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S2 Genomics to Commercialize Tissue Sample Prep Platform by Early 2020

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NEW YORK – Expecting to complete an early-access program by the end of the year, S2 Genomics plans to commercially launch its Singulator automated sample prep platform in early 2020 as a research-use-only (RUO) instrument. 

The Livermore, California-based firm aims to eliminate problems with manual tissue sample preparation — the time, difficulty and inconsistency of manual cell isolation methods — to produce highly viable and accurate products for downstream single cell-based applications.  

Founded in 2016 as a spinout of Silicon Valley Scientific, S2 Genomics first developed the cell-sorting technology as a sample preparation system for research groups working with tissue samples. The firm then began searching for a method to dissociate nucleic acids from solid tumor tissues. 

"Our initially focus was feeding the single-cell analysis pipeline," S2 Genomics CEO Stevan Jovanovich, who holds the same role at Silicon Valley Scientific, explained. "We saw that there was going to be a need for the first step of processing tissue sample for single-cell analysis to feed things like [BD] Rhapsody and 10X's Genomics [ATAC-Seq platform]." 

As part of a $280,000 Small Business Technology Transfer grant from the National Institutes of Health's Human Genome Research Institute in June 2018, S2 Genomics approached the J. Craig Venter Institute (JCVI) in La Jolla, California to improve the automated single-cell platform. Jovanovich said the collaboration aimed to optimize the Singulator for single-cell genomic DNA sequencing and RNA sequencing from single nuclei, noting that the center was "the first group to perform nuclei sequencing and had deep expertise in sequencing and the equipment to do single-cell sequencing." 

S2 Genomics later moved into its current lab and earlier this year began an early-access program with academic collaborators across the US using six of its Singulator instruments.

Explaining the process of using the Singulator, Jovanovich said a researcher places between 10 mg to 600 mg of a solid tissue sample into a single-use cartridge and inserts it into the instrument. The researcher then selects a specific protocol to run on the sample to collect either cells or nuclei suspensions.  

While Singulator requires some manual setup, Jovanovich explained the instrument can pull reagents from different containers to dissociate the tissue into single cells or nuclei. Inside the instrument, the proper dissociation solution combines with the sample and a spring-loaded rotor stirs the liquid during an incubation step to produce single cell suspensions. When the incubation step finishes, the rotor lowers and mechanically disrupts the sample's extracellular matrix (ECM), which has been enzymatically digested by the dissociation solution

"We then move the sample to a second chamber with a filter in it, which strains the samples using a 70-micron strainer and collects the cells," Jovanovich explained. 

Since the nuclei in a sample doesn't require ECM digestion, the disruption portion occurs immediately as the rotor drops to the bottom of the instrument, allowing nuclei to pass through a 30-micron filter. 

After the machine finishes straining the sample, a researcher can remove the cartridge and pipette out the filtered sample containing the cells or nuclei. 

Jovanovich said processing the sample for cells requires about 20 to 45 minutes due to the ECM digestion step, while the process for nuclei only needs about five minutes. 

Placing a Singulator instrument at the JCVI in September 2018, S2 is now working with Richard Scheuermann, director of JCVI's La Jolla campus, to run human and mouse tissue samples through the workflow and downstream sequencing. 

Scheuermann's group has primarily used the Singulator tool to collect cells from frozen post-mortem brain tissue for single-cell analysis. Working with the Allen Institute for Brain Science in Seattle, Scheuermann's group sought to manually characterize neurons in the neocortex by initially using a Dounce homogenizer to isolate the specific cell type in a brain tissue sample. 

"We recognized that tissue disruption protocol was a bottleneck in the workflow because it was a manual operation and [was] difficult to control and reproduce viable results," Scheuermann explained. "We also recognized that trying to isolate single cells from brains [is difficult] because they're so interdigitated and you can't pull them apart really easily."

Worried that users could indirectly cause bias in the type of cells during recovery using a Dounce homogenizer, Scheuermann found that the Singulator instead gave a more consistent yield of both single brain cells and nuclei after each run.  

Scheuermann's team also evaluated protocols that S2 Genomics had optimized for collecting a wide range of mouse tissues. Scheuermann noted that he was especially impressed by the firm's careful approach to protocol optimization and "recognizing that different protocols might be optimized for different tissues." 

S2 Genomics is currently developing protocols and reagents for cell isolation from mouse and rat liver, spleen, kidney, lung, gut, and brain tissue, as well for nuclei isolation "from most mammalian tissues." Jovanovich argues that the Singulator's open design and software allows researchers to significantly tailor protocols and reagents a group can choose standard S2 or customized reagents, as well as the tissue dissociation parameters, including incubation time, temperature, mixing profile, mechanical disruption profile, and hold temperature. 

In addition to mice and rat cell tissue samples, S2 Genomics has tested the Singulator's ability to collect single cells on patient-derived cells from human tumors, as well as human cells from clinical surgeries. The firm claims that the instrument can yield between 20,000 to 1.2 million cells per milligram with "viabilities of 70 to 95 percent" and 10,000 to 600,000 nuclei per milligram (depending on the tissue type).

"As a firm, we are agnostic to the tumor type but will look initially at the samples used by our partners," Jovanovich said. "Depending on the investigator, we will focus on as specific tumor type or broadly take them from surgery." 

Jovanovich said that the biggest challenge his team has encountered has been developing a platform for the wide variety of human tissues types. The firm is now attempting to further improve the tool's protocols so users can isolate the different cell types they want in "good yield" and have viable cells from different tissues, especially for cell types that are fragile or rare. 

"In any given tissue type, there are several different cell types, each with different properties," Jovanovich said. "We want to [develop] protocols that are robust and have a wide breadth of clinical applications." 

As S2 Genomics completes the early-access program with collaborators, the firm aims to commercialize the Singulator platform by Q1 2020. Jovanovich said that the firm will need to apply for a CE mark to offer the instrument in the European market, as well as improve the instrument's user interface and build a commercial team. 

S2 Genomics began filing provisional patent applications related to the instrument with the US Patent and Trademark Office in 2016. In addition to raising $1 million in convertible bridge notes, Jovanovich said S2 Genomics expects to close a round of seed funding later this year.

While the firm will initially launch the instrument for RUO purposes, it eventually hopes to see the tool used in the clinical space, which "will be dependent on when single-cell sequencing is adopted in the clinic," Jovanovich said.

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