Toward High-Throughput Fish Embryo Toxicity Tests in Aquatic Toxicology

Addressing the shift from classical animal testing to high-throughput in vitro and/or simplified in vivo proxy models has been defined as one of the upcoming challenges in aquatic toxicology. In this regard, the fish embryo toxicity test (FET) has gained significant popularity and wide standardization as one of the sensitive alternative approaches to acute fish toxicity tests in chemical risk assessment and water quality evaluation. Nevertheless, despite the growing regulatory acceptance, the actual manipulation, dispensing, and analysis of living fish embryos remains very labor intensive. Moreover, the FET is commonly performed in plastic multiwell plates under static or semistatic conditions, potentially inadequate for toxicity assessment of some organic, easily degradable or highly adsorptive toxicants. Recent technological advances in the field of mechatronics, fluidics and digital vision systems demonstrate promising future opportunities for automation of many analytical stages in embryo toxicity testing. In this review, we highlight emerging advances in fluidic and laboratory automation systems that can prospectively enable high-throughput FET testing (HT-FET) akin to pipelines commonly found in in vitro drug discovery pipelines. We also outline the existing challenges, barriers to future development and provide an outlook of ground-breaking fluidic technologies in embryo toxicity testing.