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The COVID-19 pandemic has brought about major advances in the field of vaccines. But it also spurred the development of diagnostic tools for detecting and testing infectious agents. Think of antigen and PCR testing, which have become the hallmark of COVID-19. Point-of-care testing should now benefit from these achievements. “That’s because awareness of the importance of testing as disease prevention has increased, and inexpensive tests could revolutionize health care,” says Dr. Georg Gramse from the Nanoelectronics Department at the Institute of Biophysics at Johannes Kepler University in Linz, Austria.

He is conducting research in the EU ATTRACT Phase 2 program with several partners from the Netherlands and Japan on better ways to test for viral diseases. Many diseases are transmitted by viruses. The list of viral diseases is long and includes the common cold and influenza as well as more serious diseases such as hepatitis, meningitis, AIDS and Ebola.

Improving health care

The goal of the project is to combine the speed of antigen testing and the precision of PCR testing in one system. Such a test system should also be able to detect – or exclude – more than one pathogen. That’s because broad-spectrum testing can speed up the process of diagnosis. “If patients’ symptoms reveal an unclear clinical picture, then you don’t have to go through several tests sequentially one after the other, but can test for several viruses at the same time with one test,” Gramse explains. This is the decisive advantage for preventive healthcare.

Also interesting: “Lab-on-a-Chip” to determine laboratory values directly on site

The idea is to be able to do the test in the doctor’s office or clinic without having to send the sample to the lab. This way, it is faster and involves fewer personnel and reduced effort and costs. This is why the test system is to be developed in a lab-on-a-chip to accommodate all the functions of a laboratory on a small plastic card.

Measuring principle in the microwave range

The obvious thing to do would be to adapt the PCR test. “But since this method cannot be sped up, we are trying to combine the speed of antigen tests with increased sensitivity,” Gramse says. He and his colleagues have developed extremely high-resolution electrical sensors that operate at different frequencies down to the microwave range. By combining the sensors, the measurement result should become extremely precise and robust. They published the basic principles for the microwave sensor as early as 2021. “We use the sensor in an electrochemical microscope to investigate what happens to the charges on electrode surfaces of batteries, for example,” the researcher explains.

Universal principle

The principle is universal and can be applied not only to the surface of batteries but also to other surfaces. The core mechanism is to measure how the charges change at high frequencies since sensitivity increases together with the frequency. The researchers have previously demonstrated this mechanism in electrochemical processes, but have also been able to identify buried atoms in semiconductor structures – as used in some specific concepts of quantum computing. The atoms are located under a silicon layer where they represent building blocks of quantum computers. With the method, even a few hundred atoms can be made out.

Pathogens at the single-particle level

In the ATTRACT Phase 2 project, the sensor measurement principle will be used to detect pathogens at the single-particle level. Since the principle will be integrated into a lab-on-a-chip, a new microfluidics system must also be developed. Microfluidics is concerned with the behavior of liquids and gases in the smallest of spaces. At the smallest scale, effects can dominate that are often neglected in classic fluid mechanics. Also, a special selection of biomarkers must be developed since by using different biomarkers in parallel, several viruses can be detected or excluded simultaneously.

Samples in the context of viral diseases are mostly blood or body fluids. These can be analyzed in solutions – and virus particles have the property of binding to surfaces in solutions. Even if only one virus particle is present, it can be identified with the high-resolution sensor if everything works out, says Gramse. There is no need for a lengthy amplification process, as with the PCR test. Polymerase chain reaction (PCR)-based techniques make many copies of the viral genome to quickly and correctly identify the virus.

Coordinating different worlds

The development of this new test system is complex and the researchers are still at the very beginning of the project, which has a relatively short duration of 2 ¼ years. They say it is exciting and challenging to combine different worlds: microfluidics, microwave technology and biochemistry. The linking of microfluidics and biochemistry had already been achieved in advance. Now it’s just a matter of integrating microwave technology and coordinating the different worlds in the new system, Gramse says.

Also of interest: Consortium seeks to automate design of medical lab on a chip

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