Engineering Artificial Molecular Recognition for Multidimensional Chemical Information Transfer

Abstract

Modern chemical and biological systems demand sensing platforms capable of recognizing diverse analytes with high stability, tunability, and real time responsiveness, capabilities that conventional biological receptors often fail to provide due to limited operating windows, structural fragility, and narrow design spaces. Corona phase molecular recognition (CoPhMoRe) offers a synthetic alternative, in which polymeric ligands adsorb onto single walled carbon nanotubes (SWCNTs) to form adaptive three dimensional recognition pockets without the need for traditional lock-and-key binding motifs. These corona structures function as artificial molecular interfaces that transduce chemical interactions through the exceptionally stable and tissue penetrative near infrared fluorescence of SWCNTs. In this work, we establish a design-driven framework for constructing, screening, and optimizing corona phases for broad chemical recognition. By integrating high throughput nanosensor fabrication with automated optical screening, molecular dynamics simulations, and docking based interaction analysis, we map design rules across a vast and continuously expandable library of corona structures. This combined experimental–computational strategy accelerates the discovery of selective and robust artificial receptors tailored to chemically diverse targets. These advances have produced nanosensor constructs capable of detecting biomarkers for early diagnosis, resolving molecular efflux signatures from single cells in a label free manner for the precision therapy, and enabling online chemical monitoring in complex industrial and biological reactors. CoPhMoRe thereby supports multidimensional chemical information transfer by embedding specificity, stability, and scalability into a single sensing architecture. Collectively, these results demonstrate how corona phase engineering can create a new class of programmable molecular recognition interfaces, offering a universal and durable sensing paradigm that extends far beyond the constraints of conventional diagnostic and analytical technologies.