Angeline Lim

Senior Applications Scientist
Molecular Devices, LLC.

Angeline Lim is a Senior Applications Scientist at Molecular Devices with a focus on advancing 3D biology research. In her current role, Angeline provides scientific, technical, and applications support for high-content imaging that leverages fully-automated workflow solutions and AI-powered data analytics.
She holds a PhD from the University of California Santa Cruz, where she studied mechanism of axonal transport using a combination of genetics and imaging approaches.
Prior to earning her doctorate, Angeline was at Singapore’s Institute of Biotechnology and Nanoengineering where she worked on neurodegeneration and lysosomal storage disorder disease models.

Speech title & Synopsis

Overcoming the barriers to 3D organoid adoption: A complete workflow to enable large-scale production of organoids and their use in automated high-throughput applications

Many oncology drugs fail at the later stages of the drug development pipeline and in clinical trials, despite promising data in vitro. 3D cell models, such as patient-derived organoids (PDOs), offer a promising solution to this problem. Cells grown in 3D can better mimic cell-cell interactions and the tissue microenvironment. Studies show that patients and their derived organoids respond similarly to drugs, suggesting the value of using PDOs to improve therapeutic outcomes.
A significant barrier to widespread adoption of organoids in drug discovery is that organoid production is a costly and highly labor-intensive process. Moreover, organoid culture is a skilled manual process, and thus there can be significant variability between operators.
To address the challenges associated with the use of PDOs in large scale applications, a semi-automated bioprocess has been developed for the efficient and standardized expansion of organoids at scale. The bioreactor maintains an environment that ensures constant delivery of nutrients and growth factors to the culture while preventing the accumulation of toxins. This method results in the large-scale production of organoids that can be stored in cryopreserved format and can be deployed directly into assays without further culture steps.
To demonstrate the use of these assay-ready organoids for drug discovery applications, we have used them in end-to-end, automated workflows consisting of an incubator, high content imager, liquid handler and robotic plate handler. For maintenance, the liquid handler was used for media changes with routine imaging to monitor organoid growth (pre and post treatment). PDOs were treated with selected anti-cancer compounds and analyzed using deep learning-based image segmentation.
The combination of assay-ready organoids and an automation workflow provides a significant step forwards in providing a turn-key solution for researchers to deploy next-generation 3D models into their drug discovery processes.