Gabriela Valdés-Ramírez

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.

Micromotor‐Based High‐Yielding Fast Oxidative Detoxification of Chemical Threats

Rapid field conversion of chemical weapons into non-toxic products is one of the most challenging tasks in weapons of mass destruction (WMD) science. This is particularly the case for eliminating stockpiles of chemical warfare agents (CWAs) in remote storage field locations, where the use of large quantities of decontaminating reagents, long reaction times, and controlled mechanical agitation is impossible or undesired. New efficient “clean” technologies and (bio)chemical processes are thus sought for detoxifying stored agents, counteracting nerve-agent attacks, and decommissioning chemical weapons. Environmentally friendly solutions of hydrogen peroxide, combined with suitable activators (e.g., bicarbonate), have been shown to be extremely useful for decontaminating a broad spectrum of CWAs to yield nontoxic products. These peroxide-based systems, which rely on the in situ generation of OOH nucleophiles, have recently replaced chlorine-based bleaching processes, which produce undesirable products, and have thus led to effective decontamination of the chemical agents GB (Sarin, isopropyl methylphosphonofluoridate), VX ((S)-[2-(diisopropylamino)ethyl] O-ethyl methylphosphonothioate), GD (Soman, pinacolyl methylphosphonofluoridate), and HD (sulfur mustard). Yet, such an oxidative treatment commonly requires high peroxide concentrations (20–30%; approaching a stoichiometry of 1:50), along with prolonged operation and/or mechanical agitation. Such reaction conditions are not suitable or not desired for eliminating stockpiles of CWAs in remote field settings or hostile storage locations, as large quantities of the reagents may not be transportable on military aircrafts and require special packaging and handling. The efficient elimination of chemical-weapon stockpiles in field locations thus remains a major challenge to the chemistry and defense communities. Herein, we describe a powerful strategy that is based on self-propelled micromotors, for a high-yielding accelerated oxidative decontamination of chemical threats using low peroxide levels and no external agitation. Functionalized synthetic micromotors have recently demonstrated remarkable capabilities in terms of isolation and transport for diverse biomedical and environmental applications, but not in connection to increasing the yield and speed of chemical reactions. The new motor-based method relies on the use of peroxide-driven microtubular engines for the efficient selfmixing of a remediation solution, which dramatically accelerates the decontamination process. Fluid mixing is extremely important for enhancing the yield and speed of a wide range of chemical processes, including decontamination reactions, where quiescent conditions lead to low reaction efficiency and long operations. The observed mixing, which is induced by the peroxide-driven micromotor, is analogous to that reported for the motility of E. coli bacteria, where a large-scale collective motion has been shown to enhance diffusion processes. Enhanced diffusion of passive tracers has also been observed in the presence of catalytic nanowire motors. Although the new micromotor strategy presented herein was applied to the accelerated, high-yielding, and simplified decontamination of organophosphate (OP) nerve agents, the concept could have broad implications for enhancing the efficiency and speed of a wide range of chemical processes in the absence of external agitation. The concept of the micromotor/peroxide-based decontamination of chemical threats is illustrated in Figure 1. This new strategy relies on micromotors without mechanical stirring (Figure 1A). A known number of micromotors were placed in a nerve-agent-contaminated solution, along with hydrogen peroxide (used as the oxidizing agent as well as the micromotor fuel), the peroxide activator (NaHCO3 or NaOH), and the surfactant sodium cholate (NaCh), which was essential for bubble generation. The oxidative conversion of the OP nerve agent into para-nitrophenol (p-NP) was achieved under mild quiescent conditions that involve the in situ generation of OOH nucleophiles with no external stirring (Figure 1B). The decrease in concentration of the OP [*] Dr. J. Orozco, G. Cheng, D. Vilela, Dr. S. Sattayasamitsathit, Prof. R. Vazquez-Duhalt, Dr. G. Vald s-Ram rez, Dr. O. S. Pak, Prof. J. Wang Departments of Nanoengineering and Mechanical Engineering University of California San Diego La Jolla, CA 92093 (USA) E-mail: josephwang@ucsd.edu G. Cheng, Prof. C. Kan Tsinghua University, Beijing, 100084 (China) D. Vilela, Prof. A. Escarpa University of Alcal 28871 Alcal de Henares (Spain)

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.

Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics

This article demonstrates an instrumented mouthguard capable of non-invasively monitoring salivary uric acid (SUA) levels. The enzyme (uricase)-modified screen printed electrode system has been integrated onto a mouthguard platform along with anatomically-miniaturized instrumentation electronics featuring a potentiostat, microcontroller, and a Bluetooth Low Energy (BLE) transceiver. Unlike RFID-based biosensing systems, which require large proximal power sources, the developed platform enables real-time wireless transmission of the sensed information to standard smartphones, laptops, and other consumer electronics for on-demand processing, diagnostics, or storage. The mouthguard biosensor system offers high sensitivity, selectivity, and stability towards uric acid detection in human saliva, covering the concentration ranges for both healthy people and hyperuricemia patients. The new wireless mouthguard biosensor system is able to monitor SUA level in real-time and continuous fashion, and can be readily expanded to an array of sensors for different analytes to enable an attractive wearable monitoring system for diverse health and fitness applications.

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.

Efficient Biocatalytic Degradation of Pollutants by Enzyme-Releasing Self-Propelled Motors

The first example of a self-propelled tubular motor that releases an enzyme for the efficient biocatalytic degradation of chemical pollutants is demonstrated. How the motors are self-propelled by the Marangoni effect, involving simultaneous release of SDS surfactant and the enzyme remediation agent (laccase) in the polluted sample, is illustrated. The movement induces fluid convection and leads to the rapid dispersion of laccase into the contaminated solution and to a dramatically accelerated biocatalytic decontamination process. The greatly improved degradation efficiency, compared to quiescent solutions containing excess levels of the free enzyme, is illustrated for the efficient biocatalytic degradation of phenolic and azo-type pollutants. The high efficiency of the motor-based decontamination approach makes it extremely attractive for a wide-range of remediation processes in the environmental, defense and public health fields.

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.

Enzyme-based NAND gate for rapid electrochemical screening of traumatic brain injury in serum

We report on the development of a rapid enzyme logic gate-based electrochemical assay for the assessment of traumatic brain injury (TBI). The concept harnesses a biocatalytic cascade that emulates the functionality of a Boolean NAND gate in order to process relevant physiological parameters in the biochemical domain. The enzymatic backbone ensures that a high-fidelity diagnosis of traumatic brain injury can be tendered in a rapid fashion when the concentrations of key serum-based biomarkers reach pathological levels. The excitatory neurotransmitter glutamate and the enzyme lactate dehydrogenase were used here as clinically-relevant input TBI biomarkers, in connection to the low-potential detection of the NADH product in the presence of methylene green at a glassy carbon electrode. A systematic optimization of the gate and the entire protocol has resulted in the effective discrimination between the physiological and pathological logic levels. Owing to its robust design, the enzyme-based logic gate mitigates potential interferences from both physiological and electroactive sources and is able to perform direct measurements in human serum samples. Granted further detailed clinical validation, this proof-of-concept study demonstrates the potential of the electrochemical assay to aid in the rapid and decentralized diagnosis of TBI.