Glucose sensors have had many paradigm shifts, beginning with using urine, to point of care blood, now being approved for implant. This review covers various aspects of the sensors, ranging from the types of surface chemistry, and electron transduction. All the way to the algorithms, and filters used to alter and understand the signal being transduced. Focus is given to Dr. Hellerâ’s work using redox mediators, as well as Dr. Sode in his advances for direct electron transfer. Simple process of designing sensors are described, as well as the possible errors that may come with glucose sensor use. Finally, a small window into the future trends of glucose sensors is described both from a device view point, as well as organic viewpoint. Using this history the initial point of care sensor for insulin published through LaBelle’s lab is reevaluated critically. In addition, the modeling of the possibility of continuously measuring insulin is researched. To better understand the design for a continuous glucose sensor, the basic kinetic model is set up, and ran through a design of experiments to then optimized what the binding kinetics for an ideal insulin molecular recognition element would be. In addition, the phenomena of two electrochemical impedance spectroscopy peaks is analyzed, and two theories are suggests, and demonstrated to a modest level.

Currently, the management of diabetes mellitus (DM) involves the monitoring of only blood glucose using self-monitoring blood glucose devices (SMBGs) followed by taking interventional steps, if needed. To increase the amount of information that diabetics can have to base DM care decisions off of, the development of an insulin biosensor is explored. Such a biosensor incorporates electrochemical impedance spectroscopy (EIS) to ensure an extremely sensitive platform. Additionally, anti-insulin antibody was immobilized onto the surface of a gold disk working electrode to ensure a highly specific sensing platform as well. EIS measurements were completed with a 5mV sine wave that was swept through the frequency spectrum of 100 kHz to 1 Hz on concentrations of insulin ranging from 0 pM to 100 μM. The frequency at which the interaction between insulin and its antibody was optimized was determined by finding out at which frequency the R2 and slope of the impedance-concentration plot were best. This frequency, otherwise known as the optimal binding frequency, was determined to be 459 Hz. Three separate electrodes were developed and the impedance data for each concentration measured at 459 Hz was averaged and plotted against the LOG (pM insulin) to construct the calibration curve. The response was calculated to be 263.64 ohms/LOG(pM insulin) with an R2 value of 0.89. Additionally, the average RSD was determined to be 19.24% and the LLD was calculated to be 8.47 pM, which is well below the physiological normal range. These results highlight the potential success of developing commercial point-of-care insulin biosensors or multi-marker devices operating with integrated insulin detection.

Self-monitoring of blood glucose (SMBG) is the standard of care in diabetes management. Current technologies for SMBG are based upon enzymatic electrochemical (amperometric) sensing. To increase the sensitivity and specificity of current devices, a novel method of detecting glucose using electrochemical impedance spectroscopy (EIS) technology is explored. To test the ability of EIS methods to detect glucose, the enzyme glucose oxidase (GOx) was fixed to gold electrodes through the means of a specific immobilization process. Once GOx was fixed to the gold electrode surface, a 5 mV sine wave sweeping frequencies from 100 kHz to 1 Hz was induced at a glucose range 0-500 mg/dL mixed with a ferricyanide redox mediator. Each frequency in the impedance sweep was analyzed for highest response and R-squared value. The frequency with both factors optimized is specific for the glucose-GOx binding interaction, and was determined to be 1.17 kHz in purified solutions. Four separate electrodes were constructed and date from each were averaged. The correlation between the impedance response and concentration at the low range of detection (0-100 mg/dL of gluose) was determined to be 3.19 ohm/ln (mg/dL) with an R-squared value of 0.86. Its associated lower limit of detection was found to be 41 mg/dL. The same frequency of 1.17 kHz was then verified in whole blood under the glucose range of 0-100 mg/dL while diluting the blood to observe effect. As the blood concentration increased, the response of the sensor decreased logarithmically. The maximized blood detection volume was determined to be 25% whole blood suggesting dilution, coatings, or filtration is required for future adaptation. The above data confirms that EIS offers a new method of glucose detection as an alternative technology for SMBG and offers improved detection at lower concentrations of glucose. The unique frequency response of individual markers allows for modulation of signals so that several markers could be measured with a single sensor. Future work includes assessment of other diabetes associated biomarkers that can be measured on a single sensor, integration testing and tuning of the biomarkers, impedance-time sensing development, and finally, testing on control subjects.