  Graphene-based sensors are exceptionally sensitive with high carrier mobility
and low intrinsic noise, and have been intensively investigated in the past
decade. The detection of individual gas molecules has been reported, albeit the
underlying sensing mechanism is not yet well understood. We focus on the
adsorption of NO$_2$, H$_2$O, and NH$_3$ on a molecular junction with a pyrene
core, which can be considered as a minimal graphene-like unit. We
systematically investigate the chemiresistive response within the framework of
density functional theory and non-equilibrium Green's functions. We highlight
the fundamental role of quantum interference (QI) in the sensing process, and
we propose it as a paradigmatic mechanism for sensing. Owing to the open-shell
character of NO$_2$, its interaction with pyrene gives rise to a Fano resonance
thereby triggering the strongest chemiresistive response, while the weaker
interactions with H$_2$O and NH$_3$ result in lower sensitivity. We demonstrate
that by exploiting destructive QI arising in the meta-substituted pyrene, it is
possible to calibrate the sensor to enhance both its sensitivity and chemical
selectivity by almost two orders of magnitude so that individual molecules can
be detected and distinguished. These results provide a fundamental strategy to
design high-performance chemical sensors with graphene functional blocks.
