Microfluidic Device Captures, Allows Analysis of Tumor-Specific Extracellular Vesicles

Source: Massachusetts General Hospital

Summary: A new microfluidic device developed by investigators may help realize the potential of tumor-derived extracellular vesicles (EVs) – tiny lipid particles that carry molecules through the bloodstream.

Glioblastoma (A fast-growing, malignant tumor of the brain) is a highly fatal disease with few treatment options. Due to the tumor’s location, it has been challenging to get dynamic, real-time molecular information, which limits the ability to determine tumor progression and to match patients with the most promising new therapies. Previous technologies designed to isolate extracellular vesicles were limited in their ability to distinguish tumor EVs from those carrying molecules from non-malignant cells. A new microfluidic device developed by investigators at Massachusetts General Hospital has the ability to sort tumor-specific extracellular vesicles (EVs) out from the billions of EVs carried through the bloodstream may lead to the development of much-needed diagnostic and monitoring tools for this and other hard-to-treat cancers. The study findings were published in the journal Nature Communications.

Set of micro-channels etched into a material

Extracellular vesicles (red) released from a patient’s tumor and captured on the surfaces of the EVHB-Chip. Credit: Shannon Stott, PhD, Center for Engineering in Medicine, Massachusetts General Hospital

Extracellular vesicles (EVs) – tiny lipid particles that carry molecules through the bloodstream – as biomarkers that could monitor a tumor’s response to therapy and provide detailed information to guide treatment choice. The research team combined features of the CTC (circulating tumor cell) – detecting HB-Chip with features specific to the capture of EVs. The surfaces through which a sample is passed are optimized to the physical properties of EVs – which are thousands of times smaller than cells – and contain a “cocktail” of antibodies against proteins highly expressed on GBM cells. Using the new device, dubbed the EVHB-Chip, they analyzed serum or plasma samples from 13 patients with GBM and 6 control samples from healthy donors. The captured EVs also identified genes present in the four characteristic subtypes of GBM and revealed the upregulation of more than 50 cancer-associated genes, some not previously observed in GBM EVs.

Senior author Shannon Stott said, “We are excited by this early-stage data, and we look forward to scaling the technology and increasing the number of patient samples analyzed. Specifically, we are interested in exploring how these vesicles change over time in response to treatment, and we see our blood-based assay as an ideal way to explore this in brain tumor patients.”

More Information: Eduardo Reátegui et al, “Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles”, Nature Communications (2018). DOI: 10.1038/s41467-017-02261-1

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