Fig. 1: Overview of the NanoEPIC Platform.

The NanoEPIC system relies on magnetic deflection to achieve phenotypic profiling and nanoscale sorting of sEVs. a Plasma extracted from whole blood was first treated with anti-PD-L1 conjugated MNPs. The MNPs-treated plasma sample is directly processed through NanoEPIC for exoPD-L1 profiling. The NanoEPIC device consists of a sample inlet and a buffer inlet. The sample is focused to the middle of the microchannel by the buffer during processing. Magnetic guides are embedded under the microchannel for exosomal sorting. Magnetically labeled sEVs experience a strong magnetic force in the direction normal to the magnetic guides due to the intensified magnetic gradient found at the edges of the guides. If the magnetic force is large enough to balance the Stokes’ drag force in the direction normal to the magnetic guide, the magnetically labeled sEVs will divert from the initial flow path and follow the magnetic guide. Unlabeled particles are focused on the negative outlet. Deflected sEVs are collected in the low/medium/high outlets based on PD-L1 expression. b ExoPD-L1 is used as a predictive marker for cancer immunotherapeutic outcomes through exoPD-L1 profiling. To showcase the utility of the platform for monitoring the therapeutic response to immunotherapy, mouse models under anti-PD-1 therapy were tracked for exoPD-L1 profiling using the NanoEPIC platform. The exoPD-L1 profiles were assessed in light of treatment outcomes. c Sorted sEVs can be used for downstream analysis. As illustrated, sEVs from different outlets were used to interact with cytotoxic T cells. Treatment with different sEV subpopulations resulted in variations in the level of T cell inhibition.