High content imaging and analysis system

Lead Research Organisation: Institute of Cancer Research
Department Name: Division of Molecular Pathology

Abstract

The Institute of Cancer Research (ICR) urgently needs an up-to-date High-Content Imaging and Analysis System to boost analytical capabilities in areas of investigation central to its research strategy that aims to make and translate discoveries that will benefit patients. There is demand from at least 14 research groups working in areas such as childhood brain tumours, prostate cancer, mesothelioma, sarcomas in children and adults and drug discovery and development. These researchers need a system which can efficiently capture high-quality images of living cells in 2D/3D models of cancer, or preserved samples from patients, in order to perform a wide range of complex analyses.

We are developing and using ever more sophisticated 3D living 'mini tumours' derived from patient samples that better represent how tumours grow in the body than traditional methods of growing cells flat in a petri dish. Experimental use of these new models creates a greater need for imaging cells within models, and not just at the surface/edges of models, at high sensitivity, resolution and through-put.

We have identified the Perkin Elmer Opera Phenix Plus High Content Screening System (Opera Phenix Plus) as the most suitable equipment to meet the needs of our researchers. The choice was based on direct comparison of three different systems and the quality of data generated by high-throughput, in-depth analysis and monitoring of live cancer cells over periods of time. The Opera Phenix Plus will be accommodated in our Light Microscopy Core Facility to create centralised access on site that will complement the abilities of the Facility and provide expert technical support to users to ensure the equipment is operated correctly, most efficiently and is well-maintained.

The Opera Phenix Plus will enable:
- Transformation of ICR researchers to image complex structures in 3D environments at high resolution. Our current equipment is poorly suited for imaging these new 3D cancer models, and practically unusable to image single cells in complex 3D matrices which are used to more accurately represent how cancers grow inside the human body.
- Drilling deep into the specific mechanisms that drive cancer development, growth and spread. This will help reveal the fundamental processes at work as cancers arise, change, and evolve.
- High-throughput automated imaging of cutting-edge research models including large-scale experiments that will assess and monitor several conditions and outcomes simultaneously. For example, small molecule drug screens which will test potential drug compounds and their ability to activate, perturb, or modify biological processes of interest.
- Shortening many current research workflows. Our research progress has slowed as more labour-intensive solutions are used with inferior approaches and equipment.
- Development of smaller, bespoke experiments by multiple users because of the rapid analyses possible.
- Understanding the role of the tumour microenvironment in cancer development at the cellular level. The tumour microenvironment consists of normal cells, molecules, and blood vessels that surround and feed and support tumour cells. A tumour can change its microenvironment and the microenvironment can affect how a tumour grows and spreads.
- Identification of new treatments that out-manoeuvre cancer progression and help our researchers discover novel and personalised approaches to cancer treatment, both drugs and radiotherapy.
- Enhancing our research that, in partnership with The Royal Marsden NHS Foundation Trust, will facilitate rapidly taking significant research findings from the laboratory into the clinic for patient benefit.

Technical Summary

The Opera Phenix Plus is a spinning disk confocal system which is capable of imaging cells at high sensitivity, resolution, and speed (up to 100 frames per second) with low intensity illumination that is ideal for visualising live samples under multiple experimental conditions. Its strong capabilities have a good level of through-put for high-content imaging, also within cells, and is ideal for thick samples such as organoids, spheroids and vibratome precision-cut tissue slices.

The Opera Phenix Plus will be embedded in our Light Microscopy Core Facility and will support at least 14 research groups who tested and compared it to other options to ensure it will meet our needs. We envisage rapid uptake given the new dimension this instrument will add to our available technologies.

The Opera Phenix Plus is urgently needed to accelerate our research into how cancer evolves and responds to treatment over time. The system will enable groups to study the role of the tumour microenvironment using advanced 3D models derived from patients, which more accurately recapitulate tumours. The ICR is a world leader in the discovery of novel molecularly targeted treatments for cancer, identifying 21 new drug candidates since 2005. The Opera Phenix Plus will enhance capabilities for dynamic and high-throughput assays for evaluating compounds and understanding the mechanism of action of drugs and drug resistance. These teams are currently reliant on a low resolution Celigo cytometer for these assays. The ICR has a strong track record in taking technical advances, such as intensity modulated radiotherapy, from concept through validation and into NHS practice. The Opera Phenix Plus will allow us to utilise improved assays to measure in vitro responses to treatments thus furthering and accelerating our understanding of the biological responses.

Overall, the Opera Phenix Plus will support the ICR to deliver on its strategy to transform the lives of cancer patients.

Publications

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