  Clinical biosensors with low detection limit hold significant promise in the
early diagnosis of debilitating diseases. Recent progress in sensor development
has led to the demonstration of detection capable of detecting target molecules
even down to single-molecule level. One crucial performance parameter which is
not adequately discussed is the issue of measurement fidelity in such sensors.
We define measurement fidelity based on the false positive rate of the system
as we expect systems with higher sensitivity to concomitantly respond more to
interfering molecules thus increasing the false-positive rates. We present a
model which allows us to estimate the limit of detection of a biosensor system
constrained by a specified false-positive rate. Two major results emerging from
our model is that a) there is a lower bound to the detection limit for a target
molecule determined by the variation in the concentration of background
molecules interfering with the molecular recognition process and b) systems
which use a secondary label, such as a fluorophore, can achieve lower detection
limits for a given false positive rate. We also present data collected from
literature to support our model. The insights from our model will be useful in
the systematic design of future clinical biosensors to achieve relevant
detection limits with assured fidelity.
