A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays

Abstract

This paper reports a polydimethylsiloxane microfluidic model system that can develop an array of nearly identical human microtissues with interconnected vascular networks. The microfluidic system design is based on an analogy with an electric circuit, applying resistive circuit concepts to design pressure dividers in serially-connected microtissue chambers. A long microchannel (550, 620 and 775 mm) creates a resistive circuit with a large hydraulic resistance. Two media reservoirs with a large cross-sectional area and of different heights are connected to the entrance and exit of the long microchannel to serve as a pressure source, and create a near constant pressure drop along the long microchannel. Microtissue chambers (0.12 μl) serve as a two-terminal resistive component with an input impedance > 50-fold larger than the long microchannel. Connecting each microtissue chamber to two different positions along the long microchannel creates a series of pressure dividers. Each microtissue chamber enables a controlled pressure drop of a segment of the microchannel without altering the hydrodynamic behaviour of the microchannel. The result is a controlled and predictable microphysiological environment within the microchamber. Interstitial flow, a mechanical cue for stimulating vasculogenesis, was verified by finite element simulation and experiments. The simplicity of this design enabled the development of multiple microtissue arrays (5, 12, and 30 microtissues) by co-culturing endothelial cells, stromal cells, and fibrin within the microchambers over two and three week periods. This methodology enables the culturing of a large array of microtissues with interconnected vascular networks for biological studies and applications such as drug development.

The pumping lid: investigating multi-material 3D printing for equipment-free, programmable generation of positive and negative pressures for microfluidic applications

“…Because vapor pressure is a function of temperature (eqn (15) and (16)), the equilibrium pressure of FC-72/air system increased with temperature, yielding values consistent with those predicted by the VLE model (Fig. 7F).…”

“…In this approach, the difference in height of fluid in separate reservoirs generates the desired pressure drop. 15 These methods have a wide variety of applications, and some of them showed precision in the order of 10-20% of the measured values, 10,14 and one demonstrated 10% accuracy. 12 However, none of these methods can provide precise and predictable control of pumping while exhibiting all of the following features: absence of external equipment, capability of achieving a wide range of flow rates and achieving predictable flow rates that are independent of the sample's volume, surface energy and density.…”

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

“…To date, this has been performed primarily with sprouting models in which flow is applied to 1 monolayer surface and then the tube networks connect with 2 sides of the microfluidic device (containing flow channels). 21 Directional flow ensues through the tubes that connect the flow channels. Other variations of such models have been to create tube channels artificially in 3D matrixes to enable user-defined geometries of the vascular network and then seed the channels with ECs for the creation of tube networks in the absence of EC-driven tubulogenesis and vascular guidance tunnel formation.…”

3D Anastomosed Microvascular Network Model with Living Capillary Networks and Endothelial Cell-Lined Microfluidic Channels

“…Building on our previous publications [18][19][20][21][22], this protocol seeks to provide detailed practical procedures to develop a complete and contiguous 3D perfused microvascular network without nonphysiological leakage. The enabling technologies detailed here include microfluidic device design and microfabrication, cell-seeded hydrogel preparation and loading, maintenance of cell culture in the microfluidic chip, flow control for different stages of vascular development, and immunostaining of the vascular network.…”