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Ultrasensitive Detection of Biomarkers by Using a Molecular Imprinting Based Capacitive Biosensor
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Metamaterials-based label-free nanosensor for conformation and affinity biosensing.

Cuong Cao1, Jun Zhang, Xinglin Wen

  • 1Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University , Singapore 637371.

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This study introduces tunable plasmonic metamaterials that enable simultaneous measurement of molecular binding and conformational changes. This dual-channel approach enhances biomolecular analysis for disease detection and drug development.

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Area of Science:

  • Biophysics
  • Nanotechnology
  • Biochemistry

Background:

  • Molecular interactions and conformational dynamics are crucial for biological functions, disease, and drug development.
  • Plasmonic biosensors (SPR/LSPR) detect molecular binding but cannot probe conformational changes.
  • Surface-enhanced Raman spectroscopy (SERS) detects vibrational signatures but lacks the broad applicability of plasmonic sensors.

Purpose of the Study:

  • To develop a novel biosensing platform capable of simultaneously analyzing molecular binding and conformational states.
  • To overcome the limitations of traditional plasmonic biosensors in interrogating biomolecular dynamics.
  • To demonstrate the utility of this platform for sensitive detection of specific biomolecular interactions.

Main Methods:

  • Fabrication of highly tunable plasmonic metamaterials.
  • Integration of optical transmission and surface-enhanced Raman spectroscopy (SERS) detection channels.
  • Application of the metamaterial platform to study G-quadruplexes and their interactions with nucleolin.

Main Results:

  • The metamaterials provide two parallel transducing channels for simultaneous optical transmission and SERS acquisition.
  • The platform successfully probes both conformational states and binding affinity of biomolecules like G-quadruplexes.
  • Achieved picomolar sensitivity for the detection and fingerprinting of the arginine-glycine-glycine domain of nucleolin, a cancer biomarker.

Conclusions:

  • Tunable plasmonic metamaterials offer a powerful dual-channel biosensing approach.
  • This method enables simultaneous interrogation of biomolecular conformation and binding affinity.
  • The platform demonstrates significant potential for sensitive biomarker detection and advancing molecular interaction analysis.