Simulation of epiretinal prostheses - Evaluation of geometrical factors affecting stimulation thresholds

<p>Abstract</p> <p>Background</p> <p>An accurate understanding of the electrical interaction between retinal prostheses and retinal tissue is important to design effective devices. Previous studies have used modelling approaches to simulate electric fields generated by epiretinal prostheses in saline and to simulate retinal ganglion cell (RGC) activation using passive or/and active biophysical models of the retina. These models have limited scope for studying an implanted human retinal prosthesis as they often do not account for real geometry and composition of the prosthesis-retina interface. This interface consists of real dimensions and location of stimulation and ground electrodes that are separated by the retinal tissue and surrounded by physiological fluids.</p> <p>Methods</p> <p>In this study, we combined the prosthesis-retina interface elements into a framework to evaluate the geometrical factors affecting stimulation thresholds for epiretinal prostheses used in clinical human trials, as described by Balthasar <it>et al</it>. in their Investigative Ophthalmology and Visual Science (IOVS) paper published in 2008 using the Argus I epiretinal implants. Finite element method (FEM) based computations were used to estimate threshold currents based on a threshold criterion employing a passive electric model of the retina.</p> <p>Results</p> <p>Threshold currents and impedances were estimated for different electrode-retina distances. The profiles and the values for thresholds and impedances obtained from our simulation framework are within the range of measured values in the only elaborate published clinical trial until now using Argus I epiretinal implants. An estimation of resolution for the electrodes used in these trials was provided. Our results reiterate the importance of close proximity between electrodes and retina for safe and efficient retinal stimulation.</p> <p>Conclusions</p> <p>The validation of our simulation framework being relevant for epiretinal prosthesis research is derived from the good agreement of the computed trends and values of the current study with measurements demonstrated in existing clinical trials on humans (Argus I). The proposed simulation framework could be used to generate the relationship between threshold and impedance for any electrode geometry and consequently be an effective tool for design engineers, surgeons and electrophysiologists.</p

Healthy aims: developing new medical implants and diagnostic equipment

Healthy Aims is a €23-million, four-year project, funded under the EU’s Information Society Technology Sixth Framework program to develop intelligent medical implants and diagnostic systems (www.healthyaims.org). The project has 25 partners from 10 countries, including commercial, clinical, and research groups. This consortium represents a combination of disciplines to design and fabricate new medical devices and components as well as to test them in laboratories and subsequent clinical trials. The project focuses on medical implants for nerve stimulation and diagnostic equipment based on straingauge technology

Polyimide/SU-8 catheter-tip MEMS gauge pressure sensor

This paper describes the development of a polyimide/SU-8 catheter-tip MEMS gauge pressure sensor. Finite element analysis was used to investigate critical parameters, impacting on the device design and sensing characteristics. The sensing element of the device was fabricated by polyimide-based micromachining on a flexible membrane, using embedded thin-film metallic wires as piezoresistive elements. A chamber containing this flexible membrane was sealed using an adapted SU-8 bonding technique. The device was evaluated experimentally and its overall performance compared with a commercial silicon-based pressure sensor. Furthermore, the device use was demonstrated by measuring blood pressure and heart rate in viv

Field effect modulated nanofluidic diode membrane based on Al2O3/W heterogeneous nanopore arrays

We developed Al2O3/W heterogeneous nanopore arrays for field effect modulated nanofluidic diodes. They are fabricated by transferring self-organized nanopores of anodic aluminium oxide into a W thin film. The nanopores are ∼20 nm in diameter and 400 nm in length. After mild oxidation, approximately 10 nm WO3 grows on the surface of W, forming a conformal and dense dielectric layer. It allows the application of an electrical field through the surrounding W electrode to modulate the ionic transport across the entire membrane. Our experimental findings have potential applications in high throughput controlled delivery and electrostatic sorting of biomolecules

Direct Observation of Transitions between Surface-Dominated and Bulk Diffusion Regimes in Nanochannels

The diffusion of charged proteins in liquid-filled nanometer-sized apertures with charged surfaces has been investigated with fluorescence correlation spectroscopy (FCS). Based on a two-dimensional (2D) multicomponent diffusion model, key parameters such as the number of molecules diffusing freely inside the nanochannel or interacting with the surfaces, together with the specific diffusion parameters, could be extracted. Different regimes of diffusion have been observed and described by a model, which takes into account the steric exclusion, the reversible surface adsorption of the biomolecules, and the exclusion-enrichment effect that is due to the charge of the proteins and the ionic strength of the solution. Conditions where the diffusion of proteins through nano-confined spaces can be of the same magnitude as in the bulk were both predicted and experimentally verified

Fitting the Gamma-Ray Spectrum from Dark Matter with DMFIT: GLAST and the Galactic Center Region

We study the potential of GLAST to unveil particle dark matter properties with gamma-ray observations of the Galactic center region. We present full GLAST simulations including all gamma-ray sources known to date in a region of 4 degrees around the Galactic center, in addition to the diffuse gamma-ray background and to the dark matter signal. We introduce DMFIT, a tool that allows one to fit gamma-ray emission from pair-annihilation of generic particle dark matter models and to extract information on the mass, normalization and annihilation branching ratios into Standard Model final states. We assess the impact and systematic effects of background modeling and theoretical priors on the reconstruction of dark matter particle properties. Our detailed simulations demonstrate that for some well motivated supersymmetric dark matter setups with one year of GLAST data it will be possible not only to significantly detect a dark matter signal over background, but also to estimate the dark matter mass and its dominant pair-annihilation mode.Comment: 37 pages, 16 figures, submitted to JCA

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Microstéréophotolithographie par masquage dynamique

Not availableCette étude traite de la réalisation d'une nouvelle méthode de microstéréophotolithographie utilisant un écran à cristaux liquides comme masque dynamique. Elle s'inscrit dans l'optique d'une diversification des techniques de microfabrication susceptibles d'être utilisées pour la construction de composants mécaniques miniaturisés, ces dernières étant pour le moment limitées aux procédés dérivés des techniques d'usinage du silicium qui ne permettent pas la fabrication de pièces tridimensionnelles de grande complexité géométrique. Nous présentons le principe de fonctionnement d'un tel dispositif, son intérêt. L’utilisation d'un écran à cristaux liquides comme partie active du procédé impose le choix d'un système chimique photopolymérisable approprié, réagissant dans le domaine de longueurs d'onde visibles. Une modélisation simplifiée de l'effet du photoblanchiment et de la fluorescence de la résine utilisée permet d'évaluer l'incidence de ces phénomènes sur la résolution spatiale de la photopolymérisation. Une étude expérimentale de la résolution spatiale du dispositif réalisé permet de définir ses conditions de fonctionnement. L’application du procédé à la fabrication d'objets tridimensionnels de petites dimensions formés d'un grand nombre de couches de géométries complexes illustre ses potentialités dans le domaine des microtechnique