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In this paper we demonstrate a wearable tattoobased alcohol biosensing system for noninvasive alcohol monitoring in induced sweat. The skin-worn alcohol monitoring platform integrates an iontophoretic-biosensing temporary tattoo system along with flexible wireless electronics. The wearable prototype enables the transdermal delivery of the pilocarpine drug to induce sweat via iontophoresis and amperometric detection of ethanol in the generated sweat using the alcohol-oxidase enzyme and the Prussian Blue electrode transducer. The new skin-compliant biosensor displays a highly selective and sensitive response to ethanol. On-body results with human subjects show distinct differences in the current response before and after alcohol consumption, reflecting the increase of ethanol levels. The skin-worn alcohol sensor is coupled with a flexible electronics board, which controls the iontophoresis/amperometry operation and transmits data wirelessly in real time via Bluetooth communication. The new wireless epidermal iontophoretic-biosensing system offers considerable promise for noninvasive monitoring of alcohol consumption in practical settings and can be readily expanded toward the monitoring of additional analytes.

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.

The development of wearable biosensors for continuous noninvasive monitoring of target biomarkers is limited to assays of a single sampled biofluid. An example of simultaneous noninvasive sampling and analysis of two different biofluids using a single wearable epidermal platform is demonstrated here. The concept is successfully realized through sweat stimulation (via transdermal pilocarpine delivery) at an anode, alongside extraction of interstitial fluid (ISF) at a cathode. The system thus allows on‐demand, controlled sampling of the two epidermal biofluids at the same time, at two physically separate locations (on the same flexible platform) containing different electrochemical biosensors for monitoring the corresponding biomarkers. Such a dual biofluid sampling and analysis concept is implemented using a cost‐effective screen‐printing technique with body‐compliant temporary tattoo materials and conformal wireless readout circuits to enable real‐time measurement of biomarkers in the sampled epidermal biofluids. The performance of the developed wearable device is demonstrated by measuring sweat‐alcohol and ISF‐glucose in human subjects consuming food and alcoholic drinks. The different compositions of sweat and ISF with good correlations of their chemical constituents to their blood levels make the developed platform extremely attractive for enhancing the power and scope of next‐generation noninvasive epidermal biosensing systems.

Oncosomes have recently been described as membranederived microvesicles secreted by cancer cells, which transfer oncogenic signals and protein complexes across cell boundaries. Here, we show the rapid formation and secretion of oncosomes from DU145 and LNCaP human prostate cancer cells. Oncosome formation was stimulated by epidermal growth factor receptor activation and also by overexpression of membrane-targeted Akt1. Microvesicles shed from prostate cancer cells contained numerous signal transduction proteins and were capable of activating rapid phospho-tyrosine and Akt pathway signaling, and stimulating proliferation and migration, in recipient tumor cells. They also induced a stromal reaction in recipient normal cells. Knockdown of the actin nucleating protein Diaphanous Related Formin 3 (DRF3/ Dia2) by RNA interference enhanced rates of oncosome formation, indicating that these structures resemble, and may be identical to, nonapoptotic membrane blebs, a feature of the amoeboid form of cell motility. Analysis of primary and metastatic human prostate tumors using 100K single nucleotide polymorphism arrays revealed a significantly higher frequency of deletion of the locus encoding DRF3 (DIAPH3) in metastatic tumors (P = 0.001) in comparison with organconfined tumors. Fluorescence in situ hybridization confirmed increased chromosomal loss of DIAPH3 in metastatic tumors in a different cohort of patients (P = 0.006). These data suggest that microvesicles shed from prostate cancer cells can alter the tumor microenvironment in a manner that may promote disease progression. They also show that DRF3 is a physiologically relevant protein that seems to regulate this process. [Cancer Res 2009;69(13):5601-9]