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Denmark's Samplix Shifts Focus to Single-Cell Analysis


NEW YORK – Danish microfluidics company Samplix has decided to refocus its business on the cell screening market, while continuing to support DNA target enrichment, a seemingly less lucrative area.

The company recently received a €2.5 million ($2.7 million) accelerator grant and a €7.5 million equity investment from the European Innovation Council that will be matched with another €7.5 million by the company's investors by the end of the year. The firm separately raised €5 million from its investors recently, leaving it well flushed to achieve its new aims: platform innovation and international expansion, according to CEO Lars Kongsbak.

Though the firm launched its platform for cell screening just months ago, it already has found traction in the San Francisco Bay Area and plans to open an office in California soon to serve early pharmaceutical and biotech companies. "We have placed a few instruments in the Bay Area, and it will be easier to service them this way," said Kongsbak, noting the nine-hour time difference between the West Coast and Birkerød, the northern suburb of Copenhagen where Samplix is based.

The planned West Coast office will have access to laboratories, where the company can demonstrate its offerings to existing and prospective clients.

Its Xdrop platform is a benchtop system for preparing living mammalian or microbial cells, DNA, and other biological material for downstream analysis. The instrument, which retails at about €55,000, relies on cartridges to encapsulate the cells or DNA fragments of interest in picoliter-volume, double-emulsion droplets. These remain stable through pipetting, incubation, and flow cytometry, as well as sorting and storage, the firm claims.

Scientists can use Xdrop to study cell killing and cytokine secretion by human immune cells, or enzyme secretion by microbial cells, for example. The system can also be used to encapsulate DNA for PCR-free, whole-genome amplification followed by next-generation sequencing. When Samplix introduced Xdrop three years ago, DNA target enrichment was its primary application, but changes in customer demand prompted the company to shift gears.

"The cost of sequencing just went down, and the cheaper sequencing became, the less attractive it became to offer targeted sequencing," Kongsbak said. While some applications, such as CRISPR editing, continue to require targeted sequencing to validate gene edits, it makes more sense to do whole-genome sequencing, given its lower cost, he added.

Samplix continues to support target enrichment, though, which is still generating revenue for the firm. In 2021, for example, a team of Italian and US investigators published a study that used the Samplix Xdrop platform, coupled with Oxford Nanopore and Illumina sequencing, to characterize FMR1, the gene responsible for fragile X syndrome. Also, last year, a team led by researchers at the University of Cologne in Germany described using Samplix Xdrop and Oxford Nanopore sequencing to characterize the CFH gene cluster, which has been linked to multiple diseases.

However, the company's existing customers and investors suggested using the platform for cell screening, in part because they wanted an alternative to running functional assays in a microtiter plate format.

To build out its offerings for single-cell analysis, Samplix has introduced several new products over the past years. One of them is Xdrop Sort, a benchtop instrument launched last year that can generate and sort double-emulsion droplets. Samplix markets the system for capturing DNA fragments, small single cells, and other biological materials for use in PCR and enzyme activity assays. Using fluorescence, the same instrument can sort the droplets to obtain the content of interest. The difference between Xdrop and Xdrop Sort is that the latter supports not only DNA or cell encapsulation, but also high-throughput sorting.

Samplix has also introduced multiple cartridge formats. These include its DE20 Cartridge, which supports the encapsulation of millions of microbial cells, organelles, or DNA for single-cell assays or targeted DNA enrichment and uses droplets 20 μm in diameter, and the DE50 Cartridge for the encapsulation of mammalian cells, with droplets 50 μm in diameter. Both droplet types are compatible with flow cytometry and standard cell sorters.

"We repurposed our existing technology to fit mammalian cells," said Kongsbak. "Now we can do functional profiling on millions of mammalian cells in just an hour."

Samplix also continues to offer its SE85 Cartridge for DNA amplification, including single-cell whole-genome amplification.

As part of its reorientation toward cell-based applications, the company has demonstrated the use of its technology for measuring single-cell cytokine release, antibody secretion, and cell-cell interactions, such as immune cells killing cancer cells, and plans to release assays for these applications, Kongsbak said.

The company currently employs around 35 full-time staffers, plus a roster of contractors, many of whom used to work at Exiqon, the RNA analysis-focused firm that Kongsbak led from 2003 through its acquisition by Qiagen in 2016.

With new markets come new competitors. While some larger players, such as Thermo Fisher Scientific, offer instruments for cell sorting and screening using 96-well microtiter plates, there are other companies that have developed dedicated microfluidics platforms for cell biology assays, such as Cambridge, UK-based Sphere Fluidics. Another potential competitor is Emeryville, California's PhenomeX, which was formed last month when Berkeley Lights acquired IsoPlexis.

Kongsbak said that many of these players are complementary, though, and that Samplix offers users the ability to run functional assays. "This is unique, to have tiny compartments where you have an effector cell and a target cell, and monitor that effect," he said.

Christopher Chamberlain, a researcher at Denmark's National Center for Cancer Immune Therapy in Herlev, outside of Copenhagen, has used the Xdrop system for the past six months and has made use of its DE50 format.

"Using the Xdrop, we have been encapsulating individual tumor-infiltrating lymphocytes and tumor cells together in order to monitor the tumor-killing efficiency of individual TILs," Chamberlain said. "The single-cell resolution of the technology provides a level of readout that was previously not possible with our bulk-based assays, and it is therefore aiding us in understanding the complexity of these interactions."

Previously, the cytotoxicity assays run at the center, including chromium release assays, flow cytometry-based, and imaging-based methods, had relied on a bulk co-culture approach, which has drawbacks. As the TILs have access to many tumor cells in bulk co-cultures, a measurement of 30 percent cytotoxicity "could actually represent a much smaller fraction of TILs killing multiple tumor cells," he said.

Samplix is working on developing a next-generation instrument to follow Xdrop and Xdrop Sort that will host these kinds of assays, Kongsbak said, supported by the recent EIC grant. While he did not provide a timeline, he said the new platform will overcome some limitations of flow cytometry, allowing researchers to study protein secretion, for example, and provide "a completely different way to do functional analysis with single-cell resolution."

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