Electrochemical DNA‐Based Biosensors for In Vivo Quantification of a Therapeutic Protein

Inter-subject pharmacokinetic variability limits the clinical effectiveness of many “biologics”, including monoclonal antibody drugs. This issue can be addressed through therapeutic drug monitoring (TDM), in which clinicians tailor dosing to individual patients based on measured plasma drug concentrations. In practice, TDM is inconvenient because current methods for quantifying protein drugs in blood are labor-intensive and expensive. In response, here we present an electrochemical DNA-based biosensor that addresses this issue by enabling rapid, reagentless measurement of plasma concentrations of the antibody drug trastuzumab. The approach supports real-time, in vivo monitoring in living animals (rats). Specifically, we have systematically compared two distinct sensing architectures, a DNA scaffold sensor and an electrochemical aptamer-based sensor, before developing an optimized sensor in the latter class that, when challenged in undiluted whole blood, can measure over the entire clinical range of the drug. When implanted in animals, the sensor successfully tracks in vivo drug concentrations and clearly visualizes differences in drug exposure between individual rats following intravenous infusion. Given the ability to generalize EAB sensors to almost any target of interest, this work illustrates a powerful new tool to guide real-time dosing of biologic therapeutics, enabling personalized treatments of this increasingly important class of drugs.