Multi-Body Biomarker Entrapment System: An All-Encompassing Tool for Ultrasensitive Disease Diagnosis and Epidemic Screening.

Ultrasensitive identification of biomarkers in biofluids is essential for precise diagnosis of diseases. For the gold standard approaches, polymerase chain reaction and enzyme-linked immunosorbent assay, cumbersome operational steps hinder their point-of-care applications. Here, w e implement a bionic biomarker entrapment system (BioES), which employs a multi-body Y-shaped tetrahedral DNA probe immobilized on carbon nanotube transistors. W e successfully realize clinical identification of endometriosis by detecting an estrogen receptor, ERβ, from the lesion tissue of endometriosis patients and establish a standard diagnosis procedure. The multi-body Y-shaped BioES achieves a theoretical limit of detection (LoD) of 6.74 aM and a LoQ of 141 aM in a complex protein milieu. Furthermore, the BioES is optimized into multi-site recognition module for enhanced binding efficiency, realizing the first identification of monkeypox virus antigen A35R and unamplified detection of circulating tumor DNA of breast cancer in serum. The rigid and compact probe framework with synergy effect enable the BioES to target A35R and DNA with a LoD down to 991 aM and 0.21 aM, respectively. Owing to its versatility for proteins and nucleic acids as well as ease-of-manipulation and ultra-sensitivity, the BioES can be leveraged as an all-encompassing tool for population-wide screening of epidemics and clinical disease diagnosis. This article is protected by copyright. All rights reserved.