Thin Film Based Biocompatible Sensors for Physiological Monitoring

Yihao Zhu, University of South Carolina - Columbia


The development and evolution of physiological sensors, from wearable to implantable, has enabled long term continuous physiological monitoring, making possible for the out-of-clinic treatment and management of many chronic illnesses, mental health issues and post-surgery recovery. This technology advance is gradually changing the definition of health care and the way it is delivered, from clinic/emergency room to patient’s own environment. In this dissertation, three general types of sensors have been proposed for physiological monitoring of blood pressure, oxygen content and electrolyte ion concentration level in human body, respectively. The study proved the device concepts and shows promising results with the prototype sensors for possibilities of various biomedical applications.

In the pressure sensor development, we have designed, fabricated and characterized a biocompatible, flexible pressure sensor using Au thin film patterned polydimethylsiloxane (PDMS) membrane for bio-implant application. Strain induced changes in Au film resistance was used to perform quantitative measurement of absolute pressure. The sensor was extensively modeled through COMSOL-based finite element simulations for design and performance predication. Three prototype sensors fabricated with different membrane thickness of 50, 100 and 200 μm were studied. Very high constant sensitivities of 0.1 /Kpa, 0.056 /Kpa and 0.012 /Kpa, respectively, were observed over their effective measurement ranges. The high sensitivities are attributed to the formation of microcracks in Au film resistor when the sensors are subjected to pressure. Interestingly, the formation of microcracks seemed to be quite reversible within certain pressure range. In addition, the correlation of sensitivity and effective sensing range with membrane thickness was studied for the three sensors. It was found that the device sensitivity increased with the decrease in membrane thickness but at the expense of its effective sensing range. This observation corresponds well to the simulation results. Response times of all the three sensors were found to be in millisecond range, and the best rms noise limited resolution was 0.07 mmHg (9 Pa).

In the oxygen sensor development, oxygen sensing characteristics of In2O3 thin film at room temperature have been investigated through conductivity measurements using interdigitated metal finger patterned devices. We observed that the O2 sensitivity gets affected very significantly in presence of moisture, as well as with applied dc bias. The O2 sensitivity was found to increase several times in moist ambient compared to dry ambient condition. Higher dc bias also dramatically improved the sensitivity, which varied more than two orders of magnitude as the dc bias was increased from 0.5 to 10 V. We propose that the observed increase in sensitivity in presence of moisture is caused by enhanced surface electron density on In2O3 thin film resulting from the donation of electrons by the chemisorbed water molecules. The adsorption of O2 molecules, which subsequently formed O2- ions, leads to chemical gating of the sensor devices, which under larger dc bias produced a higher fractional change in current leading to higher sensitivity.

In the development of biocompatible ion sensor, a novel ion sensitive field effect transistor (ISFET), fabricated using chemical vapor deposition (CVD) derived graphene, has been proposed and demonstrated for real-time K+ efflux measurement from living cells. Ion concentration change in electrolyte solution is transduced into an electrical (current) signal due to surface potential change in graphene (the material constructing the electrical conducting channel of the ISFET). Graphene, a two-dimensional carbon allotrope recently discovered in 2004, has a number of exceptional material properties which is much superior to silicon with respect to developing sensors for bio-detection applications, such as its ultra-high carrier mobility, excellent biocompatibility and very good chemical stability. In this work, we have extensively studied the I-V and C-V characteristics of the graphene ISFET in both electrolyte and physical buffer solutions with different K+ concentration. Valinomycin coating of the graphene ISFETs has been utilized to enhance ionic detection sensitivity and impart selectivity. With the ionophore modified graphene ISFET, we have successfully demonstrated real-time detection of K+ concentration change in both electrolyte and physiological buffer solutions.

Moreover, we have conducted cell based real-time K+ efflux measurement utilizing commercial Si based ISFETs, proving the concept of ISFET based ion channel screening assay for drug discovery. On the other hand, the prototype graphene based ISFET has also been evaluated for K+ efflux detection using a salt bridge configuration, showing promising sensing results for future study.

In the fabrication of graphene ISFET, we found the epoxy glue used for the sensor encapsulation had significant effect on the electric transport properties of graphene including conductivity, carrier concentration and field effect mobility. N-type doping effect of the epoxy on graphene has been carefully identified and confirmed by systematic experiments, which is promising for new alternative approach to dope graphene.