Systematic characterization of cleanroom-free fabricated macrovalves, demonstrating pumps and mixers for automated fluid handling tuned for organ-on-chip applications

Elsbeth G B M Bossink; Anke R Vollertsen; Joshua T Loessberg-Zahl; Andries D van der Meer; Loes I Segerink; Mathieu Odijk

doi:10.1038/s41378-022-00378-y

Systematic characterization of cleanroom-free fabricated macrovalves, demonstrating pumps and mixers for automated fluid handling tuned for organ-on-chip applications

Microsyst Nanoeng. 2022 May 23:8:54. doi: 10.1038/s41378-022-00378-y. eCollection 2022.

Authors

Elsbeth G B M Bossink¹, Anke R Vollertsen^{1

2}, Joshua T Loessberg-Zahl¹, Andries D van der Meer², Loes I Segerink¹, Mathieu Odijk¹

Affiliations

¹ BIOS Lab on a Chip Group, MESA+Institute, Technical Medical Center, Max Planck Institute for Complex Fluid Dynamics, University of Twente, Enschede, The Netherlands.
² Applied Stem Cell Technologies Group, Technical Medical Center, University of Twente, Enschede, The Netherlands.

Abstract

Integrated valves enable automated control in microfluidic systems, as they can be applied for mixing, pumping and compartmentalization purposes. Such automation would be highly valuable for applications in organ-on-chip (OoC) systems. However, OoC systems typically have channel dimensions in the range of hundreds of micrometers, which is an order of magnitude larger than those of typical microfluidic valves. The most-used fabrication process for integrated, normally open polydimethylsiloxane (PDMS) valves requires a reflow photoresist that limits the achievable channel height. In addition, the low stroke volumes of these valves make it challenging to achieve flow rates of microliters per minute, which are typically required in OoC systems. Herein, we present a mechanical 'macrovalve' fabricated by multilayer soft lithography using micromilled direct molds. We demonstrate that these valves can close off rounded channels of up to 700 µm high and 1000 µm wide. Furthermore, we used these macrovalves to create a peristaltic pump with a pumping rate of up to 48 µL/min and a mixing and metering device that can achieve the complete mixing of a volume of 6.4 µL within only 17 s. An initial cell culture experiment demonstrated that a device with integrated macrovalves is biocompatible and allows the cell culture of endothelial cells over multiple days under continuous perfusion and automated medium refreshment.

Keywords: Microengraving; Microfluidics.