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Automating the Last Mile of Targeted Sequencing Workflows on Callisto
Hybridization Capture in Next-Generation Sequencing
In the world of genomics, researchers often need to focus their sequencing efforts on specific regions of interest rather than sequencing entire genomes. This targeted approach enables focused, deeper coverage of specific genomic regions that are most relevant to research or clinical questions. In many contexts, particularly clinical applications, this focused analysis provides a more manageable dataset with fewer variants of unknown significance, reducing the computational burden while delivering the most actionable insights.
Hybridization capture represents one of the essential approaches for targeted sequencing applications, particularly when working with large panels or when discovery of novel variants is important. Common implementations of hybridization capture include DNA and RNA "bait" strategies where short oligonucleotide sequences complementary to regions of interest are used to selectively enrich target DNA, whether that's a handful of genes or the entire protein-coding portion of the genome (the exome). Various methods are used to separate and typically amplify target-bound baits from the rest of the input sample, resulting in a highly enriched pool of targeted DNA fragments that can then be sequenced more deeply and efficiently than would be practical for an entire genome.
Overall, this approach offers higher discovery power for novel variants, better coverage uniformity across target regions, including those with challenging GC content, greater scalability with larger panels, and higher analytical sensitivity. Collectively these advantages of targeted sequencing have driven diverse applications like cancer genomics, including somatic variant detection and liquid biopsy analysis, minimal residual disease (MRD) monitoring, hereditary disease testing, and carrier screening.
Challenges of Implementing Hybridization Capture Workflows
Despite its advantages, implementing hybridization capture workflows in laboratories remains challenging. The process is complex, requiring temperature sensitive heated wash steps involving magnetic beads, and is typically lengthy and time-consuming, often requiring a full day or more to complete. Traditional manual methods demand constant attention and precision from skilled technicians, which can lead to significant variability between operators and runs. Current pipetting-based lab automation platforms also fall short, as they are not built to handle the complexity of hybrid capture workflows that require extensive method development, complex programming, and dedicated engineering resources to implement and maintain effectively.
These challenges translate directly to real laboratory pain points: high failure rates requiring costly and time-consuming sample prep and sequencing re-runs, unpredictable performance across different sample types and operators, complex protocols that limit who can perform the work, and workflows that tie up valuable personnel for extensive periods. As genomic applications continue to expand into clinical and applied settings, these limitations have become increasingly problematic.
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Introducing VoltaHyb:
Automating the Last Mile of Targeted Sequencing Workflows
The Volta Labs team is revolutionizing critical targeted sequencing workflows with the introduction of the VoltaHyb™ suite of Apps and kits for the Callisto™ Sample Prep System. Designed to enrich your targets with confidence every single time, the Callisto platform brings unmatched workflow simplicity to hybridization capture. With Callisto, users no longer need to rely on multiple lab instruments (heated blocks, magnetic racks, vortexers) or perform time-sensitive heated transfer steps - such complex steps are abstracted away from the end user. Furthermore, Callisto's unique architecture enables precise magnetic bead manipulation coupled with uninterrupted and uniform temperature control during the hybrid capture enabling consistent enrichment performance.
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Callisto reduces sequencing redo rates to less than 3% while minimizing sample loss throughout the capture process. This breakthrough approach enables reliable targeted sequencing even for challenging applications where conventional tools struggle. These advantages extend across both long and short read-based hybrid capture workflows.
The scalable architecture of the Callisto system enables flexible throughput, with the capacity to process up to 96,000 exomes per year or 48,000 PacBio HiFi samples annually. Whether you're running a small research lab or a high-volume testing facility, Callisto adapts to your needs with flexible batch sizes and consistent performance.
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Key Benefits
of VoltaHyb for Hybridization Capture:
Reduced Sequencing Costs:
Lower sample preparation and sequencing costs by minimizing reruns (<3% redo rates).Fully Automated Workflow:
Enables complete walk-away automation for hybridization, capture, washes, and PCR setupBroad Panel Compatibility:
Works with panels of all sizes, from small targeted panels to comprehensive exomesSupport for Both Short and Long Read Applications:
Optimized protocols for both Illumina-style short-read sequencing and long-read technologies like PacBio and Oxford Nanopore
Consistent Results:
Dramatically reduced inter-operator variability and robust performance across repeated runsUniform Coverage:
Even coverage across challenging regions, including high-GC content areasMaximum Throughput: Process up to 480 exomes simultaneously with pooled libraries with flexible batching
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VoltaHyb’s Expanding App Menu
At Volta, we’re continually growing our support for hybrid capture workflows across both short- and long-read sequencing platforms.
On the short-read side, Callisto currently supports IDT xGEN v2 chemistry, as well as Twist’s standard v2 and Fast chemistries. For long-read applications, we support PacBio HiFi enrichment based on Twist’s standard v2 chemistry.
There are more Apps coming to the VoltaHyb menu, and we’re always listening to our users. If there’s a hybrid capture chemistry you’d like to see automated on Callisto, let us know—we’d love to hear from you.
for Twist, v2 standard
The revolution in genomic sample preparation is here. By bringing the push-button experience of a sequencer to targeted sequencing workflows, Volta Labs is transforming how laboratories approach hybridization capture. The choice is no longer between inconsistent manual methods and complex automation platforms that require dedicated engineering resources. With Callisto and VoltaHyb, you can achieve consistent, high-quality results without specialized training or extensive method development.
Ready to experience the difference? Contact our team today to learn how the VoltaHyb powered Hybridization Capture can enhance your targeted sequencing workflows and accelerate your discoveries.
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Automating the Last Mile of Targeted Sequencing Workflows on Callisto
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