Enzymatic fluorescent microsphere glucose sensors: Evaluation of response under dynamic conditions

Most previous attempts at the development of a "smart tattoo" for glucose monitoring in diabetes-implantable fluorescent microspheres that can be implanted intradermally and interrogated transdermally using light-have focused on the encapsulation of a competitive binding assay for glucose within hydrogel microspheres or polyelectrolyte microcapsules. We recently reported on the development of a microsphere sensor based on an enzymatic scheme, combined with an oxygen-quenched fluorescent reporter element. A novel feature of this design is the use of polyelectrolyte multilayer nanofilms, which are assembled stepwise on the surface of the microspheres, for modulation of glucose and oxygen mass transport, allowing them to be designed for sensitive and safe operation within the "oxygen deficit" present in the skin. In this work, a flow-through sensor testing apparatus was used to demonstrate the reversible response of the sensors under controlled, dynamic conditions. The sensors were shown to be sensitive over at least 0-140 mg/dL glucose, with a response time of less than 2 min. This report also identifies some current problems with the approach, and gives potential solutions towards the development of a practical implantable sensor for glucose monitoring in diabetes.