The lack of adequate circulating tumour DNA reference materials for developing and measuring safe, accurate, and reproducible assays continues to be a challenge for clinical labs.

Liquid biopsies are poised to revolutionise cancer diagnosis and therapy, but until now, advances in diagnostic technology, particularly at the low end of the sample input and sensitivity spectrum, have been hampered by the lack of ability of labs to reproducibly measure and assess the assay’s performance. There has been a dearth of sufficiently qualified reference materials to fully and properly develop, validate and monitor these liquid biopsy assays. As a result, many of the early adopters of these tests are the larger volume cancer centres with the patient volumes and resources to support and validate these innovative new assays. Even more labs, however, are interested in developing their own assays and leveraging the ability to potentially monitor recurrence and prognosis when the primary tumour is no longer available.

Competition between labs with different technologies and methods is resulting in many unsubstantiated performance claims with limited validation data made publically available for clinicians and patients to review.  Even more challenging for the industry is reconciling inter-laboratory performance standards, an area that is begging for better options.  If labs continue developing their own unique assays and methods, then one of the obvious solutions is the use of a universal standard or reference material calibrator to properly measure and assess performance similarities and differences.


Three types of fragmented DNA: random ultrasonicated (green), native cfDNA (orange), and the Seraseq ctDNA Mutation Mix v2 AF 0.5 (blue). Samples were characterised by the Agilent 2100 Bioanalyzer®.

In order to overcome these challenges, SeraCare has developed a unique patent-pending technology that produces a DNA fragment size-distribution which closely mimics native cfDNA, while decreasing DNA damage relative to ultrasonicated material. The result is a renewable source of highly characterised material that exhibits similar performance when treated identically to a patient sample. Unlike ultrasonicated materials, for which increased DNA input amount or sequencing depth must be used to obtain similar performance, the Seraseq ctDNA v2 requires no special workflow considerations to generate informative data. This is especially important for validation studies that require strict adherence to standard operating procedures.

Learn more about SeraCare liquid biopsy standards here or find data and in-depth technical information by reading this technical report.

These innovative new products are the most ‘patient-like’ ctDNA reference materials available to date, and are produced in scale and quality for labs to assess and monitor their performance over long periods as well as enabling large multi-site comparisons of performance and proficiency. Available as purified cell-free DNA mixes or as cell-free DNA stabilised in a human plasma-like matrix, they offer those looking to evaluate their entire workflow an appropriate tool. Being produced in an ISO 13485-certified facility, these biosynthetics can be manufactured to precise allelic frequencies spanning the range of needed detection levels from 2% down to 0.125% mutant allele frequencies.

“One of the biggest challenges in developing highly sensitive ctDNA assays is the lack of reference materials that perform like real-world samples and contain all of the relevant variants. Seraseq ctDNA reference materials resemble native cfDNA, from pre-analytic assessment of DNA quality through sequencing. We expect these new references will greatly facilitate our assay development, and they also potentially will help our customers execute an effective QC strategy,” said Dr. Jason Myers, CEO at ArcherDX. “Our longstanding relationship with SeraCare continues to result in products that fit previously unmet needs for next-generation liquid biopsy analysis.”

“As an industry leader for clinical genomics reference materials, we have spent significant time with subject experts to thoroughly understand the challenges ctDNA technologies face, and what is needed to effectively accelerate assay development and adoption in the clinic,” said Russell Garlick, PhD, Chief Scientific Officer at SeraCare. “In response, we have developed a groundbreaking technology to produce highly functional, ctDNA-like materials, or truth sets, that will enable the industry to develop, optimise, and implement more accurate and robust assays. Our innovative Seraseq ctDNA reference materials can finally provide the assurances in variant composition and performance that labs are looking for, which have so far been elusive using existing methodologies and materials.”

Learn more about SeraCare liquid biopsy standards here or find data and in-depth technical information by reading this technical report.