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Few sensing platforms have become ubiquitous to enable rapid and convenient measurements at the point‐of‐care. Those, however, are "one‐off" technologies, meaning that they can only detect a single target and are hardly adaptable. In response, we plan to develop a sensing platform that can be extended to detect other classes of molecules and that affords rapid, convenient, continuous measurements directly in undiluted complex matrices. For this, we decided to rely on a host molecule that presents reversible interactions toward specific guest molecules to develop a new class of sensors that we coined "Electrochemical DNA‐host chimeras". As a proof‐of‐concept for our sensor, we decided to use cyclobis(paraquat‐p‐phenylene) ("blue box") that we attached on an electrode‐bound DNA to allow measurements of electron‐rich guests such as dopamine and aspirin. Doing so allows to promote host‐guest complex that could be quantified using blue box's electrochemistry. Because of this unique sensor architecture, we achieve, to our knowledge, the first reagentless, continuous and rapid (<5 min) host‐guest measurements in undiluted whole blood. We envision that given the library of electroactive host molecules that this will allow the development of a sensing platform for measurements of several classes of molecules in complex matrices at the point‐of‐care. [ABSTRACT FROM AUTHOR]