TABLE 2.

The bio-medical relevance of breast cancer liquid biopsy-on-chip (BCLBoC) systems.

Chip type	Chip role	Chip design	Chip relevance	References
Vortex-GMACS-on-chip	cfDNA extraction from BC patient’s blood samples	microfluidic vortex along with a gradient magnetic-activated cfDNA sorter	analysis of DNA derived from tumor cells	Gwak et al. (2019)
Microfluidic chips	fast and accurately isolation of CTCs from BC patient’s whole blood	antibody labelled microfluidic chip	recognition of EpCAM in CTCs membrane	Abdulla et al. (2022)
	isolation of single and clustered CTCs from patient’s whole blood	label-free and size-based CTCs sorting	CTCs clusters may have a greater metastatic potential than single CTCs	Zhang et al. (2021)
	rapid and efficient isolation of HER2+ BC cells	magnetic iron oxide nanoparticles functionalized with the anti-HER2 antibody	isolation of HER2+ SKBR3 BC cell line	Parvin et al. (2023)
	separation of epithelial and mesenchymal cell-derived EVs	HO-MOFF: EMT-on-chip for EpCAM and CD49f biomarker detection in EVs	evaluation of status of BC and estimation of metastatic risk via EVs-based EMT-index in liquid biopsies	Gwak et al. (2021)
	capture of EVs derived from HER2+ positive BC cells in patient’s urine	nanochip arranged in herringbone pattern functionalized with anti-HER2 antibody	isolation of EVs from BC patient’s urine	Mun et al. (2024a)
	EVs isolation in patient’s whole blood	filter-electrochemical chip	multiple surface analysis of EVs; PSMA, EGFR, CD81, and CEA detected as tumor markers of EVs on MCF7, BT474, SKBR3, and MDA-MB-231 BC cell lines	Wang et al. (2023)
	multiple detection of miRNA biomarkers	chip based on three-segment hybridization	early detection of BC	Gao et al. (2020)
	detection of BC-derived exosomal mRNA in blood	exosomal mRNA sensing microfluidic chip	detection of HER2gene	Lim et al. (2022)
	role of fluid shear stress in induction of a more aggressive phenotype in metastatic cells compared to BC cell from primary tumor	modular microfluidic system	phenotype alteration in single and clustered MCF7 ER + BC cells; overexpression of Ki67 and phosphorylation of proteins associated with a more aggressive phenotype in CTCs (p-AKT, p-mTOR, and p-STAT3)	Ortega Quesada et al. (2024)

Abbreviations: BC, breast cancer; CEA, carcinoembryonic antigen; cfDNA, circulating cell-free tumor DNA; CTCs, circulating tumor cells; EGFR, epidermal growth factor receptor; EMT, epithelial-mesenchymal transition; EpCAM, epithelial cell adhesion molecule; EVs, extracellular vesicles; PSMA, prostate specific membrane antigen.