A Joint Venture

Hyaluronan (hyaluronic acid) plays an essential role in the physiological functions of joints, giving rise to its use as a biomarker for osteoarthritis. However, in analysis, results are only semiquantitative because of a lack of sensitivity and insufficient dynamic range. Now, researchers from Wake Forest School of Medicine, Cornell University, and the University of Oklahoma Health Sciences Center are looking to boost sensitivity to improve quantitation using a solid-state nanopore sensor (1). We spoke with Adam Hall, lead researcher and Assistant Professor of Biomedical Engineering, to find out more.

How did the investigation come about?

My lab has a strong interest in applying nanopore technology to biomarkers. Ellie Rahbar, a colleague who has prior experience working with hyaluronan as a biomarker of trauma and knows the mechanism of our technology, recognized that nanopores might be able to measure its concentration. With the help of Paul DeAngelis of the University of Oklahoma College of Medicine, we determined that we could identify the size of hyaluronan polymers very accurately on a molecule-by-molecule basis. The final piece of the puzzle came when I met Heidi Reesink, a veterinary scientist who was using conventional technology to study hyaluronan in the knee joints of osteoarthritic horses. The fit was too perfect to ignore, so we initiated a collaboration that allowed us to apply our technology to an ideal in vivo system.

How easily will this translate to the clinic?

The technology itself is well-positioned for translation. We and others have developed advanced technology to increase affordability, make the results relatively easy to collect, and keep the measurement system compact. In fact, we believe the entire apparatus could be attached to, and powered by, a smartphone at some point.

There is clear evidence that osteoarthritis strongly affects hyaluronan, but definitive linkages between the disease’s molecular characteristics and its grading and progression remain to be determined. This is mostly because of limitations in the technologies available for studying it; we believe our technology will fill that gap. A key advantage of our platform is its sensitivity: we may be able to test blood or urine (instead of synovial fluid drawn directly from the knee joint) – allowing us to make analysis less invasive.

How does your approach compare with current methods?

It rivals the precision and resolution of existing techniques, which tend to be much more expensive and time-consuming (and also require significant expertise and infrastructure). As with any new technology, it will take time for people to accept, but as our system becomes more accessible, and as we continue to show how our results compare with – or even exceed – those of conventional techniques, we think its advantages will become clear.

What’s next?

We are pushing hyaluronan analysis further with more physiological testing as well as expanding into other diseases in which it may be important. We are also extending to other related molecules to diversify the utility of the platform, including our continued development of nucleic acid biomarker analysis.