What Is High-Throughput Screening?

High-Throughput Screening (HTS) is a powerful method used in science to test thousands—even millions—of chemical, biological, or material samples quickly and automatically. Instead of testing one sample at a time, HTS uses robotics and smart software to do the heavy lifting, helping researchers:

Find active compounds (like potential new drugs or better-performing materials)
Improve product formulations (such as safer pesticides or better battery materials)
Understand complex biological systems (like how proteins interact or how genes are expressed)

To put it into perspective: HTS can process over 10,000 samples in a single day, compared to just 100 samples per week using traditional lab methods. That kind of speed is a game-changer—more than 80% of small-molecule drugs approved by the FDA were discovered through HTS (Nature Reviews Drug Discovery, 2023).

How Does HTS Actually Work?

Step-by-Step Overview of the HTS Process

Library Preparation
Scientists gather large collections of chemical compounds—these might include FDA-approved drugs, natural extracts, or newly synthesized molecules. They also set up biological tests, called assays, that will help measure activity.
Automated Liquid Handling
Robots like those made by Tecan or Hamilton precisely dispense tiny amounts of liquid into plates with 96, 384, or even 1536 mini-wells.
Running the Assay
Measurements are taken using light (fluorescence, absorbance, or luminescence) to detect which samples are active.
Analyzing the Results
A statistical value called the Z’-factor checks the reliability of the assay (a Z’ above 0.5 is generally good). Then, active compounds—called “hits”—are selected for further testing.

Types of HTS Assays (Tests)

Where Is HTS Used?

1. Drug Discovery

HTS is widely used to find new medicines, whether by screening brand-new compounds or repurposing existing drugs.

Example:
Pfizer used HTS to screen over 200,000 compounds in a matter of weeks, which helped lead to the discovery of Paxlovid, its COVID-19 antiviral (Science, 2021).

2. Materials Science

HTS helps find and optimize new materials, such as:

Better battery electrolytes
Catalysts for capturing carbon dioxide (CO₂)

3. Agricultural Chemistry

Companies like Bayer use HTS to quickly discover safer, more effective herbicides and pesticides.

Challenges (and How Scientists Solve Them)

1. False Positives

Problem: Some compounds give misleading results.
Solution: Use control tests (like detergent-based counter-screens) to weed them out.

2. High Costs

Problem: Setting up HTS can cost $500,000 to $2 million.
Solution:

Share access through collaborative networks (e.g., NIH programs)
Use virtual screening powered by AI to reduce the number of physical tests needed

3. Too Much Data

Problem: One HTS run can produce terabytes of data.
Solution:

Use machine learning to highlight the most promising results
Analyze data in the cloud (e.g., using Google Cloud tools)

What’s Next for HTS?

AI + HTS = Smarter Screening

AI can design better chemical libraries to test
Real-time optimization using active learning helps focus on the most useful experiments

Miniaturization

New nanofluidic chips can screen over 100,000 samples per day, using even less material and time.

Self-Driving Labs

Robotic systems integrated with AI—like MIT’s “AI Chemist”—can now run entire HTS workflows on their own, speeding up discovery and reducing human error.

Is HTS Right for Your Research?

HTS is a great fit if you:

✅ Need to test lots of samples quickly
✅ Are working on drug or materials discovery
✅ Want to automate time-consuming lab tasks

Want to Get Started? Here’s How:

Learn the software: Tools like KNIME or Pipeline Pilot are commonly used in HTS.
Explore compound libraries: Platforms like PubChem BioAssay offer free access to millions of samples.

High-Throughput Screening (HTS): A Simple Guide to Faster Drug and Material Discovery