Adapting Clinical Chemistry Plasma as a Source for Liquid Biopsies.

Area of Science:

• Molecular Diagnostics
• Genomics
• Biobanking

Background:

• Circulating cell-free DNA (cfDNA) is crucial for molecular testing but typically requires specialized collection or immediate processing.
• Heparin separators, common in clinical chemistry, represent an underutilized source for cfDNA analysis.

Purpose of the Study:

• To evaluate the feasibility of using residual plasma from heparin separators for cfDNA biobanking and testing.
• To assess the concordance of cfDNA analysis from heparin separator plasma with standard methods (EDTA, Streck tubes).

Main Methods:

• Matched plasma samples from healthy volunteers and a viral PCR-positive patient cohort were analyzed.
• Experiments included immediate processing comparisons and simulated clinical handling with delayed processing.
• Analyses involved whole-genome and methylation sequencing to assess cfDNA integrity, methylation patterns, fragmentomics, and viral detection.

Main Results:

• Heparin separator plasma demonstrated high concordance with EDTA and Streck plasma for methylation patterns and fragmentation features under immediate processing.
• cfDNA integrity in heparin separators was comparable to EDTA tubes when refrigerated during simulated clinical handling.
• Strong concordance was observed for viral detection, copy number alteration profiling, and methylation patterns in a clinical cohort.

Conclusions:

• Residual plasma from routine clinical chemistry tests, when processed promptly and refrigerated, is a valuable and untapped resource for cfDNA biobanking.
• This approach enhances accessibility for cfDNA testing and molecular diagnostics.
• The findings support the integration of heparin separator plasma into cfDNA biobanking strategies.