Distribution of electrical stimulation current in a planar multilayer anisotropic tissue

This study analytically addresses the problem of neuromuscular electrical stimulation for a planar, multilayer, anisotropic model of a physiological tissue (referred to as volume conductor). Both conductivity and permittivity of the volume conductor are considered, including dispersive properties. The analytical solution is obtained in the 2- D Fourier transform domain, transforming in the planes parallel to the volume conductor surface. The model is efficient in terms of computational cost, as the solution is analytical (only numerical Fourier inversion is needed). It provides the current distribution in a physiological tissue induced by an electrical current delivered at the skin surface. Three representative examples of application of the model are considered. (1) The simulation of stimulation artefact during transcutaneous electrical stimulation and EMG detection. Only the effect of the volume conductor is considered, neglecting the other sources of artefact (such as the capacitive coupling between the stimulating and recording electrodes). (2) The simulation of the electrical current distribution within the muscle and the low-pass filter effect of the volume conductor on sinusoidal stimulation currents with different stimulation frequencies. (3) The estimation of the amplitude modulated current distribution within the muscle for interferential stimulation. The model is devoted to the simulation of neuromuscular stimulation, but the same method could be applied in other fields in which the estimation of the electrical current distribution in a medium induced by the injection of a current from the boundary of the medium is of interest

Curvy surface conformal ultra-thin transfer printed Si optoelectronic penetrating microprobe arrays

Penetrating neural probe arrays are powerful bio-integrated devices for studying basic neuroscience and applied neurophysiology, underlying neurological disorders, and understanding and regulating animal and human behavior. This paper presents a penetrating microprobe array constructed in thin and flexible fashion, which can be seamlessly integrated with the soft curvy substances. The function of the microprobes is enabled by transfer printed ultra-thin Si optoelectronics. As a proof-of-concept device, microprobe array with Si photodetector arrays are demonstrated and their capability of mapping the photo intensity in space are illustrated. The design strategies of utilizing thin polyimide based microprobes and supporting substrate, and employing the heterogeneously integrated thin optoelectronics are keys to accomplish such a device. The experimental and theoretical investigations illustrate the materials, manufacturing, mechanical and optoelectronic aspects of the device. While this paper primarily focuses on the device platform development, the associated materials, manufacturing technologies, and device design strategy are applicable to more complex and multi-functionalities in penetrating probe array-based neural interfaces and can also find potential utilities in a wide range of bio-integrated systems

Biomimetic Layer-by-Layer Self-Assembly of Nanofilms, Nanocoatings, and 3D Scaffolds for Tissue Engineering

Achieving surface design and control of biomaterial scaffolds with nanometer- or micrometer-scaled functional films is critical to mimic the unique features of native extracellular matrices, which has significant technological implications for tissue engineering including cell-seeded scaffolds, microbioreactors, cell assembly, tissue regeneration, etc. Compared with other techniques available for surface design, layer-by-layer (LbL) self-assembly technology has attracted extensive attention because of its integrated features of simplicity, versatility, and nanoscale control. Here we present a brief overview of current state-of-the-art research related to the LbL self-assembly technique and its assembled biomaterials as scaffolds for tissue engineering. An overview of the LbL self-assembly technique, with a focus on issues associated with distinct routes and driving forces of self-assembly, is described briefly. Then, we highlight the controllable fabrication, properties, and applications of LbL self-assembly biomaterials in the forms of multilayer nanofilms, scaffold nanocoatings, and three-dimensional scaffolds to systematically demonstrate advances in LbL self-assembly in the field of tissue engineering. LbL self-assembly not only provides advances for molecular deposition but also opens avenues for the design and development of innovative biomaterials for tissue engineering

Proceedings of the Conference on Progress in Electrically Active Implants - Tissue and Functional Regeneration (ELAINE 2020)

The conference on Progress in Electrically Active Implants - Tissue and Functional Regeneration (ELAINE 2020) focused on novel methods in the electric stimulation of bio-material compounds of living cells and implantable electric stimulation devices. ELAINE 2020 provided international scientists a virtual platform to discuss the latest achievements in the form of invited presentations, selected talks from abstract submissions, and virtual poster sessions. In addition, we particularly invited critical reviews and contributions with negative results or unsuccessful replications to foster the scientific discussion and explicitly encourage young scientists to contribute and submit their work

EEG/MEG Source Imaging: Methods, Challenges, and Open Issues

We present the four key areas of research—preprocessing, the volume conductor, the forward problem, and the inverse problem—that affect the performance of EEG and MEG source imaging. In each key area we identify prominent approaches and methodologies that have open issues warranting further investigation within the community, challenges associated with certain techniques, and algorithms necessitating clarification of their implications. More than providing definitive answers we aim to identify important open issues in the quest of source localization

Inspired by Nature: materials biomimicry to support human activities

The classes of materials used in the biomedical field are manifold: metals, ceramics, polymers and their composites. All these materials are often used in synergic combination in order to meet different requirements. In the design of a biomedical device and in the selection of the materials it is made of, the requirements are particularly stringent since, in addition to carry out its primary function, the device itself must not hamper the host body. Therefore, biomaterials must, first and foremost, ensure biocompatibility. Aiming at the synergic integration of implanted biomaterials with the host organism, a design framework results crucial: biomimicry. It is straightforward to get inspiration from structures and solutions occurring in Nature in order to design devices intended to operate in symbiosis with a living organism. The work presented in this thesis was conceived and developed within such outlook. Two major topics were addressed: ElectroActive Polymers (EAPs), used as artificial muscles and Magnesium foams, used as orthopaedic implants. As far as EAPs are concerned, it was studied their implementation in actuation devices manufactured according to bioinspired geometries, which can reproduce as faithfully as possible the structure of natural muscle tissues. In fact, in line with the principles of biomimicry, the structures proposed recall the human physiology of muscle bundles, and allow the integration of a recruitment mechanism of the motor units. EAPs have a typical transducers behaviour: if prompted with an electric signal (in particular a voltage), they react with a mechanical deformation, and vice versa. Therefore, EAPs can be described as smart materials, suitable to be used both as actuators and as sensors. As actuators, EAPs have several advantages over the solutions currently present in the state of the art of traditional robotics. In fact, EAPs allow more fluid and biomimetic movements, if compared to those achievable with mechanical counterparts: polymers are flexible and not limited by the rigidity of devices relying on gears and bearings. For this reason, and thanks to stress and deformation values similar to those of biological tissues, EAPs are also referred to as “artificial muscles” [1]. As far as magnesium foams are concerned, within a biomimicry outlook, the context of orthopedic surgery sets the morphology of natural bone as reference. Designing choices regarding materials selection, production methods and treatments (in bulk and/or on surface) were addressed to reproduce the mechanical and functional features of natural bone. In fact, if on one side the orthopaedic implant is required not to collapse under the mechanical load applied, on the other it should not bear excessively or exclusively the forces acting on the bone in order not to induce a stress-shielding effect. This phenomenon, in fact, may be critical since it reduces considerably the stimulation of regenerative bone cells and, ultimately, slows down the recovery of natural bone. The natural bone has a complex structure, resulting from millions of years of evolution, which fulfils several functions: it provides specific structural support, locally adapted to load conditions; it does not add unnecessary weight by means of an optimized minimization of mass and it allows nutrients supply to tissues through adequate vascularization. Such multi-functionality is enabled by the peculiar structure of the spongy bone tissue. Starting from these observations, the mimesis of cancellous bone conformation is one of the most appropriate guideline in choosing and designing materials for orthopaedic applications. Among the feasible technological solutions, metallic foams with open interconnected porosity have been identified as the most promising choice [2]-[5] and this thesis is focused on this solution. In fact, these materials can be designed to combine the mechanical properties and the morphological characteristics of natural bone, as well as the vascularization function and the stimulation of bone tissue growth. Furthermore, metallic foams represent one of the most suitable option to coherently develop a biomimetic device that reproduces the main features of natural bone. In the light of the requirements outlined so far, pure magnesium represents an optimal solution. This metallic material in fact meets the multi-functionality requirement previously described: it has mechanical properties of the same order of magnitude as those of natural bone tissue, it can be produced in the form of foam, it is biocompatible and bioresorbable. This last feature enables the possibility to avoid second surgery usually needed to remove orthopedic devices once their function is fulfilled. Supporting this choice, there is a wide scientific literature which, in recent years, has recognized magnesium as a very promising material for biomedical applications, although there are still some critical aspects to be solved. In fact, the process of corrosion of magnesium in the body fluids results in the formation of gaseous hydrogen that, if produced too rapidly, can be harmful for the human body [4]. References [1] Y. Bar-Cohen, Electroactive polymer (EAP) actuators as artificial muscles: reality, potential and challenges. SPIE - The International Society for Optical Engineering, 2004. [2] R. Zeng, W. Dietzel, F. Witte, N. Hort, and C. Blawert, “Progress and Challenge for Magnesium Alloys as Biomaterials,” Adv. Eng. Mater., vol. 10, no. 8, pp. B3–B14, Aug. 2008. [3] M. P. Staiger, A. M. Pietak, J. Huadmai, and G. Dias, “Magnesium and its alloys as orthopedic biomaterials: A review,” Biomaterials, vol. 27, no. 9, pp. 1728–1734, Mar. 2006. [4] A. H. Yusop, A. A. Bakir, N. A. Shaharom, M. R. Abdul Kadir, and H. Hermawan, “Porous Biodegradable Metals for Hard Tissue Scaffolds: A Review,” International Journal of Biomaterials, vol. 2012, no. 4, pp. 1–10, 2012. [5] X. N. Gu, W. R. Zhou, Y. F. Zheng, Y. Liu, and Y. X. Li, “Degradation and cytotoxicity of lotus-type porous pure magnesium as potential tissue engineering scaffold material,” Materials Letters, vol. 64, no. 17, pp. 1871–1874, Sep. 2010

Three-dimensional electrode array for brain slice culture

Multielektroder arrays (MEA) er rækker af elektroder mest i mikrometer størrelse, som er blevet brugt i stor omfang til at stimulere og måle elektrisk aktivitet fra neuronale netværker. Brug af disse for at analysere hjerne slices (hjerneskiver) kan give indsigt i interaktioner mellem neuroner, eftersom dyrkninger af hjerneskiver in vitro beholder funktionaliteten af netværkerne i den levende hjerne. Elektroder var designet og fabrikeret med det formal at optimere MEA præstationen ved stimulering af og måling fra hjerneskiver in vitro. Meget af arbejdet beskrevet her beskæftiger sig med studiet af silicium mikrofabrikations teknikker for at opnå 3D elektroder med en høj dimensionsforhold, som er de mest egnede til at interagere med hjerneskiver. Elektroderne blev karakteriseret bade elektrisk og mekanisk for at demonstrere deres bedre egenskaber ved elektriske malinger og væv indtrægningsevne. Ved et andet sæt eksperimenter, det fabrikeret MEA system blev forsøgt integreret med et dyrkningsplatform som skal gøre længerevarende målinger mulige. Baseret på eksisterende litteratur mange forskellige platformer blev udviklet og tested med hjerneskiver. Selvom dyrkningen af væv ikke var mulig i disse systemer, eksperimenterne viser at de mikrofluidiske dele af systemet var funktionelle og det var muligt at integrere MEA systemet med ved at modificere den og lave den del af gennemstrømningsmekanismen. Til sidst en mekanisme som var I stand til at flytte elektroderne ind og ud af hjerneskiveren blev udviklet, simuleret og testet. Systemet var i stand til at flytte MEA chippen. Selvom mindre modifikationer vil være ønskelige for at forbedre bevægelsespræcisionen, integrering af denne mekanisme med MEA chippen var mulig og funktionaliteten af systemet blev påvist

In-cell recordings with 3D microelectrode arrays

Micro Electrode Arrays (MEAs) have been used for 40 years to record extracellular signal from electrically excitable cells. The development of three dimensional microstructured electrodes has been shown to improve the electrical contact between cell and electrode. This can allow to reduce the electrode dimensions to improve spatial resolution, to have a one-toone correspondence between cell and electrode and, applying an electrical stimulus, to obtain in-cell like recordings. In-cell like recordings resemble in their time course the transmembrane voltage obtained by an intracellular sharp electrode during electrical activity. Appropriate electrical stimulation transiently increases the leakage membrane conductance and gives access to a signal substantially different from the extracellular one. The aim of this thesis is to develop different electrodes designs and to investigate on cardiomyocytes cell cultures the feasability of in-cell recordings. Standard MEAs (tip-shaped and planar electrodes) were compared with self-developed MEAs. The duration of the in-cell signal, his amplitude, the voltage threshold to induce it and his repeatability over minutes and hours were studied by varying the stimulus duration and the stimulus voltage. We successfully processed solid and hollow pillars electrodes as well as mushroom-shaped electrodes. On these electrodes we recorded extracellular action potential from cardiomyocytes. The stimulation protocols successfully evoked in-cell like signals on all the electrodes. In-cell recordings could be obtained onto the same cell over several hours and occasionally days. Hollow pillars induced longer in-cell recording, tip-shaped electrode had a lower threshold. However the large variability of in-cell like recordings on the different electrode shapes does not suggest one particular shape to be used in future. A promising spontaneous in-cell recording was obtained in one culture, opening to future development on three-dimensional microelectrodes research. I Micro Electrode Array (matrici di micro elettrodi) sono stati usati negli ultimi 40 anni per registrare segnale extracellulare da cellule eccitabili come i neuroni. Lo sviluppo di elettrodi tridimensionali microstrutturati ha permesso di aumentare il contatto elettrico tra cellula ed elettrodo. Questo può essere sfruttato per aumentare la risoluzione spaziale, avere una corrispondenza unoa- uno tra cellula ed elettrodo e, applicando uno stimolo elettrico, per ottenere un segnale similintracellulare detto "in-cell". Questo tipo di segnale assomiglia al potenziale di membrana misurato da un elettrodo appuntito intracellulare durante un potenziale d'azione. La stimolazione elettrica infatti, aumentando transitoriamente la conducibilità della membrana da accesso ad un segnale sostanzialmente differente da quello extracellulare. Lo scopo di questa tesi è di sviluppare diverse forme e design di elettrodo e di investigare su colture cellulari di cardiomiociti la fattibilità di registrazioni "in-cell". Oltre agli elettrodi autoprodotti, sono stati confrontati elettrodi "a punta" e planari, disponibili in commercio. Gli elettrodi sono stati confrontati cambiando la durata e la tensione dello stimolo elettrico, per valutare le variazioni nella durata del segnale "in-cell", la sua ampiezza, la soglia di tensione che lo induce, e la ripetibilità per minuti ed ore. Abbiamo creato con successo elettrodi con la forma di cilindri pieni e vuoti e "a fungo", registrato potenziali d'azione extracellulari da cardiomiociti con essi, e ottenuto la registrazione di segnali "in-cell" con l'applicazione di protocolli di stimolazione elettrica. È stato possibile ripetere questi protocolli sulle stesse cellule per diverse ore e a volte giorni. I cilindri vuoti hanno indotto le registrazioni "in-cell" più lunghe, elettrodi a punta hanno mostrato una soglia di tensione inferiore. Ciononostante, la grande variabilità di questi risultati non suggerisce nessun tipo di forma preferenziale da usare in futuro. Un promettente segnale “in-cell” spontaneo (senza bisogno di stimolazione elettrica) è stato ottenuto in un caso, aprendo a futuri sviluppi nella ricerca sui microelettrodi tridimensionali.ope

A model for transcutaneous current stimulation: simulations and experiments

Complex nerve models have been developed for describing the generation of action potentials in humans. Such nerve models have primarily been used to model implantable electrical stimulation systems, where the stimulation electrodes are close to the nerve (near-field). To address if these nerve models can also be used to model transcutaneous electrical stimulation (TES) (far-field), we have developed a TES model that comprises a volume conductor and different previously published non-linear nerve models. The volume conductor models the resistive and capacitive properties of electrodes, electrode-skin interface, skin, fat, muscle, and bone. The non-linear nerve models were used to conclude from the potential field within the volume conductor on nerve activation. A comparison of simulated and experimentally measured chronaxie values (a measure for the excitability of nerves) and muscle twitch forces on human volunteers allowed us to conclude that some of the published nerve models can be used in TES models. The presented TES model provides a first step to more extensive model implementations for TES in which e.g., multi-array electrode configurations can be teste