Micro to Prep-Scale Purifications of Large Molecule Modalities on a Single Automated Platform and Workflow

High-throughput purification (HTP) laboratories are increasingly faced with separating complex crude reaction mixtures at both the microscale and preparative scale in support of drug discovery research. To address this point, we introduce a custom Agilent 1290 Infinity II Prep LC/MSD configuration capable of performing both microscale and preparative scale purifications on a single platform without the need to reconfigure flow paths or physically remove the 1 cm and 2 cm ID columns. 

Method selection allows for immediate switching between the columns, modifier, flow rate, and delay times for fraction triggering. Multi-detector technology allows for rapid target isolation, impurity determination, and quantitation of large molecule modalities such as cyclic peptides and bioconjugates. Sample management and predictive software tools are utilized for automation of method assignments directly into OpenLab ChemStation. The overall system platform and workflow increases throughput and lowers cost without compromising purity and recovery. 

Presenter: Kanaka Hettiarachchi (Principal Scientist, Merck)

Kanaka Hettiarachchi is a Principal Scientist in the Discovery Chemistry department at Merck Research Laboratories (MRL) South San Francisco, where he has been leading the High Throughput Purification (HTP) team since 2017. His industrial research focuses on enabling technologies to support the separation and isolation of new pharmaceuticals, from small molecules to large molecule modalities. A variety of techniques are utilized in the group including ultrafast microscale separations, multidimensional chromatography, supercritical fluid chromatography, and machine learning to optimize chromatography conditions. Prior to joining Merck, he worked as a Scientist in the Research Analytical groups of Relypsa and Theravance Biopharma. Kanaka has over 15 years of pharmaceutical industry experience leading HTP activities for drug discovery. He received a PhD in Biomedical Engineering with a focus on Microfluidics from the University of California, Irvine, and a Bachelor of Science in Bioengineering from the University of California, San Diego.