Light-guided bioassays could diagnose diseases more easily and cost-effectively

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

A SARS-CoV-2 rapid test shows whether a certain protein of the coronavirus is present in the sample fluid, the reagent, or not. A pregnancy test works in a similar way. Here, the presence of the hormone hCG causes the test line to change color.

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 single, unidirectional movement of the liquid on the paper is generated solely by capillary forces, without mechanical or electrical assistance.

This detection method is not suitable for more complex tests. Assays are required here that enable bidirectional control of the liquids, i.e. transport in and out of the test system. Unfortunately, these multi-stage assays rely on expensive and wear-prone pumps.

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

Researchers at the University of Freiburg and the INM have found a solution to enable complex test designs without the need for expensive and bulky equipment. In an article in Scientific advancesThey present biological tests in which expensive and complex mechanical pumps were replaced by simple and inexpensive light-emitting diodes (LEDs).

These OptoAssays enable bidirectional, light-induced movement of biomolecules and reading of test results without the need for additional mechanical washing steps.

An OptoAssay uses a transmitter and a receiver area that are brought into contact by adding the test reagent. In the transmitter area there is a special protein that reacts to light. This protein can either bind or release certain molecules depending on the type of light captured.

When an LED emits red light with a wavelength of 660 nanometers, the molecules bind to the protein. When switching to far-red light with a wavelength of 740 nanometers, the molecules detach from the protein. In the receiver area there are antibodies that have been specifically developed to recognize and capture the target protein in the test reagent.

The researchers took inspiration from nature for this method, particularly how plants respond to light. Every cell has a nucleus where its genetic code is stored. DNA contains the cell’s “program” that tells it what to do. To activate or deactivate this program, certain proteins must move in and out of the nucleus.

Prof. Wilfried Weber, synthetic biologist and scientific director of the INM, explains the mechanism: “In the cytoplasm, i.e. in the area around the cell nucleus, there is a photoreceptor that can be controlled by light. If it receives red light, it is activated and binds to a binding protein.”

“This binding protein then transports the photoreceptor into the cell nucleus and can, for example, trigger a growth program there. If the wavelength of the light switches to the far red range, this bond is interrupted again.”

However, the connection to nature does not only exist through the method itself. The photoreceptors in the OptoAssay, which release the reagents, are also made of natural materials – in contrast to the pumps usually used in the OptoAssay.

Genes containing the information for the photoreceptor in plant cells are extracted from the plant and introduced into bacteria. These bacteria then produce the photoreceptor and binding protein used in the OptoAssay, replacing the original mechanical components with naturally sustainable materials.

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

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