Developing an ultrawide dynamic range analytical platform for biomarker panel analysis in serum

The direct detection of biomarker species in biofluid samples via specific bioaffinity interactions is one of the most powerful tools for improving healthcare. However, for many diseases it is becoming increasingly clear that reliable diagnostics cannot be achieved by simply focusing on only one target species per measurement, despite the ongoing search for diagnostic simplicity and portability. Instead, a suite or panel of biomarkers needs to be accurately compared in order to provide an accurate disease snapshot. Particularly challenging is the robust and quantitative comparison of multiple biomolecular targets simultaneously at concentrations ranging from micromolar (~10-6 M) to below femtomolar (<10-15 M) in an environment as complex as blood serum. This project aims to address this measurement challenge utilising a combination of both optical instrumentation and data analysis design alongside the preparation and functionalisation of nanoparticles and integrated 3D-printed microfluidics for sample delivery and preparation. These will be applied to deliver a unique mutli-modal imaging instrument platform that enables rapid and high-throughput identification of both individual and nanoparticles assembled in the presence of a target molecule alongside the other species such as extracellular vesicles. The system performance will be demonstrated using biomarkers associated with two very challenging health conditions: (i) neurological disease, and (ii) pancreatic cancer, with a key objective being able to directly detect relative concentrations of multiple species in a patient serum sample within a relatively short timescale. Ultimately, being able to perform such measurements robustly also has the potential to be adapted to a large variety of other diseases as well as being a fundamental tool for nanoparticle design and characterisation, both of which further increase the potential impact and diversity of this project.