Abstract
Microfluidic devices are widely used for biomedical applications but there is still a lack of affordable, reliable and user-friendly systems for transferring microfluidic chips from an incubator to a microscope while maintaining physiological conditions when performing microscopy. The presented carrier represents a cost-effective option for sustaining environmental conditions of microfluidic chips in combination with minimizing the device manipulation required for reagent injection, media exchange or sample collection. The carrier, which has the outer dimension of a standard well plate size, contains an integrated perfusion system that can recirculate the media using piezo pumps, operated in either continuous or intermittent modes (50–1000 µl/min). Furthermore, a film resistive heater made from 37 µm-thick copper wires, including temperature feedback control, was used to maintain the microfluidic chip temperature at 37 °C when outside the incubator. The heater characterisation showed a uniform temperature distribution along the chip channel for perfusion flow rates up to 10 µl/min. To demonstrate the feasibility of our platform for long term cell culture monitoring, mouse brain endothelial cells (bEnd.3) were repeatedly monitored for a period of 10 days, demonstrating a system with both the versatility and the potential for long imaging in microphysiological system cell cultures.
Highlights
Microfluidic devices are widely used for biomedical applications but there is still a lack of affordable, reliable and user-friendly systems for transferring microfluidic chips from an incubator to a microscope while maintaining physiological conditions when performing microscopy
The carrier holds the microfluidic chip, piezo pumps and cell media reservoirs, Pump locks 1 and 2 fix the pumps to the carrier, The chip lock fixes the microfluidic chip to the carrier to facilitate the imaging and manipulation while enhancing the contact between the chip and the heater, The thermocouple hold-down clamp keeps the thermocouple against the heater to provide temperature feedback control, The thermocouple holder prevents direct contact between the thermocouple and the heater serpentine, Fig. 1
We have presented an integrated system that enables repeated transfers of microfluidic chips used for cell culture between an incubator and a microscope whilst maintaining a physiological temperature and periodic cell media turnover
Summary
The carrier, chip lock, pump locks and hold down clamp for the thermocouple are 3D printed with a commercial printer (Ultimaker 2+, Ultimaker) while the heater is obtained by UV lithography of a copper foil. The pump and heating system are interfaced with an Arduino board. The pump controller and respective driver are available on the pump producer website (Bartels Mikrotechnik GmbH), while the heat control hardware is available on the provided author repository
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