While 2D cell culture remains a staple of biological research, scientists are increasingly interested in the potential of 3D cells and organoids to help further innovation. Organoids more closely replicate the behaviour of cells in the body, opening up greater potential for scientific breakthroughs in personalized medicine and drug discovery. While the promise of organoids is vast, in practice, there have been several obstacles to adoption, including the challenge of achieving high throughput and automation due to the viscous nature of the materials.
Recently, SPT Labtech collaborated with Corning Life Sciences and brought together the liquid-handling power of SPT Labtech's dragonfly discovery and Corning's Matrigel® matrix for organoid culture, to automate a forskolin-induced swelling assay of human intestinal organoids. The team was able to effectively dispense 3 µL droplets of human intestinal organoids suspended in Corning® Matrigel® matrix for organoid culture into 96-well microplates. Interestingly, the low volume/low dead volume dispense capabilities of DFD allowed the user to make the most of precious resources, such as patient derived cells, and enabled assays that would have previously been prohibitive from a cost or cell availability point of view. Their detailed application note describes the project.
In this article, we interview Hilary Sherman, Senior Applications Scientist at Corning Life Sciences and discuss her role, the context of organoid research, the origins of the collaboration with SPT Labtech, the customer problems that it solves, and the impact on drug discovery and personalized medicine.
What is your role at Corning?
I'm a senior application scientist for Corning and have been with the company for 15 years. I work with all of Corning products from 1536-well spheroid microplates, all the way up to our bioprocess products. I create technical documents like protocols, posters, and technical application notes to help support our customers' success. I've always loved science. After graduation, I noticed a job opportunity with Corning and applied. Although I knew very little about the biotech industry at the time, the company took a chance on me, and I've never looked back. I fell in love with cell culture and biotechnology.
Can you tell us about the collaboration with SPT Labtech and the work that you've done together?
A great deal of my focus in recent years has been on 3-dimensional or organoid cell cultures. These often require an extra-cellular matrix, such as Corning's Matrigel® matrix to maintain the polarity and other unique characteristics of organoids. These materials are highly viscous and can be challenging to work with, especially in high throughput or automated applications. While many customers are interested in increasing the throughput of organoid applications, they often don't know how to tackle this in practice. I realized that SPT Labtech's dragonfly with its positive displacement, non-contact dispensing system would be an excellent fit for Matrigel matrix, and I got in touch with the team to see if they would be interested in a collaboration. I had spotted an opportunity for one particular organoid application, which requires small, uniformly sized and consistently placed droplets of Matrigel matrix in microplates. Achieving all these characteristics makes automation a challenge, requiring many customers to work manually, which can increase variability and is time-consuming.
What's driving interest in organoids?
A body of literature is now clearly pointing to the value of organoids as a more informative in-vitro model for disease and understanding organ development. There have been several scientific breakthroughs using organoid cultures that wouldn't have been possible with more traditional 2-dimensional or 3-dimensional cell cultures, especially in the area of personalized medicine. There's now a drive to adopt these organoid models to more applications to enable personalized medicine. Typically, hybrid-academic/industry research-organizations are leading these advances.
For example, the Hubrecht Institute (HUB) originally pioneered the methodology for culturing adult STEM cell derived organoids like the human intestinal organoid model we used in our collaboration with SPT Labtech. The pharmaceutical industry also clearly recognizes the potential of the approach as a way to achieve discovery hits more quickly and weed out failed compounds earlier in the research lifecycle. However, the process of culturing organoids is much more challenging than traditional 2-dimensional or even more simplistic 3-dimensional models. That's where the work between Corning and SPT Labtech has great potential because we've come up with a solution for one of the main hurdles that could inhibit the industry from adopting organoid systems- a lack of automation and throughput.
What are the advantages of organoid systems?
Traditional research methods tend to use simple models such as a 2D monolayer of a single cell type or a 3D model with one or two cell types. Organoids provide a much more physiologically relevant representation of the organ delivering superior data quality and more predictive results.
Let's take the example that formed the basis of our work with SPT Labtech, cystic fibrosis. Cystic fibrosis is the outcome of many potential gene mutations, and so no single drug is suitable for every patient. In the past, clinicians would have to try various therapy options with patients to discover which ones were helpful. This approach is not only costly but also risks unwanted side effects. Now, scientists can take a biopsy from a patient, grow intestinal organoids and dose the cell culture with various drugs to determine which treatment option would be most beneficial for that patient. This now well-established model for personalized medicine has positively impacted the treatment strategies for this debilitating disease. Together with SPT Labtech, we recreated this existing model and adapted it to a high-throughput, automated approach using SPT Labtech's dragonfly and Corning's Matrigel matrix technologies.
What feedback have you had from the industry about this work?
Customers are excited about the application and the capabilities of the technology. Ultimately, I hope these innovations will empower the industry to adopt organoid culture more fully into their research since we now know that organoids can be dispensed effectively in a high throughput manner with the right tools.
There's nothing better than offering solutions to customers' problems and helping to progress vital research- it is one of the most rewarding aspects of my job.
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