Abstract
Microfluidic platforms use controlled fluid flows to provide physiologically relevant biochemical and biophysical cues to cultured cells in a well-defined and reproducible manner. Undisturbed flows are critical in these systems, and air bubbles entering microfluidic channels can lead to device delamination or cell damage. To prevent bubble entry into microfluidic channels, we report a low-cost, Rapidly Integrated Debubbler (RID) module that is simple to fabricate, inexpensive, and easily combined with existing experimental systems. We demonstrate successful removal of air bubbles spanning three orders of magnitude with a maximum removal rate (dV/dt)max = 1.5 mL min−1, at flow rates required to apply physiological wall shear stress (1–200 dyne cm−2) to mammalian cells cultured in microfluidic channels.
Highlights
In the 1990s microfluidic systems gained popularity in analytical “lab-on-a-chip” platforms owing to unique microscale capabilities including robust sample routing, rapid multiplexed analysis, and laboratory portability [1,2]
To address hurdles related to both complex fabrication and integration of debubblers, we introduce a simple workflow to create a rapidly integrated debubbler (RID) module that can be combined with existing microfluidic systems
To ensure that Rapidly Integrated Debubbler (RID) modules could be used for shear stimulation studies relevant to human (1–50 dyne cm−2) [26] and rodent cell studies (50–200 dyne cm−2) [27], segmented air-liquid streams were introduced at flow rates corresponding to defined wall shear-stress (WSS) in a standard geometry microfluidic channel, h = 0.1 mm, w = 1 mm, and l = 1 cm, with the channel volume Vchannel = 1 μL
Summary
In the 1990s microfluidic systems gained popularity in analytical “lab-on-a-chip” platforms owing to unique microscale capabilities including robust sample routing, rapid multiplexed analysis, and laboratory portability [1,2]. Over the past two decades, these benefits have been extended to cell culture applications where favorable scaling effects (e.g., laminar flows, high surface to volume ratios, and short diffusion distances) have been leveraged to create physiologically-relevant microenvironments featuring precisely controlled biochemical and biophysical stimuli [3,4,5,6]. In these microscale systems, undisrupted flow is required to deliver cell culture media, maintain long-term cell viability, and control cellular-scale cues [7,8]. Given the challenges associated with unwanted bubbles entering microfluidic systems, several mitigation strategies have been developed
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