Analysis of physiological parameters using small model organisms is an attractive approach in pre-clinical drug discovery when studying effects of new drugs or existing drug combinations. Larval zebrafish (Danio rerio) is a small vertebrate model organism that recently emerged as an innovative experimental system for non-invasive and real-time analysis of physiological parameters such as cardiovascular activity. In this work, we demonstrate a new chip-enabled approach to perform non-invasive imaging micro-echocardiography (iμEC) on immobilized larval stages of zebrafish. The iμEC is a new assay for quantification of the temporal cardiac patterns based on analysis of video stream from a high-resolution camera. The chip-based system utilized hydrodynamic trapping principles to actively capture and immobilize individual larvae using a low-pressure suction for real-time iμEC analysis. The system coupled together with an integrated interface provided a new capability to rapidly assess pharmacologically-induced perturbation in cardiac function by real-time and non-invasive monitoring of zebrafish larvae. We demonstrated the application of the technology for proof-of-concept assessment of model cardio-active compounds delivered using continuous micro-perfusion. The optical transparency of larval stages and micro-hydrodynamic immobilization allowed for visualization of cardiac activity after drug treatment in real-time. Results obtained using micro-perfusion also enabled studies on rapid drug withdrawal that are difficult to achieve using existing protocols such as imaging in microtiter plates. This work demonstrates iμEC as a new technique for cardiological experiments utilizing zebrafish models.
Ian Harper (Manager), Stephen Firth (Manager), Alex Fulcher (Operator), Oleks Chernyavskiy (Operator), Margaret Rzeszutek (Other), David Potter (Manager), Volker Hilsenstein (Operator), Juan Nunez-Iglesias (Other), Stephen Cody (Manager), Irena Carmichael (Operator), Betty Kouskousis (Other), Chad Johnson (Operator), Sarah Creed (Manager) & Giulia Ballerin (Operator)Office of the Vice-Provost (Research and Research Infrastructure)