Category: Automation and High-Throughput Technologies
We have developed a new analytical system that is capable of directly measuring substrate-to-product conversion in-situ without the need for engineered substrates or post-reaction sample treatment. The new system consists of an acoustic liquid dispenser, an open port sampling interface and a mass spectrometer. The acoustic liquid dispenser uses ultrasound pulses to eject nano-liter scale liquid samples into an open port sampling interface, and the samples then enter the mass spectrometer for analysis. Using a dextromethorphan kinetic study in human liver microsomes as an example, we demonstrated that the new system achieved many critical improvements over the existing systems. It can sample and analyze reaction matrices at a rate of less than 1 second per sample. With a sample size as low as 2.5 nL, the system can monitor the reaction continuously with little change in reaction matrix volume. It has high reproducibility with an intra-well coefficient of variation less than 4% and an inter-well coefficient of variation less than 9%. It also has high sensitivity that is sufficient for running kinetic studies in human microsomal matrix without any post reaction sample treatment. Because of the significant improvements in sampling size, analysis speed, simplified workflow and capability of in-situ analysis, the new system will have broad applications in biological research and drug discovery.
Jianhua Liu– Senior Scientist, Pfizer, Groton, Connecticut