Rapid Recognition and Monitoring of Multiple Core Biomarkers with Point-of-Care Importance through Combinatorial DNA Logic Operation

The early diagnosis of a disease relies on the reliable identification and quantitation of multiple core biomarkers in real-time point-of-care (POC) testing. To date, most of the multiplex photoelectrochemical (PEC) assays are inaccessible to home healthcare due to cumbersome steps, long testing time, and limited detection efficiency. The rapid and fast-response generation of independent photocurrent for multiple targets is still a great challenge. Herein, a combinatorial DNA logic operation-guided multiplex PEC sensor is constructed to facilely distinguish and simultaneously monitor two core biomarkers that are essential for identifying asymptomatic Alzheimer patients and predicting the progression of the disease. The aptamers of amyloid-β oligomers (AβO) and Tau₄₄₁ protein are simply integrated at the high-performance In-TBAPy photocathode. In the presence of AβO and Tau₄₄₁ protein, the aptamer-target affinity complexes are formed and subsequently detached from the electrode surface, resulting in an increase of photocurrent. Through programming concatenated DNA molecular circuits, a 2-target input OR logic gate not only simplifies the manufacturing process of the multiplex PEC sensor but also realizes rapid and intelligent multiple-target recognition. As a conceptual prototype for the development of more sophisticated and complicated logic devices, the proposed DNA molecular logic system may open a new horizon for rapid disease diagnosis and POC analysis.