Protein Scaffold DNA-Cu²⁺ Functional Nanostructure Enable Rapid One-Pot Visual Portable Adaptable Aptasensing

Hybrid DNA nanomaterials promise the development of powerful sensing elements for transformative applications in biosensing. In this study, we proposed a strategy entitled "I@I@X", where protein scaffold DNA-Cu²⁺ functional nanospheres as sensing modules were synthesized in one step at room temperature, one-pot reactions of target biomarkers were realized, and various signal probes and output modes, including smartphone red, green, and blue, facilitated versatile detection. This sensing module consisted of aptamers, streptavidin-biotinylated DNA tetramers, and Cu²⁺, which fulfilled the multifunctional integration of healthcare biomarker recognition, signal amplification, and transduction within 45 + X min (X = different times according to distinct signal probes, ranging from 1 to 5 min). Insulin-like growth factor 1 (sarcopenia), cortisol (Cushing syndrome), circulating tumor cells, and tumor-derived exosomes (lung cancer) were selected as representatives to verify the efficiency of this strategy. Furthermore, the clinical practicability of this strategy was demonstrated in 137 plasma samples, achieving overall good consistency with clinical diagnosis indicators. This study provides subtle insight into straightforward and adaptable detection methods in precise laboratory medicine.