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Droplet Genomics Debuts New Microfluidic Screening Platform, Touting Throughput, Flexibility

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NEW YORK – Droplet Genomics, a European technology company headquartered in Vilnius, Lithuania, is rolling out a new droplet microfluidic platform for high-throughput screening for a variety of research applications.

CEO Juozas Nainys said the firm delivered the first of the instruments to customers at the end of 2021 after having spent at least two years developing the product. The benchtop system, called Styx, enables users to run millions of functional assays per day to support applications including functional metagenomics studies, DNA-encoded library screening, in vitro evolution studies, and functional antibody discovery.

For functional metagenomics, the platform enables users to screen populations of unculturable microbes to uncover genes that encode enzymes of desired function, Nainys said, while for library screening, it can be used to support small molecule drug discovery assays. Nainys declined to provide pricing information for Styx, noting it depends on the agreement with the user and other factors. The company is marketing Styx to labs looking to adopt advanced microfluidics workflows as an alternative to robotic liquid handlers, with a focus on flexibility and customization.

Each Styx instrument can contain up to four separate lasers and four independent fluorescence detection channels, and features high-speed microscopy with in-line artificial intelligence image processing. It also has a dual microscope setup for on-chip process analysis, and there is no chip lock-in required, making it compatible with elastomeric chips, he said. The company also offers customizable chips for use on the platform. Styx also comes paired with user interface software.

Droplet's new offering is a follow-on to its existing platform, called Onyx, which costs €38,000 (about $43,000) and has been on the market for several years with an installed base of more than a dozen users. Onyx has been adopted mainly by researchers for next-generation sequencing library generation and functional assays. Styx, on the other hand, is intended for screening these libraries in droplets.

"Typical users of Onyx are academic labs or people interested in general microfluidics research," he said. "They need to generate droplets, and need a lot of flexibility around the droplet generation process."

These capabilities have found use for targeting specific cell populations for transcriptome and genome sequencing, for example. Researchers use Onyx to encapsulate samples into droplets and then Styx to perform droplet selection, Nainys said.

Since its launch, Styx has seen uptake by some biotechnology companies for running functional assays. "They have to select novel compounds, proteins, and antibodies," Nainys said. "These kinds of assays are most suited for Styx. Both systems have a place on the market; they just serve different needs," he said. "Since not all workflows call for screening, Onyx is also used as a standalone system by users."

Nainys cofounded Droplet Genomics in 2016. The company currently employs 25 people, some of whom have ties to Vilnius University. Chief Scientist Linas Mažutis, who previously led research groups at Columbia University, continues to undertake research at Vilnius, for instance. The technology underpinning Droplet Genomics' products, however, was developed in house.

"All of the know-how in droplets come from the academic pedigree we have," acknowledged Nainys. "That comes from the academic side. But the hardware innovations were done purely in the company."

Nainys noted that complex droplet microfluidics is a "very powerful technology" that has been around for at least 15 years but is still underutilized.

The reason for this underutilization could be simply the complexity of the technology itself.

"If you have a very particular application based on PCR or sequencing, then [droplet microfluidics] is good, because you can deliver it to a customer and they will not even know that it's droplets, but if you want to do some applications like library screens, then those workflows are hard to implement," said Nainys. "We have tried to deliver hardware solutions that make this easy, aimed at users who have lots of ideas. I think this niche has been unaddressed."

An early adopter of Styx (and, previously, Onyx) is Orbit Discovery, an Oxford University spinout that offers a therapeutic peptide drug-discovery service based on its bead-based peptide analysis platform.

"We use novel technology in order to discover therapeutic leads for our client base," said CEO Neil Butt, who took the helm of the firm in June. "What is key for us is industrializing the platform."

Anthony Pitt, Orbit's chief technology officer, agreed, noting that the company has its own technology for displaying peptides and therapeutic targets for drug screening, and can screen against cells, distinguishing it from other platforms that screen against recombinant proteins in solution and in isolation. He said that Orbit Discovery typically generates peptide libraries on the magnitude of millions or even billions of peptides but has been hindered by an ability to screen just 10,000 to 50,000 select peptides at a time using wells on plates.

"Our prime focus has been trying to identify new technologies that would allow us to smash through that barrier of limitation," commented Pitt. "We need to be able to screen tens of millions of cells and peptides to make the platform viable."

Pitt said that Orbit received Styx last month and it has already allowed the company to make a "quantum leap in terms of numbers and throughput," scaling from screening roughly 50,000 peptides to 500,000 peptides with the first run. "We can see that we can go from half a million to a million to tens of millions with this technology," said Pitt.

When asked about competitors, Pitt said there is "not much else out there" with similar capabilities. "This has been a breakthrough technology product for us," he said.

However, one potential competitor could be Sphere Fluidics. The Cambridge, UK-based company announced in December plans to develop new applications for its Cyto-Mine single-cell isolation and assay platform, with a focus on building its client base specifically in drug discovery and development. Sphere's platform relies on microfluidic, droplet-based cell isolation technology and can be used to identify cells of interest during antibody discovery or cell line development.

One Onyx user that is considering adopting Styx is the VIB-KU Leuven Center for Brain and Disease Research. The center has developed HyDrop, a custom assay built on droplet microfluidics for single-cell ATAC and single-cell RNA sequencing. HyDrop relies on using a hydrogel-based single cell indexing strategy, where the polyacrylamide-based beads are barcoded using a combinatorial indexing strategy.

According to Suresh Poovathingal, leader of the center's single-cell and microfluidics unit, the researchers use the Onyx to generate droplets for all of its HyDrop assays, including hydrogel bead generation and single-cell encapsulation. Poovathingal said that his center is currently mulling acquiring the Styx to support microbial research, as well as to study protein aggregation.

According to Nainys, feedback on the Styx so far has been positive. "People who have dealt with the frustration of droplet microfluidics know how hard it is to transfer complex academic setups to practical setups in biotech companies," he said. He also noted that all Styx adopters to date have also had Onyx installed for library generation. "I think it's unavoidable because you have to generate your libraries before you can screen them," he said.

As it continues to roll out Styx, Droplet is also developing a new capsule-based liquid handling technology that is similar to droplets but has certain additional capabilities. Nainys described the capsules as "semi-permeable compartments" that are suspended in aqueous phase, in contrast to droplets, which are compartmentalized in oil.

"Novel assays are accessible to capsules that are not accessible to droplets," said Nainys. "I think capsules have more potential for scaling, so we want to work on development there." He said the technology would likely find users among R&D scientists, but cautioned it is too early to share more details.

A new device supporting the capsule technology could reach customers by mid-2023, Nainys said. It will include a simple interface allowing users to "push a button and get capsules" as well as reagents to do certain assays.

Plans for a Series A financing are also underway. To date, the company has funded itself through several local government grants as well as revenues from instrument sales. "We intend to focus more on our capsule technology and around the technology we have," said Nainys.

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