Accelerating high throughput screening and biochemical assay development
Dr. Jonathan Wingfield , Principal Scientist at AstraZeneca, discusses the development of acoustic mass spectrometry technology for high-throughput screening. Through the combination of acoustic technology from Labcyte and mass spectrometry systems from Waters, acoustic mass spectrometry provides rapid sample processing and analysis of a wide range of molecular targets, saving crucial time and reagents costs needed to screen millions of compounds within AstraZeneca’s small molecule and discovery programs.
Liquid chromatography–mass spectrometry (LC-MS) is a fantastically capable analytical tool. With the high resolution of new accurate-mass systems, the qualitative and quantitative performance is unrivaled. The technique’s label-free nature simplifies assay development, reducing both time and cost. LC-MS delivers high content data which not only identifies compounds from complex matrices, but can also provide molecular fragmentation data fundamental for structural elucidation.
Over the past 15 years, Labcyte has demonstrated a consistent history of innovation in the use of acoustic energy to transfer liquid samples without making actual contact with the sample. A gentle burst of ultrasonic energy creates a mound on the liquid surface in a source well and then ejects a 2.5 nL droplet of sample. Thanks to surface tension, this droplet can be captured by an inverted well located over the source well. This occurs very quickly, at a rate of up to 500 Hz. This fast, contamination- and carryover-free liquid handling technology has become a standard tool in many areas of life science research, including cancer, genomics and pharmaceutical drug discovery.
Research into droplet formation led to the ability to generate a mist of nano-droplets similar to those created in a mass spectrometer’s electrospray ionization source. Working in collaboration with the AstraZeneca and Waters Inc., a prototype of a new ionization source has been designed to demonstrate this technology’s potential.
In tests using real samples, Acoustic-MS has shown itself to be a reliable technology with unparalleled speed. In an early trial, the system enabled AstraZeneca to save 95% of the cost to develop the assay. It also reduced the development time from an estimated 6 months to 2 weeks, and screened 230,000 compounds (600 plates) in 10 working days. A subsequent screen of a 2.5 million compound library against a different target was completed in 40 days, with a demonstrated capability to process over 100,000 samples per workday. Because of the high-quality MS data, there were fewer false positives needing further investigation.
Image courtesy of AstraZeneca