Densimeter-on-chip (DoC): measuring a single-cell mass density by sedimentation in microchannel flows

Area of Science:

• Biophysics
• Cell Biology
• Microfluidics

Background:

• Label-free cell identification relies on intrinsic biophysical and morphological features.
• Cell density is a key parameter for single-cell analysis but challenging to measure.
• Existing methods for cell density measurement are often complex or lack versatility.

Purpose of the Study:

• To develop a straightforward and versatile microfluidic chip for label-free single-cell mass density measurement.
• To establish a method for precise cell density determination applicable to various cell types and shapes.
• To validate the chip's accuracy against known cell densities.

Main Methods:

• A microfluidic chip (densimeter-on-chip, DoC) was designed utilizing hydrodynamic sedimentation.
• Cells undergo precise 3D alignment followed by a cross-section change to induce calibrated sedimentation.
• A mathematical model based on force balance and cell trajectory tracking calculates single-cell densities.
• The system accommodates object diameters from 0.75-22.5 μm.

Main Results:

• The DoC system achieved a minimum measurable density of 998 kg m⁻³ with a sensitivity of 0.001.
• High agreement (∼1% error) was observed between computational and literature values for red blood cells, lymphocytes, and neutrophils.
• The method is label-free, reproducible, and requires no chip modification for different cell types.

Conclusions:

• The densimeter-on-chip (DoC) provides an easy-to-use and reproducible solution for label-free single-cell density measurement.
• This technology offers a universal approach for characterizing a wide range of cell types, irrespective of size and shape.
• Accurate cell density determination using DoC can advance single-cell analysis and cell type identification.