Reverse Avogadro number

Inaccessibility of the most part of proteome is the possible reason of low efficiency of proteomics as a tool for new biomarkers detection. This is a principle of a “proteomics iceberg”.

Proteome iceberg

“The Iceberg of Proteomics”.
Only a small tip of the proteome iceberg is accessible to state-of-the-art proteomic methods. The majority of proteins including so-called biomarkers are most probably located in bottom part at ultra-low concentrations.

According to FDA, with development of proteomics the quantity of new diagnostic tests registered per year not only has not increased but even has declined.
— Anderson & Anderson, MCP, 2004

In spite of power proteomic methods all modern diagnostic systems and medicines are directed to the same targets, the quantity of which remaining almost invariable for the last 10 years.
— Zhou, MCP, 2005

In 2001, the whole human genome has been sequenced, leading to the variety of scientific directions with new features, such as proteomics. Human genome sequencing has been based solely on unique technological principle, i.e. on self-reproduction of DNA molecules by polymerase chain reaction (PCR).

Nowadays, there are no analogues of PCR for protein molecules. There is therefore a need in change of the technological paradigm in order to create a comprehensive atlas of all the proteins found in organism. It is possible by the identification of single molecules. When the latter will be provided, the transition of molecular biology will occur, thereby joining the nanotechnology, proteomics and medicine. Up to now, prototypes of single molecule detectors are developed, e.g. multicantilever probe microscopes and nanosized sensing structures (see Technical potential). By means of such devices, researchers will be able to analyze the individual copies of protein molecules, rather the average indexes of hundreds millions of them. By the other words, the detectors of single molecules provide manipulations and measurements at the level of the concentration range close to the reverse Avogadro number, i.e. ~10^-24 M.

Since 2008, the “Proteomics” journal a new section of Nanoproteomics was opened. Besides other related research, the section is dedicated to the development of technology capable to increase the concentration sensitivity of analytical methods. An editor of the new section is Alexander I. Archakov, the Full Member of Russian Academy of Medical Sciences.

График

Experimental-theoretic dependence of protein number on concentration sensitivity of analytical devices.

Concentration sensitivity measured in mol per liter (M) is laid off as ordinates. This value reflects the least analyte concentration in studied biomaterial. Initial site of the graph contains experimental points that show the trend of increase in quantity of proteins [Archakov et al, 2009]. The approximation reaches the area of low concentrations, i.e. about 10-24 M, i.e. a reverse Avogadro number. At such sensitivity level it is possible to detect several million types of proteins.