Model-Guided Interface Probe Arrangement for Sensitive Protein Detection

Abstract

A wide range of analytical techniques in bioanalysis relies on surface-based biomolecular detection, which requires the confinement of probes onto a heterogeneous surface to react with targets. Probe arrangement on the interface is critical for target recognition and determines assay performance. Much effort has been devoted to screen the optimized probe arrangement according to experimental tests. Such a data-driven posteriori pattern faces low efficiency, ambiguous orientation, and possible deviated tested ranges from the best case. Herein, we demonstrate that a model can effectively guide probe arrangement onto the interface to facilitate probe-target recognition, embodied by the assay of human telomerase activity with DNA-conjugated gold nanoparticles (AuNPs). Both theoretical calculation and experimental results indicate that telomerase activity is maximized on the AuNP surface under guidance of the model. The detection limit is at least 1 order of magnitude lower than that of AuNP bearing densely packed DNA, comparable to that of the telomeric repeat amplification protocol (TRAP). The model-guided interface probe arrangement is proved to be highly useful in regulating interface recognition and may offer a new paradigm to promote surface-based biomolecular detection.