Array of microdroplets with various reactants on the chemBIOS chip-based...
Array of microdroplets with various reactants on the chemBIOS chip-based synthesis platform.
Source: Maximilian Benz, KIT

Turbo chip for drug development

Scientists develop process that facilitates and accelerates chemical synthesis and biological screening by combining all steps on a chip.

In spite of increasing demand, the number of newly developed drugs decreased continuously in the past decades. The search for new active substances, their production, characterization, and screening for biological effectiveness are very complex and costly. Due to the immense time expenditure and spatial and methodological separation of the synthesis of compounds, and clinical studies, development of new drugs often takes more than 20 years and costs between two and four billion dollars.

One of the reasons is that all three steps have been carried out separately so far. Scientists of Karlsruhe Institute of Technology (KIT) have now succeeded in combining these processes on a chip and, hence, facilitating and accelerating the procedures to produce promising substances. Thanks to miniaturization, also costs can be reduced significantly.

Drug development is based on high-throughput screening of large compound libraries. However, the lack of miniaturized and parallelized methodologies for high-throughput chemical synthesis in the liquid phase and incompatibility of synthesis of bioactive compounds and screening for their biological effect have led to a strict separation of these steps so far. This makes the process expensive and inefficient. “For this reason, we have developed a platform that combines synthesis of compound libraries with biological high-throughput screening on a single chip,” says Maximilian Benz of KIT’s Institute of Toxicology and Genetics (ITG). This so-called chemBIOS platform is compatible with both organic solvents for synthesis and aqueous solutions for biological screenings. “We use the chemBIOS platform to perform 75 parallel three-component reactions for synthesis of a library of lipids, i.e. fats, followed by characterization using mass spectroscopy, on-chip formation of lipoplexes, and biological cell screening,” Benz adds. Lipoplexes are nucleic acid-lipid complexes that can be taken up by eukaryotic, i.e. human and animal, cells. “The entire process from library synthesis to cell screening takes only three days and about 1 ml of total solution, demonstrating the potential of the chemBIOS technology to increase efficiency and accelerate screenings and drug development,” Benz points out. Usually, such processes need several liters of reactants, solvents, and cell suspensions.

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