Soft Epidermal Paperfluidics for Sweat Analysis by Ratiometric Raman Spectroscopy

The expanding interest in digital biomarker analysis focused on non-invasive human bodily fluids, such as sweat, highlights the pressing need for easily manufactured and highly efficient soft lab-on-skin solutions. Here, we report, for the first time, the integration of microfluidic paper-based devices (μPAD) and non-enhanced Raman-scattering-enabled optical biochemical sensing (Raman biosensing). Their integration merges the enormous benefits of μPAD, with high potential for commercialization and use in resource-limited settings, with biorecognition-element-free (but highly selective) optical Raman biosensing. The introduced thin (0.36 mm), ultra-lightweight (0.19 g), and compact footprint (3 cm²) opto-paperfluidic sweat patch is flexible, stretchable, and conforms, irritation-free, to hairless or minimally haired body regions to enable swift sweat collection. As a great advantage, this new bio-chemical sensory system excels through its absence of onboard biorecognition elements (bioreceptor-free) and omission of plasmonic nanomaterials. The proposed easy fabrication process is adaptable to mass production by following a fully sustainable and cost-effective process utilizing only basic tools by avoiding typically employed printing or laser patterning. Furthermore, efficient collection and transportation of precise sweat volumes, driven exclusively by the wicking properties of porous materials, shows high efficiency in liquid transportation and reduces biosensing latency by a factor of 5 compared to state-of-the-art epidermal microfluidics. The proposed unit enables electronic chip-free and imaging-less visual sweat loss quantification as well as optical biochemical analysis when coupled with Raman spectroscopy. We investigated the multimodal quantification of sweat urea and lactate levels ex vivo (with syntactic sweat including +30 sweat analytes on porcine skin) and achieved a linear dynamic range from 0 to 100 mmol/L during fully dynamic continuous flow characterization.