Automation using IMCStips® with
Hamilton Microlab® STAR™
Presenters and Moderator
Presenter: Carter Mitchell, PhD
Presenter: Joe Corvera, MS
Moderator: Ana Gupte, PhD
Executive Summary
Kemp Proteins have recognized that recently their clients are particularly interested in high throughput initial analyses to increase success in downstream large-scale productions. The use of IMCS and Hamilton STAR streamlined the generation of Gen1 Anti-DYK by leveraging automated high-throughput processes. This helped to accelerate biomarker and therapeutic discovery programs by broadening the ability to screen candidates in a high-throughput manner, mitigating risk of non-productive candidates through early elimination, and allowing rapid analysis throughout the program. As a result, timelines are reduced, and success is increased.
Challenges
One of Kemp's clients requested numerous small-scale test expressions with purifications using an expensive Anti-DYK affinity resin. And generally, commercial Anti-DYK resins have higher endotoxin levels than Kemp’s release criteria. This led to a unique opportunity for Kemp to develop a Gen1 Anti-DYK antibody conjugated to resin and packaged into the IMCStips platform.
How IMCS Helped
The implementation of automated processes streamlines the process of clonal selection from productivity of expression and through direct interrogation of the expressed molecules of interest. The IMCS and Hamilton platforms were instrumental in providing rapid solutions to generate material that enable higher quality downstream characterization assays and informed decisions on clone selection and scale up. These methodologies enable the acceleration of protein-based discovery programs through broadening the ability to screen candidates in high throughput manner while simultaneously of mitigating the risk of non-productive candidates through early elimination and allowing rapid analysis throughout the program which reduces timelines and increases success. This workflow has been successfully applied to other protein targets at Kemp and is quickly becoming a preferred platform for many of their clients.
Results, Return on Investment, and Future Directions
Quotes from Presentation
“Previously, we would use batch-binding methods to protein-A based resin or nickel affinity, which would require us to do it in batches as well, so maybe we could handle 10 or 20 per day. It’s kind of a balancing act of making sure you don’t make mistakes and keep the right fraction separate from the others. By doing a plate-based automated separation, we can get through 24+ samples in about 3 or 4 hours and we don’t have the risk of cross-mislabeling or moving fractions or anything like that.”
"Furthermore, it’s pretty much hands-free, where our purification scientists can set up the plate with the buffers and press the button. And in instances where we have some errors that happen from our scripts or methodologies, the purification scientists get on the phone with the specialist who can smooth out any issues that we may have. So, I think that the throughput and the minimization of mistakes from human error is really a big player here, and it allows our purification scientists to get back to doing more important large-scale purifications at that point while the smaller stuff is going on in the background.”
"Purification modalities that require elution with imidazole pH often necessitate buffer exchange to enable downstream analytics. IMCS provides a solution to his burden with their SizeX tips. The automated desalting steps follow a general size exclusion technique for the smaller buffer components for migrating through the resin pores and the large proteins of interest are excluded from the internal volume. These tips enable hands-free, rapid desalting that minimizes risk of human error in a high-throughput manner.”
"For therapeutic programs or products where purified monoclonal antibodies are needed for functional assays, the IMCStips on the Hamilton STAR provides a powerful, efficient, and scalable path to be able to provide purified antibody screening for antibody functionality and early stage of the program. This capability is critical for therapeutic-based antibody discovery programs, which are typically larger in scale, to be able to generate large amounts of IgG that can surpass multiple screening steps for binding, specificity, productivity, functionality, and other downstream requirements."
"The IMCS and Hamilton partnership has provided a comprehensive, high throughput, automated microscale purification package that includes chromatography tips, methods, and instrumentation platform with scripts that are essentially plug and play. We routinely use the IMCS and Protein A-based purification schemes for our automated processes."
