Label-free mid-infrared photothermal live-cell imaging beyond video rate

Area of Science:

• Biomedical Optics
• Microscopy
• Spectroscopy

Background:

• Mid-infrared (MIR) spectroscopy shows promise for biomedical applications like liquid biopsy.
• MIR microscopy is limited for live, aqueous biological samples due to poor spatial resolution and high water absorption.
• Mid-infrared photothermal (MIP) imaging offers high spatial resolution for cell imaging but suffers from slow measurement rates.

Purpose of the Study:

• To develop a significantly improved wide-field MIP quantitative phase microscope.
• To overcome the speed limitations of previous MIP imaging techniques for live-cell analysis.
• To achieve high signal-to-noise ratio and beyond-video-rate live-cell imaging.

Main Methods:

• Numerical simulation of thermal conduction following the photothermal effect to derive optimal system design.
• Development of a novel system using a homemade nanosecond MIR optical parametric oscillator.
• Integration of a high full-well-capacity image sensor for enhanced data acquisition.

Main Results:

• Achieved a two orders-of-magnitude higher signal-to-noise ratio compared to previous MIP imaging.
• Demonstrated live-cell imaging at rates exceeding video rate.
• Developed a high-speed and high-spatial-resolution MIR microscope.

Conclusions:

• The developed MIP microscope significantly enhances speed and signal-to-noise ratio for live-cell imaging.
• This technology overcomes previous limitations of MIR microscopy in aqueous environments.
• The high-speed MIP microscope holds great potential as a new tool for life science and live-cell analysis.