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 maximise 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.

Ultrasound (US) is a promising modality for wirelessly powering implantable devices, requiring encapsulated receivers to ensure long-term stability. Traditional hermetic packaging often limits acoustic transmission, making polymer-based encapsulation a more suitable alternative. This study investigates how implant-grade polymers, thermoplastic polyurethane (TPU), parylene-C, and medical-grade silicones (MED-1000 and MED2-4213), affect the receive performance of piezoelectric micromachined ultrasonic transducers (PMUTs). Simulations and measurements between 1 and 7 MHz show that all tested materials exhibit transmission coefficients above 94% at nanometer- and micrometer-scale thicknesses, confirming their acoustic transparency. The results show that although coated PMUTs are acoustically well matched with the surrounding water medium, the added mechanical load of the coating can hinder membrane motion and reduce the energy transferred to the PMUTs. Modeling and experimental data demonstrate that stiffer coatings, such as parylene-C, lead to a reduced sensitivity when similar thicknesses are used. Likewise, residual stress in materials like MED-1000 can also degrade the performance. These effects are not evident from acoustic transmission measurements alone, underscoring the need to assess both acoustic and mechanical properties when selecting encapsulation materials. In general, softer materials offer excellent acoustic performance for PMUT encapsulation, while stiffer materials must be applied in thinner layers to avoid impairing PMUT function.

Correction to: Nature Communicationshttps://doi.org/10.1038/s41467-024-55298-4, published online 02 January 2025 In this article the following sentence was omitted from the acknowledgements section, ‘This research was funded by the following projects: Project CANDO (Controlling Network Dynamics with Optogenetics), funded by UK EPSRC (grant ref: NS/A000026/1) and the Wellcome Trust (contract ref: 102037/Z/13/Z)’. The original article has been corrected.

Miniaturization of next-generation active neural implants requires novel micro-packaging solutions that can maintain their long-term coating performance in the body. This work presents two thin-film coatings and evaluates their biostability and in vivo performance over a 7-month animal study. To evaluate the coatings on representative surfaces, two silicon microchips with different surface microtopography are used. Microchips are coated with either a ≈100 nm thick inorganic hafnium-based multilayer deposited via atomic layer deposition (ALD-ML), or a ≈6 µm thick hybrid organic–inorganic Parylene C and titanium-based ALD multilayer stack (ParC-ALD-ML). After 7 months of direct exposure to the body environment, the multilayer coatings are evaluated using optical and cross-sectional scanning electron microscopy. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is also used to evaluate the chemical stability and barrier performance of the layers after long-term exposure to body media. Results showed the excellent biostability of the 100 nm ALD-ML coating with no ionic penetration within the layer. For the ParC-ALD-ML, concurrent surface degradation and ion ingress are detected within the top ≈70 nm of the outer Parylene C layer. The results and evaluation techniques presented here can enable future material selection, packaging, and analysis, enhancing the functional stability of future chip-embedded neural implants.

This study explores the application of a novel transfer-free method for the synthesis of multilayer Chemical Vapour Deposition (CVD) graphene directly on transparent sub-strates, specifically to create transparent Microelectrode Arrays (MEAs) for optogenetic studies. Traditional methods typically involve a graphene transfer step that can compromise the material's integrity and electrical properties. By eliminating this step, our approach simplifies the fabrication process. The developed MEAs were characterised by Raman spectroscopy, op-tical transmittance, and electrochemical impedance spectroscopy. We also assessed the stability and recording capabilities of the fabricated MEAs, alongside a comparative assessment with a commercial MEA. Turbostratic graphene grown directly on quartz and sapphire was successfully achieved. Our transfer-free MEAs exhibit promising signal detection capabilities, despite a relatively high baseline noise of ∼ 23μ V. and a significantly large impedance at 1 kHz (3.2 to 9.89 M Ω) surpassing values in other studies. The devices exhibited low stability after exposure to liquid media during the soaking and ageing tests, causing large variations in the electrochemical measurements post-exposure. This was due to the permeability of the encapsulation layer and the biodegradability of the molybdenum structures, which led to significant structural and chemical changes in the devices. While further work is required to prevent the failure mechanisms of the device, this study demonstrates the feasibility of transparent MEA fabrication by means of a transfer-free approach directly on quartz substrates.

In the emerging research field of bioelectronic medicine, it has been indicated that neuromodulation of the vagus nerve (VN) has the potential to treat various conditions such as epilepsy, depression, and autoimmune diseases. In order to reduce side effects, as well as to increase the effectiveness of the delivered therapy, sub-fascicle stimulation specificity is required. In the electrical domain, increasing spatial selectivity can only be achieved using invasive and potentially damaging approaches like compressive forces or nerve penetration. To avoid these invasive methods while obtaining a high spatial selectivity, a 2-mm diameter extraneural cuff-shaped proof-of-concept design with integrated lead zirconate titanate (PZT) based ultrasound (US) transducers is proposed in this article. For the development of the proposed concept, wafer-level microfabrication techniques are employed. Moreover, acoustic measurements are performed on the device, in order to characterize the ultrasonic beam profiles of the integrated PZT-based US transducers. A focal spot size of around 200× 200 μ m is measured for the proposed cuff. Moreover, the curvature of the device leads to constructive interference of the US waves originating from multiple PZT-based US transducers, which in turn leads to an increase of 45% in focal pressure compared to the focal pressure of a single PZT-based US transducer. Integrating PZT-based US transducers in an extraneural cuff-shaped design has the potential to achieve high-precision US neuromodulation of the VN without requiring intraneural implantation.

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 (OOK) based on backscatter modulation, or active driving of a secondary transducer. In this article, we propose to superimpose subcarriers, effectively leveraging frequency-shift keying (FSK), 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 (ASICs), field programmable gate arrays (FPGAs), 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 and through a 5 cm tissue phantom 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.