Multivalent Nanoparticle Networks Enable Point-of-Care Detection of Human Phospholipase-A2 in Serum

• Published in: ACS nano Vol. 9; no. 3; pp. 2565 - 2573
• Main Authors: Chapman, Robert, Lin, Yiyang, Burnapp, Mark, Bentham, Andrew, Hillier, David, Zabron, Abigail, Khan, Shahid, Tyreman, Matthew, Stevens, Molly M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 24.03.2015
• Subjects: Acute Disease; Animals; Biotin - chemistry; Blood Chemical Analysis - methods; Devices; Elapidae; Female; Gold; Humans; Liposomes; Liposomes - metabolism; Male; Models, Molecular; Nanoparticles - chemistry; Nanostructure; Nanotechnology - methods; Networks; Pancreatitis - diagnosis; Pancreatitis - enzymology; Phospholipase; Phospholipases A2 - blood; Phospholipases A2 - chemistry; Phospholipases A2 - metabolism; Point-of-Care Systems; Polyethylene Glycols - chemistry; Polymers; Protein Conformation; Serums; phospholipase; point of care; biosensor; lateral flow device; multivalent network
• ISSN: 1936-0851; 1936-086X; 1936-086X
• DOI: 10.1021/nn5057595

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.