Interfacial cfDNA Enrichment and Amplification with On-Chip Thermoplasmonics for Highly Sensitive Cancerous Liquid Biopsy - Research Article

Sep 21, 2026

Tumor-derived circulating cell-free DNA (cfDNA) enables noninvasive liquid biopsy for early cancer detection, yet its fragmentation and low abundance hinder highly sensitive quantification. A multifunctional plasmonic biosensor, Interfacial cfDNA Enrichment, Ampliﬁcation and Sensing with on-chip Thermoplasmonics (INEAST), integrates interfacial thermoplasmonics and localized surface plasmon resonance for in situ thermoregulation and label-free cfDNA detection. Key biomarkers (EGFR, TP53, PTEN, CDKN2A) reach femtomolar-level limits, and blood validation in lung cancer patients shows improved reliability for screening, especially with clinically available tumor-protein metrics, supporting rapid early-stage diagnosis.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

1. Introduction

1.1 Background on liquid biopsy and cfDNA

1.2 Limitations of current NAAT methods

Figure 1. Schematic illustration of the INEAST bioassay

RESEARCH ARTICLE [www.advancedscience.com](www.advancedscience.com) Interfacial cfDNA Enrichment and Ampliﬁcation with On-Chip Thermoplasmonics for Highly Sensitive Cancerous Liquid Biopsy Danhua Wang, Linlin Liu, Wenjing Chi, Zhenping Liu, Jiayun Wu, Yirou Liang, Fei He, Ruixiang Zhang, Pengxin Huang, Yunbo Li, and Guangyu Qiu* Tumor-derived cell-free DNA (cfDNA) has been exploited as an eﬀective liquid biopsy biomarker for early cancer diagnosis. However, the fragmented and low-abundance nature in circulating blood pose challenges for highly sensitive cfDNA quantiﬁcation. Herein, a multifunctional plasmonic biosensor termed Interfacial cfDNA Enrichment, Ampliﬁcation and Sensing with on-chip Thermoplasmonics (INEAST) is developed for cfDNA-based liquid biopsy and lung cancer diagnosis. The INEAST biosensor achieved in situ thermoregulation and label-free cfDNA biosensing by simultaneously harnessing interfacial thermoplasmonics and localized surface plasmon resonance. Typical cfDNA biomarkers, including epidermal growth factor receptor (EGFR), tumor protein 53 (TP53), phosphatase and tensin homologue deleted on chromosome 10 (PTEN), and cyclin-dependent kinase inhibitor (CDKN2A), are quantiﬁed with detection limits down to femtomolar-level. Through further validation using blood samples from lung cancer patients, the proposed INEAST bioassays demonstrated superior reliability for lung cancer screening, particularly when combined with clinically available tumor-protein metrics. This study demonstrated that the INEAST biosensor enables rapid and sensitive cfDNA quantiﬁcation, yielding a promising and compatible liquid biopsy for early-stage lung cancer diagnosis. 1. Introduction Early diagnosis of malignant tumors is critical for improving clinical consequences and patient survival. Currently, the overall 5-year survival rate of lung cancer is less than 20% . [1] Among them, up to 85% of these patients were diagnosed at an advanced or metastatic stage, with a 5-year survival rate of only ≈2% . [2] In contrast, the postoperative 5-year survival rate with carcinoma diagnosed at an early stage is approaching 100% . [3] Liquid biopsy based on tumor biomarker detection in the bloodstream has been proven to be an eﬀective strategy for early diagnosis. Among them, circulating cell-free DNA (cfDNA) in humoral circulatory systems like the bloodstream has been considered a valuable noninvasive liquid biopsy biomarker for cancer diagnosis and prognosis. [4] Due to ineﬃcient inﬁltration, cfDNA levels in cancer patients are signiﬁcantly elevated compared to those of healthy individuals. [5] Therefore, quantiﬁcation of alterations in circulating cfDNA levels allows for precise and D. Wang, L. Liu, J. Wu, Y. Liang, F. He, R. Zhang, P. Huang, Y. Li, G. Qiu Institute of Medical Robotics, School of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200240, China E-mail: [guangyuqiu@sjtu.edu.cn](guangyuqiu@sjtu.edu.cn) W. Chi Department of Laboratory Medicine Huadong Hospital Aﬃliated to Fudan University Shanghai 200031, China Z. Liu The First People’s Hospital of Linping District Hangzhou, Zhejiang Province 311100, China The ORCID identiﬁcation number(s) for the author(s) of this article can be found under [https://doi.org/10.1002/advs.202409708](https://doi.org/10.1002/advs.202409708)[ ](https://doi.org/10.1002/advs.202409708)© 2024 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. DOI: 10.1002/advs.202409708 noninvasive cancer screening, diagnosis, and prognosis. However, recent studies have indicated that the circulating cfDNA has a short half-life ranging from 35 to 230 min, with an average of 120 min. [6] Therefore, it is imperative to develop diagnostic tools with high sensitivity a

FAQs

What problem does the INEAST biosensor address in cfDNA liquid biopsy?

It targets the fragmented and low-abundance nature of circulating cfDNA, enabling highly sensitive and rapid quantification for cancer diagnosis.

How does INEAST perform cfDNA enrichment and detection on-chip?

INEAST uses interfacial thermoplasmonics together with localized surface plasmon resonance to achieve in situ thermoregulation and label-free cfDNA biosensing while enabling on-chip interfacial amplification.

Which cfDNA biomarkers and performance levels are reported for lung cancer screening?

EGFR, TP53, PTEN, and CDKN2A are quantified with detection limits down to femtomolar levels; validation with lung cancer patient blood shows superior screening reliability, especially when combined with tumor-protein metrics.

Sep 21, 2026

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