Stretchable bioelectronics for medical devices and systems

Advances in the microelectronics and telecommunications industries have driven important breakthroughs in medical technologies and health diagnostics over the past decade. However, there are fundamental gaps in size, sensing modalities and mechanical properties between the standard rigid electronics, employed in medical devices today, and the signals emitted by soft biological structures. Here, the author describes novel materials, mechanics, and designs for emerging classes of health monitoring systems and invasive medical devices, including soft wearable patches and flexible catheter-based systems. These emerging devices incorporate microfabricated arrays of sensors (e.g., dry electrodes, temperature sensors, and accelerometers), actuators (e.g., micro-LEDs, piezo-electric ribbons, pacing electrodes), and silicon nanomembrane semiconductors, configured in ultrathin, flexible formats for continuous monitoring, therapy delivery, and energy harvesting. Quantitative analyses of strain distributions and circuit performances under stress illustrate the ability of these systems to mechanically couple with moist soft biological tissues, in a way that is mechanically invisible to the target biological substrate and comfortable for the patient. As demonstrations of this technology, the author presents representative examples of flexible and stretchable systems for use in both noninvasive and minimally invasive applications, which leverage the same class of microfabricated circuits and flexible sensor arrays. The fabrication strategies and design concepts described in this discussion can be tailored to various biological substrates and geometries of interest, and thus have the potential to broadly bridge the gap that exists between rigid electronics and biology

Optimal Linear RGB-to-XYZ Mapping for Color Display Calibration

Color display calibration, in part, involves mapping input RGB values to corresponding output values in a standardized color space such as CIE XYZ. A linear model for RGB-to- XYZ mapping is based on a 3-by-3 linear transformation matrix T mapping data from (linearized) RGB to XYZ. Such a mapping is often determined by least squares regression on the difference between predicted and measured XYZ values. However, since displays are calibrated for viewing by human observers, it likely would be better to optimize relative to a perceptually uniform color space. Two new methods are proposed which optimize the total error relative to CIELAB or CIEDE2000. The first method uses weighted least squares with weights based on the rate of change of CIELAB coordinates as a function of change in XYZ. The second method uses Nedler-Mead nonlinear optimization to minimize directly in CIELAB or CIEDE200. Experiments based on calibrating 2 CRT monitors, 3 LCD monitors and 2 LCD projectors show significantly better results than the standard least squares calibration

The functional role of the mammalian tectorial membrane in the cochlear mechanics

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2008.Includes bibliographical references (p. 101-110).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 propagate along the basilar membrane (BM) and ultimately stimulate the mechano-sensory receptors. The tectorial membrane (TM) plays a key role in this stimulation 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 (1-20 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 (BF) 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. To test how TM waves may participate in cochlear function, we investigated waves in genetically modified mice lacking beta-tectorin, a glycoprotein found exclusively in the TM. Tectb-/- mutant mice were previously shown to exhibit significant loss of cochlear sensitivity at low frequencies and sharpened frequency tuning compared to wild types. We show that the spatial extent and propagation velocity of TM traveling waves are significantly reduced in Tectb-/- mice compared to wild types, consistent with the concept that there is a reduction in the spread of excitation via TM waves and less TM wave interaction with the BM traveling wave in Tectb-/- mice.(cont.) The differences in TM wave properties between mutants and wild types arise from changes to the mechanical properties of the TM; mutant TMs are significantly less stiff than wild type TMs are. 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, suggesting that TM waves are crucial for cochlear sensitivity and tuning.by Roozbeh Ghaffari.Ph.D

Porosity Controls Spread of Excitation in Tectorial Membrane Traveling Waves

Cochlear frequency selectivity plays a key role in our ability to understand speech, and is widely believed to be associated with cochlear amplification. However, genetic studies targeting the tectorial membrane (TM) have demonstrated both sharper and broader tuning with no obvious changes in hair bundle or somatic motility mechanisms. For example, cochlear tuning of Tectb[superscript –/–] mice is significantly sharper than that of Tecta[superscript Y1870C/+] mice, even though TM stiffnesses are similarly reduced relative to wild-type TMs. Here we show that differences in TM viscosity can account for these differences in tuning. In the basal cochlear turn, nanoscale pores of Tecta[superscript Y1870C/+] TMs are significantly larger than those of Tectb[superscript –/–] TMs. The larger pore size reduces shear viscosity (by ∼70%), thereby reducing traveling wave speed and increasing spread of excitation. These results demonstrate the previously unrecognized importance of TM porosity in cochlear and neural tuning.National Institutes of Health (U.S.) (Grant R01-DC00238)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374)National Institutes of Health (U.S.) (Training Grant

Col11a2 Deletion Reveals the Molecular Basis for Tectorial Membrane Mechanical Anisotropy

The tectorial membrane (TM) has a significantly larger stiffness in the radial direction than other directions, a prominent mechanical anisotropy that is believed to be critical for the proper functioning of the cochlea. To determine the molecular basis of this anisotropy, we measured material properties of TMs from mice with a targeted deletion of Col11a2, which encodes for collagen XI. In light micrographs, the density of TM radial collagen fibers was lower in Col11a2 –/– mice than wild-types. Tone-evoked distortion product otoacoustic emission and auditory brainstem response measurements in Col11a2 –/– mice were reduced by 30–50 dB independent of frequency as compared with wild-types, showing that the sensitivity loss is cochlear in origin. Stress-strain measurements made using osmotic pressure revealed no significant dependence of TM bulk compressibility on the presence of collagen XI. Charge measurements made by placing the TM as an electrical conduit between two baths revealed no change in the density of charge affixed to the TM matrix in Col11a2 –/– mice. Measurements of mechanical shear impedance revealed a 5.5 ± 0.8 dB decrease in radial shear impedance and a 3.3 ± 0.3 dB decrease in longitudinal shear impedance resulting from the Col11a2 deletion. The ratio of radial to longitudinal shear impedance fell from 1.8 ± 0.7 for TMs from wild-type mice to 1.0 ± 0.1 for those from Col11a2 –/– mice. These results show that the organization of collagen into radial fibrils is responsible for the mechanical anisotropy of the TM. This anisotropy can be attributed to increased mechanical coupling provided by the collagen fibrils. Mechanisms by which changes in TM material properties may contribute to the threshold elevation in Col11a2 –/– mice are discussed.National Institutes of Health (U.S.) (Grant R01-DC00238

An endoscope with integrated transparent bioelectronics and theranostic nanoparticles for colon cancer treatment

The gastrointestinal tract is a challenging anatomical target for diagnostic and therapeutic procedures for bleeding, polyps and cancerous growths. Advanced endoscopes that combine imaging and therapies within the gastrointestinal tract provide an advantage over stand-alone diagnostic or therapeutic devices. However, current multimodal endoscopes lack the spatial resolution necessary to detect and treat small cancers and other abnormalities. Here we present a multifunctional endoscope-based interventional system that integrates transparent bioelectronics with theranostic nanoparticles, which are photoactivated within highly localized space near tumours or benign growths. These advanced electronics and nanoparticles collectively enable optical fluorescence-based mapping, electrical impedance and pH sensing, contact/temperature monitoring, radio frequency ablation and localized photo/chemotherapy, as the basis of a closed-loop solution for colon cancer treatment. In vitro, ex vivo and in vivo experiments highlight the utility of this technology for accurate detection, delineation and rapid targeted therapy of colon cancer or precancerous lesions.

Motion microscopy for visualizing and quantifying small motions

Although the human visual system is remarkable at perceiving and interpreting motions, it has limited sensitivity, and we cannot see motions that are smaller than some threshold. Although difficult to visualize, tiny motions below this threshold are important and can reveal physical mechanisms, or be precursors to large motions in the case of mechanical failure. Here, we present a “motion microscope,” a computational tool that quantifies tiny motions in videos and then visualizes them by producing a new video in which the motions are made large enough to see. Three scientific visualizations are shown, spanning macroscopic to nanoscopic length scales. They are the resonant vibrations of a bridge demonstrating simultaneous spatial and temporal modal analysis, micrometer vibrations of a metamaterial demonstrating wave propagation through an elastic matrix with embedded resonating units, and nanometer motions of an extracellular tissue found in the inner ear demonstrating a mechanism of frequency separation in hearing. In these instances, the motion microscope uncovers hidden dynamics over a variety of length scales, leading to the discovery of previously unknown phenomena

Can mHealth Technology Help Mitigate the Effects of the COVID-19 Pandemic?

n/

Snake contours in three-dimensions from colour stereo image pairs

Snakes (active contour models) are extended to segment regions of interest on the surface of 3D objects. Stereo images taken with calibrated cameras are used as input. For this method the depth map for the whole image does not need to be computed. Instead, 3D external forces are designed to keep the contour on the surface of the object while moving it toward the desired boundaries. Color information is used to improve the ability of snakes in detecting the boundaries, in contrast to the majority of previous methods which are based on intensity information alone. The proposed method produces 3D contours on the surface of the object with coordinates in physical units, e.g. millimeters. These contours can be used to view the structure and dimensions of any distinguishable region on the surface of an object. Examples include oral lesions and skin diseases. The whole process requires minimal human interaction; however, user input can be used to improve segmentation

Measuring the electrically induced motion response of the isolated mouse tectorial membrane

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.Includes bibliographical references (leaves 41-42).We discovered motion during application of AC voltage (0.8 V peak amplitude, f=1 kHz) on the surface of the isolated mouse tectorial membrane (TM). The TM's motion response, which contained an average peak amplitude of 4 nm (in 5 TM preparations) was measured using a novel atomic force sensing (AFS) technique (Rousso et al, 1997). A 2-D lateral mapping of motion at several points on the TM surface shows that the TM expands near the negative electrode and contracts near the positive electrode with a stationary pivot point between the two electrodes. Lowering the pH in the bath surrounding the TM from 7.3 to 4.07 decreased the maximum amplitude of displacement from 4 nm to approximately 2.5 nm while lowering the bath pH from 4.07 to 3.96 caused the TM to undergo a [pi] phase shift in its motion response. Based on this data, the TM has an isoelectric point and pKa near pH 4.011. This supports the model that the TM motion response is altered by the state of ionization of charge groups in the TM, which varies with bath pH.by Roozbeh Ghaffari.M.Eng