Cancer Liquid Biopsy Using Integrated Microfluidic Exosome Analysis Platforms

Abstract

Liquid biopsies serve as both powerful noninvasive diagnostic tools for early cancer screening and prognostic tools for monitoring cancer progression and treatment efficacy. Exosomes are promising biomarkers for liquid biopsies, since these nano-sized extracellular vesicles (EVs) enrich proteins, lipids, mRNAs, and miRNAs from cells of origin, including cancer cells. Although exosomes are abundantly present in various bodily fluids, conventional exosome isolation and detection methods that rely on benchtop equipment are time-consuming, expensive, and involve complicated non-portable procedures. As an alternative, recently developed microfluidic platforms can perform effective exosome separation and detection for liquid biopsies using a single device. Such methods offer advantages of integrity, speed, cost-efficiency, and portability over conventional benchtop and early microfluidic-based single-functional methods which can only separate or detect exosomes separately. These advances have made exosome-based point-of-care (POC) applications possible. This review outlines recent integrated

Extracellular Endothelial Cell-Derived Vesicles: Emerging Role in Cardiac and Vascular Remodeling in Heart Failure

“…Future studies that could clearly explain the potency of EVs as biomarkers for personalized care of HF are required. Probably brand new technological solutions, such as an integrated microfluidic exosome analysis platform, will become powerful non-invasive diagnostic tools for easy screening and monitoring of the EV-based Liquid biopsy (143). There are expectations that EVs will be a promising tool for transfer of the drugs and vector signals to the target cells to regulate many processes involved in myocardium and vasculature reparation, endothelial homoeostasis, and adaptations to myocardial injury (144).…”

Microfluidic detection of human diseases: From liquid biopsy to COVID-19 diagnosis

“…For example, some surface proteins or miRNAs carried by exosomes are found specific to the disease stage in different cancers which can be potential disease markers for diagnosis ( Kalluri and LeBleu, 2020 ). Thus, much effort has recently been put into creating an integrated system that can perform exosome capture and analysis on the same chip ( Fang et al,2017 , Li et al, 2020a , Li et al, 2020b ). For example, exosomes captured by immuno-functionalized surfaces ( Zhang et al, 2019a , Zhang et al, 2019b ) or nano-herringbone structured surfaces ( Zhang et al, 2019a , Zhang et al, 2019b ) can be fluorescence-labeled in-situ to detect different surface proteins or detect tumor-specific exosomes from patient blood samples, for exosome-based diagnosis.…”

“…A nucleic acid test is the standard screening method used for disease detection in this pandemic due to its high sensitivity and specificity. However, the conventional reverse transcriptase PCR (RT-PCR) method is labor-intensive and time-consuming, making it a rate-limiting step for disease screening in most countries at the beginning of the outbreak ( Li et al, 2020a , Li et al, 2020b ). This pandemic is a vivid lesson urging us to improve on the disease detection techniques for coping with the current situation and be prepared for future outbreaks.…”

“…During this on-going COVID-19 pandemic, apart from the PCR-based screening, LFA-based fast detection assays have been widely used for disease screening in low-risk populations from as early as April in China ( Li et al, 2020a , Li et al, 2020b ). Multiple companies have quickly developed and released these products which require only a finger-prick of blood for rapid result readout ( Demey et al, 2020 , Lin et al, 2020 ).…”

Uncovering the Exosomes Diversity: A Window of Opportunity for Tumor Progression Monitoring

“…These antibodies are immobilized on different supports, such as magnetic beads on plates of microfluidic devices or chromatography matrices. In addition to the common exosomes isolation techniques, several innovative microfluidic techniques have been recently developed, including the deterministic lateral displacement (DLD) sorting, trapping on nanowires, and acoustic nanofiltration [24,25]. Then, electron (SEM and TEM) or atomic force microscopy (AFM) are necessary to analyze the nature of the single isolated vesicle [26].…”