A glowing new way to measure antibodies

An international team of researchers has come up with a quick, on-the-spot way to measure antibodies to several important diseases. This can tell if someone has been exposed to a certain disease. Tracking antibody levels over time might also help doctors figure out the best treatment plan for a patient.

When the body senses some invading bacteria or viruses have arrived, it calls out germ-fighting troops: antibodies. These special proteins can fight infections and later work as sentinels that will scout for more of the disease-causing germs.

Many antibody tests today must be processed using a lab full of expensive equipment, notes Maarten Merkx. He works at Eindhoven University of Technology in the Netherlands. As a biomolecular engineer, he analyzes, designs and manipulates molecules such as DNA, proteins and other substances produced or used by living cells. Often, a trained technician also is needed to perform antibody tests, Merkx notes. That can make them rather costly. One added challenge: So much blood may be needed, he says, that the technician must first pull out a syringe and draw a vial of blood.

Merkx and his colleagues wanted to avoid these problems. But they didn’t want to start from scratch. Instead, they decided to adapt a system they created two years ago. It works. But at a minimum, it needs more blood than a pinprick would deliver.

Their new version doesn’t. It takes just a drop of blood to trigger a glow on test strips. The result shows up in less than five minutes. The color of that glow indicates whether certain antibodies are there — or not. That telltale glow lasts about a half-hour, which should give doctors plenty of time to read the findings.

Also novel, this method can test for signs of more than one type of infection at once — from flu to AIDS. Because the proteins can in theory be designed to detect any type of antibody, this method might even be used to tell whether someone has antibodies to the new coronavirus that causes COVID-19.

Researchers described their innovation on May 22 in ACS Sensors.

“There are a lot of clever ideas in this paper,” says Charles Henry. For instance, he particularly likes that ability to look for several antibodies at once. Henry is a chemist who works at Colorado State University, in Fort Collins, and was not involved in the new study.

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Blue it’s there, green it’s not

The test relies on two types of glowing substances. One is known as luciferin (Loo-SIFF-er-un) and comes in several forms. The type used in this test glows blue when it reacts with oxygen. An enzyme called luciferase (Loo-SIFF-ur-ace) helps speed that reaction, Merkx notes. The second glowing chemical in their test is called luminescent (Loo-mun-ESS-sent) antibody-sensing protein, or LASP.

The researchers tailored LASP to detect a particular antibody, such as the one the human body makes to kill an influenza virus. Another part of LASP’s chemical recipe includes luciferase. A third part is something called GFP. That’s short for green fluorescent protein. And as its name suggests, it glows green.

The older version of this test used a layer of paper that had been soaked in a solution with luciferin, then dried. A second paper layer was dried after being soaked with LASP. The papers were then laid one atop the other. As long as both stayed dry, their chemicals wouldn’t react and glow.

Add blood, though, and its watery part — known as plasma — will soak through both layers, letting their chemicals mix. If there are none of the target antibodies in the blood, the chemicals glow bluish-green. But if those antibodies are there, they interfere with GFP. This causes a more bluish glow.

Merkx and his colleagues described that test two years ago in Angewandte Chemie International Edition. One drawback is that the paper-based test needed at least 30 microliters of blood, more than can usually be obtained from finger pricks. To use less blood, Merkx’s team figured the reacting chemicals must start out closer together. The gap between the layers of paper had just been too wide.

Their thinner alternative? Thread. They treat one strand of it with luciferin. A second gets the LASP. When twisted together, the strands stay in tight contact. As before, there is no reaction or glow when the strands are dry. But add a bit of blood and the chemicals mix. Then the telltale green or blue glow emerges.

Test for single, duos or trios of antibody types

The new test can detect and measure three antibodies at once. For the prototype, these included broadly different types. One was the antibody triggered by a flu virus. The second was the antibody to dengue fever. (Caused by a mosquito-spread virus, dengue infects up to 400 million people each year and kills thousands.) The last antibody is the type formed by exposure to HIV, the human immunodeficiency virus. It’s the virus that causes AIDS.

Merkx and his team created their triple test by dividing a long thread into several sections. A small strip of a water-repellent material separated the three sections, each treated with proteins to sense a different antibody.

Another great feature, says Henry, is the ability to measure the color of the blue-green glow with a smartphone’s camera. (This feature was also available in the earlier version of this assay). The human eye can’t easily distinguish one shade of some colors from similar shades, Henry notes. But after the phone’s camera snaps an image of the glow, a special app on the phone can measure the ratio of blue to green light. That, in turn, offers a gauge of how much of an antibody is present.

Such information can help doctors figure out the stage of someone’s disease, says Henry. Any change in antibody levels over time, he adds, could serve to guide to that patient’s progress.

If the test materials are kept cool and sealed to prevent oxygen from reaching them, they can last more than 42 days, Merkx and his team report. That means that they could be used in remote clinics, not just big-city labs.

What’s truly clever about the new test “is in its simplicity,” says Viktor Stein. He’s a molecular engineer at the Technical University of Darmstadt in Germany. He likes the phone reader, he says, because this tech “is available to anybody.”

This is one in a series presenting news on technology and innovation, made possible with generous support from the Lemelson Foundation.