flexible screen-printing electrodes（SPCE）by the lifting method to prepare the PANI-based electrochemical sensor.The PANI thin-film sensor was tested for different pH conditions,multiple ionic interferences and stability of the sensing performance indexes.The results show that the sensor exhibit a super-Nernst response.The bending experimental results of the device prove that the bending of the electrode has a small effect on the sensor.Meanwhile,PANI film sensor are also capable of detecting lactate in sweat with good sensing performance.Finally,the sensor was applied to the detection of pH and lactate in sweat after exercise,which demonstrated that as the lactate concentration in sweat increased,the sweat pH decreased accordingly.（2）To further improve the sensing performance of lactate sensor,poly（3,4-ethylenedioxy-thiophene）（PEDOT）films with carboxyl groups were prepared to enhance the adsorption of lactate oxidase（LOX）by the materials.The sensitivity of this PEDOT-LOX/SPCE sensor improves to 43.42 and0.32μA·(mmol L^-1)^-1·cm^-2 for 0.25-1 and 1-40 mmol·L^-1 lactate,respectively.When the sensor was bent 100 times,the response current value only decreased by 9.5%,and the sensor shows good stability.The PEDOT film electrochemical sensor is capable of monitoring changes in lactate concentration in sweat to enable the determation of the subject’s exercise status.The second part of this dissertation investigates PANI-based flexible electrochemical sensors for the detection of ascorbic acid.This work studies in the following areas:To solve the problems of poor sensitivity and low detection limit of non-enzymatic-based sensors for ascorbic acid（vitamin C）in sweat,a highly acidic,highly symmetric cyclic structured phytic acid（PA）was chosen as the acidic medium and PANI-PA film sensor with high sensitivity,selectivity and stabilitu to ascorbic acid was prepared in this work.The ring-like structure of phytic acid accelerates the electron transport between the PANI film surface and the ascorbic acid molecules.Meanwhile,the carboxyl group in phytic acid can form hydrogen bonds with the hydroxyl group on ascorbic acid to enhance the adsorption of the sensor on ascorbic acid.In addition,changes in ascorbic acid content in sweat and saliva were investigated in humans after taking vitamin C.The results showed that the response current of sensor to sweat was different at the same time as in saliva,due to the different metabolic pathways of vitamin C.Based on the results of the above research,a portable ascorbic acid detection system was developed.The sensing system allows real-time monitoring of ascorbic acid in the human body and shows potential for applications in nutritional guidance.The third part investigates PANI-based flexible gas sensors for the detection of ammonia gas,which consists of two main parts:（1）To solve the problems of low response value,long response recovery time and high influence by humidity in the detection of ammonia（NH₃）in exhaled breath by polymer-based sensors,PANI,a polymer material with better selectivity for NH₃,was selected.And PANI was modified with different surfactants on the surface.First,the PANI films functionalized with sodium dodecyl benzene sulfonate（SDBS）,sodium dodecyl sulfate（SDS）and lauramine（LA）were prepared by interfacial synthesis method,respectively.The addition of SDS surfactant improves the crystallinity of PANI and accelerates the movement of electrons in PANI chains.And the hydrophobic group in SDS can weaken the effect of humidity on PANI films to some extent.Then,the PANI films were transferred to ceramic-based fork finger electrodes to study the gas-sensitive performance.The sensor exhibits good selectivity,stability and humidity resistance.When the relative humidity reaches 85%,the response value to 1 ppm NH₃ only decreases 0.45.（2）Because the substrate of the above sensor is a rigid material,and to achieve the characteristics of the sensor such as flexibility and wearability,a polydimethylsiloxane（PDMS）film modified with PANI-multi-walled carbon nanotubes（MWCNTs）material was prepared.PDMS provides a flexible substrate for the sensor and MWCNTs material enhances the PANI interchain conduction to promote the protonation/deprotonation reaction of NH₃ on the PANI surface.The PANI-MWCNTs/PDMS flexible sensor improved the response value for 40 ppm NH₃ to 11.8 and reduced the detection limit to 10 ppb,and the high humidity environment promoted the adsorption of NH₃ by the sensor.When the relative humidity is 80%,the response of this flexible sensor to 1 ppm NH₃ increases to 5.25.Finally,the sensor was applied to identify healthy human exhalation and simulated exhalation of patients with kidney disease.The results show that the response value of the sensor to the exhalation of simulated kidney disease patients is 3 times higher than that of healthy human exhalation,indicating that the sensor has good recognition of simulated exhalation samples.The fourth part is the module design and integration of wearable sweat sensor.This work studies as follows:In order to achieve continuous,real-time monitoring and selective recognition of human metabolic substances by sensors,a multiplexed flexible wearable sensor was prepared by screen-printing technology using polyethylene terephthalate（PET）as a flexible substrate and polymeric film materials as the sensitive layer.The sensor can detect potassium ion（K⁺）,ammonium ion（NH₄⁺）,lactate,and ascorbic acid in sweat.The sweat sensor has good sensitivity,selectivity,and reproducibility.And the bending angle and number of bends have relatively small effects on the sensor.Finally,the back-end circuit of this sensor was designed.This integrated wearable sweat sensor enables the analysis of sweat composition and is expected to be used for real-time monitoring of sweat metabolites during human exercise.In summary,this dissertation investigates the detection of human metabolites by a flexible wearable sensor based on polymeric thin film material through the above four parts of work,and systematically investigates the sensing performance of the sensor as well as the sensitivity mechanism.The researches in this paper provide a theoretical basis for the study of human metabolite detection sensors with high sensitivity and selectivity,and also provide a feasible research idea for the application of sensors in personalized health detection,real-time physiological status monitoring and clinical research.