A Drug Molecule-Modified Graphene Field-Effect Transistor Nanosensor for Rapid, Label-Free, and Ultrasensitive Detection of Estrogen Receptor α Protein

Estrogen receptor alpha (ER alpha) is an important biomarker in breast cancer diagnosis and treatment. Sensitive and accurate detection of ER alpha protein expression is crucial in guiding selection of an appropriate therapeutic strategy to improve the effectiveness and prognosis of breast cancer treatment. Herein, we report a liquid-gated graphene field-effect transistor (FET) biosensor that enables rapid, sensitive, and label-free detection of the ER alpha protein by employing a novel drug molecule as a capture probe. The drug molecule was synthesized and subsequently immobilized onto the sensing surface of the fabricated graphene FET, which was able to distinguish the ER alpha-positive from the ER alpha-negative protein. The developed sensor not only demonstrated a low detection limit (LOD: 2.62 fM) but also achieved a fast response to ER alpha protein samples within 30 min. Moreover, depending on the relationship between the change of dirac point and the ER alpha protein concentrations, the dissociation constant (K-d) was estimated to be 7.35 +/- 0.06 pM, indicating that the drug probe-modified graphene FET had a good affinity with ER alpha protein. The nanosensor was able to analyze ER alpha proteins from 36 cell samples lysates. These results show that the graphene FET sensor was able to differentiate between ER alpha-positive and ER alpha-negative cells, indicating a promising biosensor for the ultrasensitive and rapid detection of ER alpha protein without antibody labeling.