a great technology with practical challenges
- Blood-based diagnostics can improve oncology and prenatal screening
- Sample logistics problems reduce method sensitivity
- 61% of studies call for improved sample processing*
Liquid biopsy (LB) diagnostics can improve cancer treatment monitoring and personalization. There are currently pre-analytical challenges, which include 1) the need for skilled personnel to perform sample preparation, and 2) strict logistic requirements for sample transportation, often overseas. In the current LB workflows, plasma separation includes two critical centrifugation steps either at the sample collection site or in the clinical laboratory.
If the sample is prepared on-site, a dry-ice shipment is required. Alternatively, transportation of the sample as blood is complicated by the need for fast and temperature-controlled shipment, as the release of nucleic acids from white blood cells would destroy the LB sample.
Overall, manual preparation of plasma leaves the current process vulnerable to human errors and therefore an automated, standardized technology for plasma separation, DNA extraction, and quantitation is required.
cfDNA
Cell-free DNA (cfDNA) allows non-invasive analysis of cancer-causing genetic mutations. The low amount of cfDNA circulating in the blood of a healthy person originates from apoptotic blood cells. However, in case of cancer, tumour tissue is shedding short circulating tumour DNA (ctDNA) fragments, dependent on the tumour location and volume.
In our experience with ctDNA, mutated cancer DNA varies between 0.1-60% of the cfDNA of cancer patients. Measuring the amount and genetic/epigenetic changes in the ctDNA is a potential tool for determining the origin and the burden of cancer and capturing new mutations appearing during targeted therapies. So far, the access to this rich genetic and epigenetic information available in ctDNA has been prone to errors due to variable amounts and quality of the input material for analysis. The variation in sample quality can result from interfering genomic DNA, which is thousand times more frequent than cfDNA in the blood.
*[1] https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e14529 [2] An internal review of 150 liquid biopsy studies, 2023