NEW YORK – Curio Bioscience said Tuesday that it is launching a new product based on Slide-tags, a method developed by researchers at the Broad Institute that adds spatial context to single-cell, whole-transcriptome sequencing studies.
Curio has licensed the technology from the Broad and will be offering it as Curio Trekker. A paper describing Slide-tags, which was developed in the Broad labs of Fei Chen and Evan Macosko, both cofounders of Curio, was published in Nature in December.
"Curio Trekker is the world's first product that converts single-cell genomics data into single-cell spatial data, enabling a new era of scientific discovery that is simply not possible with today's standard single-cell sequencing workflows," Christina Fan, Curio cofounder and chief technology officer, said in a statement. "By enabling researchers to routinely and easily capture the spatial context of cell populations, Curio is putting a very accessible and powerful new tool in the hands of researchers to advance discovery research in a way that is very exciting for cancer biology, neuroscience, developmental sciences, and beyond. We believe that Curio Trekker will be transformative to the single-cell market, as it delivers true single-cell spatial resolution to scientists, regardless of organism or tissue type."
Curio has tweaked the workflow to make it shorter — approximately one hour in addition to whatever single-cell sequencing protocol one wishes to follow — and more robust, Chief Commercial Officer Neil Kennedy said. The firm has also made it easier to process multiple samples and improved tissue visualization.
"It's the missing intersection between existing technologies," said Brian Kalish, a clinician scientist at Canada's Hospital for Sick Children, who has joined the Trekker early-access program to help better study neurogenesis during the course of pregnancy. "You're able to ascertain the true spatial location of cells while using a droplet approach to ensure you get single-cell transcriptomes."
He joins labs at Weill Cornell Medicine and the University of Edinburgh, among other early-access customers. Curio is looking to add early-access partners but did not say how many.
"The product configuration for the initial early-access release is a 10 mm by 10 mm tile," Kennedy said. "Customers who generate standard single-cell genomics data today will be able to convert that data into spatial for a couple thousand dollars per sample."
Trekker joins Curio's Seeker product, the commercialized version of Chen and Macosko's Slide-seq spatial transcriptomics method. It builds on Slide-seq and Curio Seeker, using the same concepts of a barcoded array of oligos that interacts with tissue sections. As with Seeker, Trekker will use square tiles rather than the circular "pucks" used in Chen and Macosko's methods.
But rather than capturing RNA from cells onto a barcoded array, Trekker's chemistry releases a barcode into the cells on a tissue slide, which are subsequently processed for single-nucleus sequencing.
"Single-cell sequencing has been an incredibly impactful technology for profiling cell populations, but the research community has been eager to understand how cells of interest are organized spatially, so we set out to develop a method that delivers this," Macosko said in a statement. "Curio Trekker is the culmination of this work and provides the spatial context that single-cell researchers are lacking today in a readily accessible format. Curio Bioscience has made it as easy to use as simply plugging it right into existing single cell-based workflows."
Kalish said his lab has used both single-cell and spatial technologies to try and understand the tissue context in which new neurons are born in a pregnant person's brain. Among the spatial methods he has used are 10x Genomics' Xenium in situ analysis platform and MERFISH (multiplex, error-resistant fluorescence in situ hybridization), the method that Vizgen is commercializing as Merscope.
These imaging-based methods have their strengths but don't necessarily provide true single-cell gene expression data, as they often rely on cell segmentation algorithms to draw artificial boundaries around detected transcripts.
For his lab, Curio's Trekker represents a "simple and cost-effective addition" to droplet-based single-cell sequencing methods. "Not only do you get a single-cell transcriptome, but you also gain the spatial location of those cells," he said. That location is "a relative position of that cell in the context of all the other cells captured on a tissue plane." In other words, a sort of map.
"You have the coordinates of any cells captured on that map and then you can infer the position of any transcriptome onto that location, relative to others," he added.
The early-access experience "has been very tailored and hand-held," Kalish said. Curio has provided his lab a detailed protocol and helped with experimental design. They've even sent scientists to the lab to help with the initial sample preparation. His lab has finished the wet work and is now working on QC, sequencing, and data analysis. "It has been an extremely positive collaborative effort," he said.
"So far, the experience has exceeded all of our expectations," Margaux Kenwood, Shane Johnson, and Devin Rocks — postdocs in Conor Liston's lab at Weill Cornell — said in an email. "Compared to spot-based methods, Trekker affords discrete single-nucleus resolution without the need for deconvolution and without the problem of dealing with incomplete cells in spots. Compared to imaging-based in situ methods, we have found that the Trekker workflow is remarkably easy to implement, and gene detection isn't restrained by probe design. Because of the high spatial resolution of Curio's platform, we are able to further refine our molecular understanding of the biological basis for interventions that treat severe depression."
Kalish noted that Trekker is not necessarily the best method for every study. "If you're hoping to look for focused validation of a specific target in a particular population, this may not be your approach," he said. Data can be "relatively sparse," he said, unless one captures and sequences many, many cells. "I think it's more amenable as a discovery platform or as an addition to droplet-based [single-cell sequencing] methods."
"As with most single-cell technologies, it can be challenging to maximize the yield of protocols, both with respect to the number of nuclei collected and the RNA content of those nuclei," the Liston lab postdocs wrote. "We've been working with Curio's team to optimize our implementation of their protocol, so we can get as much information as possible for our spatial transcriptomic studies."
Curio is now taking pre-orders for the first commercial kits that are compatible with fresh frozen tissue sections. Curio plans to add the ability to process formalin-fixed paraffin-embedded (FFPE) samples in the second half of 2024.
Curio's Kennedy noted that in addition to direct sales in the US and parts of Europe, the firm has added distribution agreements covering Belgium, the Netherlands, and Luxembourg, as well as Italy, Spain, and Japan.