Discussion

The high throughput direct measurement of substrate-to-product conversion by label-free detection has been considered the “Holy Grail” of drug discovery screening. Mass spectrometry as a detection system has the potential to be part of the ultimate screening solution. However, MS with existing sample introduction modes, despite being widely used in drug discovery typically cannot meet the throughput requirements of HTS.

Together Labcyte Inc., Waters Corp. and AstraZeneca have built a prototype acoustic source linked to a mass spectrometer. This novel acoustic source is capable of generating a mist of droplets in the 50-100fL range, analytes within these droplets can be ionized as they pass through a charged field and fired directly into the mass detector. This direct injection approach enables a sampling rate of 3 wells per second (10,000 samples per hour), fast enough to support high throughput screening (HTS). The use of acoustics to fire the samples into the detector ensures that there is no cross contamination and sample volumes are minimised.

The system is capable of generating charged ions in either +ve or -ve mode and can ionise a wide range of biomolecules including peptides and proteins. While direct injection enables speed, the lack of chromatography means that there is no way to remove salts from the sample before injection into the MS. Data will be presented which show how the technical capabilities of the system have been enhanced and how biological assays have been adapted to run on this platform.

To broaden the potential application space for this acoustic delivery system, we have started to integrate a DART (Direct Analysis in Real Time) source. Preliminary data will be presented showing progress with this second ionisation source.