Fibre-enhanced fluorescent-based immunosorbent assay.

During the manufacture of many bio-pharmaceutical products, it is difficult to monitor process yields in-line with production. This is particularly the case with egg-based influenza vaccine manufacture, where current assay methods, such as the fluorescent focus assay (for live-attenuated virus vaccines), require timescales incompatible with normal production cycles. This is due to the requirement to perform cell culture incubation as part of this assay, which takes several days to complete before a result is obtained. Other, more rapid assay methods, such as the enzyme-linked immunosorbent assay, rely on peroxidase-labelled antibodies, which are relatively expensive, and current plate-based fluorescent assays can be difficult to integrate within pharmaceutical production settings. In this paper, we propose a fluorescence-based assay using an optofluidic hollow-core photonic crystal fibre. Exploiting the fibre's waveguide modes to collect fluorescence, the system can quantitatively and specifically measure influenza concentrations below 10particles per ml in under 5 h, using less than 200l of sample. We propose that, with future improvements, this approach could ultimately be integrated directly into production lines to provide continuous feedback on virus concentration, enabling more effective optimisation of process yield.