We investigate the two-dimensional continuous size-based separation of suspended particles in gravity-driven deterministic lateral displacement (g-DLD) devices. The suspended particles are driven through a periodic array of cylindrical obstacles under the action of gravity. We perform experiments covering the entire range of forcing orientations with respect to the array of obstacles and identify specific forcing angles that would lead to vector separation, in which different particles migrate, on an average, in different directions. A simple model, based on the lateral displacement induced on the trajectory of a particle by irreversible particle-obstacle interactions, accurately predicts the dependence of the migration angle on the forcing direction. The results provide design guidance for the development of g-DLD devices. We observe directional locking, which strongly depends on the size of the particle and suggests that relatively small forcing angles are well suited for size-fractionation purposes. We demonstrate excellent separation resolution for a binary mixture of particles at relatively small forcing angles, that is, forcing angles that are close to but smaller than the first transition angle of the larger particles in the mixture.

The ability to control the oxygen level to which cells are exposed in tissue culture experiments is crucial for many applications. Here, we design, develop and test a microbioreactor (MBR) for long-term cell culture studies with the capability to accurately control and continuously monitor the dissolved oxygen (DO) level in the cell microenvironment. In addition, the DO level can be controlled independently from other cues, such as the viscous shear-stress acting on the cells. We first analyze the transport of oxygen in the proposed device and determine the materials and dimensions that are compatible with uniform oxygen tension and low shear-stress at the cell level. The device is also designed to culture a statistically significant number of cells. We use fully transparent materials and the overall design of the device is compatible with live-cell imaging. The proposed system includes real-time read-out of actual DO levels, is simple to fabricate at low cost, and can be easily expanded to control the concentration of other microenvironmental solutes. We performed control experiments in the absence of cells to demonstrate that the MBR can be used to accurately modulate DO levels ranging from atmospheric level to 1%, both under no flow and perfusion conditions. We also demonstrate cancer cell attachment and viability within the MBR. The proposed MBR offers the unprecedented capability to perform on-line measurement and analysis of DO levels in the microenvironment of adherent cultures and to correlate them with various cellular responses.

The dynamics of dissolved oxygen (DO) and shear stress in the vasculature microenvironment play a major role in determining the fate of stem cells in adults and during early embryonic development. In this study, we present a microbioreactor (MBR) that provides independent control over oxygen tension and shear stress in cultures of stem and progenitor cell types. We first describe the design principles and use a model-driven approach for the optimization of the MBR geometry and operating conditions prior to its fabrication and assembly. We then demonstrate the utilization of the MBR for culturing adult human endothelial progenitors, human umbilical vein endothelial cells, and human embryonic stem cell-derived smooth muscle cells under different DO and shear stress levels.