CCG Equipment

MSceen database for visualization of assay results

The MScreen database has more than 30 million compound entries for structure searching. The CCG continuously expands and updates its libraries to provide a SAR resource to researchers.

RNAi screens

The CCG has links to CCMB for gene network analysis using bioinformatics tools to eliminate off-target hits.

Image-based High-Throughput Screening

Image-based HTS (using IXM) allows phenotypic analysis of small molecule and siRNA screens. These assays can be performed in multiwell plates with kinetic or endpoint reads. Analysis of images is user-defined, automatic, and multi-parameterNIH also provides an assay guidance manual for HCA (High Content Analysis).

Natural Products Library

The CCG Natural Product Extract (NPE) library comes from a collection of sediments, cyanobacteria, fungi, sponges and other novel organisms from all over the world. This library is screened as mixtures and once a hit is identified, the active fraction can be purified to obtain a sample for structural characterization.

Compound High-Throughput Screening (HTS)

  • >160,000 small molecules (diversity sets)
  • Kinase activity libraries
  • Bioactive collections (clinically tested)
  • Drug-like compound library
  • 30,000 Natural Product Extracts (novel collection)

RNA interference High-Throughput Screening

  • Dharmacon siGenome SMARTpool library:
    • Human Genome siRNA set targets 18,200 genes, 68 source plates, 384-well format
    • Druggable targets, Subset targets, 3520 genes, 96- or 384-well format
    • Mouse Genome siRNA set targets 16,873 genes, 63 source plates, 384-well format

Instruments/Technology Platforms

  • Detection formats: 96-, 384-  & 1536-well plates
  • High-Content Screening: Image Xpress Micro
  • HTS Flow: Accuri/Hypercyt
  • Three Multimode plate readers: Abs, FI, FP, Lum, FRET, BRET, ALPHA, TR-FRET, HTRF

Robotics, Liquid Handling, Compound Plates

  • Multichannel plate handling robotics for compound and assay applications
  • Bulk liquid handlers
  • Multi-dispense/multichannel pipettors
  • Custom compound plate formats for secondary screening, pilot assays and non-HTS uses
  • Relational database of assays and compounds
  • Screening and chemoinformatics support
  • Structure similarity searches and links to public databases for chemical and biological profiling are available and free for CCG users.
  • Support for secondary screening experiments, toxicology assessment & ADME
  •  Ca++ Flux, Ion Channel, Membrane Potential
  • High-content automated image analysis on multiwell plate formats and slides Kinetic reads over hours or days

Instrumentation

To request training on instruments, contact mjlarsen [at] umich.edu (Martha Larsen). In addition to providing small molecule libraries, the screening facility has the following equipment and resources available:

  Sciclone ALH3000 with a V&P pintool, delivery of 50-80 nl volumes; can be used with 1536-well plates; uses Twister plate hotel to deliver source plates.
   
   
Envision Multimode Plate Reader (Perkin Elmer), two detectors enabling simultaneous dual wavelength reading; enhanced luminescence; Alpha capabilities (AlphaScreen and AlphaLisa); Stackers for automatic plate reading; FP, FI, TR-FRET, Abs, BRET, HTRF; cross talk, calibration and normalization features; Kinetic reads.
   
  Mosquito X1 (TTP Labtech), a hit-picking liquid handler with 96- and 384-well plate formats, 25-1200 nL positive displacement tips for confirmation, serial dilutions and reagent/sample transfers.
   

MDS Analytical Technologies-ImageXpress Micro Cellular Imaging and Analysis System for automated acquisition and analysis of images for high throughput cell-based screening.  Includes Acuity Xpress Informatics and MDCStore database. Several plate options (6-384-well) and slide mounts are available for high content analysis and screening.

 

   
Biomek FX dual head (Beckman): A programmable robot, utilizing both disposable tips and HDR (pin tool) to rapidly transfer compounds from library stock plates to assay plates. 96 and 384-well plate capability.
   
  Biomek FX (Beckman) 384-well nanoliter HDR (pin tool)
   
Hypercyt/Accuri : High Throughput Flow Cytometer combination system that does multiplex flow cytometry on 384-well plates (~ 10 min/plate).  Used for both cell- and bead-based HTS.
   
Plate reader: PHERAstar (BMG Labs) with luminescence, fluorescence, fluorescence polarization, time-resolved fluorescence and absorbance detection methods with 96 and 384-well plate capability. Sample sizes from 5-200ul.

Pherastar Modules:

  • Luminescence (1 channel)
  • Fluorescein/FITC (485/520)
  • FP-Fluorescein/FITC (485/520A/520B)
  • FP-TAMRA (540/590A/590B)
  • AMC (350/450)
  • AMC2 (370/480)
  • TR-FRET (337/520/490)
  • FP-Texas Red (575/620A/620B)
  • Absorbance (450)

Other filter modules available request a list from mjlarsen [at] umich.edu (Martha Larsen)

FlexStation3 (MD) plate reader that is capable of reading 5 assay formats for kinetic, endpoint, spectrum, well-scanning and “Flex.”.
   
Plate Handler: Twister (Caliper Life Sciences) microplate handler allows for automated integration of liquid dispensers, plate washers, and other HTS assay components during screening creating a stand alone module.
   

Bio-Tek ELx405 plate washer/aspirator with 96 to 384-well capability.

Bio-Tek 406 plate washer/aspirator with 96-, 384 and 1536-well capability.

   
Thermo Labsystems Multidrop plate dispensers with 96 and 384-well capability.

Tissue culture facilities. Multichannel pipettors.

Updated August, 2013.

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