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Area of Science:

  • Biomedical Engineering
  • Neuroscience
  • Analytical Chemistry

Background:

  • Long-term in vivo neurochemical sensing faces limitations due to D-DNA aptamer degradation and unstable interfaces.
  • Existing methods struggle with sensor longevity and signal consistency for real-time monitoring.

Purpose of the Study:

  • To develop a stable and durable aptamer-based electrochemical sensor for long-term in vivo neurochemical detection.
  • To overcome the limitations of enzymatic degradation in conventional D-DNA aptamer sensors.

Main Methods:

  • Generated a mirror-image L-DNA analogue of a dopamine-binding aptamer.
  • Validated aptamer folding, affinity, and selectivity using circular dichroism, binding assays, and molecular docking.
  • Integrated the L-aptamer with a stabilized electrochemical interface on carbon-fiber microelectrodes for in vivo sensing.

Main Results:

  • Chiral inversion to L-DNA preserved aptamer function, demonstrating high affinity and selectivity for dopamine.
  • The L-aptamer sensor achieved continuous in vivo dopamine monitoring for over 24 hours, a significant improvement over D-aptamer sensors.
  • The sensor successfully resolved dopamine clearance defects in a Parkinson's disease mouse model.

Conclusions:

  • Mirror-image L-DNA aptamers offer exceptional nuclease resistance, enabling durable bioelectronic sensing in vivo.
  • Engineered electrochemical interfaces combined with L-aptamers provide a robust platform for advanced neurochemical monitoring.
  • This technology holds promise for improved diagnostics and research in neurological disorders.