Researchers have unveiled a groundbreaking method that substantially reduces teh cost and increases the scalability of single-cell RNA analysis. The new technique, known as Single-Cell Transcriptomics Analysis and Multimodal Profiling through Imaging (STAMP), offers a 47-fold reduction in cost compared to existing methods, making it far more accessible to researchers.

The development comes from a collaborative effort between scientists at St. Jude ChildrenS Research Hospital, the National Center for Genomic Analysis, and the University of Adelaide. Their work, published in the journal Cell, details how STAMP combines microscopy with single-cell RNA analysis to examine millions of single cells at a fraction of the cost of current approaches.

According to Jasmine Plummer, PhD, St. Jude Center for Spatial Omics director and Department of Developmental Neurobiology member, “We’ve created a technique that gives us an advantage in the numbers game of single-cell analysis. It’s an order of magnitude more cost-effective and allows us to profile a million cells together,compared to tens of thousands typical of current methods,making it far more scalable.”

The STAMP method involves separating cells from tissues until they are individual and unconnected. These cells are then fixed or “stamped” onto microscopy slides, which preserves their shapes and expressed genes.Scientists then introduce molecules that light up under a microscope when they bind to specific RNA sequences. By comparing their results to existing gene expression atlases, the researchers were able to characterize many immune cells simultaneously and distinguish between the developmental stages of induced pluripotent stem cells.

The team estimates that analyzing immune cells from 1,000 individuals using customary methods would cost $3.56 million, while using STAMP would bring the cost down to $75,000.

Reducing Bias and Maintaining Sensitivity

“STAMP allows us to directly examine the cells… Many current single-cell approaches also bias results based on cell shape.”

“Current techniques for single-cell RNA sequencing require inference to determine things such as cell type, but STAMP allows us to directly examine the cells,” Plummer said. “Many current single-cell approaches also bias results based on cell shape, often missing irregularly shaped cells including neurons.”

unlike conventional RNA-sequencing techniques that require cells to move through a tube, STAMP is performed on a microscope slide. This eliminates the bias towards simpler, more spherical cells, allowing for a more diverse representation of cell types.

To ensure the method’s sensitivity, the researchers diluted cancer cells into a suspension of other cells. STAMP successfully detected two cancer cells within approximately 850,000 total cells on a single slide.

“Being able to profile a million cells is crucial because it only takes one cell to escape cancer treatment,” Plummer said. “We’ve shown STAMP allows us to visualize and detect these cells in a numerically advantageous and accessible way, an crucial feature for potential future development into clinical applications.”

While single-cell RNA sequencing has been limited by it’s high cost and the need for specialized equipment, STAMP offers a more accessible option, as most research institutions already have access to microscopes.

“We as scientists believe what we can see,” Plummer said. “STAMP gives us the best of both worlds in single-cell analysis: quantitative gene expression data and the ability to visually examine the cells under a microscope. We hope that these features, combined with its accessibility and cost-effectiveness, enable others to discover new biology and clinical uses in the future.”