The translational oncology landscape has changed dramatically in the past two decades, and with it, the demands on the laboratories doing this work. Today’s translational oncology workflows require DNA and RNA from the same FFPE tissue section, cell-free DNA from large plasma volumes, and nucleic acids from heterogeneous batches of sample types processed in a single run. The analyte diversity has increased dramatically, and at the same time, the downstream assays interrogating those samples have grown more sensitive. The operational pressures have grown alongside the scientific ones. Labs are processing more samples than ever, but not with proportionally more staff. Same-day extraction to analysis is increasingly the expectation, not the exception. All of that change and complexity lands at the extraction step first.
Extraction has long been treated as the step before the experiment, the part you complete before the real work begins. However, as these pressures on the translational laboratory grow, overlooking potential issues with extraction could be disastrous, particularly for labs working with limited, irreplaceable samples, because pre-analytical variability at the extraction step propagates through every downstream process. When extraction is overlooked, information in a sample can be lost and with it the insight into the biological question your downstream assay is asking.
Yield and Purity: Necessary but Not Sufficient
Determining the yield and purity of isolated DNA and RNA is critical to ensure usable material for downstream analysis. DNA yield can be assessed using absorbance/optical density, agarose gel electrophoresis, fluorescent DNA binding dyes and qPCR. The choice of method will depend on factors such as the nature of the DNA target and requirements around sensitivity and specificity of downstream applications. Likewise, there are several methods for determining RNA purity and yield including UV absorbance, fluorescent RNA binding dyes, agarose gel electrophoresis and microfluidic analysis, and RT-qPCR.
Learn More: This article has details for Determining the Concentration, Yield and Purity of a DNA Sample. Our RNA Purification Guide has valuable information for assessing the purity and yield of your RNA extraction.
While yield and absorbance measurements are important, they don’t tell you the entire story about your extracted nucleic acids. With samples like FFPE tissue, liquid biopsies and fine needle aspirates, fragmentation, co-purified inhibitors and sample variability are the rule, not the exception. For NGS and other sequencing applications, degraded or contaminated input can compress variant allele frequencies, create noise or even cause library prep failure. For PCR or qPCR assays, inhibitors can interfere with enzyme activity. For workflows that are medium- to high-throughput, you need consistency and reproducibility. So not only do you need to know about yield, but you also need to know if the nucleic acid is degraded or if inhibitors from your sample are present after extraction.
Match Chemistry to Sample. Recover More Biology
FFPE tissue, high molecular weight (HMW) DNA, cell-free DNA (cfDNA), and liquid biopsies don’t just present yield challenges. Each carries specific ways extraction can quietly fail. Because DNA and RNA are isolated from a complex matrix containing lipids, carbohydrates, proteins and other compounds, matching the sample type to the nucleic acid extraction chemistry is key (1). Get that match right, and you recover more of the story the sample can tell.
HMW DNA requires large, intact genomic fragments—the foundation of long-read sequencing techniques that are increasingly important in oncology research. Integrity is crucial for downstream success, and semi-solid magnetic phases are enabling gentler handling, reduced shearing and compatibility with high-throughput automation (2, 3). Push a sample like this through chemistry designed for a different matrix, and you may recover acceptable yield numbers while silently degrading the very fragments you need.
FFPE samples present a different challenge. Archival FFPE tissue is one of the most valuable and most demanding sample types in oncology—often irreplaceable, frequently degraded by fixation, and prone to cross-linking that inhibits downstream enzymatic reactions. Extraction chemistry optimized for FFPE addresses these failure modes specifically: decrosslinking, removing inhibitors and preserving the fragmented DNA that’s actually there (4). Standard chemistry applied to FFPE tissue may pass QC and still leave the downstream assay working with compromised input.
Liquid biopsies and cfDNA add another layer of complexity. These samples are low-input by nature—circulating tumor DNA can represent a vanishingly small fraction of the total cell-free DNA in a blood draw. Extraction chemistry that isn’t tuned for low-abundance, short-fragment input will lose signal that can’t be recovered downstream. In oncology workflows where early detection or monitoring of treatment response depends on detecting rare variants, that loss is not recoverable.
The portfolio of scalable, application-matched nucleic acid purification chemistries offered by Promega is designed for precisely these problems. Whether you are working with FFPE tissue, HMW genomic DNA, cfDNA, or liquid biopsy, each Promega chemistry delivers consistent extraction optimized for that sample type. Laboratories processing a few samples manually, or labs scaling to benchtop automation with the Maxwell® platform, and those labs running 96 or more samples on open liquid handling platforms with Maxwell® HT chemistries can all rely on the same extraction quality. Regardless of scale, Promega chemistries provide the extraction output you can trust going into your downstream analysis.
What Rigorous Evaluation Actually Looks Like
Moving beyond 260/280 ratios doesn’t require rebuilding your workflow. It requires asking a more specific question before the experiment starts: is this input fit for this application?
For DNA, that means pairing yield measurements with fragment length analysis and, where relevant, inhibitor-specific assays. For RNA, it means evaluating integrity numbers (RIN or DV200 for FFPE) alongside concentration. For liquid biopsy inputs, it means quantification methods sensitive enough to detect the low concentrations that standard methods may miss entirely. For cfDNA, where genomic DNA would be considered a contaminant, the method used should be specific for cfDNA.
It also means selecting extraction tools designed for the sample type in front of you. Automated extraction platforms, like the Maxwell instruments and chemistries and the Maxwell® HT chemistries that are purpose-built for challenging oncology sample types provide the consistency that medium- to high-throughput workflows require. When your extraction is matched to your sample and your application, confidence in a result traces all the way back to step one.
In oncology research, where samples are often scarce and results inform decisions that extend beyond the lab, extraction isn’t the step before the experiment. It’s an integral part of the experiment. Treating it that way with chemistry matched to sample type, QC matched to the downstream application, and tools designed for the biology you’re actually working with is how you ensure that what you see in your data reflects what was actually in your sample.
Learn More: Explore our DNA Purification Guide and RNA Purification Guide for comprehensive guidance on extraction methods, QC, and application-matched chemistry.
References
1. Tan SC and Yiap BC. (2009) DNA, RNA, and Protein Extraction: The Past and The Present. J Biomed Biotechnol. 2009:574398.
2. Promega Corporation. DNA Purification | DNA Extraction Methods. promega.com/resources/guides/nucleic-acid-analysis/dna-purification/
3. Atha, B. (2025) Improving Yield and Quality in Nucleic Acid Extraction. Biocompare. October 9. Accessed May 29, 2026.
4. Mayer, K. et al. (2024) Methods and Compositions for Decrosslinking Biological Samples (US- 20240369459) U.S. Patent and Trademark Office. Accessed May 29, 2026.
This post created with the assistance of AI and edited by humans.
