A micro-/nano-chip and quantum dots-based 3D cytosensor for quantitative analysis of circulating tumor cells

Abstract

Abstract Background Due to the high transfer ability of cancer cell, cancer has been regarded as a world-wide high mortality disease. Quantitative analysis of circulating tumor cells (CTCs) can provide some valuable clinical information that is particularly critical for cancer diagnosis and treatment. Along with the rapid development of micro-/nano-fabrication technique, the three-dimensional (3D) bionic interface-based analysis method has become a hot research topic in the area of nanotechnology and life science. Micro-/nano-structure-based devices have been identified as being one of the easiest and most effective techniques for CTCs capture applications. Methods We demonstrated an electrospun nanofibers-deposited nickel (Ni) micropillars-based cytosensor for electrochemical detection of CTCs. Breast cancer cell line with rich EpCAM expression (MCF7) were selected as model CTCs. The ultra-long poly (lactic-co-glycolic acid) (PLGA) nanofibers were firstly-crosswise stacked onto the surface of Ni micropillars by electrospinning to construct a 3D bionic interface for capturing EpCAM-expressing CTCs, following immuno-recognition with quantum dots functionalized anti-EpCAM antibody (QDs-Ab) and forming immunocomplexes on the micro-/nano-chip. Results The Ni micropillars in the longitudinal direction not only play a certain electrical conductivity in the electrochemical detection, but also its special structure improves the efficiency of cell capture. The cross-aligned nanofibers could simulate the extracellular matrix to provide a good microenvironment which is better for cell adhesion and physiological functions. Bioprobe containing quantum dots will release Cd2+ in the process of acid dissolution, resulting in a change in current. Beneath favourable conditions, the suggested 3D cytosensor demonstrated high sensitivity with a broad range of 101–105 cells mL−1 and a detection limit of 8 cells mL−1. Conclusions We constructed a novel 3D electrochemical cytosensor based on Ni micropillars, PLGA electrospun nanofibers and quantum dots bioprobe, which could be used to highly sensitive and selective analysis of CTCs. More significantly, the 3D cytosensor can efficiently identify CTCs from whole blood, which suggested the potential applications of our technique for the clinical diagnosis and therapeutic monitoring of cancers.

Keywords

• Micropillar
• Nanofiber
• Quantum dots
• Three-dimensional cytosensor
• Circulating tumor cells