Monolithically-integrated cytometer for measuring particle diameter in the extracellular vesicle size range using...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Analytical Chemistry

Background:

• Conventional flow cytometry faces challenges in extracellular vesicle (EV) size measurement due to high costs and optical uncertainties.
• Non-specialized free-space optics in current systems limit accuracy and precision for sub-micron particle analysis.

Purpose of the Study:

• To develop a low-cost, high-precision integrated cytometer for extracellular vesicle (EV) size measurement.
• To demonstrate the capability of multi-angle scattering analysis within an integrated microfluidic chip for sub-micron particle sizing.

Main Methods:

• Utilized Dean-based hydrodynamic focusing for tight sample core stream delivery.
• Integrated waveguides with multimode interference devices for precise excitation beam focusing.
• Employed an angular array of collection waveguides for multi-angle scattering distribution measurement.

Main Results:

• Successfully detected low-index 200 nm liposomes.
• Measured polystyrene size standards as small as 400 nm diameter with an uncertainty of ±21 nm (1/2 IQR).
• Demonstrated improved size measurement accuracy and precision compared to conventional methods.

Conclusions:

• The developed integrated cytometer shows significant promise for accurate and precise extracellular vesicle (EV) size analysis.
• This technology represents a key advancement towards high-performance, cost-effective integrated cytometry for EV research.
• The multi-angle scattering approach within a monolithic chip design is effective for sub-micron particle characterization.