Minimally Invasive Sampling for Molecular Profiling of Lymph Nodes Using a Modified Acupuncture Needle

ABSTRACT Current clinical liquid biopsy approaches predominantly rely on blood‐derived biomarkers, which are often limited in sensitivity. A paradigm shift toward lymphatic system‐based biomarker analysis could offer an alternative means of addressing these challenges. This proposition is supported by a key scientific insight: the Revised Starling Principle demonstrates that lymphatic vessels, rather than veins, absorb most interstitial fluid, which contains abundant biomarkers, in the majority of tissues. Collectively, these findings indicate that lymphatic‐derived biomarkers may offer distinct advantages for the molecular assessment of lymph node metastasis risk. However, accessing biomarkers from the lymphatic system remains technically challenging owing to the lack of minimally invasive sampling techniques. In this small‐cohort proof‐of‐concept study, we developed a minimally invasive platform (His@PDA@Needle) for the collection and molecular profiling of DNA biomarkers from lymph nodes. The performance of this platform was preliminarily validated in mouse footpad xenograft models, as well as in lymph node samples derived from patients with head and neck cancer. Compared with conventional lymph node biopsy, this DNA sampling approach is less invasive; however, it is intended as a molecular profiling tool to complement existing histopathological evaluation, rather than a tool for direct clinical diagnosis.