Light-controlled bioassays could diagnose diseases more easily and cheaply

From Velcro to solar cells, many technological innovations are inspired by nature. In the field of medical diagnostics, researchers are also drawing inspiration from biological principles. A research team from the University of Freiburg and the INM – Leibniz Institute for New Materials in Saarbrücken has developed test methods in which simple LEDs could replace complex mechanical pumps. These OptoAssays not only imitate the behavior of biological cells, but also use their genetic programming.

A rapid SARS-CoV-2 test indicates whether or not a specific coronavirus protein is present in the sampled fluid, the reagent. A pregnancy test works in a similar way. Here, the presence of the hormone hCG causes the test line to turn colored.

In both cases, a lateral flow test is used, a test in which the lateral flow of the reagent leads to the display of a result. This unique unidirectional movement of the liquid on the paper is created solely by capillary forces, without any mechanical or electrical assistance.

For more complex tests, this detection method is not suitable. In this case, tests are required that allow bidirectional control of liquids, i.e. transport to and from the test system. Unfortunately, these multi-stage tests rely on expensive and wear-prone pumps.

These pumps repeatedly remove unbound molecules from the system, ensuring that only the particles to be detected remain attached to the detection antibodies.

Researchers from the University of Fribourg and the INM have found a solution that allows complex tests to be designed without the need for expensive and bulky equipment. In an article published in Scientific progressThey feature biological tests in which expensive and complex mechanical pumps have been replaced by simple and inexpensive light-emitting diodes (LEDs).

These OptoAssays enable light-induced bidirectional movement of biomolecules and readout of test results without requiring additional mechanical washing steps.

An OptoAssay uses an emitting area and a receiving area, which are brought into contact by the addition of the test reagent. In the emitting area is a special protein that reacts to light. This protein can bind to or release specific molecules, depending on the type of light it captures.

When an LED emits red light with a wavelength of 660 nanometers, the molecules bind to the protein. When it passes to far-red light with a wavelength of 740 nanometers, the molecules detach from the protein. In the receptor area, there are antibodies specifically designed to recognize and capture the target protein in the test reagent.

The researchers took inspiration from nature to develop this method, specifically from the way plants react to light. Each cell has a nucleus in which its genetic code is stored. DNA contains the cell’s “program,” which tells it what to do. To activate or deactivate this program, certain proteins must enter and exit the nucleus.

Professor Wilfried Weber, synthetic biologist and scientific director of the INM, explains the mechanism: “In the cytoplasm, the area surrounding the nucleus, there is a photoreceptor that can be controlled by light. When it receives red light, it becomes activated and attaches to a binding protein.

“This binding protein then transports the photoreceptor with it into the nucleus, where it can trigger, for example, a growth program. Once the wavelength of light shifts to far-red, this binding is disrupted again.”

But the connection to nature is not limited to the method itself. The OptoAssay’s photoreceptors, which release the reagents, are made from natural materials, unlike the pumps typically used in OptoAssay.

The genes containing the information about the photoreceptor of plant cells are extracted from the plant and inserted into bacteria. These bacteria then produce the photoreceptor and the binding protein, which are used in the OptoAssay. Thus, the original mechanical components are replaced by naturally sustainable materials.

Researchers see great potential for the use of OptoAssays in point-of-care diagnostics, i.e. outside the laboratory, similar to lateral flow tests.

Dr. Can Dincer from the University of Fribourg explains: “OptoAssays can be easily controlled and read using smartphones and could, in the future, make external flow control systems such as pumps and signal reading devices unnecessary. They thus pave the way for new diagnostic tools that enable cost-effective and simple analyses directly on site, even in resource-limited environments.”