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Innovative Enabling Micro-Nano-Bio-technologies for Implantable systems in molecular medicine and personalized therapy - Project prolongation

English title Innovative Enabling Micro-Nano-Bio-technologies for Implantable systems in molecular medicine and personalized therapy - Project prolongation
Applicant Carrara Sandro
Number 147694
Funding scheme Sinergia
Research institution Laboratoire des systèmes intégrés EPFL - IC - ISIM - LSI
Institution of higher education EPF Lausanne - EPFL
Main discipline Microelectronics. Optoelectronics
Start/End 01.08.2013 - 31.01.2015
Approved amount 533'900.00
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All Disciplines (3)

Discipline
Microelectronics. Optoelectronics
Immunology, Immunopathology
Pathophysiology

Keywords (6)

implantable biochip ; P450 cytocrhomes; gut inflammation; continuous monitoring sensors; personalized therapy; biomarkers and drugs

Lay Summary (Italian)

Lead
Attualmente, non ci sono tecnologie mature per sistemi completamente impiantabili che consentano il monitoraggio di farmaci nel sangue, nel siero, o nel tessuto sotto-cutaneo dei pazienti. Lo scopo di questo progetto è lo sviluppo di un biochip impiantabile per il monitoraggio di farmaci in terapia personalizzata. Al fine di raggiungere gli scopi del progetto, si propone un approccio altamente multidisciplinare data la complessità del sistema e il settore medico di applicazione.
Lay summary

Motivazione Scientifica, obiettivi e ruolo dei partner

La motivazione del progetto risiede nel monitoraggio diretto nella personalizzazione della medicina specialmente in quei settori che prevedono l’uso di farmaci con elevati effetti collaterali, esempio alta tossicità.

Il progetto richiede un’elevata multidisciplinarità nei settori di micro e nano fabbricazione, biochimico, farmacologico, e medico. Questo al fine di raggiungere al meglio i seguenti obiettivi:

1. Sviluppo di nano-bio-sensori (S. Carrara/EPFL – ingegneria)

2. Fabbricazione di un biochip con potenza trasmessa (C. Dehollain / EPFL – ingegneria)

3. Effetti dei farmaci in cellule-T (F. Grassi/IRB medicina)

4. Farmaco-cinetica e studio di proteine mutanti (U. Von Mandach /Ospedale Universitario di Zurigo – Farmacologia)

Rilevanza Sociale ed Economica

La rilevanza sociale del progetto risiede in una migliore tecnologia diagnostica mentre quella economica è nel settore del mercato farmaceutico. Una parte rilevante dell’intera economica svizzera è guidata dall’industria farmaceutica. Anche nel 2008, un anno di particolare crisi a livello mondiale con l’indice Down Jones che ha chiuso vicino al 40% del suo valore d’inizio anno, l’azienda farmaceutica Novartis ha chiuso l’anno con un guadagno pari al 9%. Questo dimostra che il settore farmaceutico è uno dei più importanti anche in un momento di crisi. Un tale chip impiantabile rappresenta uno strumento unico per lo sviluppo industriale di nuovi farmaci in Svizzera.

Direct link to Lay Summary Last update: 24.07.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
A System for Wireless Power Transfer of Micro-Systems In-Vivo Implantable in Freely Moving Animals
Enver G. Kilinc et al (2014), A System for Wireless Power Transfer of Micro-Systems In-Vivo Implantable in Freely Moving Animals, in IEEE SENSORS JOURNAL,, 522.
An Integrated Control and Readout Circuit for Implantable Multi-Target Electrochemical Biosensing
Sara S. Ghoreishizadeh et al (2014), An Integrated Control and Readout Circuit for Implantable Multi-Target Electrochemical Biosensing, in IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS,, 8, 891.
ATP-Gated Ionotropic P2X7 Receptor Controls Follicular T Helper Cell Numbers in Peyer’s Patches to Promote Host-Microbiota Mutualism
Michele Proietti et al. (2014), ATP-Gated Ionotropic P2X7 Receptor Controls Follicular T Helper Cell Numbers in Peyer’s Patches to Promote Host-Microbiota Mutualism, in Immunity, 1.
Continuous monitoring of Naproxen by a cytochrome P450-based electrochemical sensor
Baj-Rossi C. Jost T. R. Cavallini A. Grassi F. De Micheli G. & Carrara S. (2014), Continuous monitoring of Naproxen by a cytochrome P450-based electrochemical sensor, in Biosensors and Bioelectronics, 53, 283-287.
Do Carbon Nanotubes contribute to Electrochemical Biosensing?
Sandro Carrara et al. (2014), Do Carbon Nanotubes contribute to Electrochemical Biosensing?, in Electrochimica Acta, 128, 102.
Electrochemical Biochip for Applications to Wireless and Batteryless Monitoring of Free-Moving Mice
Camilla Baj-Rossi et al (2014), Electrochemical Biochip for Applications to Wireless and Batteryless Monitoring of Free-Moving Mice, in IEEE EMBC Conference, Chicago.
Full Fabrication and Packaging of an Implantable Multi-Panel Device for Monitoring of Metabolites in Small Animals
Camilla Baj-Rossi et al (2014), Full Fabrication and Packaging of an Implantable Multi-Panel Device for Monitoring of Metabolites in Small Animals, in IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS,, 636.
Servo-Controlled Remote Powering and Low-Power Data Communication of Implantable Bio-Systems for Freely Moving Animals
E.G. Kilinc et al. (2014), Servo-Controlled Remote Powering and Low-Power Data Communication of Implantable Bio-Systems for Freely Moving Animals, in IEEE Biomedical Circuits and Systems Conference (BioCAS), Lausanne.
Sub-mW Reconfigurable Interface IC for Electrochemical Sensing
Sara Ghoreishizadeh et al (2014), Sub-mW Reconfigurable Interface IC for Electrochemical Sensing, in IEEE Conference BioCAS 2014, Lausanne.
A Linear Approach to Multi-Panel Sensing in Personalized Therapy for Cancer Treatment
Camilla Baj-Rossi et al (2013), A Linear Approach to Multi-Panel Sensing in Personalized Therapy for Cancer Treatment, in IEEE SENSORS JOURNAL, 4860.
Fabrication and Packaging of a Fully Implantable Biosensor Array
Camilla Baj-Rossi et al (2013), Fabrication and Packaging of a Fully Implantable Biosensor Array, in IEEE Intenrational Conference BioCAS 2013, Rotterdam (NL).
Short-Range Remote Powering for Long-Term Implanted Sensor Systems in Freely Moving Small Animals
E.G. Kilinc et al. (2013), Short-Range Remote Powering for Long-Term Implanted Sensor Systems in Freely Moving Small Animals, in IEEE Sensors , 1787.
A neural approach to drugs monitoring for personalized medicine
Benjamin Staar et al., A neural approach to drugs monitoring for personalized medicine, in IJCNN 2015.
Faradic Peaks Enhanced by Carbon Nanotubes in Microsomal Cytochrome P450 Electrodes
C. Baj-Rossi et al, Faradic Peaks Enhanced by Carbon Nanotubes in Microsomal Cytochrome P450 Electrodes, in Electroanalysis, 1.
Full System for Translational Studies of Personalized Medicine with Free-Moving Mice
Sandro Carrara et al., Full System for Translational Studies of Personalized Medicine with Free-Moving Mice, in IEEE ISCAS Conference, Lisbon.

Collaboration

Group / person Country
Types of collaboration
Dr. Dmitri Davydov, Skaggs School of Pharmacy, University of California at San Diego, (US) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Eric Johnsson, Molecular and Experimental Medicine, Scripps California Campus (US) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Dr. Ing. Francesco Valgimigli and Fabrizio Mastrantonio/A. Menarini Diagnostics S.p.A. Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration
Prof. Elisabetta Chicca, University of Bielefeld (DE) Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Dr. Gianfranco Merizzi/Medestea Research & Production S.p.A Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Industry/business/other use-inspired collaboration
Prof. Franco Maloberti/University of Pavia Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Harvard Medical School United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Dr. Fabio Acocella/Veterinary Faculty, University of Milan, Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
Prof. Willem H. Koppenol, Inorganic Chemistry Department, ETH Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof Victoria Shumyantseva/Russian Academy of Biomedical Science Moscow Russia (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
IEEE International BioCAS 2014 (Biomedical Circuits and Systems) Talk given at a conference Servo-Controlled Remote Powering and Low-Power Data Communication of Implantable Bio-Systems for Freely Moving Animals 22.10.2014 Lausanne, Switzerland Dehollain Catherine; Kilinc Enver Gürham;
IEEE BioCAS 2014 (Biomedical Circuits and Systems) Talk given at a conference Sub-mW Reconfigurable Interface IC for Electrochemical Sensing 22.10.2014 Lausanne, Switzerland Baj-Rossi Camilla; Carrara Sandro;
IEEE EMBC 2014 Talk given at a conference 6. Electrochemical Biochip for Applications to Wireless and Batteryless Monitoring of Free-Moving Mice 26.08.2014 Chicago, United States of America Baj-Rossi Camilla; Carrara Sandro;
PhyCS, International Conference on Physiological Computing Systems, organized in conjunction with Sensornets 2014 Individual talk A tiny laboratory under the skin 17.01.2014 Lisbon, Portugal Carrara Sandro;
IEEE Sensors Conference Individual talk Technologies for an Implantable Nano-Bio-Sensing Laboratory 01.11.2013 Baltomore, United States of America Carrara Sandro;
IEEE BioCAS 2013 (Biomedical Circuits and Systems) Talk given at a conference Fabrication and Packaging of a Fully Implantable Biosensor Array 31.10.2013 Rotterdam, Netherlands Carrara Sandro; Baj-Rossi Camilla; Dehollain Catherine; Kilinc Enver Gürham;


Self-organised

Title Date Place

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Innovative systems for drug monitoring in personalized therapy IEEE Life Sciences Newsletter International 2014

Associated projects

Number Title Start Funding scheme
127547 Innovative Enabling Micro-Nano-Bio-technologies for Implantable systems in molecular medicine and personalized therapy 01.01.2010 Sinergia
157139 Continuous Monitoring of Anesthetics Concentration to Control Anesthesia Delivery (acronym: CoMofA) 01.03.2015 Project funding

Abstract

A biochip system capable of continuous monitoring of drugs and biomarkers in blood, or in sub-cutaneous districts, constitutes a major breakthrough in molecular medicine for per-sonalizing therapy of complex diseases. The global aim of the present research is to undertake a multidisciplinary approach to substantially advance the state-of-the-art of on-line-monitoring implantable-devices in personalized medicine. In the previous sinergia project, we have developed components and systems for measuring inflammatory mediators and drugs. These results and progresses have been published in peer-reviewed international journals with high impact factor, as well as communicated at international meetings, and presented in keynote speeches. Nevertheless, the proposed technology has generated new challenges; we believe these novel technological issues merit to be specifically addressed. In particular: (i) some tested drugs revealed to be interfering on the same sensors based on the P450 cytochromes; (ii) the possibility to specifically design the P450 cytochromes opens to improve the drug/probe interactions on the sensor array; (iii) the designed remote powering system is able to supply the required energy but an external control unit is desirable to optimize the energy transfer; (iv) the need of a better following of the disease prognosis requires identifying better molecular mark-ers. Therefore, we propose herein a further research plan to specifically address these newly emerged issues. Moreover, this new research plan will allow the PhD students involved in the previous project to successfully complete their doctoral programs. The aim of this project is to address the novel issues listed above that emerged during the first stage of the research. To this end, the following specific goals will be pursued during the project prolongation:(i) Development of innovative multi-panel sensor array towards simultaneous detection of both disease metabolites and multiple drugs, including linear and other approaches to improve sensors specificity at level of system integration, (ii) Design and implementation of an external control unit to improve the efficiency of the Remote Powering System for the final tests in vivo with Freely Moving Mice (iii) Monitor active drugs and new biomarkers concentration in vivo opening to a dra-matic improve of the compliance of therapeutic regimens for diseases with com-plex pathogenesis,(iv) Design, cloning, and expressing mutants of some probe P450 isoforms in order to improve the enzymes-substrates kinetics to ameliorate the performance of the multi-panel sensor array.The project requires a strong synergy between sensors/CMOS/bio/medical technolo-gies. The project partnership includes experts on:(i) Nano-sensing array at system level with special focus on improved specificity (S.Carrara/EPFL - Engineering/sensors-technology), (ii) Chip fabrication with focus on implantable systems and optimization of the power ef-ficiency transfer (Dehollain/EPFL - Engineering/VLSI design), (iii) Pathophysiology of T-cells for therapy of autoimmune diseases and search for new disease markers (Grassi/IRB - biomedical/T cell physiology and intercellular commu-nications), (iv) Enzyme kinetics and new probes design and expression for improved drugs detec-tion (von Mandach’s goup/Univ. Hospital of Zurich - biomedical/Pharmacology)
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