In Vivo Flow Cytometry of Extremely Rare Circulating Cells

Area of Science:

• Biomedical Engineering
• Cancer Research
• Medical Imaging

Background:

• Circulating tumor cells (CTCs) are crucial biomarkers for cancer metastasis.
• Current methods for enumerating CTCs are often invasive and lack optimal sensitivity.
• There is a need for non-invasive techniques to detect rare cells in circulation.

Purpose of the Study:

• To develop and validate a novel non-invasive tool for detecting rare circulating cells.
• To assess the capability of the new tool for enumerating cells in vivo.
• To evaluate the tool's potential for studying hematogenous cancer metastasis.

Main Methods:

• Development of Diffuse in vivo Flow Cytometry (DiFC) using near-infrared diffuse photons.
• Utilization of custom dual fiber optic probes placed on the skin surface.
• Application of a novel signal processing algorithm for cell detection, counting, and speed/depth measurement.
• In vivo validation in small animal models.

Main Results:

• DiFC enables non-invasive detection and counting of fluorescently-labeled circulating cells directly in bloodstream.
• The technique allows sampling of entire mouse blood volume in under 10 minutes.
• Achieved a low false alarm rate (0.014 per minute), enabling detection of <1 cell/mL.
• Demonstrated capability to measure cell direction, speed, and depth.

Conclusions:

• Diffuse in vivo Flow Cytometry (DiFC) offers a highly sensitive, non-invasive method for rare cell detection.
• DiFC is well-suited for studying hematogenous cancer metastasis and other rare cell dynamics.
• This technology advances small animal research tools for critical biomedical applications.