Publications by authors named "Florian Fallegger"

10 Publications

  • Page 1 of 1

Viscoelastic surface electrode arrays to interface with viscoelastic tissues.

Nat Nanotechnol 2021 Jun 17. Epub 2021 Jun 17.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA.

Living tissues are non-linearly elastic materials that exhibit viscoelasticity and plasticity. Man-made, implantable bioelectronic arrays mainly rely on rigid or elastic encapsulation materials and stiff films of ductile metals that can be manipulated with microscopic precision to offer reliable electrical properties. In this study, we have engineered a surface microelectrode array that replaces the traditional encapsulation and conductive components with viscoelastic materials. Our array overcomes previous limitations in matching the stiffness and relaxation behaviour of soft biological tissues by using hydrogels as the outer layers. We have introduced a hydrogel-based conductor made from an ionically conductive alginate matrix enhanced with carbon nanomaterials, which provide electrical percolation even at low loading fractions. Our combination of conducting and insulating viscoelastic materials, with top-down manufacturing, allows for the fabrication of electrode arrays compatible with standard electrophysiology platforms. Our arrays intimately conform to the convoluted surface of the heart or brain cortex and offer promising bioengineering applications for recording and stimulation.
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http://dx.doi.org/10.1038/s41565-021-00926-zDOI Listing
June 2021

MRI-Compatible and Conformal Electrocorticography Grids for Translational Research.

Adv Sci (Weinh) 2021 05 8;8(9):2003761. Epub 2021 Mar 8.

Bertarelli Foundation Chair in Neuroprosthetic Technology Laboratory for Soft Bioelectronic Interfaces Institute of Microengineering Institute of Bioengineering Center for Neuroprosthetics Ecole Polytechnique Fédérale de Lausanne (EPFL) Geneva 1202 Switzerland.

Intraoperative electrocorticography (ECoG) captures neural information from the surface of the cerebral cortex during surgeries such as resections for intractable epilepsy and tumors. Current clinical ECoG grids come in evenly spaced, millimeter-sized electrodes embedded in silicone rubber. Their mechanical rigidity and fixed electrode spatial resolution are common shortcomings reported by the surgical teams. Here, advances in soft neurotechnology are leveraged to manufacture conformable subdural, thin-film ECoG grids, and evaluate their suitability for translational research. Soft grids with 0.2 to 10 mm electrode pitch and diameter are embedded in 150 µm silicone membranes. The soft grids are compatible with surgical handling and can be folded to safely interface hidden cerebral surface such as the Sylvian fold in human cadaveric models. It is found that the thin-film conductor grids do not generate diagnostic-impeding imaging artefacts (<1 mm) nor adverse local heating within a standard 3T clinical magnetic resonance imaging scanner. Next, the ability of the soft grids to record subdural neural activity in minipigs acutely and two weeks postimplantation is validated. Taken together, these results suggest a promising future alternative to current stiff electrodes and may enable the future adoption of soft ECoG grids in translational research and ultimately in clinical settings.
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http://dx.doi.org/10.1002/advs.202003761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097365PMC
May 2021

Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury.

Nature 2021 02 27;590(7845):308-314. Epub 2021 Jan 27.

Motac Neuroscience Ltd, Manchester, UK.

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival, impairs neurological recovery, increases the risk of cardiovascular disease, and reduces quality of life. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord, which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury, and restored walking after paralysis. Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This 'neuroprosthetic baroreflex' controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI.
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http://dx.doi.org/10.1038/s41586-020-03180-wDOI Listing
February 2021

Recruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord.

Nat Commun 2021 01 19;12(1):435. Epub 2021 Jan 19.

Department of Neuroscience and Movement Science, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a computational model of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of upper-limb motoneuron recruitment with EES and characterize the selectivity of cervical interfaces. We show that lateral electrodes produce a segmental recruitment of arm motoneurons mediated by the direct activation of sensory afferents, and that muscle responses to EES are modulated during movement. Intraoperative recordings suggested similar properties in humans at rest. These modelling and experimental results can be applied for the development of neurotechnologies designed for the improvement of arm and hand control in humans with quadriplegia.
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http://dx.doi.org/10.1038/s41467-020-20703-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815834PMC
January 2021

Guidelines to Study and Develop Soft Electrode Systems for Neural Stimulation.

Neuron 2020 10;108(2):238-258

Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, 1202 Geneva, Switzerland. Electronic address:

Electrical stimulation of nervous structures is a widely used experimental and clinical method to probe neural circuits, perform diagnostics, or treat neurological disorders. The recent introduction of soft materials to design electrodes that conform to and mimic neural tissue led to neural interfaces with improved functionality and biointegration. The shift from stiff to soft electrode materials requires adaptation of the models and characterization methods to understand and predict electrode performance. This guideline aims at providing (1) an overview of the most common techniques to test soft electrodes in vitro and in vivo; (2) a step-by-step design of a complete study protocol, from the lab bench to in vivo experiments; (3) a case study illustrating the characterization of soft spinal electrodes in rodents; and (4) examples of how interpreting characterization data can inform experimental decisions. Comprehensive characterization is paramount to advancing soft neurotechnology that meets the requisites for long-term functionality in vivo.
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http://dx.doi.org/10.1016/j.neuron.2020.10.010DOI Listing
October 2020

Soft, Implantable Bioelectronic Interfaces for Translational Research.

Adv Mater 2020 Apr 16;32(17):e1906512. Epub 2020 Mar 16.

Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronics Interface, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, Geneva, 1202, Switzerland.

The convergence of materials science, electronics, and biology, namely bioelectronic interfaces, leads novel and precise communication with biological tissue, particularly with the nervous system. However, the translation of lab-based innovation toward clinical use calls for further advances in materials, manufacturing and characterization paradigms, and design rules. Herein, a translational framework engineered to accelerate the deployment of microfabricated interfaces for translational research is proposed and applied to the soft neurotechnology called electronic dura mater, e-dura. Anatomy, implant function, and surgical procedure guide the system design. A high-yield, silicone-on-silicon wafer process is developed to ensure reproducible characteristics of the electrodes. A biomimetic multimodal platform that replicates surgical insertion in an anatomy-based model applies physiological movement, emulates therapeutic use of the electrodes, and enables advanced validation and rapid optimization in vitro of the implants. Functionality of scaled e-dura is confirmed in nonhuman primates, where epidural neuromodulation of the spinal cord activates selective groups of muscles in the upper limbs with unmet precision. Performance stability is controlled over 6 weeks in vivo. The synergistic steps of design, fabrication, and biomimetic in vitro validation and in vivo evaluation in translational animal models are of general applicability and answer needs in multiple bioelectronic designs and medical technologies.
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http://dx.doi.org/10.1002/adma.201906512DOI Listing
April 2020

Microstructured thin-film electrode technology enables proof of concept of scalable, soft auditory brainstem implants.

Sci Transl Med 2019 10;11(514)

Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, École Polytechnique Fédérale de Lausanne (EPFL), 1202 Geneva, Switzerland.

Auditory brainstem implants (ABIs) provide sound awareness to deaf individuals who are not candidates for the cochlear implant. The ABI electrode array rests on the surface of the cochlear nucleus (CN) in the brainstem and delivers multichannel electrical stimulation. The complex anatomy and physiology of the CN, together with poor spatial selectivity of electrical stimulation and inherent stiffness of contemporary multichannel arrays, leads to only modest auditory outcomes among ABI users. Here, we hypothesized that a soft ABI could enhance biomechanical compatibility with the curved CN surface. We developed implantable ABIs that are compatible with surgical handling, conform to the curvature of the CN after placement, and deliver efficient electrical stimulation. The soft ABI array design relies on precise microstructuring of plastic-metal-plastic multilayers to enable mechanical compliance, patterning, and electrical function. We fabricated soft ABIs to the scale of mouse and human CN and validated them in vitro. Experiments in mice demonstrated that these implants reliably evoked auditory neural activity over 1 month in vivo. Evaluation in human cadaveric models confirmed compatibility after insertion using an endoscopic-assisted craniotomy surgery, ease of array positioning, and robustness and reliability of the soft electrodes. This neurotechnology offers an opportunity to treat deafness in patients who are not candidates for the cochlear implant, and the design and manufacturing principles are broadly applicable to implantable soft bioelectronics throughout the central and peripheral nervous system.
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http://dx.doi.org/10.1126/scitranslmed.aax9487DOI Listing
October 2019

Conformable Hybrid Systems for Implantable Bioelectronic Interfaces.

Adv Mater 2020 Apr 14;32(15):e1903904. Epub 2019 Oct 14.

Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Institute of Microengineering, Institute of Bioengineering, Center for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, 1202, Geneva, Switzerland.

Conformable bioelectronic systems are promising tools that may aid the understanding of diseases, alleviate pathological symptoms such as chronic pain, heart arrhythmia, and dysfunctions, and assist in reversing conditions such as deafness, blindness, and paralysis. Combining reduced invasiveness with advanced electronic functions, hybrid bioelectronic systems have evolved tremendously in the last decade, pushed by progress in materials science, micro- and nanofabrication, system assembly and packaging, and biomedical engineering. Hybrid integration refers here to a technological approach to embed within mechanically compliant carrier substrates electronic components and circuits prepared with traditional electronic materials. This combination leverages mechanical and electronic performance of polymer substrates and device materials, respectively, and offers many opportunities for man-made systems to communicate with the body with unmet precision. However, trade-offs between materials selection, manufacturing processes, resolution, electrical function, mechanical integrity, biointegration, and reliability should be considered. Herein, prominent trends in manufacturing conformable hybrid systems are analyzed and key design, function, and validation principles are outlined together with the remaining challenges to produce reliable conformable, hybrid bioelectronic systems.
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http://dx.doi.org/10.1002/adma.201903904DOI Listing
April 2020

Long-term functionality of a soft electrode array for epidural spinal cord stimulation in a minipig model.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:1432-1435

Long-term biointegration of man-made neural interfaces is influenced by the mechanical properties of the implant materials. Substantial experimental work currently aims at replacing conventional hard implant materials with soft alternatives that can favour a lower immune response. Here we assess the performance of a soft electrode array implanted in the spinal epidural space of a minipig model for a period of 6 months. The electrode array includes platinum-silicone electrode contacts and elastic thin-film gold interconnects embedded in silicone. textbfIn-vivo electrode impedance and voltage transients were monitored over time. Following implantation, epidural stimulation produced muscle-specific evoked potentials and visible muscle contractions. Over time, postoperative and stimulation induced changes in electrode impedance were observed. Such trends provide a basis for future technological improvements aiming at ensuring the stability of soft implantable electrodes for neural interfacing.
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http://dx.doi.org/10.1109/EMBC.2018.8512584DOI Listing
July 2018

Implantable microcoils for intracortical magnetic stimulation.

Sci Adv 2016 Dec 9;2(12):e1600889. Epub 2016 Dec 9.

Boston Veterans Affairs Healthcare System, Boston, MA 02130, USA.; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Neural prostheses that stimulate the neocortex have the potential to treat a wide range of neurological disorders. However, the efficacy of electrode-based implants remains limited, with persistent challenges that include an inability to create precise patterns of neural activity as well as difficulties in maintaining response consistency over time. These problems arise from fundamental limitations of electrodes as well as their susceptibility to implantation and have proven difficult to overcome. Magnetic stimulation can address many of these limitations, but coils small enough to be implanted into the cortex were not thought strong enough to activate neurons. We describe a new microcoil design and demonstrate its effectiveness for both activating cortical neurons and driving behavioral responses. The stimulation of cortical pyramidal neurons in brain slices in vitro was reliable and could be confined to spatially narrow regions (<60 μm). The spatially asymmetric fields arising from the coil helped to avoid the simultaneous activation of passing axons. In vivo implantation was safe and resulted in consistent and predictable behavioral responses. The high permeability of magnetic fields to biological substances may yield another important advantage because it suggests that encapsulation and other adverse effects of implantation will not diminish coil performance over time, as happens to electrodes. These findings suggest that a coil-based implant might be a useful alternative to existing electrode-based devices. The enhanced selectivity of microcoil-based magnetic stimulation will be especially useful for visual prostheses as well as for many brain-computer interface applications that require precise activation of the cortex.
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http://dx.doi.org/10.1126/sciadv.1600889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148213PMC
December 2016