The High Throughput Phenomics (HTP) platform specializes in supporting medium- to large-scale high content screening campaigns, offering a versatile solution for many research needs. The platform uses a diverse array of targeted small molecule libraries in 96-/384-well Ready-To-Screen formats, facilitating efficient experimentation for the understanding of complex biological phenomena and providing novel systems-level insights.

 

KEY EXPERTISE

 

  • High Content Screening & Analytics
  • Cell Painting
  • 3D Spheroid Characterisation
  • Heterogeneous Co-culture Modelling
  • Image-based Cellular Activity (E.g., Outgrowth, Migration, Localisation, Marker Expression, etc.)

 

Below are representations of models developed at the HTP platform.

 

Cell Painting – a technique that provides a comprehensive view of changes in cellular features, contributing to a nuanced understanding of cellular morphology and function.

Osteosarcoma cells were treated with small molecules and at the end of 48-hours, cells were stained for 8 sub-cellular organelles using 6 specific dyes.

 

Co-culture Modeling – Compounds Targeting Specific Sub-populations of Head & Neck Tumour

Primary and Metastatic Head & Neck tumour cells were co-cultured. Compound 1 selectively kills primary cells, compound 2 selectively kills metastatic cells, and compound 3 kills both primary and metastatic cells.

 

Marker Expression – Compounds Inhibiting β-catenin in Colorectal Tumour

Colorectal cancer cells were stained and quantified for β-catenin expression. Compound 2 was more potent than compound 1 in inhibiting β-catenin.

 

Protein Activation – Compounds Dephosphorylating ERK in Tumour

Colorectal cancer cells were stimulated to induce phosphorylation of ERK. When cells were pre-treated with compounds that can inhibit induction of pERK (Green), we found compound 2 to be more potent than compound 1.

 

Cellular Activity – Compounds affecting Neurite Outgrowth in Amyotrophic Lateral Sclerosis Change Negative Control to Compound 1, Positive Control to Compound 2

 

3D Tumour Spheroid Modelling – Compounds Targeting Colorectal Cancer

Colorectal cancer cells were grown in ULA plates for 4 days to form spheroids and exposed to small molecule treatment for 3 days. Compound 2 exhibits higher toxicity than compound 1.

 

SERVICE ASPECTS

High Content Image Based Screen Assay Automation and Miniaturisation Expertise Training
  • Consultation on conceptualisation & design of image-based assays for medium and high throughput screening
  • Performing selection, development, and/or validation of image analysis methods and/or assay readouts
  • Aid in image data management, High Content data analysis and visualisation
    • Single-cell and subpopulation analyses in High Content Imaging
    • Cell Painting assays-morphological profiling and detection of subtle phenotypes
      • Image-based cellular target expression & translocation
  • Performing assay miniaturisation/ validation – optimising assay biology
  • Preparation and handling of compound libraries for high content/throughput screening
  • Screening small-molecule compound libraries in 96- or 384-well formats with various detection technologies
    • Cell-based HTS/HCS assays
    • Automated plate-based fluorescence confocal imaging
    • Assays with Human primary cells, iPS-derived neurons, co-cultures, and 3D Spheroid/organoids
  • For the use of Tecan Spark reader
  • For the use of Biotek-Multiflo-cell seeding and ELISA washer
  • For the use of HCS instruments – 2D/3D imaging
  • For the use of HCS-Columbus analysis software