Abstract: High throughput system for in vivo screens on vertebrate larvae. The system includes a source of vertebrate larvae in a liquid medium and loading tube means for aspirating a larva. A detector assembly is provided to differentiate passage of a larva from bubbles and/or debris. An imaging means is provided for both confocal imaging and wide-field fluorescence imaging of the larva. A laser is provided for optical manipulation of the larva.

Abstract: Distinctive components that enable high-throughput, whole-animal screening are described. These components can be used individually or in various combinations. A staging chip strains off the excess fluid that the input animals are immersed in, increasing their density (number of animals in a given volume) and rapidly bringing them close to other fluidic components. A microfluidic sorter is adapted to isolate and immobilize a single, physiologically active animal in a selected geometry. A multiplexed micro-chamber chip receives single animals and the microchamber chip includes individually addressable screening chambers for imaging, incubation and exposure of individual animals to selected chemical compounds. An imaging structure generates sub-cellular, high-resolution images of the physiologically active animals. A well-plate interface chip is used to deliver elements from a compound library to a single output of the chip.

Abstract: High throughput system for in vivo screens on vertebrate larvae. The system includes a source of vertebrate larvae in a liquid medium and loading tube means for aspirating a larva. A detector assembly is provided to differentiate passage of a larva from bubbles and/or debris. An imaging means is provided for both confocal imaging and wide-field fluorescence imaging of the larva. A laser is provided for optical manipulation of the larva.

Abstract: High throughput system for in vivo screens on vertebrate larvae. The system includes a source of vertebrate larvae in a liquid medium and loading tube means for aspirating a larva. A detector assembly is provided to differentiate passage of a larva from bubbles and/or debris. An imaging means is provided for both confocal imaging and wide-field fluorescence imaging of the larva. A laser is provided for optical manipulation of the larva.

Abstract: High-content time-lapse assays on whole animals require their repeated immobilization for high-resolution imaging and manipulation. Here, we present a simple, rapid, and minimally invasive method for repeatedly immobilizing and imaging Caenorhabditis elegans (C. elegans) over extended periods of time inside standard multiwell plates, which are compatible with industrial high-throughput screening platforms and robotics. We use this method to perform subcellular-resolution femtosecond laser microsurgery, and to image the regeneration dynamics of single neurons in vivo at cellular resolution. Our analysis shows that mechanosensory neurons often regenerate in single short bursts that occur stochastically within the first two days post-surgery. In vivo observation of many such physiological processes requires multi-time-point immobilization and imaging of large numbers of animals throughout extended periods of time.

Abstract: High throughput system for in vivo screens on vertebrate larvae. The system includes a source of vertebrate larvae in a liquid medium and loading tube means for aspirating a larva. A detector assembly is provided to differentiate passage of a larva from bubbles and/or debris. An imaging means is provided for both confocal imaging and wide-field fluorescence imaging of the larva. A laser is provided for optical manipulation of the larva.

Abstract: Distinctive components that enable high-throughput, whole-animal screening are described. These components can be used individually or in various combinations. A staging chip strains off the excess fluid that the input animals are immersed in, increasing their density (number of animals in a given volume) and rapidly bringing them close to other fluidic components. A microfluidic sorter is adapted to isolate and immobilize a single, physiologically active animal in a selected geometry. A multiplexed micro-chamber chip receives single animals and the microchamber chip includes individually addressable screening chambers for imaging, incubation and exposure of individual animals to selected chemical compounds. An imaging structure generates sub-cellular, high-resolution images of the physiologically active animals. A well-plate interface chip is used to deliver elements from a compound library to a single output of the chip.