A novel TAPP-DHTA COF cathodic photoelectrochemical immunosensor based on CRISPR/Cas12a-induced nanozyme catalytic generation of heterojunction

The level of Interleukin-4 (IL-4, a classical anti-inflammatory cytokine) in cerebrospinal fluid is in response to brain injury, infection and neurodegenerative diseases. For early prevention and treatment of related diseases, sensitive and reliable monitoring of IL-4 is urgently needed. Herein, by employing 5,10,15,20-tetrakis(4-aminophenyl)porphyrin-2,5-dihydroxyterephthaldeyde COF (TAPP-DHTA COF) as an efficient photocathode and in situ generated-polyaniline (PANI) as the signal label, we establish an immuno-HCR assisted CRISPR/Cas12a-based bioassay platform for IL-4 determination. The TAPP-DHTA COF provides an outstanding cathodic photoelectrochemical (PEC) response, profiting from the unique structural feature and high light harvesting capability. The immuno-HCR-CRISPR/Cas12a system magnifies the target signal multiply, through initiation of the unique trans-cleavage function of CRISPR/Cas12a. During the trans-cleavage process, the nanozyme that consists of MoS2 [email protected] nanowires ([email protected]) is released and a PANI layer is in situ catalytically deposited onto the porphyrin COF, leading to significantly enhanced photocurrent. As a result, an ultralow detection limit of 0.32 fg mL−1 and wide linear range of 2 fg mL−1 to 0.2 μg mL−1 are obtained. This work exemplifies a high performance 2D porphyrin-COF cathodic PEC sensing platform with a promise of biomedical applications.