Nanosilica (SiO 2 NP) is a commonly used nanomaterial in industrial and research settings [ 1 , 2 ] and with its increased presence in consumer goods, the toxicity of SiO 2 NP needs to be elucidated. It is well known that exposure to silica dust leads to silicosis, a common occupational disease in China. [ 3 ] SiO 2 NP being much smaller than silica dust may have altered properties which could present a different toxicity from the latter. [ 4 ] Recent studies have revealed that SiO 2 NP exposure exerts effects [ 4 ] such as cytotoxicity, [ 5 ] global genomic hypomethylation, [ 6 ] and alteration of protein expression in cells. [ 7 ] Numerous efforts have also been channeled towards the pathological, genomic and proteomic effects of exposure to SiO 2 NPs. There is also an incipient interest in applying metabolomics to nanotoxicity [ 8 ] but knowledge of how basic metabolic perturbation occurs due to such exposure still remains to be expanded. Here, we seek to address this knowledge gap through metabolomics. Metabolomics is defi ned as "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modifi cation" [ 9 ] and its use in nanotoxicity is a relatively new approach.Our metabolomics-based study integrates two highly sensitive and complementary chromatographic mass spectrometry platforms. With these platforms, we detected signifi cant and dose-dependent changes in the metabolic profi les of human MRC-5 fetal lung fi broblasts that were treated with different doses of SiO 2 NPs. Our results revealed that despite no evidence of morphological or viability changes, there was already a decrease of various cellular amino acid levels accompanied with increased phospholipid and urea concentrations. Glutathione, an important cellular antioxidant was also decreased in a similar dose-dependent manner. Further examinations revealed increases in cellular vacuole size and number with increasing SiO 2 NP concentration. Our work therefore brings forth a new aspect of nanotoxicity where metabolomic changes are associated with increased SiO 2 NP doses, most likely due to oxidative stress.SiO 2 NPs were synthesized using the reverse microemulsion method to achieve nanoparticles with an average diameter of 45 nm. Dye-doped nanoparticles were synthesized in a similar manner with the addition of tris(2,2'-bipyridyl)′ dichlororuthenium(II) hexahydrate (RUPBY). The fl uorescence of the dye-doped nanoparticles was measured using a PerkinElmer LS55 fl uorescence spectrometer, which showed the expected fl uorescence with maximum excitation (Ex) at 425 nm and maximum emission (Em) at 608 nm. The doped nanoparticles were of similar size to that of the uncoated SiO 2 NPs ( Figure 1 ).The human fetal lung fi broblast MRC-5 cell line, a commonly used cell line for studying respiratory diseases, was grown in 96-well culture plates at 4000 cells/well and treated with different doses of SiO 2 NPs (0, 2.5, 10.0, 40.0, 80.0 μ g mL − 1 ). Cell viability was tested using...

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We report on the development of one-dimensional microfluidic bead arrays for rapid and quantitative molecular profiling of human cancer cells. This new bioanalytical platform integrates the rapid binding kinetics of suspension bead carriers, the multiplexing and encoding capabilities of gene/protein chips, and the liquid handling advantages of microfluidic devices. Using antibody-conjugated beads in a two-site "sandwich" format, we demonstrate that the proteomic contents of as few as 56 human lung epithelial cancer cells can be determined with high sensitivity and specificity. The results indicate that each cell contains approximately 6 x 10(5) copies of the tumor suppressor protein P53. We have further examined the expression changes of P53, c-Myc, and beta-Actin as a function of anticancer drug treatment and have validated these changes by using Western blotting. This ability to quantitatively analyze normal and diseased cells raises new possibilities in studying cancer heterogeneity and circulating tumor cells.

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