Abstract

Acoustofluidic Sample Processing Enables Novel Modalities for Medical Diagnostics

Thomas Laurell, Professor, Lund University

Ultrasonic manipulation of cells and particles in microfluidic system has in the recent years gained much attention offering new means to perform unit operations such as cell separation, enrichment, buffer exchange and trapping, enabling integrated cell handling functions in lab-on-a-chip systems. Since the acoustic radiation force is proportional to the particle volume bacteria and extracellular vesicles become very challenging to capture due to Stokes drag from acoustically induced Rayleigh streaming, that start to dominate over the primary radiation force. However, recently our group demonstrated that the lower size limitation in acoustic trapping of small particles can be shifted to smaller particle sizes by utilising inter-particle forces that arise from sound scattered between particles in close proximity. By seeding a limited number of larger polystyrene particles in an acoustic trap, that can easily be retained in the trapping position against flow, and subsequently perfuse the trapping region with a nanoparticle solution, these will be captured onto the larger seed particles. Enrichment of 110 nm polystyrene particles was intially demonstrated and subsequent work has shown the possibility to efficiently enrich bacteria in blood samples from sepsis patients. More recent developments targets trapping and purification of extracellular vesicles in 20 uL blood plasma samples from patients with myocardial infarction, where proteomic profiling of platelet derived microvesicles have been performed using mass spectrometry. Data on protein analysis and RNA content of exosomes derived by acoustic trapping will also be presented. An important benefit of the seed trapping platform is that: 1) centrifugation is not needed, 2) is rapid and 3) can be employed to minute sample volumes (10-100 uL), which enables access to biobank material and thereby population based and longitudinal studies.