Abstract

New Opportunities in Acoustofluidic Processing of Liquid Biopsies

Thomas Laurell, Professor, Lund University

Blood sampling and molecular analysis of plasma is the most common clinical diagnostic modality in modern health care. With more advanced means to downstream processing, sub components of blood can be isolated, improving the diagnostic outcome. Detection and analysis of rare events is specifically an area where high performance isolation of sub components of blood is critical and where lab-on-a-chip technology has paved the way for several new approaches. Acoustic forces in combination with microfluidics has open new avenues for high performance blood cell separation, enabling isolation of cancer cells from blood, leukocyte sub populations and more recently also enrichment and purification of extracellular vesicles. Our initial efforts in isolating circulating tumor cells using acoustophoresis in clinical scale prostate cancer patients samples will be reported.

Although conventional acoustophoresis is limited in is ability to manipulate particles smaller than 1 um secondary acoustic effects can alleviate this short coming. Scattered ultrasound between larger particles, that can be retained in a local acoustic field in a microchannel, can be utilized to enrich submicron vesicles on the larger “trapping particles”. Based on this we have developed a microfluidic platform that enables isolation of extra cellular vesicles (EVs) from biofluids such a urine, blood plasma and cell culture medium without the need for ultracentrifugation. Further, benefits of isolating EVs by means of acoustic trapping is rapid processing that provides relatively high recoveries (up to 60-80%), yet handling small sample volumes (20-50 uL blood plasma), giving access to molecular profiling of extra cellular vesicles in biobanks. Our studies have demonstrated protein and miRNA profiling of blood plasma EVs from myocardial infarction patients as well as in urine samples from healthy donors. More recently we have been able to detect EV protein biomarker profiles in heart transplant patients with acute rejection which could not be detected in blood plasma.