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High-Throughput Screening (HTS)

High-Throughput Screening (HTS) is a method used in drug discovery and molecular biology to identify active compounds, antibodies, or genes that modulate a particular biomolecular pathway.

Workflows Requiring High-Throughput Screening

The primary goal of HTS is to streamline drug discovery by rapidly analyzing a large number of potential biological modulators to identify those that have a desired effect on a specific target. HTS is commonly used in these workflows:

 

An Overview of the High-Throughput Screening Process

 

Step 1: Sample and Library Compilation

This step entails selecting a biologically relevant target, typically a protein or cellular pathway known to play a role in disease or other processes of interest. Concurrently, a diverse collection of compounds is either created or procured. These compounds, which can number in the thousands to millions, form the “library” that will be screened for potential activity against the target.

 

Step 2: Development of a High-Throughput-Compatible Assay

Central to the HTS process is the design and application of an effective assay. This isn’t just any test; it’s meticulously tailored to gauge the impact of library compounds on a designated biological target. To be effective in an HTS context, the assay needs to be ultra-sensitive to even the minutest changes and flexible enough to manage vast sample volumes. Additionally, the transition to automation necessitates the assay’s optimization for devices like microplate readers, often meaning it’s tailored for formats such as 96-well or 384-well plates. Beyond this, ensuring the assay’s stability and reproducibility across a vast number of samples is paramount.

 

Step 3: Automation Infrastructure Setup

Given the sheer volume of samples and compounds, manual handling is impractical. Therefore, specialized robotic workstations are configured to automate the process. These workstations can handle tasks ranging from dispensing precise amounts of samples and compounds to transferring liquids between microplates. The entire setup is designed to minimize errors, maximize speed, and ensure consistent handling of every sample.

 

Step 4: Data Collection and Analysis

After the compounds have been screened using the assay, vast amounts of data are generated. Automated plate readers, imaging systems, or other detection methods are employed to collect this data. Specialized software then processes the information, analyzing it to identify compounds that showed desired effects, known as “hits.” This step is critical, as it sets the stage for further investigations and optimizations based on these promising compounds.

Protocol Spotlights

Opentrons helps you automate High-Throughput Screening with open-source protocols for the OT-2 and Opentrons Flex

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