WAVEGUIDE-BASED OPTRODES WITH INTEGRATED LASER DIODES FOR OPTOGENETIC INTERVENTION AND ELECTRICAL RECORDING
Relevant for Research Area
Optogenetics, a highly innovative neuroscientific method, provides the unique opportunity to control neural activity by optical stimuli of specific types of neurons. Miniaturized optoelectronic devices, i.e. optrodes, are required to interfere with genetically modified neuronal tissue. In WOLDOR we aimed for the development of sophisticated miniaturized, implantable optogenetic instruments with integrated light sources replacing the conventionally applied optical glass fibers in order to enable less restricted behavior in freely moving animals. Applications for intracortical and epicortical in vivo optogenetic experiments were focused in this project using both mechanically flexible and stiff optrodes. WOLDOR developed and validated a broad range of implantable micro-optical tools based on silicon (Si) and polymer substrates comprising integrated laser diode (LD) and light-emitting diode (LED) chips. They are grouped into devices dedicated for mid-term applications with the optoelectronic components being sealed by polymers and tools with hermetically sealed micro- packages for long-term use paving the road for future clinical applications. The hermetic micro-packages based on silica and/or silicon with electrical feedthroughs comprise integrated optical elements such as glass feedthroughs and micro lenses made of glass to couple light into flexible, long-term stable waveguides and provide light collimation, respectively. The flexible waveguides have been combined with flexible electrode arrays. The longevity of the micro-housing materials has been analyzed using innovative, capacitive humidity sensors. Optical probes combined with recording probes have been applied in vivo demonstrating the layer specific illumination of brain tissue as well as optogenetic stimulation in the cochlea and pacing of cardiac tissue. Besides tools for optogenetics, a flexible near infrared spectroscopy (NIRS) micro-array was successfully developed to be tested with gelled intralipid rat brain models.
M. T. Alt, E. Fiedler, L. Rudmann, J.S. Ordonez, P. Ruther, T. Stieglitz, Let There Be Light; Optoprobes for Neural Implants, Proc. IEEE, vol. 105/1, pp. 101 – 138, 2016, doi 10.1109/ JPROC.2016.2577518
S. Ayub, L. Gentet, R. Fiáth, M. Schwaerzle, M. Boerel, F. David, P. Barthó, I. Ulbert, O.Paul, P. Ruther, Hybrid intracerebral probe with integrated bare LED chips for optogenetic studies, Biomedical Microdevices, 2017, 19:49 (12pp); doi:10.1007/s10544-017-0190-3
M. Langenmair, L. Rudmann, J. S. Ordonez and T. Stieglitz, Development of a desiccant based dielectric for monitoring humidity conditions in miniaturized hermetic implantable packages, Current Directions in Biomedical Engineering, no. 2 (1), pp. 537–541, 2016, doi: 10.1515/cdbme-2016-0119
C.T. Moritz, P. Ruther, S. Goering, A. Stett, T. Ball, W. Burgard, E. Chudler, R. Rao, New Perspectives on Neuroengineering and Neurotechnologies: NSF-DFG Workshop Report, IEEE Transactions on Biomedical Engineering 63(7), 2016, pp. 1354-1367 DOI 10.1109/ TBME.2016.2543662
L. Rudmann, M.T. Alt, D. Ashouri Vajari, T. Stieglitz, Integrated optoelectronic microprobes, 2018 Current Opinion in Neurobiology, volume: 50, June, p. 72 – 82, doi: 10.1016/j.conb.2018. 01.010
M. Schwaerzle, O. Paul, and P. Ruther, Compact Silicon-based Optrode with Integrated Laser Diode Chips, SU-8 Waveguides and Platinum Electrodes for Optogenetic Applications, J. Micromech. Microeng., 2017, 27(6), pp. 065004 (11pp); doi.org/10.1088/1361-6439/aa6ad4
L. Sileo, S.H. Bitzenhofer B. Spagnolo, J.A. Pöpplau, T. Holzhammer, M. Pisanello, F. Pisano, E. Bellistri, E. Maglie, M. De Vittorio, P. Ruther, I.L. Hanganu-Opatz and F. Pisanello, Tapered Fibers Combined With a Multi-Electrode Array for Optogenetics in Mouse Medial Prefrontal Cortex, Frontiers in Neuroscience, 2018, vol. 12, Article771 (10pp), doi: 10.3389/fnins.2018.00771
Stieglitz, T., Introduction to Optogenetics, Fachgruppe Intelligente Implantate, microTEC Südwest, 16.05.2018, Rottweil (2018); talk
Stieglitz, T., Stability and Functionality of Thin-film Recording and Stimulation Electrodes in the Peripheral and Central Nervous System. International Conference on Advanced Neurotechnologies (ICAN), May 6-8, 2018, Ann Arbor, MI, USA (2018); talk
Stieglitz, T., Schnittstellen zum Nervensystem - Von Krüppeln zu Supermenschen ?”, Workshop “Selbst- optimierung”, 08. Juni 2018, Freiburg (2018); talk
Stieglitz, T., Stability of materials and flexible neural probes for recording, electrical and optical stimulation, Colloquium des SFB 889 “Cellular Mechanisms of Sensory Processing”, Universitätsmedizin Göttingen, 19.06.2018, Göttingen (2018); talk
Stieglitz, T., Flexible Multielectrode Arrays as Implantable Interface to the Central and Peripheral Nervous System, Plenary Talk, 11th International Meeting on Substratge-Integrated Microelectrode Arrays - MEA Meeting, July 4th-6th, 2018, Reutlingen (2018); talk
Stieglitz, T., Optoelectronic probes: Selection of materials and processes to obtain flexibility and longevity, MicroAlliance Meeting, 04.-05.10.2018, Freiburg (2018); talk
P. Ruther, LED-based MEMS Tools for Optogenetic Applications Aside from Cerebral Tissue, ICAN – International Conference for Advanced Neurotechnology, University of Michigan, Ann Arbor, USA, 7./8. May 2018; invited talk
E. Klein, C. Gossler, O. Paul, P. Ruther, Thin-film LED Arrays on Flexible Substrates With Improved Thermo- mechanical Behaviour, ICAN – International Conference for Advanced Neurotechnology, University of Michigan, Ann Arbor, USA, 7./8. May 2018; poster presentation
E. Otte, S. Ayub, O. Paul, P. Ruther, Implantable Optrode Enabling Electrophysiology and Optogenetic Stimulation, ICAN – International Conference for Advanced Neurotechnology, University of Michigan, Ann Arbor, USA, 7./8. May 2018; poster presentation
M.T. Alt, A. Mittnacht, T. Stieglitz, Long-term Stable and Low Loss Glass Waveguides for Miniaturized Implants for Optogenetics, ICAN Workshop, University of Michigan, Ann Arbor, May 7th – 8th 2018; poster presentation
P. Ruther, Interfacing the brain with micromachined implants, Seminar Talk, TU Eindhoven, 1.03.2018; invited talk
Stieglitz T., Čvančara, P., Mueller, M., Liljemalm, R., Erhardt, J., Boehler, C., Pfau, J., Ashouri Vajari, D., Vomero, M., Oliveira, A., Eickenscheidt, M., Khan, S., Asplund, M., Ordonez, J.S.: Stability and functionality of flexible electrode arrays in chronic applications, IEEE Brain Initiative Workshop on Advanced NeuroTechnologies for BRAIN Initiatives (ANTBI): Challenges and Opportunities, IEEE EMBS Neural Engineering Conference, May 25th, 2017, Shanghai, China (2017); talk
Stieglitz, T., Čvančara, P., Vomero, M., Pfau, J., Ashouri, D., Oliveira, A., Ordonez, J.S., Gueli, C., Eickenscheidt, M., Kassegne, M.: Long-Term Performance of Flexible Thin-Film Electrode Arrays in Neural Implants. International Conference BrainLinks-BrainTools, Forum Merzhausen, 28.-30.06.2017, Merzhausen (2017); talk
Stieglitz, T.: Polymer-basierte Schnittstellen zum Nervensystem, Hector Fellow Symposium “Medizin 4.0 - Organische Elektronik in der modernen Medizin”, 06.07.2017, Dresden (2017); talk
Stieglitz, T., Miniaturized Implants to Interface with the Peripheral and Central Nervous System Center for Neuroprosthetics Seminar, EPFL, 26.10.2017, Lausanne, CH (2017); talk
Stieglitz, T., Čvančara, P., Müller, M., Liljemalm, R., Erhardt, J., Boehler, C., Ashouri, D., Vomero, M., Oliveira, A., Eickenscheidt, M., Asplund, M., Ordonez, J.S.: Miniaturized Neural Implants: Design, Development and Reliability Designs of Medical Devices Conference Europe 2017, 14.-15.11.2017, Einthoven, The Netherlands (2017); talk
P. Ruther, E. Klein, S. Ayub, C. Gossler, M. Schwaerzle, O. Paul, Implantable MEMS-based tools for optogenetics, 12th International Conference on Nitride Semiconductors, July 24-28, 2017 - Strasbourg, France; invited talk, 25.7.2017
P. Ruther, S. Ayub, A. Sayed-Herbawi, E. Klein, M. Schwaerzle, F. Barz, F. Pothof, O. Paul, How to interface the brain with MEMS-based implants? 43rd International Conference on Micro and Nano Engineering, 18.-22. September 2017; invited talk
P. Ruther, Let there be light - How MEMS directly enlightens the brain?, KIT Campus North, Karlsruhe, 14.12.2016; invited talk
M. Schwaerzle, S. Ayub, F. Barz, O. Paul, P. Ruther, LED and laser diode based MEMS tools for optogenetics, International Workshop for Advanced Neurotechnology (ICAN), University of Michigan, Ann Arbor, USA, 13.-14. June 2016; poster presentation
O. Paul, P. Ruther, MEMS Tools for Bidirectional Brain-Machine Interfaces, International Workshop for Advanced Neurotechnology (ICAN), University of Michigan, Ann Arbor, USA, 13.-14. June 2016; invited talk
P. Ruther, How to illuminate brain tissue?, IGSN Workshop, University of Bochum, 9. May 2016, invited lecture
P. Ruther, MEMS-based technologies for optogenetic applications, Symposium on Restoration of sensory and motor function, Universitätsmedizin Göttingen, 26./27. May 2016; invited talk
P. Ruther, Innovative tools for electrophysiology and optogenetics based on MEMS technologies, Medizinische Hochschule Hannover, 23.3.2016; invited talk
P. Ruther, Trends in Silicon-based Neural Probe Arrays Used in Electrophysiology and Optogenetics, GDR 2904 Multielectrode Systems for Neuroscience: 6th Annual Meeting, 5-8 Jan 2016 Grenoble-Autrans (France); invited talk
Stieglitz T., Ordonez, J.S., Hassler, C., Fiedler, E., Ashouri, D., Kohler, F., Boretius, T.,Boehler, C., Asplund, M., Ball, T., Rickert, J., Cvancara, P., Schuettler, M.: Sensorik in der Medizintechnik - am Beispiel neurotechnischer Implantate, 29.01.2015, F&E Forum der Heraeus Precious Metals, Heraeus, Hanau (2015); talk
Stieglitz T., Ordonez, J.S., Hassler, C., Fiedler, E., Ashouri, D., Kohler, F., Boretius, T.,Boehler, C., Asplund, M., Ball, T., Rickert, J., Cvancara, P., Schuettler, M.: Neurotechnische Implantate im peripheren und zentralen Nervensystem. Fakultät füt Elektro- und Informationstechnik, Technische Universität Dresden, 05.02.2015 (2015); talk
Stieglitz T., Ordonez, J.S., Hassler, C., Fiedler, E., Ashouri, D., Kohler, F., Boretius, T.,Boehler, C., Asplund, M., Ball, T., Rickert, J., Cvancara, P., Schuettler, M.: Mikrosysteme im Kontakt mit dem Nervensystem - Chancen und Herausforderungen. Naturwissenschaftliches und Medizinisches Institut (NMI) an der Universität Tübingen, 13.04.2015, Reutlingen (2015); talk
Stieglitz T., Ordonez, J.S., Hassler, C., Fiedler, E., Ashouri, D., Kohler, F., Boretius, T., Boehler, C., Asplund, M., Ball, T., Rickert, J., Cvancara, P., Schuettler, M.: Intelligente Implantate-Chancen und Herausforderungen am Beispiel neurotechnischer Anwendungen. Symposium Intelligente Implantate, Hochschule Furtwangen, Campus Villingen-Schwenningen, 05.05.2015, Schwenningen (2015); talk
Stieglitz T., Ordonez, J.S., Plachta, D.T.T., Hassler, C., Fiedler, E., Ashouri, D., Kohler, F., Boretius, T., Boehler, C., Asplund, M., Ball, T., Rickert, J., Cvancara, P., Schuettler, M.: Neural Interfaces – From Basic Research to Clinical Applications Advanced Institute, The US-Turkey Advanced Study Institute on Global Healthcare Challenges, 22.-25.06.2015, Izmir, Turkei (2015); talk
Stieglitz, T., Ordonez, J.S., Kohler, F., Boretius, T., Ball, T., Rickert, J., Schuettler, M.: Neural implants in basic and translational research, MicroAlliance Meeting - Kyoto-Michigan-Freiburg, 24.-25.09.2015, Freiburg (2015); talk
Stieglitz, T., Neurotechnik – trifft den Nerv und geht unter die Haut. 23. VDE Fachtagung mit Ausstellun “Albert- Keil-Kontaktseminar”, 08.10.2015, KIT, Karlsruhe (2015); talk
Stieglitz T., Čvančara, P., Ashouri, D., Rudmann, L., Hassler, C., Kohler, F., Ordonez, J.S.: Neural implants for mice and men, Computational Neuroscience and the Hybrid Brain, 12.-14.10.2015, Freiburg (2015); talk
Stieglitz, T., Wenn Technik den Nerv trifft – Neurotechnik in Therapie und Rehabilitation. Dr. Eduard-Martin Lecture, Festvortrag an der Univeristät des Saarlandes, 22.10.2015, Saarbrücken (2015); talk
Stieglitz, T., The Oracle of Cassandra: Technology for Paralyzed Users, Impulse talk and panel discussion Neurotechnix3rd International Conferenceon Neurotechnology, Electronics and Informatix- NEUROTECHNIX 2015, Nov. 16-17, 2015 Lisbon, Portugal (2015); talk
Stieglitz, T., Miniaturized Implants on the Way into Clinical Applications. Keynote lecture, 3rd International Conferenceon Neurotechnology, Electronics and Informatix-NEUROTECHNIX 2015, Nov. 16-17, 2015 Lisbon, Portugal (2015); talk
P. Ruther, M. Schwaerzle, S. Ayub, C. Gossler, E. Klein, O. Paul, MEMS-based optical tools for advanced optogenetic studies - Optrodes with integrated light sources based on MEMS technologies, 2nd International Workshop on Technologies for Optogenetics OPTOGEN2015, Lecce, Italy, 16./17.12.2015; invited talk
P. Ruther, Optoelectronic devices Optrodes with integrated light sources based on MEMS technologies, Optogenetics Workshop, University of Bochum, 22.4.2015
P. Ruther, M. Schwaerzle, C. Gossler, S. Ayub, U.T. Schwarz, O. Paul, Highly compact MEMS-based optrodes with integrated light sources, SPIE Photonics West Conf. 2015, San Francisco, USA, 7.-12.2.2015
U. T. Schwarz, M. Schwaerzle, A. Jakob, L. Rudmann, M. Alt, E. Fiedler, T. Stieglitz, P. Ruther, MOEMS integration of (Al,In)GaN laser diodes with optical waveguides for applications in optogenetics, SPIE Photonics West, Feb. 7th – 12th 2015, San Francisco, CA, USA; invited talk
Stieglitz, T., Ordonez, J.S., Hassler, C., Fiedler, E., Kohler, F., Boretius, T., Boehler, C. Asplund, M., Schuettler, M.: Miniaturized Neural Interfaces and Implants in Fundamental and Translational Research. Massachusetts Institute of Technology (MIT), MTL Seminar Series, 25.04.2014, Boston (2014); talk
Stieglitz, T., Boretius, T., Henle, C., Meier, W., Kohler, F., Fiedler, E., Ordonez, J.S:, Rickert, J., Schuettler, M.: Flexible Neural Interfaces in Fundamental and Translational Research. Freiburg-Imperial Symposium on Neuroscience and Neurotechnology, 23rd -25th September 2014, Freiburg (2014); talk
Stieglitz T. Ordonez, J.S., Henle, C., Meier, W., Hassler, C., Fiedler, E., Kohler, F., Boretius, T.,Boehler, C., Asplund, M., Ball, T., Rickert, J., Cvancara, P., Schuettler, M. Miniaturized neural interfaces and implants in fundamental and translational research. IBBME Distinguished Lecture, 11.11.2014, Institute of Biomaterials and Biomedical Engineering, University of Toronto (2014); talk
P. Ruther, U.T. Schwarz, M. Schwaerzle, P. Elmlinger, C. Gossler, O. Paul, MEMS-based Neural Implants for Optogenetic Applications New System Developments at IMTEK, NAMIS Workshop 2014, Halong Bay, Vietnam, 2.-4.6.2014; invited talk
U.T. Schwarz, P. Ruther, O. Paul, Micro-engineered probes for optogenetics. DFG-NSF Workshop - New Perspectives on Neuroengineering and Neurotechnologies, Arlington, November 13/14, 2014; inivited talk
L. Rudmann, J. S. Ordonez, T. Stieglitz, Hermetic Feedthrough Approach for Optogenetic Tools with Integrated Lens Structures, DFG-NSF Workshop - New Perspectives on Neuroengineering and Neurotechnologies, Arlington, November 13/14, 2014; poster presentation
Stieglitz, T.: Technik, die unter die Haut geht. Frankfurter Allgemeine Zeitung, Nr. 133, N2 am 11.06.2014 (2014).
Stieglitz, T., Schuettler, M., Plachta, D.T.T.: Neuroprothetik heute und morgen. Orthopädie Technik 06/15, 32-37 Dortmund: Verlag Orthopädie-Technik (2015).
Stieglitz, T.: Neuroimplantate. Spektrum der Wissenschaft-Spezial, Physik-Mathematik-Technik: Mensch Maschine Visionen-Wenn Biologie und Technik verschmelzen, 6-13 (2015).
Stieglitz T.: Neurotechnik,, Neurostimulation, Neuro- und Sinnesimplante, in: Dössel O., Lenarz, T., Schlötelburg, C., Schmitz-Rode, T. (Hrsg.). VDE Expertenbericht Biomedizinische Technik. Frankfurt: VDE-Verlag, 69-70 (2015).
Stieglitz, T.: Intelligent Implants in Neural Engineering: from tool in neuroscience to new treatment options in an ageing society. Microsystems Technology in Germany 2016, Berlin: trials Consult, pp. 32-33 (2016)-ISSN 2191-7183
Stieglitz, T., Rudmann, L., Ordonez, J.S.: Mikrosysteme ins Auge gefasst, Physik-Journal 15(5), 33-38 (2016)
Stieglitz, T., von Metzen, R., Stett, A.: Bioelektronische Medizin-Eine Einführung in eine neue Disziplin. VDE Health Expertenbeiträge, Ausgabe 01/2018, pp. 1-4 (2018)