Quantitative phase imaging with molecular sensitivity using photoacoustic microscopy with a miniature ring transducer

Area of Science:

• Biomedical optics
• Cellular imaging
• Microscopy

Background:

• Accurate cellular structural and molecular information is crucial for diagnostics.
• Existing imaging techniques may have limitations in resolution, specificity, or cost.
• There is a need for integrated systems offering complementary imaging modalities.

Purpose of the Study:

• To develop and demonstrate a dual-modality imaging system integrating quantitative phase imaging (QPI) and photoacoustic microscopy (PAM).
• To achieve coregistered structural and molecular imaging of cells.
• To explore the potential of this system as a compact and low-cost cellular diagnostic assay.

Main Methods:

• A dual-modality system was developed, combining off-axis holography-based QPI with a sinusoidally modulated optical source and ring ultrasonic transducer-based PAM.
• Confocal alignment of excitation beams and ultrasonic detector was facilitated for simplicity.
• The system was tested using endogenous molecules in red blood cells and exogenous molecular labels (gold nanoparticles targeting EGFR) on cancer cells.

Main Results:

• Quantitative Phase Imaging (QPI) provided high-resolution imaging of cellular structures.
• Photoacoustic Microscopy (PAM) delivered molecular contrast, enabling specific molecular detection.
• The system successfully imaged both endogenous and exogenous molecular targets in cells.

Conclusions:

• The developed dual-modality QPI-PAM system enables simultaneous structural and molecular cell imaging.
• This integrated approach offers high resolution and molecular specificity.
• The technology holds potential for implementation as a compact, low-cost cellular diagnostic assay.