Lab-grown tissues hit a wall: microfluidic design flaws starve cells of oxygen
Researchers have identified fundamental limits in how microfluidic devices deliver nutrients to 3D cell cultures—a critical bottleneck for biotech companies developing tissue models and drug-testing platforms. The study reveals that poor chamber design can require 100 times more fluid flow to penetrate cell constructs, driving up costs and equipment demands for an industry racing to replace animal testing.
Originaltitel: Capacity and limitations of microfluidic flow to increase solute transport in three-dimensional cell cultures
<p>Culturing living cells in three-dimensional environments increases the biological relevance of laboratory experiments, but requires solutes to overcome a diffusion barrier to reach the centre of cellular constructs. We present a theoretical and numerical investigation that brings a mechanistic understanding of how microfluidic culture conditions, including chamber size, inlet fluid velocity and spatial confinement, affect solute distribution within three-dimensional cellular constructs. Contact with the chamber substrate reduces the maximally achievable construct radius by 15%. In practice, finite diffusion and convection kinetics in the microfluidic chamber further lower that limit. The benefits of external convection are greater if transport rates across diffusion-dominated areas are high. Those are omnipresent and include the diffusive boundary layer growing from the fluid-construct interface and regions near corners where fluid is recirculating. Such regions multiply the required convection to achieve a given solute penetration by up to 100, so chip designs ought to minimize them. Our results define conditions where complete solute transport into an avascular three-dimensional cell construct is achievable and applies to real chambers without needing to simulate their exact geometries.</p>