Experimental and Computational Analysis of High-Intensity Focused Ultrasound Thermal Ablation in Breast Cancer Cells: Monolayers vs. Spheroids.

High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic modality that uses precise acoustic energy to ablate cancerous tissues through coagulative necrosis. In this context, we investigate the efficacy of HIFU ablation in two distinct cellular configurations, namely 2D monolayers and 3D spheroids of epithelial breast cancer cell lines (MDA-MB 231 and MCF7). The primary objective is to compare the response of these two in vitro models to HIFU while measuring their ablation percentages and temperature elevation levels. HIFU was systematically applied to the cell cultures, varying ultrasound intensity and duty cycle during different sonication sessions. The results indicate that the degree of ablation is highly influenced by the duty cycle, with higher duty cycles resulting in greater ablation percentages, while sonication duration has a minimal impact. Numerical simulations validate experimental observations, highlighting a significant disparity in the response of 2D monolayers and 3D spheroids to HIFU treatment. Specifically, tumor spheroids require lower temperature elevations for effective ablation, and their ablation percentage significantly increases with elevated duty cycles. This study contributes to a comprehensive understanding of acoustic energy conversion within the biological system during HIFU treatment for 2D versus 3D ablation targets, holding potential implications for refining and personalizing breast cancer therapeutic strategies.

High-resolution acoustic mapping of tunable gelatin-based phantoms for ultrasound tissue characterization.

Background: The choice of gelatin as the phantom material is underpinned by several key advantages it offers over other materials in the context of ultrasonic applications. Gelatin exhibits spatial and temporal uniformity, which is essential in creating reliable tissue-mimicking phantoms. Its stability ensures that the phantom's properties remain consistent over time, while its flexibility allows for customization to match the acoustic characteristics of specific tissues, in addition to its low levels of ultrasound scattering. These attributes collectively make gelatin a preferred choice for fabricating phantoms in ultrasound-related research. Methods: We developed gelatin-based phantoms with adjustable parameters and conducted high-resolution measurements of ultrasound wave attenuation when interacting with the gelatin phantoms. We utilized a motorized acoustic system designed for 3D acoustic mapping. Mechanical evaluation of phantom elasticity was performed using unconfined compression tests. We particularly examined how varying gelatin concentration influenced ultrasound maximal intensity and subsequent acoustic attenuation across the acoustic profile. To validate our findings, we conducted computational simulations to compare our data with predicted acoustic outcomes. Results: Our results demonstrated high-resolution mapping of ultrasound waves in both gelatin-based phantoms and plain fluid environments. Following an increase in the gelatin concentration, the maximum intensity dropped by 30% and 48% with the 5 MHz and 1 MHz frequencies respectively, while the attenuation coefficient increased, with 67% more attenuation at the 1 MHz frequency recorded at the highest concentration. The size of the focal areas increased systematically as a function of increasing applied voltage and duty cycle yet decreased as a function of increased ultrasonic frequency. Simulation results verified the experimental results with less than 10% deviation. Conclusion: We developed gelatin-based ultrasound phantoms as a reliable and reproducible tool for examining the acoustic and mechanical attenuations taking place as a function of increased tissue elasticity and stiffness. Our experimental measurements and simulations gave insight into the potential use of such phantoms for mimicking soft tissue properties.

Single-cell fluid-based force spectroscopy reveals near lipid size nano-topography effects on neural cell adhesion.

Nano-roughness has shown great potential in enhancing high-fidelity electrogenic cell interfaces, owing to its characteristic topography comparable to proteins and lipids, which influences a wide range of cellular mechanical responses. Gaining a comprehensive understanding of how cells respond to nano-roughness at the single-cell level is not only imperative for implanted devices but also essential for tissue regeneration and interaction with complex biomaterial surfaces. In this study, we quantify cell adhesion and biomechanics of single cells to nano-roughened surfaces by measuring neural cell adhesion and biomechanics via fluidic-based single-cell force spectroscopy (SCFS). For this, we introduce nanoscale topographical features on polyimide (PI) surfaces achieving roughness up to 25 nm without chemical modifications. Initial adhesion experiments show cell-specific response to nano-roughness for neuroblastoma cells (SH-SY5Y) compared to human astrocytes (NHA) around 15 and 20 nm surface roughness. In addition, our SCFS measurements revealed a remarkable 2.5-fold increase in adhesion forces (150-164 nN) for SH-SY5Y cells cultured on roughened PI (rPI) surfaces compared to smooth surfaces (60-107 nN). Our data also shows that cells can distinguish changes in nano-roughness as small 2 nm (close to the diameter of a single lipid) and show roughness dependence adhesion while favoring 15 nm. Notably, this enhanced adhesion is accompanied by increased cell elongation upon cell detachment without any significant differences in cell area spreading. The study provides valuable insights into the interplay between nano-topography and cellular responses and offers practical implications for designing biomaterial surfaces with enhanced cellular interactions.

Obstructive sleep apnea diagnosis and beyond using portable monitors.

Obstructive sleep apnea (OSA) is a chronic sleep and breathing disorder with significant health complications, including cardiovascular disease and neurocognitive impairments. To ensure timely treatment, there is a need for a portable, accurate and rapid method of diagnosing OSA. This review examines the use of various physiological signals used in the detection of respiratory events and evaluates their effectiveness in portable monitors (PM) relative to gold standard polysomnography. The primary objective is to explore the relationship between these physiological parameters and OSA, their application in calculating the apnea hypopnea index (AHI), the standard metric for OSA diagnosis, and the derivation of non-AHI metrics that offer additional diagnostic value. It is found that increasing the number of parameters in PMs does not necessarily improve OSA detection. Several factors can cause performance variations among different PMs, even if they extract similar signals. The review also highlights the potential of PMs to be used beyond OSA diagnosis. These devices possess parameters that can be utilized to obtain endotypic and other non-AHI metrics, enabling improved characterization of the disorder and personalized treatment strategies. Advancements in PM technology, coupled with thorough evaluation and validation of these devices, have the potential to revolutionize OSA diagnosis, personalized treatment, and ultimately improve health outcomes for patients with OSA. By identifying the key factors influencing performance and exploring the application of PMs beyond OSA diagnosis, this review aims to contribute to the ongoing development and utilization of portable, efficient, and effective diagnostic tools for OSA.

Kinematics of the Upper Eyelid and the Globe During Downward Excursion With Comparative Analysis in Patients With Thyroid Eye Disease.

PURPOSE: To analyze the kinematics of the upper eyelid and the globe on downward excursion for potential use in monitoring thyroid eye disease (TED) progression in an objective manner. METHODS: Ten normal volunteers and 10 patients with TED were studied. A high-speed (240 fps) digital camera with a coaxial light source set at a constant distance from the subjects' eyes was used to record the excursion of the upper eyelid and the globe from extreme upgaze to extreme downgaze. Clinical data, including age, gender, race, thyroid function tests, Vision, Inflammation/Congestion, Strabismus/motility restriction, Appearance/exposure score (primary surgeons' preference of TED grading system), exophthalmometry, and eyelid measurements were collected for all patients with TED. Frame-by-frame analyses of the videos were performed using Python software (version 3.6) and the Open Source Computer Vision Library. Temporal resolution was obtained by measuring the number of frames from initiation of eyelid and globe movement from extreme upgaze (t 0 ) to extreme downgaze (t f ). Spatial resolution was obtained by measuring the number of pixels the eyelid margin and the globe traversed from t 0 to t f . The data were then plotted on a graph to calculate the velocity of the upper eyelid and the globe during downward excursion. RESULTS: Velocimetric calculations using high-speed photography suggests that downward excursion of the upper eyelid, and the globe occurs in 2 phases: the acceleration phase and the deceleration phase. Comparative analysis of slow-motion videography demonstrates that patients with TED were found to have attenuation in the early acceleration phase of upper eyelid excursion compared with normal subjects. In patients with TED, the difference in velocity between the eyelid and the globe occurs in the early deceleration phase. CONCLUSIONS: The upper eyelid normally synchronizes intimately with the globe during downward eye movement. Data from this study reveal that attenuation mostly in the early deceleration phase of eyelid movement relative to the globe accounts for the dynamic eyelid lag seen on clinical examination. Further analysis is needed to show if a quantified von Graefe sign can be used as an objective means of monitoring progression in TED.

Modeling ultrasound modulation of neural function in a single cell.

Background: Low intensity ultrasound stimulation has been shown to non-invasively modulate neural function in the central nervous system (CNS) and peripheral nervous system (PNS) with high precision. Ultrasound sonication is capable of either excitation or inhibition, depending on the ultrasound parameters used. On the other hand, the mode of interaction of ultrasonic waves with the neural tissue for effective neuromodulation remains ambiguous. New method: Here within we propose a numerical model that incorporates the mechanical effects of ultrasound stimulation on the Hodgkin-Huxley (HH) neuron by incorporating the relation between increased external pressure and the membrane induced tension, with a stress on the flexoelectric effect on the neural membrane. The external pressure causes an increase in the total tension of the membrane thus affecting the probability of the ion channels being open after the conformational changes that those channels undergo. Results: The interplay between varying the acoustic intensities and frequencies depicts different action potential suppression rates, whereby a combination of low intensity and low frequency ultrasound sonication proved to be the most effective in modulating neural function.Comparison with Existing Methods: Our method solely depends on the HH model of a single neuron and the linear flexoelectric effect of the dielectric neural membrane, when under an ultrasound-induced mechanical strain, while varying the ion-channels conductances based on different sonication frequencies and intensities. We study the effect of ultrasound parameters on the firing rate, latency, and action potential amplitude of a HH neuron for a better understanding of the neuromodulation modality of ultrasound stimulation (in the continuous and pulsed modes). Conclusions: This simulation work confirms the published experimental data that low intensity and low frequency ultrasound sonication has a higher success rate of modulating neural firing.

Modeling of Calcium-dependent Low Intensity Low Frequency Ultrasound Modulation of a Hodgkin-Huxley Neuron.

Non-invasive low intensity, low frequency ultrasound is a progressive neuromodulation approach that can reach deep brain areas with peak spatial and temporal resolution for highly-targeted diagnostic and therapeutic purposes. Coupling the ultrasound mechanical effects to the neural membrane comprises different mechanisms that are, to-date, still a topic of debate. The availability of calcium ions in the extracellular medium is of high significance when it comes to the effect of ultrasound on the neural tissue. Whereby the generated calcium influx can directly affect the voltage-gated ion channels, amplifying their action. We modeled the flexoelectric-induced effects of ultrasound to a single firing neuron, taking into consideration the effect of calcium channel embedding into the neural membrane on the neuron's firing rate, latency response, peak-to-peak voltage, and general shape of the action potential.Clinical Relevance- Upon Ultrasound sonication, the mechanical waves interact with the neural membrane and alter the kinetics of the calcium channels, thus changing the neural response.

Development of Inkjet-Printed PEDOT:PSS-Based Organic Electrochemical Transistor (OECT) for Biopotential Amplification.

With the ever-increasing need for miniaturized and biocompatible devices for physiological recordings, high signal fidelity and ease of fabrication are key to achieve reliable data collection. This calls for the development of active recording devices such as Organic Electrochemical Transistors (OECTs) which, compared to passive electrodes, offer local amplification. In this work, we built PEDOT:PSS based OECTs using novel inkjet printing technology, achieving a transconductance of 75 mS. The device was later used to amplify arbitrary signals simulating in vivo recordings. Gate voltage offset manipulation offered a range of current peak-to-peak amplitudes. Additionally, we demonstrate a simple circuit for voltage readings, where another resistor-dependent characterization involving voltage source and drain voltage is performed. At ideal operating point and when using a 220 Ω resistor, a gain of 14.5 is achieved.Clinical Relevance- 1This work demonstrates the ability to rapidly and easily develop OECT-based technology for potential signal sensing for more accurate diagnosis of pathologies and diseases.

Investigating malignancy-dependent mechanical properties of breast cancer cells.

Cancer invasiveness significantly impacts cellular mechanical properties which regulate cell motility and, subsequently, cell metastatic potential. Understanding the adhesion forces and stiffness/rigidity of cancer cells can provide better insights into their mechanical adaptability related to their degree of invasiveness. Here, we used single-cell force spectroscopy in conjunction with quartz crystal microbalance-with dissipation measurements to compare the mechanical properties of mammary epithelial cancer cells with different metastatic potentials, namely MCF-7 (non-invasive) and MDA-MB-231 (aggressive and highly invasive). Our results showed that MCF-7 exhibits larger adhesion forces, stronger intercellular forces, and a considerably stiff/rigid phenotype, contrary to MDA-MB-231. The biomechanical properties obtained are associated with the malignant potential of these cells such that the forces of adhesion and viscoelasticity are inversely proportional to cell invasiveness. This study integrates a new quantitative tool with real-time measurements to provide better insights into the mechanics of cancer cells across metastatic stages.

Advances in point-of-care platforms for traumatic brain injury: recent developments in diagnostics.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity, affecting 2 million people annually in the US alone, with direct and indirect costs of $76.3 billion per year. TBI is a progressive disease with no FDA-approved drug for treating patients. Early, accurate and rapid diagnosis can have significant implications for successful triaging and intervention. Unfortunately, current clinical tests for TBI rely on CT scans and MRIs, both of which are expensive, time-consuming, and not accessible to everyone. Recent evidence of biofluid-based biomarkers being released right after a TBI incident has ignited interest in developing point-of-care (POC) platforms for early and on-site TBI diagnosis. These efforts face many challenges to accurate, sensitive, and specific diagnosis and monitoring of TBI. This review includes a deep dive into the latest advances in chemical, mechanical, electrical, and optical sensing systems that hold promise for TBI-POC diagnostic testing platforms. It also focuses on the performance of these proposed biosensors compared to biofluid-based orthodox diagnostic techniques in terms of sensitivity, specificity, and limits of detection. Finally, it examines commercialized TBI-POCs present in the market, the challenges associated with them, and the future directions and prospects of these technologies and the field.

Finite Element Modeling of Magnitude and Location of Brain Micromotion Induced Strain for Intracortical Implants.

Micromotion-induced stress remains one of the main determinants of life of intracortical implants. This is due to high stress leading to tissue injury, which in turn leads to an immune response coupled with a significant reduction in the nearby neural population and subsequent isolation of the implant. In this work, we develop a finite element model of the intracortical probe-tissue interface to study the effect of implant micromotion, implant thickness, and material properties on the strain levels induced in brain tissue. Our results showed that for stiff implants, the strain magnitude is dependent on the magnitude of the motion, where a micromotion increase from 1 to 10 µm induced an increase in the strain by an order of magnitude. For higher displacement over 10 µm, the change in the strain was relatively smaller. We also showed that displacement magnitude has no impact on the location of maximum strain and addressed the conflicting results in the literature. Further, we explored the effect of different probe materials [i.e., silicon, polyimide (PI), and polyvinyl acetate nanocomposite (PVAc-NC)] on the magnitude, location, and distribution of strain. Finally, we showed that strain distribution across cortical implants was in line with published results on the size of the typical glial response to the neural probe, further reaffirming that strain can be a precursor to the glial response.

Circulating Tumor Cell Detection Technologies and Clinical Utility: Challenges and Opportunities.

The potential clinical utility of circulating tumor cells (CTCs) in the diagnosis and management of cancer has drawn a lot of attention in the past 10 years. CTCs disseminate from tumors into the bloodstream and are believed to carry vital information about tumor onset, progression, and metastasis. In addition, CTCs reflect different biological aspects of the primary tumor they originate from, mainly in their genetic and protein expression. Moreover, emerging evidence indicates that CTC liquid biopsies can be extended beyond prognostication to pharmacodynamic and predictive biomarkers in cancer patient management. A key challenge in harnessing the clinical potential and utility of CTCs is enumerating and isolating these rare heterogeneous cells from a blood sample while allowing downstream CTC analysis. That being said, there have been serious doubts regarding the potential value of CTCs as clinical biomarkers for cancer due to the low number of promising outcomes in the published results. This review aims to present an overview of the current preclinical CTC detection technologies and the advantages and limitations of each sensing platform, while surveying and analyzing the published evidence of the clinical utility of CTCs.

Highly Flexible Single-Unit Resolution All Printed Neural Interface on a Bioresorbable Backbone.

Neural interfaces are the parts of the neural prosthesis that are in contact with the target tissue. The mechanical, chemical, and electrical properties of these interfaces can be a major determinant of the life of the implant and the neural tissue for chronic and even acute integrations. In this work, we developed a fully inkjet-printed, flexible neural interface on a bioresorbable backbone capable of recording high-fidelity neural activity. We utilized room temperature fabrication processes that overcome the limitations of semiconductor fabrication techniques for processing low-melting point polymers while maintaining high spatial and single-cell recording resolution. The ∼8 µm-thick devices in this study were fabricated onto two flexible polymers: (a) polyimide (PI), a biocompatible polymer commonly used for neural interfaces, and (b) polycaprolactone (PCL), a bioresorbable polyester with outstanding mechanical properties. Electrodes for neural recording were built at 30, 50, 75, and 100 µm diameter using silver nanoparticles/(3,4-ethylenedioxytiophene)-poly(styrenesulfonate) (AgNPs/PEDOT:PSS), which through our process achieved the lowest impedance reported in the literature reaching ∼200 Ω at 1 kHz for a 50 µm electrode diameter. We further enhanced the electrochemical performance of AgNPs/PEDOT:PSS by an order of magnitude by incorporating exfoliated graphene into the electrodes. The biocompatibility of the fabricated devices and their ability to record single-unit activity were confirmed by in vitro tests on both rat PC12 cells and isolated neural rat retina, respectively.

COVID-19 in-vitro Diagnostics: State-of-the-Art and Challenges for Rapid, Scalable, and High-Accuracy Screening.

The world continues to grapple with the devastating effects of the current COVID-19 pandemic. The highly contagious nature of this respiratory disease challenges advanced viral diagnostic technologies for rapid, scalable, affordable, and high accuracy testing. Molecular assays have been the gold standard for direct detection of the presence of the viral RNA in suspected individuals, while immunoassays have been used in the surveillance of individuals by detecting antibodies against SARS-CoV-2. Unlike molecular testing, immunoassays are indirect testing of the viral infection. More than 140 diagnostic assays have been developed as of this date and have received the Food and Drug Administration (FDA) emergency use authorization (EUA). Given the differences in assasy format and/or design as well as the lack of rigorous verification studies, the performance and accuracy of these testing modalities remain unclear. In this review, we aim to carefully examine commercialized and FDA approved molecular-based and serology-based diagnostic assays, analyze their performance characteristics and shed the light on their utility and limitations in dealing with the COVID-19 global public health crisis.

Towards Point-of-Care Heart Failure Diagnostic Platforms: BNP and NT-proBNP Biosensors.

Heart failure is a class of cardiovascular diseases that remains the number one cause of death worldwide with a substantial economic burden of around $18 billion incurred by the healthcare sector in 2017 due to heart failure hospitalization and disease management. Although several laboratory tests have been used for early detection of heart failure, these traditional diagnostic methods still fail to effectively guide clinical decisions, prognosis, and therapy in a timely and cost-effective manner. Recent advances in the design and development of biosensors coupled with the discovery of new clinically relevant cardiac biomarkers are paving the way for breakthroughs in heart failure management. Natriuretic neurohormone peptides, B-type natriuretic peptide (BNP) and N-terminal prohormone of BNP (NT-proBNP), are among the most promising biomarkers for clinical use. Remarkably, they result in an increased diagnostic accuracy of around 80% owing to the strong correlation between their circulating concentrations and different heart failure events. The latter has encouraged research towards developing and optimizing BNP biosensors for rapid and highly sensitive detection in the scope of point-of-care testing. This review sheds light on the advances in BNP and NT-proBNP sensing technologies for point-of-care (POC) applications and highlights the challenges of potential integration of these technologies in the clinic. Optical and electrochemical immunosensors are currently used for BNP sensing. The performance metrics of these biosensors-expressed in terms of sensitivity, selectivity, reproducibility, and other criteria-are compared to those of traditional diagnostic techniques, and the clinical applicability of these biosensors is assessed for their potential integration in point-of-care diagnostic platforms.

Design and Development of Microscale Thickness Shear Mode (TSM) Resonators for Sensing Neuronal Adhesion.

The overall goal of this study is to develop thickness shear mode (TSM) resonators for the real-time, label-free, non-destructive sensing of biological adhesion events in small populations (hundreds) of neurons, in a cell culture medium and subsequently in vivo in the future. Such measurements will enable the discovery of the role of biomechanical events in neuronal function and dysfunction. Conventional TSM resonators have been used for chemical sensing and biosensing applications in media, with hundreds of thousands of cells in culture. However, the sensitivity and spatial resolution of conventional TSM devices need to be further enhanced for sensing smaller cell populations or molecules of interest. In this report, we focus on key challenges such as eliminating inharmonics in solution and maximizing Q-factor while simultaneously miniaturizing the active sensing (electrode) area to make them suitable for small populations of cells. We used theoretical expressions for sensitivity and electrode area of TSM sensors operating in liquid. As a validation of the above design effort, we fabricated prototype TSM sensors with resonant frequencies of 42, 47, 75, and 90 MHz and characterized their performance in liquid using electrode diameters of 150, 200, 400, 800, and 1,200 µm and electrode thicknesses of 33 and 230 nm. We validated a candidate TSM resonator with the highest sensitivity and Q-factor for real-time monitoring of the adhesion of cortical neurons. We reduced the size of the sensing area to 150-400 µm for TSM devices, improving the spatial resolution by monitoring few 100-1,000s of neurons. Finally, we modified the electrode surface with single-walled carbon nanotubes (SWCNT) to further enhance adhesion and sensitivity of the TSM sensor to adhering neurons (Marx, 2003).

High Density Individually Addressable Nanowire Arrays Record Intracellular Activity from Primary Rodent and Human Stem Cell Derived Neurons.

We report a new hybrid integration scheme that offers for the first time a nanowire-on-lead approach, which enables independent electrical addressability, is scalable, and has superior spatial resolution in vertical nanowire arrays. The fabrication of these nanowire arrays is demonstrated to be scalable down to submicrometer site-to-site spacing and can be combined with standard integrated circuit fabrication technologies. We utilize these arrays to perform electrophysiological recordings from mouse and rat primary neurons and human induced pluripotent stem cell (hiPSC)-derived neurons, which revealed high signal-to-noise ratios and sensitivity to subthreshold postsynaptic potentials (PSPs). We measured electrical activity from rodent neurons from 8 days in vitro (DIV) to 14 DIV and from hiPSC-derived neurons at 6 weeks in vitro post culture with signal amplitudes up to 99 mV. Overall, our platform paves the way for longitudinal electrophysiological experiments on synaptic activity in human iPSC based disease models of neuronal networks, critical for understanding the mechanisms of neurological diseases and for developing drugs to treat them.

Towards high-resolution retinal prostheses with direct optical addressing and inductive telemetry.

OBJECTIVE: Despite considerable advances in retinal prostheses over the last two decades, the resolution of restored vision has remained severely limited, well below the 20/200 acuity threshold of blindness. Towards drastic improvements in spatial resolution, we present a scalable architecture for retinal prostheses in which each stimulation electrode is directly activated by incident light and powered by a common voltage pulse transferred over a single wireless inductive link. APPROACH: The hybrid optical addressability and electronic powering scheme provides separate spatial and temporal control over stimulation, and further provides optoelectronic gain for substantially lower light intensity thresholds than other optically addressed retinal prostheses using passive microphotodiode arrays. The architecture permits the use of high-density electrode arrays with ultra-high photosensitive silicon nanowires, obviating the need for excessive wiring and high-throughput data telemetry. Instead, the single inductive link drives the entire array of electrodes through two wires and provides external control over waveform parameters for common voltage stimulation. MAIN RESULTS: A complete system comprising inductive telemetry link, stimulation pulse demodulator, charge-balancing series capacitor, and nanowire-based electrode device is integrated and validated ex vivo on rat retina tissue. SIGNIFICANCE: Measurements demonstrate control over retinal neural activity both by light and electrical bias, validating the feasibility of the proposed architecture and its system components as an important first step towards a high-resolution optically addressed retinal prosthesis.

Bidirectional neural interface: Closed-loop feedback control for hybrid neural systems.

Closed-loop neural prostheses enable bidirectional communication between the biological and artificial components of a hybrid system. However, a major challenge in this field is the limited understanding of how these components, the two separate neural networks, interact with each other. In this paper, we propose an in vitro model of a closed-loop system that allows for easy experimental testing and modification of both biological and artificial network parameters. The interface closes the system loop in real time by stimulating each network based on recorded activity of the other network, within preset parameters. As a proof of concept we demonstrate that the bidirectional interface is able to establish and control network properties, such as synchrony, in a hybrid system of two neural networks more significantly more effectively than the same system without the interface or with unidirectional alternatives. This success holds promise for the application of closed-loop systems in neural prostheses, brain-machine interfaces, and drug testing.

Visual evoked potential characterization of rabbit animal model for retinal prosthesis research.

Visual evoked potentials (VEP) are used to confirm the function of prosthetic devices designed to stimulate retinas with damaged photoreceptors in vivo. In this work, we focus on methods and experimental consideration for recording visual evoked potential in rabbit models and assesses the use for retinal prosthesis research. We compare both invasive and noninvasive methods for recording VEPs, the response of the rabbit retina to various light wavelengths and intensities, focal vs. full field stimulation, and the effect of light bleaching on the retinal response.