Profiling the heterogeneous phenotypes of individual circulating tumor cells (CTCs) from patients is a very challenging task, but it paves new ways for cancer management, especially personalized anticancer therapy. Herein, we propose a chip-assisted multifunctional-nanosphere system for efficient and reliable biomarker phenotype analysis of individual heterogeneous CTCs. Red fluorescent magnetic biotargeting multifunctional nanospheres and green fluorescent biotargeting nanospheres targeting to two kinds of CTC biomarkers are used for convenient dual-fluorescence labeling of CTCs along with magnetic tags. By integrating magnetic enrichment with a size-selective single-cell-trapping microfluidic chip (SCT-chip), over 90% of CTCs, even when the concentrations is as low as 10 CTCs per milliliter of blood, can be individually trapped at highly ordered micropillars, spatially separated from the minimal residual blood cells. Such single CTCs offer easy-readout fluorescence signals, facilitating efficient identification and reliable phenotype analysis in accordance with their biomarker expressions. Therefore, the phenotypes of breast tumor cells in terms of the expression level of human epidermal-growth-factor receptor 2, an important target of clinical anticancer drugs, are accurately assessed, and over 82% of them can be classified into corresponding cell subpopulations. Furthermore, this system demonstrates successful detection and subpopulation analysis of heterogeneous CTCs from seven breast cancer patients, which provides a promising new means for single-cell profiling of CTC-biomarker phenotypes and guiding of personalized anticancer therapy.
We report a single-microsphere based imaging assay method by integrating up-converting luminescence with optical tweezers for detecting microRNA-21 sequences. This method achieves a competitive detection limit of 12 fM with good selectivity and no dedicated signal amplification designs.
With the rapid advancement of nanobioscience, the interaction between nanomaterials and cells has become increasingly important, among which, understanding the nonspecific adsorption (NSA) between nanomaterials and cells is beneficial to the comprehension of nano−bio interactions. Herein, magnetic nanospheres (MNs) modified with different types of poly(ethylene glycol) (MNs-PEG) were used as models to systematically study the NSA between nanomaterials and cells. By exploring different surface properties of MNs modified with PEG, we found that the NSA between MNs and cells was greatly reduced after the modification of MNs-COOH with a long-chain (MW: 10 000), brush-conformational PEG, the extremely low NSA rate of which (less than 5%) was nearly one-fifth that of unmodified ones. Additionally, PEG modification improved the colloidal stability and adsorption uniformity of MNs to cells and remarkably reduced the number of adsorbed white blood cells (WBCs) in circulating tumor cell detection from complex blood samples. Surprisingly, the number of adsorbed WBCs by immunomagnetic nanospheres (IMNs) was 17 times more than that of PEGylated IMNs (IMNs-PEG). In a word, this work provides some perspective for the study on nanobio interactions and will be helpful to the construction and surface modification of low-adsorption nanomaterials.
The application of ultrasonication to P3HT in anisole can dramatically affect the crystallization of P3HT. The ultrasonication conditions were modulated by varying the ultrasonication time, ultrasonication power and ultrasonication temperature. Ultrasonicating at the dissolution temperature (85 °C) causes the concentration of the P3HT solution to fluctuate. When fixing the ultrasonication power at 100 W and ultrasonication time at 3 min, for P3HT crystallized in solution at 16 °C, the crystallization kinetics of ultrasonicated P3HT is slower than that of pristine P3HT. The nanofiber aggregation density and crystallinity of ultrasonicated P3HT are lower than those of pristine P3HT, and the nanofiber aggregation size is larger. For P3HT crystallized in solution at 20 °C, the crystallization kinetics, nanofiber morphology and crystallinity of ultrasonicated P3HT are similar to those of pristine P3HT. For P3HT crystallized in solution at 26 °C, the crystallization kinetics of ultrasonicated P3HT is faster than that of pristine P3HT, the nanofiber aggregation size is larger, and the crystallinity is higher. Fixing the crystallization temperature at 16 °C and varying the ultrasonication time and ultrasonication power can effectively modulate the crystallization kinetics of P3HT. When the P3HT solution is ultrasonicated at the crystallization temperature (16 °C), in addition to fluctuations in the concentration, ultrasonication promotes the disentanglement of P3HT chains. The combination of the two effects of ultrasonication is more beneficial for the crystallization of P3HT when solvophobic forces exist in a marginal solvent.
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