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Webinar

A New Very High-content Imaging Approach for 3D Cell Models

Speaker: Dr Aro Nugawela, Senior Post Doctoral Research Associate, Lancaster University
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Webinar Abstract

Spheroids are self-assembling three-dimensional (3D) cellular aggregates which, relative to monolayer cell culture, better recapitulate the complexity and heterogeneity of cell behaviours in-vivo. As such, spheroids offer distinct advantages in biomedical innovation.

However, spheroid bioimaging is time consuming, with high-cell density posing two key challenges for conventional confocal light microscopy (CCLM): Firstly, by hindering the diffusion of reporter stains and antibodies; and secondly by limiting light penetration due to higher optical density. These limitations favour the study of small spheroids arrays and drive the demand for a dedicated LM approach that is optimised for high-content screening (HCS) in 3D cell models.

Light sheet microscopy (LSM) has recently come to the forefront, offering a counterpoint to CCLM that is innately compatible with 3D visualisation, while favouring acquisition speed over spatial resolution. LSM, however, cannot overcome the challenging optical properties of spheroid models. Thus, bioimaging of dense 3D tissues remains dependent on pre-processing methods, such as chemical tissue clearing (CTC). CTC lowers the optical density of samples via de-lipidation and de-pigmentation but is prone to unpredictable and artefactual changes in sample morphology.

Taking inspiration from Expansion Microscopy, we have developed a new, CTC-free methodology for robust, versatile, and complete immune-staining of large volume spheroids. Here, we demonstrate that our approach affords detailed 3D visualisation of morphological and proliferative patterns by CCLM in large volume spheroid models. Using these high-resolution volumes as benchmarks, we further show that our method, combined with ultrafast Lightfield 4D screening and arivis Pro analysis, yields qualitative and quantitative results, providing a powerful high-content imaging solution for 3D cell models.

Register to join our webinar and learn more.

Date: Thursday 12th March 2026
Time: 12:00 - 13:00 GMT

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Dr. Aro Nugawela
Speaker Dr. Aro Nugawela Senior Post Doctoral Research Associate, Lancaster University

Dr Aro Nugawela is a Senior Research Associate in the Mort Laboratory, within the Biomedical and Life Sciences Department at Lancaster University. She undertook her PhD in the laboratory of Professor Paul McKean, where she used advanced bioimaging modalities to investigate flagellum assembly in the parasitic protist Trypanosoma brucei. During this time, she also interned at the Pasteur Institute, building skills in fluorescent particle tracking and conventional Expansion Microscopy.

  

Dr Nugawela’s independent research focusses on bioimaging protocol innovation, particularly the development of imaging strategies for optically challenging 3D tissue models. Together with Dr Alex Benedetto, she coordinated a multi-disciplinary effort at Lancaster University to develop a novel ExM-inspired methodology for complete immunostaining of large 3D tissues.

  

Dr Nugawela has gone on to drive collaborative efforts to progress this protocol towards a quantitative phenotypic screening pipeline for large-volume spheroids. This work provides a fundamental advance in the bioimaging of 3D cell models, with direct relevance to cancer research and drug discovery workflows.

  

This methodology has become the foundation for international collaborations with both academic and industrial bodies. Dr Nugawela seeks to build on these partnerships to integrate ExM-based strategies into multi-modal pipelines for conventional and high content screening approaches.

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