title: Multivalent nanoparticle networks enable point-of-care detection of human phospholipase-A2 in serum.
abstract: A rapid and highly sensitive point-of-care (PoC) lateral flow assay for phospholipase A2 (PLA2) is demonstrated in serum through the enzyme-triggered release of a new class of biotinylated multiarmed polymers from a liposome substrate. Signal from the enzyme activity is generated by the adhesion of polystreptavidin-coated gold nanoparticle networks to the lateral flow device, which leads to the appearance of a red test line due to the localized surface plasmon resonance effect of the gold. The use of a liposome as the enzyme substrate and multivalent linkers to link the nanoparticles leads to amplification of the signal, as the cleavage of a small amount of lipids is able to release a large amount of polymer linker and adhesion of an even larger amount of gold nanoparticles. By optimizing the molecular weight and multivalency of these biotinylated polymer linkers, the sensitivity of the device can be tuned to enable naked-eye detection of 1 nM human PLA2 in serum within 10 min. This high sensitivity enabled the correct diagnosis of pancreatitis in diseased clinical samples against a set of healthy controls using PLA2 activity in a point-of-care device for the first time.
authors.affiliation: Department of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Chapman
authors.affiliation: Department of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Mologic Ltd, Bedford Technology Park, Thurleigh, Bedfordshire, MK44 2YP, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Burnapp
authors.affiliation: Mologic Ltd, Bedford Technology Park, Thurleigh, Bedfordshire, MK44 2YP, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bentham
authors.affiliation: Hepatology and Gastroenterology Section, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London, W2 1NY, UK.
authors.forename: David
authors.initials: D
authors.lastname: Hillier
authors.affiliation: Hepatology and Gastroenterology Section, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London, W2 1NY, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Zabron
authors.affiliation: Hepatology and Gastroenterology Section, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London, W2 1NY, UK.
authors.forename: Shahid
authors.initials: S
authors.lastname: Khan
authors.affiliation: Mologic Ltd, Bedford Technology Park, Thurleigh, Bedfordshire, MK44 2YP, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Tyreman
authors.affiliation: Department of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Molly M
authors.initials: MM
authors.lastname: Stevens
mesh_terms: D000208:Acute Disease; D000818:Animals; D001710:Biotin / Q000737:chemistry; D001774:Blood Chemical Analysis / Q000379:methods*; D017815:Elapidae; D005260:Female; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010195:Pancreatitis / Q000175:diagnosis / Q000201:enzymology; D054467:Phospholipases A2 / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D019095:Point-of-Care Systems; D011092:Polyethylene Glycols / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D008081:Liposomes; D011092:Polyethylene Glycols; D001710:Biotin; D054467:Phospholipases A2
keywords: biosensor; lateral flow device; multivalent network; phospholipase; point of care