Drug discovery has traditionally been a slow painstaking process involving many separate steps. But new work from researchers led by Graham Cooks at Purdue University now points the way towards a future where a fully-automated ultrahigh-throughput platform can cut down that time considerably — from weeks to hours — by consolidating the steps into one system that produces, analyzes, and fine-tunes possible drug candidates.
The next-generation platform achieved this feat through the use of desorption electrospray ionization mass spectrometry (DESI-MS), a technology invented by Cooks and his group twenty years ago.
“Drug discovery is a fight against probability,” said Nicolás Morato, a chemist at Purdue University and the lead author on the new work, in the press release. “You’re searching through enormous biological space and even larger chemical space trying to find the right molecule for the right target. If you can’t make compounds fast enough and test them fast enough, it becomes a battle you’re going to lose.”
Acceleration with microdroplets
Cooks told DDN that this work was motivated by his refusal to limit MS to analysis only. “We do reaction screening, synthesis, and bioassays. All the conventional steps in early- stage drug discovery. But the experiments are fast, on a small scale, and direct, without purification at any stage,” said Cooks.
A key part of the platform that allows for its unique speed is the use of microdroplet chemistry. In 2011, Cooks’ team showed that chemical reactions in microdroplets can be accelerated up to a million-fold. “People get the analysis part, that is the forte of MS. They have trouble believing the synthesis part — that microdroplets with lifetimes of tens of milliseconds can be reaction vessels for synthesis,” said Cooks.
Plus, without the need to wait to clean and purify the sample for analysis, the new system can analyze a sample every second. The only non-automated piece that takes the longest — about 30 minutes — involves testing the bioactivity of the newly synthesized compounds. Yet, the whole drug discovery cycle can be completed in as fast as 122 minutes, Cooks said.
An expanding drug discovery platform
Currently, the new platform is the second-generation version, and it’s been operating for two years as a Purdue University core facility for high-throughput screening, synthesis, and bioassays. Cooks said that commercialization will be the next step to get the new platform into labs all over the world.
In the future, Cooks noted the platform could be particularly useful in catalyst synthesis generating nanomaterials in sprayed DESI microdroplets, as well as applying it to chiral analysis by mass spectrometry, and eventually scaling up the synthesis aspect to take its capability from producing samples in nanograms to kilograms.
For now, Cooks said that what has been most exciting “is seeing a set of concepts fit together really well — to create a technology for many tomorrows.”
