Histological evaluation of flexible neural implants; flexibility limit for reducing the tissue response?

OBJECTIVE: Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain's micromotion. However, a large discrepancy of Young's modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? APPROACH: Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (~150 GPa), polyimide (1.5 GPa), OSTE+Hard (300 MPa), and OSTE+Soft (6 MPa). MAIN RESULTS: We observed a significant reduction in the fluorescence intensity of biomarkers for activated microglia/macrophages and blood-brain barrier (BBB) leakiness around the three soft polymer probes compared to the silicon probe, both at 4 weeks and 8 weeks post-implantation. However, we did not observe any consistent differences in the biomarkers among the polymer probes. SIGNIFICANCE: The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.

Carbon fiber nanoelectrodes applied to microchip electrophoresis amperometric detection of neurotransmitter dopamine in rat pheochromocytoma (PC12) cells.

Microelectrodes have been adopted in electrochemical detection for CE or microchip CE in recent years. In this paper, the use of nanoelectrodes (with tip diameter of 100-300 nm) as the electrochemical detector in microchip CE is firstly reported. The experimental results indicated that both the sensitivity and resolution of microchip CE with the carbon fiber nanoelectrode (CFNE) amperometric detection have been improved markedly comparing with the traditional microelectrodes. The detection limit of dopamine (S/N = 3) is 5.9x10(-8) M, which is one or two orders of magnitude lower than that reported so far, and the resolution of dopamine (DA) and isoprenaline (IP) has also improved from 0.6 (using 7 mum carbon fiber microelectrodes, CFME) to 1.0. We assembled a novel and easily operated microchip CE system with end-column amperometric detection, which allows the convenient and fast replacement of the passivated electrodes. Under the optimized condition, the RSDs of peak height and migration time are 1.47 and 0.31%, respectively (n = 40), indicating that the system displays excellent reproducibility. The nanoelectrode-based microchip CE system has been successfully applied to the determination of DA in cultured rat pheochromocytoma (PC12) cells, and the average content of DA in an individual PC12 cell is 0.54 +/- 0.07 fmol, which is in good agreement with that reported in the literature.

Criteria for the selection of materials for implanted electrodes.

There are four criteria that must be considered when choosing material for an implanted electrode: (1) tissue response, (2) allergic response, (3) electrode-tissue impedance, and (4) radiographic visibility. This paper discusses these four criteria and identifies the materials that are the best candidates for such electrodes. For electrodes that make ohmic contact with tissues: gold, platinum, platinum-iridium, tungsten, and tantalum are good candidates. The preferred insulating materials are polyimide and glass. The characteristics of stimulator output circuits and the importance of the bidirectional waveform in relation to electrode decomposition are discussed. The paper concludes with an analysis, the design criteria, and the special properties and materials for capacitive recording and stimulating electrodes.

Comparison of surface EMG signals between electrode types, interelectrode distances and electrode orientations in isometric exercise of the erector spinae muscle.

The influence of electrode type, interelectrode distance (IED) and electrode orientation on EMG signals from the paraspinal muscles was investigated. Bipolar electrodes were placed at distances 2, 3, 4, 6 and 8 cm over the erector spinae in the cranio-caudal direction ("in series") as well as in the direction perpendicular to it ("in parallel"). Ten subjects performed 5 s isometric contractions of the erector spinae at 20, 40, 60, 80 and 100% MVC by pulling upward on a handlebar attached to the floor. RMS EMG signals were analyzed for mean average amplitude (AA). Mean total power (TP) and mean median frequency (MF) of the raw EMG signal were determined using fast Fourier transform. In addition to graded loading, sustained fatiguing contractions were performed from which TP and MF were obtained. With increasing IED the AA and TP increased while MF decreased. Although a trend towards higher AA, TP and MF was found for electrodes "in series", as compared to those "in parallel", the difference never reached significance. It is concluded that consistent information about muscle activity was obtained with Miniature Biopotential Skin Electrodes and 14445C Hewlett-Packard electrodes independently from IED or orientation. Orientation "in parallel" prevented the electrodes from sliding during muscle contraction. The third tested type, electrodes developed in the Neuromuscular Research Center, Boston, proved extremely sensitive to movement.

A new method for manufacturing carbon-fibre microelectrodes.

A new, fast and low-cost method using a carbon-fibre microelectrode is proposed. The microelectrode is constructed by glueing one or more carbon fibres (5 mm in diameter) with a silver resin on a silver wire or stainless steel tube. The characteristics of that microelectrode have been measured and compared with those of commercially available glass carbon-fibre microelectrodes. According to our measures, the impedance, capacity and current noise were lowered which permits these electrodes to be used in voltammetry and in detection of very low currents generated during formation of antigen-antibody complex.