A new fully automated in vivo screening system (AISS) has been developed to transform drug evaluation by enabling rapid, precise, and non-invasive multi-organ imaging in zebrafish. Integrating cutting-edge microfluidic technology with computer-vision-based control, this innovative system automates every aspect of zebrafish larvae handling— from loading and encapsulation to immobilization and drug exposure. The result is a streamlined, real-time process that enhances the accuracy of pharmaceutical screening, particularly for assessing drug-induced cardiotoxicity, without the need for anesthesia or manual handling. This advancement promises to accelerate drug discovery and improve the safety profiles of new pharmaceuticals.
Preclinical drug evaluation, especially for cardiotoxicity, is a critical stage in the drug development process. Traditional methods, often relying on in vitro assays or manual manipulation of animal models, are both inefficient and unable to fully mimic in vivo conditions. Zebrafish, with their transparent bodies, rapid development, and genetic similarities to humans, are emerging as a powerful model for high-throughput screening. However, the existing phenotyping techniques are labor-intensive and rely on anesthesia, which can compromise physiological responses. These constraints make it clear that an automated, non-invasive system is necessary for efficient, accurate drug evaluation.
A team of researchers from Sun Yat-sen University has responded to this challenge with the development of the Automated In Vivo Screening System (AISS). Published (DOI: 10.1038/s41378-024-00852-9) in Microsystems & Nanoengineering on January 27, 2025, the study showcases how the AISS can automate zebrafish larvae manipulation, allowing for precise, multi-organ imaging with minimal human intervention. This system marks a significant leap forward in high-throughput pharmaceutical screening, offering a promising tool for more efficient and reliable drug evaluation.
The AISS is designed to automate the entire process of zebrafish larvae handling. Using microfluidic chips, the system encapsulates individual larvae in droplets, enabling precise control over drug concentration gradients and real-time observation of organ responses. By eliminating the need for anesthesia, the system allows for high-resolution imaging of organs such as the heart, brain, and liver. The computer-vision-based control ensures precise immobilization and orientation of the larvae, creating an optimal environment for in vivo observations. One of the system's key innovations is its ability to generate multiple drug concentration gradients on-chip, enabling the detailed assessment of drug effects. In one example, the AISS demonstrated the cardiotoxic effects of the antipsychotic drug sertindole, revealing significant changes in heart rate and ventricular function at varying drug concentrations. Notably, the AISS also reduces drug consumption, with each droplet containing just 5.56 microliters, making the system an efficient and cost-effective solution for large-scale screening.
"This automated screening system represents a major advancement in preclinical drug evaluation," said Dr. Xudong Lin, lead researcher. "By eliminating the need for anesthesia and manual manipulation, we can now observe real-time physiological responses in zebrafish with unprecedented precision. This system has the potential to transform how we screen for drug toxicity and efficacy, ultimately leading to safer and more effective pharmaceuticals."
The AISS has vast potential in pharmaceutical research, especially in the early stages of drug development when rapid and accurate toxicity screening is paramount. With its ability to evaluate drug effects on multiple organs quickly and non-invasively, this system could dramatically reduce the time and cost of preclinical testing. The technology also enables the detection of subtle toxic effects that might otherwise be overlooked in traditional assays. The system's versatility extends beyond zebrafish and could be adapted for use in other small animal models, broadening its applications in biomedical research. The AISS stands as a powerful new tool in drug discovery, poised to enhance the safety and efficacy of future therapeutics.
