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A. Velea
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12 records found
1
Journal article
(2026)
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Raphael Panskus, Andrada Iulia Velea, Lukas Holzapfel, Christos Pavlou, Flora Nelissen, Rick Waasdorp, David Maresca, Valeria Gazzola, Vasiliki Giagka, More authors...
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.
...
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.
Bimodal neural interfaces
Design, fabrication and characterisation considerations for the seamless operation across electrical and acoustic domains
Neurological disorders are the leading cause of disability, affecting millions around the world, and often resulting in severe motor, sensory, or cognitive impairments. Conventional pharmaceutical treatments can alleviate symptoms, but rarely restore full neurological function, and their lack of specificity often leads to significant long-term side effects. Miniaturized neural interfaces, on the other hand, have the potential of providing critical insights into the nervous system, as well as, enabling more precise therapies for patients. Although electrical stimulation has primarily been the method of interaction with the nervous system, ultrasound is emerging as a minimally invasive and highly specific alternative for neuromodulation, but also communication and wireless power transfer. Bimodal neural interfaces, combining electrical and acoustic modalities, within a single, fully integrated platform, are of great importance for directly comparing their effects, yet to date, no such tools are available. Developing bimodal neural interfaces is a complex task that demands a deep understanding of the interactions between different modalities, materials, and components.
To this end, several research questions have been addressed. The first, relates to one of the final steps in the development of bimodal neural interfaces, the encapsulation. Given that miniaturized micromachined ultrasonic devices are a fundamental building block of the proposed systems, how can they be best encapsulated in polymers that are mechanically compliant with the soft biological tissue, while still preserving their acoustic performance? The second research question focuses on the development and integration of the constituent components of a bimodal neural interface. In particular, it addresses how can micromachined ultrasonic transducers and microelectrodes coexist and not interfere with each other during operation. Furthermore, the requirements differ depending on the intended application. In the case of an in-vitro bimodal neural interface, flat and rigid micromachined devices are required, whereas for implantable applications, thin, flexible, curved transducers and electrodes are required, substantially increasing the design and fabrication complexity of the devices.
This thesis aims to address current technological limitations by designing, fabricating, and validating two different types of miniaturized bimodal neural interfaces for both in-vitro and implantable applications. To achieve this, the interaction between micromachined ultrasonic transducers (MUTs) and common polymer-based coatings used in neural interface packaging was first evaluated through simulations and measurements on the individual materials as well as encapsulated transducers. All tested materials exhibited high acoustic transparency (>94 %), but performance was also influenced by mechanical factors such as stiffness, residual stress, and flexural rigidity. Building on these insights, two bimodal neural interfaces were then developed. For the first, an in-vitro microelectrode-microtransducer array (MEMTA), a less conventional, reduced-step microfabrication process was adopted, employing maskless photolithography and sputtering through shadow masks. Furthermore, characterization through a multi-domain framework, treating the device as an integrated system rather than as a collection of independent components, was also employed. Next, a cuff-shaped implantable bimodal neural interface comprising thin-film Au electrodes and flexible MUTs embedded in thermoplastic polyurethane, was prototyped to assess how encapsulation affects membrane displacement and acoustic output in curved MUTs.
This work outlines design, fabrication, and analysis approaches that overcome current technological limitations and advance the development of bimodal neural interfaces. Nevertheless, further studies are needed to evaluate the long-term stability of the devices in wet environments, including the effects of microvibrations on the encapsulated MUTs and the impact of bending on encapsulation integrity and device performance. In addition, the electroacoustic effects that may arise in the proposed bimodal neural interfaces when operating in wet ionic environments require careful investigation. Furthermore, developing ultrasonically powered bimodal neural interfaces could fully unlock the potential of next-generation, miniaturized, and versatile neural interfaces.
...
To this end, several research questions have been addressed. The first, relates to one of the final steps in the development of bimodal neural interfaces, the encapsulation. Given that miniaturized micromachined ultrasonic devices are a fundamental building block of the proposed systems, how can they be best encapsulated in polymers that are mechanically compliant with the soft biological tissue, while still preserving their acoustic performance? The second research question focuses on the development and integration of the constituent components of a bimodal neural interface. In particular, it addresses how can micromachined ultrasonic transducers and microelectrodes coexist and not interfere with each other during operation. Furthermore, the requirements differ depending on the intended application. In the case of an in-vitro bimodal neural interface, flat and rigid micromachined devices are required, whereas for implantable applications, thin, flexible, curved transducers and electrodes are required, substantially increasing the design and fabrication complexity of the devices.
This thesis aims to address current technological limitations by designing, fabricating, and validating two different types of miniaturized bimodal neural interfaces for both in-vitro and implantable applications. To achieve this, the interaction between micromachined ultrasonic transducers (MUTs) and common polymer-based coatings used in neural interface packaging was first evaluated through simulations and measurements on the individual materials as well as encapsulated transducers. All tested materials exhibited high acoustic transparency (>94 %), but performance was also influenced by mechanical factors such as stiffness, residual stress, and flexural rigidity. Building on these insights, two bimodal neural interfaces were then developed. For the first, an in-vitro microelectrode-microtransducer array (MEMTA), a less conventional, reduced-step microfabrication process was adopted, employing maskless photolithography and sputtering through shadow masks. Furthermore, characterization through a multi-domain framework, treating the device as an integrated system rather than as a collection of independent components, was also employed. Next, a cuff-shaped implantable bimodal neural interface comprising thin-film Au electrodes and flexible MUTs embedded in thermoplastic polyurethane, was prototyped to assess how encapsulation affects membrane displacement and acoustic output in curved MUTs.
This work outlines design, fabrication, and analysis approaches that overcome current technological limitations and advance the development of bimodal neural interfaces. Nevertheless, further studies are needed to evaluate the long-term stability of the devices in wet environments, including the effects of microvibrations on the encapsulated MUTs and the impact of bending on encapsulation integrity and device performance. In addition, the electroacoustic effects that may arise in the proposed bimodal neural interfaces when operating in wet ionic environments require careful investigation. Furthermore, developing ultrasonically powered bimodal neural interfaces could fully unlock the potential of next-generation, miniaturized, and versatile neural interfaces.
...
Neurological disorders are the leading cause of disability, affecting millions around the world, and often resulting in severe motor, sensory, or cognitive impairments. Conventional pharmaceutical treatments can alleviate symptoms, but rarely restore full neurological function, and their lack of specificity often leads to significant long-term side effects. Miniaturized neural interfaces, on the other hand, have the potential of providing critical insights into the nervous system, as well as, enabling more precise therapies for patients. Although electrical stimulation has primarily been the method of interaction with the nervous system, ultrasound is emerging as a minimally invasive and highly specific alternative for neuromodulation, but also communication and wireless power transfer. Bimodal neural interfaces, combining electrical and acoustic modalities, within a single, fully integrated platform, are of great importance for directly comparing their effects, yet to date, no such tools are available. Developing bimodal neural interfaces is a complex task that demands a deep understanding of the interactions between different modalities, materials, and components.
To this end, several research questions have been addressed. The first, relates to one of the final steps in the development of bimodal neural interfaces, the encapsulation. Given that miniaturized micromachined ultrasonic devices are a fundamental building block of the proposed systems, how can they be best encapsulated in polymers that are mechanically compliant with the soft biological tissue, while still preserving their acoustic performance? The second research question focuses on the development and integration of the constituent components of a bimodal neural interface. In particular, it addresses how can micromachined ultrasonic transducers and microelectrodes coexist and not interfere with each other during operation. Furthermore, the requirements differ depending on the intended application. In the case of an in-vitro bimodal neural interface, flat and rigid micromachined devices are required, whereas for implantable applications, thin, flexible, curved transducers and electrodes are required, substantially increasing the design and fabrication complexity of the devices.
This thesis aims to address current technological limitations by designing, fabricating, and validating two different types of miniaturized bimodal neural interfaces for both in-vitro and implantable applications. To achieve this, the interaction between micromachined ultrasonic transducers (MUTs) and common polymer-based coatings used in neural interface packaging was first evaluated through simulations and measurements on the individual materials as well as encapsulated transducers. All tested materials exhibited high acoustic transparency (>94 %), but performance was also influenced by mechanical factors such as stiffness, residual stress, and flexural rigidity. Building on these insights, two bimodal neural interfaces were then developed. For the first, an in-vitro microelectrode-microtransducer array (MEMTA), a less conventional, reduced-step microfabrication process was adopted, employing maskless photolithography and sputtering through shadow masks. Furthermore, characterization through a multi-domain framework, treating the device as an integrated system rather than as a collection of independent components, was also employed. Next, a cuff-shaped implantable bimodal neural interface comprising thin-film Au electrodes and flexible MUTs embedded in thermoplastic polyurethane, was prototyped to assess how encapsulation affects membrane displacement and acoustic output in curved MUTs.
This work outlines design, fabrication, and analysis approaches that overcome current technological limitations and advance the development of bimodal neural interfaces. Nevertheless, further studies are needed to evaluate the long-term stability of the devices in wet environments, including the effects of microvibrations on the encapsulated MUTs and the impact of bending on encapsulation integrity and device performance. In addition, the electroacoustic effects that may arise in the proposed bimodal neural interfaces when operating in wet ionic environments require careful investigation. Furthermore, developing ultrasonically powered bimodal neural interfaces could fully unlock the potential of next-generation, miniaturized, and versatile neural interfaces.
To this end, several research questions have been addressed. The first, relates to one of the final steps in the development of bimodal neural interfaces, the encapsulation. Given that miniaturized micromachined ultrasonic devices are a fundamental building block of the proposed systems, how can they be best encapsulated in polymers that are mechanically compliant with the soft biological tissue, while still preserving their acoustic performance? The second research question focuses on the development and integration of the constituent components of a bimodal neural interface. In particular, it addresses how can micromachined ultrasonic transducers and microelectrodes coexist and not interfere with each other during operation. Furthermore, the requirements differ depending on the intended application. In the case of an in-vitro bimodal neural interface, flat and rigid micromachined devices are required, whereas for implantable applications, thin, flexible, curved transducers and electrodes are required, substantially increasing the design and fabrication complexity of the devices.
This thesis aims to address current technological limitations by designing, fabricating, and validating two different types of miniaturized bimodal neural interfaces for both in-vitro and implantable applications. To achieve this, the interaction between micromachined ultrasonic transducers (MUTs) and common polymer-based coatings used in neural interface packaging was first evaluated through simulations and measurements on the individual materials as well as encapsulated transducers. All tested materials exhibited high acoustic transparency (>94 %), but performance was also influenced by mechanical factors such as stiffness, residual stress, and flexural rigidity. Building on these insights, two bimodal neural interfaces were then developed. For the first, an in-vitro microelectrode-microtransducer array (MEMTA), a less conventional, reduced-step microfabrication process was adopted, employing maskless photolithography and sputtering through shadow masks. Furthermore, characterization through a multi-domain framework, treating the device as an integrated system rather than as a collection of independent components, was also employed. Next, a cuff-shaped implantable bimodal neural interface comprising thin-film Au electrodes and flexible MUTs embedded in thermoplastic polyurethane, was prototyped to assess how encapsulation affects membrane displacement and acoustic output in curved MUTs.
This work outlines design, fabrication, and analysis approaches that overcome current technological limitations and advance the development of bimodal neural interfaces. Nevertheless, further studies are needed to evaluate the long-term stability of the devices in wet environments, including the effects of microvibrations on the encapsulated MUTs and the impact of bending on encapsulation integrity and device performance. In addition, the electroacoustic effects that may arise in the proposed bimodal neural interfaces when operating in wet ionic environments require careful investigation. Furthermore, developing ultrasonically powered bimodal neural interfaces could fully unlock the potential of next-generation, miniaturized, and versatile neural interfaces.
Journal article
(2025)
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Andrada I. Velea, Raphael Panskus, Benedikt Szabo, Vera A.L. Oppelt, Lukas Holzapfel, Cyril B. Karuthedath, Abhilash T. Sebastian, Thomas Stieglitz, Alessandro S. Savoia, Vasiliki Giagka
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.
...
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.
Journal article
(2024)
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Cornelis Van Damme, Gandhika K. Wardhana, Andrada Iulia Velea, Vasiliki Giagka, Tiago L. Costa
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.
...
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.
Conference paper
(2023)
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Andrada I. Velea, Joshua Wilson, Astrid Gollhardt, Cyril B. Karuthedath, Abhilash S. Thanniyil, Vasiliki Giagka
Ultrasound (US)-based neuromodulation has recently emerged as a spatially selective yet non-invasive alternative to conventional electrically-based neural interfaces. However, the fundamental mechanisms of US neuromodulation are not yet clarified. Thus, there is a need for in-vitro bimodal investigation tools that allow us to compare the effect of US versus electrically-induced neural activity in the vicinity of the transducing element. To this end, we propose a MicroElectrode-MicroTransducer Array (MEMTA), where a dense array of electrodes is co-fabricated on top of a similarly dense array of US transducers.In this paper, we test the proof of concept for such co-fabrication using a non-monolithic approach, where, at its most challenging scenario, desired topologies require electrodes to be formed directly on top of fragile piezoelectric micromachined ultrasound transducer (PMUTs) membranes. On top of the PMUTs, a thin-film microelectrode array was developed utilizing microfabrication processes, including metal sputtering, lithography, etching and soft encapsulation. The samples were analysed through focused ion beam–scanning electron microscopy (FIB-SEM), and the results have shown that damage to the membranes does not occur during any of the process steps. This paper proves that the non-monolithic development of a miniaturised bimodal neuroscientific investigation tool can be achieved, thus, opening up a series of possibilities for further understanding and investigation of the nervous system.
...
Ultrasound (US)-based neuromodulation has recently emerged as a spatially selective yet non-invasive alternative to conventional electrically-based neural interfaces. However, the fundamental mechanisms of US neuromodulation are not yet clarified. Thus, there is a need for in-vitro bimodal investigation tools that allow us to compare the effect of US versus electrically-induced neural activity in the vicinity of the transducing element. To this end, we propose a MicroElectrode-MicroTransducer Array (MEMTA), where a dense array of electrodes is co-fabricated on top of a similarly dense array of US transducers.In this paper, we test the proof of concept for such co-fabrication using a non-monolithic approach, where, at its most challenging scenario, desired topologies require electrodes to be formed directly on top of fragile piezoelectric micromachined ultrasound transducer (PMUTs) membranes. On top of the PMUTs, a thin-film microelectrode array was developed utilizing microfabrication processes, including metal sputtering, lithography, etching and soft encapsulation. The samples were analysed through focused ion beam–scanning electron microscopy (FIB-SEM), and the results have shown that damage to the membranes does not occur during any of the process steps. This paper proves that the non-monolithic development of a miniaturised bimodal neuroscientific investigation tool can be achieved, thus, opening up a series of possibilities for further understanding and investigation of the nervous system.
In an attempt to reduce the side effects caused by the chemically-based drugs used to treat neurological disorders, the field of bioelectronics has been focusing on the development of smart and reliable solutions that could, ideally, interact with the tissue at a resolution of individual cells.1 Conventionally, electrically-based systems have been used.2 However, increasing the resolution at which they interact with the body leads to the development of invasive electrode arrays, which can cause long-term side effects.3 Another approach, based on acoustic waves, has recently emerged. Ultrasound (US) neuromodulation has been proven to be effective in modulating the response of peripheral nerves, in an in-vivo setup4 and has the potential to achieve higher spatial selectivity.5
In this work, we aim to fabricate an implantable cuff for US neuromodulation, which would employ an array of US transducers to deliver focused US to specific nerve areas in a non-invasive manner. To this end, the potential of different US transducer arrays for peripheral nerve applications is evaluated, assessing the acoustic performances as well as ease of assembly and integration. More specifically, two of the most important parameters that affect neural excitation are the frequency and output pressure generated by the US transducers.4 Conventional bulk PZT transducers can generate a wide range of output pressures but these are not small enough for this application. PZT-based arrays, integrated on CMOS have recently emerged, and will be part of this evaluation6. However, these have not yet been integrated on flexible substrates. On the other hand, micromachined US transducers (MUTs) have been gaining a lot of interest, particularly capacitive MUTs (CMUTs) which can operate at high frequencies, thus reducing the focal point significantly.5 CMUTs can be fabricated on flexible substrates, using biocompatible materials, rendering them a very attractive candidate for the envisioned cuff. However, CMUTs usually feature lower Q factors compared to PZTs, hence the output pressure still has to be evaluated for neuromodulation. In addition, this work will also discuss important characteristics of the materials used for encapsulation, as these should ensure the required flexibility of the cuff without negatively affecting the acoustic performance of the transducers.
...
In an attempt to reduce the side effects caused by the chemically-based drugs used to treat neurological disorders, the field of bioelectronics has been focusing on the development of smart and reliable solutions that could, ideally, interact with the tissue at a resolution of individual cells.1 Conventionally, electrically-based systems have been used.2 However, increasing the resolution at which they interact with the body leads to the development of invasive electrode arrays, which can cause long-term side effects.3 Another approach, based on acoustic waves, has recently emerged. Ultrasound (US) neuromodulation has been proven to be effective in modulating the response of peripheral nerves, in an in-vivo setup4 and has the potential to achieve higher spatial selectivity.5
In this work, we aim to fabricate an implantable cuff for US neuromodulation, which would employ an array of US transducers to deliver focused US to specific nerve areas in a non-invasive manner. To this end, the potential of different US transducer arrays for peripheral nerve applications is evaluated, assessing the acoustic performances as well as ease of assembly and integration. More specifically, two of the most important parameters that affect neural excitation are the frequency and output pressure generated by the US transducers.4 Conventional bulk PZT transducers can generate a wide range of output pressures but these are not small enough for this application. PZT-based arrays, integrated on CMOS have recently emerged, and will be part of this evaluation6. However, these have not yet been integrated on flexible substrates. On the other hand, micromachined US transducers (MUTs) have been gaining a lot of interest, particularly capacitive MUTs (CMUTs) which can operate at high frequencies, thus reducing the focal point significantly.5 CMUTs can be fabricated on flexible substrates, using biocompatible materials, rendering them a very attractive candidate for the envisioned cuff. However, CMUTs usually feature lower Q factors compared to PZTs, hence the output pressure still has to be evaluated for neuromodulation. In addition, this work will also discuss important characteristics of the materials used for encapsulation, as these should ensure the required flexibility of the cuff without negatively affecting the acoustic performance of the transducers.
Journal article
(2022)
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Nasim Bakhshaee Babaroud, Merlin Palmar, Andrada Lulia Velea, Chiara Coletti, Sebastian Weingärtner, Frans Vos, Wouter Serdijn, Sten Vollebregt, Vasiliki Giagka
Multimodal platforms combining electrical neural recording and stimulation, optogenetics, optical imaging, and magnetic resonance (MRI) imaging are emerging as a promising platform to enhance the depth of characterization in neuroscientific research. Electrically conductive, optically transparent, and MRI-compatible electrodes can optimally combine all modalities. Graphene as a suitable electrode candidate material can be grown via chemical vapor deposition (CVD) processes and sandwiched between transparent biocompatible polymers. However, due to the high graphene growth temperature (≥ 900 °C) and the presence of polymers, fabrication is commonly based on a manual transfer process of pre-grown graphene sheets, which causes reliability issues. In this paper, we present CVD-based multilayer graphene electrodes fabricated using a wafer-scale transfer-free process for use in optically transparent and MRI-compatible neural interfaces. Our fabricated electrodes feature very low impedances which are comparable to those of noble metal electrodes of the same size and geometry. They also exhibit the highest charge storage capacity (CSC) reported to date among all previously fabricated CVD graphene electrodes. Our graphene electrodes did not reveal any photo-induced artifact during 10-Hz light pulse illumination. Additionally, we show here, for the first time, that CVD graphene electrodes do not cause any image artifact in a 3T MRI scanner. These results demonstrate that multilayer graphene electrodes are excellent candidates for the next generation of neural interfaces and can substitute the standard conventional metal electrodes. Our fabricated graphene electrodes enable multimodal neural recording, electrical and optogenetic stimulation, while allowing for optical imaging, as well as, artifact-free MRI studies. [Figure not available: see fulltext.].
...
Multimodal platforms combining electrical neural recording and stimulation, optogenetics, optical imaging, and magnetic resonance (MRI) imaging are emerging as a promising platform to enhance the depth of characterization in neuroscientific research. Electrically conductive, optically transparent, and MRI-compatible electrodes can optimally combine all modalities. Graphene as a suitable electrode candidate material can be grown via chemical vapor deposition (CVD) processes and sandwiched between transparent biocompatible polymers. However, due to the high graphene growth temperature (≥ 900 °C) and the presence of polymers, fabrication is commonly based on a manual transfer process of pre-grown graphene sheets, which causes reliability issues. In this paper, we present CVD-based multilayer graphene electrodes fabricated using a wafer-scale transfer-free process for use in optically transparent and MRI-compatible neural interfaces. Our fabricated electrodes feature very low impedances which are comparable to those of noble metal electrodes of the same size and geometry. They also exhibit the highest charge storage capacity (CSC) reported to date among all previously fabricated CVD graphene electrodes. Our graphene electrodes did not reveal any photo-induced artifact during 10-Hz light pulse illumination. Additionally, we show here, for the first time, that CVD graphene electrodes do not cause any image artifact in a 3T MRI scanner. These results demonstrate that multilayer graphene electrodes are excellent candidates for the next generation of neural interfaces and can substitute the standard conventional metal electrodes. Our fabricated graphene electrodes enable multimodal neural recording, electrical and optogenetic stimulation, while allowing for optical imaging, as well as, artifact-free MRI studies. [Figure not available: see fulltext.].
Conference paper
(2021)
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Andrada I. Velea, Joshua Wilson, Anna Pak, Manuel Seckel, Sven Schmidt, Stefan Kosmider, Nasim Babaroud, Wouter A. Serdijn, Vasiliki Giagka
Our limited understanding of the nervous system forms a bottleneck which impedes the effective treatment of neurological disorders. In order to improve patient outcomes it is highly desirable to interact with the nervous tissue at the resolution of individual cells. As neurons number in the billions and transmit signals electrically, high-density, cellular-resolution microelectrode arrays will be a useful tool for both treatment and research.This paper investigates the advantages and versatility of laser-patterning technologies for the development of such high-density microelectrode arrays in flexible polymer substrates. In particular, it aims to elucidate the mechanisms involved in laser patterning of thin polymers on top of thin metal layers. For this comparative study, a pulsed picosecond laser (Schmoll Picodrill) with two separate wavelengths (1064 nm (infrared (IR)) and 355 nm (ultraviolet (UV))) was used. A 5 $\mu$ m thick electroplated layer of gold (Au) was used to form the microelectrodes. Laser-patterning was investigated to expose the Au electrodes when encapsulated by two different thermoplastic polymers: thermoplastic polyurethane (TPU), and Parylene-C, with thicknesses of maximum 25 $\mu$ m. The electrode diameter and the distance between electrodes were reduced down to 35 $\mu$ m and 30 $\mu$ m, respectively. The structures were evaluated using optical microscopy and white light interferometry and the results indicated that both laser wavelengths can be successfully used to create high-density microelectrode arrays in polymer substrates. However, due to the lower absorption coefficient of metals in the IR spectrum, a higher uniformity of the exposed Au layer was observed when IR-based lasers were used. This paper provides more insight into the mechanisms involved in laser-patterning of thin film polymers and demonstrates that it can be a reliable and cost-effective method for the rapid prototyping of thin-film neural interfaces.
...
Our limited understanding of the nervous system forms a bottleneck which impedes the effective treatment of neurological disorders. In order to improve patient outcomes it is highly desirable to interact with the nervous tissue at the resolution of individual cells. As neurons number in the billions and transmit signals electrically, high-density, cellular-resolution microelectrode arrays will be a useful tool for both treatment and research.This paper investigates the advantages and versatility of laser-patterning technologies for the development of such high-density microelectrode arrays in flexible polymer substrates. In particular, it aims to elucidate the mechanisms involved in laser patterning of thin polymers on top of thin metal layers. For this comparative study, a pulsed picosecond laser (Schmoll Picodrill) with two separate wavelengths (1064 nm (infrared (IR)) and 355 nm (ultraviolet (UV))) was used. A 5 $\mu$ m thick electroplated layer of gold (Au) was used to form the microelectrodes. Laser-patterning was investigated to expose the Au electrodes when encapsulated by two different thermoplastic polymers: thermoplastic polyurethane (TPU), and Parylene-C, with thicknesses of maximum 25 $\mu$ m. The electrode diameter and the distance between electrodes were reduced down to 35 $\mu$ m and 30 $\mu$ m, respectively. The structures were evaluated using optical microscopy and white light interferometry and the results indicated that both laser wavelengths can be successfully used to create high-density microelectrode arrays in polymer substrates. However, due to the lower absorption coefficient of metals in the IR spectrum, a higher uniformity of the exposed Au layer was observed when IR-based lasers were used. This paper provides more insight into the mechanisms involved in laser-patterning of thin film polymers and demonstrates that it can be a reliable and cost-effective method for the rapid prototyping of thin-film neural interfaces.
This work aims to develop a smart neural interface with transparent electrodes to allow for electrical monitoring of the site of interest during optogenetic stimulation of the spinal cord. In this paper, a microfabrication process for the wafer-level development of such a compact, active, transparent and flexible implant is presented. Graphene has been employed to form the transparent array of electrodes and tracks, on top of which chips have been bonded using flip-chip bonding techniques. To provide high flexibility, soft encapsulation, using polydimethylsiloxane (PDMS) has been used. Making use of the "Flex-to-Rigid" (F2R) technique, cm-size graphene-on-PDMS structures have been suspended and characterized using Raman spectroscopy to qualitatively evaluate the graphene layer, together with 2-point measurements to ensure the conductivity of the structure. In parallel, flip-chip bonding processes of chips on graphene structures were employed and the 2-point electrical measurement results have shown resistance values in the range of kΩ for the combined tracks and ball-bonds.
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This work aims to develop a smart neural interface with transparent electrodes to allow for electrical monitoring of the site of interest during optogenetic stimulation of the spinal cord. In this paper, a microfabrication process for the wafer-level development of such a compact, active, transparent and flexible implant is presented. Graphene has been employed to form the transparent array of electrodes and tracks, on top of which chips have been bonded using flip-chip bonding techniques. To provide high flexibility, soft encapsulation, using polydimethylsiloxane (PDMS) has been used. Making use of the "Flex-to-Rigid" (F2R) technique, cm-size graphene-on-PDMS structures have been suspended and characterized using Raman spectroscopy to qualitatively evaluate the graphene layer, together with 2-point measurements to ensure the conductivity of the structure. In parallel, flip-chip bonding processes of chips on graphene structures were employed and the 2-point electrical measurement results have shown resistance values in the range of kΩ for the combined tracks and ball-bonds.
This paper reports on the characterization of a microfabricated wafer-scale, graphene-based, soft implant for spinal cord applications. Graphene is used because of its high transparency and good conductivity, making it suitable for optogenetic applications. Moreover it has a high mechanical strength and is potentially biocompatible. The implant consists of multi-layered chemical vapor deposited graphene, in the form of electrodes and tracks, encapsulated between 2 layers of silicone. Methods such as Raman spectroscopy, optical transmittance, and electrical measurements combined with bending tests and in-vitro experiments, using phosphate-buffered saline (PBS) solution, were employed to characterize the device. The results have shown high bendability and no critical damage of the graphene after immersing the device in PBS solution up to 7 days. To the authors' best knowledge, this is the first work that presents a soft and fully scalable optogenetics-compatible graphene-based spinal cord electrode array.
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This paper reports on the characterization of a microfabricated wafer-scale, graphene-based, soft implant for spinal cord applications. Graphene is used because of its high transparency and good conductivity, making it suitable for optogenetic applications. Moreover it has a high mechanical strength and is potentially biocompatible. The implant consists of multi-layered chemical vapor deposited graphene, in the form of electrodes and tracks, encapsulated between 2 layers of silicone. Methods such as Raman spectroscopy, optical transmittance, and electrical measurements combined with bending tests and in-vitro experiments, using phosphate-buffered saline (PBS) solution, were employed to characterize the device. The results have shown high bendability and no critical damage of the graphene after immersing the device in PBS solution up to 7 days. To the authors' best knowledge, this is the first work that presents a soft and fully scalable optogenetics-compatible graphene-based spinal cord electrode array.
Patients affected by spinal cord injuries (SCI) are usually unable to perform trivial motor activities and thus, for therapeutic purposes, epidural spinal cord stimulation (ESCS) is currently used. Moreover, more exploratory research, using optogenetics, is being conducted in rodents for a better understanding of the mechanisms that occur while delivering specific therapies. However, the availability of tailored neurotechnologies for such experiments is limited. This work reports the development and characterization of flexible, active spinal cord implants with optogenetic compatibility1,2 (Fig.1). A scalable and reproducible microfabrication process has been developed, using graphene3, a transparent, flexible and conductive material, to form the electrodes and interconnects of the implant. Small and thin4 electronic chips were assembled via flip-chip bonding processes either on graphene or on metal-on-graphene layers. Soft, polymeric encapsulation was employed to sustain the high flexibility and transparency of the implant. The result is an active prototype consisting of a multi-layered graphene structure between two polymeric-based encapsulation layers, with thin chips integrated on the implant and test pads for interconnection to the outside world. Raman spectroscopy and optical transmittance were employed for the characterization of the graphene layer while cyclic voltammetry and electrochemical impedance spectroscopy were performed to benchmark the electrical properties of the device. The assembly process of the chips was evaluated using four-point electrical measurements. In this work, the first transparent, graphene-based active implants have been developed (Fig. 2 and Fig. 3). The prototypes were extensively characterized and the results showed a transparency of ~80 % as well as no deterioration over time when soaked in saline solution or when bent under various angles. The graphene electrodes showed an impedance of ~8 kΩ at 1 kHz frequencies and the resistance after the bonding process ranged from 10 mΩ up to 16 Ω for individual connections, depending on the substrate used
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Patients affected by spinal cord injuries (SCI) are usually unable to perform trivial motor activities and thus, for therapeutic purposes, epidural spinal cord stimulation (ESCS) is currently used. Moreover, more exploratory research, using optogenetics, is being conducted in rodents for a better understanding of the mechanisms that occur while delivering specific therapies. However, the availability of tailored neurotechnologies for such experiments is limited. This work reports the development and characterization of flexible, active spinal cord implants with optogenetic compatibility1,2 (Fig.1). A scalable and reproducible microfabrication process has been developed, using graphene3, a transparent, flexible and conductive material, to form the electrodes and interconnects of the implant. Small and thin4 electronic chips were assembled via flip-chip bonding processes either on graphene or on metal-on-graphene layers. Soft, polymeric encapsulation was employed to sustain the high flexibility and transparency of the implant. The result is an active prototype consisting of a multi-layered graphene structure between two polymeric-based encapsulation layers, with thin chips integrated on the implant and test pads for interconnection to the outside world. Raman spectroscopy and optical transmittance were employed for the characterization of the graphene layer while cyclic voltammetry and electrochemical impedance spectroscopy were performed to benchmark the electrical properties of the device. The assembly process of the chips was evaluated using four-point electrical measurements. In this work, the first transparent, graphene-based active implants have been developed (Fig. 2 and Fig. 3). The prototypes were extensively characterized and the results showed a transparency of ~80 % as well as no deterioration over time when soaked in saline solution or when bent under various angles. The graphene electrodes showed an impedance of ~8 kΩ at 1 kHz frequencies and the resistance after the bonding process ranged from 10 mΩ up to 16 Ω for individual connections, depending on the substrate used
The most important symptoms of spinal cord injuries (SCIs) are partial or complete loss of sensory and/or motor functions caused by the disruption of the neural pathway between the brain and the extremities of the body. Recent studies have shown that epidural spinal cord stimulation (ESCS) can promote locomotor recovery in patients affected by SCIs, thus becoming one of the most promising means of treatment for the lesion. Devices currently available on the market, consist of active components, enclosed in a hard case and connected via leads to the electrodes that form the interface between the stimulator and the biological tissue. The presence of leads along the spine, may be an important cause of failure for the device. Moreover, the overall stiffness of the stimulator does not resemble best the anatomical structure of the human body. Flexibility and optical monitoring of the biological tissue during implantation and stimulation are very important aspects and both can be improved with a proper choice of materials. The goal of this work is to develop a compact, active, transparent and flexible spinal cord stimulator that could be implanted at the site of stimulation. To provide high flexibility, soft encapsulation, using polydimethylsiloxane (PDMS) has been used. To ensure transparency but also mechanical stability of the electrodes and tracks, graphene has been chosen as a replacement for the conventional metals. Integrating active components, in the form of application specific integrated circuits (ASICs), on a graphenebased substrate, constitutes the biggest challenge. To this end, flip chip bonding techniques using a metal layer as an interface between graphene and the chip’s stud-bumped pads, are being investigated. Preliminary measurements after bonding have shown resistance values in the range of kΩ, thus taking the project one step closer to achieving the desired goal.
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The most important symptoms of spinal cord injuries (SCIs) are partial or complete loss of sensory and/or motor functions caused by the disruption of the neural pathway between the brain and the extremities of the body. Recent studies have shown that epidural spinal cord stimulation (ESCS) can promote locomotor recovery in patients affected by SCIs, thus becoming one of the most promising means of treatment for the lesion. Devices currently available on the market, consist of active components, enclosed in a hard case and connected via leads to the electrodes that form the interface between the stimulator and the biological tissue. The presence of leads along the spine, may be an important cause of failure for the device. Moreover, the overall stiffness of the stimulator does not resemble best the anatomical structure of the human body. Flexibility and optical monitoring of the biological tissue during implantation and stimulation are very important aspects and both can be improved with a proper choice of materials. The goal of this work is to develop a compact, active, transparent and flexible spinal cord stimulator that could be implanted at the site of stimulation. To provide high flexibility, soft encapsulation, using polydimethylsiloxane (PDMS) has been used. To ensure transparency but also mechanical stability of the electrodes and tracks, graphene has been chosen as a replacement for the conventional metals. Integrating active components, in the form of application specific integrated circuits (ASICs), on a graphenebased substrate, constitutes the biggest challenge. To this end, flip chip bonding techniques using a metal layer as an interface between graphene and the chip’s stud-bumped pads, are being investigated. Preliminary measurements after bonding have shown resistance values in the range of kΩ, thus taking the project one step closer to achieving the desired goal.