Ultrasensitive, label-free, electrochemical detection of miRNA-206 in human plasma: A potential biomarker associated with Alzheimer’s disease
An impedance-based biosensor for the ultrasensitive, selective, and label-free detection of a blood miRNA associated to Alzheimer disease (AD), miRNA-206, was developed. The principle was grounded in the changes in the charge transfer resistance (RCT) as an effect of intramolecular forces between mi...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | Electrochemistry Communications |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S138824812400047X |
| _version_ | 1827292112658366464 |
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| author | Amanda Carrico Loanda R. Cumba Miguel Medina Tobias Engel Robert J. Forster |
| author_facet | Amanda Carrico Loanda R. Cumba Miguel Medina Tobias Engel Robert J. Forster |
| author_sort | Amanda Carrico |
| collection | DOAJ |
| description | An impedance-based biosensor for the ultrasensitive, selective, and label-free detection of a blood miRNA associated to Alzheimer disease (AD), miRNA-206, was developed. The principle was grounded in the changes in the charge transfer resistance (RCT) as an effect of intramolecular forces between miRNAs and ferro/ferricyanide in a well-structured transducer platform. A compact well-ordered mixed monolayer made of co-immobilized miRNA capture to 6-mercapto-1-hexanol (MCH) in a 1:4 M ratio (at 37 °C), uplifted the performance of the sensor through effectively assisting the orientation of the oligonucleotides. In this work, the remarkable response of the sensor was generated through new insights into the use of different moieties of miRNA capture to MCH, aiming to control interfacial constants, surface densities, and hybridization efficiency.A very low limit of detection, 0.15 aM, is achieved and the sensor has a wide linear dynamic range (from 1 aM to 1 μM), high selectivity to mismatches, low non-specific binding of proteins (BSA) and good stability (<10 % change in response after 14 days storage). Importantly, the sensor successfully measured miRNA-206 concentrations in real plasma samples (>95 % recovery), correlating directly with qPCR results. Nanomolar concentrations of miRNA-206 were found in the plasma of confirmed AD patients, while healthy controls, had a concentration of pM or lower. The biosensor's ability to quantitatively detect miRNA-206 in plasma without target amplification, e.g., using PCR, is significant, opening the possibility of developing a point-of-care diagnostic device for AD screening, contributing to clinical trials and patient care. |
| first_indexed | 2024-04-24T12:51:01Z |
| format | Article |
| id | doaj.art-52edff41f4794a7586dbece12a876163 |
| institution | Directory Open Access Journal |
| issn | 1388-2481 |
| language | English |
| last_indexed | 2024-04-24T12:51:01Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Electrochemistry Communications |
| spelling | doaj.art-52edff41f4794a7586dbece12a8761632024-04-06T04:39:37ZengElsevierElectrochemistry Communications1388-24812024-05-01162107704Ultrasensitive, label-free, electrochemical detection of miRNA-206 in human plasma: A potential biomarker associated with Alzheimer’s diseaseAmanda Carrico0Loanda R. Cumba1Miguel Medina2Tobias Engel3Robert J. Forster4National Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Dublin 9, Ireland; FutureNeuro, The SFI Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland, IrelandNational Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Dublin 9, Ireland; Corresponding authors at: National Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Dublin 9, Ireland.Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; CIEN Foundation, Queen Sofia Foundation Alzheimer Center, Madrid, SpainFutureNeuro, The SFI Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland, IrelandNational Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Dublin 9, Ireland; FutureNeuro, The SFI Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland, Ireland; Corresponding authors at: National Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Dublin 9, Ireland.An impedance-based biosensor for the ultrasensitive, selective, and label-free detection of a blood miRNA associated to Alzheimer disease (AD), miRNA-206, was developed. The principle was grounded in the changes in the charge transfer resistance (RCT) as an effect of intramolecular forces between miRNAs and ferro/ferricyanide in a well-structured transducer platform. A compact well-ordered mixed monolayer made of co-immobilized miRNA capture to 6-mercapto-1-hexanol (MCH) in a 1:4 M ratio (at 37 °C), uplifted the performance of the sensor through effectively assisting the orientation of the oligonucleotides. In this work, the remarkable response of the sensor was generated through new insights into the use of different moieties of miRNA capture to MCH, aiming to control interfacial constants, surface densities, and hybridization efficiency.A very low limit of detection, 0.15 aM, is achieved and the sensor has a wide linear dynamic range (from 1 aM to 1 μM), high selectivity to mismatches, low non-specific binding of proteins (BSA) and good stability (<10 % change in response after 14 days storage). Importantly, the sensor successfully measured miRNA-206 concentrations in real plasma samples (>95 % recovery), correlating directly with qPCR results. Nanomolar concentrations of miRNA-206 were found in the plasma of confirmed AD patients, while healthy controls, had a concentration of pM or lower. The biosensor's ability to quantitatively detect miRNA-206 in plasma without target amplification, e.g., using PCR, is significant, opening the possibility of developing a point-of-care diagnostic device for AD screening, contributing to clinical trials and patient care.http://www.sciencedirect.com/science/article/pii/S138824812400047XLabel-freeBiosensormiRNA-206Alzheimer diseaseElectrochemical impedance spectroscopy |
| spellingShingle | Amanda Carrico Loanda R. Cumba Miguel Medina Tobias Engel Robert J. Forster Ultrasensitive, label-free, electrochemical detection of miRNA-206 in human plasma: A potential biomarker associated with Alzheimer’s disease Electrochemistry Communications Label-free Biosensor miRNA-206 Alzheimer disease Electrochemical impedance spectroscopy |
| title | Ultrasensitive, label-free, electrochemical detection of miRNA-206 in human plasma: A potential biomarker associated with Alzheimer’s disease |
| title_full | Ultrasensitive, label-free, electrochemical detection of miRNA-206 in human plasma: A potential biomarker associated with Alzheimer’s disease |
| title_fullStr | Ultrasensitive, label-free, electrochemical detection of miRNA-206 in human plasma: A potential biomarker associated with Alzheimer’s disease |
| title_full_unstemmed | Ultrasensitive, label-free, electrochemical detection of miRNA-206 in human plasma: A potential biomarker associated with Alzheimer’s disease |
| title_short | Ultrasensitive, label-free, electrochemical detection of miRNA-206 in human plasma: A potential biomarker associated with Alzheimer’s disease |
| title_sort | ultrasensitive label free electrochemical detection of mirna 206 in human plasma a potential biomarker associated with alzheimer s disease |
| topic | Label-free Biosensor miRNA-206 Alzheimer disease Electrochemical impedance spectroscopy |
| url | http://www.sciencedirect.com/science/article/pii/S138824812400047X |
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