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Generalizable Molecular Switch Designs for In Vivo Continuous Biosensing.

Jason Saunders¹, Ian A P Thompson¹, Hyongsok Tom Soh^1,2,3

¹Department of Electrical Engineering, Stanford University, Stanford, California 94305, United States.

Accounts of Chemical Research

|February 15, 2025

Summary

Researchers developed generalizable molecular switches for continuous biosensing, enabling personalized medicine through rapid biomarker detection. These novel designs improve sensitivity and speed for real-time health monitoring.

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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.