Design and implementation of a microscale thermophoresis system based on complementary metal-oxide-semiconductor...

Area of Science:

• Biochemistry
• Biophysics
• Analytical Chemistry

Background:

• Microscale Thermophoresis (MST) is vital for detecting molecular interactions in drug discovery.
• Current MST instruments use single-point sensors (photodiodes or photomultiplier tubes - PMTs).
• Limitations exist in current sensor technology for sensitive molecular interaction detection.

Purpose of the Study:

• To systematically evaluate Photomultiplier Tube (PMT) versus Complementary Metal-Oxide-Semiconductor (CMOS) imaging in MST.
• To develop and validate an optimized CMOS-based MST platform for enhanced molecular interaction analysis.
• To assess the performance and reliability of CMOS imaging for sensitive biochemical assays.

Main Methods:

• Comparative performance analysis of PMT and CMOS imaging in MST.
• Development of an automated CMOS-based MST platform with intelligent region selection.
• Validation using protein-protein interactions, antigen-antibody binding, and small molecule interactions.

Main Results:

• CMOS imaging demonstrated superior signal-to-noise ratio, dynamic range, and spatial resolution.
• CMOS enabled simultaneous full-field data acquisition, improving measurement efficiency.
• The CMOS-based MST platform achieved comparable detection sensitivity to existing technologies.

Conclusions:

• CMOS imaging technology offers significant advantages for Microscale Thermophoresis applications.
• The developed CMOS-based MST platform provides a reliable and efficient solution for biochemical research.
• This advanced platform is particularly beneficial for drug development assays with strong fluorescence signals.