Managing glucose levels can be challenging for individuals with type 1 diabetes. The artificial pancreas (AP) automates glucose control by delivering insulin with dosages adjusted in real-time and in response to measurements by a continuous glucose monitor. However, despite automation using advanced control algorithms, patients reliant on the AP risk hyper and hypoglycemia, which can result from discrepancies between administered and circulating insulin levels. Thus, continuous monitoring of circulating insulin concentrations could tighten glucose regulation while improving safety and patient response to treatment. Therefore, we aim to develop a real-time insulin biosensor for APs modelled upon the human insulin receptor (InR). Through directed evolution of large (~109) phage display libraries of InR variants, we have selected soluble, specific insulin binders, which were then screened for fast binding characteristics suitable for real-time in vivo insulin sensing. To obtain a dose-dependent optical signal upon insulin binding, the selected InR variants will be developed for FRET-based sensing using site-directed, bioconjugation techniques for fluorophore labelling. We aim to transition these variants into E. coli and mammalian expression platforms to optimize protein expression, assess optical signaling, insulin binding kinetics and sensitivity.

Towards the development of a real-time insulin biosensor: Engineering the insulin receptor

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.