Small-Molecule Probes Enhance in Vivo Field-Effect Transistor-Based Biosensing by Overcoming Debye Length...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Biosensing

Background:

• Field-effect transistor (FET) biosensors offer high sensitivity for biomedical detection.
• Sensitivity is limited by the Debye length, especially in high-ionic-strength biological fluids.
• Traditional probes (antibodies, aptamers) exceed the Debye length, reducing FET biosensor performance.

Purpose of the Study:

• To design and synthesize small molecule recognition probes (approx. 1 nm) to overcome the Debye length limitation in FET biosensors.
• To maintain high sensitivity of FET biosensors in biological environments.
• To develop a novel FET biosensor for real-time in vivo monitoring of biological targets.

Main Methods:

• Designed and synthesized small molecules as recognition probes.
• Functionalized a field-effect transistor (FET) sensing channel with the small molecule probes.
• Developed an ATP-responsive Small Molecules probe functionalIzed needLE (SMILE) FET biosensor.
• Validated the biosensor's performance using ATP detection in physiological solutions and in vivo mouse models.

Main Results:

• The SMILE FET biosensor demonstrated excellent affinity, selectivity, and sensitivity for ATP detection.
• Achieved a low limit of detection of 82 fM for ATP in physiological solution.
• Successfully enabled real-time monitoring of ATP levels and dynamic variations in normal and depressed mice.
• The small molecule probes maintained sensor sensitivity within the Debye length limitation in biological environments.

Conclusions:

• Small molecule probes effectively overcome the Debye length limitation in FET biosensors for biomedical applications.
• The developed SMILE FET biosensor provides a sensitive and selective platform for in vivo detection of ATP.
• This approach offers a new solution for enhancing FET biosensor performance in complex biological systems and for in vivo studies.