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Curio Bioscience Launches Seeker Spatial Genomics Product, Based on Slide-seq


NEW YORK – Curio Bioscience emerged from stealth earlier this month with the launch of its Seeker platform, an "industrial grade" version of Slide-seq, a whole-transcriptome spatial genomics method developed by Fei Chen's lab at the Broad Institute.

The Palo Alto, California-based startup is ready to roll out the technology to customers now, having already completed an early-access program.

"No other technique provides the depth and breadth of information on cellular neighborhoods that Curio Seeker can," said Cofounder and CTO Christina Fan.

The method offers resolution of 10 micrometers, making it effectively single-cell, and is based on sequencing rather than imaging. Aside from proprietary "tiles" — essentially glass slides with a layer of barcoded beads, the workflow does not require any special hardware and can be completed in eight hours, with about 2.5 hours of hands-on time, Fan said.

Curio's products allow researchers access to spatial methods without a large upfront investment, Anoja Perera, director of sequencing and discovery genomics at the Stowers Institute told GenomeWeb. Her core lab was an early-access customer and had been using Slide-seq before that. "As long as your institute has a histologist and a sequencer, you can perform this application," she said.

Moreover, Curio has made several improvements to the original method. Perera's lab has already run them side by side. "We're getting much better resolution, as far as the data goes," Perera said, "and getting at least two times the number of genes per cell we used to get with Slide-seq."

Curio was founded in February 2021 by a group of six people whose names may be enough to garner interest. Alongside Chen, the Broad's Evan Macosko and the Francis Crick Institute's Sam Rodriques make up the firm's academic cofounders. And the trio leading the day-to-day operation of the company have a successful track record of starting — and selling — companies. Curio CEO and Cofounder Steve Fodor was a cofounder of former microarray maker Affymetrix, acquired in 2016 for $1.3 billion by Thermo Fisher Scientific. He has founded several other companies with Fan and Curio Chief Operating Officer Ari Chaney, including Enumerix, a digital PCR startup, and Cellular Research, which was acquired in 2015 by Becton Dickinson.

Chen, Macosko, and Rodriques published their first paper on Slide-seq in 2019. They have applied for a patent for the method. However, Curio Chief Commercial Officer Neil Kennedy declined to comment on the firm's IP situation.

The Slide-seq method calls for depositing tissue sections on round, rubber-coated glass coverslips, called "pucks," coated with DNA-barcoded beads. The chemistry converts RNAs to cDNA, with spatial addresses appended by the beads, ultimately analyzed by NGS. 

Curio appears to have made two major improvements. First, they've redesigned the pucks as square tiles. "The beads are more uniformly placed on the tiles," Perera said, adding that the tiles perform well consistently, something that Slide-seq pucks didn't always do.

Curio has also managed to determine the barcode addresses during manufacturing, which it provides to customers as a data file. Previously, the barcodes had to be sequenced with an old SOLiD sequencing system, a sequencing-by-ligation platform that has been discontinued.

Of course, the Seeker kits, which contain reagents and tiles for eight experiments, pull in all the materials necessary to complete the workflow. "They've also improved the workflow so that the chemistry is more robust and there are better stopping points," Perera said.

In general, the Seeker workflow has the researcher melt a fresh-frozen tissue section onto a slide, which captures poly-a RNA and converts it to cDNA. After library prep and sequencing, the company's software creates a map of differential gene expression across the entire transcriptome.

The Curio team declined to compare their method's sensitivity to fluorescence in situ hybridization, the gold standard for spatial transcriptomics methods. Kennedy suggested that the method was "at least two times better" than existing whole-transcriptome spatial methods on the market. In a paper describing Slide-seqV2, published in Nature Biotechnology in 2021, Chen, Macosko, and Rodriques claimed that improvements to the method resulted in sensitivity "approaching the detection efficiency of droplet-based single-cell RNA-seq techniques."

"At the end of the day, it's tissue- and tissue quality-dependent," Fan added.

In a study of mouse colon and spleen samples at Stowers, Seeker captured "more distinct" transcripts than Slide-seq and had a higher percentage of usable reads, according to Perera.

Curio declined to discuss pricing, but Perera said the tiles come in two sizes: a 3-mmtile that costs about $1,000 and a 1-cm2 tile that costs about three times that.

Each 3-mmtile costs about $1,000 to sequence on an Illumina NextSeq, she added. "It depends on the area you’re covering. If tissue doesn’t cover the entire tile, it costs less," she said. Fan suggested that sequencing costs about $500 on Illumina's highest throughput NovaSeq instruments.

Curio joins a crowded field for whole-transcriptome spatial genomics, joining imaging-based methods such as Vizgen's Merscope and other sequencing-based methods, such as 10x Genomics' Visium, NanoString Technologies GeoMx, and MGI Tech's Stereo-seq.

"One downside to Curio is that right now it works only for fresh-frozen samples," Perera said. The ability to work with formalin-fixed, paraffin-embedded samples is "something we’re hearing a lot of requests for and something we’re actively looking into," Fan said.

On the upside, the tiles provide a large area with uninterrupted coverage. "There are no dead spots," Fan said. Visium, for comparison, offers capture areas of 6.5 mm2, but is limited to 55-µm "spots" whose centers are 100 µm apart.

And because of the chemistry, it can work with RNA from almost any organism. That has been important for Stowers, whose researchers work with a lot of "weird critters," Perera said. "You don't have to design probes to target a set of genes."

Furthermore, Curio has been "fantastic to work with," she said. "They are keeping communication going."

As a whole-transcriptome method, Seeker will likely be used for discovery research. "Seeker can be upstream of hypothesis generation," Fan suggested. "You can jump on your tissue of interest and within two days get your data."

"Our organs and tissues are highly complex, with so many different cell types," Perera said. "Spatial methodologies allow us to understand the functions of individual cells, and this is powerful."