This Small Business Innovation Research (SBIR) Phase I project aims to develop a wireless, needle implantable miniaturized (0.5 x 0.5 x 5 mm) sensor for continuous glucose monitoring, with provisions for internal self-calibration without the need for frequent, external fingerpricking. The proposed internal self-calibration is enabled through the use of novel pulse-mode sensor operation which quantifies sensitivity drifts internally. Pulsed-mode operation also results in improved power management as well as long sensor lifetime. Biocompatible coatings release various tissue response modifiers to control tissue inflammation. The device can be inserted under the skin and similarly removed via a needle, thus avoiding surgical implantation/removal. Phase-I seeks to develop the internal self-calibration routines and demonstrate proof-of-concept ex vivo. Phase II will focus on extensive in vivo studies thereby facilitating commercialization.
The broader/commercial impacts of this research are enormous considering that there is an urgent need for continuous glucose monitoring devices in view of the growing number of diabetics. Implantable glucose sensors that afford minimal user intervention present a viable alternative, although their "user-independent" nature is often undermined by necessity for frequent external calibration by finger-pricking. The proposed project will result in a truly "user-independent" operation of implantable glucose sensors. In addition, the proposed internal calibration methodology is universal to all biosensors used for metabolic monitoring, rendering competitive market edge and job creation. The project will be performed in the Technology Incubation Program (TIP), at University of Connecticut. This industrial/academic collaboration provides training for the graduate and undergraduate students in the field ofbiosensors.
Summary of the Research Performed: Over the past three years, Biorasis Inc. has been developing a totally implantable, miniaturized (0.5 x 0.5 x 5 mm) biosensor platform capable of continuous glucose monitoring. The device can be inserted under the skin and similarly removed via a needle, thus avoiding surgical implantation/removal and also affords wireless operation. The localized release of various tissue response modifiers has afforded effective inflammation/fibrosis suppression, and neo-angiogenesis. This has eliminated the major 1-10 days sensor failure processes, and allowed prolonged sensor operation. However, during long-term operation, sensor sensitivity gradually drifts contributing to inaccuracies in the measured glucose levels. The Phase I NSF/SBIR project entitled "Self Calibrating, Wireless, Needle Implantable Sensor for Continuous Glucose Monitoring" aimed to develop a continuous glucose monitoring sensor with provisions for an internal calibration routine that accounts for a number of long-term sensory drifts and permits self-calibration. Phase-I developed an internal calibration routine and demonstrate proof-of-concept in an ex vivo environment (serum model). The proposed Phase II is intended to extend the developed concept in an in vivo environment as well development the proximity communicator and associated electronics. The Phase-I of the NSF-SBIR has been successfully accomplished and the scientific accomplishments as well as the expertise gained will aid in a timely of the Phase-II project. The Phase-I has resulted in 4 publications (2 accepted, 1 submitted and 1 under preparation) and 6 conference presentation, which are presented below. Publications: L. Qiang, S. Vaddiraju, D. Patel, F. Papadimitrakopoulos, ‘Edge-plane microwire electrodes for highly sensitive H2O2 and glucose detection’, Biosens. Bioelec. 2011; 26: 3755-3760. S. Vaddiraju, A. Legassey, Y. Wang, L. Qiang, D. J. Burgess, F. C. Jain, F. Papadimitrakopoulos, ‘Design and Fabrication of a High-Performance Electrochemical Glucose Sensor’, J. Diabetes Sci Technol. 5(5) 1044-1051 Robert A Croce Jr., SanthiSagar Vaddiraju, Jun Kondo, Yan Wang, Liang Zuo, Kai Zhu, Syed K. Islam, Diane Burgess, Faquir C. Jain and Fotios Papadimitrakopoulos, ‘A Miniaturized Transcutaneous System for Continuous Glucose Monitoring’, Biomedical Microdevices, Submitted (Dec. 29, 2011). S. Vaddiraju, A. Legassey, Y. Wang, L. Qiang, D. J. Burgess, F. C. Jain, F. Papadimitrakopoulos, ‘Microsphere Degradation in Outer Hydrogel Membranes as Means to Enhance Glucose Permeability and Sensor Sensitivity With Time’, Manuscript under preparation. Conference Presentations: L. Qiang, S. Vaddiraju, F. Papadimitrakopoulos, ‘Highly sensitive in vivo glucose biosensor based on selective deposition of PPD on microelectrode’ Gordon Research Conference, Macromolecular Materials, Ventura, CA, 2011. F. Papadimitrakopoulos, S. Vaddiraju, D. J. Burgess, F. C. Jain, ‘Miniaturized, Needle Implantable, Wireless Biosensor for Continuous Monitoring of Multiple Bio-analytes’, DARPA/FDA Workshop-Expanding In Vivo Biomarker Detection Devices, Arlington, VA, 2011. Y. Wang, S. Vaddiraju, L. Qiang, F. Papadimitrakopoulos, D.J. Burgess, ‘Glucose diffusive characteristics of PVA Hydrogel/PLGA microsphere composite coatings for implantable biosensors’ 38th Annual Meeting & Exposition of the Controlled Release Society, National Harbor, MD, 2011. Robert Croce Jr., S. Vaddiraju, Liang Zuo, Melika Roknshariki, Kai Zhu, Mukesh Gogna, Pawan Gogna, Fotios Papadimitrakopoulos, Syed Islam, Faquir Jain, ‘Implantable Biosensing Platform Using Photovoltaic Powering and Optical Communication Links’, Biomedical Engineering Society Annual Meeting, Hartford, CT, 2011. Robert A. Croce Jr., Santhisagar Vaddiraju, Liang Zuo, Melika Roknshariki, Kai Zhu, Mukesh Gogna, Pawan Gogna, Fotios Papadimitrakopoulos, Syed Islam and Faquir Jain, ‘Needle-Implantable Platform for Continuous Glucose Monitoring Using Photovoltaic Powering and Optical Communication,’ Diabetes Technology Meeting, San Francisco, CA, 2011. L. Qiang, S. Vaddiraju, Y.Wang, R. Croce, D.J. Burgess, F. Jain, F. Papadimitrakopoulos, "Edge-plane microwire electrodes for high sensitive glucose detection", Diabetes Technology Meeting, San Francisco, CA, 2011.
