Sorting measurement queues to speed up the flow injection analysis mass spectrometry of combinatorial chemistry syntheses Original Research Article

A high-throughput flow injection analysis mass spectrometry system was developed for the purity estimation of multiple parallel combinatorial chemistry synthetic samples. Surreptitious inter-sample carry-over represents a threat to the accuracy of the purity estimates. The visualisation of carry-over in 96-well racks via a surveillance program was improved by introducing the automatic sorting of the intra-rack sample measurement queues. This was necessary as the logical arraying of building blocks by synthetic dispensing robots imparts an underlying row and/or column order to the 96-well racks, which complicates the estimation of carry-over. In a primary sorting step, the molecular weight difference between the expected synthetic products in consecutively measured wells was maximised; in a secondary sorting step, the consecutive measurement of wells with similar building blocks was minimised. Over four hundred samples drawn equally from five diverse combinatorial synthetic families were measured to explore the use of this two-stage sorting to ease the measurement of carry-over, and so to facilitate the optimisation of the flow injection analysis measurement duty cycle. Subsequently the duty cycle in daily use, of 168 s was reduced to 70 s, while maintaining the median inter-sample carry-over at levels below 1%.