Photovoltaic, wireless wide-field epiretinal prosthesis to treat retinitis pigmentosa.

PURPOSE: To develop and evaluate a photovoltaic, wireless wide-field epiretinal prosthesis for the treatment of retinitis pigmentosa. METHODS: A mosaic array of thinned silicon-based photodiodes with integrated thin-film stimulation electrodes was fabricated with a flexible polyimide substrate film to form a film-based miniaturized electronic system with wireless optical power and signal transmission and integrated electrostimulation. Manufactured implants were characterized with respect to their optoelectronic performance and biocompatibility following DIN EN ISO 10993. RESULTS: A 14 mm diameter prosthesis containing 1276 pixels with a maximum sensitivity at a near infrared wavelength of 905 nm and maximized stimulation current density 30-50 µm below the electrodes was developed for direct activation of retinal ganglion cells during epiretinal stimulation. Fabricated prostheses demonstrated mucosal tolerance and the preservation of both metabolic activity, proliferation and membrane integrity of human fibroblasts as well as the retinal functions of bovine retinas. Illumination of the prosthesis, which was placed epiretinally on an isolated perfused bovine retina, with infrared light resulted in electrophysiological recordings reminiscent of an a-wave (hyperpolarization) and b-wave (depolarization). CONCLUSIONS: A photovoltaic, wireless wide-field epiretinal prosthesis for the treatment of retinitis pigmentosa using near infrared light for signal transmission was designed, manufactured and its biocompatibility and functionality demonstrated in vitro and ex vivo.

Bio-potential noise of dry printed electrodes: physiology versus the skin-electrode impedance.

Objective. To explore noise characteristics and the effect physiological activity has on the link between impedance and noise.Approach. Dry-printed electrodes are emerging as a new and exciting technology for skin electro-physiology. Such electrode arrays offer many advantages including user convenience, quick placement, and high resolution. Here we analyze extensive electro-physiological data recorded from the arm and the face to study and quantify the noise of dry electrodes, and to characterize the link between noise and impedance. In particular, we studied the effect of the physiological state of the subject (e.g. rapid eye movement sleep) on noise.Main results. We show that baseline noise values extracted from dry electrodes in the arm are in agreement with the Nyquist equation. In the face, on the other hand, the measured noise values were higher than the values predicted by the Nyquist equation. In addition, we studied how different electrode properties affect performances, including electrode size, shape, and material properties.Significance. Altogether, the results presented here provide a basis for understanding dry electrode performances and substantiate their great potential in electro-physiological investigations.

Novel Cost-Efficient Graphene-Based Impedance Biosensor for the Analysis of Viral Cytopathogenicity and the Effect of Antiviral Drugs.

Biosensors become increasingly relevant for medical diagnostics, pharmaceutical industry, and environmental technology, for example, to test new drugs easily and reliably or to detect cell growth in changing environmental conditions. Novel materials like graphene are promising candidates to produce biosensors on an industrial scale by means of printing processes. To reach this aim, methods for the reliable and automated production of electrode structures and their coating are required. We present an impedance biosensor in the format of a microtiter plate, fabricated by highly efficient roll-to-roll printing of graphene-based microstructures on large-area polymer foils. Proof-of-principle experiments show the evidence of the suitability of the printed graphene biosensors for impedance-based monitoring of viral cytopathogenicity and its inhibition in the presence of antiviral drugs. The developed system is a promising approach toward cost-efficient impedimetric biosensors for high-throughput screening in vaccine research and antiviral drug development.

Microfluidic In Vitro Platform for (Nano)Safety and (Nano)Drug Efficiency Screening.

Microfluidic technology is a valuable tool for realizing more in vitro models capturing cellular and organ level responses for rapid and animal-free risk assessment of new chemicals and drugs. Microfluidic cell-based devices allow high-throughput screening and flexible automation while lowering costs and reagent consumption due to their miniaturization. There is a growing need for faster and animal-free approaches for drug development and safety assessment of chemicals (Registration, Evaluation, Authorisation and Restriction of Chemical Substances, REACH). The work presented describes a microfluidic platform for in vivo-like in vitro cell cultivation. It is equipped with a wafer-based silicon chip including integrated electrodes and a microcavity. A proof-of-concept using different relevant cell models shows its suitability for label-free assessment of cytotoxic effects. A miniaturized microscope within each module monitors cell morphology and proliferation. Electrodes integrated in the microfluidic channels allow the noninvasive monitoring of barrier integrity followed by a label-free assessment of cytotoxic effects. Each microfluidic cell cultivation module can be operated individually or be interconnected in a flexible way. The interconnection of the different modules aims at simulation of the whole-body exposure and response and can contribute to the replacement of animal testing in risk assessment studies in compliance with the 3Rs to replace, reduce, and refine animal experiments.

High-throughput electrochemical sensing platform for screening nanomaterial-biomembrane interactions.

A high-throughput, automated screening platform has been developed for the assessment of biological membrane damage caused by nanomaterials. Membrane damage is detected using the technique of analyzing capacitance-current peak changes obtained through rapid cyclic voltammetry measurements of a phospholipid self-assembled monolayer formed on a mercury film deposited onto a microfabricated platinum electrode after the interaction of a biomembrane-active species. To significantly improve wider usability of the screening technique, a compact, high-throughput screening platform was designed, integrating the monolayer-supporting microfabricated electrode into a microfluidic flow cell, with bespoke pumps used for precise, automated control of fluid flow. Chlorpromazine, a tricyclic antidepressant, and a citrate-coated 50 nm diameter gold nanomaterial (AuNM) were screened to successfully demonstrate the platform's viability for high-throughput screening. Chlorpromazine and the AuNM showed interactions with a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) monolayer at concentrations in excess of 1 µmol dm-3. Biological validity of the electrochemically measured interaction of chlorpromazine with DOPC monolayers was confirmed through quantitative comparisons with HepG2 and A549 cytotoxicity assays. The platform also demonstrated desirable performance for high-throughput screening, with membrane interactions detected in <6 min per assay. Automation contributed to this significantly by reducing the required operating skill level when using the technique and minimizing fluid consumption.

Diagnosing early Barrett's neoplasia and oesophageal squamous cell neoplasia by bioimpedance spectroscopy in human tissue.

BACKGROUND: Detection of early oesophageal cancer in surrounding normal tissue can be challenging, but detection is essential to determine the subsequent treatment. Dysplastic tissue can be detected by using electrical impedance spectroscopy (EIS). OBJECTIVE: The aim of the present study was to evaluate the feasibility and value of EIS in the diagnosis of oesophageal neoplasia. METHODS: This prospective ex-vivo study included 23 patients with early oesophageal cancer (17 with Barrett's cancer and six with early squamous cell cancer). Immediately after endoscopic resection, the electrical properties of the resected specimens were investigated using a pencil probe (5 mm in diameter, frequency range from 100 Hz to 1 MHz). Punch biopsies were taken from the measured site in order to compare the results of EIS with histology. RESULTS: EIS was able to detect dysplastic oesophageal mucosa with a high rate of accuracy (82% in Barrett's oesophagus and 100% in squamous oesophagus) A total of 54 different sites in 26 tumours were evaluated. CONCLUSIONS: EIS was able to differentiate reliably between non-neoplastic and neoplastic oesophageal mucosa. Using EIS, it might be possible to use it for targeted biopsies and to avoid unnecessary biopsies during cancer surveillance in future.

On-chip integrated lensless microscopy module for optical monitoring of adherent growing mammalian cells.

Lab-on-a-chip systems are increasingly applied in cell-based assays for toxicology and drug testing. In this paper, an on-chip integrated lensless microscopy module using a direct projection method for optical monitoring of the shadow images of adherent growing mammalian cells is presented. The biological cells are conserved and interfaced by a microfabricated cavity chip with a 1 microm thick silicon nitride (Si(3)N(4)) substrate onto the surface of a 5 megapixel CMOS image sensor with 2.2 microm pixel size. The optical resolution of the assembly is estimated by the contact/proximate printing theory from optical lithography. Further characterization is made by imaging microbeads in chips with the Si(3)N(4)-membrane as well as in cavity chips with membranes made from dry film resist (DFR, thickness 20, 40 and 60 microm). The module represents a 3 × optical microscope for cell morphology imaging. The function is demonstrated by the growth monitoring of L929 cells cultured in cavity chips with Si(3)N(4) substrate for 2 days and by checking the colorimetric staining of cells with a compromised membrane.

Fully integrated monolithic optoelectronic transducer for real-time protein and DNA detection: the NEMOSLAB approach.

The development and testing of a portable bioanalytical device which was capable for real-time monitoring of binding assays was demonstrated. The device was based on arrays of nine optoelectronic transducers monolithically integrated on silicon chips. The optocouplers consisted of nine silicon avalanche diodes self-aligned to nine silicon nitride waveguides all converging to a single silicon detector. The waveguides were biofunctionalized by appropriate recognition molecules. Integrated thick polymer microchannels provided the necessary fluidic functions to the chip. A single sided direct contact scheme through a board-to-board receptacle was developed and combined with a portable customized readout and control instrument. Real-time detection of deleterious mutations in BRCA1 gene related to predisposition to hereditary breast/ovarian cancer was performed with the instrument developed using PCR products. Detection was based on waveguided photons elimination through interaction with fluorescently labeled PCR products. Detection of single biomolecular binding events was also demonstrated using nanoparticles as labels. In addition, label-free monitoring of bioreactions in real time was achieved by exploiting wavelength filtering on photonic crystal engineered waveguides. The proposed miniaturized sensing device with proper packaging and accompanied by a portable instrument can find wide application as a platform for reliable and cost effective point-of-care diagnosis.