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Future Testing of Compound Toxicity Using Robotic System

The Tox21 robot has been installed at NCATS and will be used to test hundreds of thousands of chemicals against multiple in vitro assays to establish a signature of chemical compounds that can be used to predict in vivo human and rodent toxicity. This robust automated platform brings together a diverse collection of equipment including, but not limited to, plate readers, liquid handlers, incubators and centrifuge to run a diverse array of biochemical and cell-based assays yielding reproducible high-quality data.

Schematic Diagram
Schematic diagram depicting the Tox21 robotic platform

Tox21 Consortium Members

National Institute of Environmental Health Sciences/National Toxicology Program
U.S. Environmental Protection Agency
NIH Chemical Genomics Center, NCATS
U.S. Food and Drug Administration

Key Investigators

National Center for Advancing Translational Sciences
Sam Michael
Menghang Xia, Ph.D.
Anton Simeonov, Ph.D.
Christopher P. Austin, M.D.

Public Health Impact

This robotic system provides unparalleled speed, reliability and high-quality reproducible data. The millions of data points generated from robotic screening will be transformed into in vitro chemical signatures that may be used to study the mechanism of action of compounds, predict toxicity and minimize traditional animal toxicity testing.

Publications

Collins FS, Gray GM, Bucher JR. Transforming environmental health protection. Science, 2008;319(5865):906-907.

Huang R, Southall N, Cho MH, et al. Characterization of diversity in toxicity mechanism using in vitro cytotoxicity assays in quantitative high throughput screening. Chem Res Toxicol, 2008;21:659-667.

Huang R, Southall N, Xia M, et al. Weighted feature significance (WFS): a simple, interpretable model of compound toxicity based on the statistical enrichment of structural features. Toxicol Sci, 2009;112:385-393.

Parham F, Austin C, Southall N, et al. Dose-response modeling of high-throughput screening data. J Biomolec Screen, 2009;14:1216-1227.

Xia M, Huang R, Witt KL, et al. Compound cytotoxicity profiling using quantitative high-throughput screening. Environ Health Perspect, 2008;116:284-291.

Outcomes

Agencies hope robot can speed toxics evaluations, end animal testing. May 13, 2011.

New robot system to test 10,000 chemicals for toxicity. March 10, 2011.

Tox21 collaboration: robot video clips. March 10, 2011.

Toxicology testing in the 21st century - a new strategy. October 24, 2011.

Project Details

The screening system consists of a series of peripherals and workstations arranged around a central anthropomorphic robotic arm. The key components include the Kalypsys Director software, a pin tool device for nanoliter compound transfer, plate storage and environmentally controlled assay incubation units, nanoliter reagent dispensers (BioRPTR, Multidrop, acoustic/noncontact), centrifuge (V-spin), and plate readers (ViewLux and EnVision).


A photograph of the Tox21 robot in its current configuration

Contacts

Sam Michael

Menghang Xia, Ph.D.

Anton Simeonov, Ph.D.

Christopher Austin, M.D.


Tox21 robot and representatives from NHGRI, NIEHS,FDA and EPA
Institution leadership representing NHGRI, NIEHS, FDA and EPA at the Tox21 Ribbon-cutting ceremony