Sequencing by expansion
| Sequencing by expansion | |
|---|---|
| Classification | Nanopore sequencing |
| Analytes | DNA, RNA |
| Inventor | Stratos Genomics |
| Year | 2008 (first patent filing) |
| Related | Biological nanopore |
Sequencing by expansion (SBX) is a method of reading DNA or RNA in which each strand is first copied into a much longer surrogate molecule, called an Xpandomer, that carries the sequence as an ordered series of reporters. The Xpandomer, not the original strand, is then passed through a nanopore on a silicon chip. Stratos Genomics invented the method and filed the first patent for it in 2008, and Roche acquired the company in 2020. Roche unveiled SBX on February 20, 2025, and on June 29, 2026 launched an instrument built on it, the AXELIOS 1, for research use only.[1][2][3]
Method
An unmodified strand of DNA has its bases less than a nanometer apart, and in a nanopore it must be read as it moves. Oxford Nanopore Technologies solves the problem with a motor protein that sets the strand's speed and with software that interprets the current. SBX gives the pore something else to read. The February 2025 release calls it "a novel sequencing approach which uses a sophisticated biochemical process to encode the sequence". In Roche's later description the target molecule is encoded into "Xpandomers, which are fifty times longer than the original molecule", and these act as "high signal-to-noise reporters" when threaded through a nanopore. The account on Roche's science pages puts it as "50 times longer than the original single stranded DNA template".[1][2][4]
The patent family that describes the method calls the state of an Xpandomer as it is made its "constrained configuration" and the state in which it is read the "expanded configuration". Cleaving selectively cleavable bonds brings about the change from one to the other. Roche's 2025 release adds that two co-founders of Stratos Genomics invented the chemistry.[3][1]
Sensor
Xpandomers are read on a reusable sensor chip of the CMOS (complementary metal oxide semiconductor) kind, which the 2025 release says has "parallel processing capabilities". Roche says the module "contains eight million microscopic wells, each one spanned by a thin membrane with a single nanopore". Its membranes are lipid, and the same module serves both short and long runs.[1][4] A trade-press report of the unveiling, in March 2025, says the Xpandomer is routed "through a biological nanopore" on a sensor module "developed by Genia Technologies".[5]
Genia was a nanopore company in Mountain View, California. Its own method, NanoTag, did not thread the DNA through the pore: "instead of extending the growing DNA product through the nanopore, Genia allows a cleavable label to enter the pore."[6] The chip, then, came from Genia, and the chemistry from Stratos Genomics.
Timeline
| Date | Event |
|---|---|
| June 19, 2008 | Stratos Genomics files the first patent application of the family "High throughput nucleic acid sequencing by expansion"; it is granted on May 10, 2011.[3] |
| June 2, 2014 | Roche announces its intention to buy Genia Technologies.[6] |
| 2020 | Roche acquires Stratos Genomics.[1] |
| February 20, 2025 | Roche unveils SBX.[1] |
| October 2025 | A Roche, Broad Clinical Labs and Boston Children's Hospital team reports a whole genome sequenced in under four hours.[7] |
| June 29, 2026 | Roche launches the AXELIOS 1.[2] |
Speed record
At the American Society of Human Genetics meeting in October 2025, Roche reported that a team from Roche Sequencing Solutions, Broad Clinical Labs and Boston Children's Hospital had sequenced "a human whole genome in less than 4 hours with a reference sample", against a previous record of 5 hours and 2 minutes. Roche says the work has been published in the New England Journal of Medicine.[7][8] The clock ran from DNA extraction to a final variant call file.[8]
AXELIOS 1
Roche's launch release describes a reusable CMOS sensor "containing millions of nanopores", reads of "up to ~1500bp under appropriate sample and library prep conditions", and whole-genome results the same day. Roche said it would offer library prep kits and a free open-source analysis suite named XOOS. It describes the instrument as "for research use only."[2] Oxford Nanopore states read lengths "from 20 to 4,000,000 bases" for its own sequencers.[9]
In Molecular Reality's usage
The Hole World, the atlas of molecular-sensing groups published by Molecular Reality Corporation, marks the Roche program that began as Genia as one of its 38 hand-picked flagship entries and captions it "Tag-based protein nanopore sequencing".[10] The company's own pore is a different design: a solid-state pore with a mechanical opening, and the company's field guide describes the pores it streams today as "larger than a nanometer".[11]
See also
References
- ^ a b c d e f "Roche unveils a new class of next-generation sequencing with its novel sequencing by expansion technology" (Press release). Roche. February 20, 2025.
- ^ a b c d "Roche announces the launch of AXELIOS 1, a transformative next-generation sequencing platform" (Press release). Roche. June 29, 2026.
- ^ a b c "US7939259B2: High throughput nucleic acid sequencing by expansion". Google Patents. Retrieved October 25, 2026.
- ^ a b "Nanopore SBX sequencing". Roche. Retrieved October 25, 2026.
- ^ "Roche unveils completely new sequencing approach". European Biotechnology. March 4, 2025.
- ^ a b "Roche acquires nanopore sequencing firm Genia". Decibio. June 3, 2014.
- ^ a b "SBX sequencing world record". Roche. Retrieved October 25, 2026.
- ^ a b "Roche and partners push sequencing boundaries with record-breaking SBX technology". Dark Daily. November 7, 2025.
- ^ "Technology". Oxford Nanopore Technologies. Retrieved October 25, 2026.
- ^ "The Hole World: build metadata". Molecular Reality Corporation. September 26, 2026.
- ^ "Keltar's Field Guide to Molecular Reality". Molecular Reality Corporation. August 2026.