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Cascaded logic gate-based electrochemical analysis of multiple miRNAs for cancer recognition

Ding Ma1, Yaojun Wang1, Yi Xu2

  • 1Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, 865 Changning Road, Shanghai, 200050, China; University of Chinese Academy of Sciences, Beijing, 100049, China.

Biosensors & Bioelectronics
|April 26, 2025
PubMed

Insights

This study introduces a novel electrochemical sensor using DNA logic gates to detect specific microRNA (miRNA) combinations for distinguishing pancreatic, breast, and lung cancers. The method offers precise and rapid multi-cancer detection in biological samples.

Area of Science:

  • Biomedical Engineering
  • Molecular Diagnostics
  • Cancer Biomarkers

Background:

  • Current microRNA (miRNA) detection methods often analyze single targets, neglecting complex biological interdependencies.
  • Accurate multi-cancer diagnosis requires methods that can analyze combinations of miRNAs and their logical relationships.

Purpose of the Study:

  • To develop a novel cascaded logic gate-based electrochemical (EC) analysis strategy for discriminating between pancreatic cancer (PC), breast cancer (BC), and lung cancer (LC).
  • To leverage the logical relationships among specific miRNAs for enhanced cancer detection accuracy.

Main Methods:

  • Fabrication of an electrochemical sensor integrated with DNA framework probes and DNA logic gate technology.
  • Construction of cascaded AND logic gates based on the expression patterns of specific miRNAs (miR-21, miR-155, miR-373, miR-6746, miR-1343) linked to PC, BC, and LC.
  • Utilizing output strands from logic gates captured by tetrahedral DNA framework probes on EC sensor electrodes.

Main Results:

  • Achieved low limits of detection (LOD) for miRNA combinations: 0.62 nM (PC), 0.37 nM (BC), and 0.41 nM (LC).
  • Demonstrated excellent linear relationships (R² > 0.99) between current values and miRNA concentrations (1 nM to 1 μM).
  • Successfully distinguished between PC, BC, and LC using specific miRNA combinations in both buffer and serum samples.

Conclusions:

  • The developed cascaded logic gate-based EC method enables precise and rapid discrimination of multiple cancers based on miRNA signatures.
  • This approach offers a new tool for system and precision medicine, enhancing diagnostic capabilities for complex diseases.
  • The sensor's ability to analyze logical relationships among miRNAs represents a significant advancement over discrete target detection.
Keywords:
Electrochemical biosensorLogical analysisMulti-cancer discriminationMultiple miRNAs detectionTetrahedral DNA nanostructure

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