Controllable nanofabrication of aggregate-like nanoparticle substrates and evaluation for surface-enhanced Raman spectroscopy.

The development of new and better substrates is a major focus of research aimed at improving the analytical capabilities of surface-enhanced Raman spectroscopy (SERS). Perhaps the most common type of SERS substrate, one consistently exhibiting large enhancements, is simple colloidal gold or silver nanoparticles in the 10-150 nm size range. The colloidal systems that are used most for ultrasensitive detection are generally aggregated clusters that possess "hot spot(s)" within some of the aggregates. A significant limitation of these synthetic substrates is that the "hot" aggregates are extremely difficult to create consistently or predict. Electron beam lithography (EBL) along with combinatorial spectral mapping can be used to overcome this limitation. Our previous work, and that of other researchers, invokes the special capabilities of EBL to design and fabricate periodic, highly ordered nanoparticle arrays for SERS. Building on this work, EBL, in conjunction with ancillary fabrication steps, can be used to create complex patterns that mimic random aggregates. These aggregates, unlike those created by colloidal deposition methods, can be uniquely reproduced within the resolution limits of EBL. In the work reported herein, we use a unique approach to create substrates containing a large number of randomly generated cells with different morphologies that are arrayed on silicon wafers. Instead of isolated metal nanoparticles, these structures resemble the aggregates of colloid. By spectral mapping, we investigate the SERS activity of the combinatorial arrays of cells using probe analytes. Two general categories of shapes are randomly designed in different sizes and densities into several hundred different 5 mum square cells. Following fabrication, it is shown that a SERS performance contrast of more than a factor of 44 is achieved among these cells and that the best performing cells can be cloned into uniformly high performing macropatterns of lithographically defined nanoaggregates (LDNAs). In this manner, extended LDNA surfaces with uniform 5 x 10(8) enhancement factors are created. Furthermore, the LDNAs can be further dissected and studied in an effort to increase the SERS enhancement per unit geometric substrate area.

Surface-enhanced Raman spectroscopy substrates created via electron beam lithography and nanotransfer printing.

The development of quantitative, highly sensitive surface-enhanced Raman spectroscopy (SERS) substrates requires control over size, shape, and position of metal nanoparticles. Despite the fact that SERS has gained the reputation as an information-rich spectroscopy for detection of many classes of analytes, in some isolated instances down to the single molecule detection limit, its future development depends critically on techniques for nanofabrication. Herein, an unconventional nanofabrication approach is used to produce efficient SERS substrates. Metallic nanopatterns of silver disks are transferred from a stamp onto poly(dimethysiloxane) (PDMS) to create nanocomposite substrates with regular periodic morphologies. The stamp with periodic arrays of square, triangular, and elliptical pillars is created via electron beam lithography (EBL) of ma-N 2403 resist. A modified cyclodextrin is thermally evaporated onto the stamp to overcome the adhesive nature of the EBL resist and to function as a releasing layer. Subsequently, Ag is physically vapor deposited onto the stamp at a controlled rate and thickness and used directly for nanotransfer printing (nTP). Stamps, substrates, and the efficiency of the nTP process were explored by scanning electron microscopy. Transferred Ag nanodisk-PDMS substrates are studied by SERS using Rhodamine 6G as the probe analyte. There are observed optimal conditions involving both Ag and cyclodextrin thickness. The SERS response of metallic nanodisks of various shapes and sizes on the original stamp is compared to the corresponding nTP created substrates with similar trends observed. Limits of detection for crystal violet and Mitoxantrone are approximately 10(-8) and 10(-9) M, respectively. As an innovative feature of this approach, we demonstrate that physical manipulation of the PDMS post-nTP can be used to alter morphology, e.g., to change internanodisk spacing. Additionally, stamps are shown to be reusable after the nTP process, adding the potential to scale-up regular morphology substrates by a stamp-and-repeat methodology.

Multiplexed microfluidic surface-enhanced Raman spectroscopy.

Over the past few decades, surface-enhanced Raman spectroscopy (SERS) has garnered respect as an analytical technique with significant chemical and biological applications. SERS is important for the life sciences because it can provide trace level detection, a high level of structural information, and enhanced chemical detection. However, creating and successfully implementing a sensitive, reproducible, and robust SERS active substrate continues to be a challenging task. Herein, we report a novel method for SERS that is based upon using multiplexed microfluidics (MMFs) in a polydimethylsiloxane platform to perform parallel, high throughput, and sensitive detection/identification of single or various analytes under easily manipulated conditions. A facile passive pumping method is used to deliver Ag colloids and analytes into the channels where SERS measurements are done under nondestructive flowing conditions. With this approach, SERS signal reproducibility is found to be better than 7%. Utilizing a very high numerical aperture microscope objective with a confocal-based Raman spectrometer, high sensitivity is achieved. Moreover, the long working distance of this objective coupled with an appreciable channel depth obviates normal alignment issues expected with translational multiplexing. Rapid evaluation of the effects of anion activators and the type of colloid employed on SERS performance are used to demonstrate the efficiency and applicability of the MMF approach. SERS spectra of various pesticides were also obtained. Calibration curves of crystal violet (non-resonant enhanced) and Mitoxantrone (resonant enhanced) were generated, and the major SERS bands of these analytes were observable down to concentrations in the low nM and sub-pM ranges, respectively. While conventional random morphology colloids were used in most of these studies, unique cubic nanoparticles of silver were synthesized with different sizes and studied using visible wavelength optical extinction spectrometry, scanning electron microscopy, and the MMF-SERS approach.