Microfluidic devices have led to novel biological advances through the improvement of micro systems that can mimic and measure. Microsystems easily handle sub-microliter volumes, obviously with guidance presumably through laminated fluid flows. Microfluidic systems have production methods that do not need expert engineering, away from a centralized laboratory, and can implement basic and point of care analysis, and this has attracted attention to their widespread dissemination and adaptation to specific biological issues. The general use of microfluidic tools in clinical settings can be seen in pregnancy tests and diabetic control, but recently microfluidic platforms have become a key novel technology for cancer diagnostics. Cancer is a heterogeneous group of diseases that needs a multimodal paradigm to diagnose, manage, and treat. Using advanced technologies can enable this, providing better diagnosis and treatment for cancer patients. Microfluidic tools have evolved as a promising tool in the field of cancer such as detection of a single cancer cell, liquid biopsy, drug screening modeling angiogenesis, and metastasis detection. This review summarizes the need for the low-abundant blood and serum cancer diagnosis with microfluidic tools and the progress that has been followed to develop integrated microfluidic platforms for this application in the last few years.

The heterogeneity and metastatic features of cancer cells lead to a great number of casualties in the world. Additionally, its diagnosis as well as its treatment is highly expensive. Therefore, development of simple but effective diagnostic systems which detect the molecular markers of cancer is of great importance. The molecular changes on cancer cell membranes serve as targets, such as HER2/neu receptor which is detected on the surface of highly metastatic breast cancer cells. We have aimed to develop a specific and simple quartz crystal microbalance (QCM)-based system to identify HER2/neu expressing breast cancer cells via a receptor-specific monoclonal antibody. First, the QCM chip was coated with polymeric nanoparticles composed of hydroxyethylmethacrylate (HEMA) and ethylene glycol dimethacrylate (EDMA). The nanoparticle coated QCM chip was then functionalized by binding of HER2/neu antibody. The breast cancer cells with/without HER2/neu receptor expression, namely, SKBR3, MDA-MB 231 and also mouse fibroblasts were passed over the chip at a rate of 10–500 cells/mL and the mass changes (Δm) on cell/cm² unit surface of sensor were detected in real-time. The detection limit of the system was 10 cells/mL. Thus, this QCM-based HER2/neu receptor antibody functionalized system might be used effectively in the detection of HER2/neu expressing SKBR3 breast cancer cells.

Voltage-gated sodium channel (VGSC) activity enhances cell behaviors related to metastasis, such as motility, invasion, and oncogene expression. Neonatal alternative splice form of Nav1.5 isoform is expressed in metastatic breast cancers. Furthermore, aberrant Notch signaling pathway can induce oncogenesis and may promote the progression of breast cancers. In this study, we aimed to analyze the effect of the nNav1.5 inhibitor phenytoin and Notch signal inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine-t-butyl ester (DAPT) on triple negative breast cancer cell line (MDA-MB-231) via inhibition of nNav1.5 VGSC activity and Notch signaling, respectively. In order to determine the individual and combined effects of these inhibitors, the 4-[3-(4-iyodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) test, wound healing assay, and zymography were performed to detect the proliferation, lateral motility, and matrix metalloproteinase-9 (MMP9) activity, respectively. The expressions of nNav1.5, Notch4, MMP9, and tissue inhibitor of metalloproteinases-1 (TIMP1) were also detected by quantitative real-time reverse transcriptase–polymerase chain reaction. DAPT caused an antiproliferative effect when the doses were higher than 10 µM, whereas phenytoin showed no inhibitory action either alone or in combination with DAPT on the MDA-MB-231 cells. Furthermore, it was found that the lateral motility was inhibited by both inhibitors; however, this inhibitory effect was partially rescued when they were used in combination. Meanwhile, the results showed that the MMP9 activity and the ratio of MMP9 mRNA to TIMP1 mRNA were only decreased by DAPT. Thus, we conclude that the combined effect of DAPT and phenytoin is not as beneficial as using DAPT alone on MDA-MB-231 breast cancer cells.