Preaggregated Ag Nanoparticles in Dry Swellable Gel Films for Off-the-Shelf Surface-Enhanced Raman Spectroscopy

Large, thin (50 mu m) dry polymer sheets containing numerous surface-enhanced Raman spectroscopy (SERS) active Ag nanopartide aggregates have been prepared by drying aqueous mixtures of hydroxyethylcelloulose (HEC) and preaggregated Ag colloid in 10 x 10 cm molds. In these dry films, the particle aggregates are protected from the environment during storage and are easy to handle; for example, they can be cut to size with scissors. When in use, the highly swellable HEC polymer allowed the films to rapidly absorb aqueous analyte solutions while simultaneously releasing the Ag nanoparticle aggregates to interact with the analyte and generate large SERS signals. Either the films could be immersed in the analyte solution or 5 mu L droplets were applied to the surface; in the latter method, the local swelling caused the active area to dome upward, but the swollen film remained physically robust and could be handled as required. Importantly, encapsulation and release did not significantly compromise the SERS performance of the colloid; the signals given by the swollen films were similar to the very high signals obtained from the parent citrate-reduced colloid and were an order of magnitude larger than a commercially available nanoparticle substrate. These "Poly-SERS" films retained 70% of their SERS activity after being stored for 1 year in air. The films were sufficiently homogeneous to give a standard deviation of 3.2% in the absolute signal levels obtained from a test analyte, primarily due to the films' ability to suppress "coffee ring" drying marks, which meant that quantitative analysis without an internal standard was possible. The majority of the work used aqueous thiophenol as the test analyte; however, preliminary studies showed that the Poly-SERS films could also be used with nonaqueous solvents and for a range of other analytes including theophylline, a therapeutic drug, at a concentration as low as 1.0 x 10(-5) mol dm(-3) (1.8 mg/dm(3)), well below the sensitivity required for theophylline monitoring where the target range is 10-20 mg/dm(3).

Swellable polymer films containing Au nanoparticles for point-of-care therapeutic drug monitoring using surface-enhanced Raman spectroscopy

Large (10 × 10 cm) sheets of surface-enhanced Raman spectroscopy (SERS) active polymer have been prepared by stabilising metal nanoparticle aggregates within dry hydroxyethylcellulose (HEC) films. In these films the aggregates are protected by the polymer matrix during storage but in use they are released when aqueous analyte droplets cause the films to swell to their gel form. The fact that these "Poly-SERS" films can be prepared in bulk but then cut to size and stored in air before use means that they provide a cost effective and convenient method for routine SERS analysis. Here we have tested both Ag and Au Poly-SERS films for use in point-of-care monitoring of therapeutic drugs, using phenytoin as the test compound. Phenytoin in water could readily be detected using Ag Poly-SERS films but dissolving the compound in phosphate buffered saline (PBS) to mimic body fluid samples caused loss of the drug signal due to competition for metal surface sites from Cl^- ions in the buffer solution. However, with Au Poly-SERS films there was no detectable interference from Cl^- and these materials allowed phenytoin to be detected at 1.8 mg L^-1, even in PBS. The target range of detection of phenytoin in therapeutic drug monitoring is 10-20 mg L^-1. With the Au Poly-SERS films, the absolute signal generated by a given concentration of phenytoin was lower for the films than for the parent colloid but the SERS signals were still high enough to be used for therapeutic monitoring, so the cost in sensitivity for moving from simple aqueous colloids to films is not so large that it outweighs the advantages which the films bring for practical applications, in particular their ease of use and long shelf life.

SERS of meso-droplets supported on superhydrophobic wires allows exquisitely sensitive detection of dipicolinic acid, an anthrax biomarker, considerably below the infective dose

Surface-enhanced Raman measurements of <1 μL analyte/colloid meso-droplets on superhydrophobic wires with hydrophilic tips allowed dipicolinic acid, a spore biomarker for Bacillus anthracis (anthrax), to be detected at 10(-6) mol dm(-3). This is equivalent to 18 spores, significantly below the infective dose of 10(4) spores and 2 orders of magnitude better than previous measurements.