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HTS Core Facility Director, Dr. Jair Lage de Siqueira-Neto, demonstrates "high content" image to the colleagues, Diane Thomas and Brian Suzuki.

CDIPD maintains a unique screening facility to test potential drugs against both protozoan and helminth (worm) parasites requiring Biosafety Level II. This facility is on the fourth floor of the Pharmaceutical Sciences Building at the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego. It includes storage room, compounds management room and tissue culture rooms, dedicated to protozoan parasites, mammalian cells and other pathogens. An adjacent helminth laboratory is configured to allow maintenance and analysis of parasites such as Brugia species, C. elegans, and schistosome. A temperature-controlled room is available for a "snail farm" allowing maintenance of the intermediate host snails of the schistosome parasite.

A robotic enhanced screening room is equipped with an acoustic nanoliter liquid transfer instrument [1] and contact microliter liquid handlers [2, 3, 4 and 5], allowing assays to be handled in all types of microplates ranging from 6 to 1536 wells per plate. A robotic arm [6] enables unsupervised experiments, improving our experimental throughput to industry standards. Fluorescence [7, 8, 9], luminescence [7, 9], image-based phenotypic image analyses [8] readouts can be used in the assays. This entire infrastructure is built in Biosafety Level II facility, required to handle a number of human pathogens and mammalian cells.

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The first generation Worminator built in CDIPD to detect large Brugia adult parasites

Aside from conventional microscopy, the laboratory is building a third edition of the movement-based analizer, "Worminator" [10], designed after the original instrument produced at the University of California San Francisco by Chris Marcellino and Jiri Gut. The UCSD Worminator is built in collaboration with the UCSD Bioengineering Department. It has a newer video camera and computer and features software developed by Marcelino to monitor the effect of drugs on worm movement. Originally configured to allow analysis of large Brugia adult parasites, it is being modified to allow analysis of the smaller schistosome and C. elegans organisms. Currently compounds from the Structural Genomics Center and other library sources are lining up to be tested against Brugia pahangi and Brugia malayi using the new edition of the Worminator.

Jair L. Siqueira Neto and Stephan Meister were responsible for the design and instrumentation of the screening facility laboratory.

[1] ATS (EDC Biosystems) – non-contact acoustic nanoliter liquid transfer
[2] Biomek FXP (Beckman Coulter) - 8,96 and 384 channel liquid transfer and pintool transfers
[3] EL 406 (BioTek) – contact microliter liquid dispenser & washer (96/384/1536)
[4] WDII (GNF Systems) – contact microliter liquid dispenser & washer (96/384/1536)
[5] Multidrop Combi Reagent Dispenser (Thermo Scientific) - contact microliter liquid dispenser (6- to 1536-well plates)
[6] Precise Flex 400 (Precise Automation) - multi-axis robotic platform and random access plate hotel
[7] EnVision Multilabel Reader (Perkin Elmer) – multimode plate reader with onboard plate stacker
[8] ImageExpress Micro XLS (Molecular Devices, LLC) – high content imager
[9] IVIS Lumina Series III - In Vivo Imaging System
[10] Worminator - motion-based plate reader to assess helminths viability