Weiying Zhang

PDMS micropillar-based microchip for efficient cancer cell capture

We introduce a micropillar-based microfluidic device for efficient and rapid cancer cell capture. The microfluidic chip consists of two linear arrays of micropillars integrated with a herringbones flow-derived microstructure, and the separation distance between two adjacent micropillars is similar to the size of tumor cells. Cancer cells can be forced to come into contact with the micro-columns and are then captured by specific immune antibody–antigen interactions. Both previously published data and new available experimental data confirm the superiority of the proposed device. Different cancer cell lines were utilized to investigate the capture efficiency of our microfluidic device. MCF-7 cancer cells spiked into DMEM culture medium can be captured from a suspension with over 90% efficiency. The results of the present work provide a promising method for separation of rare cells, such as circulating tumor or fetal cells.

A dual biomarker detection platform for quantitating circulating tumor DNA (ctDNA)

Circulating tumor DNA (ctDNA), which includes DNA mutations, epigenetic alterations and other forms of tumor-specific abnormalities, is a promising “real-time” biomarker for noninvasive cancer assessment. Tumor DNA is of great value in the process of cancer treatment, including diagnostic and prognostic information before, during treatment and at progression. Here we introduce a peptide nucleic acids probe-gold nanoparticles (PNA-AuNPs) and lead phosphate apoferritin (LPA)-based dual biomarker detection platform, which could be used in a DNA biosensor to quantify ctDNA by detection of tumor-specific mutations and methylation of PIK3CA gene. On the one hand, PNA probe and anti-5-Methylcytosine monoclonal antibody (anti-5-mC) were used to recognize the different parts of ctDNA, forming a sandwich-structure on a screen-printed electrode (SPE) surface. On the other hand, AuNPs and LPA were introduced to construct the biosensor for double signal amplification. Square-wave voltammetry (SWV) was used to monitor the electrochemical signal of lead ions released from apoferritin. The proposed DNA biosensor yielded a linear current response to ctDNA concentrations over a broad range of 50-10000 fM with a detection limit of 10 fM. It also successfully detected ctDNA collected from cancer patient serum. Therefore, we anticipate this new platform opens up an approach to detect and monitor diverse malignancies, facilitating personalized cancer therapy.

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

BackgroundDue 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.MethodsWe 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.ResultsThe 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 101–105xa0cellsxa0mL−1 and a detection limit of 8xa0cellsxa0mL−1.ConclusionsWe 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.

TiO2 Nanorods Arrays with Mesoscopic Micro-nano Interfaces for In Situ Regulation of Cell Morphology and Nucleus Deformation

Cell morphology and nucleus deformation are important when circulating tumor cells break away from the primary tumor and migrate to a distant organ. Cells are sensitive to the microenvironment and respond to the cell-material interfaces. We fabricated TiO2 nanorod arrays with mesoscopic micro-nano interfaces through a two-step hydrothermal reaction method to induce severe changes in cell morphology and nucleus deformation. The average size of the microscale voids was increased from 5.1 to 10.5 μm when the hydrothermal etching time was increased from 3 to 10 h, whereas the average distances between voids were decreased from 0.88 to 0.40 μm. The nucleus of the MCF-7 cells on the TiO2 nanorod substrate that was etched for 10 h exhibited a significant deformation, because of the large size of the voids and the small distance between voids. Nucleus defromation was reversible during the cells proliferate process when the cells were cultured on the mesoscopic micro-nano interface.This reversible process was regulated by combining of the uniform pressure applied by the actin cap and the localized pressure applied by the actin underneath the nucleus. Cell morphology and nucleus shape interacted with each other to adapt to the microenvironment. This mesoscopic micro-nano interface provided a new insight into the cell-biomaterial interface to investigate cell behaviors.

Visible-light-controllable drug release from multilayer-coated microneedles

A method for the generation of visible-light-controllable drug release polyelectrolyte multilayers on poly(l-lactide) (PLLA) microneedles is developed by host-guest chemistry. In response to visible light irradiation, model drugs encapsulated on polyelectrolyte multilayers transfer into the skin following brief microneedle application.

Artificial honeycomb-inspired TiO2 nanorod arrays with tunable nano/micro interfaces for improving poly(dimethylsiloxane) surface hydrophobicity

This work demonstrates a bottom-up model of fabricating a honeycomb-inspired interface consisting of micro- and nanostructures for improving poly(dimethylsiloxane) (PDMS) hydrophobicity. TiO2 nanorod arrays and microsized voids were fabricated by a two-step hydrothermal reaction method. First, rutile TiO2 nanorod arrays were hydrothermally fabricated on the fluorine-doped SnO2 conductive substrates substrate. Second, microsized TiO2 voids were synthesized through HCl hydrothermal etching to obtain a honeycomb-inspired interface with tunable size. The size of the etched voids increased from 0.22xa0±xa00.06 to 8.0xa0±xa02.8xa0μm. The interfaces were then transferred on the PDMS surface to improve hydrophobic property. The contact angles of the corresponding positive PDMS replicas reached 140° after etching with the TiO2 nanorod arrays for 10xa0h. The size of mastoid structures on the PDMS surfaces was 7.5xa0μm, which is similar to the size of microstructures on the lotus leaf surface. The fabricated PDMS surface with tunable hydrophobicity properties can be used in the microfluidic channels in the future.