Seamless integration of CMOS microsensors into open microfluidic systems

Area of Science:

• Biomedical Engineering
• Microfluidics
• Microelectronics

Background:

• Traditional 2D cell cultures lack predictive power for drug development.
• 3D tissue models, like microtissues, better mimic physiological conditions.
• The hanging-drop method is effective for microtissue formation and fluidic interconnection.

Purpose of the Study:

• To develop a multifunctional microelectrode array (MEA) integrated into an open microfluidic system.
• To enable in situ microtissue readouts in hanging-drop mode and conventional MEA use in standing-drop mode.
• To combine microfluidics with complementary metal-oxide-semiconductor (CMOS) technology for advanced biosensing.

Main Methods:

• Fabrication of a CMOS-MEA chip using a 0.18 microm CMOS process.
• Integration of the CMOS-MEA chip into an open microfluidic system.
• Development of a strategy for incorporating discrete CMOS sensors into microfluidic devices.

Main Results:

• The CMOS-MEA chip features two reconfigurable electrode arrays (1024 electrodes each).
• The system supports electrophysiology, impedance spectroscopy, and electrochemical sensing.
• Proof-of-concept experiments successfully analyzed hiPSC-derived cardiac microtissues and detected analytes like hydrogen peroxide and epinephrine.

Conclusions:

• The novel multifunctional CMOS-MEA integrated into a microfluidic system advances 3D tissue modeling.
• This technology provides a broad spectrum of biologically relevant information for drug development.
• The system demonstrates versatile applications in tissue engineering and biosensing.