The Analytical Scientist Innovation Awards 2024: #7
Frank Steemers, co-founder and CSO of Scale Biosciences, tells us the story of ScalePlex – the 7th ranked innovation on this year’s Awards
| 4 min read | Technology
Cell Image: Adobe Stock
7 – ScalePlex
Multiplexing technology for large-scale single-cell omics
Produced by Scale Biosciences
ScalePlex enables the simultaneous analysis of over 300 samples, conditions, or time points – far exceeding the limits of traditional single-cell sequencing methods, which typically process only 12 samples at a time. Powered by Scale Bio’s Quantum barcoding technology, the workflow adds an oligo tagging step during fixation, avoiding the limitations of lipid- or antibody-based tagging. This streamlined process eliminates individual fixation and washing steps, preserving small or valuable samples often used in oncology and neuroscience research.
What the judges say…
“Essential innovation in high throughput single cell multiomics.”
Meet the expert
Here, we speak with Frank Steemers, co-founder and CSO of Scale Biosciences, and responsible for the company’s scientific strategy and innovation. He tells us the story of ScalePlex.
We identified a need for massively parallelized sample multiplexing along with exponentially scalable single cell analysis. Such technology would enable experimental flexibility from small to large scale, multi-sample, multi-condition studies at single cell resolution. This was an area of unmet scientific need, particularly in drug discovery, where testing many samples, many conditions, replicates, controls, and additional cell lines is critical. (Controls and replicates, often overlooked, allow researchers to compare against conditions and to assess variability and improve the reliability of findings in light of biological variation between individual cells.)
The “aha moment” came when we discovered that oligonucleotides simply attach to nuclei or cells during fixation. We realized we could leverage this functionality as a sample barcode for single cell profiling.
The ScalePlex reagent enables a simple workflow and lower cell or nuclei inputs per sample for processing many samples or conditions (10’s to 100’s). Samples, each with a unique ScalePlex barcode,can be pooled prior to single cell profiling or time-consuming washing steps .
The magic is its simplicity with cell fixation and sample barcoding performed simultaneously. Further, the sooner samples or conditions are pooled into a single workflow, the less batch effects occur.
Related methods rely on antibodies to cell surface proteins or oligonucleotide-tagged lipids that assemble within the cell membrane but can be sensitive to the presence of specific proteins, prone to dissociation or undesired barcode “hopping” (a process where a barcode moves from one cell to another). These errors are less likely when the sample barcode is fixed to the cell as it is with ScalePlex.
What impact could your innovation have?
ScalePlex technology enables experimental flexibility from small to large scale, multi-sample, multi-condition studies at single cell resolution. Researchers across many areas, including in the pharmaceutical space, want or need to profile many samples, many conditions, replicates, controls, and additional cell lines, and need ways to do this efficiently, with high accuracy, and at scale.
Did you collaborate with any external teams during development? If so, how important was the collaboration in achieving the end result? See first answer above.
Do you have a “philosophy of innovation”?
Our innovation philosophy is built on three main pillars: (1) collaboration – innovation comes from teamwork and the combination of multiple perspectives and ideas; (2) curiosity – imagining new possibilities together; (3) uniqueness – breaking free from traditional thinking and constraints.
We bring together people with expertise in different fields (chemistry, molecular biology/genomics, and engineering). We start from scratch without being constrained by the status quo and look for new ways to solve a problem.
Are you driven more by scientific curiosity or the desire to make an impact?
Scale Biosciences aims to make an impact by enabling our customers to study the biology of health and disease at scale and with single cell resolution.
Is there anything missing from the analytical scientist’s toolbox today?
Currently we are limited by the breath and depth of information we can extract from single cell populations. Scalable and cost effective single cell tools, together with maximum information collection per cell (methylation, transcripts diversity, epigenomics, proteomics,multi-omics) and low cost sequencing, will accelerate our understanding of the biology of health and disease.
What big problems could analytical innovation help to solve over the next decade?
We continue to innovate to enable our customers to study exponentially more cells and parameters with new simple workflows. We believe that new technologies will enable researchers to answer many more questions about the underlying nature of human biology and the underpinnings of disease.
What’s next for your team?
ScalePlex is compatible with cells or nuclei illustrating the broad applicability of the approach. In the future, we plan to enable more sample types such as FFPE tissues and to continue to expand the scale of our technology beyond the 96 ScalePlex barcodes to enable even larger studies. In 2025, we will also be launching our Quantum Barcoding workflow, a single cell RNA sequencing technology capable of preparing up to 2 million cells in parallel.
