Intelligent implants for diagnosis and therapy



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Dr. Alfred Stett 04.12.2012 IMAPS Workshop Paris Intelligent implants for diagnosis and therapy Natural and Medical Sciences Institute at the University of Tübingen

Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen established 1985 nonprofit foundation under the civil code 180 staff turnover 13.1 million euros @ 2011 application-oriented research services targetting industry, in particular small and medium-sized enterprises accredited quality management system according to ISO 17025 institute affiliated to the university of Tübingen member of the Innovation Alliance of Baden Württemberg (innbw) premium partner of the Spitzencluster microtec Südwest business areas Pharma and biotechnology Biomedical technology Surface and interface technology 2 04.12.2012 Intelligent implants

Microsystems and Nanotechniques for Life Science applications manipulation and analysis of molecules, cells, tissues and interfaces micro nano bio 3 04.12.2012 Intelligent implants

Microelectrode Arrays (MEA) for electrophysiology and biosensor applications Flexible MEA biocompatible thin-film microelectrodes (Au, Pt, TiN, Ir, C) rigid (glass, Si) and flexible (polyimide) substrates Active MEA boards flexible boards with integrated electronic circuits and components flexible barrier layers for hermetic encapsulation of microimplants biotechnology and material engineering microsystems technology and nanotechnology thinfilm and interface technology micro nano bio 4 04.12.2012 Intelligent implants

Miniaturisation of Medical Technology

Key technologies in medical technology Progressive lines Computerisation Miniaturisation Molecularisation Personalisation Network connectivity corresponding key technologies Inormation and Communication technology Microsystems technology, Nanotechnology, Optical technologies Biotechnology, Tissue Engineering individualized treatment, Theranostics BMBF study, 2005 Medical technology digitalized networks for data exchange VDE position paper 2011 and communication Innovations in medical tech. Miniaturised medical devices Instruments for minimally invasive diagnosis and surgery (active) implants cardiovascular implants neurostimulators drug delivery systems 6 04.12.2012 Intelligent implants

Global market for microelectronic medical implants innovative and dynamically growing segment of medical technology global market for medical implants, accessories and supplies: US$ 15.4 billion, 2011 8.9% compound annual growth rate (CAGR) fastest growing segments (CAGR) ear implants (18.2%). neurostimulators (10.5%) implantable drug pumps (10.5%) cardiac implants (7,4 %) 23,1 b. US$ BCC Research, 2011: http://www.bccresearch.com/report/microelectronicmedical-implants-produts-hlc016d.html 7 04.12.2012 Intelligent implants

Neurostimulation Cochlea Implant Retina Implant Brain-Computer- Interfaces Deep brain stimulation Hyppglossal nerve stimulation Vagus Nerve Stimulation Spinal cord stimulation Diaphragm stimulation Esophageal sphincter stimulation Stomage stimulation Bladder stimulation drop foot stimulator 8 04.12.2012 Intelligent implants

Cardiac pacemaker and sensors

Cardiac pacemaker http://www.healthcentral.com//common/images/1/19566_20826_5.jpg metallic housing containing battery and electronic circuitry header leads 10 04.12.2012 Intelligent implants

Telemonitoring COMPASS Cardiac Output Monitor with pulmonalarteriel Sensors 11 04.12.2012 Intelligent implants

BioMonitor TM subcutaneous implanted device automatically detects arrhythmias stores and transmitts electrocardiogram (ECG) recordings A C B 12 04.12.2012 Intelligent implants

Implants for restoring lost sensory functions

Cochlear implant 1978 first implantation at Melbourne University 1984 first implantation in Europe > 220.000 implants worldwide Headpiece Implant Auditory Nerve Microphone Audio Processor Cochlea external audio processor with microphone, batteries and coil Electrode System flexible electrode array, wave-shaped wires Implant - housing - electronics - coil with magnet - electrode array 14 04.12.2012 Intelligent implants http://www.medel.com

Retina Implant restoring vision by a subretinal implant retina Implant photoreceptors optic nerve 15 04.12.2012 Intelligent implants

16 04.12.2012 Intelligent implants

Subretinal implant system Silicone cable Flexible Substrate CMOS Chip Reference electrode Polyimide multilayer Ceramic housing with HF power supply 17 04.12.2012 Intelligent implants External Supply Unit

Retina implant chip for subretinal electrical stimulation chip with 1500 pixels (each 70x70 µm) chip size 3x3 mm external power supply, clinical trials reading words object and face recognition moving without assistance (Picture by Retina Implant AG) 18 04.12.2012 Intelligent implants active circuitry microelectrode photodiode

Brain implants for diagnosis and therapy

Pacemaker for the brain Deep Brain Stimulation Tremor, Parkinson Depression, obsessive-compulsive disorders Medtronic, 1997 FDA approval > 80.000 patients worldwide 400 implantations per year in Germany Prof. Thomas Schläpfer/ Uni Bonn 20 22.11.2012 04.12.2012 Intelligente implants Implantate

Responsive Neurostimulator for the treatment of epilepsy detects abnormal electrical activity in the brain and respond by delivering electrical stimulation to normalize brain activity before the patient experiences seizure symptoms. intracranial implant detects electrocorticogram (ECoG), depth leads for stimulation Neuropace (CA): Multi-center clinical trial Premarket Approval (PMA) application to the U.S. Food and Drug (June 2010) 21 http://www.neuropace.com/ 21

Flexible electrode arrays for brain recording 252 electrodes size 35 mm x 60 mm leads to external electronics 22 04.12.2012 Intelligent implants 22

Intelligent implant projects at NMI

Pre-surgical invasive evaluation of epilepsy epilepsy surgery is a treatment option for patients with intractable epilepsy, precise localization of the seizure focus by invasive electroencephalography (EEG) monitoring by means of subdural grid or depth electrodes, intensive care monitoring up to 2 weeks with restriction to mobility, risk for complications (infection, bleeding) due to cables, long-term recording is desired for repeated measuring of epileptic activity.

Intracranial implant for invasive evaluation of epileptic activity safe longterm recording of brain activity without restriction to mobility of patients during pre-surgical evaluation intracranial implantat for continuous recording of EEG wireless transfer of power and data implantation max. 4 weeks 25 04.12.2012 Intelligent implants

Brainboard: Flexible MEA with integrated electronis SMD/IC thin-film encapsulation multilayer flexpcb Board with data and power management, telemetry, microelectrodes 26 04.12.2012 Intelligent implants 8x8 mm

Integrated assistance system for stroke rehabilitation restoring of grasp function of handicaped people after stroke Paralysis of the forearm moving assistance to controll grasp function

Intracranial implantat for stroke rehabilitation Intracranial implantat for continuous recording of EEG wireless transfer of power and data BCI-Algorithm: extraction of intended potentials, generation of control signals for moving assistance interfaces to external stimulation devices moving assistance: cortical controlled electrical stimulation of the muscle of forearm and hand permanent intracranial implantation EEG classification with BCI algorithms FES electrodes EMG implant motion motion sensors :::: add. sensors 28 04.12.2012 Intelligent implants

Challenge

Intelligent Implants microimplants with (a lot of) sensors, actors, electronic circuits, power supply digital algorithms, telemetry, connectivity small sizes and custom designs high complexity and functionality controlled integration into tissue by bioactive surfaces challenge: active implants with lifetime > 10 years. flexible thin-film Leiterbahnen cable CMOS Chip chip with mit Elektroden electrodes packaging Aufbau- und and Verbindungstechnik encapsulation Medtronic 30 04.12.2012 Intelligent implants Retina Implant

Challenge: safety of active micro implants Implants are foreign bodies minimalinvasive, sparing surgical techniques miniaturization control of foreign body response electronic components neither are biocompatible nor biostable encapsulation of electronic circuits and chips low power IC and optimized heat dissipation safe operating state following a device failure life time of implants is limited reduce the need for replacement surgery biostable designs and batteries with long life time elimination of leads implants may interfere with external devices and conditions electromagnetic compatibility MRT-compatibility 31 04.12.2012 Intelligent implants gass bubbles on imperfectly encapsulated retina chip Adhesion of proteins and cells on brain implant

Longterm stability of flexible implants Protection of electronics from ingressing water and ions by flexible encapsulation SMD/IC-devices multilayer flexpcb thin film electrodes lead Polymer layers are not suitable for longterm stable encapsulations, aren t they? 32 04.12.2012 Intelligent implants

Flexible and impermeable encapsulation by multi-layer systems Water vapour barrier coating inorganic water vapour barrier coating H 2 O-permeation through defects Biocompatible polymer layer system Implant Reduction of water vapour transmission by use of multilayers Improving adhesion of polymer coating on implant 33 04.12.2012 Intelligent implants

Vision of micro medical engineering intelligent implants facilitate more specific diagnosis, more effectice therapies and daily-use aids for rehabilitation prerequisites advanced combinations of materials and designs innovative processing and fabrication methods combination of microsystems-, nano-, biotechnology and ICT close interdisciplinar collaboration between basic researcher, developer, health professionals and regulatory authorities. 34 04.12.2012 Intelligent implants

Thank you very much. www.facebook.com/nmiinaction 35 04.12.2012 Intelligent implants