Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor

• Published in: Nature communications Vol. 9; no. 1; pp. 1037 - 9
• Main Authors: Rivas, Felipe, Zahid, Osama K., Reesink, Heidi L., Peal, Bridgette T., Nixon, Alan J., DeAngelis, Paul L., Skardal, Aleksander, Rahbar, Elaheh, Hall, Adam R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.03.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 45/29; 631/61/350/1058; 631/61/475; 639/925/927/59; 9/10; 9/97; 96/10; Animals; Biocompatibility; Bioindicators; Biomarkers; Biomedical materials; Computational fluid dynamics; Disease Models, Animal; Electrochemical Techniques - instrumentation; Electrochemical Techniques - methods; Electrophoresis - instrumentation; Electrophoresis - methods; Horses; Humanities and Social Sciences; Humans; Hyaluronic acid; Hyaluronic Acid - chemistry; Hyaluronic Acid - metabolism; Lubrication; Molecular Weight; multidisciplinary; Nanopores; Osteoarthritis; Osteoarthritis - metabolism; Particle Size; Physiology; Polymers; Porosity; Progressions; Science; Science (multidisciplinary); Size distribution; Solid state; Synovial fluid; Synovial Fluid - chemistry; Synovial Fluid - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03439-x

Hyaluronan (or hyaluronic acid, HA) is a ubiquitous molecule that plays critical roles in numerous physiological functions in vivo, including tissue hydration, inflammation, and joint lubrication. Both the abundance and size distribution of HA in biological fluids are recognized as robust indicators of various pathologies and disease progressions. However, such analyses remain challenging because conventional methods are not sufficiently sensitive, have limited dynamic range, and/or are only semi-quantitative. Here we demonstrate label-free detection and molecular weight discrimination of HA with a solid-state nanopore sensor. We first employ synthetic HA polymers to validate the measurement approach and then use the platform to determine the size distribution of as little as 10 ng of HA extracted directly from synovial fluid in an equine model of osteoarthritis. Our results establish a quantitative method for assessment of a significant molecular biomarker that bridges a gap in the current state of the art. Involved in various diseases, hyaluronic acid is an important indicator of pathophysiology. Here, the authors report on a solid-state nanopore for the detection of the molecular weight and abundance of hyaluronic acid and demonstrate the system by studying an equine model of osteoarthritis