The growing need for reliable and rapid insulin testing to enhance glycemic management has spurred intensive exploration of new insulin-binding bioreceptors and innovative biosensing platforms for detecting this hormone, along with glucagon, in biological samples. Here, by leveraging the native protein receptors on the HepG2 cell membrane, we construct a simple and chemical-free biomimetic molecular recognition layer for the detection of insulin and glucagon. Unlike traditional affinity sensors, which require lengthy surface modifications on the electrochemical transducers and use of two different capture antibodies to recognize each analyte, this new biomimetic sensing strategy employs a simple drop-casting of a natural cell membrane recognition layer onto the electrochemical transducer. This approach allows for the concurrent capture and detection of both insulin and glucagon. We investigate the presence of insulin and glucagon receptors on the HepG2 cell membrane and demonstrate its multiplexing bioelectronic sensing capabilities through the binding of the captured insulin and glucagon to enzyme-tagged signaling antibodies. This new molecular recognition layer offers highly sensitive simultaneous detection of insulin and glucagon under decentralized conditions, holding considerable promise for the management of diabetes and the development of diverse biomimetic diagnostic platforms.
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