Developing novel simple and ultrasensitive
strategies for detecting
microRNAs (miRNAs) is highly desirable because of their association
with early cancer diagnostic and prognostic processes. Here a new
chronocoulometric sensor, based on semiconducting 2H MoS2 nanosheets (MoS2 NSs) decorated with a controlled density
of monodispersed small gold nanoparticles (AuNPs@MoS2),
was fabricated via electrodeposition, for the highly sensitive detection
of miRNA-21. The size and interparticle spacing of AuNPs were optimized
by controlling nucleation and growth rates through the tuning of deposition
potential and Au precursor concentration and by getting simultaneous
feedback from morphological and electrochemical activity studies.
The sensing strategy, involved the selective immobilization of the
thiolated capture probe DNA (CP) at AuNPs and hybridization of CP
to a part of the miRNA target, whereas the remaining part of the target
was complementary to a signaling nonlabeled DNA sequence that served
to amplify the target upon hybridization. Chronocoulometry provided
precise quantification of nucleic acids at each step of the sensor
assay by interrogating [Ru(NH3)6]3+ electrostatically bound to phosphate backbones of oligonucleotides.
A detailed and systematic optimization study demonstrated that the
thinnest and smallest MoS2 NSs improved the sensitivity
of the AuNP@MoS2 sensor, achieving an impressive detection
limit of ≈100 aM, which is 2 orders of magnitude lower than
that of a bare Au electrode and also enhanced the DNA–miRNA
hybridization efficiency by 25%. Such an improved performance can
be attributed to the controlled packing density of CPs achieved by
their self-assembly on AuNPs, large interparticle density, small size,
and intimate coupling between AuNPs and MoS2. Alongside
the outstanding sensitivity, the sensor exhibited an excellent selectivity
down to femtomolar concentrations, for discriminating a complementary
miRNA-21 target in a complex system composed of different foreign
targets including mismatched and noncomplementary miRNA-155. These
advantages make our sensor a promising contender in the point of care
miRNA sensor family for medical diagnostics.