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OptoAssays make disease diagnosis easier and cheaper

Research team from Freiburg and Saarbrücken develops new light-controlled tests for pathogens and biomarkers

SARS-CoV-2 rapid tests or pregnancy tests work on a similar principle. The test line changes colour depending on whether a particular protein or hormone is present. In both cases, a lateral flow assay is used. A test in which the lateral flow of the sample fluid leads to the display of a result. This single unidirectional movement of the fluid on the paper is generated by capillary forces without mechanical or electrical assistance. This detection method is not suitable for more complex tests. Here, assays are required that allow bi-directional control of liquids, i.e. transport into and out of the test system. Until now, this has required expensive and wear-prone pumps.

Researchers led by Dr. Can Dincer from the Institute of Microsystems Engineering (IMTEK) at the University of Freiburg and Prof. Dr. Wilfried Weber from the INM - Leibniz Institute for New Materials at Saarland University in Saarbrücken and the Cluster of Excellence CIBSS - Centre for Integrative Biological Signalling Studies at the University of Freiburg have now found a solution that allows complex test designs to work without them. In the latest issue of the journal Science Advances, they present biological assays in which the mechanical pumps are replaced by light-emitting diodes (LEDs). These OptoAssays enable the bidirectional, light-induced movement of biomolecules and the reading of test results without additional mechanical washing steps.

3D printed PhotoBox for sample illumination and signal acquisition in a POC scenario. A smartphone controls the illumination via Bluetooth and Arduino Nano and captures images through an aperture. From DOI: 10.1126/sciadv.adp0911, Open Access

Light on - light off: The test result is there

An OptoAssay uses a transmitter and receiver area that are brought into contact by the addition of test fluid. The emitter area contains a special protein that reacts to light. It can bind or release certain molecules depending on the type of light it detects. When an LED emits red light with a wavelength of 660 nanometres, the molecules bind to the protein. When the LED is switched to dark red light with a wavelength of 740 nanometres, the molecules separate from the protein. The receiving section contains antibodies specifically designed to recognise and retain the protein in the test fluid.

The model for the method comes from nature

The method was inspired by how plants respond to light. Every cell has a nucleus in which its genetic code is stored. The DNA contains the cell's 'programme', which tells the cell what to do. To activate or deactivate this programme, certain proteins have to enter and leave the nucleus. In the cytoplasm of the cell, the area surrounding the nucleus, there is a photoreceptor that can be controlled by light. When it receives red light, it is activated and docks onto a binding protein. The binding protein then transports the photoreceptor into the nucleus. This triggers, for example, a growth programme in the nucleus. As soon as the wavelength of the light changes to dark red, the binding is interrupted.

However, the link to nature is not only provided by the method. The photoreceptors in the OptoAssay are also made from natural materials. Genes containing the information for the photoreceptor of the plant cell are taken from the plant and introduced into bacteria. These bacteria then produce the photoreceptor and binding protein used in the OptoAssay. The original mechanical components are thus replaced by sustainable natural components. The researchers see great potential for the use of OptoAssays in on-site diagnostics, i.e. outside the laboratory, similar to lateral flow assays. “Used in conjunction with smartphones, OptoAssays could eliminate the need for external flow control systems such as pumps and signal readers, paving the way for new diagnostic devices that enable low-cost, easy-to-use on-site analysis even in resource-poor environments," says Dincer.

 

Original publication: 

Urban, Nadine; Hörner, Maximilian; Weber, Wilfried; Dincer, Can (2024): OptoAssay—Light-controlled dynamic bioassay using optogenetic switches, In: Science Advances, Vol. 10, Issue 39. DOI: 10.1126/sciadv.adp0911

CIBSS profile of Prof. Dr. Wilfried Weber

Original press release