Epidermal mechano-acoustic sensing electronics for cardiovascular diagnostics and human-machine interfaces.

Physiological mechano-acoustic signals, often with frequencies and intensities that are beyond those associated with the audible range, provide information of great clinical utility. Stethoscopes and digital accelerometers in conventional packages can capture some relevant data, but neither is suitable for use in a continuous, wearable mode, and both have shortcomings associated with mechanical transduction of signals through the skin. We report a soft, conformal class of device configured specifically for mechano-acoustic recording from the skin, capable of being used on nearly any part of the body, in forms that maximize detectable signals and allow for multimodal operation, such as electrophysiological recording. Experimental and computational studies highlight the key roles of low effective modulus and low areal mass density for effective operation in this type of measurement mode on the skin. Demonstrations involving seismocardiography and heart murmur detection in a series of cardiac patients illustrate utility in advanced clinical diagnostics. Monitoring of pump thrombosis in ventricular assist devices provides an example in characterization of mechanical implants. Speech recognition and human-machine interfaces represent additional demonstrated applications. These and other possibilities suggest broad-ranging uses for soft, skin-integrated digital technologies that can capture human body acoustics.

Epidermal radio frequency electronics for wireless power transfer.

Epidermal electronic systems feature physical properties that approximate those of the skin, to enable intimate, long-lived skin interfaces for physiological measurements, human-machine interfaces and other applications that cannot be addressed by wearable hardware that is commercially available today. A primary challenge is power supply; the physical bulk, large mass and high mechanical modulus associated with conventional battery technologies can hinder efforts to achieve epidermal characteristics, and near-field power transfer schemes offer only a limited operating distance. Here we introduce an epidermal, far-field radio frequency (RF) power harvester built using a modularized collection of ultrathin antennas, rectifiers and voltage doublers. These components, separately fabricated and tested, can be integrated together via methods involving soft contact lamination. Systematic studies of the individual components and the overall performance in various dielectric environments highlight the key operational features of these systems and strategies for their optimization. The results suggest robust capabilities for battery-free RF power, with relevance to many emerging epidermal technologies.

Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products.

Most biopharmaceutical therapeutics elicit some level of antibody response against the product. This antibody response can, in some cases, lead to potentially serious side effects and/or loss of efficacy. Therefore, the immunogenicity of therapeutic proteins is a concern for clinicians, manufacturers and regulatory agencies. In order to assess immunogenicity of these molecules, appropriate detection, quantitation and characterization of antibody responses are necessary. Inadequately designed antibody assays have led to the hampering of product development or, during licensure, post-marketing commitments. This document provides scientific recommendations based on the experience of the authors for the development of anti-product antibody immunoassays intended for preclinical or clinical studies. While the main focus of this document is assay design considerations, we provide scientific focus and background to the various assay performance parameters necessary for developing a valid assay. Sections on assay performance parameters, including those that appear in regulatory guidances, are contained in this manuscript.