24 jun 2025
Cyclomics has secured a Dutch patent for its innovative single-pot multi-omics sequencing technology, enabling simultaneous extraction of sequence, methylation, and structural DNA information from minimal input samples.
Cyclomics proudly announces the grant of its latest patent in the Netherlands, marking a significant milestone in the development of next-generation multi-omics technologies.
The patent protects a unique single-pot workflow that enables the simultaneous extraction of genetic and epigenetic data, specifically sequence, methylation, and molecular structure, from a single sequencing run.
The technology is designed to maximize the information yield from limited DNA samples, such as circulating cell-free DNA (cfDNA) found in blood plasma. Expansion of the patent protection to additional geographies is underway.
“This patent underscores the originality and power of our platform, purpose-built for liquid biopsy and personalized cancer diagnostics,” said Alessio Marcozzi, R&D Director at Cyclomics. “By eliminating the need for PCR and bisulfite conversion, we preserve the native DNA sequence, enabling accurate methylation analysis and mutation detection in a single assay. Importantly, our method retains the true ends of DNA fragments, allowing cfDNA end-motif analysis and more precise fragmentomics, unlocking richer insights from less input, without compromising accuracy.”
How It Works – A Simple Breakdown
At its core, the patented method uses three key steps:
Unique Barcoding Without PCR, Blunting or Ligation – Short DNA fragments are tagged using a stretch of random nucleotides. These tags serve as unique molecular identifiers (UMIs), enabling the accurate tracking of each original molecule.
Molecule Circularization and Amplification – The tagged DNA is efficiently circularized without the need for linkers or backbones, and then amplified, generating long concatemeric reads suitable for both long-read and short-read sequencing, as well as single-molecule analysis.
Integrated Methylation Detection – A methylation-sensitive approach is used in the same reaction to introduce "scars" in non-methylated DNA. These signatures allow direct inference of methylation status, eliminating the need for harsh bisulfite treatment.
The result? A single assay that preserves the native DNA sequence, reveals epigenetic (methylation) marks, and distinguishes linear from circular DNA molecules, all from a low-input sample, and without complex multi-step procedures.
A Game Changer for Liquid Biopsy and Beyond
The implications of this technology are far-reaching:
Cancer Diagnostics – The method enhances sensitivity and specificity in detecting tumor-derived circulating free DNA (cfDNA), including rare mutations and epigenetic changes.
Multi-Omics in One Go – Researchers can now extract and amplify both genomic and epigenomic information from the same DNA fragment, enabling integrative analyses critical to personalized medicine.
Non-Invasive Testing – Applicable to cfDNA from blood, urine, and other fluids, the method opens the door to high-resolution, non-invasive diagnostics.
Future-Proof Design – Unlike bisulfite conversion or PCR-based methods, this approach maintains full DNA integrity, supporting mutation detection even in GC-rich or fragile regions.
Cyclomics’ patented method is platform-agnostic and can be deployed on both short-read (e.g., Illumina) and long-read (e.g., Oxford Nanopore) sequencing technologies.
Next Steps
Following the Dutch grant, Cyclomics is pursuing international patent protection to support global adoption of the technology. The company is also working with academic, clinical, and industrial partners to bring the method into routine diagnostic pipelines.
For more information on licensing, partnerships, or technical collaborations, please contact: info@cyclomics.com