Abstract
The development of continuous bioprocesses—which require cell retention systems in order to enable longer cultivation durations—is a primary focus in the field of modern process development. The flow environment of microfluidic systems enables the granular manipulation of particles (to allow for greater focusing in specific channel regions), which in turn facilitates the development of small continuous cell separation systems. However, previously published systems did not allow for separation control. Additionally, the focusing effect of these systems requires constant, pulsation-free flow for optimal operation, which cannot be achieved using ordinary peristaltic pumps. As described in this paper, a 3D printed cell separation spiral for CHO-K1 (Chinese hamster ovary) cells was developed and evaluated optically and with cell experiments. It demonstrated a high separation efficiency of over 95% at up to 20 × 106 cells mL−1. Control over inlet and outlet flow rates allowed the operator to adjust the separation efficiency of the device while in use—thereby enabling fine control over cell concentration in the attached bioreactors. In addition, miniaturized 3D printed buffer devices were developed that can be easily attached directly to the separation unit for usage with peristaltic pumps while simultaneously almost eradicating pump pulsations. These custom pulsation dampeners were closely integrated with the separator spiral lowering the overall dead volume of the system. The entire device can be flexibly connected directly to bioreactors, allowing continuous, pulsation-free cell retention and process operation.
Highlights
Microfluidic systems in biology and biochemistry are often focused on combining several lab procedures into a single system, thereby creating a so-called lab-on-a-chip [1,2,3].Significant attention has recently been given to adherent cell cultivation on microfluidic systems in the field of organ-on-a-chip, with the aim of furthering technological advances for medical testing and research [4,5,6,7]
The unique physical environment that is created inside microfluidic channels allows for a high degree of fluid control and facilitates interesting and frequently useful particle−fluid interactions—which can be exploited for cell handling purposes
These interactions define the field of inertial microfluidics, which focuses on identifying and refining channel shapes and structures that transfer, mix, focus, and/or separate particles within microfluidic systems [8]
Summary
Microfluidic systems in biology and biochemistry are often focused on combining several lab procedures into a single system, thereby creating a so-called lab-on-a-chip [1,2,3].Significant attention has recently been given to adherent cell cultivation on microfluidic systems in the field of organ-on-a-chip, with the aim of furthering technological advances for medical testing and research [4,5,6,7]. The unique physical environment that is created inside microfluidic channels allows for a high degree of fluid control and facilitates interesting and frequently useful particle−fluid interactions—which can be exploited for cell handling purposes. These interactions define the field of inertial microfluidics, which focuses on identifying and refining channel shapes and structures that transfer, mix, focus, and/or separate particles within microfluidic systems [8]. The flow inside the microfluidic channels is considered laminar (Reynolds number Re
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