Magnetic nanoparticles and the capture of influenza antigens for rapid diagnosis

The avian influenza situation worldwide and the possibility of a new pandemic has been of great concern for the general public and has received vocal coverage in the press. Central to the prevention of this possibility is the ability to rapidly and accurately diagnose the presence of the virus in suspect cases. This allows patient isolation to occur as soon as possible and, equally importantly, prevents mis-diagnosis which could cause panic. The applicants expertise is in the detection of virus components and in the field of nanomaterials. Together, these technologies have the potential to offer new and powerful approaches to rapid diagnosis of infections as they may be well suited to use in rural communities that have no possibility to access a regional reference centre. Both applicants are active in responding to media queries in their respective fields and take in interest in applying leading edge technology to significant real-world problems. The applicants will make every effort to be as open as possible about what is being achieved during the course of this award.

In this application we seek to generate, characterise and test a range of protein conjugated nanomaterials designed to capture influenza antigens from (typically) nasopharyngeal washes. Nanomaterials offer a number of advantages for the development of diagnostics, the most important of which is the extremely high surface area to volume ratio which, assuming the material is addressable by a biological ligand, allows for an astonishingly high antigen capture surface in a very small volume (the equivalent of the surface of several ELISA plates in a few microlitres of solution). However, despite extensive discussion of their applicability in a variety of fields of medicine, particularly imaging and trans-dermal drug delivery, the application of nanomaterials to the field of diagnostics has been limited to date as the fabrication of many compounds is still difficult and the options to remove them following distribution within a sample remain limited. An area of notable success however has been in the field of fine chemical manufacture where paramagnetic nanomaterials coupled to chemical catalysts have been shown to be stable to harsh chemical conditions (e.g. boiling in acid) and have been successfully captured for re-use following dispersal by magnetic retrieval. Importantly for this application, in preliminary experiments, excellent data has been also obtained using such magnetised nanomaterials as bio-catalysts where they have been shown to successfully carry beta-lactamase via chemical linkage to the silica overlayer, to have enzyme activities as good as the free enzyme and to allow recovery and reusability upon application of magnetic separation. Here we seek to develop magnetised nanomaterials coupled with a range of proteins designed to capture influenza antigens from dilute solutions such as nasopharyngeal washes. The efficient capture of antigens is the rate limiting step in current rapid diagnostics and is the primary cause of false negatives. The developed materials will allow a step change in the sensitivity of diagnosis and, as importantly, will be stable in a variety of climates and easy to use in the non clinical setting.