To obtain a coding system for multiplex detection, we have developed a method to synthesize a new type of nanomaterial called composite organic-inorganic nanoparticles (COINs). The method allows the incorporation of a broad range of organic compounds into COINs to produce surface enhanced Raman scattering (SERS)-like spectra that are richer in variety than fluorescence-based signatures. Preliminary data suggest that COINs can be used as Raman tags for multiplex and ultrasensitive detection of biomolecules.

This paper presents a generalization of the hydrodynamic focusing technique to three-dimensions. Three-dimensional (3-D) hydrodynamic focusing offers the advantages of precision positioning of molecules in both vertical and lateral dimensions and minimizing the interaction of the sample fluid with the surfaces of the channel walls. In an ideal approach, 3-D hydrodynamic focusing could be achieved by completely surrounding the sample flow by a cylindrical sheath flow that constrains the sample flow to the center of the channel in both the lateral and the vertical dimensions. We present here design and simulation, 3-D fabrication, and experimental results from a piecewise approximation to such a cylindrical flow. Two-dimensional (2-D) and 3-D hydrodynamic focusing chips were fabricated using micromolding methods with polydimethylsiloxane (PDMS). Three-dimensional hydrodynamic focusing chips were fabricated using the "membrane sandwich" method. Laser scanning confocal microscopy was used to study the hydrodynamic focusing experiments performed in the 2-D and 3-D chips with Rhodamine 6G solution as the sample fluid and water as the sheath fluid.[1027]

To keep pace with the ever-shrinking feature sizes required in the microelectronics industry, suitable developers with high diffusivities, selectivity, and adjustable solvating power are required. Supercritical fluid (SCF) CO2 possesses many of the above unique properties and could serve as an “environmentally responsible” alternative developer to aqueous base. In this study, the high solubility of fluorinated block copolymers in supercritical CO2 and the selectivity of supercritical CO2 to both polarity changes and the molecular structure of the polymer were utilized to develop an environmentally friendly lithographic process. Polymers with acid-cleavable tetrahydropyranyl groups and supercritical CO2 soluble, fluoro-side-chain-containing methacrylate groups were synthesized with varying volume fractions of the components, and their solubilities in supercritical CO2 were characterized. Chemical amplification was used to effect the polarity change leading to the solubility difference in supercritical CO2, and the lithographic performance was evaluated. Important parameters such as sensitivity, contrast, and resolution were investigated, and 0.2 μm features using supercritical CO2 development were demonstrated.

Posttranslational modification (PTM) of proteins is likely to be the most common mechanism of altering the expression of genetic information. It is essential to characterize PTMs to establish a complete understanding of the activities of proteins. Here, we present a sensitive detection method using surface-enhanced Raman spectroscopy (SERS) that can detect PTMs from as little as zeptomoles of peptide. We demonstrate, using model peptides, the ability of SERS to detect a variety of protein modifications, such as acetylation, trimethylation, phosphorylation, and ubiquitination. In addition, we show the capability to obtain positional information for modifications such as trimethylation and phosphorylation using SERS and wavelet decomposition data analysis techniques. We further show that it is possible to apply SERS to detect PTMs from biological samples such as histones. We envision that this detection method might be a valuable technique that is complementary to mass spectrometry in obtaining orthogonal chemical and modification-specific information from biological samples at sensitive levels.