A Differential Impedance Flow Cytometry Front-End With Baseline Current Cancellation.

Area of Science:

• Electrical Engineering
• Biomedical Engineering
• Microfluidics

Background:

• Impedance-based flow cytometry requires sensitive readout circuits to detect cellular or particle properties.
• Existing analog front-end (AFE) circuits often face challenges with baseline current, TIA saturation, and noise, limiting performance.
• A robust AFE is crucial for accurate and efficient particle analysis in microfluidic systems.

Purpose of the Study:

• To design and demonstrate a high-performance analog front-end (AFE) circuit for impedance-based flow cytometry.
• To address limitations of existing AFEs, such as TIA saturation and noise, through innovative circuit design.
• To validate the AFE's capability for detecting small particles in a microfluidic flow cell.

Main Methods:

• Designed a novel AFE circuit using a 180nm CMOS process, featuring a digitally tunable and calibrated cancellation current path.
• Interfaced the AFE with a three-electrode sensor topology for center electrode excitation and differential current output.
• Implemented digital calibration using an off-chip ADC and automated algorithm for precise operation.
• Characterized the AFE's performance, including input-referred current noise density and excitation frequency range.

Main Results:

• Achieved a low input-referred current noise density of $1.7 \text{pA}/\sqrt{\text{Hz}}$ at 1MHz excitation with floating inputs.
• Demonstrated detection of 3um diameter particles in a microfluidic flow cell, confirming practical utility.
• Operated across an excitation frequency range of 0.5MHz to 10MHz with a power consumption of 15.6mW.
• The cancellation current path effectively prevented TIA saturation, enabling higher gain and improved noise rejection.

Conclusions:

• The developed AFE circuit offers high performance and power efficiency for impedance-based flow cytometry.
• The digitally tunable cancellation current path is key to overcoming TIA saturation and enhancing signal integrity.
• The AFE's demonstrated particle detection capability validates its suitability for advanced microfluidic diagnostic applications.