The key building block used is a cyclooctyne tailed with a disulfide ring (2) (Scheme S1). Disulfide 2 was coated to bare AuNPs by the thiol-gold bonding interaction, forming an alkynyl shell on the surface. Then, the core−shell structure was directly subjected to a copper-free click reaction28 with mannosyl azide 1. After centrifuging, the resulting mannose-coated AuNP (Man-AuNP) was used as is for the agglutination with a lectin, owing to the fact that no particular catalyst or byproduct existed in the system. Next, we used the mannose-selective, dimeric LcA (Lens culinaris lectin)29 for agglutination of Man-AuNP. We observed a gradual bathochromic shift accompanied by peak broadening of the Man-AuNP upon the addition of increasing LcA in the UV−vis spectrum (Figure 2a). This is in agreement with the typical aggregation behavior of the AuNPs.20−25