Exosomal micro RNA(mi RNA) is an ideal candidate of noninvasive biomarker for the early diagnosis of cancer. Sensitive and accurate sensing of abnormal exosomal mi RNA plays essential role for clinical promotion due t...Exosomal micro RNA(mi RNA) is an ideal candidate of noninvasive biomarker for the early diagnosis of cancer. Sensitive and accurate sensing of abnormal exosomal mi RNA plays essential role for clinical promotion due to its close correlation with tumor proliferation and progression. Herein, a microfluidic surface-enhanced Raman scattering(SERS) sensor was proposed for an on-line detection of exosomal mi RNA based on rolling circle amplification(RCA) and tyramine signal amplification(TSA) strategy. The microfluidic chip consists of a magnetic enrichment chamber, a serpentine fluidic mixer and a plasmonic SERS substrate functionalized with capture probes. The released mi RNA activates the capture probe, triggers RCA reaction, and generates a large number of single-stranded DNA products to drive the catalysis of nanotags deposition via TSA, producing numerous “hot spots” to enhance the SERS signals. In merit of the microfluidics chip and nucleic acid-tyramine cascade amplification, the developed SERS sensor significantly improves the sensitivity for the exosomal mi RNA assay, resulting in a limit of detection(LOD) as low as 1 pmol/L and can be successfully applied in the analysis of exosomes secreted from breast tumor cells, which demonstrates the potential utility in practical applications.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 31671013, 22004096, 21874105and 21705124)the China Postdoctoral Science Foundation (Nos.2019M663658 and 2020T130096ZX)+2 种基金the Natural Science Basic Research Program of Shaanxi (Nos. 2020JQ-020, 2020JQ-021 and2018JC-001)the Fundamental Research Funds for the Central Universities (No. xzy012020034)“Young Talent Support Plan” of Xi’an Jiaotong University。
文摘Exosomal micro RNA(mi RNA) is an ideal candidate of noninvasive biomarker for the early diagnosis of cancer. Sensitive and accurate sensing of abnormal exosomal mi RNA plays essential role for clinical promotion due to its close correlation with tumor proliferation and progression. Herein, a microfluidic surface-enhanced Raman scattering(SERS) sensor was proposed for an on-line detection of exosomal mi RNA based on rolling circle amplification(RCA) and tyramine signal amplification(TSA) strategy. The microfluidic chip consists of a magnetic enrichment chamber, a serpentine fluidic mixer and a plasmonic SERS substrate functionalized with capture probes. The released mi RNA activates the capture probe, triggers RCA reaction, and generates a large number of single-stranded DNA products to drive the catalysis of nanotags deposition via TSA, producing numerous “hot spots” to enhance the SERS signals. In merit of the microfluidics chip and nucleic acid-tyramine cascade amplification, the developed SERS sensor significantly improves the sensitivity for the exosomal mi RNA assay, resulting in a limit of detection(LOD) as low as 1 pmol/L and can be successfully applied in the analysis of exosomes secreted from breast tumor cells, which demonstrates the potential utility in practical applications.
