Ultrasensitive DNA‐Biomacromolecule Sensor for the Detection Application of Clinical Cancer Samples

Abstract Diagnostic testing of biological macromolecules is of great significance for early warning of disease and cancer. Nevertheless, restricted by limited surface area and large steric hindrance, sensitive detection of macromolecules with interface‐based sensing method remains challenging. Here, a “biphasic replacement” electrochemical aptamer‐based (BRE‐AB) sensing strategy which placed capture reaction of the biomacromolecule in a homogeneous solution phase and replaced with a small diameter of single‐stranded DNA to attach to the interface is introduced. Using the BRE‐AB sensor, the ultrasensitive detection of luteinizing hormone (LH) with the detection limit of 10 × 10 −12 m is demonstrated. Molecular Dynamics simulations are utilized to explore the binding mechanism of aptamer and target LH. Moreover, it is confirmed that the BRE‐AB sensor has excellent sensing performance in whole blood and undiluted plasma. Using the BRE‐AB sensor, the LH concentrations in 40 clinical samples are successfully quantified and it is found that LH is higher expressed in breast cancer patients. Furthermore, the sensor enables simple, low‐cost, and easy to regenerate and reuse, indicating potentially applicable for point‐of‐care biological macromolecules diagnostics.