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2025 Resolution: Automate the Best of 2024

Sample prep automation is the cornerstone of democratizing spatial biology

Nature Methods named spatial proteomics the “Method of the Year” for 2024, with good reason. Assays including PhenoCycler Fusion (PCF), multiplex immunofluorescence (mIF), and imaging mass cytometry (IMC) push the boundaries of spatial proteomics at subcellular resolution. Combined with transcriptomics barcoding, spatial biology provides a “Google Maps” approach to studying tissue architecture, cell-cell interactions, and molecular processes within their native context. While these techniques steal headlines in terms of multiplexing, multiomics, and higher resolution, they also require increasingly precise and tedious manual sample preparation on behalf of scientists.

Spatial biology today is akin to studying Mars with the cutting-edge Perseverance rover's planetary sensors using the antiquated Apollo computers and controls to travel there. Anyone who has watched Apollo 13’s Tom Hanks trying to keep Earth in the window for a reentry burn understands that automating routine yet precise tasks is crucial for the humans responsible to execute appropriately. Most spatial biology experiments utilize FFPE or flash-frozen preserved tissue. Before achieving advanced imaging analysis, researchers subject their slides to meticulous and labor-intensive sample preparation procedures, including baking, dewaxing, rehydration, epitope retrieval, and probe/antibody staining—essentially unchanged workflows in 20–30 years that lack standardization.

Spatial to the Core

Many institutions, biotech companies, and biopharmaceutical companies have taken a core lab approach to spatial biology. Multiple imaging technologies are combined with expertise to manage sophisticated sample prep workflows and data analysis under one roof. Savvy core lab directors are investigating how sample prep automation can address laboratory inefficiencies, increase throughput, and maximize the time trained staff spend on high-value tasks rather than staining slides.

At the National Cancer Institute (NCI), Staff Scientist Noemi Kedei, M.D., leads the Spatial Imaging Technology Resource (SpITR) lab, which houses the state-of-the-art spatial technologies available to its world-class oncology investigators. As a “biology-first” core director, Dr. Kedei understands spatial biology's value in cancer research and recognizes the need for efficiency in managing many diverse and essential imaging studies. Her goal in implementing automation solutions in SpITR is to optimize workflows to achieve “high-throughput spatial assays.”

Paula Montero Llopis, Ph.D., manages the Microscopy Resources on the North Quad (MicRoN) at the Harvard Medical School Longwood campus. The lab handles a plethora of imaging assays, few of which are “off-the-shelf.” She views sample prep automation as a vehicle to “empower her users” to do the best science with reduced variability and pushbutton efficiency. When trusty robotics handle the sample prep, researchers can focus on the science and worry less about whether they remembered to add all the antibodies to their cocktail.
Core labs at universities have established themselves as leaders in high-content analysis. Some of the sample processing, such as FFPE dewaxing and antigen retrieval, is frequently performed in a histology lab.

Subsequently, the fluorescent or oligonucleotide probe staining is accomplished in the spatial biology or genomics core prior to imaging. For the core lab tasked with producing spatial data, integrating automation solutions that encompass end-to-end slide processing, from baking to staining, and including antibody cocktail panel mixing capabilities give them complete control over the workflow, reducing the probability of error and eliminating extraneous storage or handling situations.
As with any biomedical laboratory setting, the market for trained staff is scarce, and competition for talent is fierce. Automation of routine sample preparation workflows in core labs enables more throughput per staff member, whether by increasing the number of samples processed simultaneously or taking advantage of non-work hours, such as overnight runs. 10X Genomics Sr. Sales Executive Ross Guarnera summarizes, “Many of my core lab customers want to run more spatial biology projects, but they just don’t have the staff to do the work.” Sample preparation automation that is affordable and straightforward to train staff complements their expertise, standardizes workflows, and increases core lab efficiency.

Why automate?

The value that robust, reliable, and reproducible sample prep automation imparts to spatial biology may be obvious, but let’s summarize them here:

• Optimized laboratory efficiency: Arguably the most important, a single operator can process more samples per hands-on time, freeing them to accomplish more high-value tasks, such as data analysis or customer consultation. This is particularly valuable in core labs, contract research labs, and startups, where maximizing FTE hours is a premium.
• Reduced variability: Robotic liquid handling, temperature modulation, and timing eliminate manual steps that introduce inconsistencies, ensuring consistent and reproducible results. This is crucial for large or multi-site studies, where consistency across operators and locations is essential.
• Enhanced data quality: When much of the sample prep hands-on time is reduced, optimizing processes and assays and maintaining consistent reaction conditions becomes more feasible. This can improve signal-to-noise and extract substantial cost savings by requiring fewer samples to achieve statistical significance.
• Reduced training requirements: Pushbutton automation solutions simplify the sample preparation processes, reducing the need for extensive laboratory staff training and making complex procedures accessible to entry-level staff. Furthermore, talented scientists given more time to pursue scientific goals rather than mundane tasks are more likely to be satisfied with their jobs and not seek other employment opportunities.
• Flexibility in scheduling: Automated systems can function around the clock, enabling samples to be processed overnight or according to a flexible timetable. This is especially beneficial for laboratories with limited personnel or those meeting tight deadlines.

Purpose-built automation technology

Nikolay Samusik, Ph.D., and Yury Goltsev, Ph.D., developed CODEX (now PhenoCycler) while postdocs at Stanford in the lab of Garry Nolan, Ph.D.  After co-founding Akoya Biosciences and pushing the boundaries of the spatial biology proteomics technology they pioneered, the entrepreneurs recognized how manual sample preparation represented a significant, unaddressed barrier to the wide adoption of spatial techniques. While automation solutions existed in the market, they were often prohibitively costly, consumed excess expensive chemistries, and lacked the flexibility required of discovery biology. Thus, they co-founded Parhelia Biosciences, an automation company born to democratize spatial biology and scale its potential for bench-to-bedside therapeutics. The purpose-built Parhelia Spatial Station, launched in 2024, provides researchers with a cost-effective, pushbutton solution to automating spatial sample prep end-to-end, from baking to staining.

Working with leading spatial biology technology companies and academic researchers, Parhelia is developing a menu of selectable and customizable assays that will enable scientists to focus on the study design and data rather than the sample prep. In 2025, Parhelia expects to announce several collaborations that further unify advanced imaging analysis methods with the robotic sample prep precision they deserve.

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Geoffrey Feld, Ph.D, Founder & Principal Consultant of Geocyte LLC

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