Renewable turbulent flow chromatography for exposomics

The project entitled Renewable turbulent flow chromatography for exposomics will be developed by Dr. David J. Cocovi-Solberg in BOKU under supervision of Dr. Stephan Hann and involves the design of novel analytical systems for automating all analysis steps in exposome studies. Traditional studies for detection of environmental contaminants refer to the total amount of specific target substances found in different environmental compartments. Contrariwise, exposome studies try to investigate potential toxicity based on the whole pool of substances and metabolites to which human beings might be exposed to during their lifetime cycle. Those exposome studies are very complicated because up to thousands of substances present in very small amounts (down to parts per billion) are to be measured in each sample, and many samples must be analyzed to get conclusive results. Mass spectrometers are the instruments of choice for such studies. As a drawback, these analytical platforms are very sensitive to external conditions, and exposome samples cannot be analyzed directly. Samples must be pretreated with cumbersome procedures involving many steps, high amounts of chemicals and many working hours in order to remove sample constituents that could falsify the LC-MS results and negatively affect instrument performance and durability. For this reason, the project carried out at the University of BOKU aims at designing novel approaches based on pumps, valves and 3D printed components that will automatically, that is, without analyst intervention, take the sample, remove interfering sample constituents, concentrate the substances of interest that are present in very small amounts, and in general, prepare the sample for the LC-MS analysis. The heart of the instrument to be designed is based on the principle named Turbulent Flow Chromatography (TFC), that is known for long time ago but passed unnoticed until very recently. This principle relies upon the favorable effects that happen when the sample is passed at a high speed on a bed of microscopic beads for separation of substances of interest. Thanks to advances in new materials, computer control and 3D printing technology, the TFC principle will be revisited and a proof of concept of the instrument designed. The computer- controlled operation along with the flexibility of the designed instrument will allow very complicated sequences to be executed, for analyzing different families of substances, and all in unmanned operation, that is, no scientific supervision will be needed during the entire analysis workflow.

In this project we have improved analytical methodology, which is commonly used in clinical and environmental laboratories, so that the operations that are needed before the analysis, are performed all together automated in a very short time. The developed system is built around one special switching valve, so it is small enough to be portable. Additionally, an industrial collaboration within the project allowed to also integrate the chromatographic separation into the system, so from now on we can perform the sample preparation and the separation of the sample into individual components in a portable platform. The motivation of this research starts with the concept of the exposome. We all know that our genes condition our individual susceptibility to illnesses, but now we begin to understand that our environment is even more important. We do not currently have universal tools for quantifying all that we are exposed to all the time (soil, water, air, food, medicines, stress...), but it is clear that for analyzing it all, we need faster, portable, affordable and easily parallelizable analyzers, in one word - miniaturization. Samples need to be processed before the analysis, for getting high quality data and extend instrument lifetime. Those operations usually take a long time, but in this work and thanks to the turbulent flow chromatography principle we could reduce this time significantly. The principle of turbulent flow chromatography resorts to very expensive consumables, but we managed to get the same results by manipulating inexpensive sorbents in the tubing under software control, according to a method called bead injection. Subsequently, we developed a new valve configuration for additionally including chromatographic functionalities. We want to disseminate those results, since they show that our developed systems are working under their best capabilities. It is important that both our colleagues as well as the companies realize that analytical methods can be improved just by a better software control, without resorting to new hardware. The in situ and real time analysis are every time closer, which will have a huge impact in medical diagnosis and environmental risk assessment. Up to 10 papers will be published before the end of the year related to this research, and 2 bachelor theses will be fulfilled. In the future we will try to miniaturize the mass spectrometric detector. This would allow to cover a large amount of compounds in the field, similar to what we currently achieve in the laboratory.