Digital microfluidics with integrated Raman sensor for high-sensitivity in-situ bioanalysis.

This study introduces an advanced bioanalytical platform that combines digital microfluidics (DMF) with Raman spectroscopy, effectively addressing common issues in bioanalysis such as sample contamination, excessive consumption of samples and reagents, and manual handling. Our innovative system is engineered to handle diverse sample types and enables both sample preparation and in-situ analysis on a single device, utilizing less than 5 μL of samples and reagents. It incorporates a Translucent Raman Enhancement Stack (TRES) sensor, which boosts the detection signal, and includes droplet-driving functionality for automated processing of complex samples in a compact setting. The hydrophilic surface of the TRES sensor draws analytes into the detection zone, expediting sample attachment and enhancing the surface-enhanced Raman scattering (SERS). Moreover, the TRES sensors are cost-effective, straightforward to manufacture, and scalable, making them suitable for widespread production and single-use bioanalytical applications. This integrated and automated approach streamlines the sample preparation and analysis processes, enhances detection efficiency, and achieves high sensitivity, excellent linearity, and effective detection of different biochemical analytes. We validate the system's accuracy through on-device enrichment and analysis of exosomes from serum, demonstrating its capability for real-time, on-site analysis of complex biological samples.