Scientists have developed a nanodroplet array platform that enables the synthesis, biological testing, and chemical analysis of hundreds of potential drug candidates on a single chip. The system, which uses only 200 nanoliters of liquid and around 300 cells per test, could significantly lower the cost and complexity of early-stage drug development.
In a proof-of-concept study, the team from the Karlsruhe Institute of Technology (KIT), Germany, used the platform to generate and test 325 potential MEK inhibitors, identifying 46 that matched the performance of the FDA-designated “breakthrough therapy” drug mirdametinib. The entire process – from synthesis to screening – was completed in just seven days.
“[Our platform] combines the previously separate processes for the development of new anti-cancer drugs on a single chip – using a single, miniaturized workflow,” said project lead Pavel Levkin, whose group specializes in biofunctional materials at KIT.
The team employed a “direct-to-biology” approach that enabled immediate cell-based screening of synthesized molecules without purification, dramatically conserving both reagents and time. For biological assessment, each nanodroplet – containing just 200 nL of solution and 300 HT-29 colon cancer cells – served as an independent viability assay, allowing drug effects to be probed in parallel across hundreds of candidate MEK inhibitors.
To characterize molecular products, the researchers used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which offered both chemical specificity and spatial resolution at nanoliter scale. MALDI-MSI also mapped compound distribution directly on the chip, confirming MEK inhibitor formation and validating the platform’s analytical performance at ultralow volumes. The ability to resolve compound identity and distribution in situ – without disrupting the miniaturized format – was key to demonstrating the feasibility of fully integrated synthesis and analysis.
By streamlining synthesis, testing, and analysis into a single miniaturized system, the platform could democratize drug discovery for academic and smaller biotech labs, which typically don’t have the means for resource-heavy screening methods. “Our technology removes this barrier and could open the door for many more players to contribute to drug discovery,” Levkin added. “This is a big step toward faster, cheaper, and more efficient discovery of urgently needed new drugs.”
Newsletters
Receive the latest analytical science news, personalities, education, and career development – weekly to your inbox.
