From Proteomics to the Analysis of Single Protein Molecules

• Published in: International journal of molecular sciences Vol. 25; no. 19; p. 10308
• Main Authors: Ponomarenko, Elena A, Ivanov, Yuri D, Valueva, Anastasia A, Pleshakova, Tatyana O, Zgoda, Victor G, Vavilov, Nikita E, Ilgisonis, Ekaterina V, Lisitsa, Andrey V, Archakov, Alexander I
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2024; MDPI
• Subjects: atomic force microscopy; Biomarkers; Biopsy; Diagnostic equipment (Medical); Humans; Limit of Detection; Mass Spectrometry - methods; Methods; molecular counters; Opinion; protein detection; Proteins; Proteins - analysis; proteomics; Proteomics - methods; sensitivity in bioanalysis; Sensors; single biomacromolecule; Israel; molecular counters; proteomics; mass spectrometry; protein detection; sensitivity in bioanalysis; single biomacromolecule; atomic force microscopy; limit of detection
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251910308

Limit of detection (LoD) is a term that is used to characterize the sensitivity of an analytical method. The existing limitation of the sensitivity of analysis using modern mass spectrometry methods has been experimentally shown to be a limiting factor in the application of proteomic technologies in medicine. This article proposes a concept of a new technology that will set a new vector of development in the development of systems for solving problems of medical diagnostics and deals with theoretical and practical aspects of creating a new technology for the detection of single biomacromolecules (in particular, proteins) in biological samples. Such technology should be based on the principle of signal registration similar to that used in a Geiger counter (also known as a Geiger-Müller counter or G-M counter), a device that automatically counts the number of ionizing particles that hit it. This counter is free from probabilistic components; it registers a signal if there is at least one target molecule in the analysis chamber. Predictive medical diagnostics require technology based on methods where sensitivity allows for the detection of single marker molecules in a biological sample volume of 1-10 µL, the smallest volume of biomaterial used in laboratory diagnostics. Creation of a detector with a sensitivity of 10 M would allow for the detection of one molecule in 1 µL of the sample, which fundamentally makes this approach analogous to a G-M counter for solutions. To date, bioanalytical methods are limited to a sensitivity of 10 M (which is approximately 1 million molecules per 1 μL), which is insufficient to capture the early stages of pathological processes.