Automated Drug Discovery 2.0

Automation in drug discovery and development is not new—medium-to-high throughput screening with liquid handling robots has been routine for years. But recent technological advantages are causing a sea change in the benefits offered by laboratory automation. Beyond just reduced costs and improved productivity, modern R&D laboratories that have automated parts or all of their processes enjoy reproducibility and standardization, superior contamination control, efficient quality control, and improved data security. And in the future, it is likely that automation will support the integration of AI into drug discovery and development workflows to further increase the speed of innovation as well as the number of druggable targets. In this article we discuss some of the most exciting new developments in laboratory automation for drug discovery and development.

Automating early drug discovery

Virtually every aspect of drug discovery and development—from target identification to regulatory compliance—can be automated or directly benefit from automating other parts of the workflow. While the earliest steps in drug discovery and development—the identification and validation of potential targets followed by compound screening— have been automated to some degree (particularly through the availability of large phage display libraries and high-throughput screening capabilities), these early discovery steps remain a significant bottleneck. This is especially true as alternative design approaches (i.e., allosteric inhibition, protein-protein/DNA interaction inhibition, and more) and AI introduce even more target and compound options, particularly for traditionally “undruggable” proteins.

ArrayJet and SCIEX are two companies aiming to improve target discovery and hit identification through their revolutionary technologies. Both require significantly less sample than most current solutions, increasing discovery potential and permitting faster-than-ever screening, accelerating decision-making and transitioning hits to the next stages of the pipeline even faster. With these technologies, time bottlenecks are now on data analysis, rather than data production—a problem that can be addressed through machine learning and other computational tools.

“It’s about significantly moving the needle for all workflows within early drug discovery, rather than just moving the bottleneck elsewhere in the process,” explains Susan Darling, Senior Director of CE Product Management at SCIEX.

ArrayJet achieved these improvements through their bioprinting technology. The company prints proteins or compounds onto slides, microplates, and biochips that can then be used for an array of applications, such as antibody discovery and validation, drug target identification, functional assays, PROTAC development, and even training AI drug discovery models. Only picoliters of sample are used, facilitating target identification using limited volume or hard-to-acquire samples. Additionally, spot-on-spot printing permits combinatorial library screening and generates millions of data points weekly.

SCIEX is also transforming drug discovery for both small and large molecule development through their Echo MS+ system (launched at SLAS in Boston this past February), which leverages proprietary Acoustic Ejection Mass Spectrometry (AEMS) technology to achieve high sampling speed along with highly selective, sensitive, and reproducible analytical measurement (it takes only 30 minutes to acquire data from a 1536-well plate) while minimizing sample consumption.

The platform, says Darling, facilitates workflows like medicinal chemistry, compound library management, high-throughput screening, and intact biomolecule analysis, making it a holistic solution that has the potential to cause a “paradigm shift in how people strategize and execute small and large molecule early drug discovery.” Already companies like Bristol-Meyers Squibb and Novartis have used the Echo^® MS+ system to increase the efficiency and speed of their hit identification and validation workflows.

Automating the latest trends in drug discovery

One of the fastest growing trends in early drug discovery is the use of 3D cell models (i.e. spheroids, organoids, and organ-on-a-chip models). Such models not only facilitate better safety and efficacy assessments of hit leads prior to clinical trials, but also eliminate the species-to-species differences that often lead to failed drugs. Automating their use, however, comes with a new set of challenges, including poor reproducibility and low throughput.

Tecan, a leader in advanced automation solutions, is addressing these challenges through their end-to-end cellomics workflows. Built on a suite of instruments including single-cell dispensers, automated liquid handling workstations, and multimode plate readers, Tecan’s cellomics solutions enable entirely automated workflows from cell seeding to live-cell imaging and analysis. They’ve paired their instruments with lab digitalization tools that enhance equipment and personnel efficiency and keep data secure for a comprehensive solution that meets market demands.

Microfluidics capabilities can also support 3D models, and a growing number of companies are developing microfluidics tools for 3D models. For example, Xellar Biosystems manufactures microfluidic device-based consumables supporting 3D organ-on-chip culture. But microfluidics can play an important role in automating many other aspects of drug discovery and development. Nuclera has partnered with Sharp Life Science to leverage microfluidics for complex, custom protein design for drug discovery, and Eli Lilly have built an entirely remotely operated, fully automated microfluidics-based chemical synthesis laboratory.

A fully custom, fully automated pipeline

As the number and diversity of automation tools increases, more organizations seek to automate multiple parts of their processes or even their entire processes from start to finish. This task can be both daunting and tricky—but can yield great rewards in areas like workflow efficiency, reproducibility, and getting results faster. Danaher Corporation has introduced an elegant model for consulting and implementing full-pipeline automation solutions by bringing together leading companies across expertise areas under a single umbrella.

“It’s simply teamwork,” says Dr. Peter Braun, Field Project Manager, Automation, at Beckman Coulter Life Sciences. “We have experts in automation like Beckman Coulter Life Sciences, in imaging at Molecular Devices, and in mass spectrometry at SCIEX, all working together to cover different aspects of the overall workflow. We aren’t just trying to deliver the best box with the shiniest features—we’re working to tailor the single solution that is best for you. We understand the customers and their workflow requirements, and build on our expertise to deliver the best solution.”

“We are a united company, and we partner together really well, but we’re also agnostic,” adds Sarah Simons, Market Development Manager at Beckman Coulter Life Sciences. “So when a customer says, ‘I need to automate this part of my process I’m currently doing manually,’ I can specifically point them to several options in the marketplace, including potentially introducing them to colleagues at other Danaher operating companies. This approach ensures that organizations seeking guidance on automating their processes will find the complete solution that is best for them, which at the end of the day, is the approach that will ensure patients receive quality, safe, effective drugs faster.”