Development of a Minimally Invasive Flexible Continuous Glucose Sensor

Every year, hundreds of millions of people worldwide are affected by diabetes mellitus. While the symptoms and treatment regimens vary from each individual, a lifelong commitment to monitoring and balancing blood glucose concentration can be expensive and psychologically exhausting. To provide patients with an increased ability to control this disease, continuous blood glucose biosensors are used to provide on demand measurements of relevant biomarkers. This allows users to readily regulate the concentration of glucose in their blood. Traditional sensor devices analyze small samples of blood, requiring invasive techniques of obtaining the sample. There is also a lack of continuous glucose measurements in these devices, as fluctuating analyte concentrations during day-to-day activities cannot be monitored. To address these limitations, a device that utilize soft and flexible materials that can integrate with the skin and offer a minimally invasive method to continuously detect glucose concentration is proposed. A temporary tattoo platform that incorporates a sensitive electrode system can provide the patient with the ability to comfortably monitor their condition. Flexible bioelectronics has emerged as a promising platform to develop biosensors because of their seamless integration into biological systems. The abundance of soft and flexible tissues within the body interacts well with other flexible systems, hence the need to develop devices that interact with the body in the same way.<br/><br/>This glucose sensor device extracts interstitial fluid from below the skin through reverse iontophoresis, a process by which low current is precisely applied to the epidermis. Following this extraction process, the fluid interfaces with a three-electrode system that utilizes a substrate-enzyme interaction to detect glucose through a hydrogen peroxide intermediate. The electrodes were fabricated utilizing a PCB printer to extrude conductive inks onto a flexible polyimide substrate. The system was created from a carbon-graphite Prussian blue mediator paste which contains redox active molecules necessary for detection of the hydrogen peroxide intermediate. Onto the surface of the working electrode, the glucose oxidase enzyme was immobilized along with a solution of single walled carbon nanotubes and chitosan. Upon binding of glucose within the interstitial fluid to the glucose oxidase enzyme, the hydrogen peroxide by-product can be measured in terms of current by the working electrode.<br/><br/>To determine electrochemical function of the sensors, a variety of experiments including cyclic voltammetry, linear sweep voltammetry, amperometry, and chronography were used. These techniques demonstrated the performance of the Prussian blue working electrode by recording oxidation and reduction peaks, which align precisely with commercially available alternatives. Additionally, characterization of the reference and counter electrodes indicate proper electrochemical function of the entire sensor system. Following this analysis, the ability for the electrode to detect the hydrogen peroxide intermediate was evaluated. In target concentrations ranging from 2mM/L to 12mM/L of hydrogen peroxide, the device clearly possesses the ability to systematically and consistently respond to various H₂O₂ concentrations. The current density response is then used to develop a linear response curve to correlate H₂O₂with electrical output.<br/><br/>Within this flexible biosensor system, hydrogen peroxide concentration was related to electrical output quantitatively. Hydrogen peroxide’s direct relationship with glucose upon binding with glucose oxidase suggests this platform can provide a promising alternative from conventional methods of detecting glucose within the blood.