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.

Development of a multivariable online monitoring system for the thermoforming process

The thermoforming industry has been relatively slow to embrace modern measurement technologies. As a result researchers have struggled to develop accurate thermoforming simulations as some of the key aspects of the process remain poorly understood. For the first time, this work reports the development of a prototype multivariable instrumentation system for use in thermoforming. The system contains sensors for plug force, plug displacement, air pressure and temperature, plug temperature, and sheet temperature. Initially, it was developed to fit the tooling on a laboratory thermoforming machine, but later its performance was validated by installing it on a similar industrial tool. Throughout its development, providing access for the various sensors and their cabling was the most challenging task. In testing, all of the sensors performed well and the data collected has given a powerful insight into the operation of the process. In particular, it has shown that both the air and plug temperatures stabilize at more than 80C during the continuous thermoforming of amorphous polyethylene terephthalate (aPET) sheet at 110C. The work also highlighted significant differences in the timing and magnitude of the cavity pressures reached in the two thermoforming machines. The prototype system has considerable potential for further development.