Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glass
Abstract MicroRNAs (miRNAs) are small non-coding RNAs with ~ 22 nucleotides, playing important roles in the post-transcriptional regulation of gene expression. The expression profiles of many miRNAs are closely related to the occurrence and progression of cancer and can be used as biomarkers for can...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-022-01664-7 |
| _version_ | 1811257226823729152 |
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| author | Ying Gan Mingxing Zhou Huiqiang Ma Jiameng Gong Shan-Yu Fung Xian Huang Hong Yang |
| author_facet | Ying Gan Mingxing Zhou Huiqiang Ma Jiameng Gong Shan-Yu Fung Xian Huang Hong Yang |
| author_sort | Ying Gan |
| collection | DOAJ |
| description | Abstract MicroRNAs (miRNAs) are small non-coding RNAs with ~ 22 nucleotides, playing important roles in the post-transcriptional regulation of gene expression. The expression profiles of many miRNAs are closely related to the occurrence and progression of cancer and can be used as biomarkers for cancer diagnosis and prognosis. However, their intrinsic properties, such as short length, low abundance and high sequence homology, represent great challenges in miRNA detection of clinical samples. To overcome these challenges, we developed a simple, ultrasensitive detection platform of electrochemical miRNAs chip (e-miRchip) with a novel signal amplification strategy using silver nanoparticle reporters (AgNRs) for multiplexed, direct, electronic profiling of miRNAs. A two-step hybridization strategy was used to detect miRNAs, where the target miRNA hybridizes with a stem-loop probe to unlock the probe first, and the opened stem-loop can further hybridize with AgNRs for signaling amplification. To enhance the detection sensitivity, the gold nanoflower electrodes (GNEs) were constructed in the microaperture arrays of the e-miRchips by electroplating. With the optimal size of the GNEs, the e-miRchip showed excellent performance for miR-21 detection with a detection limit of 0.56 fM and a linear range extended from 1 fM to 10 pM. The e-miRchip also exhibited good specificity in differentiating the 3-base mismatched sequences of the target miRNA. In addition, the e-miRchip was able to directly detect miR-21 expression in the total RNA extracts or cell lysates collected from lung cancer cells and normal cells. This work demonstrated the developed e-miRchip as an efficient and promising miniaturized point-of-care diagnostic device for the early diagnosis and prognosis of cancers. Graphical Abstract |
| first_indexed | 2024-04-12T17:54:10Z |
| format | Article |
| id | doaj.art-e728781ec9c1459989c92991a2548ec6 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-12T17:54:10Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-e728781ec9c1459989c92991a2548ec62022-12-22T03:22:25ZengBMCJournal of Nanobiotechnology1477-31552022-10-0120111410.1186/s12951-022-01664-7Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glassYing Gan0Mingxing Zhou1Huiqiang Ma2Jiameng Gong3Shan-Yu Fung4Xian Huang5Hong Yang6The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Pharmacology, School of Basic Medical Sciences, School of Biomedical Engineering, Intensive Care Unit, The Second Hospital, Tianjin Medical UniversityDepartment of Biomedical Engineering, Tianjin UniversityThe Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Pharmacology, School of Basic Medical Sciences, School of Biomedical Engineering, Intensive Care Unit, The Second Hospital, Tianjin Medical UniversityThe Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Pharmacology, School of Basic Medical Sciences, School of Biomedical Engineering, Intensive Care Unit, The Second Hospital, Tianjin Medical UniversityDepartment of Immunology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Biomedical Engineering, Tianjin UniversityThe Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Pharmacology, School of Basic Medical Sciences, School of Biomedical Engineering, Intensive Care Unit, The Second Hospital, Tianjin Medical UniversityAbstract MicroRNAs (miRNAs) are small non-coding RNAs with ~ 22 nucleotides, playing important roles in the post-transcriptional regulation of gene expression. The expression profiles of many miRNAs are closely related to the occurrence and progression of cancer and can be used as biomarkers for cancer diagnosis and prognosis. However, their intrinsic properties, such as short length, low abundance and high sequence homology, represent great challenges in miRNA detection of clinical samples. To overcome these challenges, we developed a simple, ultrasensitive detection platform of electrochemical miRNAs chip (e-miRchip) with a novel signal amplification strategy using silver nanoparticle reporters (AgNRs) for multiplexed, direct, electronic profiling of miRNAs. A two-step hybridization strategy was used to detect miRNAs, where the target miRNA hybridizes with a stem-loop probe to unlock the probe first, and the opened stem-loop can further hybridize with AgNRs for signaling amplification. To enhance the detection sensitivity, the gold nanoflower electrodes (GNEs) were constructed in the microaperture arrays of the e-miRchips by electroplating. With the optimal size of the GNEs, the e-miRchip showed excellent performance for miR-21 detection with a detection limit of 0.56 fM and a linear range extended from 1 fM to 10 pM. The e-miRchip also exhibited good specificity in differentiating the 3-base mismatched sequences of the target miRNA. In addition, the e-miRchip was able to directly detect miR-21 expression in the total RNA extracts or cell lysates collected from lung cancer cells and normal cells. This work demonstrated the developed e-miRchip as an efficient and promising miniaturized point-of-care diagnostic device for the early diagnosis and prognosis of cancers. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01664-7Electrochemical biosensorMicroarrayNanostructured electrodesmicroRNAsSilver nanoparticle |
| spellingShingle | Ying Gan Mingxing Zhou Huiqiang Ma Jiameng Gong Shan-Yu Fung Xian Huang Hong Yang Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glass Journal of Nanobiotechnology Electrochemical biosensor Microarray Nanostructured electrodes microRNAs Silver nanoparticle |
| title | Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glass |
| title_full | Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glass |
| title_fullStr | Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glass |
| title_full_unstemmed | Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glass |
| title_short | Silver nano-reporter enables simple and ultrasensitive profiling of microRNAs on a nanoflower-like microelectrode array on glass |
| title_sort | silver nano reporter enables simple and ultrasensitive profiling of micrornas on a nanoflower like microelectrode array on glass |
| topic | Electrochemical biosensor Microarray Nanostructured electrodes microRNAs Silver nanoparticle |
| url | https://doi.org/10.1186/s12951-022-01664-7 |
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