An implantable biosensor array for personalized therapy applications

At present, most of the tests involved in personalized medicine are complex and must be conducted in specialized centers. The development of appropriate, fast and inexpensive diagnostic technologies can encourage medical personnel in performing preventive tests, providing the driving force to push users, industry and administrations to the adoption of personalized therapy policies. In this respect, the development of new biosensors for various healthcare applications needs may represent a concrete incentive. The objective of this PhD project is the development of a fully implantable biosensor plat- form for personalized therapy applications. The thesis present innovative research on the electrochemical detection of common marketed drugs, drug cocktails, glucose and ATP with biosensors based on cytochromes P450 and different oxidases. The inclusion of carbon nan- otubes provided increased sensitivity and detection limit, enabling the detection of several drugs in their therapeutic range in undiluted human serum. A miniaturized, passive substrate capable to host 5 independent biosensor electrodes, a pH sensor, a temperature sensor as well as an interface for the signal processing electron- ics has been designed, microfabricated and tested. Different and reproducible nano-bio- functionalization for the single electrodes was obtained with high spatial resolution via selec- tive electrodeposition of chitosan/carbon nanotubes/enzyme solutions at the various elec- trodes. The array, completely fabricated with biocompatible materials, was then integrated with a CMOS circuit and a remote powering coil for the realization of a fully implantable device. The assembled system has been packaged with an inner moisture barrier in parylene C, to prevent circuit corrosion and toxic metals leaking, and an external biocompatible silicone shell to improve the host tolerance and reduce the local inflammation. The efficacy of the parylene barrier, as well as the toxicity of carbon nanotubes, has been assessed with in-vitro cytotoxicity tests conform to the ISO-109931 standards. The final packaged device was then implanted in mice to assess its short-term biocompatibility. Comparison between 7 and 30 days in in vivo implantations showed significant reduction of the inflammatory response in time, suggesting normal host recovery.