ADVANCED INTRACORTICAL NEURAL PROBES WITH ELECTRONIC DEPTH CONTROL
In view of the next generation of CMOS-based highly integrated, electronically switchable brain-computer interfaces for intracortical, high-density recordings, in the inter- disciplinary project AdvancedEDC we addressed four main objectives. Objective 1 – Reduction of probe dimensions while increasing the available channel count by implementing innovative schemes for probe reconfiguration. Objective 2 – Integration of additional circuitry into the probe shaft for a localized low noise signal amplification and analog-to-digital conversion (ADC). Objective 3 – Development of advanced algorithms based on machine learning approaches to analyze the recorded data, extract relevant information from the neural signals and use this information for planning the optimal probe reconfiguration. Objective 4 – Integration of algorithms from Objective 3 in a separate chip bringing the data analysis and probe reconfiguration closer to the subject.
Related to Objective 1 we successfully realized CMOS-based probes with 1600 recording sites integrated along 100-µm-wide probe shafts and flexibly addressable via 32 output channels. The probes have been applied in vivo in anaesthetized rats enabling to record single- unit activity and local field potentials. Objective 2 resulted in two fully integrated CMOS-based active probes. The first design successfully validated in vivo, comprises 144 simultaneously addressable recording sites each with an embedded ADC. The slender probe geometry enables its complete immersion in brain tissue and thus deep-brain monitoring applications due to the small base dimensions. The second design with 160 electrodes, each of which comprise an embedded low-noise signal amplifier, allows to simultaneously address 32 channels by means of area-efficient ADCs. In view of Objective 3, we developed advanced algorithms based on machine learning techniques to analyze the recorded data, extract relevant information and use it for planning optimal probe reconfigurations online. Moving the channel selection algorithm as close as possible to the probe, we have developed for Objective 4 a so-called System-on-Chip (SoC) comprising among others a dual core ARM processor and a field programmable gate array (FPGA) logic integrated in a single chip. It allows reducing the hardware size from a traditional PC to a mobile and wearable system maintaining the execution speed of the algorithms.
[Barz2017] F. Barz, A. Livi, M. Lanzilotto, M. Maranesi, L. Bonini, O. Paul and P. Ruther. Versatile, modular three- dimensional microelectrode arrays for neuronal ensemble recordings: from design to fabrication, assem- bly, and functional validation in non-human primates, J. Neural Engineering, 2017, 14, 036010 (16pp)
[DeDorigo2018a] D. De Dorigo, C. Moranz, H. Graf, M. Marx, D. Wendler, B. Shui, A. Sayed Herbawi, M. Kuhl, P. Ruther, O. Paul, Y. Manoli, Fully immersible deep brain neural probes with modular architecture and a Delta-Sigma ADC integrated under each electrode for parallel readout of 144 recording sites, IEEE Journal of Solid State Circuits, 2018, vol. 53(11), doi 10.1109/JSSC.2018.2873180
[Gordillo2016] C. Gordillo, B. Frank, I. Ulbert, O. Paul, P. Ruther and W. Burgard, Automatic channel selection in neural microprobes: A combinatorial multi-armed bandit approach, 2016 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS), Daejeon, 2016, pp. 1844-1850.
[Lanzilotto2016] M. Lanzilotto, A. Livi, M. Maranesi, M. Gerbella, F. Barz, P. Ruther, L. Fogassi, G. Rizzolatti, L. Bonini, Extending the cortical grasping network: Presupplementary motor neuron activity during vision and grasping of objects, Cerebral Cortex, 2016, 26, 4435-4449, doi: 10.1093/cercor/bhw315
[Moritz2016] 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 Trans. on Biomed. Eng., vol 63(7), 2016, pp. 1354-1367, DOI 10.1109/ TBME.2016.2543662.
[Ruther2015] P. Ruther, O. Paul, New approaches for CMOS-based devices for large-scale neural necording,
Current Opinion in Neurobiology, 2015, 32, 31-37, http://arxiv.org/pdf/1706.10058
[Sayed Herbawi2018] A. Sayed Herbawi, O. Christ, L. Kiessner, S. Mottaghi, U. G. Hofmann, O. Paul, and P. Ruther, CMOS neural probe with 1600 close-packed recording sites and 32 analog output channels, Journal of Microelectromechanical Systems, 2018, DOI: 10.1109/JMEMS.2018.2872619
[Vysotska2014] O. Vysotska, B. Frank, I. Ulbert, O. Paul, P. Ruther, C. Stachniss, W. Burgard, Automatic channel selection and neural signal estimation across channels of neural probes, 2014 IEEE/RSJ International Conference on Intelligent Robots and Systems, Chicago, IL, 2014, pp. 1453-1459.
[Cota2015] C. Cota, D. Plachta, T. Stieglitz, Y. Manoli, M Kuhl, In-vivo characterization of a 0.8 – 3 µVRMS input- noise versatile CMOS pre-amplifier, Proc. Int. IEEE/EMBS Conf. Neural Engineering, 2015, pp. 458-461
[Cota2016] C. Cota, D. Plachta, T. Stieglitz, S. Mohanan, Y. Manoli, M. Kuhl, In vivo characterization of a versatile 8-channel digital biopotential recording system with sub µVRMS input noise, Proc. Int. IEEE/EMBS Conf. Neural Engineering, 2016, pp. 6311 – 6314
[DeDorigo2018b] D. De Dorigo, C. Moranz, H. Graf, M. Marx, B. Shui, M. Kuhl, Y. Manoli, A fully immersible deep- brain neural probe with modular architecture and a Delta-Sigma ADC integrated under each electrode for parallel readout of 144 recording sites, IEEE International Solid-State Circuits Conference (ISSCC), Digest of Technical Papers, 2018, pp. 462 – 464
[Kuhl2016] M. Kuhl, Y. Manoli, Area reduction techniques for deep-brain probes with electronic depth control, invited paper, Proc. IEEE Int. Symp. Circuits Syst. (ISCAS), 2016, pp. 1834 – 1837
[Kuhl2015] M. Kuhl, Y. Manoli, A 0.01 mm² fully-differential 2-stage amplifier with reference-free CMFB using an architecture-switching-scheme for bandwidth variation, 2015 Proc. Europ. Solid-State Circuits Conf. (ESSCIRC), 2015, pp. 287 – 290
[Sayed Herbawi2017] A. Sayed Herbawi, L. Kiessner, O. Paul, and P. Ruther, High-density CMOS neural probe implementing a hierarchical addressing scheme for 1600 recording sites and 32 output channels, in 19th Int. Conf. on Solid-State Sens., Act. And Microsyst. (Transducers ’17), June 18-22, 2017, Kaohsiung, Taiwan, pp. 20-23
[Sayed Herbawi2015a] A. Sayed Herbawi, B. Mildenberger, F. Larramendy, T. Holzhammer, T. Galchev, O. Paul, P. Ruther, CMOS-based high-density neural probes with improved scheme for addressing recording and stimulation channels, Proc. Eurosensors Conf. 2015, 6.-9. September 2015, Freiburg, Germany
[Sayed Herbawi2015b] A. Sayed Herbawi, F. Larramendy, T. Galchev, T. Holzhammer, B. Mildenberger, O. Paul, and P. Ruther, CMOS-based neural probe with enhance electronic depth control, Dig. Tech. Papers IEEE Transducers Conf. 2015, Anchorage, Alaska, USA, June 21-25, 2015, pp. 1723-1726
[Shui2018] B. Shui, M. Keller, M. Kuhl, Y. Manoli, A 70.1dB 0.0045mm² low-power continuous-time incremental Delta-Sigma modulator for multi-site neural recording interfaces, Proc. IEEE Int. Symp. Circuits Syst. (ISCAS), 2018, DOI: 10.1109/ISCAS.2018.8351249
[Stieglitz2016] T. Stieglitz, O. Paul, U. Wallrabe, P. Ruther, BrainLinks-BrainTools – Methods and tools for neural engineering, Biomed Tech 2016; 61 (s234)
Other publications
De Dorigo D, Manoli Y, Fully integrated active neural probes for deep brain monitoring applications, 2018, IEEE Brain Initiative Workshop on Advanced NeuroTechnologies, November 1-2, San Diego, California, USA
Ruther P, High-density neural probe arrays using CMOS and MEMS technologies, Neuroelectronic Interfaces, Beyond Feasibility - Bridging the Gap in Neuroelectronic Interfaces,Gordon Research Conference, March 25-30, 2018, Galveston,TX, USA; invited talk
Ruther P, Pothof F, Barz F, Bonini L, Orban G, Stieglitz T, Paul O, MEMS Technologies for high-channel count SEEG probes, Insights from the inside Workshop, Intracranial studies of the human brain, 30.11.16- 01.12.16, Tel-Aviv, Israel; invited talk
Ruther P, CMOS-based probe arrays for high-density neural recordings, Bernstein Sparks Workshop, Tutzing, 28./29. June 2016; invited talk
Gordillo C, Kuhner A, Schubert T, Burgard W, Bast H, Becker B, Bennewitz M, Galchev T, Keller M, Manoli Y, Maurer C, Paul O, Ruther P, Stachniss C, Robotics meets neuroscience: Electode selection and motion analysis, International Workshop for Advanced Neurotechnology (ICAN), University of Michigan, Ann Arbor, USA, 13.-14. June 2016, poster presentation
Paul O, Ruther P, 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
Kuhl M, Keller M, Muller N, Shui B, Mohamed S, Cota O, Rossbach D, Taschwer A, Manoli Y, Entwurf neuronaler Schnittstellenschaltungen – Mikroelektronik im Exzellenzcluster BrainLinks-BrainTools“, 2015, Work- shop Analogschaltungen; talk
Ruther P, High-density neural recording based on advanced silicon probe technologies, Magnetrodes Workshop, Lisbon, Portugal, 23.-25.11.2015; invited talk
Ruther P, Advanced silicon probes for large-scale neural recording, DFG-NSF Workshop - New Perspectives on Neuroengineering and Neurotechnologies, Arlington, USA, November 13/14, 2014; inivited talk