A Metabolic Biofuel Cell: Conversion of Human Leukocyte Metabolic Activity to Electrical Currents

<p>Abstract</p> <p>An investigation of the electrochemical activity of human white blood cells (WBC) for biofuel cell (BFC) applications is described. WBCs isolated from whole human blood were suspended in PBS and introduced into the anode compartment of a proton exchange membrane (PEM) fuel cell. The cathode compartment contained a 50 mM potassium ferricyanide solution. Average current densities between 0.9 and 1.6 μA cm^-2and open circuit potentials (V_oc) between 83 and 102 mV were obtained, which were both higher than control values. Cyclic voltammetry was used to investigate the electrochemical activity of the activated WBCs in an attempt to elucidate the mechanism of electron transfer between the cells and electrode. Voltammograms were obtained for the WBCs, including peripheral blood mononuclear cells (PBMCs - a lymphocyte-monocyte mixture isolated on a Ficoll gradient), a B lymphoblastoid cell line (BLCL), and two leukemia cell lines, namely K562 and Jurkat. An oxidation peak at about 363 mV vs. SCE for the PMA (phorbol ester) activated primary cells, with a notable absence of a reduction peak was observed. Oxidation peaks were not observed for the BLCL, K562 or Jurkat cell lines. HPLC confirmed the release of serotonin (5-HT) from the PMA activated primary cells. It is believed that serotonin, among other biochemical species released by the activated cells, contributes to the observed BFC currents.</p

In Vivo Electrochemical Analysis of a PEDOT/MWCNT Neural Electrode Coating

Neural electrodes hold tremendous potential for improving understanding of brain function and restoring lost neurological functions. Multi-walled carbon nanotube (MWCNT) and dexamethasone (Dex)-doped poly(3,4-ethylenedioxythiophene) (PEDOT) coatings have shown promise to improve chronic neural electrode performance. Here, we employ electrochemical techniques to characterize the coating in vivo. Coated and uncoated electrode arrays were implanted into rat visual cortex and subjected to daily cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) for 11 days. Coated electrodes experienced a significant decrease in 1 kHz impedance within the first two days of implantation followed by an increase between days 4 and 7. Equivalent circuit analysis showed that the impedance increase is the result of surface capacitance reduction, likely due to protein and cellular processes encapsulating the porous coating. Coating’s charge storage capacity remained consistently higher than uncoated electrodes, demonstrating its in vivo electrochemical stability. To decouple the PEDOT/MWCNT material property changes from the tissue response, in vitro characterization was conducted by soaking the coated electrodes in PBS for 11 days. Some coated electrodes exhibited steady impedance while others exhibiting large increases associated with large decreases in charge storage capacity suggesting delamination in PBS. This was not observed in vivo, as scanning electron microscopy of explants verified the integrity of the coating with no sign of delamination or cracking. Despite the impedance increase, coated electrodes successfully recorded neural activity throughout the implantation period

Mechanical failure modes of chronically implanted planar silicon-based neural probes for laminar recording

Penetrating intracortical electrode arrays that record brain activity longitudinally are powerful tools for basic neuroscience research and emerging clinical applications. However, regardless of the technology used, signals recorded by these electrodes degrade over time. The failure mechanisms of these electrodes are understood to be a complex combination of the biological reactive tissue response and material failure of the device over time. While mechanical mismatch between the brain tissue and implanted neural electrodes have been studied as a source of chronic inflammation and performance degradation, the electrode failure caused by mechanical mismatch between different material properties and different structural components within a device have remained poorly characterized. Using Finite Element Model (FEM) we simulate the mechanical strain on a planar silicon electrode. The results presented here demonstrate that mechanical mismatch between iridium and silicon leads to concentrated strain along the border of the two materials. This strain is further focused on small protrusions such as the electrical traces in planar silicon electrodes. These findings are confirmed with chronic in vivo data (133–189 days) in mice by correlating a combination of single-unit electrophysiology, evoked multi-unit recordings, electrochemical impedance spectroscopy, and scanning electron microscopy from traces and electrode sites with our modeling data. Several modes of mechanical failure of chronically implanted planar silicon electrodes are found that result in degradation and/or loss of recording. These findings highlight the importance of strains and material properties of various subcomponents within an electrode array

Batch Fabrication of Microelectrode Arrays with Glassy Carbon Microelectrodes and Interconnections for Neurochemical Sensing: Promises and Challenges

Flexible multielectrode arrays with glassy carbon (GC) electrodes and metal interconnection (hybrid MEAs) have shown promising performance in multi-channel neurochemical sensing. A primary challenge faced by hybrid MEAs fabrication is the adhesion of the metal traces with the GC electrodes, as prolonged electrical and mechanical stimulation can lead to adhesion failure. Previous devices with GC electrodes and interconnects made of a homogeneous material (all GC) demonstrated exceptional electrochemical stability but required miniaturization for enhanced tissue integration and chronic electrochemical sensing. In this study, we used two different methods for the fabrication of all GC-MEAs on thin flexible substrates with miniaturized features. The first method, like that previously reported, involves a double pattern-transfer photolithographic process, including transfer-bonding on temporary polymeric support. The second method requires a double-etching process, which uses a 2 µm-thick low stress silicon nitride coating of the Si wafer as the bottom insulator layer for the MEAs, bypassing the pattern-transfer and demonstrating a novel technique with potential advantages. We confirmed the feasibility of the two fabrication processes by verifying the practical conductivity of 3 µm-wide 2 µm-thick GC traces, the GC microelectrode functionality, and their sensing capability for the detection of serotonin using fast scan cyclic voltammetry. Through the exchange and discussion of insights regarding the strengths and limitations of these microfabrication methods, our goal is to propel the advancement of GC-based MEAs for the next generation of neural interface devices

Tracheal Aspirate Levels of the Matricellular Protein SPARC Predict Development of Bronchopulmonary Dysplasia

<div><p>Background</p><p>Isolation of tracheal aspirate mesenchymal stromal cells (MSCs) from premature infants has been associated with increased risk of bronchopulmonary dysplasia (BPD). MSCs show high levels of mRNAs encoding matricellular proteins, non-structural extracellular proteins that regulate cell-matrix interactions and participate in tissue remodeling. We hypothesized that lung matricellular protein expression predicts BPD development.</p><p>Methods</p><p>We collected tracheal aspirates and MSCs from mechanically-ventilated premature infants during the first week of life. Tracheal aspirate and MSC-conditioned media were analyzed for seven matricellular proteins including SPARC (for Secreted Protein, Acidic, Rich in Cysteine, also called osteonectin) and normalized to secretory component of IgA. A multiple logistic regression model was used to determine whether tracheal aspirate matricellular protein levels were independent predictors of BPD or death, controlling for gestational age (GA) and birth weight (BW).</p><p>Results</p><p>We collected aspirates from 89 babies (38 developed BPD, 16 died before 36 wks post-conceptual age). MSC-conditioned media showed no differences in matricellular protein abundance between cells from patients developing BPD and cells from patients who did not. However, SPARC levels were higher in tracheal aspirates from babies with an outcome of BPD or death (<i>p</i><0.01). Further, our logistic model showed that tracheal aspirate SPARC (p<0.02) was an independent predictor of BPD/death. SPARC deposition was increased in the lungs of patients with BPD.</p><p>Conclusions</p><p>In mechanically-ventilated premature infants, tracheal aspirate SPARC levels predicted development of BPD or death. Further study is needed to determine the value of SPARC as a biomarker or therapeutic target in BPD.</p></div