Category: Automation and High-Throughput Technologies

1098-D - Delivering custom integration solutions to enable high throughput screening on a qPCR platform

Tuesday, February 6, 2018
5:00 PM - 6:00 PM

For the unfortunate scientist, hours of the day are spent stringing together tedious processes that could be streamlined using automation. A project team formed by a collaboration between screening and engineering groups sought to identify and eliminate particularly tedious pain points within an existing qPCR workflow by implementing a custom automated solution that reduces variability and maximizes walkaway time. The procedure consisted of demanding, time-critical steps - plating qPCR reagents which are not stable at room temperature, followed by manually feeding two or three plates at a time to mini Thermo Momentum automation systems. The first step of system design was the creation of novel Solidworks CAD models of an upgraded Thermo Momentum platform to be reviewed with the team. Design iterations ranged from a fully automated qPCR process to the optimization of particular steps, allowing the screeners to “tour” the virtual platform, visualizing it in their lab reality. All designs were constrained to the devices on-hand, the existing Thermo Orbitor robot envelope, and the allowable footprint within the lab space. These computer-generated models helped to explain and demonstrate additional design considerations such as robot reach, the use of custom device slides and ease of access, enabling the screeners to provide better feedback toward engineering enhancements. By the end of the interactive design phase, the group selected a design that doubled walkaway time by adding cold storage to improve data quality through increased plate stability, and significantly decreased processing time by integrating additional thermal cyclers. The integration was simplified by 3D Printing thermal cycler foot mounts directly from the Solidworks design, and repurposing existing devices where suitable. The iterative virtual design process enabled the team to limit downtime to one week on a heavily used system, including the complete integration of equipment, Momentum database reconfiguration, and testing. The impact of the redesign on the qPCR system’s performance was validated by executing a proof of concept study. Two batches of plates under room temperature versus cold storage conditions were read at time points over 20 hours. By preparing identical plates and reducing the variables solely to storage environment, the data demonstrates that the housekeeping genes remain active for a longer period in cold storage with acceptable variation in signal, while plates stored at room temperature show increased variability and loss of signal due to reagent degradation. As a result of this redesign, user intervention loading plates incrementally is replaced with automated runs of large batches of qPCR plates processing overnight. With this increased throughput, improved consistency, and significantly reduced preparation time, the system enables a 1536-well 250K-target screen that previously required 23 days of qPCR processing time to be completed in six days, leading to faster drug discovery.

A. Rose Lassos

Automation Engineer II
Novartis Institutes for BioMedical Research
Cambridge, MA

Rose Lassos is an Automation Engineer II at Novartis Institutes for BioMedical Research. At NIBR she plays a pivotal role as the technical lead in screening system design projects, as well as custom engineering projects throughout the Chemical Biology and Therapeutics Department. Rose also works with screening associates to ensure smooth transitions from benchtop to complex integrated screening systems for any assay requiring automation. She comes to us from the University of Colorado at Boulder, where she earned a Bachelor’s degree in Mechanical Engineering with an emphasis in biotechnology. After working in field engineering for QIAGEN Inc. across the Midwest, Rose landed at the Broad Institute where she spent two years as an Automation Engineer, transitioning screens onto the large integrated systems within the Chemical Biology platform.