How Automating Metabolomics Workflows Accelerates Toxicology Research

Technological advancements are driving the rapid adoption of in vitro toxicology testing across a wide range of industries, including food production, agrochemicals, drug development and consumer products.

North America and Europe hold two-thirds of the market for in vitro toxicology testing, with the Asia Pacific region growing quickly thanks to government incentives that are encouraging toxicology testing. The global in vitro toxicology testing market is forecast to rise at a compound annual growth rate of nearly 11% during the next eight years, from approximately $12 billion in 2024, to $30 billion by 2033. 

One of the biggest technological advances driving the growth of toxicology testing is metabolomics, the study of metabolites in cells, biofluids and tissues. Metabolomic research reveals details about physiological states and responses to external factors like diet and chemical exposures.

With increasing automation of metabolomics workflows, toxicology researchers can now analyze thousands of metabolites simultaneously across thousands of samples, working at a faster pace with greater consistency – and at a lower cost –than was possible with manual workflows.

To fully realize the potential of automation in metabolomics, it’s essential for researchers to collaborate closely with technology providers that can assemble the optimal collection of tools and reagents for the project at hand, and design an efficient, flexible workflow.

A good case study of a successful deployment of automation in toxicology is the University of Birmingham’s Metabolomics and Systems Toxicology Laboratory. Researchers there are working with the European Commission and the Organisation for Economic Co-operation and Development (OECD) to conduct studies that could help set new international standards for toxicity testing. 

Alternatives to animal testing

The task of determining how safe chemicals are for human exposure has traditionally relied on rodent testing, which is not only imprecise but also raises ethical concerns related to animal welfare.

In an effort to shift away from animal testing, regulatory agencies around the world are actively evaluating new approach methodologies (NAMs), including in vitro methods, and metabolomics, as well as other next-generation approaches such as proteomics and gene-expression profiling. These have the potential to provide much richer toxicology data compared to animal testing.

In vitro toxicology testing involves exposing a range of biological models to chemicals and conducting assays to determine their potential effects on the human body. In addition to studying the effects of chemicals on human cells, human and environmental toxicology researchers are increasingly turning to organisms that share many features of human biology, including zebrafish embryos, fruit flies and Daphnia magna, a species of water flea.  

Automating metabolomics workflows

One project that’s benefiting from automated high-throughput omics workflows is the Precision Toxicology Initiative, an international consortium of researchers who are exposing model organisms to chemicals, generating more than 10,000 biological samples. Simultaneous extraction of metabolites and RNA at the University of Birmingham is allowing for both metabolomic and transcriptomic analysis of chemical exposure.

The University of Birmingham team uses an automated workstation to enable the extraction of polar metabolites and lipids from biological samples. Researchers there can measure sets of pre-selected metabolites with both targeted and untargeted detection. But it’s challenging, as separate processes must be set up for different classes of metabolites, specifically for polar and non-polar compounds.

Historically, extraction was a labor-intensive process that involved taking individual samples in tubes and loading them onto a homogenizer, then manually pipetting the pulverized samples, using different solvents for the extractions depending on the characteristics of each metabolite. One researcher could typically prepare 50 samples a day manually, explained Mark Viant, PhD, professor of metabolomics at the University of Birmingham and director of Phenome Centre Birmingham.

The introduction of automation at various points in the workflow now allows a single researcher to process 192 samples in a day. “With a four-fold proximate increase in the speed in which we can deliver the work, there’s a significant reduction in staff time and cost,” said Viant.

“Historically, for the Precision Toxicology project it would have taken a researcher just over 200 days of standing at the bench, manually pipetting. We still need to have somebody interacting with the technology throughout the day, but now we can get the entire sample prep for this really large toxicology study conducted in only 50 workdays.” 

Improving consistency and reliability

The advantages of automated omics workflows extend far beyond time and cost savings. Automation also offers a higher level of consistency and reliability in laboratory processes. Researchers using manual methods do follow standard operating procedures, but there are typically slight variations in quality from person-to-person and from day-to-day. “Automation offers highly standardized input, coupled with real time tracking of the extractions,” said Viant. “So we feel that we have a much higher level of consistency.”

That’s important in completing large-scale projects such as the Precision Toxicology Initiative, which aims to define complex biological reactions that have yet to be discovered. Reducing the technical variances that could arise from manual processes allows researchers to more easily detect biological reactions in model organisms exposed to potential toxicants.

Sample extraction for the Precision Toxicology Initiative will continue until mid-2026, after which researchers who are part of the consortium will compile and analyze the data. As the project advances, researchers will present some of their interim findings to the scientific community, including chemical regulators and the OECD.

We hope this public-private partnership provides a model to other regulatory bodies around the world that rely on toxicology research. With advances in technology, we are demonstrating how non-animal models and automation can enhance toxicology research, making it more efficient and accurate – and improving processes for protecting people from harmful chemical exposures.