Generalizable Molecular Switch Designs for In Vivo Continuous Biosensing

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Analytical Chemistry

Background:

• Continuous biosensors offer potential for personalized and preventative medicine.
• Current biosensors often lack the necessary specificity, sensitivity, and temporal resolution for in vivo applications.
• Molecular switches are promising for label-free, specific sensing but require generalizable designs.

Purpose of the Study:

• To develop generalizable molecular switch designs for rapid creation of high-performance biosensors.
• To engineer aptamer-based and antibody-based molecular switches for diverse biomarker detection.
• To enable continuous, real-time monitoring of health indicators.

Main Methods:

• Rational design and structural engineering of aptamer switches.
• High-throughput screening of aptamer libraries for switch discovery.
• Development of antibody-based molecular switches using competitive immunoassay principles.

Main Results:

• Demonstrated continuous optical detection of cortisol and dopamine using engineered aptamer switches.
• Achieved 100-fold enhanced sensitivity for a protein target using a chimeric antibody-aptamer switch.
• Developed a competitive antibody-switch for continuous cortisol detection in whole blood with minute-scale resolution.

Conclusions:

• Advances in molecular switch design accelerate the development of continuous biosensors.
• Engineered molecular switches enhance sensitivity, specificity, and temporal resolution for biomarker detection.
• These developments pave the way for more personalized and preventative healthcare through real-time diagnostics.