Biology subjects

Holzapfel, L.

Publications and source records attributed to Holzapfel, L..

5 recordsLinked to original sources

bioRxiv2025

Ultrasound Transparent Neural Interfaces for Multimodal Interaction

Neural interfaces that unify diagnostic and therapeutic functionalities hold particular promise for advancing both fundamental neuroscience and clinical neurotechnology. Functional ultrasound imaging (fUSI) has recently emerged as a powerful modality for high-resolution, non-invasive monitoring of brain function and structure. However, conventional metal-based microelectrodes typically impede ultrasound propagation, limiting compatibility with fUSI. Here, we present flexible, ultrasound-transparent neural interfaces that retain practical metal thicknesses while achieving high acoustic transparency. We introduce a theoretical and simulation-based framework to investigate the conditions under which commonly used polymers and metals in neural interfaces can become acoustically transparent. Based on these insights, we propose design guidelines that maximize ultrasound transmission through soft neural interfaces. We experimentally validate our approach through immersion experiments and by demonstrating the acoustic transparency of a suitably engineered interface using fUSI in phantom and in vivo experiments. Finally, we discuss the potential extension of this approach to therapeutic focused ultrasound (FUS). This work establishes a foundation for the development of multimodal neural interfaces with enhanced diagnostic and therapeutic capabilities, enabling both scientific discovery and translational impact.

bioengineering↗

bioRxiv2025

Transparent transfer-free multilayer graphene microelectrodes enable high quality recordings in brain slices

Resolving the underlying mechanisms of complex brain functions and associated disorders remains a major challenge in neuroscience, largely due to the difficulty in mapping large-scale neural network dynamics with high temporal and spatial resolution. Multimodal neural platforms that integrate optical and electrical modalities offer a promising approach that surpasses resolution limits. Over the last decade, transparent graphene microelectrodes have been proposed as highly suitable multimodal neural interfaces. However, their fabrication commonly relies on the manual transfer process of pre-grown graphene sheets which introduces reliability and scalability issues. In this study, multilayer graphene microelectrode arrays (MEAs) with electrode sizes as small as 10-50 {micro}m in diameter, are fabricated using a transfer-free process on a transparent substrate for in vitro multimodal platforms. Through acute experiments using cerebellar brain slices, their ability to detect spontaneous extracellular spiking activity from neural cells, with a high signal-to-noise ratio up to 30-40 dB, is demonstrated. The recorded signal quality is found to be more limited by the electrode-tissue coupling than the MEA technology itself. Overall, this study shows the potential of transfer-free multilayer graphene MEAs to interface with neural tissue, which paves the way to advance neuroscientific research through the next-generation of multimodal neural interfaces.

bioengineering↗

bioRxiv2025

Ultrasonically Powered Neuromodulation Platform Intended for Spatially and Directionally Selective Electrical Stimulation

Vagus nerve stimulation (VNS), a well-established application of electrical neuromodulation, has been effective in treating dis-orders such as epilepsy and depression. Recent neuroscientific advancements have identified further potential in VNS, calling for technical advancements to explore these possibilities. To address this, we developed a neuromodulation platform that can perform both neural activity excitation and inhibition, to further explore spatially and directionally selective stimulation. The platform can be powered wirelessly through ultrasound and includes a charge balancing mechanism to enhance stimulation safety. The platform performs biphasic and monophasic voltage-controlled stimulation, using 6 electrodes for excitation and 2 for inhibition. The pulse width can be varied between 0 and 1500 {micro}s, and the pulse repetition rate between 1 Hz and 1 kHz for excitation and 1 kHz to 50 kHz for inhibition. The implemented charge balancing mechanism uses a digital PID controller to reduce the voltage offset at the stimulation site to values as low as 2 mV. The introduced neuromodulation platform provides a versatile experimental tool intended for, but not limited to, VNS in pre-clinical and clinical settings. It is designed using only commercially available components and is easily reproducible, allowing to explore the possibilities of VNS while identifying the necessary components and processes for developing a miniaturized version.

bioengineering↗

bioRxiv2025

Effects of Soft Encapsulation on the Receive Performance of PMUTs for Implantable Devices

Recent studies present ultrasound (US) as a promising candidate for powering implantable devices, requiring in-tegrated and encapsulated receivers to ensure longevity. Conventional hermetic packaging can hinder acoustic transmission, making polymer-based approaches desirable. This study evaluates how polymers commonly used for implants (i.e., thermoplastic polyurethane, parylene-C, medical-grade silicones, and polyimide) affect the receive performance of piezoelectric micromachined ultrasound transducers (PMUTs). Simulations and measurements between 1 and 7 MHz show transmission coefficients above 94 % for material thicknesses in the nm and m ranges. A theoretical analysis of the mechanical properties guides material selection for later PMUT encapsulation, focusing on polyurethane, parylene-C, and two medical-grade silicones (MED-1000, MED2-4213). In a complete system comprising encapsulated PMUTs, mechanical and acoustic properties, along with interface mismatch between the encapsulation and the PMUTs, influence the receive performance of the devices. Finite element modeling (FEM) and measurements evaluate the impedance and receive sensitivity of encapsulated PMUTs. The results show that residual stress or higher stiffness in some polymers, reduces the receive sensitivity, an effect not evident from only analysing the acoustic transmission through coatings. However, this study demonstrates that upon careful consideration of the acoustic and mechanical properties as well as thickness selection, polymers commonly used for implantable devices can effectively be used for PMUT encapsulation.

bioengineering↗

bioRxiv2022

A robust backscatter modulation scheme for uninterrupted ultrasonic powering and back-communication of deep implants

Traditionally, implants are powered by batteries, which have to be recharged by an inductive power link. In the recent years, ultrasonic power links are being investigated, promising more available power for deeply implanted miniaturized devices. These implants often need to transfer back information. For ultrasonically powered implants, this is usually achieved with On-Off Keying based on backscatter modulation, or active driving of a secondary transducer. In this paper, we propose to superimpose subcarriers, effectively leveraging Frequency-Shift Keying, which increases the robustness of the link against interference and fading. It also allows for simultaneous powering and communication, and inherently provides the possibility of frequency domain multiplexing for implant networks. The modulation scheme can be implemented in miniaturized application specific integrated circuits, field programmable gate arrays, and microcontrollers. We have validated this modulation scheme in a water tank during continuous ultrasound and movement. We achieved symbol rates of up to 104 kBd, and were able to transfer data through 20 cm of water, with additional misalignment and during movements. This approach could provide a robust uplink for miniaturized implants that are located deep inside the body and need continuous ultrasonic powering.

bioengineering↗