Julian Hengsteler

Last Name

Hengsteler

First Name

Julian

ORCID

0000-0002-6635-7673

Organisational unit

03741 - Vörös, Janos / Vörös, Janos

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Publications1 - 10 of 15

An Implantable Biohybrid Neural Interface Toward Synaptic Deep Brain Stimulation
Sifringer, Léo; Fratzl, Alex; Clément, Blandine F.; et al. (2025)
Advanced Functional Materials
In patients with sensory nerve loss, such as those experiencing optic nerve damage that leads to vision loss, the thalamus no longer receives the corresponding sensory input. To restore functional sensory input, it is necessary to bypass the damaged circuits, which can be achieved by directly stimulating the appropriate sensory thalamic nuclei. However, available deep brain stimulation electrodes do not provide the resolution required for effective sensory restoration. Therefore, this work develops an implantable biohybrid neural interface aimed at innervating and synaptically stimulating deep brain targets. The interface combines a stretchable stimulation array with an aligned microfluidic axon guidance system seeded with neural spheroids to facilitate the development of a 3 mm long nerve-like structure. A bioresorbable hydrogel nerve conduit is used as a bridge between the tissue and the biohybrid implant. Stimulation of the spheroids within the biohybrid structure in vitro and use of high-density CMOS microelectrode arrays show faithful activity conduction across the device. Although functional in vivo innervation and synapse formation has not yet been achieved in this study, implantation of the biohybrid nerve onto the mouse cortex shows that neural spheroids grow axons in vivo and remain functionally active for more than 22 days post-implantation.
Nanopores in Action - Advancing Metal 3D Printing and Single-Molecule Sensing
Hengsteler, Julian (2025)
Nanopores have emerged as valuable tools in nanotechnology, finding diverse applications from DNA sequencing to advanced manufacturing. Their ability to confine and control matter at the nanoscale has led to breakthrough technologies in biosensing, where biological nanopores have enabled commercial DNA sequencing platforms. In parallel, solid-state nanopores, particularly in the form of glass nanopipettes, have shown utility in high-resolution microscopy, single-cell analysis, and electrochemical fabrication. However, several challenges remain in both the manufacturing and sensing applications of solid-state nanopores, particularly regarding spatial resolution, long-term stability, and control over molecular transport. This thesis explores the applications of nanopores in nanotechnology, focusing on two main areas: electrochemical 3D printing and single-molecule biosensing. The work demonstrates how nanometric apertures - from nanopipettes to nanofluidic channels and interface nanopores - can be harnessed for precise control of ion and molecule movement at the nanoscale, addressing current technological limitations. In electrochemical 3D printing, this thesis introduces new methodologies to overcome key limitations in nanoscale metal fabrication. While current approaches struggle to achieve features below 100 nm due to nozzle clogging and limited control over material deposition, this work presents an approach for meniscus-confined electrodeposition that enables the creation of metal structures with voxel sizes down to 25 nm. The work also presents a technique for multi-material printing from a single nozzle, allowing the selective deposition of different metals with voxel sizes as small as 125 nm - an advance toward fabricating functional devices such as 3D micro- or nanobatteries. For biosensing applications, the thesis develops an on-chip, size-tunable interfacial nanopore system capable of dynamic pore size adjustment. Unlike conventional solid-state nanopores with fixed dimensions, this platform enables real-time control over pore size and the creation of multiple pores in series, representing a step toward single-molecule protein analysis and potential sequencing applications. The system's architecture allows for repeated measurements of the same molecule, potentially enabling higher accuracy in molecular analysis than single-pore systems. This work examines fundamental aspects of both applications, including ion transport physics, surface chemistry considerations, and implementation challenges. The thesis provides insights and practical guidelines for advancing nanopore technology in both 3D printing and biosensing applications. The developed methodologies and platforms present new possibilities for nanoscale fabrication and analysis, with potential applications ranging from electronics to medical diagnostics. Our investigation of nanopores in action advances our understanding of nanoscale phenomena while providing solutions for current technological challenges in nanofabrication and molecular analysis.
Beginner's Guide to Micro- and Nanoscale Electrochemical Additive Manufacturing
Hengsteler, Julian; Kanes, Karuna Aurel; Khasanova, Liaisan; et al. (2023)
Annual Review of Analytical Chemistry
Electrochemical additive manufacturing is an advanced microfabrication technology capable of producing features of almost unlimited geometrical complexity. A unique combination of the capacity to process conductive materials, design freedom, and micro- to nanoscale resolution offered by these electrochemical techniques promises tremendous opportunities for a multitude of future applications spanning microelectronics, sensing, robotics, and energy storage. This review aims to equip readers with the basic principles of electrochemical 3D printing at the small length scale. By describing the basic principles of electrochemical additive manufacturing technology and using the recent advances in the field, this beginner's guide illustrates how controlling the fundamental phenomena that underpin the print process can be used to vary dimensions, morphology, and microstructure of printed structures.
Nanoscale Patterning of in Vitro Neuronal Circuits
Mateus, José C.; Weaver, Sean; van Swaay, Dirk; et al. (2022)
ACS Nano
Methods for patterning neurons in vitro have gradually improved and are used to investigate questions that are difficult to address in or ex vivo. Though these techniques guide axons between groups of neurons, multiscale control of neuronal connectivity, from circuits to synapses, is yet to be achieved in vitro. As studying neuronal circuits with synaptic resolution in vivo poses significant challenges, we present an in vitro alternative to validate biophysical and computational models. In this work we use a combination of electron beam lithography and photolithography to create polydimethylsiloxane (PDMS) structures with features ranging from 150 nm to a few millimeters. Leveraging the difference between average axon and dendritic spine diameters, we restrict axon growth while allowing spines to pass through nanochannels to guide synapse formation between small groups of neurons (i.e., nodes). We show this technique can be used to generate large numbers of isolated feed-forward circuits where connections between nodes are restricted to regions connected by nanochannels. Using a genetically encoded calcium indicator in combination with fluorescently tagged postsynaptic protein, PSD-95, we demonstrate functional synapses can form in this region.
Driving electrochemical reactions at the microscale using CMOS microelectrode arrays
Duru, Jens; Rüfenacht, Arielle; Löhle, Josephine; et al. (2023)
Lab on a Chip
Precise control of pH values at electrode interfaces enables the systematic investigation of pH-dependent processes by electrochemical means. In this work, we employed high-density complementary metal-oxide-semiconductor (CMOS) microelectrode arrays (MEAs) as miniaturized systems to induce and confine electrochemical reactions in areas corresponding to the pitch of single electrodes (17.5 mu m). First, we present a strategy for generating localized pH patterns on the surface of the CMOS MEA with unprecedented spatial resolution. Leveraging the versatile routing capabilities of the switch matrix beneath the CMOS MEA, we created arbitrary combinations of anodic and cathodic electrodes and hence pH patterns. Moreover, we utilized the system to produce polymeric surface patterns by additive and subtractive methods. For additive patterning, we controlled the in situ formation of polydopamine at the microelectrode surface through oxidation of free dopamine above a threshold pH > 8.5. For subtractive patterning, we removed cell-adhesive poly-L-lysine from the electrode surface and backfilled the voids with antifouling polymers. Such polymers were chosen to provide a proof-of-concept application of controlling neuronal growth via electrochemically-induced patterns on the CMOS MEA surface. Importantly, our platform is compatible with commercially available high-density MEAs and requires no custom equipment, rendering the findings generalizable and accessible.
Bringing Electrochemical Three-Dimensional Printing to the Nanoscale
Hengsteler, Julian; Mandal, Barnik; van Nisselroy, Cathelijn; et al. (2021)
Nano Letters
Nanoscale 3D printing is attracting attention as an alternative manufacturing technique for a variety of applications from electronics and nanooptics to sensing, nanorobotics, and energy storage. The constantly shrinking critical dimension in state-of-the-art technologies requires fabrication of complex conductive structures with nanometer resolution. Electrochemical techniques are capable of producing impurity-free metallic conductors with superb electrical and mechanical properties, however, true nanoscale resolution (<100 nm) remained unattainable. Here, we set new a benchmark in electrochemical 3D printing. By employing nozzles with dimensions as small as 1 nm, we demonstrate layer-by-layer manufacturing of 25 nm diameter voxels. Full control of the printing process allows adjustment of the feature size on-the-fly, printing tilted, and overhanging structures. On the basis of experimental evidence, we estimate the limits of electrochemical 3D printing and discuss the origins of this new resolution frontier.
An experimental paradigm to investigate stimulation dependent activity in topologically constrained neuronal networks
Ihle, Stephan J.; Girardin, Sophie; Felder, Thomas; et al. (2022)
Biosensors and Bioelectronics
We present a stimulate and record paradigm to examine the behavior of multiple neuronal networks with controlled topology in vitro. Our approach enabled us to electrically induce and record neuronal activity from 60 independent networks in parallel over multiple weeks. We investigated the network performance of neuronal networks of primary hippocampal neurons until 29 days in vitro. We introduced a systematic stimulate and record protocol during which well-defined 4-node neural networks were stimulated electrically 4 times per second (4Hz) and their response was recorded over many days. We found that the network response pattern to a stimulus remained fairly stable for at least 12 h. Moreover, continuous stimulation over multiple weeks did not cause a significant change in the stimulation-induced mean spiking frequency of a circuit. We investigated the effect of stimulation amplitude and stimulation timing on the detailed network response. Finally, we could show that our setup can apply complex stimulation protocols with 125 different stimulation patterns. We used these patterns to perform basic addition tasks with the network, revealing the highly non-linear nature of biological networks’ responses to complex stimuli.
Additive Manufacturing of Nanoscale Multimaterial Voxels Via Meniscus-Confined Electrodeposition
Sprengel, Simon; Hengsteler, Julian; Zeng, Peng; et al. (2026)
ACS Nano
Advanced applications featuring sub-microscale and nanoscale metallic structures, which include energy storage devices, nanophotonic elements, and nanoelectronic interfaces, require three-dimensional multimaterial structural elements. Here, we present an approach for highly localized meniscus-confined electrodeposition based on double-barrel nanopipettes capable of producing high-aspect ratio metallic structures with a wide range of elemental compositions. This is enabled by the possibility of finely tuning local ionic content directly inside the liquid meniscus by applying voltage bias between the barrels filled with different electrolytes. This provides a platform for fast switching between materials within a single voxel and the fabrication of smooth material gradients via tunable electrodeposition, which is also characterized by improved mass-transport and faster print rates. We demonstrate the capability of this approach by producing various arrangements of Cu-Au and Au-Pt voxels with ca. 200 nm lateral resolution, which are formed from fully dense (non-porous) polycrystalline metallic alloys with the evidence of metastable microstructural features.
Microstructure-driven electrical conductivity optimization in additively manufactured microscale copper interconnects
Menétrey, Maxence; van Nisselroy, Cathelijn; Xu, Mengjia; et al. (2023)
RSC Advances
As the microelectronics field pushes to increase device density through downscaling component dimensions, various novel micro- and nano-scale additive manufacturing technologies have emerged to expand the small scale design space. These techniques offer unprecedented freedom in designing 3D circuitry but have not yet delivered device-grade materials. To highlight the complex role of processing on the quality and microstructure of AM metals, we report the electrical properties of micrometer-scale copper interconnects fabricated by Fluid Force Microscopy (FluidFM) and Electrohydrodynamic-Redox Printing (EHD-RP). Using a thin film-based 4-terminal testing chip developed for the scope of this study, the electrical resistance of as-printed metals is directly related to print strategies and the specific morphological and microstructural features. Notably, the chip requires direct synthesis of conductive structures on an insulating substrate, which is shown for the first time in the case of FluidFM. Finally, we demonstrate the unique ability of EHD-RP to tune the materials resistivity by one order of magnitude solely through printing voltage. Through its novel electrical characterization approach, this study offers unique insight into the electrical properties of micro- and submicrometer-sized copper interconnects and steps towards a deeper understanding of micro AM metal properties for advanced electronics applications.
Engineered Biological Neural Networks on High Density CMOS Microelectrode Arrays
Duru, Jens; Küchler, Joël; Ihle, Stephan J.; et al. (2022)
Frontiers in Neuroscience
In bottom-up neuroscience, questions on neural information processing are addressed by engineering small but reproducible biological neural networks of defined network topology in vitro. The network topology can be controlled by culturing neurons within polydimethylsiloxane (PDMS) microstructures that are combined with microelectrode arrays (MEAs) for electric access to the network. However, currently used glass MEAs are limited to 256 electrodes and pose a limitation to the spatial resolution as well as the design of more complex microstructures. The use of high density complementary metal-oxide-semiconductor (CMOS) MEAs greatly increases the spatial resolution, enabling sub-cellular readout and stimulation of neurons in defined neural networks. Unfortunately, the non-planar surface of CMOS MEAs complicates the attachment of PDMS microstructures. To overcome the problem of axons escaping the microstructures through the ridges of the CMOS MEA, we stamp-transferred a thin film of hexane-diluted PDMS onto the array such that the PDMS filled the ridges at the contact surface of the microstructures without clogging the axon guidance channels. This method resulted in 23 % of structurally fully connected but sealed networks on the CMOS MEA of which about 45 % showed spiking activity in all channels. Moreover, we provide an impedance-based method to visualize the exact location of the microstructures on the MEA and show that our method can confine axonal growth within the PDMS microstructures. Finally, the high spatial resolution of the CMOS MEA enabled us to show that action potentials follow the unidirectional topology of our circular multi-node microstructure.

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Julian Hengsteler

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