Flexible Microfluidics for Raman Measurements on Skin

The present modalities of body chemistry monitoring via invasive skin penetration sampling have potential safety hazards in long-term continuous biomarker analysis due to utilizing biorecognition elements. Non-invasive optical sensing modalities show promise in biosensing by providing accurate biomolecule measurements. For instance, Raman spectroscopy provides quantifiable information about specific vibrational energy levels of the molecule’s chemical bonds that can be selectively linked to the molecule’s concentration even in a complex medium. However, these emerging modalities for medical measurements require precision measures on human tissues. This can be enabled by microfluidics. Therefore, merging Raman spectroscopy and microfluidics can provide inherently selective, extremely sensitive, repeatable, and highly accurate in situ optical biosensing from small sample volumes without acquiring biorecognition elements. To that aim, microfluidics devices are required to operate on the skin to provide precise Raman scattering measurements of sweat. However, the material choice for Raman-microfluidics is not trivial because, other than system usability and material/skin interface biocompatibility, the material selection also depends on Raman instrumentation parameters as well as on the target molecule and sensing medium. Therefore, this paper aims to show optimizations of such design for soft epidermal microfluidics for Raman scattering-based biosensing on skin. First, we investigate the Raman activity of three soft polymeric materials in experiments mimicking real testing scenarios. Then, we select the best materials to develop a flexible “lab-on-skin” platform compatible with Raman spectroscopy. Next, we develop multilayer microfluidic devices with simple, cleanroom-free, and soft lithography-free processes using laser patterning, controlled casting, and layer bonding with acrylic adhesives or O
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plasma activation. Finally, we characterize the developed soft microfluidic devices in ex vivo sweat lactate monitoring with syntactic sweat, including +30 sweat analytes which correctly mimic actual human sweat on porcine skin and show sensitive and repeatable medical measurement.