Thermally Engineered Ferric Yolk‐Shells for Vaginal Secretion Based Cervical Cancer Screening

Abstract Engineering of materials is crucial for the advanced detection of bio‐molecules, particularly in laser desorption/ionization mass spectrometry (LDI‐MS). However, effective screening with enhanced LDI performance remains challenging due to the lack of engineered substrate materials. Herein, thermally engineered ferric yolk‐shells are designed for enhanced metabolic screening of cervical cancer (CC) using vaginal secretion. A facile thermal engineering strategy is developed to prepare amorphous ferric yolk‐shells with integrated properties. Notably, the amorphous mesoporous yolk‐shells offer signal amplification up to orders of magnitude in LDI‐MS for standard metabolites and diverse bio‐samples. High‐performance CC screening (including identification of human papillomavirus (HPV) infection, high‐grade squamous intraepithelial lesion (HSIL), and CC) is achieved, with the areas under the curve of 0.842–0.963. Finally, a metabolic panel for CC screening, covering the stages of HPV, HSIL, and CC, is established. This work elucidates the LDI‐MS mechanism for enhanced metabolic detection and highlights potential applications in cancer screening.