In E-AB sensors, the signal between electrochemical response and absence of target is small. The aptamer can be reengineered to a large-scale, conformational change. Long flexible loops or complementary strands can also force a change in the aptamers conformation. These techniques to modify aptamers increase the signal ratio, but does not guarantee that it is sufficient enough to be measured.
E-AB sensors are only as sensitive as the aptamer deployed. The selectivity of the aptamer can be a concern when there are similar compounds in the blood or other bodily fluids. cross-reactivity causes interference in in-vivo monitoring and requires understanding of how the aptamer reacts with similar compounds that may be in the sample.