François Lévesque

We report advanced applications of the DILCTM system as a powerful automated tool for monitoring reaction conversions in flow processes for the first time. By applying the DILCTM system to a photocatalytic flow reaction, we systematically mapped the reaction conversions across various residence times and temperatures. The DILCTM system has demonstrated significant effectiveness in flow reactions by facilitating reaction optimization, enhancing sustainability, and minimizing human intervention. Furthermore, the DILCTM has proven to be an excellent online tool for calibrating spectroscopic data. This innovative methodology not only streamlines analytical workflows but also lays the groundwork for future advancements in automated in-process control (IPC) technologies.

This manuscript reports the identification of hydrophobic interaction chromatography (HIC)-shifting, non-toxic linker-payload surrogates as tool molecules for the optimization of maleimide/cysteine conjugations relevant to antibody-drug conjugates (ADCs). These tool molecules are demonstrated to allow conjugation measurement via HIC with a mAb (mono-clonal antibody) bearing engineered cysteines, and for conjugation to mAb interchain cysteines. The linker/payload (LP) mimics were employed to optimize conjugations via high-throughput experimentation and employed to facilitate the development of continuous flow conjugations in a microfluidic reactor and on larger scale. Putative identification of the novel ADC mimics by HIC was confirmed by mass spectrometry. Overall, our studies provide confidence that commercially available, non-toxic LP mimics can be employed successfully to optimize ADC-type conjugations in batch and flow, while minimizing materials needs and experimental work in specialized facilities required for potent compound handling.