Development of a microfluidic device with precise on-chip temperature control by integrated cooling and heating components for single cell-based analysis

An integrated microfluidic device with active cooling and heating systems was developed in aiming a precise and rapid temperature control in the range between 2 °C and 37 °C. The platform, which consisted of a cooling chamber, a microheater, and a temperature sensor, achieved an active feedback control of on-chip local temperature. Multiphysics simulation was conducted in the coupled modeling of heat transfer, fluid flow, and Joule heating. These modeling and simulation validated the design parameters to achieve a precise and quick control of on-chip local temperature control. The main principle of the design is to enhance the external heat transfer by utilizing micro-channel array on the chip surface and increase the sample surface versus its volume by holding the sample inside the system as an ultra-thin film. Using the precooled saturated calcium chloride aqueous solution as the coolant, and the on-chip microheater as the heating unit, the temperature was able to be precisely adjusted, and meanwhile, the temperature was sensed by a thermal sensor at the region of interest. We demonstrated an actual temperature control and manipulation of the developed microfluidic cooling/heating system. The recorded temperature data showed that the developed integrated platform offered the capability of manipulating on-chip localized temperature ranging from 2 °C to 37 °C with active cooling/heating, especially for the temperature range from 2 °C to room temperature chosen due to typical cytotoxic issues with additive cryoprotective agents (CPAs). Additionally, this device provided valuable tools for studying temperature-dependent biological and chemical processes at microscale, for example, the determination of permeability of the cell membrane to water and CPAs in cryobiology study.