HIGH THROUGHPUT SCREENING (HTS)

High Throughput Screening Automation: An Introduction for Laboratory Scientists 

In the world of scientific research, particularly within drug discovery, efficiency is paramount—this is especially true of High Throughput Screening (HTS). My own scientific journey transitioned from labor-intensive manual assays to exploring and embracing automated technologies that expand the potential for novel discoveries. Let's explore the landscape of HTS.

Fundamentals of High Throughput Screening

Those of us seeking automation in HTS are driven by goals beyond speed. We strive to miniaturize assays, enhance data collection volumes, and integrate redundancy within instruments to ensure reliability and continuous operation. You’ll need to manage a vast array of plates and consumables, each requiring strategic storage solutions, data handling, and variability in how they’re processed (like selecting the appropriate downstream assay based on upstream data, for example). 

However much I appreciate liquid handlers, they often need to be supplemented with other equipment in order for HTS to be more efficient. The transition from traditional tip-based liquid handlers to non-contact dispensers marked a significant milestone in how I think about enhancing efficiency – thanks to my experience working for High Res Bio, an integrator of large HTS systems (and much more). Tip based liquid handlers have their place in HTS in almost every case, but it’s wise to consider non-contact dispensers as well for the time and cost savings.

The evolution of HTS includes a recent shift towards more intricate, longer-running cellular assays using valuable cells, necessitating rigorous sterility and aseptic techniques – workflows performed by “streaming” in new assay plates instead of setting up “batches” of plates periodically – all within a clean, enclosed environment.

Selecting appropriate instrumentation is a critical strategic decision, encompassing a range of tools from liquid handlers to multimodal readers, washers and dispensers. For example, the integration with cell culture maintenance systems may be crucial, as these systems supply the fresh cells vital for subsequent HTS applications. I’ve helped dozens of clients make difficult decisions about which equipment to choose, balancing cost with capability, flexibility, and reliability – and there’s rarely the “best choice” but rather choices ranked by your priorities and tolerance for certain constraints.

Central Concerns in HTS 

Maximizing throughput remains a top priority, alongside ensuring assay uniformity, robust storage solutions, redundancy and reliability (ensuring uptime), and the ability to run multiple assays concurrently. As we navigate these priorities, we also focus on future-proofing our labs. This means selecting systems and instrumentation that can adapt to the evolving demands of scientific research, balancing flexibility with cost and complexity—a strategic and visionary approach that deserves our focus here because it’s often used as a buzz-word and the pros/cons of such a feature are often misunderstood. 

Running HTS systems effectively involves a delicate balance between automation and human oversight, ensuring that reagents are used efficiently and remain stable under various conditions, as well as troubleshooting quickly as challenges arise. The challenge of minimizing waste, whether it involves tips, plates, or valuable reagents, is a continual focus, guiding us toward more sustainable and economical laboratory practices. Costs can pile up very quickly and it can be hard to predict exactly what your operating costs will be if you haven’t built automated systems around HTS.

Workflows and Equipment Limitations and Bottlenecks

Reflecting on the range of workflows, from cellular reporter assays to sophisticated high-content imaging, highlights the diversity of tools required for effective HTS. Each phase, from cell seeding to compound addition via advanced dispensing methods, illustrates the intricate interplay of technological and scientific limitations. There are always limitations and bottlenecks and it’s our responsibility to predict and control how and where we choose to place those constraints. Decisions on techniques like centrifugation (like BlueCat Bio) versus plate washing can impact overall workflow efficiency, and introduce limitations that you can learn by asking me or your colleagues. 

Just remember there are always bottlenecks and limitations in any process, and that’s especially true in our industry when you’re working with robotic and biological systems at the same time. You want to choose the bottleneck and maintain control and transparency so you can stay up and running. I’ll write more on this in a future post because it’s a huge topic that is universal in process engineering – too broad for this post.

Reflecting on HTS

Embarking on HTS necessitates addressing several critical questions, from assay types and throughput capabilities to the operational duration of screening processes. Every detail is crucial, including the management of lids and seals and ensuring that instruments are up-to-date and compatible with current lab workflows. If you want to explore every consideration, please reach out and I’ll help you uncover insights to improve your processes, equipment choice, and overall approach to a solution to HTS.

HTS plays a pivotal role in advancing the frontiers of scientific discovery, and is not merely about adopting new technologies; it is about fundamentally rethinking how we conduct scientific research.

To ensure you've considered every detail of your HTS goals, and that your requirements for solutions are solid, contact us today for a free consultation.