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ROBOTICS APPLICATION SOLUTION Drug Discovery Solution: FULLY AUTOMATED MADIN-DARBY CANINE KIDNEY (MDCK) PERMEABILITY ASSAY Permeability assays elucidate the structure-activity relationships in the hit-to-lead stage, rank order compounds for in vivo pharmacokinetics studies and predict the potential for oral absorption. Reliability, accuracy and precision are critical for these assays, particularly when they are used in medium- and high-throughput screening. Madin Darby Canine Kidney (MDCK) cells are a common model for studying drug transport mechanisms in distal renal epithelia. MDCK cells grown to confluence on permeable membranes are widely used to examine passive permeability and active transport. These assays have typically been run manually or have been partially automated, requiring an operator’s presence at all times. Hamilton Robotics successfully automated the 24-well MDCK permeability assay using the MICROLAB® STAR Automated Liquid Handling Workstation, integrated with select third-party peripheral devices. System Features: • • • BioTek plate reader Thermo Cytomat incubator Hamilton CO-RE Grippers Deck Layout: System and Materials: System Requirements Hamilton Part Number MICROLAB STAR with Autoload, 12 independent channels, iSWAP microplate gripper, CO-RE 96 Probe Head CO-RE Gripper VENUS one software DWP Carrier (five SBS positions) MTP Carrier (five SBS positions) Tip Carrier (five 96 Tips) Multiflex Carrier Base (Landscape Orientation) Multiflex Tip Module Multiflex Tilt module Multiflex DWP Module x 3 Labware Required 173000-027 184089 911004-V1, 911004 182090 182085 188160 188039 188160 188061APE 188042 Hamilton Part Number 50 µL CO-RE disposable tips without filters 300 µL CO-RE disposable tips without filters 1000 µL CO-RE disposable tips without filters 235966 (black conductive) 235902 (black conductive) 235904 (black conductive) User-supplied Materials Part Number Millipore Millicell 24-well Cell Culture Plate BD Falcon Flat Bottom UV Plates w/lid E&K Scientific 12-Column Reservoirs, Deep Well, Pyramid Bottom Axygen 12-Column Reservoirs, Low Profile, Partitioned Seahorse Bioscience Custom 36-well Deep Well Plate Thermo Scientific Matrix 2D Bar-coded ScrewTop Storage Tubes & Caps: 500 μl 2D Bar-coded, V Bottom ScrewTop Tubes w/ Caps, Sterile PSRP010R5 353293 EK-2033 Axygen RES-MW-12-LP S30052 3744 Data: The figure below shows the correlation of the compounds tested in a 24-well format using MDCK cells and the published Papp data. The grouping classifies the compounds into low, medium and high Papp categories, and the data suggests that there is a good correlation between published data and results obtained from the MDCK assay automated on the Hamilton STAR platform. Data provided by Plise et al. (Genentech, Inc. South San Francisco, USA). For more information, please visit www.hamiltonrobotics.com or contact your regional sales manager. MICROLAB is a registered trademark of Hamilton Robotics Lit. No. AS005 Hamitlon Robotics Reno, NV 06/11