Conference Agenda

Despite groundbreaking papers, much neuromodulation knowledge stagnates, failing to transition into patient care. The clinical need exists, with the neurological technologies market estimated at $13 billion in 2022, growing at 11.5% CAGR between 2023 and 2032.

Why are these research technologies failing to reach real-life applications?

Challenges in safety, cost, and acceptance hinder real-life applications. These include long-term stability, biocompati-bility, ease of surgical handling, power efficiency, miniaturization, regulatory compliance, and ethical considerations. To overcome these challenges, strategic planning and risk reduction are vital. In this presentation, we describe how a systematic and structured development strategy can facilitate the transition of ambitious medical devices from the ear-ly technology stage to the medical market.

To illustrate this strategy, we use a fictional neuromodulation product, “CEPHALFUSE”. Each development stage is discussed using real examples that are representative for the technical challenges that must be addressed.

We will follow together the story of “CEPHALFUSE”, a revolutionary health monitoring brain implant, from early con-cept to functional demonstration device. After carefully planning the itinerary of our innovation journey and collecting the technical requirements, we will embark for the conceptual phase, in which creative solutions are proposed for every function. We will then travel through the design phase, where we build purposeful prototypes and iterate towards inte-gration, miniaturization and reduction of risks. In the last step we verify and validate the neuromodulation device for the obtention of market approval. We will also see that the usability engineering can serve as a helpful travelling com-panion in the development.

With this example, we show that a solid process for innovation, testing, and regulatory compliance provides a useful structure to successfully complete the long, yet exciting journey from laboratory discovery to transformative neuro-technology applications.

Introduction: Preoperative electrically auditory evoked potentials (= eAEP, i.e., eABR for brainstem, eAMLR for midbrain, and eALR for cortex) can be performed under local anesthesia, achieving subjective sensation and hearing in patients having a functional auditory nerve. For intraoperative eAEP, we stimulate the auditory nerve with an intra-cochlear test electrode like a cochlear implant (= CI) and stimulate basally when using an extra-cochlear electrode. These measurements aim to confirm preoperative findings (e.g. uncertain preoperative eABR) or intraoperative decisions (e.g. vestibular schwannoma resection). Methods: Preoperative eAEP can be performed with the trans-tympanic stimulation electrode and a neurological EP system for recording the responses. In addition, eAEP under local anesthesia allows for preoperative diagnostics of subjective sensation. For intraoperative eAEP, the intra-cochlear auditory nerve test system (= ANTS) system is preferable showing similar results to the gold standard CI-eABR (i.e., eABR using a CI for stimulation). The eAMLR can be used only preoperatively in case of ambiguous EABR or for extended analysis of the auditory pathway. Results: During preoperative eAEP in local anesthesia, an eABR is essential. eAMLR and eALR are optional. The subjective sensation can be recorded in parallel. A reliable response often avoids eAEP under general anesthesia. eAEP under general anesthesia should be performed as rarely as possible preoperatively to avoid unnecessary intraoperative eAEP, performed usually directly before cochlear implantation. Extra-cochlear stimulation avoids mechanical trauma and possible intra-cochlear infections. However, intra-cochlear stimulation is usually recommended due to larger response amplitudes; in fact, the ANTS electrode provides more stable monitoring. Conclusion: eAEP can be diagnostically useful preoperatively and intraoperatively with the concept presented here. Since not all clinics are familiar with these methods, a learning curve may be necessary.

The corrosion behavior of platinum electrodes in cochlear implant (CI) systems is a critical factor affecting their long-term functionality. This study investigated the influence of surface roughness of the platinum electrodes on their corrosion behavior. The results of in vitro experiments indicate that higher surface roughness tends to accelerate corrosion by providing numerous initiation sites. Although the electrochemical measurements on platinum electrodes with different surface roughnesses showed only slight differences in terms of shifts in potentials and higher corrosion current densities, data from literature suggests an enhanced charge capacity with rougher surfaces. These findings contribute to an understanding of the failure mechanisms of CIs and can ultimately help to improve the design and durability of CI systems.

Acoustic or visual warning signals for workers in hazardous situations might fail under loud and/or low-visibility work situations. A warning system that uses electrocutaneous stimulation can overcome this problem. This study aimed to compare vertical, diagonal, and horizontal current stimulation directions at the upper arm to select the one with the lowest amount of muscle twitching. Fourteen electrodes were attached in two rows to the upper right arm of 15 participants. The stimulation was conducted with bi-phasic rectangular pulses of 150 μs and amplitudes of up to 25 mA. Muscle twitch thresholds have been determined and a circumferential stimulation signal was presented as warning pattern for the three current stimulation directions and evaluated regarding alertness, discomfort, and urgency. For single stimulation pulses, muscle twitches occurred slightly less often at the horizontal stimulation direction compared to the other two and muscle twitch thresholds showed no systematic differences. For the warning patterns, no considerable differences were found regarding the evaluation of alertness, discomfort, and urgency and no differences were found for muscle twitching. In conclusion, all orientations seem suitable for warning pattern presentation and none of the directions has a clear advantage in reducing muscle twitch.

Introduction

Bioelectronic medicine aims to miniaturize and implant devices deeper into the body. This requires alternative forms of energy transmission than inductive coupling. Ultrasound offers an alternative approach to power deep-seated implants. Novel membrane-based ultrasound transducers allow implants to be miniaturized and thus being supplied with energy at almost any point in the body. Since encapsulation of ultrasonic transducers with hermetic packaging severely attenuates the power of ultrasonic waves, the aim is to encapsulate the implants with non-hermetic materials, in this case PDMS. In this contribution, one-component silicone is used, in which by-products evaporate during curing, leading to shrinkage in the silicone and to inner stresses.

Methods

A computational model of the physical properties of a micromachined ultrasonic transducer membrane and the silicone coating was created in COMSOL. Maximum deflections of the membranes under forced excitation and the inner stresses in cured silicone as a result of the shrinkage were calculated. These values were applied to simulate the stress at the membrane’s interface, the eigenmodes of the membrane and a possible shift in the resonance frequency.

Results

The inner stresses (σ = 4 kPa) inside the silicone coating result in stress at the interface between the membrane and the silicone, with a maximum at the center of the membrane. This stress also leads to an additional damped deflection (Δd = 7 nm), when the membrane is excited. In order to achieve an equally strong deflection, the membrane must now be excited with greater energy or an adjusted resonance frequency.

Conclusion

A computational model was developed and simulated in COMSOL to compute the effect of a one-component silicone adhesive on a micromachined ultrasonic membrane. The stress at the interface changed the membrane’s oscillation characteristics, and the maximum deflection was damped. The simulation of a single membrane can be extrapolated and used for micromachined ultrasonic transducers for further suitable coating materials.