Nuclear magnetic resonance (NMR) is an important tool in drug research, since it can quantify and spatially resolve binding of drugs to pathogens. So far, however, NMR has lacked the sensitivity and throughput to scan large libraries of drug candidates. Within the "HiSCORE" project, research teams of Professor Jan Gerrit Korvink and Dr. Benno Meier from Karlsruhe Institute of Technology (KIT), in cooperation with partners from Paris and Nijmegen, will now develop a method for high-throughput screening (HTS). This project will be funded by a Synergy Grant awarded by the European Research Council (ERC).
The team of Jan Gerrit Korvink, Director of the Institute of Microstructure Technology of KIT, will use MEMS miniaturization technology to conduct a large number of measurements in parallel. "The available space in NMR magnets is completely underutilized," Korvink says. Use of its full potential would largely increase functionality and efficiency.
The teams of Benno Meier from KIT's Institute for Biological Inter-faces and Professor Arno Kentgens from Radboud University in Nijmegen will develop methods for parallel orientation or polarization of nuclear spins in the samples. Nearly all spins contribute to the signal and signal intensity can be increased by up to four orders of magnitude compared to standard NMR experiments. It is also important to generate these hyperpolarized liquids at a sufficiently high rate. A boost in signal strength enables a significant reduction in sample size and required material. This reduction in sample size will pave the way towards parallelization.
In Paris, the team of Professor Geoffrey Bodenhausen will improve methods to quantitatively evaluate interactions between biomolecules and drug molecules. The HiSCORE team will be advised by Dr. Alvar Gossert, ETH Zurich, and Claudio Dalvit, Trieste, both experts in pharmaceutical drug screening.
"HiSCORE" Will Highly Accelerate Process Steps
At all sites, technical systems will be developed and experiments will be conducted in parallel, Korvink says. "Within this ambitious project, we will build a system that will be improved continuously by all partners. In the first steps, this will be a complex process, but further development steps will be greatly accelerated."
Conventional HTS methods are able to test up to one million sub-stance candidates, but provide information of low dimensionality and poor quality. NMR provides very rich information, but with a low throughput and at high cost so far.
HiSCORE (Highly Informative Drug Screening by Overcoming NMR Restrictions) merges all most innovative branches in the field of NMR - hyperpolarization, microcoils, microfluidics, parallel acquisition, and machine learning - to tackle these pharmacological challenges. In this way, processes will be accelerated by a factor of 10,000. "Together, we will develop and test a number of technologies at the three sites Karlsruhe, Paris, and Nijmegen," says Benno Meier, "so that we can quickly identify and push the most promising strategies for the various biophysical assays that we want to implement."
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