A Wearable System for Continuous Monitoring and Assessment of Speech, Gait, and Cognitive Decline for Early Diagnosis of ADRD.

Early detection of cognitive decline is essential to study mild cognitive impairment and Alzheimer's Disease in order to develop targeted interventions and prevent or stop the progression of dementia. This requires continuous and longitudinal assessment and tracking of the related physiological and behavioral changes during daily life. In this paper, we present a low cost and low power wearable system custom designed to track the trends in speech, gait, and cognitive stress while also considering the important human factor needs such as privacy and compliance. In the form factors of a wristband and waist-patch, this multimodal, multi-sensor system measures inertial signals, sound, heart rate, electrodermal activity and pulse transit time. A total power consumption of 2.6 mW without any duty cycling allows for more than 3 weeks of run time between charges when 1500 mAh batteries are used.Clinical Relevance- Much earlier detection of Alzheimer's disease and related dementias may be possible by continuous monitoring of physiological and behavioral state using application specific wearable sensors during the activities of daily life.

Mobile health: the power of wearables, sensors, and apps to transform clinical trials.

Mobile technology has become a ubiquitous part of everyday life, and the practical utility of mobile devices for improving human health is only now being realized. Wireless medical sensors, or mobile biosensors, are one such technology that is allowing the accumulation of real-time biometric data that may hold valuable clues for treating even some of the most devastating human diseases. From wearable gadgets to sophisticated implantable medical devices, the information retrieved from mobile technology has the potential to revolutionize how clinical research is conducted and how disease therapies are delivered in the coming years. Encompassing the fields of science and engineering, analytics, health care, business, and government, this report explores the promise that wearable biosensors, along with integrated mobile apps, hold for improving the quality of patient care and clinical outcomes. The discussion focuses on groundbreaking device innovation, data optimization and validation, commercial platform integration, clinical implementation and regulation, and the broad societal implications of using mobile health technologies.

Low-Power Wearable Systems for Continuous Monitoring of Environment and Health for Chronic Respiratory Disease.

We present our efforts toward enabling a wearable sensor system that allows for the correlation of individual environmental exposures with physiologic and subsequent adverse health responses. This system will permit a better understanding of the impact of increased ozone levels and other pollutants on chronic asthma conditions. We discuss the inefficiency of existing commercial off-the-shelf components to achieve continuous monitoring and our system-level and nano-enabled efforts toward improving the wearability and power consumption. Our system consists of a wristband, a chest patch, and a handheld spirometer. We describe our preliminary efforts to achieve a submilliwatt system ultimately powered by the energy harvested from thermal radiation and motion of the body with the primary contributions being an ultralow-power ozone sensor, an volatile organic compounds sensor, spirometer, and the integration of these and other sensors in a multimodal sensing platform. The measured environmental parameters include ambient ozone concentration, temperature, and relative humidity. Our array of sensors also assesses heart rate via photoplethysmography and electrocardiography, respiratory rate via photoplethysmography, skin impedance, three-axis acceleration, wheezing via a microphone, and expiratory airflow. The sensors on the wristband, chest patch, and spirometer consume 0.83, 0.96, and 0.01 mW, respectively. The data from each sensor are continually streamed to a peripheral data aggregation device and are subsequently transferred to a dedicated server for cloud storage. Future work includes reducing the power consumption of the system-on-chip including radio to reduce the entirety of each described system in the submilliwatt range.

Molecular sentinel-on-chip for SERS-based biosensing.

The development of DNA detection techniques on large-area plasmonics-active platforms is critical for many medical applications such as high-throughput screening, medical diagnosis and systems biology research. Here, we report for the first time a unique "molecular sentinel-on-chip" (MSC) technology for surface-enhanced Raman scattering (SERS)-based DNA detection. This unique approach allows label-free detection of DNA molecules on chips developed on a wafer scale using large area nanofabrication methodologies. To develop plasmonics-active biosensing platforms in a repeatable and reproducible manner, we employed a combination of deep UV lithography, atomic layer deposition, and metal deposition to fabricate triangular-shaped nanowire (TSNW) arrays having controlled sub-10 nm gap nanostructures over an entire 6 inch wafer. The detection of a DNA sequence of the Ki-67 gene, a critical breast cancer biomarker, on the TSNW substrate illustrates the usefulness and potential of the MSC technology as a novel SERS-based DNA detection method.

Plasmonic Nanoparticles and Nanowires: Design, Fabrication and Application in Sensing.

This study involves two aspects of our investigations of plasmonics-active systems: (i) theoretical and simulation studies and (ii) experimental fabrication of plasmonics-active nanostructures. Two types of nanostructures are selected as the model systems for their unique plasmonics properties: (1) nanoparticles and (2) nanowires on substrate. Special focus is devoted to regions where the electromagnetic field is strongly concentrated by the metallic nanostructures or between nanostructures. The theoretical investigations deal with dimers of nanoparticles and nanoshells using a semi-analytical method based on a multipole expansion (ME) and the finite-element method (FEM) in order to determine the electromagnetic enhancement, especially at the interface areas of two adjacent nanoparticles. The experimental study involves the design of plasmonics-active nanowire arrays on substrates that can provide efficient electromagnetic enhancement in regions around and between the nanostructures. Fabrication of these nanowire structures over large chip-scale areas (from a few millimeters to a few centimeters) as well as FDTD simulations to estimate the EM fields between the nanowires are described. The application of these nanowire chips using surface-enhanced Raman scattering (SERS) for detection of chemicals and labeled DNA molecules is described to illustrate the potential of the plasmonics chips for sensing.

Large area nanorings fabricated using an atomic layer deposition Al(2)O(3) spacer for magnetic random access memory application.

We have designed a novel atomic layer deposition (ALD) Al(2)O(3) spacer mask technique for fabricating large area high density nanoscale magnetic rings by photolithography for magnetic random access memory applications. A simple mask design and a low temperature ALD process were utilized to simplify the process. Dry etching of Al(2)O(3) and cobalt was investigated for optimizing the nanostructure dimension control. A ring array with density and dimensions below the limits for photolithography tools has been achieved. The magnetic behavior of the ring array was characterized using a SQUID (superconducting quantum interference device). The switching distribution and effects of interaction among ring arrays were studied by correlating simulation with experimental results.

Redox-active monolayers on nano-scale silicon electrodes.

Uniform arrays of nano-scale electrolyte-molecule-silicon capacitors have been successfully fabricated. This was done by a combination of reactive ion etch and a selective wet etch through an anodic aluminium oxide mask to form nano-holes in silicon oxide/silicon nitride insulator layers on silicon. Self-assembled monolayers of 4-ferrocenylbenzyl alcohol were then attached to the exposed silicon surfaces at the bottom of the nano-holes. Characterization by conventional capacitance and conductance techniques showed very high capacitance and conductance peaks near -0.6 V, that were attributed to the charging and discharging of electrons into and from discrete levels in the monolayer owing to the presence of the redox-active ferrocenes.

Porphyrin architectures tailored for studies of molecular information storage.

A molecular approach to information storage employs redox-active molecules tethered to an electroactive surface. Zinc porphyrins tethered to Au(111) or Si(100) provide a benchmark for studies of information storage. Three sets of porphyrins have been synthesized for studies of the interplay of molecular design and charge-storage properties: (1) A set of porphyrins is described for probing the effect of surface attachment atom on electron-transfer kinetics. Each porphyrin bears a meso-CH2X group for surface attachment where X = OH, SAc, or SeAc. (2) A set of porphyrins is described for studying the effect of surface-charge density in monolayers. Each porphyrin bears a benzyl alcohol for surface attachment and three nonlinking meso substituents of a controlled degree of bulkiness. (3) A set of porphyrins is described that enables investigation of on-chip patterning of the electrolyte. Each porphyrin bears a formyl group distal to the surface attachment group for subsequent derivatization with a molecular entity that comprises the electrolyte. Taken together, this collection of molecules enables a variety of studies to elucidate design issues in molecular-based information storage.

Synthesis of porphyrins bearing hydrocarbon tethers and facile covalent attachment to si(100).

The use of redox-active molecules as the active storage elements in memory chips requires the ability to attach the molecules to an electroactive surface in a reliable and robust manner. To explore the use of porphyrins tethered to silicon via carbosilane linkages, 17 porphyrins have been synthesized. Fourteen porphyrins bear a tether at a single meso site, and three porphyrins bear functional groups at two beta sites for possible two-point attachment. Two high-temperature processing methods (400 degrees C under inert atmosphere) have been developed for rapid (minutes), facile covalent attachment to Si platforms. The high-temperature processing conditions afford attachment either by direct deposition of a dilute solution (1 microM-1 mM) of the porphyrin sample onto the Si substrate or sublimation of a neat sample onto the Si substrate. The availability of this diverse collection of porphyrins enables an in-depth examination of the effects of the tether (length, composition, terminal functional group, number of tethers) and steric bulk of nonlinking substituents on the information-storage properties of the porphyrin monolayers obtained upon attachment to silicon. Attachment proceeds readily with a wide variety of hydrocarbon tethers, including 2-(trimethylsilyl)ethynyl, vinyl, allyl, or 3-butenyl directly appended to the porphyrin and iodo, bromomethyl, 2-(trimethylsilyl)ethynyl, ethynyl, vinyl, or allyl appended to the 4-position of a meso-phenyl ring. No attachment occurs with substituents such as phenyl, p-tolyl, mesityl, or ethyl. Collectively, the studies show that the high-temperature attachment procedure (1) has broad scope encompassing diverse functional groups, (2) tolerates a variety of arene substituents, and (3) does not afford indiscriminate attachment. The high-temperature processing conditions are ideally suited for use in fabrication of hybrid molecular/semiconductor circuitry.

Porphyrins bearing arylphosphonic acid tethers for attachment to oxide surfaces.

Synthetic molecules bearing phosphonic acid groups can be readily attached to oxide surfaces. As part of a program in molecular-based information storage, we have developed routes for the synthesis of diverse porphyrinic compounds bearing phenylphosphonic acid tethers. The routes enable (1) incorporation of masked phosphonic acid groups in precursors for use in the rational synthesis of porphyrinic compounds and (2) derivatization of porphyrins with masked phosphonic acid groups. The precursors include dipyrromethanes, monoacyldipyrromethanes, and diacyldipyrromethanes. The tert-butyl group has been used to mask the dihydroxyphosphoryl substituent. The di-tert-butyloxyphosphoryl unit is stable to the range of conditions employed in syntheses of porphyrins and multiporphyrin arrays yet can be deprotected under mild conditions (TMS-Cl/TEA or TMS-Br/TEA in refluxing CHCl(3)) that do not cause demetalation of zinc or magnesium porphyrins. The porphyrinic compounds that have been prepared include (1) A(3)B-, trans-AB(2)C-, and ABCD-porphyrins that bear a single phenylphosphonic acid group, (2) a trans-A(2)B(2)-porphyrin bearing two phenylphosphonic acid groups, (3) a chlorin that bears a single phenylphosphonic acid group, and (4) a porphyrin dyad bearing a single phenylphosphonic acid group. For selected porphyrin-phosphonic acids, the electrochemical characteristics have been investigated for molecules tethered to SiO(2) surfaces grown on doped Si. The voltammetric behavior indicates that the porphyrin-phosphonic acids form robust, electrically well-behaved monolayers on the oxide surface.

Porphyrins bearing mono or tripodal benzylphosphonic acid tethers for attachment to oxide surfaces.

The ability to attach redox-active molecules to oxide surfaces in controlled architectures (distance, orientation, packing density) is essential for the design of a variety of molecular-based information storage devices. We describe the synthesis of a series of redox-active molecules wherein each molecule bears a benzylphosphonic acid tether. The redox-active molecules include zinc porphyrins, a cobalt porphyrin, and a ferrocene-zinc porphyrin. An analogous tripodal tether has been prepared that is based on a tris[4-(dihydroxyphosphorylmethyl)phenyl]-derivatized methane. A zinc porphyrin is linked to the methane vertex by a 1,4-phenylene unit. The tripodal systems are designed to improve monolayer stability and ensure vertical orientation of the redox-active porphyrin on the electroactive surface. For comparison purposes, a zinc porphyrin bearing a hexylphosphonic acid tether also has been prepared. The synthetic approaches for introduction of the phosphonic acid group include derivatization of a bromoalkyl porphyrin or use of a dimethyl or diethyl phosphonate substituted precursor in a porphyrin-forming reaction. The latter approach makes use of dipyrromethane building blocks bearing mono or tripodal dialkyl phosphonate groups. The zinc porphyrin-tripodal compound bearing benzylphosphonic acid legs tethered to a SiO(2) surface (grown on doped Si) was electrically well-behaved and exhibited characteristic porphyrin oxidation/reduction waves. Collectively, a variety of porphyrinic molecules can now be prepared with tethers of different length, composition, and structure (mono or tripodal) for studies of molecular-based information storage on oxide surfaces.