Nonspecific Binding-Fundamental Concepts and Consequences for Biosensing Applications.

Area of Science:

• Biomolecular interactions
• Biosensor technology
• Molecular recognition

Background:

• Distinguishing specific from nonspecific binding is crucial for biosensor accuracy.
• Nonspecific binding remains a significant bottleneck in biosensor development.
• A fundamental understanding of nonspecific binding is lacking, leading to ongoing debate.

Purpose of the Study:

• To review the evolution of the concept of nonspecific binding over five decades.
• To provide classification frameworks for biomolecular interactions.
• To introduce theoretical models for biosensor performance prediction and optimization.

Main Methods:

• Thermodynamic, intermolecular, and structural perspectives on binding.
• Review of theoretical models for biosensor behavior in physiological environments.
• Discussion of practical approaches to mitigate nonspecific binding.

Main Results:

• Classification frameworks for biomolecular interactions based on binding perspectives.
• Theoretical models to predict biosensor detection limits and optimize performance.
• Overview of strategies to address and utilize nonspecific binding.

Conclusions:

• Understanding nonspecific binding is key to advancing biosensor technology.
• Theoretical models aid in predicting and optimizing biosensor performance.
• Practical solutions exist for in vitro applications, with potential for in vivo systems.