Wearable systems could offer noninvasive and real-time solutions for monitoring of biomarkers in human sweat as an alternative to blood testing. Recent studies have demonstrated that the concentration of certain biomarkers in sweat can be directly correlated to their concentrations in blood, making sweat a trusted biofluid candidate for noninvasive diagnostics. We introduce a fully on-chip integrated wearable sweat sensing system to track biochemical information at the surface of the skin in real time. This system heterogeneously integrates, on a single silicon chip, state-of-the-art ultrathin body (UTB) fully depleted silicon-on-insulator (FD-SOI) ISFET sensors with a biocompatible microfluidic interface, to deliver a “lab-on-skin” sensing platform. A full process for the fabrication of this system is proposed in this work and is demonstrated by standard semiconductor fabrication procedures. The system is capable of collecting small volumes of sweat from the skin of a human and posteriorly passively driving the biofluid, by capillary action, to a set of functionalized ISFETs for analysis of pH level and Na+ and K+ concentrations. Drop-casted ion-sensing membranes on different sets of sensors on the same substrate enable multiparameter analysis on the same chip, with small and controlled cross-sensitivities, whereas a miniaturized quasireference electrodes set a stable analyte potential, avoiding the use of a cumbersome external reference electrode. The progress of lab-on-skin technology reported here can lead to autonomous wearable systems enabling real-time continuous monitoring of sweat composition, with applications ranging from medicine to lifestyle behavioral engineering and sports.

Ion sensitive field effect transistors (ISFETs) form a very attractive solution for wearable sensors due to their capacity for ultra-miniaturization, low power operation, and very high sensitivity, supported by complementary metal oxide semiconductor (CMOS) integration. This paper reports for the first time, a multianalyte sensing platform that incorporates high performance, high yield, high robustness, three-dimensional-extended-metal-gate ISFETs (3D-EMG-ISFETs) realized by the postprocessing of a conventional 0.18 μm CMOS technology node. The detection of four analytes (pH, Na+, K+, and Ca2+) is reported with excellent sensitivities (58 mV/pH, −57 mV/dec­(Na+), −48 mV/dec­(K+), and −26 mV/dec­(Ca2+)) close to the Nernstian limit, and high selectivity, achieved by the use of highly selective ion selective membranes based on postprocessing integration steps aimed at eliminating any significant sensor hysteresis and parasitics. We are reporting simultaneous time-dependent recording of multiple analytes, with high selectivities. In vitro real sweat tests are carried out to prove the validity of our sensors. The reported sensors have the lowest reported power consumption, being capable of operation down to 2 pW/sensor. Due to the ultralow power consumption of our ISFETs, we achieve and report a final four-analyte passive system demonstrator including the readout interface and the remote powering of the ISFET sensors, all powered by an radio frequency (RF) signal.

Active control of ion transport plays important roles in chemical and biological analytical processes. Nanofluidic systems hold the promise for such control through electrostatic interaction between ions and channel surfaces. Most existing experiments rely on planar geometry where the nanochannels are generally very long and shallow with large aspect ratios. Based on this configuration the concepts of nanofluidic gating and rectification have been successfully demonstrated. However, device minimization and throughput scaling remain significant challenges. We report here an innovative and facile realization of hetero-structured Al(2)O(3)/SiO(2) (Si) nanopore array membranes by using pattern transfer of self-organized nanopore structures of anodic aluminum oxide (AAO). Thanks to the opposite surface charge states of Al(2)O(3) (positive) and SiO(2) (negative), the membrane exhibits clear rectification of ion current in electrolyte solutions with very low aspect ratios compared to previous approaches. Our hetero-structured nanopore arrays provide a valuable platform for high throughput applications such as molecular separation, chemical processors and energy conversion.

We developed Al2O3/W heterogeneous nanopore arrays for field effect modulated nanofluidic diodes. They are fabricated by transferring self-organized nanopores of anodic aluminium oxide into a W thin film. The nanopores are ∼20 nm in diameter and 400 nm in length. After mild oxidation, approximately 10 nm WO3 grows on the surface of W, forming a conformal and dense dielectric layer. It allows the application of an electrical field through the surrounding W electrode to modulate the ionic transport across the entire membrane. Our experimental findings have potential applications in high throughput controlled delivery and electrostatic sorting of biomolecules.

This paper reports a novel fully integrated low power multi-sensing smart system, which, by wafer-level 3D heterogeneous integration of Ion Sensitive Fully Depleted (FD) FETs and SU-8 micro/nanofludics, achieves the first of its kind wearable multi-sensing system, called Lab on Skin TM , capable to detect biomarkers in human sweat. In the reported configuration, the multi-sensing system exploits arrays of functionalized sensors capable to simultaneously detect pH, Na + and K + concentrations in sweat in real time. We present a detailed electrical DC and dynamic characterization, showing excellent sensitivities (52mV/dec for pH and-37mV/dec for Na + sensors) with ultra-low power consumption (less than 50 nWatts/sensor). We report ion cross-sensitivities and a differential measurement approach that allows calibrated measurements. Overall, the paper reports significant advances in the design and fabrication of micro/nanofludics channels, inlets compatible with human skin pore size and density, and outlet passive pumps with flow rates of tens of pl/s; all capable of exploiting capillary forces in order to provide a zero energy pumping of sweat into sensing channels. Moreover, we report the first integration of a miniaturized Ag/AgCl Quasi-Reference Electrodes (QRE) into the sensing system, with long term stability, paving the way for fully wearable electronic chips in flexible patches or as plug-in modules in wrist based devices. I. INTRODUCTION AND RATIONALE Wearable biosensors [1-2] hold promise for playing a significant role in future personalized and preventive healthcare as they enable non-invasive and real time monitoring of a large variety of biomarkers in human biofluids. They add significant value to activity monitoring, which is tracked by MEMS sensor technology (accelerometers and gyroscopes), and, to other biosignals (such as heart rate and blood oxygenation). Moreover, sweat is easily accessible via the largest human organ, the skin, and can take advantage of patch and wrist-based device embodiments. Previous reports on the detection of biomarkers in sweat were based on large electrochemical sensors [3-4] requiring large amounts of sweat, which limits the field of applications to sport with abundant sweating or requires pilocarpine-induced cholinergic sweating, which is not user friendly and can even modify the physiological composition of sweat. A recent comprehensive review [5] reported that there are hundreds of biomarkers that can be tracked in human sweat and, for some, the correlations with the concentrations of same