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Volta Labs Launches Electrowetting-Based Automated NGS Sample Prep Platform

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This article has been updated to note a new partnership between Volta Labs and Qiagen's OEM business.

ORLANDO, FLORIDA – Lab automation startup Volta Labs has launched its first electrowetting-based sample preparation platform for next-generation sequencing.

Dubbed Callisto, the instrument promises to support a variety of short- and long-read sequencing workflows.

"Over the last year and a half, the company has been both developing the product and preparing for the commercial launch," said Volta Labs Founder and CEO Udayan Umapathi.

Roughly the size of a minifridge, Callisto is a benchtop instrument that can accommodate up to 24 samples while carrying out a single protocol, such as DNA extraction and library preparation. The instrument allows batches of four samples to be loaded at a time, with each sample having its individual electrowetting surface module.

Currently, Volta Labs is enabling four applications on the Callisto platform: DNA extraction, library preparation, hybridization capture, and auxiliary protocols such as bead cleanup. The company uses pre-optimized reagents developed in-house or in collaboration with third-party vendors.

Specifically, for DNA extraction, the platform is compatible with blood, buffy coat, and cell line samples. For library prep, Volta Labs currently enables the Pacific Biosciences SMRTbell prep kit 3.0 as well as a kit for enzymatic fragmentation-based DNA library preparation for short-read sequencing. For hybrid capture, the company is offering the xGen Hybridization and Wash Kit from Integrated DNA Technologies.

In the second half of this year, Volta Labs plans to enable the Oxford Nanopore Technologies Native Barcoding Kit, the IDT xGen DNA Ez Library Prep Kit, the Illumina DNA PCR-Free Prep kit for library preparations, and the IDT xGen NGS Hybridization Capture kit.

While Callisto processes samples using digital fluidics technology, the instrument is equipped with a liquid handling robotic arm to load and offload reagents and samples onto the electrowetting surfaces. The platform promises "push-button operation" for each protocol but currently does not support multiple tasks, such as DNA extraction combined with library preparation, in one continuous workflow.

Once the samples and reagents are loaded onto the electrowetting surface, the reactions happen in "a very compact format," Umapathi said, noting that the reaction volume for nucleic acid extractions is typically in the range of hundreds of microliters, while that for library preparation is in the single-digit microliter range. 

Volta Labs has not yet disclosed much of the platform's technical details, other than noting that it "combines electrowetting, magnetics, precise liquid transfer, and temperature control all on one instrument."

Umapathi said Callisto deploys "a very advanced form of electrowetting" but did not provide further details.

According to Volta Lab's website, the company processed 10,000 samples on the platform last year. The company said it has benchmarked both DNA extraction and library preparation methods for various sequencing platforms, including from Illumina, Pacific Biosciences, Element Biosciences, and Oxford Nanopore Technologies.

During a company workshop at the Advances in Genome Biology and Technology meeting here on Wednesday, Volta Labs highlighted preliminary data and experiences from early-access customers, including the Hartwig Medical Foundation in the Netherlands and Broad Clinical Labs (BCL), the diagnostic arm of the Broad Institute.

According to Ewart de Bruijn, Hartwig's lead for technology innovation, his institution, which currently operates Beckman Coulter systems and Qiagen's QiaSymphony for some of its automated NGS workflows, is interested in testing Callisto for automating its hybridization capture protocol.

Volta Labs' technology "could be ideal for manipulating sample, bead, and temperature in one go, which is really important for target sequencing," de Bruijn said.

As a proof-of-concept experiment, his lab, which does not currently operate a Callisto instrument, generated library pools from standard control samples and shipped them to Volta Labs for automated bead-based hybridization capture. The processed samples were then shipped back to him for further benchmarking with Illumina sequencing.

"Long story short, the technology works," de Bruijn noted. "In our setup, we think there is every reason to continue the development of the hybridization capture [protocol] into a full walkway solution."

Still, given the early stage of their collaboration with Volta Labs, de Bruijn said, questions remain as to how flexible and customizable the platform will really be in customers' labs.

Brendan Blumenstiel, ​​director of genomics research and development at the BCL, said his lab is drawn to the Callisto platform because of its flexible batching.

"You can't have a system that operates in 384-well plates running three samples," he said. "These are the challenges that drove us to come to understand how Volta could play a role in solving some of these problems."

According to Blumenstiel, BCL became an early-access customer for Volta Labs last year. His team has not tested the new Callisto platform but rather a beta prototype, he noted.

So far, his lab has performed DNA extraction and library prep on 12 blood samples using Volta Labs' platform for both long-read and short-read whole-genome sequencing. The libraries were then pooled and sequenced on corresponding platforms for quality benchmarking.

For short-read Illumina sequencing, Blumenstiel said the Volta Labs data has shown "equivalent sensitivity and specificity performance" compared to samples processed by the Broad's standard clinical genome sequencing workflow. Similarly, for long-read PacBio sequencing, the primary metrics were "consistent" with the samples processed with the team's standard PacBio workflow.

Additionally, Blumenstiel said the sample processing time for both DNA extraction and library preparation is "greatly reduced" using Volta Labs' platform compared with standard protocols, roughly cutting it in half.

Neither speaker commented on the cost associated with using the platform. According to Volta Labs, the listing price for the Callisto is $125,000.

With the first platform, Umapathi said Volta Labs is hoping to target a broad range of customers, including genome centers, core facilities, academic labs, and biotech companies. The firm has also been teaming up with other NGS players. Earlier this week, Volta Labs announced partnerships with IDT and Watchmaker Genomics to make some of their products compatible with the Callisto instrument.

The company also announced a collaboration with Element Biosciences on Wednesday to enable users to prepare automated libraries for the Aviti sequencer using Callisto. Under another partnership announced this week, with Qiagen's OEM business, the two firms will produce reagents and other elements for Callisto sample prep kits.

Based in Cambridge, Massachusetts, and founded in 2018 as a Massachusetts Institute of Technology spinout, Volta Labs has garnered financial backing from high-profile investors such as Illumina Cofounder John Stuelpnagel.

Previously, Volta Labs raised $20 million from a Series A financing round in 2022, and Umapathi said the company has raised more capital since then, although he did not disclose the amount.

According to a Form D Volta filed with the US Securities and Exchange Commission in December 2023, the company offered $9.0 million in equity for sale, which generated $4.3 million. Umapathi said the money raised will be used toward commercialization.

Volta Labs said it hired 24 new employees in 2023, doubling its workforce to about 50. The company also filed seven global patents last year, which Umapathi said pertain to the platform's hardware, software, and biochemistry.

Moving forward, Umapathi said a large focus of Volta Labs will be to expand its commercial team, as well as its R&D and manufacturing capacities. The company plans to start shipping the Callisto in the first half of this year, he said.

Volta is not the first or the only company to tackle NGS sample prep with electrowetting. In 2015, Illumina launched NeoPrep, a sample prep instrument that also used electrowetting, but the platform was discontinued just two years later, reportedly because of poor performance.

Meanwhile, San Francisco-based Miroculus launched its digital microfluidics system, Miro Canvas, in 2022. The company was acquired by Integra Biosciences last year.

"There is a real need for better, more automated, more reliable methods for extraction and library prep, and especially for high molecular weight DNA and for long read [sequencing] methods," Winston Timp, a biomedical engineering professor at Johns Hopkins University, said at the sidelines of the conference.

Timp's lab has also worked with Volta Labs as an early-access customer, processing cell lines and human blood on Volta Labs' beta prototype. While the lab generated "good results" — the same data quality as manual preparation — on that version of the platform, Timp said the instrument was "relatively labor-intensive" at the time.

"If they have actually packaged it into a nice box that is easy to use, I'm excited about it," he said.