Roche SBX Aims for Nanopore’s Portability Crown

Roche announced its breakthrough in Next Gen Sequencing with the Sequencing by Expansion (SBX) tech. The tech which has many innovations combined can be defined as unzipping the natural DNA bases and reading it via CMOS sensors. While the the full picture nor the size of the sequencer is not yet clear, what we can say it that this development marks a pivotal moment in the field of genomics and pits Roche directly against Oxford Nanopore in terms of speed and accessibility of DNA sequencing.

For the first time scientists are able to expand the tightly packed DNA and read it, thereby minimizing errors that come with signal overlaps. With SBX Roche aims to address some of the key challenges in DNA sequencing, such as reducing the errors, time and cost required to process complex genomic data. Roche has emphasised that its approach leverages novel chemistry and engineering to deliver high-throughput sequencing with improved precision.

Comparison with Nanopore Sequencing Technology

Roche’s breakthrough is likely to draw comparisons with Nanopore, even their Preprint on biorXiv mentions that it was meant to improve Nanopore sequencing. Oxford Nanopore’s ION based sequencing is renowned for its unique approach, which involves threading single DNA strands through tiny pores and reading the sequence in real-time. This method is highly regarded for its portability and ability to produce ultra-long reads, making it particularly useful for applications like field research and rapid pathogen identification.

However, Nanopore’s technology faces challenges related to accuracy, especially in homopolymeric regions (stretches of the same nucleotide) due to its reliance on complex data analysis to correct errors. Roche’s SBX by contrast, appears to focus on enhancing accuracy and throughput within a more traditional sequencing framework. We aren’t yet certain if Roche’s approach will lack the portability of Nanopore’s devices or not but from what we read it could offer a more robust solution for high-volume, high-precision applications, such as clinical diagnostics and large-scale genomic studies.

	Roche SBX	Oxford Nanopore
Accuracy	Above 99%	96%
Preparation	Multi Step	Fewer Steps
Real Time Analysis	Not Yet	Capable
Cost	Uncertain	Starts at 3k
Application	Whole genome sequencing Whole exome sequencing RNA sequencing	Whole-genome sequencing Epigenetics Transcriptomics SNVs and phasing Multiomics Metagenomics Fusion transcripts Targeted sequencing

Key Innovations that Make Roche SBX Possible

Coming out of the acquision of Stratos Genomics and Genia Technologies, researchers integrate sequencing-by-expansion technology with a massively parallel, single-molecule nanopore platform. Some of the key innovation are mentioned below:

Matching Powerful Signals from Nucleotides: XNTPs, nucleoside triphosphates modified with structures engineered to control translocation, expand, provide well-resolved nanopore based reporter codes and enable template-dependent incorporation with a modified polymerase (Xp Synthase).

Extending two Nucleotides to Better Read Signals: PEMs, a class of critical cofactors that enable polymerase extension of XNTPs beyond 10 bases by stabilizing the elongating heteroduplex structure.

Sticking these Signals to the Bases: Xp Synthases, highly mutated DNA polymerases that processively and accurately incorporate XNTPs to synthesize Xpandomers (Xp).

Reaction formulations and processes, optimized for accurate, template-dependent synthesis of Xp using a solidphase workflow.

Reusable Sensing Pores: Xp end structures and sequencing conditions, engineered to efficiently and accurately thread Xp molecules though a nanopore

Implications for the NGS Market

The NGS market is highly competitive, with players like Illumina, Thermo Fisher Scientific, and Oxford Nanopore Technologies dominating various segments. Roche’s new technology could disrupt this landscape by offering a compelling alternative that combines the reliability of established sequencing methods with cutting-edge advancements.

For researchers and clinicians, this development could translate into more accessible and cost-effective sequencing solutions, potentially democratizing access to genomic insights. For Roche, it represents an opportunity to expand its footprint in the diagnostics and life sciences sectors, further solidifying its reputation as a pioneer in healthcare innovation. As the NGS landscape continues to evolve, the competition between Roche, Nanopore, and other key players will undoubtedly spur further advancements, benefiting researchers, clinicians, and patients alike.