Integrated microfluidic platform for continuous downstream purification and in-line residual ethanol monitoring of exosome-mimetic nanoparticles

Information from the abstract

Exosome-mimetic nanoparticles (ENPs) are promising drug delivery vehicles with superior biocompatibility and targeting capabilities. However, their clinical translation is bottlenecked by traditional batch purification methods, which suffer from low throughput, intensive labor, and batch-to-batch inconsistency. To address these limitations, this study presents an integrated microfluidic platform that combines continuous sample purification with in-line solvent monitoring within a unified workflow. The platform integrates a spiral microfluidic module for rapid buffer exchange with an alcohol dehydrogenase (ADH)-functionalized screen-printed carbon electrode (SPCE) sensor positioned at the ENP outlet for real-time residual ethanol detection. At the optimized inertial focusing condition (Reynolds number (Re) = 42.5), the spiral module achieved rapid continuous buffer exchange, effectively eliminating ~94% of residual ethanol with an ENP recovery rate of ~88% and preserving high RNA encapsulation efficiency ~94%. The integrated biosensor enabled sensitive in-line detection of residual ethanol with a limit of detection of 0.8% (v/v) (R² = 0.983). The purified ENPs retained a uniform hydrodynamic size (82 nm average, Polydispersity index (PDI) of 0.09) and demonstrated robust colloidal stability over four weeks. This continuous purification and in-line monitoring strategy provides a scalable framework for nanomedicine downstream processing and establishes a foundation toward future feedback-controlled process analytical technology.

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Related topics: Microfluidic and Capillary Electrophoresis Applications · Extracellular vesicles in disease · Innovative Microfluidic and Catalytic Techniques Innovation