Ultrasensitive Detection of Circulating Tumor DNA of Lung Cancer via an Enzymatically Amplified SERS-Based Frequency Shift Assay

Jie Zhang, Yuhang Dong, Wenfeng Zhu, Dan Xie, Yuliang Zhao, Dayong Yang, Min Li

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Circulating tumor DNA (ctDNA) is a promising noninvasive biomarker for the early diagnosis of cancers. However, it is challenging for accurate and sensitive detection of pico-to-femtomolar serum concentration of ctDNA, especially in the presence of its analogues that produce strong background noise. Herein, a DNA-rN1-DNA-mediated surface-enhanced Raman scattering frequency shift assay is developed, which enables sensitive detection of ctDNA with one single base pair mutation (KARS G12D mutation) from the normal ones (KARS G12D normal) of lung cancer. This sensing platform features in both the designed hairpin DNA-rN1-DNA probe for specific ctDNA recognition and the employed RNase HII enzyme that specifically hydrolyzes the DNA-rN1-DNA/ctDNA hybrid and thus allows ctDNA recycling in the system to realize signal amplification. The detection system shows sub-femtomolar-level sensitivity in the phosphate-buffered saline solution and is demonstrated to function well in both fetal bovine serum and human physiological media. In particular, the sensitive assay of ctDNA in serum samples from lung cancer patients is achieved, suggesting its high potential applications in clinical settings for early diagnosis and prognosis of lung cancer.

Original languageEnglish (US)
Pages (from-to)18145-18152
Number of pages8
JournalACS Applied Materials and Interfaces
Volume11
Issue number20
DOIs
StatePublished - May 22 2019

Keywords

  • DNA nanostructures
  • RNase
  • circulating tumor DNA (ctDNA)
  • frequency shift
  • surface-enhanced Raman scattering (SERS)

ASJC Scopus subject areas

  • Materials Science(all)

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