4. Open in another window Fig. flexible SERS systems for differentiating cancerous from noncancerous cells. Introduction Uncovered almost four years ago, surface improved Raman spectroscopy (SERS)1 and following techniques such as for example surface improved fluorescence (SEF)2 and surface area improved infrared spectroscopy (SEIRS)3C5 are suffering from into mature solutions to provide unprecedented degrees of awareness. SERS specifically provides ultra-high awareness right down to attomolar concentrations as well as to an individual molecule level.3,6C11 Moreover, the use of these surface enhanced techniques has enabled biosensing and biomolecular acknowledgement with ultra-high sensitivity, opening possibilities for a wealth of applications to probe intimate biological processes with minimal intrusion, better specificity and high reproducibility.10,12C16 The interactions between biomolecules and their changes in conformation in response to stimuli are processes that can be probed at the monolayer level with lower light irradiance and shorter acquisition time, thereby reducing experimental invasion and physiological stress. Keys to the success of surface-enhanced spectroscopies are improvements in micro and nanofabrication techniques such as electron-beam lithography and focused ion beam milling that allow one to reproducibly fabricate plasmonic platforms with a 10 nm resolution.17C22 The opto-geometric parameters of these platforms can be finely tailored to tune the localized surface plasmon resonance to a determined probe wavelength. Nanosphere lithography is an inexpensive and high throughput technique ideally suited to produce large surfaces of 2D and 3D periodic nanostructures with a variety of shapes such as nanoscale triangles, pyramids, rings, overlaps, gaps, rod chains, and holes.2,23C26 Such homogeneous platforms can be further functionalized enabling the study of monolayers of molecules or biomolecules. For example, SERS platforms functionalized with aptamers have been successfully utilized for toxin and protein acknowledgement.27,28 Antibody functionalization of SERS substrates to detect biomarkers of endocrine disrupting compounds was also explained.29 Furthermore, simultaneous detection and quantification of bacterial pathogens and enzymatic processes such as histone demethylase activity have been probed using SERS-based assays.30,31 However, using such platforms, significant difficulties are still encountered in the study of biological processes, such as intracellular sensing,32 chemical exchanges between cells or responses of cells to endogenous or exogenous stimuli.33,34 One significant challenge arises from the inherently random growth of cells over most surfaces.35 The positional control of cell growth over an array of plasmonic platforms would open new possibilities for multiplexed parallel screening using SERS, SEF or other optical techniques involving BIBF0775 a plasmon resonance that has been tuned to enhance a specific spectral region. Each cell position over a plasmonic platform would be defined by a set of spatial coordinates, allowing automated measurements over a large number of individual cells. This enables acquisition of statistically relevant ensembles of data. The control of cell density over the surface would provide the possibility to control and study cell-substrate and cellCcell interactions.36,37 Our group has previously introduced a new method for cell positioning using plasma deposition of fluoropolymer BIBF0775 thin films.35 However, a plasmonic platform was not incorporated, so it was not possible to perform optical studies of analytes or cells mediated by surface-enhanced Rabbit Polyclonal to CROT methods. Herein, we expose the development of a new device that embeds an NSL plasmonic platform into a micro-scale pattern that directs cell adhesion and growth. The micropatterning allows one to locate the analyte around the plasmonic BIBF0775 platform and to further perform surface-enhanced measurements with improved sensitivity. We demonstrate that different cell lines such as immortalized cells and neurons can.