Joshua Ray Windmiller

Electrochemical tattoo biosensors for real-time noninvasive lactate monitoring in human perspiration.

The present work describes the first example of real-time noninvasive lactate sensing in human perspiration during exercise events using a flexible printed temporary-transfer tattoo electrochemical biosensor that conforms to the wearers skin. The new skin-worn enzymatic biosensor exhibits chemical selectivity toward lactate with linearity up to 20 mM and demonstrates resiliency against continuous mechanical deformation expected from epidermal wear. The device was applied successfully to human subjects for real-time continuous monitoring of sweat lactate dynamics during prolonged cycling exercise. The resulting temporal lactate profiles reflect changes in the production of sweat lactate upon varying the exercise intensity. Such skin-worn metabolite biosensors could lead to useful insights into physical performance and overall physiological status, hence offering considerable promise for diverse sport, military, and biomedical applications.

Epidermal tattoo potentiometric sodium sensors with wireless signal transduction for continuous non-invasive sweat monitoring

This article describes the fabrication, characterization and application of an epidermal temporary-transfer tattoo-based potentiometric sensor, coupled with a miniaturized wearable wireless transceiver, for real-time monitoring of sodium in the human perspiration. Sodium excreted during perspiration is an excellent marker for electrolyte imbalance and provides valuable information regarding an individuals physical and mental wellbeing. The realization of the new skin-worn non-invasive tattoo-like sensing device has been realized by amalgamating several state-of-the-art thick film, laser printing, solid-state potentiometry, fluidics and wireless technologies. The resulting tattoo-based potentiometric sodium sensor displays a rapid near-Nernstian response with negligible carryover effects, and good resiliency against various mechanical deformations experienced by the human epidermis. On-body testing of the tattoo sensor coupled to a wireless transceiver during exercise activity demonstrated its ability to continuously monitor sweat sodium dynamics. The real-time sweat sodium concentration was transmitted wirelessly via a body-worn transceiver from the sodium tattoo sensor to a notebook while the subjects perspired on a stationary cycle. The favorable analytical performance along with the wearable nature of the wireless transceiver makes the new epidermal potentiometric sensing system attractive for continuous monitoring the sodium dynamics in human perspiration during diverse activities relevant to the healthcare, fitness, military, healthcare and skin-care domains.

Epidermal Biofuel Cells: Energy Harvesting from Human Perspiration†

The healthcare industry has recently experienced a major paradigm shift towards wearable biomedical devices. Such devices have the ability to monitor vital physiological parameters, such as heart rate or blood pressure. Particular recent attention has been directed towards skin-worn electronic devices fabricated by novel hybrid techniques for the measurement of these vital signs. Despite dramatic technological advances, further progress in the arena of on-body biomedical devices has been hindered by the lack of effective wearable power sources able to scavenge sufficient energy from the wearer. Major efforts have thus been directed towards the identification of a suitable wearable power source that offers conformal integration with the wearer s body. This activity has resulted in the development of flexible thin-film batteries, piezoelectric nanogenerators, wearable solar cells, mircosupercapacitors, and endocochlear-potential-based biobatteries. Nevertheless, new body-worn conformal power sources able to extract biochemical energy from the wearer s body (and his/her epidermis, in particular) are still highly desired. Herein we demonstrate the ability to generate substantial levels of electrical power from human perspiration in a noninvasive and continuous fashion through the use of epidermal biofuel cells based on temporary transfer tattoos (tBFCs). Enzymatic BFCs have attracted considerable interest owing to their ability to generate power from the bioelectrocatalytic reaction of common chemicals and metabolites, such as glucose and alcohol, under physiological conditions. Recent efforts resulted in implantable glucose BFCs that can generate significant power densities in small animals, such as snails, insects, and rats. However, there are no reports on harvesting the chemical energy from a human in connection with the rapidly developing field of wearable electronics. The successful development of non-invasive tBFCs requires the judicious integration of new manufacturing processes and advanced surface functionalization for efficient power generation from lactate present in the wearer s perspiration. The development of the tBFC builds on our recent introduction of epidermal electrochemical sensors. The two electrode constituents of the new wearable tBFC were designed in the shape of “UC” (acronym for “University of California”; Figure 1; see Figure S1 in the Supporting

Wearable electrochemical sensors for in situ analysis in marine environments

The development of wearable screen-printed electrochemical sensors on underwater garments comprised of the synthetic rubber neoprene is reported. These wearable sensors are able to determine the presence of environmental pollutants and security threats in marine environments. Owing to its unique elastic and superhydrophobic morphology, neoprene is an attractive substrate for thick-film electrochemical sensors for aquatic environments and offers high-resolution printing with no apparent defects. The neoprene-based sensor was evaluated for the voltammetric detection of trace heavy metal contaminants and nitroaromatic explosives in seawater samples. We also describe the first example of enzyme (tyrosinase) immobilization on a wearable substrate towards the amperometric biosensing of phenolic contaminants in seawater. Furthermore, the integration of a miniaturized potentiostat directly on the underwater garment is demonstrated. The wearable sensor-potentiostat microsystem provides a visual indication and alert if the levels of harmful contaminants have exceeded a pre-defined threshold. The concept discussed here is well-suited for integration into dry- and wetsuits worn by divers and recreational surfers/swimmers, thereby providing them with the ability to continuously assess their surroundings for environmental contaminants and security hazards.

Enzyme logic gates for the digital analysis of physiological level upon injury.

A biocomputing system composed of a combination of AND/IDENTITY logic gates based on the concerted operation of three enzymes: lactate oxidase, horseradish peroxidase and glucose dehydrogenase was designed to process biochemical information related to pathophysiological conditions originating from various injuries. Three biochemical markers: lactate, norepinephrine and glucose were applied as input signals to activate the enzyme logic system. Physiologically normal concentrations of the markers were selected as logic 0 values of the input signals, while their abnormally increased concentrations, indicative of various injury conditions were defined as logic 1 input. Biochemical processing of different patterns of the biomarkers resulted in the formation of norepiquinone and NADH defined as the output signals. Optical and electrochemical means were used to follow the formation of the output signals for eight different combinations of three input signals. The enzymatically processed biochemical information presented in the form of a logic truth table allowed distinguishing the difference between normal physiological conditions, pathophysiological conditions corresponding to traumatic brain injury and hemorrhagic shock, and abnormal situations (not corresponding to injury). The developed system represents a biocomputing logic system applied for the analysis of biomedical conditions related to various injuries. We anticipate that such biochemical logic gates will facilitate decision-making in connection to an integrated therapeutic feedback-loop system and hence will revolutionize the monitoring and treatment of injured civilians and soldiers.

Microneedle array-based carbon paste amperometric sensors and biosensors

The design and characterization of a microneedle array-based carbon paste electrode towards minimally invasive electrochemical sensing are described. Arrays consisting of 3 × 3 pyramidal microneedle structures, each with an opening of 425 µm, were loaded with a metallized carbon paste transducer. The renewable nature of carbon paste electrodes enables the convenient packing of hollow non-planar microneedles with pastes that contain assorted catalysts and biocatalysts. Smoothing the surface results in good microelectrode-to-microelectrode uniformity. Optical and scanning electron micrographs shed useful insights into the surface morphology at the microneedle apertures. The attractive performance of the novel microneedle electrode arrays is illustrated in vitro for the low-potential detection of hydrogen peroxide at rhodium-dispersed carbon paste microneedles and for lactate biosensing by the inclusion of lactate oxidase in the metallized carbon paste matrix. Highly repeatable sensing is observed following consecutive cycles of packing/unpacking the carbon paste. The operational stability of the array is demonstrated as well as the interference-free detection of lactate in the presence of physiologically relevant levels of ascorbic acid, uric acid, and acetaminophen. Upon addressing the biofouling effects associated with on-body sensing, the microneedle carbon paste platform would be attractive for the subcutaneous electrochemical monitoring of a number of physiologically relevant analytes.

Enzymatic AND Logic Gates Operated Under Conditions Characteristic of Biomedical Applications

Experimental and theoretical analyses of the lactate dehydrogenase and glutathione reductase based enzymatic AND logic gates in which the enzymes and their substrates serve as logic inputs are performed. These two systems are examples of the novel, previously unexplored class of biochemical logic gates that illustrate potential biomedical applications of biochemical logic. They are characterized by input concentrations at logic 0 and 1 states corresponding to normal and pathophysiological conditions. Our analysis shows that the logic gates under investigation have similar noise characteristics. Both significantly amplify random noise present in inputs; however, we establish that for realistic widths of the input noise distributions, it is still possible to differentiate between the logic 0 and 1 states of the output. This indicates that reliable detection of pathophysiological conditions is indeed possible with such enzyme logic systems.

155-nm Continuous-Wave Two-Pump Parametric Amplification

We investigate the synthesis of flat parametric response of a dual-pumped device with a distant pump separation ranging from 130 to 180 nm. The Raman contribution to the nonlinear polarization introduced predictable gain ripple and dispersion fluctuation along the highly nonlinear fiber had to be precisely accounted for. A 3-dB equalized gain was observed over 100 nm using 130-nm separated pumps. Record gain bandwidth of 155 nm was also measured for the first time.

730-nm optical parametric conversion from near- to short-wave infrared band

A record 730 nm parametric conversion in silica fiber from the near-infrared to the short-wave infrared band is reported and analyzed. A parametric gain in excess of 30 dB was measured for a signal at 1300 nm (with corresponding idler at 2030 nm). This conversion was performed in a travelling single-pass one-pump parametric architecture and high efficiency is achieved by a combination of high peak power and a nonlinear fiber with a reduced fourth-order dispersion coefficient.

Multiplexed and Switchable Release of Distinct Fluids from Microneedle Platforms via Conducting Polymer Nanoactuators for Potential Drug Delivery.

We report on the development of a microneedle-based multiplexed drug delivery actuator that enables the controlled delivery of multiple therapeutic agents. Two individually-addressable channels on a single microneedle array, each paired with its own reservoir and conducting polymer nanoactuator, are used to deliver various permutations of two unique chemical species. Upon application of suitable redox potentials to the selected actuator, the conducting polymer is able to undergo reversible volume changes, thereby serving to release a model chemical agent in a controlled fashion through the corresponding microneedle channels. Time-lapse videos offer direct visualization and characterization of the membrane switching capability and, along with calibration investigations, confirm the ability of the device to alternate the delivery of multiple reagents from individual microneedles of the array with higher precision and temporal resolution than conventional drug delivery actuators. Analytical modeling offers prediction of the volumetric flow rate through a single microneedle and accordingly can be used to assist in the design of subsequent microneedle arrays. The robust solid-state design and lack of mechanical components circumvent reliability issues that challenge fragile conventional microelectromechanical drug delivery devices. This proof-of-concept study demonstrates the potential of the drug delivery actuator system to aid in the rapid administration of multiple therapeutic agents and indicates the potential to counteract diverse biomedical conditions.