High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing

Area of Science:

• Biotechnology
• Genomics
• Molecular Biology

Background:

• Current DNA sizing methods lack resolution for fragments under 200 bp.
• This limitation hinders non-invasive prenatal testing (NIPT) by failing to differentiate fetal and maternal DNA (143 bp vs. 166 bp peaks).
• Existing NIPT workflows face sample rejection and reduced clinical utility due to this sizing gap.

Purpose of the Study:

• To develop a high-resolution DNA size enrichment workflow for fragments under 200 bp.
• To exploit the size difference between fetal and maternal cell-free DNA for improved NIPT.
• To enhance the fetal fraction in maternal plasma for more accurate NIPT.

Main Methods:

• Developed MiniEnrich, an automatable magnetic nano-platform workflow.
• Utilized two types of magnetic nanoparticles for high-resolution DNA filtering and recovery.
• Applied the method to enrich fetal DNA fragments from maternal plasma.

Main Results:

• Achieved high-resolution DNA size enrichment for fragments under 200 bp.
• Increased the average fetal fraction from 13% to 20% post-enrichment, as measured by plasma DNA sequencing.
• Demonstrated the workflow's ability to exploit the 20 bp size difference between fetal and maternal DNA.

Conclusions:

• MiniEnrich offers a novel tool for precise DNA size enrichment below 200 bp.
• This technology has the potential to improve NIPT accuracy, rescue rejected samples, and enable earlier NIPT.
• The workflow may also advance screening for fetal monogenic disorders, liquid biopsy analysis, and autoimmune disease diagnosis.