Soon after joining Novartis in 2004, Adam recognized the power of a multiplex LC/ MS system implemented by Tom Roddy and Karen Wang in the Analytical Sciences group.
The concept was brought within the screening group and many different assays were enabled by John Peltier and his team. Applications ranged from compound QC – concentration, identity, purity; solubility; affinity selection; covalent modification; and screening. The screening LC/MS was fully automated and could run 24 hours unattended, running 4 samples a minute.
LC/MS generated what we termed “gold standard” data in primary screens, follow up assays and lead optimization. The lack of compound interference, and measurement of multiple analytes, was critical in sorting out a number of “PAINS”, removing false positives from our hit lists.
The technology itself was also enabling – for example looking at racemization through deuterium exchange and efflux of amino acids from cells.
While powerful LC/MS could not compete with fluorescence readouts for throughput.
In 2010, prompted by increased demand to screen targets without detection reagents, Adam took a sabbatical in the mass spec imaging lab of Markus Stoeckli in Novartis Basel and worked on the logistics of using MALDI as a high throughput readout. Eventually with the help of Bruker, TTP and HighResBio we built the first of what would become the MALDI PharmaPulse. This system, capable of reading 3 wells per second gave us a huge boost in throughput without compromising the fidelity of the mass readout. Additional advantages included rapid assay development using unlabeled, more relevant, substrates.
The next evolution was an enhanced MALDI readout system from Revolution BioSiences. This technology again provides interference free analysis of analytes and the readouts can be highly multiplexed.
The third enabling technology came into view while working with Prospective Research, a life science start-up in Beverly, MA. We needed a rapid method to determine which bacterial stimulants would generate new compounds in fermentation broths. Using solid phase extraction and DART technology from IonSense we could screen approximately 300 samples an hour for novel chemical entities, with high reproducibility, processing the data with Nonlinear Dynamics software to generate PCA plots from mass spectra.
Subsequent work with IonSense has led to the development of their DART-Pulse system. An automated reader for 384 samples at less than 3 seconds per sample, with integrated sample processing software. This product has applications in high throughput chemistry, PK/PD studies as well as in forensics and workplace testing.