Three-dimensional(3D)nanoprinting via two-photon polymerization offers unparalleled design flexibility and precision,thereby enabling rapid prototyping of advanced micro-optical elements and systems that have found im...Three-dimensional(3D)nanoprinting via two-photon polymerization offers unparalleled design flexibility and precision,thereby enabling rapid prototyping of advanced micro-optical elements and systems that have found important applications in endomicroscopy and biomedical imaging.The potential of this versatile tool for monolithic manufacturing of dynamic micro-opto-electro-mechanical systems(MOEMSs),however,has not yet been sufficiently explored.This work introduces a 3D-nanoprinted lens actuator with a large optical aperture,optimized for remote focusing in miniaturized imaging systems.The device integrates orthoplanar linear motion springs,a self-aligned sintered micro-magnet,and a monolithic lens,actuated by dual microcoils for uniaxial motion.The use of 3D nanoprinting allows complete design freedom for the integrated optical lens,whereas the monolithic fabrication ensures inherent alignment of the lens with the mechanical elements.With a lens diameter of 1.4 mm and a compact footprint of 5.74 mm,it achieves high mechanical robustness at resonant frequencies exceeding 300 Hz while still providing a large displacement range of 200μm(±100μm).A comprehensive analysis of optical and mechanical performance,including the effects of coil temperature and polymer viscoelasticity,demonstrates its advantages over conventional micro-electro-mechanical system actuators,showcasing its potential for next-generation imaging applications.展开更多
Recording neural signals from delicate autonomic nerves is a challenging task that requires the development of a lowinvasive neural interface with highly selective,micrometer-sized electrodes.This paper reports on the...Recording neural signals from delicate autonomic nerves is a challenging task that requires the development of a lowinvasive neural interface with highly selective,micrometer-sized electrodes.This paper reports on the development of a three-dimensional(3D)protruding thin-film microelectrode array(MEA),which is intended to be used for recording low-amplitude neural signals from pelvic nervous structures by penetrating the nerves transversely to reduce the distance to the axons.Cylindrical gold pillars(O 20 or 50μm,~60μm height)were fabricated on a micromachined polyimide substrate in an electroplating process.Their sidewalls were insulated with parylene C,and their tips were optionally modified by wet etching and/or the application of a titanium nitride(TiN)coating.The microelectrodes modified by these combined techniques exhibited low impedances(~7 kΩ at 1 kHz for ∅ 50μm microelectrode with the exposed surface area of~5000μm^(2))and low intrinsic noise levels.Their functionalities were evaluated in an ex vivo pilot study with mouse retinae,in which spontaneous neuronal spikes were recorded with amplitudes of up to 66μV.This novel process strategy for fabricating flexible,3D neural interfaces with low-impedance microelectrodes has the potential to selectively record neural signals from not only delicate structures such as retinal cells but also autonomic nerves with improved signal quality to study neural circuits and develop stimulation strategies in bioelectronic medicine,e.g.,for the control of vital digestive functions.展开更多
Demands for neural interfaces around functionality,high spatial resolution,and longevity have recently increased.These requirements can be met with sophisticated silicon-based integrated circuits.Embedding miniaturize...Demands for neural interfaces around functionality,high spatial resolution,and longevity have recently increased.These requirements can be met with sophisticated silicon-based integrated circuits.Embedding miniaturized dice in flexible polymer substrates significantly improves their adaptation to the mechanical environment in the body,thus improving the systems’structural biocompatibility and ability to cover larger areas of the brain.This work addresses the main challenges in developing a hybrid chip-in-foil neural implant.Assessments considered(1)the mechanical compliance to the recipient tissue that allows a long-term application and(2)the suitable design that allows the implant’s scaling and modular adaptation of chip arrangement.Finite element model studies were performed to identify design rules regarding die geometry,interconnect routing,and positions for contact pads on dice.Providing edge fillets in the die base shape proved an effective measure to improve die-substrate integrity and increase the area available for contact pads.Furthermore,routing of interconnects in the immediate vicinity of die corners should be avoided,as the substrate in these areas is prone to mechanical stress concentration.Contact pads on dice should be placed with a clearance from the die rim to avoid delamination when the implant conforms to a curvilinear body.A microfabrication process was developed to transfer,align,and electrically interconnect multiple dice into conformable polyimide-based substrates.The process enabled arbitrary die shape and size over independent target positions on the conformable substrate based on the die position on the fabrication wafer.展开更多
Direct stimulation of peripheral nerves with implantable electrodes successfully provided sensory feedback to amputees while using hand prostheses.Longevity of the electrodes is key to success,which we have improved f...Direct stimulation of peripheral nerves with implantable electrodes successfully provided sensory feedback to amputees while using hand prostheses.Longevity of the electrodes is key to success,which we have improved for the polyimide-based transverse intrafascicular multichannel electrode(TIME).The TIMEs were implanted in the median and ulnar nerves of three trans-radial amputees for up to six months.We present a comprehensive assessment of the electrical properties of the thin-film metallization as well as material status post explantationem.The TIMEs stayed within the electrochemical safe limits while enabling consistent and precise amplitude modulation.This lead to a reliable performance in terms of eliciting sensation.No signs of corrosion or morphological change to the thin-film metallization of the probes was observed by means of electrochemical and optical analysis.The presented longevity demonstrates that thin-film electrodes are applicable in permanent implant systems.展开更多
文摘Three-dimensional(3D)nanoprinting via two-photon polymerization offers unparalleled design flexibility and precision,thereby enabling rapid prototyping of advanced micro-optical elements and systems that have found important applications in endomicroscopy and biomedical imaging.The potential of this versatile tool for monolithic manufacturing of dynamic micro-opto-electro-mechanical systems(MOEMSs),however,has not yet been sufficiently explored.This work introduces a 3D-nanoprinted lens actuator with a large optical aperture,optimized for remote focusing in miniaturized imaging systems.The device integrates orthoplanar linear motion springs,a self-aligned sintered micro-magnet,and a monolithic lens,actuated by dual microcoils for uniaxial motion.The use of 3D nanoprinting allows complete design freedom for the integrated optical lens,whereas the monolithic fabrication ensures inherent alignment of the lens with the mechanical elements.With a lens diameter of 1.4 mm and a compact footprint of 5.74 mm,it achieves high mechanical robustness at resonant frequencies exceeding 300 Hz while still providing a large displacement range of 200μm(±100μm).A comprehensive analysis of optical and mechanical performance,including the effects of coil temperature and polymer viscoelasticity,demonstrates its advantages over conventional micro-electro-mechanical system actuators,showcasing its potential for next-generation imaging applications.
基金financed by the German Federal Ministry of Education and Research(BMBF)within the funding program"Individualisierte Medizintechnik"under grant 13GW0271C(NEPTUN)received financial support from the State Ministry of Baden-Wuerttemberg for Economic Affairs,Labor and Tourism+1 种基金Thomas Stieglitz was partly supported by the BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation-DFG(EXC 1086)funded by the Federal Ministry of Economics,Science and Arts of Baden-Württemberg within the sustainability program for projects of excellence initiative II.
文摘Recording neural signals from delicate autonomic nerves is a challenging task that requires the development of a lowinvasive neural interface with highly selective,micrometer-sized electrodes.This paper reports on the development of a three-dimensional(3D)protruding thin-film microelectrode array(MEA),which is intended to be used for recording low-amplitude neural signals from pelvic nervous structures by penetrating the nerves transversely to reduce the distance to the axons.Cylindrical gold pillars(O 20 or 50μm,~60μm height)were fabricated on a micromachined polyimide substrate in an electroplating process.Their sidewalls were insulated with parylene C,and their tips were optionally modified by wet etching and/or the application of a titanium nitride(TiN)coating.The microelectrodes modified by these combined techniques exhibited low impedances(~7 kΩ at 1 kHz for ∅ 50μm microelectrode with the exposed surface area of~5000μm^(2))and low intrinsic noise levels.Their functionalities were evaluated in an ex vivo pilot study with mouse retinae,in which spontaneous neuronal spikes were recorded with amplitudes of up to 66μV.This novel process strategy for fabricating flexible,3D neural interfaces with low-impedance microelectrodes has the potential to selectively record neural signals from not only delicate structures such as retinal cells but also autonomic nerves with improved signal quality to study neural circuits and develop stimulation strategies in bioelectronic medicine,e.g.,for the control of vital digestive functions.
基金The authors thank the colleagues at IMTEK and UUlm for their technical support.This work was funded by the German Research Foundation(DFG,grant no.401023906 and OR 245/15-1)is part of BrainLinks-BrainTools,which was funded by the German Research Foundation(DFG,grant no.EXC 1086)and is currently funded by the Federal Ministry of Economics,Science and Arts of Baden Württemberg within the sustainability program for projects of the excellence initiative.
文摘Demands for neural interfaces around functionality,high spatial resolution,and longevity have recently increased.These requirements can be met with sophisticated silicon-based integrated circuits.Embedding miniaturized dice in flexible polymer substrates significantly improves their adaptation to the mechanical environment in the body,thus improving the systems’structural biocompatibility and ability to cover larger areas of the brain.This work addresses the main challenges in developing a hybrid chip-in-foil neural implant.Assessments considered(1)the mechanical compliance to the recipient tissue that allows a long-term application and(2)the suitable design that allows the implant’s scaling and modular adaptation of chip arrangement.Finite element model studies were performed to identify design rules regarding die geometry,interconnect routing,and positions for contact pads on dice.Providing edge fillets in the die base shape proved an effective measure to improve die-substrate integrity and increase the area available for contact pads.Furthermore,routing of interconnects in the immediate vicinity of die corners should be avoided,as the substrate in these areas is prone to mechanical stress concentration.Contact pads on dice should be placed with a clearance from the die rim to avoid delamination when the implant conforms to a curvilinear body.A microfabrication process was developed to transfer,align,and electrically interconnect multiple dice into conformable polyimide-based substrates.The process enabled arbitrary die shape and size over independent target positions on the conformable substrate based on the die position on the fabrication wafer.
文摘Direct stimulation of peripheral nerves with implantable electrodes successfully provided sensory feedback to amputees while using hand prostheses.Longevity of the electrodes is key to success,which we have improved for the polyimide-based transverse intrafascicular multichannel electrode(TIME).The TIMEs were implanted in the median and ulnar nerves of three trans-radial amputees for up to six months.We present a comprehensive assessment of the electrical properties of the thin-film metallization as well as material status post explantationem.The TIMEs stayed within the electrochemical safe limits while enabling consistent and precise amplitude modulation.This lead to a reliable performance in terms of eliciting sensation.No signs of corrosion or morphological change to the thin-film metallization of the probes was observed by means of electrochemical and optical analysis.The presented longevity demonstrates that thin-film electrodes are applicable in permanent implant systems.
