Towards High Throughput Cell Growth Screening: A New CMOS 8 × 8 Biosensor Array for Life Science Applications

Area of Science:

• Biomedical Engineering
• Microelectronic Sensors
• Cell Biology

Background:

• Cell growth monitoring is crucial for drug discovery and biological research.
• Existing methods can be time-consuming, expensive, or lack real-time capabilities.
• Need for compact, low-cost, high-throughput platforms for cell monitoring.

Purpose of the Study:

• To develop and validate a CMOS capacitive sensor array for label-free, real-time cell growth monitoring.
• To demonstrate the sensor's sensitivity and reliability using various materials and cell lines.
• To provide a platform for high-throughput screening of cell behavior.

Main Methods:

• Design and fabrication of an 8x8 CMOS fully differential charge-based capacitive sensor array.
• Integration of a DC-input Sigma-Delta (ΣΔ) modulator for signal digitization.
• Calibration circuitry to compensate for transistor mismatch and reduce output voltage offset.
• Validation using organic solvents, polystyrene beads, and H1299 lung carcinoma cells.

Main Results:

• Successful compensation of current mirror transistor mismatch with <8.2% error.
• Detection of polystyrene bead concentrations from 10 to 100,000 beads/ml.
• Real-time monitoring of H1299 cell attachment and growth over 30 hours, consistent with standard assays.
• Demonstrated label-free and highly sensitive detection capabilities.

Conclusions:

• The developed CMOS capacitive sensor array offers a compact, low-cost, and high-throughput solution for cell growth monitoring.
• The biosensor's high sensitivity and real-time capabilities are suitable for label-free detection.
• This technology presents significant opportunities for rapid screening of living cells and drug development.