Abstract
Tumor-associated cell-free DNA (cfDNA) is a dynamic biomarker for genetic analysis, early diagnosis and clinical treatment of cancers. However, its detection has limitations because of its low abundance in blood or other complex bodily fluids. Herein, we developed an ultrasensitive cfDNA electrochemical biosensor (E-cfDNA sensor) based on tetrahedral DNA framework (TDF)-modified gold nanoparticles (Au NPs) with an interface for cfDNA detection. By accurately controlling the numbers of base pairs on each DNA framework, three types of TDFs were programmed: 26 base pairs of TDF; 17 base pairs of TDF; and 7 base pairs of TDF (TDF-26, TDF-16 and TDF-7, respectively). We also combined the TDF with hybridization chain reaction (HCR) to achieve signal amplification. Under optimal conditions, we detected the breast cancer susceptibility gene 1 (BRCA-1), a representative cfDNA closely related to breast cancer. An ultra-low detection limit of 1 aM with a linear range from 1 aM to 1 pM by TDF-26 was obtained, which was superior to the existing methods. Each type of TDF has excellent discrimination ability, which can distinguish single mismatch. More significantly, we also detected BRCA-1 in mimic serum samples, demonstrating that the E-cfDNA sensor has potential use in clinical research.
Highlights
Tumor-associated cell-free DNA is a dynamic biomarker derived from different release mechanisms, such as necrosis, apoptosis and active release from carcinoma cells [1,2]. cfDNA can be used for early cancer diagnosis, gene mutation diagnosis, assisted targeted therapy and prognosis, etc. [3,4]
We fabricated a home-made AuNP-deposited multi-channel electrode, and exploited the ultrasensitive E-cfDNA sensor for specific cell-free DNA detection based on the programmed tetrahedral DNA framework (TDF) and hybridization chain reaction (HCR)
The TDF nanostructures immobilized on the electrode interface served as rigid scaffolds, and hybridized with the target sequence to trigger the HCR reaction, which achieved signal amplification
Summary
Tumor-associated cell-free DNA (cfDNA) is a dynamic biomarker derived from different release mechanisms, such as necrosis, apoptosis and active release from carcinoma cells [1,2]. cfDNA can be used for early cancer diagnosis, gene mutation diagnosis, assisted targeted therapy and prognosis, etc. [3,4]. A certain number of technologies have been reported for the analysis of cfDNA, including polymerase chain reaction, DNA sequencing [5,6], microarray [7], nanomaterial-based biosensors [8,9], etc. Among these technologies, electrochemicalbased biosensors are regarded as a promising direction for cfDNA detection because. Inorganic nanomaterials such as gold nanoparticles (AuNPs) can be modified on the electrode surface, providing excellent electrical conductivity, high surface area to volume ratio, superior catalytic capability and stability, and the ability to control the electrode microenvironment [15,16,17]
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