Fascicle-Selective Ultrasound-Powered Bidirectional Wireless Peripheral Nerve Interface IC.

This paper presents an innovative, minimally invasive, battery-free, wireless, peripheral nervous system (PNS) neural interface, which seamlessly integrates a millimeter-scale, fascicle-selective integrated circuit (IC) with extraneural recording and stimulating channels. The system also incorporates a wearable interrogator equipped with integrated machine-learning capabilities. This PNS interface is specifically tailored for adaptive neuromodulation therapy, targeting individuals with paralysis, amputation, or chronic medical conditions. By employing a neural pathway classifier and temporal interference stimulation, the proposed interface achieves precise deep fascicle selectivity for recording and stimulation without the need for nerve penetration or compression. Ultrasonic energy harvesters facilitate wireless power harvesting and data reception, enhancing the usability of the system. Key circuit performance metrics encompass a 2.2 µVrms input-referred noise, 14-bit ENOB, and a 173 dB Schreier figure of merit (FOM) for the neural analog-to-digital converter (ADC). Additionally, the ultra-low-power radio-frequency (RF) transmitter boasts a remarkable 1.38 pJ/bit energy efficiency. In vivo experiments conducted on rat sciatic nerves provide compelling evidence of the interface's ability to selectively stimulate and record neural fascicles. The proposed PNS neural interface offers alternative treatment options for diagnosing and treating neurological disorders, as well as restoring or repairing neural functions, improving the quality of life for patients with neurological and sensory deficits.

Nucleic acid based point-of-care diagnostic technology for infectious disease detection using machine learning empowered smartphone-interfaced quantitative colorimetry.

We report a nucleic acid-based point of care testing technology for infectious disease detection at resource limited settings by integrating a low-cost portable device with machine learning-empowered quantitative colorimetric analytics that can be interfaced via a smartphone application. We substantiate our proposition by demonstrating the efficacy of this technology in detecting COVID-19 infection from human swab samples, using the RT-LAMP protocol. Comparison with gold standard results from real-time PCR evidences high sensitivity and specificity, ensuring simplicity, portability, and user-friendliness of the technology at the same time. Colorimetric analytics of the reaction output without necessitating the opening of the reaction microchambers enables execution of the complete test workflow without any laboratory control that may otherwise be required stringently for safeguarding against carryover contamination. Seamless sample-to-answer workflow and machine learning-based readout further assures minimal human intervention for the test readout, thus eliminating inevitable inaccuracies stemming from erroneous execution of the test as well as subjectivity in interpreting the outcome. Our results further indicate the possibilities of upgrading the technology to predict the pathogenic load on the infected patients akin to the cyclic threshold value of the real-time PCR, when calibrated with reference to a wide range of 'training' data for the machine learner, thereby putting forward the same as viable alternative to the resource-intensive PCR tests that cannot be made readily accessible at underserved community settings.

Enhanced Substrate Specificity of Thermostable Cytochrome P450 CYP175A1 by Site Saturation Mutation on Tyrosine 68.

Thermostable cytochrome P450 (CYP175A1) cloned from Thermus thermophilus shows mid-point unfolding temperature (Tm) of 88 °C (361 K) along with high thermodynamic stability making it a potential industrially viable biocatalyst. Molecular docking analyses, and structural superposition with steroidogenic and fatty acid metabolizing cytochrome P450 s suggested that the tyrosine 68 may have important role in binding as well as metabolism of substrates by the enzyme. Site-saturation mutation of the tyrosine 68 residue was carried out and several unique mutations were obtained that were properly folded and showed high thermostability. We investigated the effects of variation of the single residue, Tyr68 at the substrate binding pocket of the enzyme on the substrate specificity of CYP175A1. Screening of the mutant colonies of CYP175A1 obtained after saturation mutagenesis of Tyr68 using saturated fatty acid, myristic acid and poly unsaturated fatty acids showed that the Y68K had notable binding and catalytic activity for mono-oxygenation of the saturated fatty acid (myristic acid), which had no major detectable binding affinity towards the WT enzyme. The Y68R mutant of CYP175A1, on the other hand was found to selectively bind and catalyse reaction of cholesterol. The wild type as well as both the mutants of the enzyme however bind poly unsaturated fatty acids. The results thus show that saturation mutation of a single amino acid at the substrate binding pocket of the thermostable cytochrome P450 could induce sufficient changes in the substrate binding pocket of the enzyme that can efficiently change substrate specificity of the enzyme.

Ultra-selective tin oxide-based chemiresistive gas sensor employing signal transform and machine learning techniques.

Selective detection of gases has been a major concern among metal-oxide based chemiresistive gas sensors due to their intrinsic cross-sensitivity. In this endeavor, we report integration of single metal-oxide based chemiresistive sensor with different soft computing tools to obtain perfect recognition of tested analyte molecules by means of signal processing, feature extraction and machine learning. The fabricated sensor device consists of SnO2 hollow-spheres as the sensing material, which was synthesized chemically. A remarkable gas sensing performance has been observed towards every target volatile organic compound (VOC); which exhibits the sensor having cross-sensitivity. The transient response curves obtained from the sensor were processed using fast Fourier transform (FFT) and discrete wavelet transform (DWT) to squeeze out distinct characteristic features associated with each tested VOC. The signal transform tools were taken in a comparative fashion to examine their credibility in terms of feature extraction and assistance for pattern recognition. The extracted features were assigned as input information to the machine learning algorithms in a supervised manner to discriminate among the tested VOCs qualitatively. Moreover, a quantitative estimation of concentration for corresponding VOCs was also obtained with acceptable accuracy. The main highlight of the paper is the vigilant and efficient selection of features from the transformed signal which adequately allows the machine learning algorithms to achieve excellent classification (best average accuracy: 96.84%) and quantification. The collective results promote a step towards the realization of an automated and real-time detection.

Selective Discrimination of VOCs Applying Gas Sensing Kinetic Analysis over a Metal Oxide-Based Chemiresistive Gas Sensor.

Semiconducting metal oxide-based gas sensors have inadequate selectivity as they are responsive toward a variety of gases. Here, we report the implementation of gas sensing kinetic analysis of the sensor to identify the tested volatile organic compounds (VOCs) (2-propanol, formaldehyde, methanol, and toluene) precisely. A single chemiresistive sensor was employed having tin oxide-based hollow spheres as the sensing material, which were obtained by chemical synthesis. The gas sensing measurements were conducted in a dynamic manner where the sensor displayed excellent response with high sensitivity. Eley-Rideal model was adopted to obtain the kinetic properties of the gas sensing phenomenon through theoretical fitting of response transient curves and their corresponding kinetic parameters. The calculated characteristic kinetic properties were further examined to discriminate among different VOCs. The approach of using gas sensing kinetic analysis for multiple gas discrimination is an attractive solution to mitigate the problem of cross-sensitivity for resistive gas sensors.

Protein-stabilized silver nanoparticles encapsulating gentamycin for the therapy of bacterial biofilm infections.

Aim: An antibiotic-conjugated protein-stabilized nanoparticle hybrid system was developed to combat the challenges faced during the treatment of drug-resistant bacterial biofilm-associated infections. Materials & methods: Biocompatible silver nanoparticles were synthesized using intracellular protein and gentamycin was attached. The resulting nanohybrid was characterized and its antibacterial efficiency was assessed against Gram-positive, Gram-negative and drug-resistant bacteria. Results: Spectroscopic and electron microscopic analysis revealed that the nanoparticles were spherical with a diameter of 2-6 nm. Red-shifting of the surface plasmon peak and an increase in hydrodynamic diameter confirmed attachment of gentamycin. The nanohybrid exhibited antibacterial efficiency against a range of bacteria with the ability to inhibit and disrupt bacterial biofilm. Conclusion: A unique nanohybrid was designed that has potential to be used to control drug-resistant bacterial infections in the future.

Phytochemical composition analysis and evaluation of in vitro medicinal properties and cytotoxicity of five wild weeds: A comparative study.

Background: Medicinal plants are a source of phytochemicals and they are used for the treatment of several oxidative stress-related or other diseases for their effectiveness, low toxicity and easy availability. Five traditionally used and less characterized herbaceous weeds of West Bengal, India, namely, Heliotropium indicum, Tridax procumbens, Cleome rutidosperma, Commelina benghalensis and Euphorbia hirta, were investigated for the current research study. Methods: Aqueous and 70% ethanolic extracts of the leaves were analyzed for estimation of essential phytochemicals and to evaluate their in vitro antioxidant status, medicinal properties and cytotoxic effects. To the best of our knowledge, several assays and comparative evaluations using these herbs are reported for the first time. For quantitative study, UV-vis spectrophotometry and high-performance liquid chromatography with diode array detector HPLC-DAD techniques were used. Antibacterial properties were investigated using the Kirby-Bauer disc diffusion method. For in vitro anti-lithiatic study, a titration method was used. The cell viability assay was done using peripheral blood mononuclear cells. Results: The aqueous extract exhibits higher content of polyphenols, flavonoids, tannins and inhibition percentage values for free radical scavenging assays, whereas the 70% ethanolic extract exhibits higher content of alkaloids and cardiac glycosides. HPLC-DAD analysis of 70% ethanolic extracts led us to identify 10 predominant phenolic constituents. Euphorbia hirta extracts showed minimum cytotoxicity (cell death ~2.5% and 4% in water and 70% ethanolic extract, respectively ), whereas Cleome rutidosperma and Tridax procumbens' 70% ethanolic extracts showed higher cell death (~13% and 28%, respectively), compared with the control (cell death ~10-12%). Conclusions: The study concluded that of all the medicinal weeds selected for the current study, Euphorbia hirta possesses the highest amount of bioactive compounds and hence exhibits the highest in vitro antioxidant activity and promising in vitro medicinal properties.

Protein assembled nano-vehicle entrapping photosensitizer molecules for efficient lung carcinoma therapy.

The efficiency of drug depends not only on its potency but also on its ability to reach the target sites in preference to non-target sites. In this regard, protein assembled nanocarrier is the most promising strategy for intracellular anti-cancer drug delivery. The key motive of this study is to fabricate biocompatible protein assembled nanocarrier conjugated photosensitizer system for stimuli-responsive treatment of lung carcinoma. Here, we have synthesized a unique nanohybrid of protein assembled gold nanoparticles (AuNPs), attaching a model photosensitizer, Protoporphyrin IX (PpIX) to the protein shell of the nanoparticles (NPs) imparting an ideal drug-carrier nature. Photo-induced alteration in hydrodynamic diameter suggests structural perturbation of the nanohybrid which in terms signifies on-demand drug delivery. The drug release profile has been further confirmed by using steady-state fluorescence experiments. AuNP-PpIX showed excellent anti-cancer efficiency upon green light irradiation on lung adenocarcinoma cell line (A549) through intracellular reactive oxygen species (ROS) generation. The cellular morphological changes upon PDT and internalization of nanohybrid were monitored using confocal laser scanning microscope. This anti-cancer effect of nanohybrid was associated with apoptotic pathway which was confirmed in the flow cytometric platform. The developed nanomedicine is expected to find relevance in clinical anti-cancer PDT models in the near future.

Nano MOF Entrapping Hydrophobic Photosensitizer for Dual-Stimuli-Responsive Unprecedented Therapeutic Action against Drug-Resistant Bacteria.

Multidrug resistance (MDR) of bacteria is a major threat to public health globally and its unprecedented increase calls for immediate alternative medical strategies. Antimicrobial photodynamic therapy (aPDT) offers alternative modalities to combat the growing MDR typically by means of targeted cellular internalization of a photosensitizer (PS) capable of producing photoinduced reactive oxygen species (ROS). However, aPDT is severely limited by the self-aggregation behavior and hydrophobicity of PS molecules, which significantly curbs its viability for clinical application. The present study reports the use of modified nanoscale metal-organic frameworks (NMOFs) encapsulating a hydrophobic PS drug squaraine (SQ) to enhance aPDT efficacy against drug-resistant planktonic bacteria and its biofilm for the first time. Zeolitic imidazolate framework (ZIF-8) NMOF nanocrystals are attached postsynthetically with SQ (designated as ZIF8-SQ) and the resultant drug-doped NMOF is characterized by TEM, FESEM, PXRD, Raman spectroscopy, UV-vis spectroscopy, and steady-state and time-resolved fluorescence techniques. The microporous structures of ZIF-8 behave as molecular cages ceasing the self-aggregation of hydrophobic SQ. In addition, the formulated ZIF8-SQ produces cytotoxic ROS under red-light irradiation (650 nm) in a pH sensitive way primarily due to molecular level interaction and charge separation between ZIF-8 and SQ depicting a dual-stimuli-responsive nature. Most notably, ZIF8-SQ provides unparalleled aPDT action against methicillin-resistant Staphylococcus aureus (MRSA) and leads to complete loss of adherence of structurally robust bacterial biofilms. Finally, the nontoxic nature of the nanoconjugate toward human cells holds great promise for effective treatment of MRSA and other detrimental antibiotic-resistant microbes in clinical models.

Subcellular Optogenetic Stimulation Platform for Studying Activity-Dependent Axon Myelination In Vitro.

Activity-dependent myelination modulates neuron conduction velocity and as such it is essential for a correct wiring of a whole nervous system. Increasing myelination through inducing neuron activity has been proposed as a treatment strategy for demyelination diseases. Yet, the mechanisms and the effects of activity-dependent myelination remain elusive-new tools are needed. In this chapter, we describe a novel compartmentalized device integrated with an optogenetic stimulator for studying activity-dependent myelination in vitro. The platform can be modified to include multiple cell types, stimulation modes, and experimental readouts to answer a specific research question. This versatility combined with a precise control over spatial extent of the stimulation and the stimulation pattern make the proposed platform a valuable tool for molecular myelination studies.

Green-fabrication of gold nanomaterials using Staphylococcus warneri from Sundarbans estuary: an effective recyclable nanocatalyst for degrading nitro aromatic pollutants.

Microbial synthesis of gold nanoparticles (GNPs) has attracted considerable attention in recent times due to their exceptional capability for the bioremediation of industrial wastes and also for the treatment of wastewater. A bacterial strain Staphylococcus warneri, isolated from the estuarine mangroves of Sundarbans region produced highly stable GNPs by reducing hydrogen auric chloride (HAucl4) salt using intracellular protein extract. The nanoparticles were characterized utilizing ultraviolet-visible spectrophotometry, transmission electron microscopy, scanning electron microscopy, atomic force microscopy, X-ray diffraction, and surface enhanced Raman scattering. Highly dispersed, spherically shaped GNPs varied around 15-25 nm in size and were highly crystalline with face-centered cubic structures. Recyclable catalytic activity of as-synthesized GNPs was evidenced by complete degradation of nitro aromatic pollutants like 2-nitroaniline, 4-nitroaniline, 2-nitrophenol and 4-nitrophenol. Our GNPs show excellent and efficient catalytic activity with significantly high rate constant (10-1 order) and high turnover frequency (103 order) in recyclable manner up to three times. To our knowledge, this is the first report of Staphylococcus warneri in the production of gold nanoparticles. This green technology for bioremediation of toxic nitro aromatic pollutants is safe and economically beneficial to challenge the development and sustainability issue.

Subcellular Optogenetic Stimulation for Activity-Dependent Myelination of Axons in a Novel Microfluidic Compartmentalized Platform.

Myelination is governed by neuron-glia communication, which in turn is modulated by neural activity. The exact mechanisms remain elusive. We developed a novel in vitro optogenetic stimulation platform that facilitates subcellular activity induction in hundreds of neurons simultaneously. The light isolation was achieved by creating a biocompatible, light-absorbent, black microfluidic device integrated with a programmable, high-power LED array. The system was applied to a compartmentalized culture of primary neurons whose distal axons were interacting with oligodendrocyte precursor cells. Neural activity was induced along whole neurons or was constrained to cell bodies with proximal axons or distal axons only. All three modes of stimulation promoted oligodendrocyte differentiation and the myelination of axons as evidenced by a decrease in the number of oligodendrocyte precursor cells followed by increases in the number of mature oligodendrocytes and myelin sheath fragments. These results demonstrated the potential of our novel optogenetic stimulation system for the global and focal induction of neural activity in vitro for studying axon myelination.

Bacterial diversity assessment of pristine mangrove microbial community from Dhulibhashani, Sundarbans using 16S rRNA gene tag sequencing.

The global knowledge of microbial diversity and function in Sundarbans ecosystem is still scarce, despite global advancement in understanding the microbial diversity. In the present study, we have analyzed the diversity and distribution of bacteria in the tropical mangrove sediments of Sundarbans using 16S rRNA gene amplicon sequencing. Metagenome is comprised of 1,53,926 sequences with 108.8 Mbp data and with 55 ± 2% G + C content. Metagenome sequence data are available at NCBI under the Bioproject database with accession no. PRJNA245459. Bacterial community metagenome sequences were analyzed by MG-RAST software representing the presence of 56,547 species belonging to 44 different phyla. The taxonomic analysis revealed the dominance of phyla Proteobacteria within our dataset. Further taxonomic analysis revealed abundance of Bacteroidetes, Acidobactreia, Firmicutes, Actinobacteria, Nitrospirae, Cyanobacteria, Planctomycetes and Fusobacteria group as the predominant bacterial assemblages in this largely pristine mangrove habitat. The distribution of different community datasets obtained from four sediment samples originated from one sampling station at two different depths providing better understanding of the sediment bacterial diversity and its relationship to the ecosystem dynamics of this pristine mangrove sediment of Dhulibhashani in, Sundarbans.

Implantable neurotechnologies: electrical stimulation and applications.

Neural stimulation using injected electrical charge is widely used both in functional therapies and as an experimental tool for neuroscience applications. Electrical pulses can induce excitation of targeted neural pathways that aid in the treatment of neural disorders or dysfunction of the central and peripheral nervous system. In this review, we summarize the recent trends in the field of electrical stimulation for therapeutic interventions of nervous system disorders, such as for the restoration of brain, eye, ear, spinal cord, nerve and muscle function. Neural prosthetic applications are discussed, and functional electrical stimulation parameters for treating such disorders are reviewed. Important considerations for implantable packaging and enhancing device reliability are also discussed. Neural stimulators are expected to play a profound role in implantable neural devices that treat disorders and help restore functions in injured or disabled nervous system.

Self-organization of "fibro-axonal" composite tissue around unmodified metallic micro-electrodes can form a functioning interface with a peripheral nerve: A new direction for creating long-term neural interfaces.

INTRODUCTION: A long-term peripheral neural interface is an area of intense research. The use of electrode interfaces is limited by the biological response to the electrode material. METHODS: We created an electrode construct to harbor the rat sciatic nerve with interposition of autogenous adipose tissue between the nerve and the electrode. The construct was implanted for 10 weeks. RESULTS: Immunohistochemistry showed a unique laminar pattern of axonal growth layered between fibro-collagenous tissue, forming a physical interface with the tungsten micro-electrode. Action potentials transmitted across the intrerface showed mean conduction velocities varying between 6.99 ± 2.46 and 20.14 ± 4 m/s. CONCLUSIONS: We have demonstrated the feasibility of a novel peripheral nerve interface through modulation of normal biologic phenomena. It has potential applications as a chronic implantable neural interface.

Diversity and Distribution of Archaea in the Mangrove Sediment of Sundarbans.

Mangroves are among the most diverse and productive coastal ecosystems in the tropical and subtropical regions. Environmental conditions particular to this biome make mangroves hotspots for microbial diversity, and the resident microbial communities play essential roles in maintenance of the ecosystem. Recently, there has been increasing interest to understand the composition and contribution of microorganisms in mangroves. In the present study, we have analyzed the diversity and distribution of archaea in the tropical mangrove sediments of Sundarbans using 16S rRNA gene amplicon sequencing. The extraction of DNA from sediment samples and the direct application of 16S rRNA gene amplicon sequencing resulted in approximately 142 Mb of data from three distinct mangrove areas (Godkhali, Bonnie camp, and Dhulibhashani). The taxonomic analysis revealed the dominance of phyla Euryarchaeota and Thaumarchaeota (Marine Group I) within our dataset. The distribution of different archaeal taxa and respective statistical analysis (SIMPER, NMDS) revealed a clear community shift along the sampling stations. The sampling stations (Godkhali and Bonnie camp) with history of higher hydrocarbon/oil pollution showed different archaeal community pattern (dominated by haloarchaea) compared to station (Dhulibhashani) with nearly pristine environment (dominated by methanogens). It is indicated that sediment archaeal community patterns were influenced by environmental conditions.

Enabling wireless powering and telemetry for peripheral nerve implants.

Wireless power delivery and telemetry have enabled completely implantable neural devices. Current day implants are controlled, monitored, and powered wirelessly, eliminating the need for batteries and prolonging the lifetime. A brief overview of wireless platforms for such implantable devices is presented in this paper alongside an in-depth discussion of wireless platform for peripheral nerve implants covering design requirements, link design, and safety. Initial acute studies on the performance of the wireless power and data links in rodents are also presented.

Changing bacterial profile of Sundarbans, the world heritage mangrove: impact of anthropogenic interventions.

Mangrove microbial communities and their associated activities have profound impact on biogeochemical cycles. Although microbial composition and structure are known to be influenced by biotic and abiotic factors in the mangrove sediments, finding direct correlations between them remains a challenge. In this study we have explored sediment bacterial diversity of the Sundarbans, a world heritage site using a culture-independent molecular approach. Bacterial diversity was analyzed from three different locations with a history of exposure to differential anthropogenic activities. 16S rRNA gene libraries were constructed and partial sequencing of the clones was performed to identify the microbial strains. We identified bacterial strains known to be involved in a variety of biodegradation/biotransformation processes including hydrocarbon degradation, and heavy metal resistance. Canonical Correspondence Analysis of the environmental and exploratory datasets revealed correlations between the ecological indices associated with pollutant levels and bacterial diversity across the sites. Our results indicate that sites with similar exposure of anthropogenic intervention reflect similar patterns of microbial diversity besides spatial commonalities.

Spatiotemporal analysis of bacterial diversity in sediments of Sundarbans using parallel 16S rRNA gene tag sequencing.

The influence of temporal and spatial variations on the microbial community composition was assessed in the unique coastal mangrove of Sundarbans using parallel 16S rRNA gene pyrosequencing. The total sediment DNA was extracted and subjected to the 16S rRNA gene pyrosequencing, which resulted in 117 Mbp of data from three experimental stations. The taxonomic analysis of the pyrosequencing data was grouped into 24 different phyla. In general, Proteobacteria were the most dominant phyla with predominance of Deltaproteobacteria, Alphaproteobacteria, and Gammaproteobacteria within the sediments. Besides Proteobacteria, there are a number of sequences affiliated to the following major phyla detected in all three stations in both the sampling seasons: Actinobacteria, Bacteroidetes, Planctomycetes, Acidobacteria, Chloroflexi, Cyanobacteria, Nitrospira, and Firmicutes. Further taxonomic analysis revealed abundance of micro-aerophilic and anaerobic microbial population in the surface layers, suggesting anaerobic nature of the sediments in Sundarbans. The results of this study add valuable information about the composition of microbial communities in Sundarbans mangrove and shed light on possible transformations promoted by bacterial communities in the sediments.

Correlation between muscular and nerve signals responsible for hand grasping in non-human primates.

Neuroprosthetic devices that interface with the nervous system to restore functional motor activity offer a viable alternative to nerve regeneration, especially in proximal nerve injuries like brachial plexus injuries where muscle atrophy may set in before nerve re-innervation occurs. Prior studies have used control signals from muscle or cortical activity. However, nerve signals are preferred in many cases since they permit more natural and precise control when compared to muscle activity, and can be accessed with much lower risk than cortical activity. Identification of nerve signals that control the appropriate muscles is essential for the development of such a `bionic link'. Here we examine the correlation between muscle and nerve signals responsible for hand grasping in the M. fascicularis. Simultaneous recordings were performed using a 4-channel thin-film longitudinal intra-fascicular electrode (tf-LIFE) and 9 bipolar endomysial muscle electrodes while the animal performed grasping movements. We were able to identify a high degree of correlation (r > 0.6) between nerve signals from the median nerve and movement-dependent muscle activity from the flexor muscles of the forearm, with a delay that corresponded to 25 m/s nerve conduction velocity. The phase of the flexion could be identified using a wavelet approximation of the ENG. This result confirms this approach for a future neuroprosthetic device for the treatment of peripheral nerve injuries.