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DNA纳米技术
JOURNAL OF CHROMATOGRAPHY A · 2020 · IF 4.049

A signal transduction approach for multiplexed detection of transcription factors by integrating DNA nanotechnology, multi-channeled isothermal amplification, and chromatography

Yue Chen,Xiaoqiang Yan,Wei Yang,Jing Wang,Qiaoyun Lu,Bingzhi Li,Wanying Zhu,Xuemin Zhou

The variation patterns of transcription factors (TFs) provide direct information for the states of cell populations, which is of significance for biomedical research and clinical diagnostics. Herein, we show that through multi-channeled isothermal amplification, it is feasible to connect DNA-based signal transduction with chromatography for multiplexed detection of TFs. The described system is referred to as "PAC" which includes three major steps: (i) P rotection, which uses DNA-modified magnetic beads to capture TFs and converts the capturing event into triggering signal; (ii) A mplification, which receives the triggering signal and generate DNA reporters through multi-channeled extension and nicking of oligonucleotides; and (iii) C hromatography, which separates and detects the DNA reporters in liquid chromatography. The quantitative detection of five essential TFs includes p50, p53, AP-1, MITF, and c-Myc is realized in a multiplexed manner, with the lowest detection limit of 0.5 pM. PAC can also provide effective means to measure the above five TFs in real samples, including cultured cells, xenograft tumors, and blood-based liquid biopsy. This study not only established a solution for multiplexed measurement of TFs for molecular diagnostics, but also paved avenue for bridging the gap between DNA nanotechnology and chromatography.

CAS / MDL: 64-19-7
研究领域: 生物医学工程 · 分子诊断学 · 纳米生物学
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DALTON TRANSACTIONS · 2023 ·Vol. 52 ·期 6 ·1524-1532 · IF 4

A DNA-Schiff base functional nanopore sensing platform for the highly sensitive detection of Al3+ and Zn2+ ions

Shuailong Zhou,Jianhan Ye,Xiaohuan Zhao,Zihao Zhou,Yuanchen Dong,Qian Shi,Nannan Liu,Fen Wu

The combination of DNA nanotechnology and nanopore sensing technology has greatly promoted research on target molecule or ion detection. The large solid-state nanopores/nanochannels show better mechanical stability and reproducibility, but metal ion detection in the large nanopores with diameters of hundreds of nanometers or several micrometers is rarely reported. Hence, it is meaningful and urgent to develop a large nanopore-based sensing platform for the detection of metal ions. Herein, we employed a salicylic aldehyde-modified DNA network in conjunction with a glass nanopipette (GN) with a diameter of hundreds of nanometers as a sensing platform for the detection of target metal ions. Upon the addition of different receptors with the amino group, the salicylic aldehyde could in situ specifically recognize and bind with Zn2+ and Al3, forming Schiff base-metal ion complexes at the four vertices of one face per nanocube unit. The steric hindrance effect of multiple Schiff bases and metal ion complexes leads to the blockage of internal structure and decrease of ion current in the GN. Owing to this signal amplification strategy, the detection limit of the target metal ion reaches a level of fM in the GN with a diameter of about 300 nm. In the future, this functional nanopore sensing platform is expected to realize highly sensitive detection for more biological metal ions by choosing appropriate receptors.

研究领域: 生物化学 · 纳米技术 · 分析化学
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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

Cascaded amplification-based modular ternary DNA logic circuit for precise identification of circulating tumor cells

Hexiang Li,Yao Yao,Ziyi Gao,Yinghui Feng,Qi Liu,Xiaoqing Chen

Precise identification of tumor cells is paramount for disease diagnosis and treatment, where tumor markers play a pivotal role. However, relying solely on a single tumor marker detection method often falls short in differentiating various types of tumor cells, leading to potential false-positive signals. To address this challenge, we have developed a ternary DNA logic gate system. This logic circuit is supported by multi-aptamers and performs identification operations by targeting different cell surface proteins. It fully leverages the functionality and framework characteristics of DNA nanostructures, employing a Toehold-Mediated Strand Displacement (TMSD) cascade amplification reaction to convert the strand signal into an electrical signal. This integrated multi-module ternary DNA logic gate system demonstrates accurate recognition among six cell lines while achieving highly sensitive detection of target tumor cells. Biosensors that integrate DNA logic computing with aptamers not only facilitate accurate tumor cell identification but also exhibit significant potential in the realms of drug delivery and cancer therapy.

CAS / MDL: 1633-78-9
研究领域: 分子诊断 · DNA纳米技术 · 生物传感 · 癌症诊断 · 逻辑计算 · 靶向治疗
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ANALYTICA CHIMICA ACTA · 2025 · IF 6

Investigation of intramolecular split G-quadruplex-hemin systems and development of DNAzyme-based probes

Lu Lin,Mengmeng Lv,Jiangtao Ren,Jin Wang,Erkang Wang

Background G-quadruplex DNAzymes, known for their peroxidase-like activity and ease of rational design, have emerged as promising tools in biosensing applications. Despite the fundamental importance of structural topology, investigations into how the split mode of intramolecular split G-quadruplex (IntrSG)-based DNAzymes modulates their catalytic properties, as well as their implications for the development of DNAzyme-based probes, remain scarce. In this work, eleven IntrSG strands of different split modes were engineered with a classical parallel G-quadruplex sequence ( PW17 ). The catalytic activity of IntrSG-hemin mixtures was systematically investigated via various techniques. Results Most IntrSG strands incubated with hemin exhibited apparent catalytic activity, which was influenced by split modes and hybridization of inserted spacer. Interestingly, the mixture of hemin and IntrSG of split mode 5:7 (IntrSG(5:7)) exhibited drastic catalytic activity response after hybridization between its spacer and target, and the underlying mechanism was disclosed, which was hybridization-facilitated G-quadruplex assembling and catalytic enhancement. The IntrSG(5:7)-hemin system can be utilized as an effective “signal-on” signal transducer, owing to its simpleness and universality. Subsequently, influence of sequence context changes on the catalytic response was explored by extending and truncating the target sequence. Ignorable effect of protruding DNA was validated, and robust hybridization was critical for catalytic responses, which were unrelated to hybridization location. Finally, an IntrSG(5:7)-based catalytic probe was employed for quantitative analysis of miRNA ( Let-7a ), and favorable performance was achieved. Significance Taken together, a mechanistic framework for topological control of G-quadruplex DNAzyme catalysis was established, highlighting the potential of IntrSG as a versatile platform for biosensing and molecular diagnostics.

CAS / MDL: 16009-13-5
研究领域: 生物化学 · 分子诊断学 · 生物传感 · 核酸工程 · DNA纳米技术
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ACS Nano · 2025 · IF 16

Dynamics of Reconfigurable Plasmonic Metamolecules Characterized by High-Throughput Time-Resolved Circular Differential Scattering

Run Pan,Hao Li,Xiaoyao Wang,Heng Zhang,Luis M. Liz-Marzán,Chao Zhou,Weihai Ni

Characterization of the dynamics of individual reconfigurable chiral plasmonic nanostructures (metamolecules) in various local environments provides critical information toward understanding the principles and mechanisms involved in designing and constructing metamolecules. However, time-resolved statistical analysis of transition trajectories is required at the single-metamolecule level. Therefore, we developed a high-throughput time-resolved circular differential scattering (TRCDS) method for characterizing dynamic processes in single metamolecules immobilized on a substrate. This method allowed us to perform time-resolved trajectory measurements during the conformational transition of individual reconfigurable plasmonic metamolecules between two enantiomeric states, driven by the hybridization of single DNA strands in situ in an aqueous environment. High-throughput optical characterization supported a statistical analysis based on simultaneous measurements of hundreds of reconfigurable metamolecules with slight differences in their individual structures and local environments, within the field-of-view of the microscope. Statistical analysis revealed a transition path time τTP = 123.7 ms for the conformational transition. Engineering of the dynamic reconfiguration of metamolecules was demonstrated by varying the dynamic DNA strands from 8 to 11 and 14 nucleotides, resulting in an increased stability of the enantiomeric states. Our study enables the dynamic manipulation of reconfigurable plasmonic nanostructures and the rational construction of smart systems.

CAS / MDL: 6381-92-6 7791-18-6
研究领域: 纳米光子学 · 等离激元学 · 超材料 · 单分子分析 · 生物光子学 · DNA纳米技术
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MICROCHIMICA ACTA · 2025 ·Vol. 192 ·期 9 ·1-13 · IF 5.3

Simultaneous EGFR mutation detection using a sensitive dual-target biosensor based on 3D hollow carbon nanosphere synergy with circular bipedal DNA walkers

He Linxin,Wei Yuxin,Chen Cizhi,Li Chuanhai,Xu Ying,Chen Mei

A sensitive dual-target electrochemical biosensor was developed integrating circular bipedal DNA walkers with a three-dimensional hollow carbon nanospheres-tetrametallic nanoparticle (3D HCNs-TT NPs) modified platform, enabling concurrent detection of two critical epidermal growth factor receptor (EGFR) exon 19 mutations: E746_A750 deletion (Mut DNA A) and L747_S752delinsS (Mut DNA B). The circular bipedal DNA walkers address the limitations of low amplification efficiency in traditional single-legged DNA walkers and mitigate the sensitivity reduction caused by excessively long walking strands. Additionally, we used the 3D HCNs-TT NPs nanocomposite materials to modify the electrodes, which significantly increased the electron transfer rate and provided more active sites for molecular probe loading, thereby further enhancing the performance of the detection platform. This biosensor demonstrated good performance, with detection limits as low as 3.4 fM (Mut DNA A) and 2 fM (Mut DNA B) (S/N = 3). The designed sensor was applied for detection using clinical samples, including cells with gene mutations and diluted human serum, and these results confirm the sensor’s potential for clinical translation, offering a potential tool for early non-small cell lung cancer (NSCLC) diagnosis and personalized tyrosine kinase inhibitors (TKI) therapy guidance. Graphical abstract

研究领域: 生物传感器 · 分子诊断学 · 纳米技术 · 癌症遗传学 · 电化学 · DNA纳米技术 · 临床诊断学
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ANALYTICAL CHEMISTRY · 2025 · IF 6.7

Programming Ion Gating and Dynamic Response of Nanopores with Responsive Tetrahedral DNA Nanostructures

Yaqin Wang,Huiping Yang,Zhaoquan Li,Qian Mo,Shuang Li,Longda Li,Fan Yang,Xinchun Li,Yong Huang

Mimicking ion-gating function with artificial nanopores empowered by well-designed responsive DNA architectures represents one of the leading maneuvers in the nanopore sensing field. However, due to the rarely preponderant orientation and uncontrollable assembly of conventional DNA constructs at heterogeneous interfaces, the recognition ability and gating efficiency remain a considerable challenge. Here, we show that manipulating the ion-gating efficiency can be readily achieved by the assembly of responsive tetrahedral DNA nanostructures in glass nanopipettes. We design a set of 3D-DNA nanostructures consisting of size-tunable DNA tetrahedrons and Pb2+-dependent DNAzyme structural domain in the nanopipettes, which served as the ion gate and recognition element, respectively, and thus enabled the sensing of Pb2+ in a label-free manner. Using the constructed 3D-DNA-nanostructured ion-gating systems, we can program stimulus–response capacity and ionic current rectification behaviors in the Pb2+ sensing events. We found that larger-size DNA tetrahedrons resulted in more efficient ion gating and importantly could achieve dynamic linear response to Pb2+, with the concentration spanning from 10 pM to 10 μM. Finite element simulations revealed that steric hindrance, rather than surface charge, may be a principal cause for regulating trans-pore ion transport. This work opens an avenue for the design of DNA nanostructure-based responsive nanopores for sensing applications.

研究领域: 纳米技术 · 生物工程 · 生物传感器 · DNA纳米技术 · 电化学 · 分析化学
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Small · 2025 · IF 12.1

Nano-Impact Electrochemistry of 3D DNA Nanostructure

Jiarong Guo,Jiayue Shi,Peng Miao

Nano-impact electrochemistry (NIE) has made significant advances in the fields of electrochemistry and analytical chemistry. Nevertheless, the choice of entities used for NIE is usually confined to inorganic nanoparticles. The interest in DNA nanotechnology prompts the exploration of DNA materials as signal sources for NIE. In this study, tetrahedral DNA nanostructure (TDNA) is designed as an example. Various sizes and base compositions of TDNAs are assembled. Corresponding NIE signals are successfully detected at the interface of gold ultramicroelectrode. The results indicate that 3D DNA nanostructures can proficiently replicate the roles of inorganic nanoparticles in NIE without requiring additional modifications. Furthermore, it is demonstrated that TDNA not only adheres to the electrode surface, acting as a diffusion barrier but also exhibits NIE effects through base redox reactions and charge conduction. The findings supplement new types of materials with NIE effects and may inspire novel bioanalytical applications.

研究领域: 电化学 · 分析化学 · DNA纳米技术 · 生物分析
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ANALYTICA CHIMICA ACTA · 2023 · IF 6.2

Inverting the DNA tetrahedron: A novel strategy for sensitive and stable detection of aging-related enzyme MMP2

Jihua Wei,Zichun Song,Jiuying Cui,Yuanxun Gong,Qianli Tang,Kai Zhang,Xinlei Song,Xianjiu Liao

In the current study, a novel electrochemiluminescence biosensor based on the entropy-driven DNA tetrahedron for the detection of matrix metalloproteinase 2 (MMP2), an enzyme that regulates extracellular matrix remodeling and affects aging was reported. The biosensor utilizes an inverted DNA tetrahedron structure, which exposes three vertices to the solution, as molecular recognition units for capturing specific biomolecules. The biosensor also employs a ratiometric method and an entropy-driven reaction, which enhance the response rate and sensitivity of the detection. The biosensor can detect MMP2 with a detection limit of 55.2 fM, which is lower than that of conventional sensors. The biosensor also exhibits excellent stability and reproducibility, and can accurately measure MMP2 levels in complex samples, such as human serum. The paper demonstrates the feasibility and effectiveness of using the “inverted” DNA tetrahedron structure and the entropy-driven process to construct interfacial biosensors. The paper also discusses the potential applications of the biosensor in clinical diagnosis and anti-aging research, where MMP2 plays a crucial role in tissue damage and repair. The paper provides a valuable contribution to the field of biosensor development, and opens up new possibilities for using DNA nanotechnology for sensitive and reliable detection of various biomolecules.

研究领域: 生物传感器开发 · DNA纳米技术 · 衰老研究 · 临床诊断
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