System-on-Chip for Flow Cytometry With Impedance Measurement and Integrated Real-Time Size Classification

Area of Science:

• Electrical Engineering
• Biomedical Engineering
• Microfluidics

Background:

• Flow cytometry is crucial for cell counting and analysis.
• Accurate impedance measurements are key for label-free cell characterization.
• Existing systems may lack real-time processing capabilities or require bulky instrumentation.

Purpose of the Study:

• To develop an integrated system-on-chip (SoC) for impedance-based flow cytometry.
• To enable real-time cell counting and size determination.
• To demonstrate the SoC's performance in particle detection and classification.

Main Methods:

• A source-differential, three-electrode sensing scheme in a microfluidic flow cell.
• A front-end lock-in amplifier with a 60 MHz TIA, passive mixers, and low-pass filters.
• Back-end processing with an 8-bit level-crossing ADC (LCADC) for I/Q signal digitization, feature extraction, and linear classification.
• Fabrication in a 180 nm CMOS process.

Main Results:

• Achieved a noise floor of 733 fA/sqrt(Hz) and 23 pArms input-referred noise (1-1 kHz).
• Demonstrated particle counting using polymer beads (3-10 µm diameters).
• On-chip classification of 4.5 µm and 6 µm beads with 86.16% accuracy (offline) and 73.6% (real-time).

Conclusions:

• The developed SoC is effective for impedance-based flow cytometry applications.
• The system enables real-time particle counting and size determination.
• The integrated solution offers a promising approach for portable and efficient cell analysis systems.