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High-throughput screening (HTS) is an essential part of the current drug discovery process. It allows for rapid automated testing of large libraries of biological or chemical compounds to assess their effect on a specific biological target. Once a lead molecule has been identified, additional testing is required to further characterize lead compounds and assess their potential efficacy.
Creating a highly specific and novel biologic involves high-throughput antibody screening of hundreds of candidate clones. An unparalleled combination of speed, sensitivity, and multiparameter analysis are all required when assessing antibody clones to find those that bind strongly and specifically to target antigens with the potential to become commercialized products.
Phenotypic screening is often described as a target agnostic approach to drug discovery. Here, molecules are assessed for their ability to promote a desired phenotype associated with a therapeutic effect. Typically, phenotypic screening is used in small molecule drug discovery often utilizing cellular models of human disease pathophysiology. It may encompass multiple parameters to assess the likely efficacy of drug candidates including elucidation of a desired effect as well as monitoring of adverse events such as toxicity.
Once a lead molecule has been selected, it is necessary to evaluate its characteristics and performance. This can involve several preclinical assays including safety, pharmacokinetics (PK), Absorption, Distribution, Metabolism, Excretion (ADME), internalization, and functional studies. Functional assays may include neutralization, agonism, antagonism, proliferation, and apoptosis assays.
Flow Cytometry as a Tool for Screening
To perform this array of tests throughout the whole drug discovery process, flexible and sensitive instrumentation is needed to manage the required assay speed, without sacrificing high-parameter data collection and rare-event detection. For these reasons, flow cytometry has become the gold standard for performing antibody and phenotypic screening as well as characterization assays. Importantly, flow cytometry allows for unparalleled multiplexing, while providing the flexibility, speed, and reproducibility to analyze a high number of individual events and determine their distributions.
Challenge of High-Throughput Antibody Screening & Analysis
In the drug discovery process, it is necessary to screen for candidate hits, filter those hits into lead candidates, and then analyze each candidate’s clinical potential. Flow cytometry is an excellent technique to perform the necessary experimental volumes and conditions. There are three important characteristics of high-throughput flow cytometry workflows: multiparameter/multiplexed analysis, acquisition speed, and automation readiness.
Combining High-Parameter, High-Speed Flow Cytometry with Automation
Collecting data on multiple parameters at once enables more complex and informative multiplexed analysis. This can be achieved by using flow cytometers with multiple lasers and detectors. Fundamentally, the more lasers and parameters are involved the more data is collected each time.
Acquisition speed describes the rate at which a flow cytometer moves, counts, and collects data. Speed of acquisition is a key variable for improving the detection of rare events, such as T-cell and other immune-cell population changes. By collecting more data within a limited amount of time, the likelihood of capturing these rare events increases. For optimal results, select a flow cytometer that avoids sample carryover by automatically washing the probe between samples.
Flow cytometry instruments built with automation in mind can also help actualize the high-throughput potential of an instrument, as analysis demands increase further. Flow cytometers ready for robotic integration and with automation features can simplify operations, save time, and improve lab performance.
High-Throughput Screening Instruments
Introducing the Market Leading Instrument for HTS
We know you are under increasing pressure to deliver ever more data, more quickly and that you need the right tools to support you. In the past, you may have had to compromise between speed, the number of parameters measured, the number of events collected, or even data resolution.
With the ZE5 Cell Analyzer, the market leading HTS instrument, this is no longer the case. Achieve unprecedented speed without having to compromise on performance. You can screen your samples faster and with better data quality than with any other flow cytometer.
A Screening Flow Cytometer without Limits
- High-throughput ready hardware and software
- Maximal productivity with integrated automation and 24/7 operation
- High-speed acquisition without compromising data quality
- Superior assay design and instrumentation flexibility
The impressive features of the ZE5 Cell Analyzer enable you to design experiments that no other flow cytometer available today can do. Five lasers and 30 detectors, fast sampling from 96-well or 384-well plates, and speed up to 100,000 events per second means you can design larger panels and run them at unparalleled speeds.
Speed up Your Discovery without Compromise
Integrates with laboratory robotics system via a device-agnostic application programming interface (API)
96-well plates in 15 min
384-well plates in 50 min
ensuring low carryover at high speed with high-throughput screening
100,000 EVENTS per sec
without data loss or compromised resolution
24/7 with a single operator
using high-capacity fluidics tanks
Built for Screening
Efficient and Flexible Sample Handling
For high-throughput a plate loader is essential - the ZE5 Cell Analyzer enables:
- Hands-free hardware switch over — switch between plates formats or tubes using the integrated sample loader
- Compatibility with any plate format — round bottom, flat bottom, V bottom, deep-well
- Sample preservation — on‑board temperature control and orbital agitator
- Prevent blockages — with the innovative bi-directional sample pump and superior fluidics
- Minimize carry-over — the sample line is cleaned between each sample quickly and automatically
- Elimiate manual well parsing — sample parsing is done on the fly as the data is collected
24/7 Operation with Large-Capacity Fluidics Upgrades
Go for longer without filling back up
- 20-liter level-sensed external fluidics cart
- Direct house dH2O connection as sheath source
Seamless Integration into Robotic Workcells and Laboratory Information Management Systems (LIMS)
Unleash the full potential of the ZE5 Cell Analyzer by combining it with robotics
- Automate plate loading using robotics within a workcell
- Integrate with LIMS and scheduling software through an application programming interface (API)
- Experience a vendor-agnostic API allowing seamless integration with a wide range of automation providers for full customization
Antibodies & Reagents
Suitable antibodies and reagents are critical components for HTS. Bio-Rad is dedicated to providing cutting edge reagents for all flow cytometry applications, and has recently launched an exclusive range of StarBright Dyes to allow you to build superior panels. Bio-Rad also has an extensive range of high-quality antibodies and reagents validated for flow cytometry, to help you conduct successful experiments.
High-Throughput Screening Data
Acquisition Speed & Data Quality
Dragon Beads from Bangs Laboratories Inc were acquired on the ZE5 Cell Analyzer and other competitor instruments at serial dilutions. The ZE5 Cell Analyzer shows consistent linearity between expected and measured event count up to 100,000 events per sec (eps), whereas other systems drop off around 20,000 eps due to significant data abort.
FITC-labeled beads were acquired on the ZE5 Cell Analyzer at increasing event rates from 4,000–129,000 events per sec (eps) and showed consistent population resolution as determined by %CV.
Fast Plate Sampling — Competitive Comparison
Samples were run on a 384-well plate with the ZE5 Cell Analyzer and a leading competitor. 10 µl sample acquisition volume, HT mode, flow rate 2 µl/sec, 5 sec agitation on column 1 and 13.
The ZE5 Cell Analyzer finishes the 384-well plate in 50 min; the competitor system took 90 min.
See more data: Download "Get more from your experiments PDF"
Our Automation Partners
The cytometer's application programming interface (API) facilitates integration into any workcell, so you can power through screening campaigns faster and with larger panels than ever before. We can advise you on your project, as we have already worked with many automation providers to integrate the ZE5 Cell Analyzer into robotic workcells
Evolution of Flow Cytometry as a Screening Platform
Flow cytometry has evolved, the latest generation of screening flow cytometers provide easy-to-use, high-plex assays at speeds only previously seen using ELISA and imaging cytometry systems. Learn about the advantages of flow cytometry and the superior capabilities of the ZE5 Cell Analyzer.
High-Throughput Screening Publications
Below are a set of useful articles relating to groundbreaking HTS work and considerations for automation.
Automation in Action
Automated high-throughput screening is enabled with the ZE5 Cell Analyzer integrated into any laboratory robotic system such as Green Button Go from Biosero.
Acquisition to Analysis
Learn how to analyze your plate-based high-throughput screening data with FCS Express Software bundled with the ZE5 Cell Analyzer.
Get Reliable Results Faster
Discover why the ZE5 Cell Analyzer is a better solution for your high-throughput screening needs.
Read our guide to learn everything you need to know about flow cytometry, from basics to multicolor panel building.
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Lay the foundations to better flow cytometry multicolor panels with this easy-to-use interactive online tool from Bio-Rad.
Bio-Rad flow cytometers offer automated, high-parameter, large-scale screening capabilities, or enable novice users to sort cells on their own.