Isolation of Extracellular Vesicles from Cell Culture and Blood Through Nano-Targeted DLD Microfluidic Device.

Extracellular vesicles (EVs) are secreted by cells and found in biological fluids such as blood, with concentration correlated with oncogenic signals, making them attractive biomarkers for liquid biopsy. The current gold-standard method for EVs isolation requires an ultracentrifugation (UC) step among others. The cost and complexity of this technique are forbiddingly high for many researchers, as well as for routine use in biological laboratories and hospitals. This chapter reports on a simple microfluidic method for EVs isolation, based on a microfluidic size sorting technique named Deterministic Lateral Displacement (DLD). With the design of micrometric DLD array, we demonstrated the potential of our DLD devices for the isolation of nano-biological objects such as EVs, with main population size distribution consistent with UC technique.

Separation of Biological Particles in a Modular Platform of Cascaded Deterministic Lateral Displacement Modules.

Deterministic lateral displacement (DLD) has been extensively implemented in the last decade for size-based sample preparation, owing to its high separation performances for a wide range of particle dimensions. However, separating particles from 1 µm to 10 µm in one single DLD device is challenging because of the required diversity of pillar dimensions and inherent fabrication issues. This paper presents an alternative approach to achieve the extraction of E. coli bacteria from blood samples spiked with prostate cancer cells. Our approach consists in cascading individual DLD devices in a single automated platform, using flexible chambers that successively collect and inject the sample between each DLD stage without any external sample manipulation. Operating DLD separations independently enables to maximize the sorting efficiency at each step, without any disturbance from downstream stages. The proposed two-step automated protocol is applied to the separation of three types of components (bacteria, blood particles and cancer cells), with a depletion yield of 100% for cancer cells and 93% for red blood cells. This cascaded approach is presented for the first time with two DLD modules and is upscalable to improve the dynamic range of currently available DLD devices.