Cookies

Like most websites The Pathologist uses cookies. In order to deliver a personalized, responsive service and to improve the site, we remember and store information about how you use it. Learn more.
Diagnostics Analytical science, Biochemistry and molecular biology, Clinical care, Liquid biopsy, Precision medicine, Screening and monitoring, Technology and innovation

Sensing the Tiniest Change

Molecules that are essential for the body, such as proteins and hormones, can often yield significant insight into a patient’s health status. But many of these molecules are present in the blood in pico- or nanomolar concentrations. The best-known assay to measure such low concentrations outside the body is an elaborate, multi-step process that yields a single concentration value: ELISA. In contrast, continuous monitoring dynamically follows biomarker concentration in solution, leading to a stream of data rather than an isolated result. For continuous monitoring to work, molecular binding must be reversible and lead directly to a measurable signal without consumption or production of chemical reactants. The sensing principle should be self-contained, reversible, and stable over a long period of time. Still, the assay should be as sensitive and as specific as ELISA. And that’s the challenge my colleagues at Eindhoven University of Technology and I are addressing (1).

BPM refers to “Biomarker monitoring based on sensing of Particle Mobility.” The technique exploits the fact that tiny particles in liquid are constantly in random motion because water molecules collide with them. What we did is couple the particles to a substrate via a flexible molecular tether, so that the particles wiggle back and forth. To detect a specific biomarker, the particles and the substrate are provided with affinity molecules; this enables specific, reversible interactions with the biomarker molecules in solution. When a biomarker molecule attaches to both particle and substrate, they form a molecular sandwich bond that greatly reduces the particle’s mobility. When the biomarker is released, the particle regains its original mobility. So these mobility changes, which we detect via dark-field optical video microscopy, indicate the capture or release of a single biomarker molecule – and the number of changes per minute reveals, with high sensitivity and specificity, the concentration of the biomarker in the liquid.

The beauty of the BPM sensor technology is that increases and decreases in biomarker concentration can be precisely monitored over time. We have demonstrated its use in monitoring protein and DNA, but the technology is widely applicable; affinity molecules such as antibodies and aptamers are available for almost all biomarkers.

We think that BPM sensing can become an early warning system that signals patient deterioration – useful for postoperative, immunocompromised, or chronically ill patients, as well as those in critical condition. Furthermore, patients who receive potent drugs with a narrow therapeutic range might benefit from a sensor that enables rapid and robust dosing regulation. Before that can become a reality, though, we need to develop assays for several medically relevant biomarkers and demonstrate the required analytical performance. This will be followed by clinical proof-of-concept studies, which should give solid ground for subsequent development of a product. In total, we expect the process to take five to 10 years. We are now defining key applications and markets to determine our technical and clinical direction. Are we going to focus on measuring early warning markers, or on therapy monitoring? What patient group will we target? What value will we add? The answers to these questions will define our work in the coming years.

Continuous biomarker monitoring will go through several stages of maturity – and, in the future, may be as easy to perform as today’s blood pressure or heart rate measurements. As technology development increasingly focuses on important medical needs, we have an interesting road ahead.

Enjoy our FREE content!

Log in or register to read this article in full and gain access to The Pathologist’s entire content archive. It’s FREE and always will be!

Login if you already created an account

Or register now - it’s free and always will be!

You will benefit from:

  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Pathologist magazine
Register

Or Login as a Guest or via Social Media

  1. EWA Visser et al., “Continuous biomarker monitoring by particle mobility sensing with single molecule resolution”, Nat Commun, 9, 2541 (2018). PMID: 29959314.

About the Author

Menno Prins

Menno Prins is Professor in the Department of Biomedical Engineering at Technische Universiteit Eindhoven, The Netherlands.

Newsletter

Send me the latest from The Pathologist.

Sign up now

Related Articles

Subspecialties

A Lasting Legacy

| Mary J. Wirth

Inside the Lab

Shining a Brighter Light

| Srikanth Singamaneni

Inside the Lab

No Label? No Problem!

Most Popular

Register here

Register to access our FREE online portfolio, request the magazine in print and manage your preferences.

You will benefit from:

  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Pathologist magazine

Register