Diabetes is an international health concern with millions of patients worldwide. There is an unmet need to develop a biosensor technology that is a fast and convenient way to continuously monitor blood glucose levels in diabetics. The proposed work seeks to develop an implantable glucose biosensor which can monitor glucose levels over a long period of time (3-6 months). The proposed implanted glucose biosensor design is distinctively different compared to existing continuous glucose monitoring devices (which have a disappointing lifetime of 3-7 days) and is expected to result in improved long-term efficacy. The innovative aspects of the proposed implantable glucose biosensor includes: (1) a self-cleaning membrane, (2) a fluorescent glucose sensing assay which is contained in the membrane to form the biosensor and (3) an end-use biosensor design which enables complete subcutaneous dwelling and convenient glucose monitoring by the patient. Membrane biofouling is considered to be the leading cause of failure for in vivo biosensors. The proposed """"""""self-cleaning"""""""" membrane is distinct in its approach to control biofouling;it is designed to display active """"""""self-cleaning"""""""" as a result of its thermoresponsive nature. The membrane will be based on a thermoresponsive nanocomposite hydrogel which is thermally cycled via an external heating source. This membrane will be used to house a glucose sensing assay which has been shown to have a larger dynamic range for physiologic glucose levels versus other optical fluorescent glucose sensing methods. Finally, the membrane and sensing assay will be combined to form a biosensor with a cylindrical geometry (expected dimensions of <5 mm diameter and <10 mm length) which permits a convenient end-use design for implantation, replacement and patient glucose monitoring. Ultimately, after injection into the subcutaneous tissue of the wrist, a watch device worn over the implanted biosensor site would contain the optical probe for non-invasive continuous glucose sensing and as well as the thermal heating element for membrane cleaning (i.e. thermal cycling). The multidisciplinary team of Drs. Grunlan, Cote, Clubb and Pishko and the facilities at Texas A&M University will enable the successful completion of the proposed research. The team brings the expertise to develop the proposed membrane and biosensors and conduct the in vitro and in vivo analysis.

Public Health Relevance

Diabetes is a chronic disease affecting over 180 million people worldwide and is associated with over $110 billion dollars of direct medical costs in the USA alone. The conventional finger prick test to monitor blood sugar has severe deficiencies which leads to poor control of blood sugar levels and a long list of serious health complications. Thus, the goal of this work is the development of an implantable glucose biosensor that, because of a self-cleaning membrane to improve biocompatibility, could be used to continuously monitor blood sugar levels over extended periods of time.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Arreaza-Rubin, Guillermo
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Texas Engineering Experiment Station
Biomedical Engineering
Schools of Engineering
College Station
United States
Zip Code
Locke, Andrea K; Means, Anna Kristen; Dong, Ping et al. (2018) A Layer-by-Layer Approach To Retain a Fluorescent Glucose Sensing Assay within the Cavity of a Hydrogel Membrane. ACS Appl Bio Mater 1:1319-1327
Means, A Kristen; Ehrhardt, Daniel A; Whitney, Lauren V et al. (2017) Thermoresponsive Double Network Hydrogels with Exceptional Compressive Mechanical Properties. Macromol Rapid Commun 38:
Hawkins, Melissa L; Schott, Samantha S; Grigoryan, Bagrat et al. (2017) Anti-protein and anti-bacterial behavior of amphiphilic silicones. Polym Chem 8:5239-5251
Locke, Andrea K; Cummins, Brian M; Coté, Gerard L (2016) High Affinity Mannotetraose as an Alternative to Dextran in ConA Based Fluorescent Affinity Glucose Assay Due to Improved FRET Efficiency. ACS Sens 1:584-590
Fei, Ruochong; Means, A Kristen; Abraham, Alexander A et al. (2016) Self-Cleaning, Thermoresponsive P (NIPAAm-co-AMPS) Double Network Membranes for Implanted Glucose Biosensors. Macromol Mater Eng 301:935-943
Rufin, Marc A; Barry, Mikayla E; Adair, Paige A et al. (2016) Protein resistance efficacy of PEO-silane amphiphiles: Dependence on PEO-segment length and concentration. Acta Biomater 41:247-52
Rufin, M A; Gruetzner, J A; Hurley, M J et al. (2015) Enhancing the protein resistance of silicone via surface-restructuring PEO-silane amphiphiles with variable PEO length. J Mater Chem B 3:2816-2825
Cummins, Brian M; Li, Mingchien; Locke, Andrea K et al. (2015) Overcoming the aggregation problem: a new type of fluorescent ligand for ConA-based glucose sensing. Biosens Bioelectron 63:53-60
Locke, Andrea K; Cummins, Brian M; Abraham, Alexander A et al. (2014) PEGylation of concanavalin A to improve its stability for an in vivo glucose sensing assay. Anal Chem 86:9091-7
Cummins, Brian M; Garza, Javier T; Coté, Gerard L (2013) Optimization of a Concanavalin A-based glucose sensor using fluorescence anisotropy. Anal Chem 85:5397-404

Showing the most recent 10 out of 11 publications