A Wearable Real-Time System for Simultaneous Wireless Power and Data Transmission to Cortical Visual Prosthesis.

Wireless, miniaturised and distributed neural interfaces are emerging neurotechnologies. Although extensive research efforts contribute to their technological advancement, the need for real-time systems enabling simultaneous wireless information and power transfer toward distributed neural implants remains crucial. Here we present a complete wearable system including a software for real-time image capturing, processing and digital data transfer; an hardware for high radiofrequency generation and modulation via amplitude shift keying; and a 3-coil inductive link adapt to operate with multiple miniaturised receivers. The system operates in real-time with a maximum frame rate of 20 Hz, reconstructing each frame with a matrix of 32 × 32 pixels. The device generates a carrier frequency of 433.92 MHz. It transmits the highest power of 32 dBm with a data rate of 6 Mbps and a variable modulation index as low as 8 %, thus potentially enabling wireless communication with 1024 miniaturised and distributed intracortical microstimulators. The system is primarily conceived as an external wearable device for distributed cortical visual prosthesis covering a visual field of 20 °. At the same time, it is modular and versatile, being suitable for multiple applications requiring simultaneous wireless information and power transfer to large-scale neural interfaces.

Development of a PPG-based hardware and software system deployable on elbow and thumb for real-time estimation of pulse transit time.

Blood pressure (BP) is a vital parameter used by clinicians to diagnose issues in the human cardiovascular system. Cuff-based BP devices are currently the standard method for on-the-spot and ambulatory BP measurements. However, cuff-based devices are not comfortable and are not suitable for long-term BP monitoring. Many studies have reported a significant correlation between pulse transit time (PTT) with blood pressure. However, this relation is impacted by many internal and external factors which might lower the accuracy of the PTT method. In this paper, we present a novel hardware system consisting of two custom photoplethysmography (PPG) sensors designed particularly for the estimation of PTT. In addition, a software interface and algorithms have been implemented to perform a real-time assessment of the PTT and other features of interest from signals gathered between the brachial artery and the thumb. A preclinical study has been conducted to validate the system. Five healthy volunteer subjects were tested and the results were then compared with those gathered using a reference device. The analysis reports a mean difference among subjects equal to -3.75±7.28 ms. Moreover, the standard deviation values obtained for each individual showed comparable results with the reference device, proving to be a valuable tool to investigate the factors impacting the BP-PTT relationship.Clinical Relevance- The proposed system proved to be a feasible solution to detect blood volume changes providing good quality signals to be used in the study of BP-PTT relationship.

Kinetic Perimetry on Virtual Reality Headset.

OBJECTIVE: We present a portable automatic kinetic perimeter based on a virtual reality (VR) headset device as an innovative and alternative solution for the screening of clinical visual fields. We compared the performances of our solution with a gold standard perimeter, validating the test on healthy subjects. METHODS: The system is composed of an Oculus Quest 2 VR headset with a clicker for participant response feedback. An Android app was designed in Unity to generate moving stimuli along vectors, following a standard Goldmann kinetic perimetry approach. Sensitivity thresholds are obtained by moving centripetally three different targets (V/4e, IV/1e, III/1e) along 24 or 12 vectors from an area of non-seeing to an area of seeing and then transmitted wirelessly to a PC. A Python real-time algorithm processes the incoming kinetic results and displays the hill of vision in a two-dimensional map (isopter). We involved 21 subjects (5 males and 16 females, age range 22-73 years) for a total of 42 eyes tested with our proposed solution, and results were compared with a Humphrey visual field analyzer to test reproducibility and efficacy. RESULTS: isopters generated with the Oculus headset were in good agreement with those acquired with a commercial device (Pearson's correlation values r > 0.83 for each target). CONCLUSIONS: we demonstrate the feasibility of VR kinetic perimetry by comparing performances between our system and a clinically used perimeter in healthy subjects. SIGNIFICANCE: proposed device leads the way for a portable and more accessible visual field test, overcoming challenges in current kinetic perimetry practices.

Moving perfusion culture and live-cell imaging from lab to disc: proof of concept toxicity assay with AI-based image analysis.

In vitro, cell-based assays are essential in diagnostics and drug development. There are ongoing efforts to establish new technologies that enable real-time detection of cell-drug interaction during culture under flow conditions. Our compact (10 × 10 × 8.5 cm) cell culture and microscope on disc (CMoD) platform aims to decrease the application barriers of existing lab-on-a-chip (LoC) approaches. For the first time in a centrifugal device, (i) cells were cultured for up to six days while a spindle motor facilitated culture medium perfusion, and (ii) an onboard microscope enabled live bright-field imaging of cells while the data wirelessly transmitted to a computer. The quantification of cells from the acquired images was done using artificial intelligence (AI) software. After optimization, the obtained cell viability data from the AI-based image analysis proved to correlate well with data collected from commonly used image analysis software. The CMoD was also suitable for conducting a proof-of-concept toxicity assay with HeLa cells under continuous flow. The half-maximal inhibitory time (IT50) for various concentrations of doxorubicin (DOX) in the case of HeLa cells in flow, was shown to be lower than the IT50 obtained from a static cytotoxicity assay, indicating a faster onset of cell death in flow. The CMoD proved to be easy to handle, enabled cell culture and monitoring without assistance, and is a promising tool for examining the dynamic processes of cells in real-time assays.

Wearable Heart Rate Monitoring Device Communicating in 5G ISM Band for IoHT.

Advances in wearable device technology pave the way for wireless health monitoring for medical and non-medical applications. In this work, we present a wearable heart rate monitoring platform communicating in the sub-6GHz 5G ISM band. The proposed device is composed of an Aluminium Nitride (AlN) piezoelectric sensor, a patch antenna, and a custom printed circuit board (PCB) for data acquisition and transmission. The experimental results show that the presented system can acquire heart rate together with diastolic and systolic duration, which are related to heart relaxation and contraction, respectively, from the posterior tibial artery. The overall system dimension is 20 mm by 40 mm, and the total weight is 20 g, making this device suitable for daily utilization. Furthermore, the system allows the simultaneous monitoring of multiple subjects, or a single patient from multiple body locations by using only one reader. The promising results demonstrate that the proposed system is applicable to the Internet of Healthcare Things (IoHT), and particularly Integrated Clinical Environment (ICE) applications.

Quantitative high-resolution 7T MRI to assess longitudinal changes in articular cartilage after anterior cruciate ligament injury in a rabbit model of post-traumatic osteoarthritis.

Objective: To demonstrate an ultra-high field (UHF) 7 â€‹T delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) protocol for quantitative post-traumatic osteoarthritis (PTOA) detection and monitoring in a rabbit anterior cruciate ligament transection (ACLT) model. Design: ACL transections were performed unilaterally in 5 rabbits (33-weeks-old, 3.5 â€‹± â€‹0.5 â€‹kg) to induce PTOA. MRI exams were performed at 7 â€‹T prior to and 2, 4, 7 and 10-weeks after ACLT using a modified dGEMRIC protocol. Voxel-based T1 and T2 maps were created over manually drawn femoral cartilage ROIs from the center of the tibial plateau to the posterior meniscus. Femoral, tibial, and patellar epiphyses were harvested 10-weeks post-surgery and processed for µCT imaging and histology. Results: Quantitative analysis revealed a 35% and 39% decrease in dGEMRIC index in the medial ACLT knee compartment 7- and 10-weeks post-surgery, respectively (p â€‹= â€‹0.009 and p â€‹= â€‹0.006) when compared to baseline. There was no significant change in the lateral ACLT compartment or in either compartment of the control knees. Visual inspection of histology confirmed PTOA in the ACLT knees. Osteophytes were found only in ACLT knees (osteophyte volume in femur: 94.53 â€‹± â€‹44.08 â€‹mm3, tibia: 29.35 â€‹± â€‹13.79 â€‹mm3, and patella: 3.84 â€‹± â€‹0.92 â€‹mm3) and were significantly larger in the medial compartments of the femur than lateral (p â€‹= â€‹0.0312). Conclusion: The dGEMRIC technique quantitatively applied at 7 â€‹T UHF-MRI demonstrates site-specific cartilage degeneration in a large animal PTOA model. This should encourage further investigation, with potential applications in drug and therapeutic animal trials as well as human studies.

Zonal Intratumoral Delivery of Nanoparticles Guided by Surface Functionalization.

Delivery of small molecules and anticancer agents to malignant cells or specific regions within a tumor is limited by penetration depth and poor spatial drug distribution, hindering anticancer efficacy. Herein, we demonstrate control over gold nanoparticle (GNP) penetration and spatial distribution across solid tumors by administering GNPs with different surface chemistries at a constant injection rate via syringe pump. A key finding in this study is the discovery of different zone-specific accumulation patterns of intratumorally injected nanoparticles dependent on surface functionalization. Computed tomography (CT) imaging performed in vivo of C57BL/6 mice harboring Lewis lung carcinoma (LLC) tumors on their flank and gross visualization of excised tumors consistently revealed that intratumorally administered citrate-GNPs accumulate in particle clusters in central areas of the tumor, while GNPs functionalized with thiolated phosphothioethanol (PTE-GNPs) and thiolated polyethylene glycol (PEG-GNPs) regularly accumulate in the tumor periphery. Further, PEG functionalization resulted in larger tumoral surface coverage than PTE, reaching beyond the outer zone of the tumor mass and into the surrounding stroma. To understand the dissimilarities in spatiotemporal evolution across the different GNP surface chemistries, we modeled their intratumoral transport with reaction-diffusion equations. Our results suggest that GNP surface passivation affects nanoparticle reactivity with the tumor microenvironment, leading to differential transport behavior across tumor zones. The present study provides a mechanistic understanding of the factors affecting spatiotemporal distribution of nanoparticles in the tumor. Our proof of concept of zonal delivery within the tumor may prove useful for directing anticancer therapies to regions of biomarker overexpression.

Hand Gestures Recognition for Human-Machine Interfaces: A Low-Power Bio-Inspired Armband.

Hand gesture recognition has recently increased its popularity as Human-Machine Interface (HMI) in the biomedical field. Indeed, it can be performed involving many different non-invasive techniques, e.g., surface ElectroMyoGraphy (sEMG) or PhotoPlethysmoGraphy (PPG). In the last few years, the interest demonstrated by both academia and industry brought to a continuous spawning of commercial and custom wearable devices, which tried to address different challenges in many application fields, from tele-rehabilitation to sign language recognition. In this work, we propose a novel 7-channel sEMG armband, which can be employed as HMI for both serious gaming control and rehabilitation support. In particular, we designed the prototype focusing on the capability of our device to compute the Average Threshold Crossing (ATC) parameter, which is evaluated by counting how many times the sEMG signal crosses a threshold during a fixed time duration (i.e., 130 ms), directly on the wearable device. Exploiting the event-driven characteristic of the ATC, our armband is able to accomplish the on-board prediction of common hand gestures requiring less power w.r.t. state of the art devices. At the end of an acquisition campaign that involved the participation of 26 people, we obtained an average classifier accuracy of 91.9% when aiming to recognize in real time 8 active hand gestures plus the idle state. Furthermore, with 2.92 mA of current absorption during active functioning and 1.34 ms prediction latency, this prototype confirmed our expectations and can be an appealing solution for long-term (up to 60 h) medical and consumer applications.

Wirelessly Powered 3D Printed Hierarchical Biohybrid Robots with Multiscale Mechanical Properties.

The integration of flexible and stretchable electronics into biohybrid soft robotics can spur the development of new approaches to fabricate biohybrid soft machines, thus enabling a wide variety of innovative applications. Inspired by flexible and stretchable wireless-based bioelectronic devices, we have developed untethered biohybrid soft robots that can execute swimming motions, which are remotely controllable by the wireless transmission of electrical power into a cell simulator. To this end, wirelessly-powered, stretchable, and lightweight cell stimulators were designed to be integrated into muscle bodies without impeding the robots' underwater swimming abilities. The cell stimulators function by generating controlled monophasic pulses of up to ∼9 V in biological environments. By differentiating induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) directly on the cell stimulators using an accordion-inspired, three-dimensional (3D) printing construct, we have replicated the native myofiber architecture with comparable robustness and enhanced contractibility. Wirelessly modulated electrical frequencies enabled us to control the speed and direction of the biohybrid soft robots. A maximum locomotion speed of ∼580 µm/s was achieved in robots possessing a large body size by adjusting the pacing frequency. This innovative approach will provide a platform for building untethered and biohybrid systems for various biomedical applications.

Raspberry Pi based Modular System for Multichannel Event-Driven Functional Electrical Stimulation Control.

This paper describes the implementation and testing of a modular software for multichannel control of Functional Electrical Stimulation (FES). Moving towards an embedded scenario, the core of the system is a Raspberry Pi, whose different models (with different computing powers) best suit two different system use-cases: user-supervised and stand-alone. Given the need for real-time and reliable FES applications, software processing timings were analyzed for multiple configurations, along with hardware resources utilization. Among the results, the simultaneous use of eight channels has been functionally achieved (0% lost packets) while minimizing system timing failures (excessive processing latency). Further investigations included stressing the system using more constraining acquisition parameters, eventually limiting the usable channels (only for the stand-alone use-case).

Comprehensive Analysis of Electrostatic Gating in Nanofluidic Systems.

Molecular transport in nanofluidic systems exhibits properties that are unique to the nanoscale. Here, the electrostatic and steric interactions between particle and surfaces become dominant in determining particle transport. At the solid-liquid interface of charged surfaces an electric double layer (EDL) forms due to electrostatic interactions between surfaces and charged particles. In these systems, tunable charge-selective nanochannels can be generated by manipulating electrostatic gating via co-ions exclusion and counterions enrichment of the EDL at the solid-liquid interface. In this context, electrostatic gating has been used to modulate the selectivity of nanofluidic membranes for drug delivery, nanofluidic transistors, and FlowFET, among other applications. While an extensive body of literature investigating nanofluidic systems exists, there is a lack of a comprehensive analysis accounting for all major parameters involved in these systems. Here we performed an all-encompassing modeling investigation corroborated by experimental analysis to assess the influence of nanochannel size, electrolyte properties, surface chemistry, gate voltage, dielectric properties, and molecular charge and size on the exclusion and enrichment of charged analytes in nanochannels. We found that the leakage current in electrostatic gating, often overlooked, plays a dominant role in molecular exclusion. Importantly, by independently considering all ionic species, we found that counterions compete for EDL formation at the surface proximity, resulting in concentration distributions that are nearly impossible to predict with analytical models. Achieving a deeper understanding of these nanofluidic phenomena will help the development of innovative miniaturized systems for both medical and industrial applications.

Electrical Impedance-Based Characterization of Hepatic Tissue with Early-Stage Fibrosis.

Liver fibrosis is a key pathological precondition for hepatocellular carcinoma in which the severity is confidently correlated with liver cancer. Liver fibrosis, characterized by gradual cell loss and excessive extracellular matrix deposition, can be reverted if detected at the early stage. The gold standard for staging and diagnosis of liver fibrosis is undoubtedly biopsy. However, this technique needs careful sample preparation and expert analysis. In the present work, an ex vivo, minimally destructive, label-free characterization of liver biopsies is presented. Through a custom-made experimental setup, liver biopsies of bile-duct-ligated and sham-operated mice were measured at 8, 15, and 21 days after the procedure. Changes in impedance were observed with the progression of fibrosis, and through data fitting, tissue biopsies were approximated to an equivalent RC circuit model. The model was validated by means of 3D hepatic cell culture measurement, in which the capacitive part of impedance was proportionally associated with cell number and the resistive one was proportionally associated with the extracellular matrix. While the sham-operated samples presented a decrease in resistance with time, the bile-duct-ligated ones exhibited an increase in this parameter with the evolution of fibrosis. Moreover, since the largest difference in resistance between healthy and fibrotic tissue, of around 2 kΩ, was found at 8 days, this method presents great potential for the study of fibrotic tissue at early stages. Our data point out the great potential of exploiting the proposed needle setup in clinical applications.

A novel system for measuring visual potentials evoked by passive head-mounted display stimulators.

PURPOSE: The objective of this work is to evaluate the performances of a novel integrated device, based on passive head-mounted display (HMD), for the pattern reversal visual evoked potential (PR-VEP) clinical test. METHODS: Google Cardboard® is used as passive HMD to generate the checkerboard pattern stimuli through an Android® application. Electroencephalographic signals are retrieved and processed over 20 subjects, 12 females and 8 males between 20 and 26 years. Morphological PR-VEPs and frequency response were compared with previous literature results, to test the reproducibility and the efficacy of the proposed solution. RESULTS: PR-VEPs evoked by our novel prototype showed typical triphasic waveforms in moderate agreement with those obtained with other more expensive HMDs and standard commercial devices. Statistical analysis did not highlight strong differences among the systems over the features analyzed except for the P100 amplitude and peak time (**p < 0.005). CONCLUSION: The proposed solution opens the door for a new generation of non-invasive first-level diagnostic devices of optic nerve pathologies inexpensive and easy to access.

Motion Analysis for Experimental Evaluation of an Event-Driven FES System.

In this work, a system for controlling Functional Electrical Stimulation (FES) has been experimentally evaluated. The peculiarity of the system is to use an event-driven approach to modulate stimulation intensity, instead of the typical feature extraction of surface ElectroMyoGraphic (sEMG) signal. To validate our methodology, the system capability to control FES was tested on a population of 17 subjects, reproducing 6 different movements. Limbs trajectories were acquired using a gold standard motion tracking tool. The implemented segmentation algorithm has been detailed, together with the designed experimental protocol. A motion analysis was performed through a multi-parametric evaluation, including the extraction of features such as the trajectory area and the movement velocity. The obtained results show a median cross-correlation coefficient of 0.910 and a median delay of 800 ms, between each couple of voluntary and stimulated exercise, making our system comparable w.r.t. state-of-the-art works. Furthermore, a 97.39% successful rate on movement replication demonstrates the feasibility of the system for rehabilitation purposes.

Translating node of Ranvier currents to extraneural electrical fields: a flexible FEM modeling approach.

Simulations of electroneurogram recording could help find the optimal set of electrodes and algorithms for selective neural recording. However, no flexible methods are established for selective neural recording as for neural stimulation. This paper proposes a method to couple a compartmental and a FEM nerve model, implemented in NEURON and COMSOL, respectively, to translate Node of Ranvier currents into extraneural electric fields. The study simulate ex-vivo experimental conditions, and the method allows flexibility in electrode geometries and nerve topologies. This model has been made available in a public repository4. So far, the model behavior complies with available experimental results and expectations from literature. There is good agreement in terms of signal amplitude and waveform, and computational times are acceptable, leaving room for flexible simulation studies complementary to animal tests.

Eye Accommodation Sensing for Adaptive Focus Adjustment.

Over 2 billion people across the world are affected by some visual impairment - mostly related to optical issues, and this number is estimated to grow. Often, particularly in the elderly, more than one condition can affect the eyes at the same time, e.g., myopia and presbyopia. Bifocal or multifocal lenses can be used, these however may become uncomfortable or disturbing and are not adapted to the user. There is therefore a need and opportunity for a new type of glasses able to adaptively change the lenses' focus. This paper explores the feasibility of recording the eye accommodation process in a non-invasive way using a wearable device. This can provide a way to measure eye convergence in real-time to determine what a person's eye is focused on. In this study, Electro-oculography (EoG) is used to observe eye muscle activity and estimate eye movement. To assess this, a group of 11 participants we each asked to switch their gaze from a near to far target and vice versa, whilst their EoG was measured. This revealed two distinct waveforms: one for the transition from a far to near target, and one for the transition from a near to far target. This informed the design of a correlation-based classifier to detect which signals are related to a far to near, or near to far transition. This achieved a classification accuracy of 97.9±1.37% across the experimental results gathered from our 11 participants. This pilot data provides a basic starting point to justify future device development.

Combining Action Observation Treatment with a Brain-Computer Interface System: Perspectives on Neurorehabilitation.

Action observation treatment (AOT) exploits a neurophysiological mechanism, matching an observed action on the neural substrates where that action is motorically represented. This mechanism is also known as mirror mechanism. In a typical AOT session, one can distinguish an observation phase and an execution phase. During the observation phase, the patient observes a daily action and soon after, during the execution phase, he/she is asked to perform the observed action at the best of his/her ability. Indeed, the execution phase may sometimes be difficult for those patients where motor impairment is severe. Although, in the current practice, the physiotherapist does not intervene on the quality of the execution phase, here, we propose a stimulation system based on neurophysiological parameters. This perspective article focuses on the possibility to combine AOT with a brain-computer interface system (BCI) that stimulates upper limb muscles, thus facilitating the execution of actions during a rehabilitation session. Combining a rehabilitation tool that is well-grounded in neurophysiology with a stimulation system, such as the one proposed, may improve the efficacy of AOT in the treatment of severe neurological patients, including stroke patients, Parkinson's disease patients, and children with cerebral palsy.

Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer.

Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular biomolecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using inductively coupled plasma-optical emission spectrometry (ICP-OES) and trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (** p < 0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer.

Silicon Carbide-Gated Nanofluidic Membrane for Active Control of Electrokinetic Ionic Transport.

Manipulation of ions and molecules by external control at the nanoscale is highly relevant to biomedical applications. We report a biocompatible electrode-embedded nanofluidic channel membrane designed for electrofluidic applications such as ionic field-effect transistors for implantable drug-delivery systems. Our nanofluidic membrane includes a polysilicon electrode electrically isolated by amorphous silicon carbide (a-SiC). The nanochannel gating performance was experimentally investigated based on the current-voltage (I-V) characteristics, leakage current, and power consumption in potassium chloride (KCl) electrolyte. We observed significant modulation of ionic diffusive transport of both positively and negatively charged ions under physical confinement of nanochannels, with low power consumption. To study the physical mechanism associated with the gating performance, we performed electrochemical impedance spectroscopy. The results showed that the flat band voltage and density of states were significantly low. In light of its remarkable performance in terms of ionic modulation and low power consumption, this new biocompatible nanofluidic membrane could lead to a new class of silicon implantable nanofluidic systems for tunable drug delivery and personalized medicine.