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...

Full description

Bibliographic Details
Main Authors: Fang Wei, Peter Yu, Jordan Cheng, Feng Li, David Chia, David T. W. Wong
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/12/10387
_version_ 1797594217476784128
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.
first_indexed 2024-03-11T02:20:31Z
format Article
id doaj.art-906c8a4dd47647edbd23ed11941bc9e6
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
record_format Article
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
work_keys_str_mv AT fangwei singledropletmicrosensorforultrashortcirculatingefgrmutationdetectioninlungcancerbasedonmultiplexefirmliquidbiopsy
AT peteryu singledropletmicrosensorforultrashortcirculatingefgrmutationdetectioninlungcancerbasedonmultiplexefirmliquidbiopsy
AT jordancheng singledropletmicrosensorforultrashortcirculatingefgrmutationdetectioninlungcancerbasedonmultiplexefirmliquidbiopsy
AT fengli singledropletmicrosensorforultrashortcirculatingefgrmutationdetectioninlungcancerbasedonmultiplexefirmliquidbiopsy
AT davidchia singledropletmicrosensorforultrashortcirculatingefgrmutationdetectioninlungcancerbasedonmultiplexefirmliquidbiopsy
AT davidtwwong singledropletmicrosensorforultrashortcirculatingefgrmutationdetectioninlungcancerbasedonmultiplexefirmliquidbiopsy