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Journal of Neural Engineering Jun 2024The wireless transfer of power for driving implantable neural stimulation devices has garnered significant attention in the bioelectronics field. This study explores the...
OBJECTIVE
The wireless transfer of power for driving implantable neural stimulation devices has garnered significant attention in the bioelectronics field. This study explores the potential of photovoltaic (PV) power transfer, utilizing tissue-penetrating deep-red light-a novel and promising approach that has received less attention compared to traditional induction or ultrasound techniques. Our objective is to critically assess key parameters for directly powering neurostimulation electrodes with PVs, converting light impulses into neurostimulation currents.
APPROACH
We systematically investigate varying PV cell size, optional series configurations, and coupling with microelectrodes fabricated from a range of materials such as Pt, TiN, IrOx, Ti, W, PtOx, Au, or poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate). Additionally, two types of PVs, ultrathin organic PVs and monocrystalline silicon PVs, are compared. These combinations are employed to drive pairs of electrodes with different sizes and impedances. The readout method involves measuring electrolytic current using a straightforward amplifier circuit. Main Results: Optimal PV selection is crucial, necessitating sufficiently large PV cells to generate the desired photocurrent. Arranging PVs in series is essential to produce the appropriate voltage for driving current across electrode/electrolyte impedances. By carefully choosing the PV arrangement and electrode type, it becomes possible to emulate electrical stimulation protocols in terms of charge and frequency. An important consideration is whether the circuit is photovoltage-limited or photocurrent-limited. High charge-injection capacity electrodes made from pseudo-faradaic materials impose a photocurrent limit, while more capacitive materials like Pt are photovoltage-limited. Although organic PVs exhibit lower efficiency than silicon PVs, in many practical scenarios, stimulation current is primarily limited by the electrodes rather than the PV driver, leading to potential parity between the two types.
SIGNIFICANCE
This study provides a foundational guide for designing a photovoltaic-powered neurostimulation circuit. The insights gained are applicable to both in vitro and in vivo applications, offering a resource to the neural engineering community.
PubMed: 38885680
DOI: 10.1088/1741-2552/ad593d -
Journal of Neural Engineering Jun 2024Study of the foreign body reaction to implanted electrodes in the brain is an important area of research for the future development of neuroprostheses and experimental...
Study of the foreign body reaction to implanted electrodes in the brain is an important area of research for the future development of neuroprostheses and experimental electrophysiology. After electrode implantation in the brain, microglial activation, reactive astrogliosis, and neuronal cell death create an environment immediately surrounding the electrode that is significantly altered from its homeostatic state. To uncover physiological changes potentially affecting device function and longevity, spatial transcriptomics was implemented to identify changes in gene expression driven by electrode implantation and compare this differential gene expression to traditional metrics of glial reactivity, neuronal loss, and electrophysiological recording quality. For these experiments, rats were chronically implanted with functional Michigan-style microelectrode arrays, from which electrophysiological recordings (multi-unit activity, local field potential) were taken over a six-week time course. Brain tissue cryosections surrounding each electrode were then mounted for spatial transcriptomics processing. The tissue was immunolabeled for neurons and astrocytes, which provided both a spatial reference for spatial transcriptomics and a quantitative measure of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) immunolabeling surrounding each implant. Results from rat motor cortex within 300µm of the implanted electrodes at 24 hours, 1 week, and 6 weeks post-implantation showed up to 553 significantly differentially expressed (DE) genes between implanted and non-implanted tissue sections. Regression on the significant DE genes identified the 6-7 genes that had the strongest relationship to histological and electrophysiological metrics, revealing potential candidate biomarkers of recording quality and the tissue response to implanted electrodes .
PubMed: 38885679
DOI: 10.1088/1741-2552/ad5936 -
IEEE Transactions on Biomedical... Jun 2024Electrical capacitance tomography (ECT) can be used to predict information about the interior volume of an object based on measured capacitance at its boundaries. Here,...
Electrical capacitance tomography (ECT) can be used to predict information about the interior volume of an object based on measured capacitance at its boundaries. Here, we present a microscale capacitance tomography system with a spatial resolution of 10 microns using an active CMOS microelectrode array. We introduce a deep learning model for reconstructing 3-D volumes of cell cultures using the boundary capacitance measurements acquired from the sensor array, which is trained using a multi-objective loss function that combines a pixel-wise loss function, a distribution-based loss function, and a region-based loss function to improve model's reconstruction accuracy. The multi-objective loss function enhances the model's reconstruction accuracy by 3.2% compared to training only with a pixel-wise loss function. Compared to baseline computational methods, our model achieves an average of 4.6% improvement on the datasets evaluated. We demonstrate our approach on experimental datasets of bacterial biofilms, showcasing the system's ability to resolve microscopic spatial features of cell cultures in three dimensions. Microscale capacitance tomography can be a low-cost, low-power, label-free tool for 3-D imaging of biological samples.
PubMed: 38885101
DOI: 10.1109/TBCAS.2024.3415360 -
ACS Applied Materials & Interfaces Jun 2024Electrode/electrolyte interfacial ion transfer is a fundamental process occurring during insertion-type redox reactions at battery electrodes. The rate at which ions...
Electrode/electrolyte interfacial ion transfer is a fundamental process occurring during insertion-type redox reactions at battery electrodes. The rate at which ions move into and out of the electrode, as well as at interphase structures, directly impacts the power performance of the battery. However, measuring and quantifying these ion transfer phenomena can be difficult, especially at high electrolyte concentrations as found in batteries. Herein, we report a scanning electrochemical microscope method using a common ferri/ferrocyanide (FeCN) redox mediator dissolved in an aqueous electrolyte to track changes in alkali ions at high electrolyte concentrations (up to 3 mol dm). Using voltammetry at a platinum microelectrode, we observed a reversible shift of ∼60 mV per decade change in K concentrations. The response showed high stability in sequential measurements and similar behavior in other aqueous electrolytes. From there, we used the same FeCN mediator to position the microelectrode at the surface of a potassium-insertion electrode. We demonstrate tracking of local changes in the K concentration during insertion and deinsertion processes. Using a 2D axisymmetric, finite element model, we further estimate the effective insertion rates. These developments enable characterization of a key parameter for improving batteries, the interfacial ion transfer kinetics, and future work may show mediators appropriate for molar concentrations in nonaqueous electrolytes and beyond.
PubMed: 38885040
DOI: 10.1021/acsami.4c03645 -
Frontiers in Endocrinology 2024Pancreatic islets are important in nutrient homeostasis and improved cellular models of clonal origin may very useful especially in view of relatively scarce primary...
BACKGROUND
Pancreatic islets are important in nutrient homeostasis and improved cellular models of clonal origin may very useful especially in view of relatively scarce primary material. Close 3D contact and coupling between β-cells are a hallmark of physiological function improving signal/noise ratios. Extracellular electrophysiology using micro-electrode arrays (MEA) is technically far more accessible than single cell patch clamp, enables dynamic monitoring of electrical activity in 3D organoids and recorded multicellular slow potentials (SP) provide unbiased insight in cell-cell coupling.
OBJECTIVE
We have therefore asked whether 3D spheroids enhance clonal β-cell function such as electrical activity and hormone secretion using human EndoC-βH1, EndoC-βH5 and rodent INS-1 832/13 cells.
METHODS
Spheroids were formed either by hanging drop or proprietary devices. Extracellular electrophysiology was conducted using multi-electrode arrays with appropriate signal extraction and hormone secretion measured by ELISA.
RESULTS
EndoC-βH1 spheroids exhibited increased signals in terms of SP frequency and especially amplitude as compared to monolayers and even single cell action potentials (AP) were quantifiable. Enhanced electrical signature in spheroids was accompanied by an increase in the glucose stimulated insulin secretion index. EndoC-βH5 monolayers and spheroids gave electrophysiological profiles similar to EndoC-βH1, except for a higher electrical activity at 3 mM glucose, and exhibited moreover a biphasic profile. Again, physiological concentrations of GLP-1 increased AP frequency. Spheroids also exhibited a higher secretion index. INS-1 cells did not form stable spheroids, but overexpression of connexin 36, required for cell-cell coupling, increased glucose responsiveness, dampened basal activity and consequently augmented the stimulation index.
CONCLUSION
In conclusion, spheroid formation enhances physiological function of the human clonal β-cell lines and these models may provide surrogates for primary islets in extracellular electrophysiology.
Topics: Humans; Insulin-Secreting Cells; Spheroids, Cellular; Electrophysiological Phenomena; Insulin Secretion; Glucose; Insulin; Action Potentials; Animals
PubMed: 38883608
DOI: 10.3389/fendo.2024.1402880 -
Electrochimica Acta Aug 2024Laser-induced graphene (LIG) electrodes have become popular for electrochemical sensor fabrication due to their simplicity for batch production without the use of...
Laser-induced graphene (LIG) electrodes have become popular for electrochemical sensor fabrication due to their simplicity for batch production without the use of reagents. The high surface area and favorable electrocatalytic properties also enable the design of small electrochemical devices while retaining the desired electrochemical performance. In this work, we systematically investigated the effect of LIG working electrode size, from 0.8 mm to 4.0 mm diameter, on their electrochemical properties, since it has been widely assumed that the electrochemistry of LIG electrodes is independent of size above the microelectrode size regime. The background and faradaic current from cyclic voltammetry (CV) of an outer-sphere redox probe [Ru(NH3)6] showed that smaller LIG electrodes had a higher electrode roughness factor and electroactive surface ratio than those of the larger electrodes. Moreover, CV of the surface-sensitive redox probes [Fe(CN)6] and dopamine revealed that smaller electrodes exhibited better electrocatalytic properties, with enhanced electron transfer kinetics. Scanning electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy showed that the physical and chemical surface structure were different at the electrode center versus the edges, so the electrochemical properties of the smaller electrodes were improved by having rougher surface and more density of the graphitic edge planes, and more oxide-containing groups, leading to better electrochemistry. The difference could be explained by the different photothermal reaction time from the laser scribing process that causes different stable carbon morphology to form on the polymer surface. Our results give a new insight on relationships between surface structure and electrochemistry of LIG electrodes and are useful for designing miniaturized electrochemical devices.
PubMed: 38881690
DOI: 10.1016/j.electacta.2024.144452 -
The European Journal of Neuroscience Jun 2024Age is a primary risk factor for Parkinson's disease (PD); however, the effects of aging on the Parkinsonian brain remain poorly understood, particularly for deep brain...
Age is a primary risk factor for Parkinson's disease (PD); however, the effects of aging on the Parkinsonian brain remain poorly understood, particularly for deep brain structures. We investigated intraoperative micro-electrode recordings from the subthalamic nucleus (STN) of PD patients aged between 42 and 76 years. Age was associated with decreased oscillatory beta power and non-oscillatory high-frequency power, independent of PD-related variables. Single unit firing and burst rates were also reduced, whereas the coefficient of variation and the structure of burst activity were unchanged. Phase synchronization (debiased weighed phase lag index [dWPLI]) between sites was pronounced in the beta band between electrodes in the superficial STN but was unaffected by age. Our results show that aging is associated with reduced neuronal activity without changes to its temporal structure. We speculate that the loss of activity in the STN may mediate the relationship between PD and age.
PubMed: 38880896
DOI: 10.1111/ejn.16435 -
NPJ Parkinson's Disease Jun 2024The subthalamic nucleus (STN) is pivotal in basal ganglia function in health and disease. Micro-electrode recordings of >25,000 recording sites from 146 Parkinson's...
The subthalamic nucleus (STN) is pivotal in basal ganglia function in health and disease. Micro-electrode recordings of >25,000 recording sites from 146 Parkinson's patients undergoing deep brain stimulation (DBS) allowed differentiation between subthalamic input, represented by local field potential (LFP), and output, reflected in spike discharge rate (SPK). As with many natural systems, STN neuronal activity exhibits power-law dynamics characterized by the exponent α. We, therefore, dissected STN data into aperiodic and periodic components using the Fitting Oscillations & One Over F (FOOOF) tool. STN LFP showed significantly higher aperiodic exponents than SPK. Additionally, SPK beta oscillations demonstrated a downward frequency shift compared to LFP. Finally, the STN aperiodic and spiking parameters explained a significant fraction of the variance of the burden and treatment efficacy of Parkinson's disease. The unique STN input-output dynamics may clarify its role in Parkinson's physiology and can be utilized in closed-loop DBS therapy.
PubMed: 38879564
DOI: 10.1038/s41531-024-00737-8 -
Analytical and Bioanalytical Chemistry Jun 2024Organic-inorganic hybrid nanocomposites (OIHN), with tailored surface chemistry, offer ultra-sensitive architecture capable of detecting ultra-low concentrations of...
Organic-inorganic hybrid nanocomposites (OIHN), with tailored surface chemistry, offer ultra-sensitive architecture capable of detecting ultra-low concentrations of target analytes with precision. In the present work, a novel nano-biosensor was fabricated, acquainting dynamic synergy of reduced graphene oxide (rGO) decorated hexagonal boron nitride nanosheets (hBNNS) for detection of carcinoembryonic antigen (CEA). Extensive spectroscopic and microscopic analyses confirmed the successful hydrothermal synthesis of cross-linked rGO-hBNNS nanocomposite. Uniform micro-electrodes of rGO-hBNNS onto pre-hydrolyzed ITO were obtained via electrophoretic deposition (EPD) technique at low DC potential (15 V). Optimization of antibody incubation time, pH of supporting electrolyte, and immunoelectrode preparation was thoroughly investigated to enhance nano-biosensing efficacy. rGO-modified hBNNS demonstrated 29% boost in electrochemical performance over bare hBNNS, signifying remarkable electro-catalytic activity of nano-biosensor. The presence of multifunctional groups on the interface facilitated stable crosslinking chemistry, increased immobilization density, and enabled site-specific anchoring of Anti-CEA, resulting in improved binding affinity. The nano-biosensor demonstrated a remarkably low limit of detection of 5.47 pg/mL (R = 0.99963), indicating exceptional sensitivity and accuracy in detecting CEA concentrations from 0 to 50 ng/mL. The clinical evaluation confirmed its exceptional shelf life, minimal cross-reactivity, and robust recovery rates in human serum samples, thereby unraveling the potential for early, highly sensitive, and reliable CEA detection.
PubMed: 38878180
DOI: 10.1007/s00216-024-05379-6 -
The Journal of Physiology Jun 2024Large trans-sarcolemmal ionic shifts occur with fatiguing exercise or stimulation of isolated muscles. However, it is unknown how resting membrane potential (E) and...
Large trans-sarcolemmal ionic shifts occur with fatiguing exercise or stimulation of isolated muscles. However, it is unknown how resting membrane potential (E) and intracellular sodium concentration ([Na]) change with repeated contractions in living mammals. We investigated (i) whether [Na] (peak, kinetics) can reveal changes of Na-K pump activity during brief or fatiguing stimulation and (ii) how resting E and [Na] change during fatigue and recovery of rat soleus muscle in situ. Muscles of anaesthetised rats were stimulated with brief (10 s) or repeated tetani (60 Hz for 200 ms, every 2 s, for 30 s or 300 s) with isometric force measured. Double-barrelled ion-sensitive microelectrodes were used to quantify resting E and [Na]. Post-stimulation data were fitted using polynomials and back-extrapolated to time zero recovery. Mean pre-stimulation resting E (layer 2-7 fibres) was -71 mV (surface fibres were more depolarised), and [Na] was 14 mM. With deeper fibres, 10 s stimulation (2-150 Hz) increased [Na] to 38-46 mM whilst simultaneously causing hyperpolarisations (7.3 mV for 2-90 Hz). Fatiguing stimulation for 30 s or 300 s led to end-stimulation resting E of -61 to -53 mV, which recovered rapidly (T, 8-22 s). Mean end-stimulation [Na] increased to 86-101 mM with both fatigue protocols and the [Na] recovery time-course (T, 21-35 s) showed no difference between protocols. These combined findings suggest that brief stimulation hyperpolarises the resting E, likely via maximum Na-induced stimulation of the Na-K pump. Repeated tetani caused massive depolarisation and elevations of [Na] that together lower force, although they likely interact with other factors to cause fatigue. [Na] recovery kinetics provided no evidence of impaired Na-K pump activity with fatigue. KEY POINTS: It is uncertain how resting membrane potential, intracellular sodium concentration ([Na]), and sodium-potassium (Na-K) pump activity change during repeated muscle contractions in living mammals. For rat soleus muscle fibres in situ, brief tetanic stimulation for 10 s led to raised [Na], anticipated to evoke maximal Na-induced stimulation of the Na-K pump causing an immediate hyperpolarisation of the sarcolemma. More prolonged stimulation with repeated tetanic contractions causes massive elevations of [Na], which together with large depolarisations (via K disturbances) likely reduce force production. These effects occurred without impairment of Na-K pump function. Together these findings suggest that rapid activation of the Na-K pump occurs with brief stimulation to maintain excitability, whereas more prolonged stimulation causes rundown of the trans-sarcolemmal K gradient (hence depolarisation) and Na gradient, which in combination can impair contraction to contribute to fatigue in living mammals.
PubMed: 38877870
DOI: 10.1113/JP285870