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ACS Nano. 2018 Jul 24;12(7):6777-6783. doi: 10.1021/acsnano.8b01950. Epub 2018 Jun 27.

An Ultrasensitive Diagnostic Biochip Based on Biomimetic Periodic Nanostructure-Assisted Rolling Circle Amplification.

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College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education) , Wuhan University , Wuhan 430072 , China.
Center for Gene Diagnosis , Zhongnan Hospital of Wuhan University, Wuhan University , Wuhan 430072 , China.


Developing portable and sensitive devices for point of care detection of low abundance bioactive molecules is highly valuable in early diagnosis of disease. Herein, an ultrasensitive photonic crystals-assisted rolling circle amplification (PCs-RCA) biochip was constructed and further applied to circulating microRNAs (miRNAs) detection in serum. The biochip integrated the optical signal enhancement capability of biomimetic PCs surface with the thousand-fold signal amplification feature of RCA. The biomimetic PCs displayed periodic dielectric nanostructure and significantly enhanced the signal intensity of RCA reaction, leading to efficient improvement of detection sensitivity. A limit of detection (LOD) as low as 0.7 aM was obtained on the PCs-RCA biochip, and the LOD was 7 orders of magnitude lower than that of standard RCA. Moreover, the PCs-RCA biochip could discriminate a single base variation in miRNAs. Accurate quantification of ultralow-abundance circulating miRNAs in clinical serum samples was further achieved with the PCs-RCA biochip, and patients with the nonsmall cell lung carcinoma were successfully distinguished from healthy donors. The PCs-RCA biochip can detect bioactive molecules with ultrahigh sensitivity and good specificity, making it valuable in clinical disease diagnosis and health assessment.


biochip; cancer; circulating miRNA; photonic crystals; rolling circle amplification


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