Electrochemical biosensors: from flexible electrodes to point-of-Care disease management

Today, a large number of devices denoted as biosensors can be found in laboratories around the world but the only cheap handheld sensing devices in market are glucose sensors. The inability to miniaturize the sensing device and the lack of cost-effective production method are the two obstacles in realizations of point-of-care biosensors in most of the cases. Therefore, fabrication of low-cost miniaturized transducing materials (electrodes) together with enhancement in selectivity and sensitivity are the lead research topics in the field. The increasing interest in using wearable biosensors shows an attitude change from centralized hospital-based patient care to home-based personal management, as the latter results in lowering health-care costs. The major efforts towards on-body monitoring of wearer’s health or physical activity have focused on development of physical sensor devices such as temperature and body motion. Unlike well-developed wearable physical sensors, non-invasive chemical sensors and biosensors are still in their infancy. The limitations toward development of wearable chemical sensors has hindered further progress in continuous personal health monitoring. This is due to several key issues that have yet to be successfully solved like obtaining sensor response in presence of low analyte concentrations, small sampling volumes of the bio-fluid, mechanical stability of the transducer, biofouling, and biocompatibility of the sensors. This dissertation is dedicated to development of bioanalytical devices that can cope with the current limitations of electrochemical biosensors. First, to address the physical limitations (bulkiness and rigidity of bioanalytical devices), flexible electrodes were developed based on electroless metallization technique which is a cost-effective process. This fabrication technique had the potential for miniaturization of the device. All-wet metallization of polydimethylsiloxae (PDMS) was carried out by Nickel-phosphorous-boron (NiPB) electroless deposition. Self-assembled monolayers (SAM) of n-(2-aminoethyl) 3-aminopropyl-trimethoxysilane (AEAPTMS) was used to improve the metal thin film adhesion. The electrode was able to catalyst the electro-oxidation process of ethanol. This phenomenon was exploited as a sensing mechanism to detect the level of ethanol in an alkaline solution. Following the same electrode fabrication strategy, an enzymatic glucose biosensor with acceptable linear range, sensitivity and selectivity was fabricated based on a flexible silver electrode. An activation-free silver electroless metallization was performed to fabricate the electrode. In order to further enhance the design and functionality of the glucose biosensor, a single-use thin film gold electrode was designed and fabricated. The conventional three-electrode configuration consisted of a 50 nm thin gold film used as working and counter electrodes and a thick-film printed Ag/AgCl reference electrode. Thin gold film was deposited on polyethylene terephthalate (PET) by sputtering technique without any binder and the biosensor was patterned by laser ablation technique. The combination of sputtering and laser ablation techniques resulted in producing a very thin and yet uniform gold layer featuring high-reproduction and low-cost at the same time. This promising and unique fabrication technique allowed for mass production of single-use disposable biosensors. To address the limitations of using a biocatalyst (enzyme) for glucose sensing (such as low stability), a thin film of copper oxide was printed on the working electrode of the sensor to serve as nano-catalyst for glucose oxidation reaction. A profound enhancement in electrochemical performance of biosensor was achieved through printing the nano-catalyst film. The developed glucose biosensor was highly suitable for portable single-use applications such as in-vitro glucose monitoring because of its small dimensions and low-cost in manufacturing. The linear range of this biosensor can be used not only for blood glucose measurements but also for non-invasive glucose detection in other biological fluids, which have lower glucose levels such as urine or saliva. Regarding point-of-care application of biosensors to detect biomarkers, single-use electrochemical biosensors for detection of HbA1c and t-tau protein were developed. HbA1c can be used as a robust biomarker for diabetes detection. Anti-HbA1c was used as a selective HbA1c capturing probe. Self-assembled monolayers were employed to covalently immobilize anti-HbA1c on the surface of gold electrode. Differential pulse voltammetry (DPV) was employed as the electrochemical detection method to enhance the sensitivity through minimization of the charging current. This research suggested that a cost-effective, single-use, disposable in vitro HbA1c biosensor could be used alone or together with blood glucose biosensor for better diabetic management applications. Finally, to extend the platform technology to other biomarkers, an in-vitro electrochemical biosensor was developed to monitor the level of T-Tau protein in blood which can be an indicator of neuro-degenerative disorders like Alzheimer’s disease. DPV measurements showed excellent sensing responses with a good calibration curve. Thus, a practical tool for simple detection of T-Tau protein, a biomarker of neuro-degenerative disorders was successfully developed and it could be extended to detect other biomarkers such as P-Tau protein and β-amyloid 42. Finally, the current dissertation was another contribution to realization of bioanalytical devices suitable for point-of-care application based on cost effective disposable electrodes. The developed platform technology can be easily extending to number of different biomarkers for biomedical, food safety and environmental applications.