Outer-surface functionalized solid-state nanochannels have emerged as a new powerful tool for label-free and sensitive detection of biotargets, owing to the unique advantages, such as the target's size is not limited by the nanochannel size, probes on the outer surface are easier to modify and characterize. Despite the advancements, the current outer-surface functionalized nanochannels can only achieve single target detection, which is insufficient for understanding disease pathogenesis and clinical diagnosis. Herein, we develop an ordered mesoporous carbon-silicon/anodic aluminum oxide hybrid membrane (MCS/AAO) with outer surface probes for in situ detecting living cells released secretions with a wide size ra... More
Outer-surface functionalized solid-state nanochannels have emerged as a new powerful tool for label-free and sensitive detection of biotargets, owing to the unique advantages, such as the target's size is not limited by the nanochannel size, probes on the outer surface are easier to modify and characterize. Despite the advancements, the current outer-surface functionalized nanochannels can only achieve single target detection, which is insufficient for understanding disease pathogenesis and clinical diagnosis. Herein, we develop an ordered mesoporous carbon-silicon/anodic aluminum oxide hybrid membrane (MCS/AAO) with outer surface probes for in situ detecting living cells released secretions with a wide size range (from nano-scale to micron-scale). Due to asymmetric nanochannel structure and charge distribution, the hybrid membrane exhibits cation selectivity and a high ionic current rectification value of 29.21. By taking advantage of this mechanism, different cell secretions can be selectively and sensitively detected through replacing the modified aptamers on the outer surface of hybrid membrane. ATP (adenosine triphosphate), VEGF (vascular endothelial growth factor), and HepG2-MVs (micro vesicles) are chosen as model secretions representing different sizes. The detection limits are 0.64 fmol/L for ATP, 3.31 fg/mL for VEGF, and 5.37 × 104 particles/mL for HepG2-MVs, which was over 10-fold higher than that of commercial assay kits. In addition, the prepared hybrid membrane has exceptional mechanical stability, the detection interface could be regenerated at least 5 times. This work provides a promising platform for in situ detection of cell secretions with different types and sizes by one sensing device and facilitates the clinical diagnosis of secretion-related diseases.
