Increasing MS Throughput
Improving the HPLC process itself is an obvious solution and several vendors have been actively involved in this area. Others have attempted to solve the HPLC bottleneck by designing parallel HPLC systems coupled to a single MS detector that allow for injections to be staggered, facilitating overlapping analyses. Another attempt to overcome the sample preparation bottleneck is an MS source that facilitates multiple HPLC systems being simultaneously coupled to a single detector.
While these approaches do have shortcomings such as complicated method development and decreased sensitivity, in the case of parallel MS, they enable faster throughput. Reports in the literature claim that throughputs under one minute per sample have been achieved in some applications, facilitating analysis of four 384-well plates in 24 hours.
Yet another solution to the MS throughput bottleneck is to decouple the LC from the analysis. A parallel sample preparation is performed, typically with a 96-well SPE plate. The time associated with the sample preparation is amortized over the 96-samples.
Several methods are available for the MS analysis of such samples, including flow-injection analysis. These approaches have unique strengths and weaknesses. Parallel LC or MS systems integrate sample preparation and analysis into a single automated step but provide only incremental increases in throughput. Decoupling the sample preparation facilitates much higher throughputs but puts the throughput burden on the sample-preparation step. Even with advanced robotics, running large numbers of 96-well SPE-plates per day is an expensive, labor-intensive, and error-prone process.
Ideally, high-throughput MS systems are highly automated and address all steps of analysis, including sample preparation, data acquisition, data analysis, and generation of reports for exportation to databases. Any method that doesn’t solve all steps pushes the throughput bottleneck on other steps.