Capture and biological release of circulating tumor cells in pancreatic cancer based on peptide-functionalized silicon nanowire substrate

Abstract

BackgroundEfficient and precise circulating tumor cells’ (CTCs) capture and release with minimal effect on cell viability for CTCs’ analysis are general requirements of CTCs’ detection device in clinical application. However, these two essential factors are difficult to be achieved simultaneously.MethodsIn order to reach the aforementioned goal, we integrated multiple strategies and technologies of staggered herringbone structure, nanowires’ substrate, peptides, enzymatic release, specific cell staining, and gene sequencing into microfluidic device and the sandwich structure peptide-silicon nanowires’ substrate was termed as Pe-SiNWS.ResultsThe Pe-SiNWS demonstrated excellent capture efficiency (95.6%) and high release efficiency (92.6%). The good purity (28.5%) and cell viability (93.5%) of CTCs could be obtained through specific capture and biological release by using Pe-SiNWS. The good purity of CTCs facilitated precise and quick biological analysis, and five types of KRAS mutation were detected in 16 pancreatic cancer patients but not in healthy donors.ConclusionThe results proved that the effective capture, minor damage release, and precise analysis of CTCs could be realized simultaneously by our novel strategy. The successful clinical application indicated that our work was anticipated to open up new opportunities for the design of CTC microfluidic device.

Perspectives on liquid biopsy for label‐free detection of “circulating tumor cells” through intelligent lab‐on‐chips

“…These immune‐based methods still most often require preselection step to concentrate the CTCs, either by density gradient or via diverse microfluidic approaches, with more sophisticated techniques emerging daily, such as dielectrophoretic array, which discriminates CTCs based on a combination of properties including cell size, shape, and polarization 62 . Moreover, combining immunostaining with nanotechnology platforms is gaining momentum 63‐66 . Interestingly, flow cytometers are available today, which combine marker‐based phenotyping with fluorescence microscopy, providing both functional and morphologic information 67 .…”

Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

“…For the captured A549 cells, cell viability was 78–83%. They also integrated multiple strategies and technologies of unique staggered herringbone mixer, peptide-silicon nanowires’ substrate (Pe-SiNWs) and enzymatic release into a microfluidic chip ( Figure 3 C) [ 54 ]. When the flow rate was 1.0 mL h −1 , the Pe-SiNWs modified by EpCAM and specific peptides CKAAKN demonstrated the highest capture efficiency of 91.4%.…”

“…Reproduced with permission from [ 78 ]; ( C ) Unique staggered herringbone structure and Pe-SiNWs were adopted in microfluidic device to enhance the interactions between cells and channel substrate. Reproduced with permission from [ 54 ]; ( D ) A microchip comprised of a serpentine PDMS microchannel and a glass substrate with MnO 2 nanofibers to capture anti-EpCAM positive-expressing cells. Reproduced with permission from [ 81 ]; ( E ) The microfluidic device embedding functionalized poly(lactic-co-glycolic acid) (PLGA) nanofibers for capturing CD44 receptor-overexpressing cancer cells.…”

“… Classification of nanotechnology-assisted methods using microfluidic devices developed for isolation and analysis of circulating tumor cells. All figures are reproduced with permission from [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. …”

Influence of thickness of SiO 2 layer on the performance of SINW sensors

“…The ultrahigh surface to volume ratios leads to the super-sensitivity and extremely low detection limits of silicon nanowires [11,12]. Moreover, silicon nanowire can be easily modified by various biological and chemical molecules that can be used to specifically detect target molecules, including a wide range of chemical and biological species [13][14][15]. In addition, it is compatible with the scale of target biochemical molecular for silicon nanowires with diameters less than 100 nm, whose unique advantages in biochemical detection is given to silicon nanowires [16,17].…”