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18. Feb. 2022
Antonin Hlavacek from the Institute of Analytical Chemistry of the Czech Academy of Sciences, Zdenek Farka from CEITEC Masaryk University (MU), Hans-Heiner Gorris from the Faculty of Science MU, and their colleagues developed a new diagnostic methodology using photon-upconversion nanoparticles for faster and more sensitive detection of cancer biomarkers. This new approach enables the early detection of several oncological disorders and allows medical doctors to diagnose even a slightly worsening condition in cancer patients during the initial stages of the disease. The results of this multidisciplinary applied research conducted in collaboration with the Swedish company Lumito were published on 18th February, 2022 in the scientific journal Nature Protocols.
Immunochemical methods are considered the gold standard in clinical diagnostics. The best-known products in this category are rapid tests for home diagnostics, such as pregnancy tests or covid antigen tests. However, the current immunochemical methods often do not have sufficient sensitivity in detecting biomarkers present only in low amounts. "Our methodology challenged this problem and can achieve much higher sensitivity," explains Zdenek Farka, one of the corresponding authors of the study.
The published work summarizes the research results that the authors achieved and published during previous years. It compares various methods for the preparation of labels based on photon-upconversion nanoparticles, from their synthesis, through surface modification, to the binding of biomolecules allowing the specific function of each label. Subsequently, the application potential of the labels is demonstrated by the detection of prostate-specific antigen, a biomarker used for prostate cancer screening. In addition to the conventional approach based on measuring the luminescence intensity, an innovative readout based on the counting of individual labels has been used, significantly improving the assay sensitivity.
The research team also demonstrated the use of nanoparticles in immunohistochemistry, specifically in imaging the distribution of the HER2 biomarker, which is used to diagnose breast cancer. In histopathology, the identification of cancer cells is typically based on the labelling of biomarkers on their surface, followed by microscopic examination and evaluation of the images by an experienced pathologist. "The current focus is to automate this process by using advanced algorithms. We have shown that with the use of nanoparticles, it is possible to achieve a sufficiently high signal-to-background ratio, which is one of the main prerequisites for the automated evaluation of histochemical samples in the so-called digital pathology," says Zdenek Farka.
"Even the presence of tiny amounts of biomarkers in the blood may indicate the onset of cancer. Their sensitive detection will allow doctors to see even slight changes at the beginning of the disease, enabling early diagnosis. Thanks to this, the treatment can be started even before the clinical symptoms of the disease appear, which increases the chance of successful recovery," explains Zdenek Farka. In addition, the obtained know-how can also be easily modified to detect other biomarkers, such as cardiac troponin, a marker of myocardial infarction. The research team also collaborates with the Swedish company Lumito, which is currently commercializing an immunohistochemical imaging system based on photon-upconversion nanoparticles.
"It was highly multidisciplinary research. We first explored various methods for the synthesis and modification of nanoparticles. Afterwards, a methodology for imaging individual nanoparticles was developed. Finally, we developed the immunochemical methods and verified their functionality on the analysis of real clinical samples," added Zdenek Farka.
This research was the result of international multidisciplinary cooperation. In addition to scientists from CEITEC MU and the Faculty of Science MU (Dr. Zdeněk Farka, Assoc. Prof. Petr Skladal, Dr. Hans-Heiner Gorris), the following institutes were involved: the Institute of Analytical Chemistry of the Czech Academy of Sciences (Dr. Antonin Hlavacek, Dr. Frantisek Foret), the Institute of Macromolecular Chemistry of the Czech Academy of Sciences (Dr. Uliana Kostiv, Dr. Daniel Horak), the Swedish company Lumito (Dr. Matthias J. Mickert) and the University of Regensburg (Julian C. Brandmeier).
The research was supported by the project GAČR 21-03156S "Photon-upconversion labeling for microfluidic single-molecule immunoassays of protein biomarkers."