Implantable Multi-panel Platform for Continuous Monitoring of Exogenous and Endogenous Metabolites for Applications in Personalized Medicine

Nowadays, scientific advances are leading to the discovery of newer, better, more targeted treatments that will improve the human health. However, despite the promising results and the major advantages in treatments offered to patients, these personalized medical treatments are limited to few cases. Translational medicine research with animals is needed to find innovative, safe and life-saving solutions for patients, especially in drug development. Although technological improvements may lead one day to the end of animal testing, today those strategies are not sufficient, due to the complexity of living organisms. The living conditions of these animals are of primary importance because high stress levels can affect the experimental results. In this respect, the monitoring of the animals in a small living space by means of a fully implantable device, can contribute to minimize the human intervention, increasing the comfort for the animals. The objective of this thesis is the design and characterization of a fully implantable biosensor array for the real-time detection of endogenous and exogenous metabolites, for the monitoring of small caged animals in drug development, and for future applications in personalized medicine. The fully implantable device consists of: a passive sensing platform consisting of an array of four independent electrochemical biosensors, together with a pH sensor and a temperature sensor for the optimization of the sensing performances in different physiological conditions; integrated circuits capable of performing multiple electrochemical measurements; a coil for remote powering of the integrated circuit and the short-range data transmission to an external device; a membrane packaging ensuring measurements with high signal-to-noise ratio, biocompatibility and selectivity against possible interfering molecules in biological fluids. • In vitro monitoring of four anti-cancer drugs and an anti-inflammatory drug within the pharmacological ranges in undiluted human serum; • Demonstration of the in vitro functionality of the complete system, showing that the external powering system correctly operate the device, and receive the data from the sensors; • In vivo biocompatibility tests of the packaging, showing after 30 days a significant reduction of the inflammatory response in time, suggesting normal host recovery; • In vivo continuous monitoring of an anti-inflammatory drug, demonstrating the proof of-concept of the system for future personalized medicine applications.

    Keywords: biosensors ; drug monitoring ; carbon nanotubes ; cytochrome P450 ; packaging ; implantable

    Thèse École polytechnique fédérale de Lausanne EPFL, n° 6604 (2015)
    Programme doctoral Microsystèmes et Microélectronique
    Faculté informatique et communications
    Institut des systèmes informatiques et multimédias
    Laboratoire des systèmes intégrés (IC/STI)
    Jury: Prof. Catherine Dehollain (présidente) ; Prof. Giovanni De Micheli, Dr Sandro Carrara (directeurs) ; Prof. Nico de Rooij, Dr Maaike Op de Beeck, Dr Victor Erokhin (rapporteurs)

    Public defense: 2015-9-11


    Record created on 2015-09-02, modified on 2016-08-09

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