Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine

Abstract

Exosomes, the smallest sized extracellular vesicles (30 ~ 150 nm) packaged with lipids, proteins, functional messenger RNAs and microRNAs, and double-stranded DNA from their cells of origin, have emerged as key players in intercellular communication. Their presence in bodily fluids, where they protect their cargo from degradation, makes them attractive candidates for clinical application as innovative diagnostic and therapeutic tools. But routine isolation and analysis of high purity exosomes in clinical settings is challenging, with conventional methods facing a number of drawbacks including low yield and/or purity, long processing times, high cost, and difficulties in standardization. Here we review a promising solution, microfluidic-based technologies that have incorporated a host of separation and sensing capabilities for exosome isolation, detection, and analysis, with emphasis on point of care and clinical applications. These new capabilities promise to advance fundamental research while paving the way toward routine exosome-based liquid biopsy for personalized medicine.

Proteomic Analysis of Extracellular Vesicles for Cancer Diagnostics

“…They may select EVs with different sizes and sort out specific subpopulation with defined biomarkers (e.g., HER2, EGFRvIII) for subsequent analyses . Microfluidic devices may be especially useful in cancer EV capture for both research and clinical applications due to their flexibility and efficiency . In summary, affinity‐based isolation methods generally yield a high sample purity but the relatively high cost and nonspecific binding of antibodies should also be taken into consideration.…”

Manipulation of micro‐ and nanoparticles in viscoelastic fluid flows within microfluid systems

“…Conventional separation techniques have been utilized to isolate nanoparticles, including ultracentrifugation, gradient centrifugation, ultrafiltration, precipitation, and antibody‐coated magnetic beads (Chiriacò et al, ; Contreras‐Naranjo, Wu, & Ugaz, ). However, these methods are associated with challenges comprising high cost, complex sample preparation, low recovery yield, and low purity (Gholizadeh et al, ).…”

Engineering Precision Medicine

“…[181] Capturing other biocomponents from the blood, such as exosomes [182] or circulating DNA, [183] also provides additional personalized molecular information about a patient. Besides CTCs, however, the capture of other circulating cells, such as trophoblasts, has been demonstrated to provide prenatal diagnostics.…”