An on-chip microfluidic pressure regulator that facilitates reproducible loading of cells and hydrogels into microphysiological system platforms

Abstract

Coculturing multiple cell types together in 3-dimensional (3D) cultures better mimics the in vivo microphysiological environment, and has become widely adopted in recent years with the development of organ-on-chip systems. However, a bottleneck in set-up of these devices arises as a result of the delivery of the gel into the microfluidic chip being sensitive to pressure fluctuations, making gel confinement at a specific region challenging, especially when manual operation is performed. In this paper, we present a novel design of an on-chip regulator module with pressure-releasing safety microvalves that can facilitate stable gel delivery into designated microchannel regions while maintaining well-controlled, non-bursting gel interfaces. This pressure regulator design can be integrated into different microfluidic chip designs and is compatible with a wide variety of gel injection apparatuses operated automatically or manually at different flow rates. The sensitivity and working range of this pressure regulator can be adjusted by changing the width of its pressure releasing safety microvalve design. The effectiveness of the design is validated by its incorporation into a microfluidic platform we have developed for generating 3D vascularized micro-organs (VMOs). Reproducible gel loading is demonstrated for both an automatic syringe pump and a manually-operated micropipettor. This design allows for rapid and reproducible loading of hydrogels into microfluidic devices without the risk of bursting gel-air interfaces.

Consensus guidelines for the use and interpretation of angiogenesis assays

“…During normal loading, perfusion burst valves at the interface between the tissue chamber and the microfluidic channels ensure a gel/air interface (later a gel/fluid interface) is formed. To simplify loading and minimize specialized training for new users of the platform, current iterations of the VMO platform incorporate a pressure release valve at the loading tunnel that minimizes unintended gel bursting [ 92 ]. Second, robust vascular network formation requires that vessels within the chamber anastomose with the outer microfluidic channels.…”

Inspired by Nature: Hydrogels as Versatile Tools for Vascular Engineering

“…When such microfluidic channels are fused with micro-capillary networks, the whole engineered vascularized model can be perfused. [143][144][145][146] Conceivably, the dominant field in microfluidics perfused tissue models is cancer. 147 In this regard, vascularized microtumors (VMT) have been generated in hydrogels.…”

Analysis of tumoral spheres growing in a multichamber microfluidic device

“…The microdevice used in this study resulted in the simplest and easiest form of seeding, compared to the aforementioned device filling methods. It is known that increased pressure can affect cell division and other mechanical properties of the cell, as observed in other studies (Liu & Tai, ; Wang et al, ). In this work, differences in the distribution of pressure was observed, that could be affecting the localization and growth of spheres inside of the microdevice.…”