Metal‐Organic Framework‐Enabled Protection of Plasma DNA for Long‐Term Storage and Rare Mutation Detection

ABSTRACT

Plasma DNA analysis remains a pivotal noninvasive approach for cancer diagnosis; however, the low abundance and rapid degradation of circulating tumor DNA (ctDNA) present significant challenges for sample preservation and transport. Existing stabilization methods often fail to maintain DNA integrity at room temperature and may interfere with high‐sensitivity downstream assays. Here, we develop a ZIF‐67‐based metal‐organic framework (MOF) strategy that robustly protects ctDNA from ultraviolet irradiation, enzymatic cleavage, and oxidative stress. Both simulations and experimental results confirm that synergistic electrostatic interactions and π – π stacking effectively preserve more than 85% of DNA integrity after four weeks of storage at room temperature. Crucially, this platform is fully compatible with blocker displacement amplification (BDA), enabling reliable detection of rare mutations at variant allele frequencies (VAFs) as low as 0.37%. Validated with clinical colorectal cancer samples, our approach provides a scalable, material‐based solution that eliminates the need for cold‐chain logistics. This strategy not only guarantees diagnostic fidelity but also establishes a versatile framework to advance precision oncology across diverse clinical settings.