Speaker: Gustavo Stolovitzky, IBM T.J. Watson Research Center, Yorktown Heights, NY and Icahn School of Medicine at Mount Sinai, New York, NY


Title: Smaller, Faster and Chip-er: Isolation of exosomes by nanoDLD lab-on-a-chip technology and application to prostate cancer biomarker discovery


Abstract: Exosomes are an exciting target for liquid biopsies. However, isolation of exosomes and reproducible detection of RNA and proteins (biomarkers) remains an ongoing challenge. We have developed nanoscale Deterministic Lateral Displacement (nanoDLD) a lab-on-a-chip technology that allows for size-based sorting of colloidal particles, including exosomes, at tens of nanometers scale efficiently and with high yield [1]. The chips consist of a periodic arrangement of pillar where nanofluidics flow patterns sort exosomes from larger and smaller components. We theoretically studied particle trajectories in this pillar array geometries and found non-trivial behavior such as anisotropic permeability which we used to improve chip design [2]. We scale nanoDLD technology to clinically relevant volumes and developed an automated tool for isolation of exosomes [3]. Analysis of nanoDLD isolation of exosomes show comparable or improved resolution, recovery, and concentration compared to standard techniques. To understand the strengths and limitations of nanoDLD for RNA based biomarker discvory and detection we characterized and compared the reproducibility of RNAseq measurement from exosomes isolated using nanoDLD and Ultracentrifugation. As an application, I will present preliminary data of the use of nanoDLD to study the transcriptome of separated exosomes in serum of Prostate Cancer patients. We studied the potential prostate provenance of these exosomes, by comparing the tumor transcriptome and the exosome transcriptome in the same patients. We identified known Prostate Cancer biomarkers and discovered potential new biomarkers which were not examined before. These preliminary results indicate the potential of nanoDLD technology for sorting exosomes and for detecting biomarkers in liquid biopsies.


[1] Wunsch et al., Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm, Nat Nanotechnol. 2016 Nov;11(11):936-940.

[2] Kim et al., Broken flow symmetry explains the dynamics of small particles in deterministic lateral displacement arrays, PNAS 2017, Jun 27;114(26):E5034-E5041

[3] Smith et al., Integrated Nanoscale Deterministic Lateral Displacement Arrays for Separation of Extracellular Vesicles from Clinically-Relevant Volumes of Biological Samples, Lab-on-a-chip 2018, https://doi.org/10.1039/C8LC01017J