Design, Fabrication, and Testing of a Hybrid CMOS/PDMS Microsystem for Cell Culture and Incubation

Abstract

We discuss the design, fabrication, and testing of a hybrid microsystem for stand-alone cell culture and incubation. The micro-incubator is engineered through the integration of a silicon CMOS die for the heater and temperature sensor, with multilayer silicone (PDMS) structures namely, fluidic channels and a 1.5-mm diameter 12-muL culture well. A 90-mum-thick PDMS membrane covers the top of the culture well, acting as barrier to contaminants while at the same time allowing the cells to breath and exchange gases with the ambient environment. The packaging for the microsystem includes a flexible polyimide electronic ribbon cable and four fluidic ports that provide external interfaces to electrical energy, closed-loop sensing and electronic control as well as solid and liquid supplies. The complete structure has a size of (2.5times2.5times0.6) cm(3). We have employed the device to successfully culture BHK-21 cells autonomously over a three day period in ambient environment.

System-on-Chip Considerations for Heterogeneous Integration of CMOS and Fluidic Bio-Interfaces

“…Modeling temperature variations: Ceramic dual inline packages (CerDIPs) are designed to act as heat sinks [36], but lab-on-CMOS packages present new thermal boundary conditions. Typical thermal analysis of IC operation assumes a boundary condition of room temperature.…”

“…This two-step iterative modeling approach requires an initial SPICE simulation to find the power dissipation of the circuit blocks. Power dissipated over the circuit layout areas is used to model thermal heating effects using a finite element simulator [36] such as COMSOL, adding information on materials and the environment. Then, the results of the thermal simulation can be fed back into the SPICE simulation to specify the operating temperature of the circuits for determination of changes in operation and power consumption.…”

“…However, when the IC is operated, power dissipation raises the chip surface temperature. This causes hot spots that can exceed the acceptable range for cell culture [36]. Fig.…”

“…For use of the lab-on-CMOS system outside an incubator, on-chip heaters can be employed advantageously to warm the cell medium [36], at the expense of significant power draw. However, many biological experiments require fluid flow over the cells.…”

A Self-Contained System With CNTs-Based Biosensors for Cell Culture Monitoring

“…The electrical properties of RTD varies according to the temperature. Temperature can also be measured by using a diode-based proportional-to-absolute temperature (PTAT) thermometer, which generates an output voltage proportional to the temperature [20].…”