Analytical and Bioanalytical Chemistry

, Volume 410, Issue 28, pp 7285–7293 | Cite as

Toehold integrated molecular beacon system for a versatile non-enzymatic application

  • Zhenping Liu
  • Yiyun Wang
  • Xuchu Wang
  • Weiwei Liu
  • Yibei Dai
  • Pan Yu
  • Zhaoping Liao
  • Ying Ping
  • Zhihua TaoEmail author
Paper in Forefront


A molecular beacon (MB) is an oligonucleotide hybridization probe with a hairpin-shaped structure that leads to specific and instantaneous nucleic acid hybridization, enabling a variety of applications. However, integration of additional module sequences interferes with the performance of MBs and increases the complexity of sequence design. Herein, we develop and characterize a toehold integrated molecular beacon (ToMB) strategy for nucleic acid hybridization, where the reaction rate can be flexibly regulated by a target-induced MB conformational switch. Using this basic mechanism, the ToMB is capable of identifying nucleic acids with high specificity and a wider linearity range compared with the conventional molecular beacon system. We further applied the ToMB to the construction of a hybridization chain reaction system and a basic OR logic gate VJHto explore its programmability and versatility. Our results strongly suggest that the novel ToMB can act as a powerful nano-module to construct universal and multifunctional biosensors or molecular computations.

Graphical abstract

Molecular beacon is employed as a flexible and switchable spacer to control the toehold-mediated strand displacement reaction.


Molecular beacon Toehold-mediated strand displacement reaction Nucleic acid hybridization 



We thank the Clinical Research Center from the Second Affiliated Hospital of Zhejiang University School of Medicine for essential technical supports. We thank the American Journal Experts (AJE) for English language editing.


This study was supported by grant from Natural Science Foundation of Zhejiang Province (Grant nos. LY14H200002, LY15H200002, and LY16H160023).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supplementary material

216_2018_1340_MOESM1_ESM.pdf (552 kb)
ESM 1 (PDF 551 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Zhenping Liu
    • 1
  • Yiyun Wang
    • 1
  • Xuchu Wang
    • 2
  • Weiwei Liu
    • 2
  • Yibei Dai
    • 2
  • Pan Yu
    • 2
  • Zhaoping Liao
    • 3
  • Ying Ping
    • 2
  • Zhihua Tao
    • 1
    • 2
  1. 1.Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouChina
  2. 2.Department of Laboratory Medicinethe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
  3. 3.Department of Transfusionthe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina

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