How Can Automation Accelerate Laboratory Experiments?

High throughput, unwavering precision, and consistent efficiency are three important factors in pre-clinical research. This research serves as the crucial foundation for the development of groundbreaking therapies, and the demand from customers is remarkably high.

The traditional sample pretreatment procedures of the experiments including in vitro ADME (absorption, distribution, metabolism, and excretion) research, and in vivo pharmacokinetic experiments, or bioanalysis, are heavily reliant on the manual manipulation of tools, reagents, and instruments. Moreover, the extensive range of analytes and substrates involved has also constrained the capabilities of conventional liquid workstations.

At WuXi AppTec, we embrace new capabilities and technologies, constantly improving the efficiencies of drug research and development. Following the introduction of the first automated liquid handling workstation in 2014, the in vitro ADME team of WuXi AppTec DMPK has continuously expanded the platform and upgraded the automation level of the workstation to improve work efficiency and the quality of research data.

Currently, a fully automated platform with multiple high-throughput integrated liquid handling workstations that are well aligned with the in vitro ADME business has been established. It covers various types of in vitro ADME assays and efficiently supports new drug development projects.

More Than Assisting with Pipetting

To automate frequently repeated pipetting tasks, small semi-automatic liquid workstations were applied with limited throughput. Manual operations including sealing, peeling, and sample addition were still needed and the overall efficiency was not desirable. However, the situation was greatly improved with the deployment of upgraded automation workstations that could handle liquids in batches, and then automated standard solutions were developed for each type of assay accordingly. The assay throughput and efficiency in the lab were considerably improved thanks to this technology upgrade.

High-throughput integrated liquid handling workstations come standard with 96-channel pipetting heads, which allows the processing of entire 96-well plates in a single run. The workstations can also be upgraded to 384-channel pipetting heads. Routine laboratory operations such as substrate, compound, and termination solution addition can be quickly performed.

Additionally, the workstation typically has approximately 50 plate positions (expandable to accommodate additional positions), which enables batch processing of multiple 96-well plates or multiple assay rounds. The liquid handling of the workstation is greatly accelerated, considerably improving throughput.

Continuous Integration Enables Overnight Assay Performance

However, the completion of assays by decentralized liquid handling workstations still required numerous manual steps at that time. To meet customers’ demands, WuXi AppTec’s DMPK team built a high-throughput integrated liquid handling workstation with an automated pipetting workstation as the core and peripheral integrated functional equipment. The automation functions of the workstation were expanded beyond automated liquid handling and plate transfer and are controlled by the software incorporated.

Compared to the decentralized workstation, the upgraded platform with automation integration can perform functions other than liquid handling, including constant temperature and uniform oscillation incubation, centrifugation and solid-liquid separation, sealing and peeling, and cryopreservation of sample plates.

The fully automated processes free the scientists from the need to closely monitor the reaction process, reducing human errors in repetitive sample preparation prior to analysis. The workstations can further extend the 8-hour working limit of instruments and automatically perform assays overnight. This expedites project advancement and significantly reduces the waiting time for initiating IND projects.

Through the application of a cutting-edge, high-throughput integrated liquid workstation platform, DMPK has successfully realized automation in various experiment operations including continuous enzyme reactions, continuous cell reactions, and more.

The continuous integration was also applied in automating enhancements across various other experiments. For example, the WuXi AppTec DMPK team has integrated a high-throughput intelligent system for biological sample pretreatment into pharmacokinetic experiments, with around 30 instruments intelligently connected. This system eliminates the need for manual intervention throughout the entire process, from sample placement in the refrigerator to completion of processing and experiment recording, allowing for a seamless “one-click generation” experience.

For the GLP Bioanalysis team, in order to meet the unique sample preparation requirements for the seven major experiment types: LCMS/PK/PD/ADA/Nab/FACS/PCR, the configuration combination of the liquid handling workstation allows for more precise and convenient personalized settings. Prior to use, the instruments and corresponding methods of the liquid workstation undergo dual validation to ensure that the processes meet regulatory requirements, and run smoothly and accurately. The success rate of sample preparation has increased from 96.5% with manual operation to over 99%.

BAS bioanalysis clinical large molecular team has implemented the fully automatic biological sample analysis system, which integrates all the equipment required for large molecular drug detection (TECAN? automated liquid workstation, plate washing machine, plate reader, incubator, shaker), realizing the automation of the whole process from sample pretreatment to data generation. Through the intelligent sequencing of the software and the collaborative of multiple robotic arms, multiple analysis batches can be parallel analysis, which can improve efficiency by up to 300%.

Remarkable Precision Achieved Through Extensive Collaboration

Building a full-process automation laboratory is not a straightforward endeavor. Despite the remarkable improvement in efficiency and throughput, scientists still need to address concerns about the accuracy of the experiment results, the possibility of repeating the experiment, and whether the data generated by the experiment aligns with the standards needed for analysis and regulatory submissions.

Thanks to the remarkable precision achieved through extensive collaboration and rigorous validation efforts conducted by both scientists and automation engineers, all these concerns are properly handled. For instance, in terms of pipetting of small volumes (0.5 μl), The High-Throughput Integrated Liquid Workstation allows accurate setting of appropriate liquid parameters according to the type of liquid to ensure accurate pipetting. Different pipetting speeds and air column volumes can be set according to the characteristics of the liquid, such as viscosity, to ensure accurate pipetting. As a result, the experimental results performed by the workstation are highly reliable and reproducible. For example, when applied to the configuration of standard curves, the accuracy (Accuracy (%)) is about 100 (Fig. 2), greatly exceeding the accuracy acceptance standard of 80 ≤ Accuracy (%) ≤ 120 for Non-GLP analysis, as well as 85 ≤ Accuracy (%) ≤ 115 for GLP analysis.

The BAS bioanalysis clinical large molecular team has completed the development of the whole process automation protocol for three types of experiments, including pharmacokinetics, biomarker, and immunogenicity. More than 50 methods have been qualified, the stable and reliable data have been obtained. The Bias of most quality samples is ± 10%, which is above the accepted standard of ± 20%.

Through the digital and visualized platform for operation management and the use of automation instruments, resource configuration, and platform management across multiple sites have become a reality, thereby continuously improving efficiency. The management platform enables collaborative management across multiple users, programs, instruments, and sites, thereby facilitating reasonable and efficient deployment, ensuring adherence to the project timelines, and streamlining project implementation.

WuXi AppTec's dedicated researchers and technicians consistently enhance and rigorously validate the automation platform to align precisely with the evolving needs of our customers. Looking to the future, we remain committed to embracing new capabilities and cutting-edge technologies, constantly pushing the boundaries of innovation. Each day, we are getting closer to a bright future where "every drug can be made and every disease can be treated."