Multi-parameter Inputted Logic-Gating on Aptamer-Encoded Extracellular Vesicles for Colorectal Cancer Diagnosis

Extracellular vesicles (EVs) have emerged as a potential biomarker in liquid biopsy. However, cancer heterogeneity poses significant challenge to precise molecular diagnosis based on single-parameter input. Hence, strategies for analyzing multiple inputs with molecular computing were developed with the aim of improving diagnostic accuracy in liquid biopsy. In the present study, based on the surface of aptamer-encoded EVs, three toehold extended DNA aptamers served as specific inputs to perform AND-logic-gating to distinguish between healthy and cancerous EVs. In addition, this strategy has been successfully employed to analyze circulating EVs in clinical samples from colorectal cancer patients and healthy donors. The developed method has a promising future in the analysis of multiplex EV membrane proteins and the identification of early cancer.

Automated summary

Extracellular vesicles (EVs) have been recognized as potential biomarkers in liquid biopsy. However, the heterogeneity of cancer poses challenges in precise molecular diagnosis based on single-parameter input. Therefore, strategies employing molecular computing to analyze multiple inputs have been developed to improve diagnostic accuracy in liquid biopsy. In this study, DNA aptamers were used as specific inputs to perform AND-logic-gating on aptamer-encoded EVs, enabling the distinction between healthy and cancerous EVs. This method has shown promising results in the analysis of circulating EVs in clinical samples from colorectal cancer patients and healthy donors, and has potential in the analysis of multiplex EV membrane proteins and early cancer identification.