Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy
Liquid biopsy is a rapidly emerging field that involves the minimal/non-invasive assessment of signature somatic mutations through the analysis of circulating tumor DNA (ctDNA) shed by tumor cells in bodily fluids. Broadly speaking, the unmet need in liquid biopsy lung cancer detection is the lack o...
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MDPI AG
2023-06-01
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Series: | International Journal of Molecular Sciences |
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Online Access: | https://www.mdpi.com/1422-0067/24/12/10387 |
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author | Fang Wei Peter Yu Jordan Cheng Feng Li David Chia David T. W. Wong |
author_facet | Fang Wei Peter Yu Jordan Cheng Feng Li David Chia David T. W. Wong |
author_sort | Fang Wei |
collection | DOAJ |
description | Liquid biopsy is a rapidly emerging field that involves the minimal/non-invasive assessment of signature somatic mutations through the analysis of circulating tumor DNA (ctDNA) shed by tumor cells in bodily fluids. Broadly speaking, the unmet need in liquid biopsy lung cancer detection is the lack of a multiplex platform that can detect a mutation panel of lung cancer genes using a minimum amount of sample, especially for ultra-short ctDNA (usctDNA). Here, we developed a non-PCR and non-NGS-based single-droplet-based multiplexing microsensor technology, “Electric-Field-Induced Released and Measurement (EFIRM) Liquid Biopsy” (m-eLB), for lung cancer-associated usctDNA. The m-eLB provides a multiplexable assessment of usctDNA within a single droplet of biofluid in only one well of micro-electrodes, as each electrode is coated with different probes for the ctDNA. This m-eLB prototype demonstrates accuracy for three tyrosine-kinase-inhibitor-related EGFR target sequences in synthetic nucleotides. The accuracy of the multiplexing assay has an area under the curve (AUC) of 0.98 for L858R, 0.94 for Ex19 deletion, and 0.93 for T790M. In combination, the 3 EGFR assay has an AUC of 0.97 for the multiplexing assay. |
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institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-11T02:20:31Z |
publishDate | 2023-06-01 |
publisher | MDPI AG |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-906c8a4dd47647edbd23ed11941bc9e62023-11-18T10:52:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124121038710.3390/ijms241210387Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid BiopsyFang Wei0Peter Yu1Jordan Cheng2Feng Li3David Chia4David T. W. Wong5School of Dentistry, University of California, Los Angeles, CA 90095, USADepartment of Physics, University of California, Los Angeles, CA 90095, USASchool of Dentistry, University of California, Los Angeles, CA 90095, USASchool of Dentistry, University of California, Los Angeles, CA 90095, USADepartment of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USASchool of Dentistry, University of California, Los Angeles, CA 90095, USALiquid biopsy is a rapidly emerging field that involves the minimal/non-invasive assessment of signature somatic mutations through the analysis of circulating tumor DNA (ctDNA) shed by tumor cells in bodily fluids. Broadly speaking, the unmet need in liquid biopsy lung cancer detection is the lack of a multiplex platform that can detect a mutation panel of lung cancer genes using a minimum amount of sample, especially for ultra-short ctDNA (usctDNA). Here, we developed a non-PCR and non-NGS-based single-droplet-based multiplexing microsensor technology, “Electric-Field-Induced Released and Measurement (EFIRM) Liquid Biopsy” (m-eLB), for lung cancer-associated usctDNA. The m-eLB provides a multiplexable assessment of usctDNA within a single droplet of biofluid in only one well of micro-electrodes, as each electrode is coated with different probes for the ctDNA. This m-eLB prototype demonstrates accuracy for three tyrosine-kinase-inhibitor-related EGFR target sequences in synthetic nucleotides. The accuracy of the multiplexing assay has an area under the curve (AUC) of 0.98 for L858R, 0.94 for Ex19 deletion, and 0.93 for T790M. In combination, the 3 EGFR assay has an AUC of 0.97 for the multiplexing assay.https://www.mdpi.com/1422-0067/24/12/10387biosensorultra-short circulating tumor DNAlung cancerliquid biopsyEGFR |
spellingShingle | Fang Wei Peter Yu Jordan Cheng Feng Li David Chia David T. W. Wong Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy International Journal of Molecular Sciences biosensor ultra-short circulating tumor DNA lung cancer liquid biopsy EGFR |
title | Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy |
title_full | Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy |
title_fullStr | Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy |
title_full_unstemmed | Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy |
title_short | Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy |
title_sort | single droplet microsensor for ultra short circulating efgr mutation detection in lung cancer based on multiplex efirm liquid biopsy |
topic | biosensor ultra-short circulating tumor DNA lung cancer liquid biopsy EGFR |
url | https://www.mdpi.com/1422-0067/24/12/10387 |
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