Quantifying ultralow
analyte concentrations is a continuing challenge
in the analytical sciences in general and in electrochemistry in particular.
Typical hurdles for affinity sensors at low concentrations include
achieving sufficiently efficient mass transport of the analyte, dealing
with slow reaction kinetics, and detecting a small transducer signal
against a background signal that itself fluctuates slowly in time.
Recent decades have seen the advent of methods capable of detecting
single analytes ranging from the nanoscale to individual molecules,
representing the ultimate mass sensitivity to these analytes. However,
single-entity detection does not automatically translate into a superior
concentration sensitivity. This is largely because electrochemical
transducers capable of such detection are themselves miniaturized,
exacerbating mass transport and binding kinetic limitations. In this
Perspective, we discuss how these challenges can be tackled through
so-called digital sensing: large arrays of separately addressable
single-entity detectors that provide real-time information on individual
binding events. We discuss the advantages of this approach and the
barriers to its implementation.