Optogenetic and biosensing technologies for a bioartificial pancreas system

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Almost ten percent of the U.S. population suffers from diabetes. The associated healthcare costs for this disease are the highest amongst major maladies. The goal of this research project is to engineer a novel bioartificial pancreas (BAP) device. The BAP device will require no patient intervention. It will contain human pancreatic beta-cells, which are cells whose insulin secretion is enhanced by blue light that is free of significant side effects. The BAP device also will continuously monitor and respond to blood glucose level. This feature should improve the regulation of blood glucose relative to daily insulin injection therapies. A successfully developed BAP device would reduce many of the long-term health complications resulting from large blood glucose swings associated with daily injection therapies. The planned outreach activities for this project feature inter-disciplinary training and research opportunities for high school, undergraduate and graduate students in STEM fields.The goal of this research project is to build an autonomous, closed-loop BAP platform. Glucose-stimulated insulin secretion will be regulated by blue light, and embedded light-emitting diodes (LEDs) regulated wirelessly will control the blue light application. The light will effect a change in a photo-sensitive adenylyl cyclase. Coupling the BAP to a transdermally-implanted, thread-based wireless glucose sensor will allow for autonomous, closed-loop operation of the device. Specific project tasks will include: (i) generating human beta-cells with photosensitive glucose-stimulated insulin secretion, (ii) designing a hybrid LED/hydrogel device for delivery of the photo-sensitive adenylyl cyclase-expressing human beta-cells, (iii) realizing flexible glucose-sensing threads and wireless circuitry and (4) integrating them with the hybrid LED/hydrogel. The project entails addressing significant fundamental challenges in interfacing glucose sensors, electronics, and LEDs with the function of living components for optimal operation in vivo. This advance will offer broadly applicable insights for the manufacturing of implantable devices. The generated photo-sensitive adenylyl cyclase-expressing human beta-cells will be a valuable resource for screening diabetes drug candidates and for increasing understanding of pancreatic cell function.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.