LIQUID BIOPSY
kits (research use only [RUO]) represent a significant advancement in this field, enabling efficient extraction of cfDNA from fresh/frozen plasma (derived from various blood collection tubes, including EDTA and BCT Streck tubes), exosomes, serum and even cerebrospinal fluid and cell culture supernatant. Available in both manual and automated formats, these kits use proprietary M-PVA Magnetic Bead technology to specifically and efficiently enrich nucleic acids from complex matrices, allowing for easy scale up to higher throughputs when needed.5 The chemagic 360 instrument (RUO),
coupled with these specialised kits, has revolutionised cfDNA extraction workflows in research setings. This automated system uses established chemagic separation technology to isolate cfDNA from sample volumes ranging up to 18 mL. The gentle rotating rod resuspension avoids shearing stress seen with silica columns or pipeting, preventing cfDNA fragmentation and obtaining more intact nucleic acids for detailed downstream analysis. The process takes only 90–120 minutes with a hands-on time of 10–15 minutes, significantly reducing processing time compared to traditional methods.5 At the Zealand University Hospital, the chemagic 360 instrument has helped reduce turnaround time from sample to result down to just 24 h in the areas of colorectal and anal cancer.6 A key advantage of the chemagic
cfDNA purification workflow is its consistency, efficiency, and suitability for scaling up. The automated process reduces cross-contamination risks, and movement of beads across separate reaction vessels avoids the carryover of inhibitors – critical considerations for large-scale research studies. The ability to accommodate large volumes and the lack of bias towards short and long cfDNA, as well as single or double- stranded cfDNA, also makes it amenable to answer varying research questions. Comparative studies have demonstrated that the chemagic cfDNA kits provide equivalent yields and purities to manual silica-based methods, while offering the significant advantages of automation, scalability, and reproducibility.5
Ravvity’s chemagic 360 instrument is a flexible compact solution for automated nucleic acid extraction from diverse sample materials.
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WWW.PATHOLOGYINPRACTICE.COM February 2026
Advanced detection technologies for research
The evolution of cfDNA analysis technologies has enabled increasingly sophisticated research applications: Digital PCR (dPCR): This technology partitions a sample into thousands of individual reactions, enabling absolute quantification of rare variants with sensitivity approaching 0.01%.1
While
limited to detecting known mutations, dPCR offers rapid turnaround time and relatively low cost, making it suitable for targeted research questions. Next-generation sequencing (NGS): Targeted sequencing panels covering dozens to hundreds of cancer-related genes have become the workhorse of cfDNA research. These panels typically achieve sensitivities of 0.1–0.5% variant allele frequency.2
For discovery
research, whole-exome and whole- genome sequencing of cfDNA provide comprehensive views of the cancer genome, albeit with lower sensitivity for rare variants. Error-suppression methods: Innovative molecular approaches like unique molecular identifiers (UMIs), duplex sequencing, and integrated digital error suppression have dramatically improved detection limits for research applications.3
By tagging individual
DNA molecules and creating consensus sequences from multiple reads of the same molecule, these methods can reduce error rates by several orders of magnitude, enabling detection of variants at 0.001–0.01% frequency.
The quality of input cfDNA is paramount for these advanced detection methods. The chemagic cfDNA extraction workflow produces high-quality cfDNA that is immediately compatible with downstream
The preservation of epigenetic marks in cfDNA requires careful extraction methods that maintain the integrity of these modifications. The chemagic cfDNA extraction technology is compatible with downstream epigenetic analyses, enabling that valuable methylation paterns and fragmentation signatures are preserved during the purification process for research applications.
Future directions in liquid biopsy research The future of liquid biopsy research lies in integrating multiple analytes and data types to create comprehensive profiles of cancer biology. Combined analysis of ctDNA, CTCs, exosomes, and circulating proteins can provide complementary information about tumour genetics, transcriptomics, proteomics, and metabolomics.2 This multi-omics approach is particularly powerful for
understanding complex phenomena like metastasis, where different circulating biomarkers may reflect different aspects of the process. For example, CTCs can reveal the phenotypic characteristics of cells capable of entering circulation, while ctDNA can identify genetic drivers of metastatic potential.
applications including NGS and digital PCR, ensuring optimal performance of these sensitive analytical techniques in research setings.5,6
Epigenetic analysis of cfDNA in cancer research
Beyond sequence alterations, epigenetic modifications in cfDNA have emerged as powerful research tools with unique advantages: Methylation paterns: Cancer-specific DNA methylation paterns occur early in carcinogenesis and affect larger genomic regions than point mutations, providing amplified signals for detection.4
Methylation analysis
of cfDNA has opened new avenues for understanding the epigenetic landscape of tumours and how it changes during progression and treatment. Nucleosome positioning: The fragmentation paterns of cfDNA reflect nucleosome positioning in the cells of origin, which differs between tissue types and between normal and cancer cells.4
insights into chromatin structure and gene regulation in tumours that cannot be easily obtained from conventional tissue samples.
This information provides
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