Multidimensional Interactive Cascading Nanochips for Detection of Multiple Liver Diseases via Precise Metabolite Profiling.

It is challenging to detect and differentiate multiple diseases with high complexity/similarity from the same organ. Metabolic analysis based on nanomatrix-assisted laser desorption/ionization mass spectrometry (NMALDI-MS) is a promising platform for disease diagnosis, while the enhanced property of its core nanomatrix materials has plenty of room for improvement. Herein, a multidimensional interactive cascade nanochip composed of iron oxide nanoparticles (FeNPs)/MXene/gold nanoparticles (AuNPs), IMG, is reported for serum metabolic profiling to achieve high-throughput detection of multiple liver diseases. MXene serves as a multi-binding site and an electron-hole source for ionization during NMALDI-MS analysis. Introduction of AuNPs with surface plasmon resonance (SPR) properties facilitates surface charge accumulation and rapid energy conversion. FeNPs are integrated into the MXene/Au nanocomposite to sharply reduce the thermal conductivity of the nanochip with negligible heat loss for strong thermally-driven desorption, and construct a multi-interaction proton transport pathway with MXene and AuNPs for strong ionization. Analysis of these enhanced serum fingerprint signals detected from the IMG nanochip through a neural network model results in differentiation of multiple liver diseases via a single pass and revelation of potential metabolic biomarkers. The promising method can rapidly and accurately screen various liver diseases, thus allowing timely treatment of liver diseases.