High-throughput vertebrate total analysis/screening platform

Abstract

High-throughput screening (HTS) is seen as one of the most promising technologies to facilitate biomedical studies and pharmaceutical discoveries. Although large varieties of in vitro HTS technologies have opened great opportunities, the speed of improvement has been limited by lack of advanced tools for in vivo screening on whole complex organisms, such as vertebrates. To address this issue, a high-throughput platform as a vertebrate total analysis/screening system (V-TAS) is proposed. This platform consists of two independent parts: an automated imaging system and an automated microinjection system. These two systems are designed for general high-content high-throughput pharmaceutical and genetic screens on whole zebrafish larvae, and therefore, are well-modularized for adapting different situations. Furthermore, to demonstrate the capability of V-TAS, a screen of lipidoid library for biologics delivery on thousands of animals was conducted. Very limited damage to the larvae was shown during the screening. In the end, the author also validated the hits discovered by V-TAS can be applied to more advanced animal models such as rats, and be more predictable than cell-based assays.