Multidimensional Tunability of Nucleic Acids Enables Sensing over Unknown Backgrounds

Area of Science:

• Biotechnology
• Analytical Chemistry
• Molecular Sensing

Background:

• Quantitative analysis faces challenges aligning sensor dynamic range with background values for reliable measurements.
• This misalignment is particularly critical for sensing systems with sharp response characteristics.
• Existing methodologies struggle with accurate detection in the presence of unknown or variable backgrounds.

Purpose of the Study:

• To address the longstanding problem of response range/background misalignment in quantitative sensing.
• To design and demonstrate sensing systems capable of autonomously adjusting their response to unknown backgrounds.
• To develop a general methodology for adaptive sensing systems based on nucleic acid scaffolds.

Main Methods:

• Utilized nucleic acid scaffolds, specifically a DNA i-motif, for sensor design.
• Leveraged the multidimensional tunability of nucleic acid structures to assess and adapt to background conditions.
• Established a general methodology for creating background-adaptive sensing systems.

Main Results:

• Successfully designed sensing systems that adjust their response range to actual unknown backgrounds.
• Demonstrated a proof-of-concept using a DNA i-motif sensor for detecting proton concentration changes.
• Achieved reliable measurement of proton concentration changes three orders of magnitude lower than current methodologies.

Conclusions:

• The developed nucleic acid-based sensing systems effectively solve the response range/background misalignment problem.
• The multidimensional tunability of DNA i-motifs enables highly sensitive and adaptive quantitative analysis.
• This approach offers a significant advancement for detecting subtle changes in complex aqueous environments.