Microfluidic Exosome Analysis toward Liquid Biopsy for Cancer

Abstract

Assessment of a tumor’s molecular makeup using biofluid samples, known as liquid biopsy, is a prominent research topic in precision medicine for cancer, due to its noninvasive property allowing repeat sampling for monitoring molecular changes of tumors over time. Circulating exosomes recently have been recognized as promising tumor surrogates because they deliver enriched biomarkers, such as proteins, RNAs, and DNA. However, purification and characterization of these exosomes are technically challenging. Microfluidic lab-on-a-chip technology effectively addresses these challenges owing to its inherent advantages in integration and automation of multiple functional modules, enhancing sensing performance, and expediting analysis processes. In this article, we review the state-of-the-art development of microfluidic technologies for exosome isolation and molecular characterization with emphasis on their applications toward liquid biopsy–based analysis of cancer. Finally, we share our perspectives on current challenges and future directions of microfluidic exosome analysis.

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

“…Previous reviews have traced the development of miniaturized solutions to address various aspects of the exosomal analysis workflow, and we encourage readers to consult these references for a deeper perspective on the rapid evolution of this field. 24,65–69 These liquid biopsy platforms employ a range of exosome isolation approaches such as immunoaffinity, membrane-based filtration, trapping on nanowires, acoustic nanofiltration, and deterministic lateral displacement (DLD) sorting (Figure 2). In acoustics and DLD research, microfluidic-based exosome isolation represented a first-of-a-kind application for separation of biocolloids at the nanoscale using these technologies.…”

“…Exosomes, on the other hand, can be collected from bodily fluid samples via a minimally invasive liquid biopsy . 24,25 And since the material packaged within exosomes originates directly from the parent cell, analysis of this cargo may enable a snapshot of the host cell state to be obtained in a much simpler manner than conventional physical biopsy, making it feasible for this kind of analysis to be broadly implemented as a routine diagnostic platform. The potential for exosomes to contain individualized information related to disease state, therapeutic response, exposure to environmental cues, and a myriad of other health factors, all contained in a vesicular package that can be collected from bodily fluid samples, has generated considerable excitement as a pathway to enable personalized medicine.…”

Clinical application of a microfluidic chip for immunocapture and quantification of circulating exosomes to assist breast cancer diagnosis and molecular classification

“…The techniques developed so far for microfluidic-based exosomal concentration can be classified into two categories, including sized-based and biomarker-based approaches [19]. According to the different size of exosomes from other EVs, several microlfuidic devices were developed.…”

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

“…Recent studies that utilized microfluidic technologies and VEFs for separation of nanoparticle are summarized in Table . Among them, a great example of nanobioparticle separation is related to the isolation of salient exosomes and extracellular vesicles from biofluids as an essential step for detection of various diseases, for example, early stage cancer detection (He & Zeng, ), kidney diseases detection (Gámez‐Valero, Lozano‐Ramos, Bancu, Lauzurica‐Valdemoros, & Borràs, ), and risk assessment in patients with heart failure (Shi et al, ). Further numerical and experimental works for nanoparticle manipulation in VEFs are needed to make this technology applicable for clinical and nonclinical uses.…”