The considerable activity in the area of organic thin films, involving very thin polymeric films and molecular monolayers and multilayers, led to the formation of a panel, sponsored by the Materials Sciences Division of the Department of Energy, to review this field. Its purpose was to better understand the relevant scientific topics and to suggest suitable areas of research. In particular, a number of potential applications were identified, which require further scientific advances for them to see fruition. These include nonlinear and active optical devices, chemical, biochemical, and physical sensors, protective layers (e.g., for passivation), patternable materials both for resists and for mass information storage, surface modification (e.g., wetting and electrochemical electrode properties), and synthetic biomacromolecules. Studies of these films have the added advantage that they could lead to a better scientific understanding of such subjects as the relationships between the microstructure of ordered molecular arrays and their collective properties, the tailoring of interfaces and surfaces, especially when used to model multibody interactions, and the physical and chemical reactions of films involving phase transitions and intraand interfilm transport. The areas that appear to require the most attention include the application of new characterization techniques, such as the scanning tunneling microscope, the improvement of mechanical and thermal stability, the identification and characterization of physical and chemical defects, and the effects of internal ordering on macroscopic properties. It is further recommended that strong interdisciplinary efforts be mounted to address and solve these problems.
BackgroundTo improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery.Methodology/Principal FindingsWe purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy.Conclusions/SignificanceFor the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs on a cell-by-cell basis is possible and may facilitate the application of ‘liquid biopsies’ to better model drug discovery.
The molecular organization in ultrathin polymer films (thicknesses less than 1000 angstroms) and thin polymer films (thicknesses between 1000 and 10,000 angstroms) may differ substantially from that of bulk polymers, which can lead to important differences in resulting thermophysical properties. Such constrained geometry films have been fabricated from amorphous poly(3-methyl-4-hydroxy styrene) (PMHS) and semicrystalline poly(di-n-hexyl silane) (PD6S) by means of spin-casting. The residual solvent content is substantially greater in ultrathin PMHS films, which suggests a higher glass transition temperature that results from a stronger hydrogen-bonded network as compared with that in thicker films. Crystallization of PD6S is substantially hindered in ultrathin films, in which a critical thickness of 150 angstroms is needed for crystalline morphology to exist and in which the rate of crystallization is initially slow but increases rapidly as the film approaches 500 angstroms in thickness.
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