Platforms

High Throughput Phenomics

Introduction

High Throughput Phenomics platform (HTP) enables, High Content Screening (HCS), that combines automated imaging and quantitative data analysis in a high-throughput format suitable for large-scale applications such as drug discovery and systems biology utilising high throughput image phenotyping.

HTP support medium-scale high throughput/content screening campaigns. HTP hold diverse targeted small molecule probes/libraries and genome wide siRNA/shRNA libraries in 384-well Ready-To-Screen format. Overall, HTP can provide novel systems-level insight for your complex biological questions.


Key Expertise

High Content Screening

3D Spheroid Characterisation

High Content Analytics

Heterogeneous Co-culture Modeling

Cell Painting

Image-based Cellular Activity (Outgrowth, Migration, Localisation, Marker Expression, etc.)

Cell Painting – Detailed Morphometric Characterisation

 

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

Pri. (Green) and Met (Red) cells-DMSO Compound target Pri. (Green) cells Compound target Met (Red) cells Compound target both Pri. and Met

 

 

Marker Expression – Compounds Inhibiting β-catenin in Colorectal Tumour

High Content Screening Nucleus (Blue) + β-catenin (Green) + Cell Marker (Red)

DMSO Control Compound 1 Compound 2

 

 

Protein Activation – Compounds Dephosphorylating ERK in Tumour

High Content Screening Nucleus (Blue) + pERK (Green)

Uninduced Control Induced Control Induced + Compound 1 Induced + Compound 2

 

 

Cellular Activity – Compounds Promoting Neurite Regression in ALS

DMSO Control Negative Control Positive Control

 

 

3D Tumour Spheroid Modelling – Compounds Targeting Colorectal Cancer

Brightfield 3D-live cell detection-Calcein AM staining
Brightfield 3D-live/dead cell detection-Calcein AM/Propidium Iodide staining

 


HTP Technologies

State of the Art Technologies Available at HTP

a) High-content Imaging and Analysis Instruments
Our systems for high-content imaging (HCI) and high-content analysis (HCA) provide flexible scalability for your research. They feature options and modules to address your specific research including objectives, filters, imaging modes, and environmental conditions. All our systems support a wide range of applications, increased throughput, and we have streamlined workflows.

Operetta CLS
High Content Imaging System
Opera Phenix
High Content Imaging System
Vectra Polaris
Automated Quantitative Pathology System
  • Powerful LED Light Source
  • Confocal Spinning Disk
  • sCMOS Low Noise Camera
  • 3D Imaging
  • Water Objectives for thick samples
  • Live Cell Chamber
  • PreciScan for Tracking Objects
  • Solid State Lasers
  • Spinning Disk Confocal
  • 2 Cameras for Speed & Accuracy
  • Large Field of View – 290%
  • Reduce Crosstalk
  • Water Objectives Ideal for 3D Objects
  • Phenologic Application
  • Multispectral Imaging
  • Automated Slide Scanning
  • FFPE Tissue Sections and TMAs
  • 7–Colour Opal Polaris Compatible
  • Liquid Crystal Tunable Filter (LCTF)
  • MOTiF Technology at 40x magnification
  • 10x – 40x in Brightfield and Fluorescence
ImageStreamX mkII
Imaging Flow Cytometer
Li-Cor Odyssey SA
Infrared Signal Scanner
High Content Image Analysis
  • Up to 5000 cell/sec
  • Flexible Sample Prep
  • Easy Interface
  • Recover Unused Sample
  • Analysis Modules for Many Research Areas
  • 96-well Auto-sampler
  • Ideal for non-adherent cells
  • Highly Sensitive Signal
  • Multi-target at Coordinates
  • Stable Signal Unaffected by Time
  • In-Cell Western System
  • Assay Detection Using IR-Dye
  • Harmony – HCS building blocks for real-time image feature testing
  • Columbus Image analysis – web-based analysis for batch analysis
  • 50 TB dedicated image server

 

b) High-throughput Liquid Handling and Assay Instruments
At HTP, we have modular assay automation systems that provide greater flexibility in complex cell-based assay development and screening. We have state-of-the-art instrumentation, for distribution of compound or siRNA/cDNA libraries, and large-scale data analytics solutions.

Agilent – Bravo Benchcel
96- & 384-well formats

PerkinElmer – Janus
96- & 384-well formats

LabCyte – Echo 550
96-, 384- & 1536-well formats

Tecan SPARK
Multimode reader

  • Assay-ready Plates
  • Plate reformatting
  • Barcode Labelling
  • Automated Microplate Sealing
  • HEPA enclosure
  • HEPA Enclosure
  • Library Reformatting
  • Cherry Picking
  • Cell-based Assay Automation

 

  • Fast & Versatile
  • Acoustic Contactless Liq. Transfer
  • Dug Combination Matrix
  • Cherry picking
  • Easy IC50 Setups

 

  • Luminescence
  • Fluorescence Monochromator
  • Fluorescence Variable Bandwidth
  • Fluorescence Polarisation
  • Absorbance
  • Alpha Technology

 

 


Library Resources

Libraries Available in HTP (Small Molecules & Genome Wide siRNA/shRNA/cDNA)

Small Molecule Libraries for Validation/Repurposing Projects Small Molecule Libraries for Discovery Projects Genome-wide siRNA/shRNA/cDNA libraries
  • Anticancer – 400+
  • Kinase Inhibitors – 400+
  • Epigenetic Modulators – 150+
  • GPCR Modulators – 500+
  • Natural & Bioactive Compounds – 2000+
  • Cardio, Nephro, Hepato-Toxic Compounds – 500+
  • Target-Class Bioactive Compounds – 1000+
  • Focused Discovery Sets – 50,000+
  • Scaffold-Diversity Set – 10,000+
  • Whole Genome siRNA (Pools)
  • Whole Genome Arrayed shRNA (Clones)
  • microRNA Mimics & Inhibitors (Clones)
  • Long non-coding RNA (lncRNA) siRNA
  • Open Reading Frames (ORF) Clones

 

  • Smart collection of small molecule libraries in which targets are annotated significantly, that can be used for target validation/re-purpose studies.
  • Small molecule diversity sets from Enamine and ChemDiv.
  • Access to SMILE structures for custom sets based on your target(s) or assay needs.
  • Genome wide siRNA/shRNA and cDNA libraries for genetic manipulation studies.
  • Web-based data analysis portal for pipeline analysis support for your screens-plate uniformity, %CV between your replicates and show you the top hits in waterfall graph.


Milestone Projects

Partner Institute: National Cancer Centre Singapore and Genome Institute of Singapore – A*STAR

HTP Libraries:

  • SeleckChem Anti-cancer
  • SeleckChem Kinase Inhibitors

Screening Objectives: To identify alternative therapeutic sensitivity to inhibitors of cell proliferation in Gefitinib-resistant cells.

  • Phospho-histone H3 (S10) Status
  • Target Validation with siRNA Screening
  • High Content Screening

Publication: A chemical genetic screen identifies Aurora kinases as a therapeutic target in EGFR T790M negative, gefitinib-resistant head and neck squamous cell carcinoma (HNSCC). Joo Leng, et al., Jan 2021. EBioMedicine, Doi/10.1016/j.ebiom.2021.103297


Partner Institute: Cancer Science Institute of Singapore – NUS

HTP Libraries:

  • Combination Screen (SeleckChem Anti-cancer + SeleckChem Kinase Inhibitors)

Screening Objectives: To identify compounds selective for cancer cells with p53R158G mutation.

  • NFĸB signaling
  • Drug Combination Screening
  • High Content Screening

Publication: Targeting codon 158 p53-mutant cancers via the induction of p53 acetylation. Li Ren Kong, et al., April 2020. Nature Communications, Doi/10.1038/s41467-020-15608-y


Partner Institute: Cancer Science Institute of Singapore NUS, Genome Institute of Singapore A*STAR, and Bioinformatics Institute A*STAR

HTP Libraries:

  • Natural Product extracts (21,575 compounds)

Screening Objectives: To identify compounds that reduce viability of Liver Cancer Cells expressing high levels of SALL4.

  • Oxidative Phosphorylation Sensing
  • High Content Screening

Publication: New High-Throughput Screening Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation. Li Ren Kong, et al., April 2020. Gastroenterology, Doi/10.1053/j.gastro.2019.08.022


Partner Institute: National Cancer Centre Singapore and Genome Institute of Singapore A*STAR

HTP Libraries:

  • siRNA for transcription factors
  • siRNA for chromatin remodelers
  • ChemDiv Epigenetics

Screening Objectives: To identify the underlying epigenetic mechanism in drug-induced cellular anomalies of HN120Pri and HN137Pri primary cancer cells.

  • Synthetic Lethal Screening
  • BRD4 and JQ1 signaling
  • High Content Screening

Publication: Longitudinal single-cell RNA sequencing of patient-derived primary cells reveals drug-induced infidelity in stem cell hierarchy. Sharma et al., November 2018. Nature Communications, Doi/10.1038/s41467-018-07261-3


Partner Institute: National Cancer Centre Singapore and Genome Institute of Singapore A*STAR

HTP Libraries:

  • SeleckChem Anti-cancer
  • SeleckChem Kinase Inhibitors

Screening Objectives: To identify compounds specifically targeting HN137-Primary / HN137-Metastatic cell population or both.

  • Co-culture Modelling
  • High Content Screening

Publication: Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time. Shumei Chia et al., September 2017. Nature Communications, Doi/10.1038/s41467-017-00451-5

 


Services

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 read-outs
  • 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
    • Imaging based Cellular translocation and target expression studies
  • 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 assay
    • Automated fluorescence confocal imaging – Plate based
    • 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

 


People @ HTP

Dr Giridhanran Periyasamy

Head-HTP

Expert in Automation and Imaging
Expert in Target and Lead Discovery

Dr Narmada Balakrishnan

Research Fellow

Expert in HTS and HCS Assay and Imaging Technology and HBV Pathogenesis and Drug Discovery

Shivaji Rikka

Research Manager

Expert in Screening Technology
Expert in Optimising Assay Biology

Matan Thangavelu T

Senior Research Associate

Expert in HTS and HCS Automation and Imaging
Expert in High Content Image Analysis

Yi Li Gian

Research Associate

Expert in Assay Technology and Miniaturisation
Expert in HT-Liquid Handling


HTP Community

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