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Enhanced capture and release of circulating tumor cells using hollow glass microspheres with a nanostructured surface.

ABSTRACT: Self-floating hollow glass microspheres (HGMS) modified with tumor-specific antibodies have been developed for the capture of circulating tumor cells (CTCs), and have demonstrated effective cell isolation and good viability of isolated cancer cells. However, the capture efficiency decreases dramatically if the spiked cell concentration is low, possibly due to insufficient interactions between cancer cells and the HGMS surface. In order to apply HGMS-based CTC isolation to clinically relevant samples, it is desirable to create nanostructures on the surface of HGMS to enhance cell-surface interactions. Nevertheless, current microfabrication methods cannot generate nanostructured-surfaces on microspheres. The authors have developed a new HGMS with a controlled nanotopographical surface structure (NSHGMS), and demonstrated isolation and recovery of rare cancer cells. NSHGMS are achieved by applying layer-by-layer (LbL) assembly of negatively charged SiO2 nanoparticles and positively charged poly-l-arginine molecules, then sheathing the surface with an enzymatically degradable LbL film made from biotinylated alginate and poly-l-arginine, and capping with anti-EpCAM antibodies and anti-fouling PEG molecules. Compared to smooth-surfaced HGMS, NSHGMS showed shorter isolation time (20 min), enhanced capture efficiency (93.6 ± 4.9%) and lower detection limit (30 cells per mL) for commonly used cancer cell lines (MCF7, SK-BR-3, PC-3, A549 and CCRF-CEM). This NSHGMS-based CTC isolation method does not require specialized lab equipment or an external power source, and thus, can be used for the separation of targeted cells from blood or other body fluids in a resource-limited environment.

SUBMITTER: Dong Z

PROVIDER: S-EPMC6693900 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Enhanced capture and release of circulating tumor cells using hollow glass microspheres with a nanostructured surface.

Dong Ziye Z Yu Dan D Liu Qingye Q Ding Zhenya Z Lyons Veronica J VJ Bright Robert K RK Pappas Dimitri D Liu Xinli X Li Wei W

Nanoscale 20180901 35

Self-floating hollow glass microspheres (HGMS) modified with tumor-specific antibodies have been developed for the capture of circulating tumor cells (CTCs), and have demonstrated effective cell isolation and good viability of isolated cancer cells. However, the capture efficiency decreases dramatically if the spiked cell concentration is low, possibly due to insufficient interactions between cancer cells and the HGMS surface. In order to apply HGMS-based CTC isolation to clinically relevant sam ...[more]

PMID: 30160287

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Project description:Circulating tumor cells (CTCs) from peripheral blood hold important information for cancer diagnosis and disease monitoring. Analysis of this "liquid biopsy" holds the promise to usher in a new era of personalized therapeutic treatments and real-time monitoring for cancer patients. But the extreme rarity of CTCs in blood makes their isolation and characterization technologically challenging. This paper reports the development of a geometrically enhanced mixing (GEM) chip for high-efficiency and high-purity tumor cell capture. We also successfully demonstrated the release and culture of the captured tumor cells, as well as the isolation of CTCs from cancer patients. The high-performance microchip is based on geometrically optimized micromixer structures, which enhance the transverse flow and flow folding, maximizing the interaction between CTCs and antibody-coated surfaces. With the optimized channel geometry and flow rate, the capture efficiency reached >90% with a purity of >84% when capturing spiked tumor cells in buffer. The system was further validated by isolating a wide range of spiked tumor cells (50-50,000) in 1 mL of lysed blood and whole blood. With the combination of trypsinization and high flow rate washing, captured tumor cells were efficiently released. The released cells were viable and able to proliferate, and showed no difference compared with intact cells that were not subjected to the capture and release process. Furthermore, we applied the device for detecting CTCs from metastatic pancreatic cancer patients' blood; and CTCs were found from 17 out of 18 samples (>94%). We also tested the potential utility of the device in monitoring the response to anti-cancer drug treatment in pancreatic cancer patients, and the CTC numbers correlated with the clinical computed tomograms (CT scans) of tumors. The presented technology shows great promise for accurate CTC enumeration, biological studies of CTCs and cancer metastasis, as well as for cancer diagnosis and treatment monitoring.

Project description:The design and development of thermal insulation materials is very important for the treatment of offshore oil pipelines. Understanding thermal energy transport in thermal insulation materials and predicting their thermal conductivities have important theoretical and practical value for the design of thermal insulation materials. In this work, lightweight and thermally insulated (LWTI) composites with the desired mechanical strength for offshore oil pipelines applications were prepared using epoxy resin (EP) as the matrix and hollow glass microspheres (HGMs) as the filler. The morphology, density, and mechanical properties of HGM/EP LWTI composites were studied first. The flexural strength and the flexural modulus of HGM/EP LWTI composites could still be as high as 22.34 ± 2.75 Mpa and 1.34 ± 0.03 GPa, respectively, while the density was only 0.591 g/cm3. The relationship between the effective thermal conductivity of HGM/EP LWTI composites and material parameters (sizes and contents together) has been studied systematically. A three-phase prediction model was built using the self-consistent approximation method to predict the effective thermal conductivity of HGM/EP LWTI composites, and the resin matrix, the wall thickness, the HGM particle size, and other parameters (such as air) were fully considered during the derivation of this three-phase thermal conductivity model. Finally, the insulation mechanism of HGM/EP LWTI composites was systematically analyzed. The thermal conductivities of HGM/EP LWTI composites with different diameters and HGM contents calculated by the three-phase prediction model agreed well with the experimental test results, with a minimum error of only 0.69%. Thus, this three-phase thermal conductivity model can be used to theoretically simulate the thermal conductivity of epoxy resin-based LWTI composites and can be the theoretical basis for the design and prediction of the thermal conductivity of other similar hollow spheres filled materials.

Dataset Information

Enhanced capture and release of circulating tumor cells using hollow glass microspheres with a nanostructured surface.

Publications

Enhanced capture and release of circulating tumor cells using hollow glass microspheres with a nanostructured surface.

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