Dr. Marius Dagys about Biosensors and How They Can Benefit the Society

Researchers are often approached by medical professionals or businessmen to solve challenges that they cannot solve on their own. Such requests are also received by the Bioanalysis Department of the Biochemistry Institute of the Life Sciences Center of Vilnius University, headed by Dr. Marius Dagys . According to the Head of the Department, biosensors developed by the team will soon appear in intensive care units, which will help patients in the hospital maintain vital functions. And this is just one example.

VU LSC researcher Dr. M. Dagys represents the field of biosensor research. His team is researching the fundamental properties of biosensors, while also looking for practical applications - the kind that doctors or entrepreneurs need most. According to him, the public is sometimes surprised when they learn what amazing things take place in laboratories.

Q: How do biosensors work and what do they detect?

A: By definition, they are analytical tools that have a biomolecule as an essential recognition component. It can be an enzyme that catalyzes a specific chemical reaction, it can be an antibody, or it can be a nucleic acid.

Our job is to recognize the reaction signal of that biomolecule, and there are several ways to do it. One of them is the electrochemical method, when, during the reaction, the device can record the specific current strength.

Q: Since you are also researching the application of biosensors, what kind of biosensors are we talking about? Why did you choose these?

A: Let’s start with fundamental and applied research. In general, we, researchers, are interested in how to connect the biomolecules I’ve mentioned to nanostructures, electrode surfaces, etc. How to do it efficiently without damaging the structure of the biomolecules so that they live longer to get a better specificity of the biosensor. We write scientific articles on findings of new enzymes, new analytes, new detection methods, etc.

But we also have an applied aspect. Our department is notable because, even during the Soviet occupation, we were the first in Eastern Europe, the third in the world, to commercialize a blood glucose analyzer. I was a kid when the researchers built it, and the machine still works!

Q: What other applications are we talking about besides blood glucose measurements?

A: What else we measure - urea. This is a compound that is the main end product of nitrogen metabolism and accumulates in the body, and if kidney function is impaired, the patient needs dialysis. There is no such mobile device that directly measures the concentration of urea in the blood. There are dialysis machine attachments that measure urea in dialysis fluid using a spectrophotometric cell, but not directly in the blood. We also have a two-parameter device that additionally measures creatinine.

There is a procedure called peritoneal dialysis, which is performed at home. However, it is not suitable for everyone, as the patient’s heart must be strong, and the patient cannot have complications or additional aggravating circumstances. As the number of people grows, and not necessarily the number of doctors, remote medicine will become more and more relevant. A bedside device that can show how well the blood has cleared after an overnight stay will be of great value.

The next device we are developing will soon be in hospitals, next to patient beds in the intensive care unit. This is a device for determining the amount of amino acids and urea in the blood. Its idea was born after talking with doctors from Vilnius University hospital Santaros klinikos. We are talking about patients who are lying unconscious, possibly for days. They can’t eat, so they need an aided protein introduction. The question is how much protein do you need?

The doctors told us that to solve the problem they needed a machine that could measure the total amount of L-amino acids in the blood. We discovered the necessary enzyme, and developed a membrane electrode that reacts to all main amino acids. We are developing an according device with which we can obtain the total amount of amino acids in the blood, and then the doctors will know exactly what kind of drip to prepare for the patient, and what they are lacking. No need to guess.

Q: In your laboratory, biosensors were also developed that could help control the pandemic. Can you tell us more about it?

A: When the pandemic started, it was a surprise to many, including us, in the world of biosensors. I mean, there was no commercial virus analyzer, there was no market need for it. There were only RT-PCR and strip tests, but it was not enough. This is where all the biosensor researchers in the world got off to a crouch start. We have also developed our own COVID-19 infection sensor that works with real saliva samples. Its principle of operation is to detect a specific sequence of viral RNA on the surfaces of disposable gold electrodes. Although gold sounds expensive, it’s actually only needed for a very thin layer, so it’s not that expensive.

A single-stranded nucleic acid corresponding to the sequence of the spike protein of the virus is anchored on the sensor of the SARS-CoV-2 virus - a nanostructured electrode. The idea is that we put the sample in a tube that contains a buffer liquid that breaks down the virus, and then we introduce it into the medium on the electrode, and the electronic system immediately sees whether the sequence we’re looking for “sticks” to the functionalized surface.

We’ve been working on it, but the market eventually became oversaturated with coronavirus tests. We have improved our system, i.e. we repurposed the method. There are such enzymes as nucleases. There is a problem if biotech products become contaminated with them, for example, if they get from contaminated surfaces into product tubes, the customer gets a degraded oligonucleotide. So, we developed a nuclease activity sensor that can help biotech companies avoid that contamination.

Q: Do company representatives often contact you with problems they ask for help in solving?

A: For example, we met the representatives of AB Achema, who needed to analyze fertilizers. They produce urea as a component of nitrogen fertilizers. Its concentration in fertilizers is very important for the company because customers expect to receive no less urea than is written in the product composition. To protect against errors in the production process, the manufacturer adds a little more urea, which costs money. Therefore, we are completing the development of a fertilizer analyzer that measures not only urea, but also all forms of nitrogen in liquid fertilizers, and we hope that accurate measurement with this device will allow the company to add less excess material to the product.

So, we work with medicine, biotechnology, as well as with the chemical industry.

Q: Let’s return a little to medicine, to the diagnosis and monitoring of diseases. What other biosensors are worth mentioning?

A: The advantage offered by biosensors is fast measurement at a specific location. In one of the James Bond movies, Casino Royale, there was a scene in which agent Bond was playing poker and was poisoned. He managed to get into his car and inserted a needle sensor into his vein, which sent the data to his agency, where specialists analyzed what kind of poison the agent had taken. It was a biosensor! It is possible to create such one in reality, but it is needed only for a very narrow market and thus would be very expensive. However, it was perfect for a fictional intelligence agency.

With Russia’s war in Ukraine in mind, the military industry is also relevant for us. For example, we are developing a biosensor that can monitor blood inflammation, whether the injured person’s body is not infected, and whether drugs need to be given. It can be paired with, for example, a glucose or amino acid biosensor into a single device used in extreme conditions. We are highly motivated, we have all the necessary competencies in the department: biochemists, engineers, electricians, programmers, etc.

Q: Your contribution to biotechnology is also very important. You’ve been featured in the prestigious ACS Sensors journal. How did you manage to do that?

A: Yes, it is very difficult to get there. We managed to do this together with my colleagues from Malmö University (Sweden) and the Lithuanian professor Tautgirdas Ruzgas who works there and was my mentor during my doctoral studies.

We handed over to them an enzyme, which is extremely stable on a surface, developed by our colleagues and tested by us - membranous glucose dehydrogenase - and we helped connect it to a nanostructured gold electrode. Swedish colleagues then developed a wireless glucose sensor that works, for example, on the skin, and it can send data using the RFID principle via an antenna to a remote recorder. We managed to publish the results in ACS Sensors, the highest-level journal in the field of analytical chemistry in the world, and we became the third group of Lithuanian authors who managed to do so. Later that year, we managed to publish another invention in this journal describing the previously mentioned L-amino acid biosensor, the authors of which were, for the first time in history, exclusively Lithuanians, employees of our Bioanalysis Department. It is very difficult to be published in such journals, but if some researchers succeed, then it is a well-trodden path for others. Probably, from now on it will be really easier for Lithuanians to be published in that journal.

Read the full interview at our website: https://www.gmc.vu.lt/en/about/news/3333-dr-marius-dagys-about-biosensors-and-how-they-can-benefit-the-society

Interviewed by Goda Raibytė-Aleksa 🚀

Photo credits: M. Dagys personal archive