Molecularly imprinted polymers for small cell lung cancer diagnosis

According to the World Health Organisation, cancer is the second leading cause of death globally and lung cancer is the most common type of cancer. Despite the progress that has been made over the years, there is still a need for improved early-stage diagnostic tools and better cancer treatment options. The detection of cancer at an early stage is of particular importance for aggressive cancer types, such as Small Cell Lung Cancer (SCLC), since intervention with therapy at an early-stage is critical for patient survival. In this thesis, the design and synthesis of highly crosslinked, magnetic and non-magnetic molecularly imprinted polymer (MIP) microspheres for exploitation in the early-stage diagnosis of SCLC is described, where a bottom-up proteomics approach was taken to target the signature peptide of the SCLC biomarker neuron-specific enolase (NSE). A prime focus was on the synthesis of MIPs using a template analogue approach, but also the production of microspheres with diameters around 2 μm since such particles are well-suited to demanding chemical separation work. MIPs and their non-imprinted analogues were synthesised by precipitation polymerisation using free radical polymerisation, photoinitiated polymerisation, and atom transfer radical polymerisation (ATRP), and packed into columns for on-line molecularly imprinted solid-phase extraction (MISPE) LC-MS/MS. The polymers had selectivity for the NSE signature peptide target, which enabled it to be extracted efficiently from water-rich samples, allowing its determination at clinically relevant levels. Next, the first example of activators regenerated by electron transfer atom transfer (ARGET) ATRP under precipitation polymerisation (PP) conditions is reported. This new method for polymer synthesis (called ARGET ATRPP) requires only very low levels of metal catalyst for success, a distinctive feature that enables the production of uniform polymer microspheres under reversible-deactivation radical polymerisation control but without a requirement to remove dissolved molecular oxygen rigorously from monomer solutions before polymerisation.According to the World Health Organisation, cancer is the second leading cause of death globally and lung cancer is the most common type of cancer. Despite the progress that has been made over the years, there is still a need for improved early-stage diagnostic tools and better cancer treatment options. The detection of cancer at an early stage is of particular importance for aggressive cancer types, such as Small Cell Lung Cancer (SCLC), since intervention with therapy at an early-stage is critical for patient survival. In this thesis, the design and synthesis of highly crosslinked, magnetic and non-magnetic molecularly imprinted polymer (MIP) microspheres for exploitation in the early-stage diagnosis of SCLC is described, where a bottom-up proteomics approach was taken to target the signature peptide of the SCLC biomarker neuron-specific enolase (NSE). A prime focus was on the synthesis of MIPs using a template analogue approach, but also the production of microspheres with diameters around 2 μm since such particles are well-suited to demanding chemical separation work. MIPs and their non-imprinted analogues were synthesised by precipitation polymerisation using free radical polymerisation, photoinitiated polymerisation, and atom transfer radical polymerisation (ATRP), and packed into columns for on-line molecularly imprinted solid-phase extraction (MISPE) LC-MS/MS. The polymers had selectivity for the NSE signature peptide target, which enabled it to be extracted efficiently from water-rich samples, allowing its determination at clinically relevant levels. Next, the first example of activators regenerated by electron transfer atom transfer (ARGET) ATRP under precipitation polymerisation (PP) conditions is reported. This new method for polymer synthesis (called ARGET ATRPP) requires only very low levels of metal catalyst for success, a distinctive feature that enables the production of uniform polymer microspheres under reversible-deactivation radical polymerisation control but without a requirement to remove dissolved molecular oxygen rigorously from monomer solutions before polymerisation