A universal stimuli-responsive biosensor for disease biomarkers through their cysteine residues: A proof of concept on carcinoembryonic antigen (CEA) biomarker
Mahnaz D. Gholami, Serena Nihal, Qian Liu, Daniel K. Sarfo, Prashant Sonar, Emad L. Izake
Abstract
Carcinoembryonic antigen (CEA) is the gold standard biomarker for the clinical diagnosis of cancers diseases. Accurate, fast, and sensitive screening of CEA plays an important role in cancer disease detection and prognosis. This work reports the development of a new stimuli-responsive biosensor that determines the CEA blood plasma concentration within 10 min. Tert-butyl carbonate Naphthalene-flanked diketopyrroloprrole (mono-TBC-DPPN) fluorescent agent was synthesised, characterised and immobilised gold nanoparticles to develop the stimuli-responsive sensor. The target protein was purified from spiked plasma (from human blood), using an antibody-coated gold substrate. The purified CEA was then chemically modified to provide thiol groups (SH) that interact with the mono-TBC-DPPN on the surface of the stimuli-responsive biosensor to spontaneously displace it, thus leading to its fluorescence emission at 532 nm to a turn on. The new method and sensor was implemented to quantify CEA in spiked blood plasma down to 10 pg.mL-1 within 45 min (35 min for the protein purification and modification and 10 min for its quantification using the sensor)