# Microfluidics for detection of exosomes and microRNAs in cancer: State of the art

**Authors:** Seyed Mojtaba Mousavi, Seyed Mohammad Amin Mahdian, Mohammad Saeid Ebrahimi, Mohammad Taghizadieh, Massoud Vosough, Javid Sadri Nahand, Saereh Hosseindoost, Nasim Vousooghi, Hamid Akbari Javar, Bagher Larijani, Mahmoud Reza Hadjighassem, Neda Rahimian, Michael R. Hamblin, Hamed Mirzaei

PMC · DOI: 10.1016/j.omtn.2022.04.011 · 2022-04-27

## TL;DR

This review discusses how microfluidics can improve the detection of exosomes and microRNAs in cancer, offering faster and more efficient diagnostic tools.

## Contribution

The paper reviews recent advances in microfluidics for exosome and microRNA detection, focusing on their potential for clinical applications.

## Key findings

- Microfluidics devices offer improved efficiency in isolating exosomes and microRNAs from small sample volumes.
- These devices can enhance the detection and monitoring of cancer-related biomarkers in body fluids.
- Microfluidics holds promise for developing point-of-care diagnostic tools for cancer.

## Abstract

Exosomes are small extracellular vesicles with sizes ranging from 30–150 nanometers that contain proteins, lipids, mRNAs, microRNAs, and double-stranded DNA derived from the cells of origin. Exosomes can be taken up by target cells, acting as a means of cell-to-cell communication. The discovery of these vesicles in body fluids and their participation in cell communication has led to major breakthroughs in diagnosis, prognosis, and treatment of several conditions (e.g., cancer). However, conventional isolation and evaluation of exosomes and their microRNA content suffers from high cost, lengthy processes, difficult standardization, low purity, and poor yield. The emergence of microfluidics devices with increased efficiency in sieving, trapping, and immunological separation of small volumes could provide improved detection and monitoring of exosomes involved in cancer. Microfluidics techniques hold promise for advances in development of diagnostic and prognostic devices. This review covers ongoing research on microfluidics devices for detection of microRNAs and exosomes as biomarkers and their translation to point-of-care and clinical applications.

The emergence of microfluidics devices with increased efficiency in sieving, trapping, and immunological separation of small volumes could provide improved detection and monitoring of exosomes and micoRNAs involved in cancer.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** GPC1 (glypican 1) [NCBI Gene 2817] {aka glypican}, ACE (angiotensin I converting enzyme) [NCBI Gene 1636] {aka ACE1, CD143, DCP, DCP1}, TSPAN8 (tetraspanin 8) [NCBI Gene 7103] {aka CO-029, TM4SF3}, MIR215 (microRNA 215) [NCBI Gene 406997] {aka MIRN215, miRNA215, mir-215}, VIM (vimentin) [NCBI Gene 7431], PDPN (podoplanin) [NCBI Gene 10630] {aka AGGRUS, D2-40, GP36, GP40, Gp38, HT1A-1}, MIR574 (microRNA 574) [NCBI Gene 693159] {aka MIR574-3p, MIRN574, hsa-mir-574, mir-574}, RAB27B (RAB27B, member RAS oncogene family) [NCBI Gene 5874] {aka C25KG}, DGCR8 (DGCR8 microprocessor complex subunit) [NCBI Gene 54487] {aka C22orf12, DGCRK6, Gy1, pasha}, EPCAM (epithelial cell adhesion molecule) [NCBI Gene 4072] {aka Ber-Ep4, BerEp4, DIAR5, EGP-2, EGP314, EGP40}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, CSPG4 (chondroitin sulfate proteoglycan 4) [NCBI Gene 1464] {aka CSPG4A, HMW-MAA, MCSP, MCSPG, MEL-CSPG, MSK16}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, ABCC2 (ATP binding cassette subfamily C member 2) [NCBI Gene 1244] {aka ABC30, CMOAT, DJS, MRP2, cMRP}, GDE1 (glycerophosphodiester phosphodiesterase 1) [NCBI Gene 51573] {aka 363E6.2, MIR16}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, CLDN3 (claudin 3) [NCBI Gene 1365] {aka C7orf1, CPE-R2, CPETR2, HRVP1, RVP1}, NOTCH3 (notch receptor 3) [NCBI Gene 4854] {aka CADASIL, CADASIL1, CARASIL1, CASIL, FPLD1, IMF2}, LRG1 (leucine rich alpha-2-glycoprotein 1) [NCBI Gene 116844] {aka HMFT1766, LRG}, MIR141 (microRNA 141) [NCBI Gene 406933] {aka MIRN141, mir-141}, MIR20A (microRNA 20a) [NCBI Gene 406982] {aka C13orf25, MIR20, MIRH1, MIRHG1, MIRN20, MIRN20A}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, PLAAT4 (phospholipase A and acyltransferase 4) [NCBI Gene 5920] {aka HRASLS4, HRSL4, PLA1/2-3, PLAAT-4, RARRES3, RIG1}, MIR107 (microRNA 107) [NCBI Gene 406901] {aka MIRN107, miR-107}, FOSL1 (FOS like 1, AP-1 transcription factor subunit) [NCBI Gene 8061] {aka FRA, FRA1, fra-1}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, Ccnd1 (cyclin D1) [NCBI Gene 12443] {aka CycD1, Cyl-1, PRAD1, bcl-1, cD1}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, MIR224 (microRNA 224) [NCBI Gene 407009] {aka MIRN224, miRNA224}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, HSPA8 (heat shock protein family A (Hsp70) member 8) [NCBI Gene 3312] {aka HEL-33, HEL-S-72p, HSC54, HSC70, HSC71, HSP71}, EBAG9 (estrogen receptor binding site associated antigen 9) [NCBI Gene 9166] {aka EB9, PDAF}, MIR944 (microRNA 944) [NCBI Gene 100126340] {aka MIRN944, hsa-mir-944, mir-944}, ITGA2B (integrin subunit alpha 2b) [NCBI Gene 3674] {aka BDPLT16, BDPLT2, CD41, CD41B, FMAIT2, GP2B}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, ABCB6 (ATP binding cassette subfamily B member 6 (LAN blood group)) [NCBI Gene 10058] {aka ABC, LAN, MTABC3, PRP, umat}, MIR17HG (miR-17-92a-1 cluster host gene) [NCBI Gene 407975] {aka C13orf25, LINC00048, MIHG1, MIRH1, MIRHG1, NCRNA00048}, MIR130A (microRNA 130a) [NCBI Gene 406919] {aka MIRN130A, miRNA130A, mir-130a}, MIR451A (microRNA 451a) [NCBI Gene 574411] {aka MIR451, MIRN451, hsa-mir-451, hsa-mir-451a, mir-451a}, MIR4732 (microRNA 4732) [NCBI Gene 100616385] {aka mir-4732}, MIR200C (microRNA 200c) [NCBI Gene 406985] {aka MIRN200C, mir-200c}, DICER1 (dicer 1, ribonuclease III) [NCBI Gene 23405] {aka DCR1, Dicer, Dicer1e, GLOW, HERNA, K12H4.8-LIKE}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, MIR200B (microRNA 200b) [NCBI Gene 406984] {aka MIRN200B, mir-200b}, BCL2L1 (BCL2 like 1) [NCBI Gene 598] {aka BCL-XL/S, BCL2L, BCLX, Bcl-X, PPP1R52}, MIR500A (microRNA 500a) [NCBI Gene 574502] {aka MIR500, MIRN500, hsa-mir-500, hsa-mir-500a, mir-500a}, ZFAS1 (ZNFX1 antisense RNA 1) [NCBI Gene 441951] {aka C20orf199, HSUP1, HSUP2, NCRNA00275, ZNFX1-AS1}, CDK2 (cyclin dependent kinase 2) [NCBI Gene 1017] {aka CDKN2, p33(CDK2)}, MIF (macrophage migration inhibitory factor) [NCBI Gene 4282] {aka GIF, GLIF, MMIF}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, MIR423 (microRNA 423) [NCBI Gene 494335] {aka MIRN423, hsa-mir-423, mir-423}, WNT3A (Wnt family member 3A) [NCBI Gene 89780], Wnt3a (wingless-type MMTV integration site family, member 3A) [NCBI Gene 22416] {aka Wnt-3a, vt}, RAN (RAN, member RAS oncogene family) [NCBI Gene 5901] {aka ARA24, Gsp1, TC4}, MIR1207 (microRNA 1207) [NCBI Gene 100302175] {aka MIRN1207, hsa-mir-1207}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, GRIA2 (glutamate ionotropic receptor AMPA type subunit 2) [NCBI Gene 2891] {aka GLUR2, GLURB, GluA2, GluR-K2, HBGR2, NEDLIB}, MIR182 (microRNA 182) [NCBI Gene 406958] {aka MIRN182, miRNA182, mir-182}, MCAM (melanoma cell adhesion molecule) [NCBI Gene 4162] {aka CD146, HEMCAM, METCAM, MUC18, MelCAM}
- **Diseases:** infectious diseases (MESH:D003141), carcinogenesis (MESH:D063646), pancreatic cancer (MESH:D010190), brain metastasis (MESH:D009362), ascites (MESH:D001201), glioblastoma (MESH:D005909), autoimmune diseases (MESH:D001327), leukemic (MESH:D007938), ovarian and prostate cancer (MESH:D010051), renal cell carcinoma (MESH:D002292), brain cancer (MESH:D001932), meningitis (MESH:D008580), PDAC (MESH:D021441), inflammatory conditions (MESH:D007249), nasopharyngeal cancer (MESH:D009303), pleural effusions (MESH:D010996), bacterial pathogen (MESH:D001424), breast and stomach tumors (MESH:D001943), hypoxic (MESH:D002534), diabetes mellitus (MESH:D003920), COVID-19 (MESH:D000086382), Tumor (MESH:D009369), virus infections (MESH:D014777), NSCLC (MESH:D002289), hypoxia (MESH:D000860), infection (MESH:D007239), neurodegeneration (MESH:D019636), brain pathology (MESH:D005598), GBM (MESH:D005910), Colorectal CRNDE (MESH:D015179), hyperthermia (MESH:D005334), MIA (MESH:D008545), death (MESH:D003643), EV (MESH:D004819), cardiovascular disease (MESH:D002318), HCC (MESH:D006528), food-borne disease (MESH:D005517), Alzheimer's disease (MESH:D000544), coagulation (MESH:D001778), hepatitis B (MESH:D006509), atherosclerotic plaque (MESH:D058226), lung cancer (MESH:D008175), ESCC (MESH:D000077277), PCa (MESH:D011471), neurological disorders (MESH:D009461), B cell chronic lymphocyte leukemia (MESH:D015451)
- **Species:** Dengue virus (no rank) [taxon 12637], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** T790M
- **Cell lines:** Panc1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), LIM1863 — Homo sapiens (Human), Colorectal adenocarcinoma, Cancer cell line (CVCL_4434), MRC5 — Homo sapiens (Human), Finite cell line (CVCL_0440), Paca44 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_7087), SW620 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0547), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC9130092/full.md

---
Source: https://tomesphere.com/paper/PMC9130092