(146c) Tangential Flow for Analyte Capture (TFAC): A Method for the Purification of Nanoparticle Biomarkers Enabled By Ultrathin Silicon Membranes

Extracellular vesicles (EVs) are lipid vesicles ranging from 30 – 1000 nm in diameter secreted by cells to serve a variety of functions. Certain members of the EV family, such as exosomes, are thought to be important for intercellular communication. Exosomes contain cell specific biomarkers (i.e. miRNA, protein) that are useful for point-of-care (POC) diagnostics. A variety of techniques are used to isolate EVs, including ultracentrifugation, affinity-based capture, precipitation and filtration, but these often require large sample volumes (50 – 300 mL) which are not feasible for a POCsystem. Additionally, these isolations are often contaminated with protein, leading to difficulty in the identification of biomarkers. Therefore, an alternative method of isolating EVs from small volumes is requiredfor POC. Silicon nanomembranes are ultrathin (50-100nm) nanoporous membranes discovered during the rapid crystallization of pure silicon films. These membranes are manufactured with a variety of pore diameters (~ 5 nm – 100 nm) and have high porosities (20% – 40%) and exceptional permeabilities. These membranes are manufactured in a ‘chip’ format that is 5.4 mm x 5.4 mm, making them perfect for small volume applications such as microfluidic filtration. In this work, we present a novel exosome capture methodforsmall volume (~ 1 mL)samples.We callthis methodtangential flow analyte capture (TFAC). After demonstrating the capture ofexosomes from undiluted serum, wepresenta computational model for TFACthat is validated with 60 nm gold nanoparticleswith and without the addition of serum albumin (2mg/ml). We usethe model to define optimalcaptureconditions, and thendemonstrate the capture of > 75% of exosomes from defined protein/exosome sampleand compare these results to capture from raw urine.