System of Implantable Electrodes for Neural Signal Acquisition and Stimulation for Wirelessly Connected Forearm Prosthesis.

There is great interest in the development of prosthetic limbs capable of complex activities that are wirelessly connected to the patient's neural system. Although some progress has been achieved in this area, one of the main problems encountered is the selective acquisition of nerve impulses and the closing of the automation loop through the selective stimulation of the sensitive branches of the patient. Large-scale research and development have achieved so-called "cuff electrodes"; however, they present a big disadvantage: they are not selective. In this article, we present the progress made in the development of an implantable system of plug neural microelectrodes that relate to the biological nerve tissue and can be used for the selective acquisition of neuronal signals and for the stimulation of specific nerve fascicles. The developed plug electrodes are also advantageous due to their small thickness, as they do not trigger nerve inflammation. In addition, the results of the conducted tests on a sous scrofa subject are presented.

Functional Enhancement and Characterization of an Electrophysiological Mapping Electrode Probe with Carbonic, Directional Macrocontacts.

Electrophysiological mapping (EM) using acute electrode probes is a common procedure performed during functional neurosurgery. Due to their constructive specificities, the EM probes are lagging in innovative enhancements. This work addressed complementing a clinically employed EM probe with carbonic and circumferentially segmented macrocontacts that are operable both for neurophysiological sensing ("recording") of local field potentials (LFP) and for test stimulation. This paper illustrates in-depth the development that is based on the direct writing of functional materials. The unconventional fabrication processes were optimized on planar geometry and then transferred to the cylindrically thin probe body. We report and discuss the constructive concept and architecture of the probe, characteristics of the electrochemical interface deduced from voltammetry and chronopotentiometry, and the results of in vitro and in vivo recording and pulse stimulation tests. Two- and three-directional macrocontacts were added on probes having shanks of 550 and 770 µm diameters and 10-23 cm lengths. The graphitic material presents a ~2.7 V wide, almost symmetric water electrolysis window, and an ultra-capacitive charge transfer. When tested with clinically relevant 150 µs biphasic current pulses, the interfacial polarization stayed safely away from the water window for pulse amplitudes up to 9 mA (135 µC/cm2). The in vivo experiments on adult rat models confirmed the high-quality sensing of LFPs. Additionally, the in vivo-prevailing increase in the electrode impedance and overpotential are discussed and modeled by an ionic mobility-reducing spongiform structure; this restricted diffusion model gives new applicative insight into the in vivo-uprisen stimulation overpotential.

Different Extraction Approaches for the Analysis of Melatonin from Cabernet Sauvignon and Feteasca Neagra Wines Using a Validated HPLC-FL Method.

In recent years, the wine industry has shown a considerable degree of interest in the occurrence of melatonin in wines. Sample pretreatment may be the most important step in trace analysis. Since wine is a complex matrix and melatonin is present in low amounts (ppb), an adequate extraction technique is required. In this study, the effect of several extraction methods, such as solid phase extraction (SPE), Quick, Easy, Cheap, Effective, Rugged, and Safe extraction (QuEChERS), and dispersive liquid-liquid micro-extraction (DLLME) was studied and the variable parameters that can arise throughout the extraction process were optimized to obtain the best results. A high-performance liquid chromatography with fluorescence detector (HPLC-FL) method was adapted and validated, including measurement uncertainty, for the analysis of melatonin in wines and to assess the efficiency of the extraction yield. After comparing the acquired results, the DLLME method was optimized. Extraction recoveries values ranging from 95 to 104% demonstrated that the approach may be successfully applied for the extraction and concentration (enrichment factor of almost eight) of melatonin in wine samples prior to HPLC-FL analysis. The first report of melatonin levels in Feteasca Neagra wines has been made. The data obtained for Cabernet Sauvignon revealed that the final levels of melatonin in the wines are dependent on the winemaking process.

Remote Sensing System for Motor Nerve Impulse.

In this article, we present our research achievements regarding the development of a remote sensing system for motor pulse acquisition, as a first step towards a complete neuroprosthetic arm. We present the fabrication process of an implantable electrode for nerve impulse acquisition, together with an innovative wirelessly controlled system. In our study, these were combined into an implantable device for attachment to peripheral nerves. Mechanical and biocompatibility tests were performed, as well as in vivo testing on pigs using the developed system. This testing and the experimental results are presented in a comprehensive manner, demonstrating that the system is capable of accomplishing the requirements of its designed application. Most significantly, neural electrical signals were acquired and transmitted out of the body during animal experiments, which were conducted according to ethical regulations in the field.

Design and Fabrication of a New Wearable Pressure Sensor for Blood Pressure Monitoring.

In recent years, research into the field of materials for flexible sensors and fabrication techniques directed towards wearable devices has helped to raise awareness of the need for new sensors with healthcare applicability. Our goal was to create a wearable flexible pressure sensor that could be integrated into a clinically approved blood pressure monitoring device. The sensor is built from a microfluidic channel encapsulated between two polymer layers, one layer being covered by metal transducers and the other being a flexible membrane containing the microfluidic channel, which also acts as a sealant for the structure. The applied external pressure deforms the channel, causing changes in resistance to the microfluidic layer. Electrical characterization has been performed in 5 different configurations, using alternating current (AC) and (DC) direct current measurements. The AC measurements for the fabricated pressure sensor resulted in impedance values at tens of hundreds of kOhm. Our sensor proved to have a high sensitivity for pressure values between 0 and 150 mm Hg, being subjected to repeatable external forces. The novelty presented in our work consists in the unique technological flow for the fabrication of the flexible wearable pressure sensor. The proposed miniaturized pressure sensor will ensure flexibility, low production cost and ease of use. It is made of very sensitive microfluidic elements and biocompatible materials and can be integrated into a wearable cuffless device for continuous blood pressure monitoring.

Platform with biomimetic electrochemical sensors for adiponectin and leptin detection in human serum.

Two new biomimetic sensors for the detection of adiponectin (A) and leptin (L) through molecularly imprinted polymers (MIPs) onto gold working electrodes (GWEs) were fabricated. Based on electrochemical impedance spectroscopy (EIS) results and cyclic voltammetry (CV) characteristics recorded in the development stages of the fabricated sensors, the sensors were electrochemically optimized and used in an integrated microfluidic platform to detect adiponectin/leptin via conductance signals and non-imprinted electrodes were used as references. To overcome the limitation of the low response signals after template binding non-conductive polyphenol (PP) and poliscopoletin (PS) were used for templates formation. Under optimized experimental conditions the conductance and resistance signals were obtained in the linear range of 0-50 µg ml-1 for A and 1-32 ng∙ml-1 for L with low limits of detection (0.25 µg ml-1 for A and 0.110 ng ml-1 for L). The dedicated platform exhibited an excellent response with great selectivity and stability. Finally, the proposed biomimetic sensors were successfully applied to enable the determination of A and L in human patient's serum with very high accuracy when compared to enzyme-linked immunosorbent assay ELISA reference methods.

A quantum dot-based lateral flow immunoassay for the sensitive detection of human heart fatty acid binding protein (hFABP) in human serum.

We describe the preparation and validation of a novel lateral flow immunoassay test for the detection of human heart fatty acid binding protein (hFABP). Water-soluble CdTe quantum dots (QDs) were selected as the fluorescent label and were linked covalently to anti-hFABP antibodies. Upon conjugation, the secondary structure of the anti-hFABP was preserved and the fluorescence quantum yield of the CdTe QDs increased. The labelled antibodies were transferred to the immunoassay test strip and the antigen-antibody reaction was successfully performed. This evidenced the preserved antibody activity of QD-labelled anti-hFABP towards hFABP, and provided a rapid means for the quantitation of hFABP in human serum within the range of 0-160ng ∙ ml-1, with a much lower detection limit of 221pg.∙ ml-1 compared with other rapid tests based on lateral flow immunoassays. This new immunoassay test has been successfully used for the early detection of acute myocardial infarction.