A. J. Aranyosi

Longitudinally propagating traveling waves of the mammalian tectorial membrane.

Sound-evoked vibrations transmitted into the mammalian cochlea produce traveling waves that provide the mechanical tuning necessary for spectral decomposition of sound. These traveling waves of motion that have been observed to propagate longitudinally along the basilar membrane (BM) ultimately stimulate the mechano-sensory receptors. The tectorial membrane (TM) plays a key role in this process, but its mechanical function remains unclear. Here we show that the TM supports traveling waves that are an intrinsic feature of its visco-elastic structure. Radial forces applied at audio frequencies (2–20 kHz) to isolated TM segments generate longitudinally propagating waves on the TM with velocities similar to those of the BM traveling wave near its best frequency place. We compute the dynamic shear storage modulus and shear viscosity of the TM from the propagation velocity of the waves and show that segments of the TM from the basal turn are stiffer than apical segments are. Analysis of loading effects of hair bundle stiffness, the limbal attachment of the TM, and viscous damping in the subtectorial space suggests that TM traveling waves can occur in vivo. Our results show the presence of a traveling wave mechanism through the TM that can functionally couple a significant longitudinal extent of the cochlea and may interact with the BM wave to greatly enhance cochlear sensitivity and tuning.

Tunable Nanostructured Coating for the Capture and Selective Release of Viable Circulating Tumor Cells

A layer-by-layer gelatin nanocoating is presented for use as a tunable, dual response biomaterial for the capture and release of circulating tumor cells (CTCs) from cancer patient blood. The entire nanocoating can be dissolved from the surface of microfluidic devices through biologically compatible temperature shifts. Alternatively, individual CTCs can be released through locally applied mechanical stress.

Tectorial membrane travelling waves underlie abnormal hearing in Tectb mutant mice

Remarkable sensitivity and exquisite frequency selectivity are hallmarks of mammalian hearing, but their underlying mechanisms remain unclear. Cochlear insults and hearing disorders that decrease sensitivity also tend to broaden tuning, suggesting that these properties are linked. However, a recently developed mouse model of genetically altered hearing (Tectb−/−) shows decreased sensitivity and sharper frequency selectivity. In this paper, we show that the Tectb mutation reduces the spatial extent and propagation velocity of tectorial membrane (TM) travelling waves and that these changes in wave propagation are likely to account for all of the hearing abnormalities associated with the mutation. By reducing the spatial extent of TM waves, the Tectb mutation decreases the spread of excitation and thereby increases frequency selectivity. Furthermore, the change in TM wave velocity reduces the number of hair cells that effectively couple energy to the basilar membrane, which reduces sensitivity. These results highlight the importance of TM waves in hearing.

Epithelial cell guidance by self-generated EGF gradients

Cancer epithelial cells often migrate away from the primary tumor to invade into the surrounding tissues. Their migration is commonly assumed to be directed by pre-existent spatial gradients of chemokines and growth factors in the target tissues. Unexpectedly however, we found that the guided migration of epithelial cells is possible in vitro in the absence of pre-existent chemical gradients. We observed that both normal and cancer epithelial cells can migrate persistently and reach the exit along the shortest path from microscopic mazes filled with uniform concentrations of media. Using microscale engineering techniques and biophysical models, we uncovered a self-guidance strategy during which epithelial cells generate their own guiding cues under conditions of biochemical confinement. The self-guidance strategy depends on the balance between three interdependent processes: epidermal growth factor (EGF) uptake by the cells (U), the restricted transport of EGF through the structured microenvironment (T), and cell chemotaxis toward the resultant EGF gradients (C). The UTC self-guidance strategy can be perturbed by inhibition of signalling through EGF-receptors and appears to be independent from chemokine signalling. Better understanding of the UTC self-guidance strategy could eventually help devise new ways for modulating epithelial cell migration and delaying cancer cell invasion or accelerating wound healing.

Flexible opto-electronics enabled microfluidics systems with cloud connectivity for point-of-care micronutrient analysis

In developing countries, the deployment of medical diagnostic technologies remains a challenge because of infrastructural limitations (e.g. refrigeration, electricity), and paucity of health professionals, distribution centers and transportation systems. Here we demonstrate the technical development and clinical testing of a novel electronics enabled microfluidic paper-based analytical device (EE-μPAD) for quantitative measurement of micronutrient concentrations in decentralized, resource-limited settings. The system performs immune-detection using paper-based microfluidics, instrumented with flexible electronics and optoelectronic sensors in a mechanically robust, ultrathin format comparable in size to a credit card. Autonomous self-calibration, plasma separation, flow monitoring, timing and data storage enable multiple devices to be run simultaneously. Measurements are wirelessly transferred to a mobile phone application that geo-tags the data and transmits it to a remote server for real time tracking of micronutrient deficiencies. Clinical tests of micronutrient levels from whole blood samples (n=95) show comparable sensitivity and specificity to ELISA-based tests. These results demonstrate instantaneous acquisition and global aggregation of diagnostics data using a fully integrated point of care system that will enable rapid and distributed surveillance of disease prevalence and geographical progression.

Two modes of motion of the alligator lizard cochlea: Measurements and model predictions

Measurements of motion of an in vitro preparation of the alligator lizard basilar papilla in response to sound demonstrate elliptical trajectories. These trajectories are consistent with the presence of both a translational and rotational mode of motion. The translational mode is independent of frequency, and the rotational mode has a displacement peak near 5 kHz. These measurements can be explained by a simple mechanical system in which the basilar papilla is supported asymmetrically on the basilar membrane. In a quantitative model, the translational admittance is compliant while the rotational admittance is second order. Best-fit model parameters are consistent with estimates based on anatomy and predict that fluid flow across hair bundles is a primary source of viscous damping. The model predicts that the rotational mode contributes to the high-frequency slopes of auditory nerve fiber tuning curves, providing a physical explanation for a low-pass filter required in models of this cochlea. The combination of modes makes the sensitivity of hair bundles more uniform with radial position than that which would result from pure rotation. A mechanical analogy with the organ of Corti suggests that these two modes of motion may also be present in the mammalian cochlea.

Skin mounted accelerometer system for measuring knee range of motion

Sufficient range of motion of the knee joint is necessary for performing many activities of daily living. Ambulatory monitoring of knee function can provide valuable information about progression of diseases like knee osteoarthritis and recovery after surgical interventions like total knee arthroplasty. In this paper, we describe a skin-mounted, conformal, accelerometer-based system for measuring knee angle and range of motion that does not require a skilled operator to apply devices. We establish the accuracy of this technique with respect to clinical gold standard goniometric measurements on a dataset collected from normative subjects during the performance of repeated bouts of knee flexion and extension tests. Results show that knee angle and range of motion estimates are highly correlated with goniometer measurements, and track differences in knee angle and range of motion to within 1%. These results demonstrate the ability of this system to characterize knee angle and range of motion, enabling future longitudinal monitoring of knee motion in naturalistic environments.

Intraoperative monitoring of neuromuscular function with soft, skin-mounted wireless devices

Peripheral nerves are often vulnerable to damage during surgeries, with risks of significant pain, loss of motor function, and reduced quality of life for the patient. Intraoperative methods for monitoring nerve activity are effective, but conventional systems rely on bench-top data acquisition tools with hard–wired connections to electrode leads that must be placed percutaneously inside target muscle tissue. These approaches are time and skill intensive and therefore costly to an extent that precludes their use in many important scenarios. Here we report a soft, skin-mounted monitoring system that measures, stores, and wirelessly transmits electrical signals and physical movement associated with muscle activity, continuously and in real-time during neurosurgical procedures on the peripheral, spinal, and cranial nerves. Surface electromyography and motion measurements can be performed non-invasively in this manner on nearly any muscle location, thereby offering many important advantages in usability and cost, with signal fidelity that matches that of the current clinical standard of care for decision making. These results could significantly improve accessibility of intraoperative monitoring across a broad range of neurosurgical procedures, with associated enhancements in patient outcomes.Wireless biosensors: easing intraoperative monitoringA small skin-mounted biosensing device accurately and non-invasively monitors neuromuscular activity in real-time during surgery. With many surgical procedures there is a risk of nerve damage. Although this is often temporary, in some cases it can significantly affect patients’ quality of life. Existing monitoring systems that rely on the accurate placement of needle electrodes into target nerves are cumbersome and expensive. The device developed by a team led by John Rogers, at Northwestern University, and Michel Kliot, at Stanford University, can easily be accommodated to any part of the body to monitor muscle activity in response to nerve impulses and stimulation during surgery. Furthermore, it can wirelessly transmit signals of comparable quality to needle-based systems. These devices could not only increase the use of intraoperative monitoring in hospitals but also contribute to make surgery safer.

A wearable computing platform for developing cloud-based machine learning models for health monitoring applications

Wearable sensors have the potential to enable clinical-grade ambulatory health monitoring outside the clinic. Technological advances have enabled development of devices that can measure vital signs with great precision and significant progress has been made towards extracting clinically meaningful information from these devices in research studies. However, translating measurement accuracies achieved in the controlled settings such as the lab and clinic to unconstrained environments such as the home remains a challenge. In this paper, we present a novel wearable computing platform for unobtrusive collection of labeled datasets and a new paradigm for continuous development, deployment and evaluation of machine learning models to ensure robust model performance as we transition from the lab to home. Using this system, we train activity classification models across two studies and track changes in model performance as we go from constrained to unconstrained settings.

Tectorial Membrane Traveling Waves Underlie Impaired Hearing in Tectb Mutant Mice

We show that the Tectb mutation reduces the spatial extent and propagation velocity of tectorial membrane (TM) traveling waves. These results can account for all of the hearing abnormalities associated with the Tectb mutation, as follows. By reducing the spatial extent of TM waves, the Tectb mutation decreases spread of excitation and thereby increases frequency selectivity at mid‐ to high frequencies. Furthermore, the decrease in Tectb TM wave velocity at low frequencies reduces the number of hair cells that effectively couple energy to the basilar membrane, which thereby reduces sensitivity.