Flexible-Arranged Biomimetic Array Integrated with Parallel Entropy-Driven Circuits for Ultrasensitive, Multiple, and Reliable Detection of Cancer-Related MicroRNAs

Abstract

With the emergence of microRNA (miRNA) as a promising biomarker in cancer diagnosis, it is significant to develop multiple analyses of miRNAs. However, it still faces difficulties in ensuring the sensitivity and accuracy during multiplex detection owing to the low abundance and experimental deviation of miRNAs. In this work, a flexible-arranged biomimetic array integrated with parallel entropy-driven circuits (EDCs) was developed for ultrasensitive, multiplex, reliable, and high-throughput detection of miRNAs. The biomimetic array was fabricated by arrangement of various photonic crystals (PCs) for adjustable photonic band gaps (PBGs) and specific fluorescence enhancement. Meanwhile, two cancer-related miRNAs and one reference miRNA were introduced as multiple analytes as a proofof-concept. The parallel EDCs with negligible crosstalk were designed based on the modular property. Because of the one-to-one match between the emitted fluorescence of parallel EDCs and the PBGs of the flexible-arranged biomimetic array, the generated fluorescence signal triggered by target miRNAs can be enhanced on the corresponding domain of the array. Furthermore, the amplified signal of the array was detected with high-throughput scanning, which could reveal specific information on cancer-related miRNAs as well as reference miRNA, enhancing the abundance and reliability of the analysis. The proposed array has the merits of a modular design, flexible deployment, simple operation (nonenzymatic and isothermal), improved accuracy, high sensitivity, and multiplex analysis, showing potential in disease diagnosis.

Ultrasensitive Electrochemiluminescence Biosensor Based on DNA-Bio-Bar-Code and Hybridization Chain Reaction Dual Signal Amplification for Exosomes Detection

“…The ingenious and rational integration of signal amplification strategies in detection systems can significantly improve the sensitivity, which has received considerable attention in constructing various biosensors for analyzing cancer-related biomarkers. , The distinct programmability and remarkable predictability of the canonical Watson–Crick nuclide acid endow DNA the capacity to fabricate versatile DNA-based systems with precise nanostructures for signal amplification in bioanalysis. − Especially, various enzyme-free isothermal amplification strategies have been regarded as powerful tools for the improvement of sensitivity in the identification and quantification of biological molecules, including entropy-driven catalytic reaction, hybridization chain reaction (HCR), and catalytic hairpin assembly (CHA). − Among them, HCR involves an initiator to trigger the repeated hybridization of two hairpin DNA strands, leading to the “polymerization” into a nicked double helix for the signal amplification. − Taking advantage of the long double-stranded DNA produced by HCR, which provides abundant insertion sites for hemin, we propose a dual signal amplification system combining bio-bar-code amplification (BCA) assay and bio-bar-code DNA initiated HCR for the ultrasensitive electrochemiluminescent detection of breast cancer cell (MCF-7)-derived exosomes.…”