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Multichannel pipette tips aspirate reaction mixture for PCR DNA amplification in plastic wells.
More people have been turning to droplet digital PCR technology to quantify tumor DNA in liquid biopsies because of its unmatched precision, ultrahigh sensitivity, and streamlined workflow.
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Ultrasensitive MRD Assays for Rapid Turnaround Times

Liquid biopsies require a modern quantification approach to maximize sensitivity

Photo portrait of Jeremiah McDole
Jeremiah McDole, PhD
Photo portrait of Jeremiah McDole

Jeremiah McDole, PhD, is the marketing oncology segment manager at Bio-Rad Laboratories

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Published:Sep 27, 2023
|2 min read
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Photo portrait of Jeremiah McDole
Jeremiah McDole, PhD, is the oncology segment manager at Bio-Rad Laboratories. He received his PhD in neuroimmunology from the University of Cincinnati and spent his postdoctoral years on a number of successful research projects in the immunology department at Washington University School of Medicine in St. Louis.

Cancer remains a leading cause of death. Its incidence will continue to rise with increasing global life expectancy, adding pressure to already fragile healthcare systems. While scientific and medical advances have dramatically improved approaches to cancer treatment, recurrence remains a significant concern. Investigators need a highly sensitive method to detect the slightest trace of residual disease, which, if left undetected, could lead to a drug-resistant relapse.

Increased sensitivity enables earlier detection of circulating tumor DNA (ctDNA), increasing the likelihood of successful outcomes. In this article, we explain how ultrasensitive liquid biopsy methods allow teams of researchers to precisely detect trace levels of cancer mutations, potentially expanding therapeutic time frames, and ultimately enabling personalized treatment adjustments in the future. 

What are liquid biopsies?

Small populations of remnant cancer cells may escape curative treatments such as surgery, radiation, and/or chemotherapy. These cells can shed small amounts of ctDNA in the blood, enabling the measurement of molecular residual disease (MRD), which may expand into malignant relapse. 

Traditional monitoring methods such as imaging and tissue pathology have limited capacity to effectively detect changes in tumor status, including recurrence. Fortunately, liquid biopsies offer a solution for rapid, cost-effective, and minimally invasive serialized analyses. When paired with a highly sensitive platform for precisely detecting levels of mutation markers, this diagnostic method could one day provide critical information used to guide therapeutic steps when treating relapse.

Quantitative PCR (qPCR) has been used to identify mutation markers in blood samples. Though popular, this technique has critical drawbacks that limit its effectiveness for liquid biopsy analysis. The lower detection threshold of qPCR falls between 0.1–1.0 percent, which can miss clinically significant levels of MRD markers. Additionally, qPCR requires a standard curve for each run, which can lead to human error and batch variability.

A modern approach to MRD detection

In recent years, more people have been turning to droplet digital PCR (ddPCR) technology to quantify ctDNA in liquid biopsies because of its unmatched precision, ultrahigh sensitivity, and streamlined workflow. Unlike traditional qPCR, ddPCR assays partition samples into tens of thousands of discrete droplets, allowing individual PCR reactions to occur within each droplet. 

Upon detection of a nucleic acid target, the droplets produce a fluorescent signal for straightforward and absolute quantification that doesn't depend on a standard curve. This approach gives ddPCR assays precision that cannot be matched by other platforms, creating a critical tool for the advancement of MRD research. 

Enabling efficiency

Highly sensitive assays with rapid turnaround times allow researchers to detect drug-resistant markers within cancer samples quickly. MRD signals are subtle, and ddPCR technology provides the ultrasensitive detection researchers need to rapidly detect and analyze changes in ctDNA levels. Streamlined workflows with rapid analysis times in research labs have the potential to translate into enhanced decision-making in the clinic. 

With the growing incidence of cancer, demand for MRD analysis is expected to increase. It's imperative we systematically meet this need with an ultrasensitive platform to maximize data collection and shorten turnaround times while reducing costs. This provides the best chance to advance health care and improve the quality of lives in patients.