High-Throughput Discovery Sciences

Mission


Our mission is to accelerate drug discovery and development from academia and industry with the infrastructure and expertise to generate, test, and validate new hypotheses driven by the rapidly evolving field of high-throughput discovery sciences. 

Overview


High Throughput Discovery ServicesOur core facility specializes in the discovery of probes and drugs, including small molecules, biologics, and cell therapies. We achieve this by adapting cellular and biochemical assays for high-throughput and high-content screening (HTS/HCS). Additionally, we excel in generating and printing complex organotypic three-dimensional (3D) disease models, such as organoids and tumor organoids derived from cell lines or patients, which are compatible with HTS/HCS. Our facility is equipped with state-of-the-art robotic automation (G3 Explorer) and integrated instrumentation from Revvity and other leading vendors. 

Instrumentation and Services Available


Liquid Handling:

  • Janus G3 Automated Liquid Handling PlatformJanus G3 Automated Liquid Handling Platform: Equipped with 96- and 384-channel MDTheads, an 8-channel Varispan, gripper tool, an integrated 70 tip box carousel, and a large deck size. The Janus G3 MDT heads are capable of dispensing and mixing precise volumes of diverse viscosities (0.5-200 µL) to 96-, 384-, and 1536-well plates in a single step. The 8-channel Varispan allows for rapid and precise dispensing of volumes (0.5 µL to 1 mL), generally, for cherry-picking, and drug dilution plate generation.

  • FlexDrop iQ Non-Contact Dispenser: The FlexDrop iQ can dispense directly into wells in any desired pattern down to 8 nL drops with <1 µL dead volume. The instrument is equipped with an internal camera for droplet detection, can dispense a 384-well plate in 20 seconds, and supports multiple liquid classes, including water, DMSO, and glycerol. Some example uses for this instrument are drug combinations, complex assays with multiple components (i.e. enzyme assays), and manually time-consuming stepwise drug dilutions (i.e. 0.5-1 µM). 

High-Content Imaging and HTS Plate Reader:

  • Opera Phenix Plus High-Content Screening SystemOpera Phenix Plus High-Content Screening System: The Opera Phenix Plus is a true high-content imaging system that is equipped with 4 cameras for simultaneous image acquisition. Our system is configured with 4 excitation lasers (405, 488, 561, and 640) and 14 emission filters, enabling the acquisition of high-quality confocal images for all the most common fluorescent dyes. Additionally, the system is equipped with 5 objectives (5x air, 10x air, 20x air, 20x water, and 40x water). The Opera Phenix Plus software (Harmony 5.2) is fully automated and can be set up to acquire multiple fields of view, multiple Z-stacks, and partial or full plates from 6- to 1536-wells. For example, a 96-well plate with 3 fluorophores and 9 fields of view can be imaged in 15 minutes. In addition, the software enables cell segmentation, machine learning analysis, maximum projection, flat field correction, among other features that streamline image analysis. 

    A few popular assays utilizing the Phenix Plus are:
    • 2D/3D Cell Viability Staining
    • 2D/3D Reactive Oxygen Species Stains
    • Multiplexed Immunofluorescence
    • Cell Painting
    • Time series experiments
    • Cell Tracking

  • Phenix PlusEnvision HTS Plate Reader:The Envision HTS is fully equipped for all leading detection modalities: Fluorescence, Luminescence, Absorbance, Fluorescence Polarization, AlphaScreen, and Homogeneous Time-Resolved Fluorescence (HTRF). The instrument is equipped with a barcode reader, high sensitivity cameras to enable quick plate reads (i.e. assays in 384-well format <1 min), monochromators, custom filter sets, bottom read capability, and temperature control. 

G3 Explorer Robotics

G3 Explorer RoboticPlate::handler™ Flex (PFlex): The PFlex is a robotic arm equipped with a gripper for plate handling. The arm moves on a vertical and horizontal rail system to two deck levels on the G3 Explorer system (HEPA filtered enclosure) to place plates in landscape or portrait mode on several instruments. The PFlex can access the following equipment within the G3 Explorer: 

  • Liconic STX220 Incubator: Temperature, Humidity, and CO2 controlled incubator for SBS plates (220 positions)
  • Liconic STX500 Freezer: -20°C, self-defrosting, and nitrogen gas equipped freezer for long-term sample storage (500 positions)
  • Agilent Automated Centrifuge Loader
  • Room Temperature Rack (22 positions)
  • Envision HTS Plate Reader
  • Opera Phenix Plus HCS System
  • Janus G3 Automated Liquid Handling Platform
  • 4titude 4AS Automated Heat Sealer
  • Brooks Automated Depeeler
  • 3x Inheco Teleshakers: Room temperature precise plate shaking
  • 1x Inheco Thermoshaker: Temperature controlled plate shaking

3D Bioprinting (Coming Soon)

BIO CELLX: The BIO CELLX is a recently released fully automated and high throughput bioprinting instrument capable of dispensing droplets in desired patterns to generate complex 3D biostructures. Our core facility is currently developing protocols to validate drug screens and phenotypical analysis using the Envision HTS and Opera Phenix Plus. Our core facility seeks to meet the demands for the establishment of more in vivo representative cell models, and this newly acquired instrument will help us achieve that goal. 

 


Medicinal Chemistry


Pharmaceutics


In Vivo Pharmacology

 

Contact Us


 

Dan LaBarbera, PhD

Dan LaBarbera, PhD
Professor and Director, the CU Anschutz Center for Drug Discovery
Emaildaniel.labarbera@cuanschutz.edu
Phone: 303-724-4116

Qiong Zhou, MS

Qiong Zhou, MS
D3SR Research Services Program Director
Email: qiong.zhou@cuanschutz.edu 
Phone: 303-724-9278

Hector Esquer

Hector Esquer, PhD 
Research Instructor and Automation Scientist
Email: hector.esquer@cuanschutz.edu 
Phone: 303-724-9278


To learn more visit the D3SR core facility links below and navigate to the D3SR iLabs website to request for consultation or drug discovery and development services. 

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