Jeffrey Michael Ashe

Towards Maintenance-Free Biosensors for Hundreds of Bind/Release Cycles†

A single aptamer bioreceptor layer was formed using a common streptavidin-biotin immobilization strategy and employed for 100-365 bind/release cycles. Chemically induced aptamer unfolding and release of its bound target was accomplished using alkaline solutions with high salt concentrations or deionized (DI) water. The use of DI water scavenged from the ambient atmosphere represents a first step towards maintenance-free biosensors that do not require the storage of liquid reagents. The aptamer binding affinity was determined by surface plasmon resonance and found to be almost constant over 100-365 bind/release cycles with a variation of less than 5% relative standard deviation. This reversible operation of biosensors based on immobilized aptamers without storage of liquid reagents introduces a conceptually new perspective in biosensing. Such new biosensing capability will be important for distributed sensor networks, sensors in resource-limited settings, and wearable sensor applications.

Unobtrusive vital signs monitoring with range-controlled radar

Researchers at General Electric have developed a prototype demonstration system that can identify motion and measure breathing and heart rate in periods without general body motions using a range-controlled radar device, similar to motion detectors available in home security systems. With continuous monitoring of the activity and physical vital signs, warning criteria can be used to identify potential crises augmenting existing observational systems without requiring the observed individual to wear or attach any special devices. This has potential applications in correctional facilities to complement observation for inmates at risk of suicide. It has healthcare applications where attaching traditional vital sign monitoring equipment is difficult such as for neonatal or burn patients.

Efficient Simultaneous Reconstruction of Time-Varying Images and Electrode Contact Impedances in Electrical Impedance Tomography

Objective: In electrical impedance tomography (EIT), we apply patterns of currents on a set of electrodes at the external boundary of an object, measure the resulting potentials at the electrodes, and, given the aggregate dataset, reconstruct the complex conductivity and permittivity within the object. It is possible to maximize sensitivity to internal conductivity changes by simultaneously applying currents and measuring potentials on all electrodes but this approach also maximizes sensitivity to changes in impedance at the interface. Methods: We have, therefore, developed algorithms to assess contact impedance changes at the interface as well as to efficiently and simultaneously reconstruct internal conductivity/permittivity changes within the body. We use simple linear algebraic manipulations, the generalized singular value decomposition, and a dual-mesh finite-element-based framework to reconstruct images in real time. We are also able to efficiently compute the linearized reconstruction for a wide range of regularization parameters and to compute both the generalized cross-validation parameter as well as the L-curve, objective approaches to determining the optimal regularization parameter, in a similarly efficient manner. Results: Results are shown using data from a normal subject and from a clinical intensive care unit patient, both acquired with the GE GENESIS prototype EIT system, demonstrating significantly reduced boundary artifacts due to electrode drift and motion artifact.

Multi-channel electrical impedance tomography for regional tissue hydration monitoring

Poor assessment of hydration status during hemodialysis can lead to under- or over-hydration in patients with consequences of increased morbidity and mortality. In current practice, fluid management is largely based on clinical assessments to estimate dry weight (normal hydration body weight). However, hemodialysis patients usually have co-morbidities that can make the signs of fluid status ambiguous. Therefore, achieving normal hydration status remains a major challenge for hemodialysis therapy. Electrical impedance technology has emerged as a promising method for hydration monitoring due to its non-invasive nature, low cost and ease-of-use. Conventional electrical impedance-based hydration monitoring systems employ single-channel current excitation (either 2-electrode or 4-electrode methods) to perturb and extract averaged impedance from bulk tissue and use generalized models from large populations to derive hydration estimates. In the present study, a prototype, single-frequency electrical impedance tomography (EIT) system with simultaneous multi-channel current excitation was used to enable regional hydration change detection. We demonstrated the capability to detect a difference in daily impedance change between left leg and right leg in healthy human subjects, who wore a compression sock only on one leg to reduce daily gravitational fluid accumulation. The impedance difference corresponded well with the difference of lower leg volume change between left leg and right leg measured by volumetry, which on average is ~35 ml, accounting for 0.7% of the lower leg volume. We have demonstrated the feasibility of using multi-channel EIT to extract hydration information in different tissue layers with minimal skin interference. Our simultaneous, multi-channel current excitation approach provides an effective method to separate electrode contact impedance and skin condition artifacts from hydration signals. The prototype system has the potential to be used in clinical settings for helping optimize patient fluid management during hemodialysis as well as for home monitoring of patients with congestive heart failure, chronic kidney disease, diabetes and other diseases with peripheral edema symptoms.

Real-time 3D electrical impedance imaging for ventilation monitoring of the lung: Pilot study.

We report an Electrical Impedance Tomography device capable of detecting gravity-induced regional ventilation changes in real-time without averaging or using a contrast medium. Changes in lung ventilation are demonstrated in right and left lateral decubitus position and compared to those seen in an upright and supine normal subject.

Tripulse: an accurate orientation/attitude estimation system for satellite borne phased arrays

Tripulse is a novel orientation/attitude estimation system that is designed to accurately estimate the orientation of a satellite borne phased array relative to one or more Earth stations. This system has an accuracy potential that is significantly better than conventional Earth-Moon-Sun attitude sensors. Tripulse has conceptual similarities to amplitude comparison monopulse systems used in tracking radars. Detailed Tripulse statistical performance analyses for noise, beam-forming quantization errors, and hardware failures are presented.

Estimating a regional ventilation-perfusion index

This is a methods paper, where an approximation to the local ventilation-perfusion ratio is derived. This approximation, called the ventilation-perfusion index since it is not exactly the physiological ventilation-perfusion ratio, is calculated using conductivity reconstructions obtained using electrical impedance tomography. Since computation of the ventilation-perfusion index only requires knowledge of the internal conductivity, any conductivity reconstruction method may be used. The method is explained and results are presented using conductivities obtained from two EIT systems, one using an iterative method and the other a linearization method.

Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity

Significance Evolution conferred animals with molecular sensors that monitor cellular and organ function to detect changes in the environment. These activate sensory neural responses that drive the action of reflexes that maintain cellular and physiological homeostasis. Recent advances reveal that neural reflexes modulate the immune system, but it was previously unknown whether cytokine mediators of immunity mediate specific neural signals. Here we develop methods to isolate and decode specific neural signals recorded from the vagus nerve to discriminate between the cytokines IL-1β and TNF. This methodological waveform successfully detects and discriminates between specific cytokine exposures using neural signals. The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1β and TNF were sorted into groups based on their shape and amplitude, and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1β in a dose-dependent manner. These cytokine-mediated responses were subsequently decoded using a Naive Bayes algorithm that discriminated between no exposure and exposures to IL-1β and TNF (mean successful identification rate 82.9 ± 17.8%, chance level 33%). Recordings obtained in IL-1 receptor-KO mice were devoid of IL-1β–related signals but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1β, and distal lidocaine nerve block attenuated all vagus neural signals recorded. The results obtained in this study using the methodological framework suggest that cytokine-specific information is present in sensory neural signals within the vagus nerve.

EKG‐based detection of deep brain stimulation in fMRI studies

To assess the impact of synchronization errors between the assumed functional MRI paradigm timing and the deep brain stimulation (DBS) on/off cycling using a custom electrocardiogram‐based triggering system

Tissue-Susceptibility Matched Carbon Nanotube Electrodes for Magnetic Resonance Imaging

Test disk electrodes were fabricated from carbon nanotubes (CNT) using the Carbon Nanotube Templated Microfabrication (CNT-M) technique. The CNT-M process uses patterned growth of carbon nanotube forests from surfaces to form complex patterns, enabling electrode sizing and shaping. The additional carbon infiltration process stabilizes these structures for further processing and handling. At a macroscopic scale, the electrochemical, electrical and magnetic properties, and magnetic resonance imaging (MRI) characteristics of the disk electrodes were investigated; their microstructure was also assessed. CNT disk electrodes showed electrical resistivity around 1 Ω·cm, charge storage capacity between 3.4 and 38.4 mC/cm2, low electrochemical impedance and magnetic susceptibility of -5.9 to -8.1 ppm, closely matched to that of tissue (∼-9 ppm). Phantom MR imaging experiments showed almost no distortion caused by these electrodes compared with Cu and Pt-Ir reference electrodes, indicating the potential for significant improvement in accurate tip visualization.