By James DeRosa, MPH
Technologies are in a constant state of evolution. When we think of cellphones, we expect a new generation to be released every year. Keeping up with demand in the technology space is daunting, but necessary for continued progress. In the field of spatial biology, we see a similar demand. Innovative technologies depreciate over time. It’s part of the process, as we learn what we do not know and therefore inspired to create something new capable of answering novel questions being posed. In spatial biology, what drives innovation is the pursuit of a truly comprehensive understanding of a tissue. What stalls innovation in this space, however, is the trifecta of plex, throughput, and resolution. It seems we can only improve upon two of those elements simultaneously, but not all three.
With the launch of PhenoCycler™-Fusion, Akoya Biosciences broke the iron triangle of spatial biology, by the virtue of speed. The PhenoCycler™-Fusion system is the fastest spatial biology solution that enables ultrahigh-plex spatial phenotyping of whole slides at single-cell resolution by integrating automated fluidics and iterative imaging. Capable of imaging 1 million cells in 10 minutes, the system allows unbiased spatial phenotyping of tissues, accounting for every single cell across the whole slide.
Tissue biology is undeniably complex and multifaceted. To garner mechanistic insights into the complex processes and pathways orchestrating inside the tissue, a multiomics approach is a must. However, the process for measuring more analytes via multiomics must not only be practical, but also maintain the plex-throughput-resolution trifecta.
Like other players, Akoya is going multiomic. To gain additional perspective on multiomics becoming the new gold standard and what sets Akoya apart as an industry leader, I sat down with Dr. Julia Kennedy-Darling, Senior Director of Research and Development at Akoya. She received her training in the lab of Professor Garry Nolan at Stanford, where she was on the pioneering team of scientists who developed the Co-detection by Indexing (CODEX) solution now known as PhenoCycler. She joined Akoya Biosciences as the second employee to lead the R&D efforts to commercialize PhenoCycler. Over the past five years, she has helped drive the dramatic expansion of the field of spatial biology and continues to be at the forefront of innovation, ushering in a new era of multiomic technologies.
Julia, thank you so much for joining me today. Before we dive into multiomics, I have heard a lot about the speed of the recently launched PhenoCycler-Fusion. Can you shed some light on how it has impacted you and your team at Akoya?
As biotechnology developers, we tend to immerse ourselves in the intricacies of the chemistries needed to address a particular need. But the biggest roadblock for us is the time it takes to complete an ultrahigh-plex experiment. This is where PhenoCycler-Fusion has made the biggest impact. Before PhenoCycler-Fusion, we were limited to smaller tissue regions, or would compromise on resolution or an experiment would take a solid week to run. Now we run experiments daily. This has changed our lives in R&D. Ultrahigh-plex assays have become the norm in the lab. The effect on the scale has been massive and it has really allowed us to ramp up innovation. For a scientist, few things are more satisfying than getting your data back in a day.
So why spatial multiomics and why now?
The first part is obvious. Imaging-based spatial multiomics has the potential to reveal cell state and cellular phenotypes. In situ quantification of RNA and proteins provide a systems biology view of the tissue microenvironment, allowing us to translate their transcriptomic findings and hypotheses to whole tissue and observe their role in the interplay between cells in their native states. It is this step that links RNA to protein to cellular organization and behavior. As I said earlier, ultrahigh-plex spatial proteomics assays have become the norm at Akoya. So, the next logical step was to add an additional layer of insight—enabling RNA to capture maximal insights from whole tissue at single-cell resolution.
Obviously, the idea of more powerful technologies and multiomic assays is exciting but with more data comes more challenges. How do you overcome data bottlenecks and are multiomic assays capable of becoming a feasible gold standard in the average laboratory?
That’s a great question, and one we think about often! PhenoCycler-Fusion is all about identifying key cell types and mapping them in an unbiased manner, across whole tissue sections to discover key signatures that wouldn’t otherwise be evident with bulk or dissociative technologies. But, add RNA data to the equation and now we are dealing with truly massive amounts of data. To deal with this issue Akoya is making substantial investments into software solutions that support AI-driven analysis and algorithms for comprehensively understanding underlying biological systems. Multiomic assays will likely become the gold standard once we identify the most biologically relevant targets and our workflows are fast and robust enough to support these assays.
The goal is to use these data to generate new biomarkers or diagnostic signatures; how do you see these more sophisticated assays making their way into clinical practice?
This is the part that really excites me! There is clearly a need for new signatures for both diagnosis and treatment. The real value of Akoya’s platform, as well as others within this space, is the ability to discover new signatures comprised of both cells types and their spatial localization. Akoya’s solutions can be used with large panels to discover new signatures and can also be used to screen for these signatures in a high throughput manner. Both sides of the continuum are needed to serve the clinical need—Akoya is focused on ensuring we have solutions across the spectrum to deliver on the clinical promise of spatial biology.