Nanoscale measurements for osteoarthritis biomarker

There’s a new technique for measuring hyaluronic acid (HA), which appears to be associated with osteoarthritis. A March 12, 2018 news item on ScienceDaily makes the announcement,

For the first time, scientists at Wake Forest Baptist Medical Center have been able to measure a specific molecule indicative of osteoarthritis and a number of other inflammatory diseases using a newly developed technology.

This preclinical [emphasis mine] study used a solid-state nanopore sensor as a tool for the analysis of hyaluronic acid (HA).

I looked at the abstract for the paper (citation and link follow at end of this post) and found that it has been tested on ‘equine models’. Presumably they mean horses or, more accurately, members of the horse family. The next step is likely to be testing on humans, i.e., clinical trials.

A March 12, 2018 Wake Forest Baptist Medical Center news release (also on EurekAlert), which originated the news item, provides more details,

HA is a naturally occurring molecule that is involved in tissue hydration, inflammation and joint lubrication in the body. The abundance and size distribution of HA in biological fluids is recognized as an indicator of inflammation, leading to osteoarthritis and other chronic inflammatory diseases. It can also serve as an indicator of how far the disease has progressed.

“Our results established a new, quantitative method for the assessment of a significant molecular biomarker that bridges a gap in the conventional technology,” said lead author Adam R. Hall, Ph.D., assistant professor of biomedical engineering at Wake Forest School of Medicine, part of Wake Forest Baptist.

“The sensitivity, speed and small sample requirements of this approach make it attractive as the basis for a powerful analytic tool with distinct advantages over current assessment technologies.”

The most widely used method is gel electrophoresis, which is slow, messy, semi-quantitative, and requires a lot of starting material, Hall said. Other technologies include mass spectrometry and size-exclusion chromatography, which are expensive and limited in range, and multi-angle light scattering, which is non-quantitative and has limited precision.

The study, which is published in the current issue of Nature Communications, was led by Hall and Elaheh Rahbar, Ph.D., of Wake Forest Baptist, and conducted in collaboration with scientists at Cornell University and the University of Oklahoma.

In the study, Hall, Rahbar and their team first employed synthetic HA polymers to validate the measurement approach. They then used the platform to determine the size distribution of as little as 10 nanograms (one-billionth of a gram) of HA extracted from the synovial fluid of a horse model of osteoarthritis.

The measurement approach consists of a microchip with a single hole or pore in it that is a few nanometers wide – about 5,000 times smaller than a human hair. This is small enough that only individual molecules can pass through the opening, and as they do, each can be detected and analyzed. By applying the approach to HA molecules, the researchers were able to determine their size one-by-one. HA size distribution changes over time in osteoarthritis, so this technology could help better assess disease progression, Hall said.

“By using a minimally invasive procedure to extract a tiny amount of fluid – in this case synovial fluid from the knee – we may be able to identify the disease or determine how far it has progressed, which is valuable information for doctors in determining appropriate treatments,” he said.

Hall, Rahbar and their team hope to conduct their next study in humans, and then extend the technology with other diseases where HA and similar molecules play a role, including traumatic injuries and cancer.

Here’s a link to and a citation for the paper,

Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor by Felipe Rivas, Osama K. Zahid, Heidi L. Reesink, Bridgette T. Peal, Alan J. Nixon, Paul L. DeAngelis, Aleksander Skardal, Elaheh Rahbar, & Adam R. Hall. Nature Communications volume 9, Article number: 1037 (2018) doi:10.1038/s41467-018-03439-x
Published online: 12 March 2018

This paper is open access.

4 thoughts on “Nanoscale measurements for osteoarthritis biomarker

  1. Susan

    Not really sure we need a nano (or any other) marker for osteoarthritis – most people can tell if their joints have osteoarthritis. As for inflammation, well, the real issue with inflammation is in rheumatoid arthritis (an auto immune disease) not osteoarthritis, which is the result of wear-and-tear as it were. But hey, if there’s a cool marker to be found, who am I to quibble .. 🙂

  2. Maryse de la Giroday Post author

    Hi Susan! Before agreeing with your points I want to note that the news release is not clear about what benefit there is with finding these markers at the molecular level so I’m having to stretch a very fuzzy bit “The abundance and size distribution of HA in biological fluids is recognized as an indicator of inflammation, leading to osteoarthritis and other chronic inflammatory diseases. It can also serve as an indicator of how far the disease has progressed.” Here’s where I’m stretching: there seems to be a belief that if you can catch it at an earlier stage, you’ll be able to do something about it.
    As you note, osteoarthritis is a ‘wear and tear’ problem for which they have no solutions other medications for inflammation and pain, injectable materials to give cushioning for joints that no longer have that, and/or replacement surgery. (Please do correct me if I got this wrong.) Finding out that someone has a problem or a ‘market that indicates there could be a problem’ at an earlier stage has no impact whatsoever for someone who’s currently suffering. It’s a little hard to remain optimistic but there’s a possibility these insights might lead to something, some day.
    Thanks so much for dropping in and making me look at that piece again. I too get caught up in the pursuit of ‘???’ to the exclusion of other considerations. Cheers, Maryse

  3. Susan

    We who read your blog appreciate your “pursuit of ???” Maryse. And you are dead on when it comes to osteoarthritis.
    With RA it can help to catch it early; the new biologic drugs (Humera has become the biggest selling drug in the world wouldn’t you know) can prevent further joint damage. But osteoarthritis develops years down the road – in some ways the best defense is to be a lazy slob in your early years. I wonder how the young people who are bent over their phones today will fare in 20, 30 years; wonder if they will have osteoarthritis in their wrists, necks … Certainly runners end up with hip and knee damage.
    Joint “replacement” is an interesting term. (As you know I am always interested in the semantics of such phrases.) By calling the surgery knee replacement or hip replacement we mechanize the body. But .. talk to anybody who’s had one of those surgeries and they will tell you that the range and facility of motion is a pale reflection of the real one. For people in constant pain they are a godsend of course.
    As I was writing that it occurred to me that perhaps this osteoarthritis test you wrote about could perhaps serve a purpose with younger, more active people. Give them a hint that they are damaging their joints and remind them to be cautious lest they develop worse problems down the road?

  4. Maryse de la Giroday Post author

    Hi Susan! I had not realized that joint replacements are a “pale reflection.” The people I’ve talked to have been happy so happy to have easier mobility they tend to skip over any reservations they might have. It never occurred to me to ask but now that you point it out … well it makes sense (once you’ve seen one of these devices) that the ‘replacement’ would not perfectly mimic the joint. Thanks so much for dropping by and enriching my and other readers’ understanding. Cheers, Maryse

Leave a Reply

Your email address will not be published. Required fields are marked *