(1061-B) Integration of Direct Nano-volume OPI-MS with Unchained Labs Junior for rapid sampling high throughput reaction screening in drug discovery

Abstract: The Open-Port Interface (OPI) allows direct droplet MS sampling delivered through automation. For dispensing liquids, we used an Unchained Labs Junior automated solid/liquid handling platform. By taking advantage of the Junior’s precise sub-microliter robotic pipetting capability in concert with in-line dilution through the OPI, we demonstrate the automated monitoring of chemical reactions in real time. While the reaction is in progress, the Junior dilutes an aliquot of the reaction mix and dispenses 100 nL of the diluted sample to the OPI-MS interface. This enables rapid reaction optimization and accurate kinetic profiling, addressing a common bottleneck in drug discovery and high throughput experimentation.

The Junior was capable of accurately delivering 100 nL samples to the OPI-MS inlet via positive displacement pipets. This had several advantages over the six-tip needle head, which could not reliably dispense samples below 10uL. Aliquots could be automatically dispensed to the OPI-MS every 80 seconds allowing for rapid sampling using the positive displacement pipets. However, the positive displacement pipets could only reach a limited area of the Junior which restricted the types of chemistry that could be run while the OPI-MS inlet was on the Junior. Thus, we redesigned the Junior and created a new space for the OPI-MS inlet while retaining the rack space for chemical reaction set up, execution, and dilution.

Presently, we have set up, executed, and sampled chemical reactions using through automation on the Unchained Labs Junior and the OPI-MS working in tandem for real time reaction analysis for kinetic analysis of single reactions and high throughput reaction screens. The SCIEX 6500-mass spectrometer monitored reactions via the progress of starting material, the product, and byproducts peaks. The real time analysis that was possible with this method demonstrated precisely when the reaction reached its optimal yield. This platofmr is highly effective for monitoring reactions that are particularly time sensitive or where the product degrades over time in the reaction conditions creating a window of peak product yield. The OPI/Junior integration is currently being used for monitoring reactions screens to provide real-time reaction analysis of 10s of reaction in parallel.