Isolation of circulating tumor cells using a microvortex-generating herringbone-chip.

Rare circulating tumor cells (CTCs) present in the bloodstream of patients with cancer provide a potentially accessible source for detection, characterization, and monitoring of nonhematological cancers. We previously demonstrated the effectiveness of a microfluidic device, the CTC-Chip, in capturing these epithelial cell adhesion molecule (EpCAM)-expressing cells using antibody-coated microposts. Here, we describe a high-throughput microfluidic mixing device, the herringbone-chip, or "HB-Chip," which provides an enhanced platform for CTC isolation. The HB-Chip design applies passive mixing of blood cells through the generation of microvortices to significantly increase the number of interactions between target CTCs and the antibody-coated chip surface. Efficient cell capture was validated using defined numbers of cancer cells spiked into control blood, and clinical utility was demonstrated in specimens from patients with prostate cancer. CTCs were detected in 14 of 15 (93%) patients with metastatic disease (median = 63 CTCs/mL, mean = 386 ± 238 CTCs/mL), and the tumor-specific TMPRSS2-ERG translocation was readily identified following RNA isolation and RT-PCR analysis. The use of transparent materials allowed for imaging of the captured CTCs using standard clinical histopathological stains, in addition to immunofluorescence-conjugated antibodies. In a subset of patient samples, the low shear design of the HB-Chip revealed microclusters of CTCs, previously unappreciated tumor cell aggregates that may contribute to the hematogenous dissemination of cancer.

A spectral approach to determine location and orientation of azo dyes within surfactant aggregates.

The UV-vis absorption properties of azo dyes are known to exhibit a variation with the polarity and acidity of the dye environment. The spectral properties of a series of anionic azo dyes were characterized to further probe the interaction of these dyes with two types of surfactant aggregates: (1) the spherical micelles formed in aqueous solution by alkyltrimethylammonium bromide (C(n)TAB) surfactants with n=10-16 and (2) the unilamellar vesicles spontaneously formed in water from binary mixtures of the oppositely-charged double-tailed surfactants cationic didodecyldimethylammonium bromide (DDAB) and anionic sodium dioctylsulfosuccinate (Aerosol OT or AOT). The observed dye spectra reflect the solvatochromic behavior of the dyes and suggest the location and orientation of the dye within the surfactant aggregates. Deconvolution of the overall spectra into sums of Gaussian curves more readily displays any contributions of tautomeric forms of the azo dyes resulting from intramolecular hydrogen bonding. The rich variation in UV/vis absorption properties of these anionic azo dyes supports their use as sensitive tools to explore the nanostructures of surfactant aggregates.