While sweat has been recognized as an interesting and easily accessible biofluid for non-invasive health monitoring, current lab-on-chip solutions require excessive sweat quantities to perform. That is, they either require the patient to sweat through exercise, or they must collect sweat and data over large skin areas.
That’s two issues the researchers at the École Polytechnique Fédérale de Lausanne (EPFL), incidentally also staff at Swiss startup Xsensio SA, focused on solving. In a paper titled “Three-Dimensional Integrated Ultra-Low-Volume Passive Microfluidics with Ion-Sensitive Field-Effect Transistors for Multiparameter Wearable Sweat Analyzers” published in the ACS Nano journal, the researchers detail the heterogeneous integration of ISFET sensors with a biocompatible microfluidic interface to enhance the collection of sweat, all on a single silicon chip less than one square centimetre.
It has been shown that biomarkers in sweat can be directly correlated to their concentrations in blood, hence the choice of sweat as an analyte. The prototype described in the paper was aimed at two biomarkers, sodium and potassium, useful to individuate hormonal changes which prelude ovulation but also to diagnose cystic fibrosis.
Ion-sensitive FETs (ISFETs) have no metallic gate, instead the gate oxide is directly exposed to a liquid environment and the gate electrode is replaced with a reference electrode (RE). Hence the potential at the silicon surface is a function of the RE bias and the influence of the ions or charged molecules inside the analyte.
The researchers first created n-type nanoribbon ISFETs on an ultrathin body fully depleted silicon-on-insulator (UTB FD SOI) substrate, with a thin layer of buried oxide, (30nm Si on 20nm BOx). This precaution ensured good electrostatic control by eliminating the parasitic capacitances and reducing the OFF state current by preventing the formation of parasitic current paths, the authors report. In total, 16 ISFETs were laid out in a 9.1×9.1mm chip, divided in four groups independently functionalized for sensing different biomarkers.
Key to feed these ISFETs with the right amount of analyte for operation, the researchers then stacked a microfluidic interface on top of the devices. Using biocompatible SU-8 resist, they designed an arborescent pattern of microchannels as narrow as 50µm wide and 25µm thick, able to enhance capillary forces and drag liquid droplets towards the sensors, on their path from a sweat collector area to a sweat outlet area.
While the sweat is gathered directly from the skin by an array of narrow inlets, the microfluidic channels end up in a honeycomb structure (defined by 80µm diameter hexagonal nanopillars) acting as a passive pump and a reservoir of liquid for the continuous flow of sweat over a long period. The nanopillars, explains the paper, change the capillary pressure inside the system, hence the passive pump effect dragging the sweat through the microfluidic channels and into contact with a quasireference electrode (QRE) and the ISFETs.
With a total volume capacity of 170nL, this design allows the collection of sweat quantities well below that generated under exercise conditions (typically 1.5µL/cm2/min on the arm). Instead, the microfluidics interface can collect enough sweat for the sensors even at rest, when the average sweat rate decreases to 20nL/cm2/min, the paper reports.
Because their lab-on-chip is very low power (each nanoribbon ISFET drawing only 20nW), the authors anticipate that once integrated into wearable products and skin patches such sensors could be designed for 24/7 multianalyte sensing in real time.
Indeed, the Lab On Skin sensing technology is currently transferred and exploited by Xsensio SA who aims to exploit what it describes as a goldmine of information available at the surface of our skin, electrolytes, metabolites, small molecules and proteins, for continuous health monitoring. One of the authors, Adrian M. Ionescu, is not only Professor at EPFL where he leads the Nanolab, but also Senior Technology Adviser and Co-Founder of Xsensio.
EPFL’s Nanolab – https://nanolab.epfl.ch
Xsensio SA – www.xsensio.com