Recent advances in nanotechnology have led to the development of nano-electro-mechanical systems (NEMS) such as nanomechanical resonators, which have recently received significant attention from the scientific community. This has not only been for their capability for the label-free detection of bio/chemical-molecules at single-molecule (or atomic) resolution for future applications such as the early diagnostics of diseases such as cancer, but also for their unprecedented ability to detect physical quantities such as molecular weight, elastic stiffness, surface stress, and surface elastic stiffness for adsorbed molecules on the surface. Most experimental works on resonator-based molecular detection have been based on the principle that molecular adsorption onto a resonator surface increases the effective mass, and consequently decreases the resonant frequencies of the nanomechanical resonator. However, this principle is insufficient to provide fundamental insights into resonator-based molecular detection at the nanoscale; this is due to recently proposed novel nanoscale detection principles including various effects such as surface effects, nonlinear oscillations, coupled resonance, and stiffness effects. Furthermore, these effects have only recently been incorporated into existing physical models for resonators, and therefore the universal physical principles governing nanoresonator-based detection have not been completely described. Therefore, our objective in this review is to overview the current attempts to understand the underlying mechanisms in nanoresonator-based detection using physical models coupled to computational simulations and/or experiments. Specifically, we will focus on issues of special relevance to the dynamic behavior of nanoresonators and their applications in biological/chemical detection: the resonance behavior of micro/nano-resonators; resonator-based chemical/biological detection; physical models of various nanoresonators such as nanowires, carbon nanotubes, and graphene. We pay particular attention to experimental and computational approaches that have been useful in elucidating the mechanisms underlying the dynamic behavior of resonators across multiple and disparate spatial/length scales, and the resulting insight into resonator-based detection that has been obtained. We additionally provide extensive discussion regarding potentially fruitful future research directions coupling experiments and simulations in order to develop a fundamental understanding of the basic physical principles that govern NEMS and NEMS-based sensing and detection applications.

Purpose: Most breast cancers have chromosomal instability that seems related to defective mitotic spindle checkpoints. Because the molecular basis of this defect is unknown, we evaluated breast cancer cell lines and tissues for possible defects involving the major mitotic checkpoint genes responsible for maintaining chromosomal stability. Experimental Design:We analyzed sequences and expression levels (RNA and protein) of eight major spindle checkpoint genes (MAD1L1, MAD2L1, MAD2L2, BUB1, BUB1B, BUB3, CDC20, and TTK) in a panel of 12 breast cancer cell lines, most with established genetic instability and defective spindle damage checkpoint response. mRNA levels of these genes were also measured in primary tumor samples, and immunohistochemical staining was used to evaluate BUB1B protein levels in a panel of 270 additional cases of breast cancer. Results: No functionally significant sequence variations were found for any of the eight genes in the breast cancer cell lines with chromosomal instability. More surprisingly, the mRNA and protein levels for these checkpoint genes are significantly higher in the genetically unstable breast cancer cell lines and in high-grade primary breast cancer tissues than in the stable (and checkpoint proficient) MCF-10A and normal mammary epithelial cells, or in normal breast tissues. In fact, overexpression of the BUB1B protein is a marker that recognizes nearly 80% of breast cancers in paraffin-embedded tissues. Conclusions: Defective mitotic spindle checkpoints in breast cancer are most likely not caused by low expression or mutations of these eight checkpoint genes. High levels of these particular transcripts could represent a cellular compensation for defects in other molecular components of the mitotic spindle damage checkpoint, and increased expression of these genes might be markers of breast cancers with chromosomal instability.Most breast cancers have significantly aberrant genomic structure, including abnormal numbers of chromosomes. We have previously shown that in breast cancer cell lines, chromosome numbers are both variable and unstable (1), a phenomenon that seems related to defective mitotic spindle checkpoint controls. This chromosomal instability in breast cancer is similar to what has been observed in other cancers, where defective mitotic spindle checkpoint genes have been implicated as a basis of chromosomal instability. For example, mutations in the BUB1 mitotic checkpoint gene were initially reported in a small number of colorectal cancers with chromosomal instability (2, 3), Subsequently, mutations of BUB1 were reported in colon and pancreatic cancers (3, 4), and a truncating mutation of the MAD2L1 gene was reported for a single breast cancer cell line (4).Further analyses of the BUB1, BUB1B, and MAD2L1 checkpoint genes, however, have revealed that these mutations are relatively uncommon in cancer. Supporting a possible alternative mechanism for reducing the activity of checkpoint proteins, several studies have provided evidence that low expression ...

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Localized surface plasmon resonance (LSPR) is induced by incident light when it interacts with noble metal nanoparticles that have smaller sizes than the wavelength of the incident light. Recently, LSPR-based nanobiosensors were developed as tools for highly sensitive, label-free, and flexible sensing techniques for the detection of biomolecular interactions. In this paper, we describe the basic principles of LSPR-based nanobiosensing techniques and LSPR sensor system for biomolecule sensing. We also discuss the challenges using LSPR nanobiosensors for detection of biomolecules as a biomarker.