Precision at Scale: Redefining High-Throughput Screening for Challenging Therapeutic Targets
New HTS advances are making complex assays scalable and precise.
As drug discovery continues to evolve, the need to scale High-Throughput Screening (HTS) has become increasingly critical. While simple aqueous liquid handling has long been automated, laboratories are increasingly tackling a range of complex biochemical assays that involve viscous reagents and intricate protocols—areas where precision and reproducibility have historically been difficult to achieve at scale.
Chief executive officer of SPT Labtech, Rob Walton, has overseen the evolution of liquid handling technologies designed to lower barriers to automation while improving precision and throughput. In this article, he explains the challenges of modern HTS and what the recent collaboration between SPT Labtech and BellBrook Labs demonstrates about the feasibility of scalable, high-throughput discovery.
The strategic shift: why HTS automation is now essential
The drug discovery industry is pivoting toward automation not just for speed, but to ensure the data fidelity required for modern discovery. By automating complex screens, labs can drive the right clinical and biological outcomes more efficiently than traditional manual methods.
“Automation helps to lower costs. Ultimately, you can actually perform tasks more cheaply and efficiently with higher throughput.” — Rob Walton
Beyond cost-savings, automation delivers the high-fidelity, reproducible data required for modern discovery. It also democratizes science by making complex HTS workflows accessible to smaller labs and freeing scientists from manual labor to focus on high-value research.
Key benefits of this shift:
- Higher throughput and more efficient use of resources.
- Accurate and repeatable results for advanced analysis.
- Freeing up highly qualified staff from repetitive manual tasks.
The barrier: why complex HTS workflows resist automation
Although the need for robust screening has grown, automating complex biochemical assays has historically been challenging. As Rob explains, the behavior of different reagent types can become a major hurdle when automating workflows for modern drug discovery.
Standard automated systems often struggle with the non-uniform, highly viscous liquids found in these assays. These reagents can clog in conventional air-displacement or valve-based systems, pushing traditional laboratory robotics beyond their limits.
“When you start to work with more complicated assays, the viscosity of the liquid changes... you have to have a technology that can handle those difficult workflows and drive the right outcomes.” — Rob Walton
Critical bottlenecks in standard automation:
- Viscous reagents clog conventional systems.
- Data variability from inconsistent fluid handling
The solution: positive displacement and the Bellbrook collaboration
Effective and accurate automation of complex screening workflows can be achieved using positive displacement technology. Unlike standard air-displacement systems, this method uses a physical piston in direct contact with the liquid. This makes the mechanism inherently insensitive to liquid thickness or viscosity, ensuring the exact same volume is dispensed every time.
This enhanced accuracy across a variety of sample and reagent types was leveraged in the collaboration between SPT Labtech and BellBrook Labs to successfully automate a challenging assay setup. By combining BellBrook’s Transcreener® ADP2 fluorescence polarization assay with SPT Labtech’s dragonfly® discovery system, an automated low-volume liquid dispenser, the teams proved that even the most “difficult-to-handle” assays could be automated with absolute precision.
“I think that's where innovation is really at its best, when you have a need, and you have a technology that can come together to really solve problems that exist within the industry.” — Rob Walton
How positive displacement overcomes complexity:
- Physical pistons eliminate air-buffer errors.
- Uniform dispensing regardless of reagent thickness.
- Simplified protocols for challenging assays.
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A primary outcome of this collaboration was the development of a robust, scalable screening approach for VPS4B, a novel therapeutic target in oncology. Identifying effective inhibitors for this ATPase has previously been a hindered by the complexity of the reagents involved.
The dragonfly® discovery platform enabled precise dispensing across diverse reagent classes using a single set of dispensing parameters, allowing a complex assay workflow to be automated with ease.
Impact on oncology drug discovery:
- Successfully automated screening for the challenging VPS4B cancer target
- Established a scalable model for targeting complex enzymes and ATPases
Evolving perceptions around automation
Rob has seen a clear shift: more labs are adopting automation than in the past, driven by lower barriers to use, improved usability, and the need for higher throughput and efficiency.
“There’s a myth about automation being expensive and difficult to use… that barrier is starting to come down.” — Rob Walton
Key trend shaping the future:
- Misconceptions about automation are gradually decreasing
By bridging the gap between sophisticated assay chemistry and precision robotics, the transition to positive displacement technology is transforming complex biochemical hurdles into scalable, data-rich discovery pipelines.
“At the end of the day, it’s about the data… delivering the right clinical and biological information that can then be used within researchers’ future work.” — Rob Walton
Top Takeaways:
- Positive displacement: this technology enables the reliable automation of complex HTS assays involving viscous reagents that were once considered “un-automatable.”
- Data integrity drives discovery: high-throughput screening is no longer just about speed; it is about generating the high-fidelity data required for reliable biological insights.
- The collaboration advantage: The SPT Labtech and BellBrook Labs partnership proves that combining industry-leading assay chemistry with world-class liquid handling can unlock difficult oncology targets like VPS4B.
This content includes text that has been created with the assistance of generative AI and has undergone editorial review before publishing. Technology Networks' AI policy can be found here.
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