No abstract

Colon cancer stem cells are believed to originate from a rare population of putative CD133 + intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133 + cancer cells are capable of tumor initiation. However, the precise contribution of CD133 + tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133 lacZ/+ ), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10 -/-CD133 lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133 -population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133 + and CD133 -metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133 -cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44 + CD24 -), whereas the CD133 + fraction is composed of CD44 low CD24 + cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic transition, CD133 + tumor cells might give rise to the more aggressive CD133 -subset, which is also capable of tumor initiation in NOD/SCID mice.

Refractive index (RI) sensors based on optical resonance techniques are receiving a high degree of attention because of the need to develop simple, low-cost, high-throughput detection technologies for a number of applications. While the sensing mechanism of most of the reported RI sensors is similar, the construction is quite different from technique to technique. It is desirable to have a uniform mechanism for comparing the various RI sensing techniques, but to date there exists a degree of variation as to how the sensing performance is quantified. Here we set forth a rigorous definition for the detection limit of resonant RI sensors that accounts for all parameters that affect the detection performance. Our work will enable a standard approach for quantifying and comparing the performance of optical resonance-based RI sensors. Additionally, it will lead to design strategies for performance improvement of RI sensors.

Optofluidics – the synergistic integration of photonics and microfluidics – has recently emerged as a new analytical field that provides a number of unique characteristics for enhanced sensing performance and simplification of microsystems. In this review, we describe various optofluidic architectures developed in the past five years, emphasize the mechanisms by which optofluidics enhances bio/chemical analysis capabilities, including sensing and the precise control of biological micro/nanoparticles, and envision new research directions to which optofluidics leads.

We have demonstrated a novel sensor architecture based on a liquid-core optical ring-resonator (LCORR) in which a fused silica capillary is utilized to carry the aqueous sample and to act as the ring resonator. The wall thickness of the LCORR is controlled to a few micrometers to expose the whispering gallery mode to the aqueous core. Optical characterization with a water-ethanol mixture shows that the spectral sensitivity of the LCORR sensor is approximately 2.6 nm per refractive index unit. A model based on Mie theory is established to explain the experimental results. The LCORR takes advantage of the high sensitivity, small footprint, and low sample consumption with the ring resonator, as well as the efficient fluidic sample delivery with the capillary, and will open an avenue to future multiplexed sensor array development.