Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture.

Hydrogel microcapsules provide miniaturized and biocompatible niches for three-dimensional (3D) in vitro cell culture. They can be easily generated by droplet-based microfluidics with tunable size, morphology, and biochemical properties. Therefore, microfluidic generation and manipulation of cell-laden microcapsules can be used for 3D cell culture to mimic the in vivo environment towards applications in tissue engineering and high throughput drug screening. In this review of recent advances mainly since 2010, we will first introduce general characteristics of droplet-based microfluidic devices for cell encapsulation with an emphasis on the fluid dynamics of droplet breakup and internal mixing as they directly influence microcapsule's size and structure. We will then discuss two on-chip manipulation strategies: sorting and extraction from oil into aqueous phase, which can be integrated into droplet-based microfluidics and significantly improve the qualities of cell-laden hydrogel microcapsules. Finally, we will review various applications of hydrogel microencapsulation for 3D in vitro culture on cell growth and proliferation, stem cell differentiation, tissue development, and co-culture of different types of cells.

Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans.

Although the process of drug development requires efficacy and toxicity testing in animals prior to human testing, animal models have limited ability to accurately predict human responses to xenobiotics and other insults. Societal pressures are also focusing on reduction of and, ultimately, replacement of animal testing. However, a variety of in vitro models, explored over the last decade, have not been powerful enough to replace animal models. New initiatives sponsored by several US federal agencies seek to address this problem by funding the development of physiologically relevant human organ models on microscopic chips. The eventual goal is to simulate a human-on-a-chip, by interconnecting the organ models, thereby replacing animal testing in drug discovery and development. As part of this initiative, we aim to build a three-dimensional human liver chip that mimics the acinus, the smallest functional unit of the liver, including its oxygen gradient. Our liver-on-a-chip platform will deliver a microfluidic three-dimensional co-culture environment with stable synthetic and enzymatic function for at least 4 weeks. Sentinel cells that contain fluorescent biosensors will be integrated into the chip to provide multiplexed, real-time readouts of key liver functions and pathology. We are also developing a database to manage experimental data and harness external information to interpret the multimodal data and create a predictive platform.

Lattice-Boltzmann simulations of the dynamics of polymer solutions in periodic and confined geometries.

A numerical method to simulate the dynamics of polymer solutions in confined geometries has been implemented and tested. The method combines a fluctuating lattice-Boltzmann model of the solvent [Ladd, Phys. Rev. Lett. 70, 1339 (1993)] with a point-particle model of the polymer chains. A friction term couples the monomers to the fluid [Ahlrichs and Dunweg, J. Chem. Phys. 111, 8225 (1999)], providing both the hydrodynamic interactions between the monomers and the correlated random forces. The coupled equations for particles and fluid are solved on an inertial time scale, which proves to be surprisingly simple and efficient, avoiding the costly linear algebra associated with Brownian dynamics. Complex confined geometries can be represented by a straightforward mapping of the boundary surfaces onto a regular three-dimensional grid. The hydrodynamic interactions between monomers are shown to compare well with solutions of the Stokes equations down to distances of the order of the grid spacing. Numerical results are presented for the radius of gyration, end-to-end distance, and diffusion coefficient of an isolated polymer chain, ranging from 16 to 1024 monomers in length. The simulations are in excellent agreement with renormalization group calculations for an excluded volume chain. We show that hydrodynamic interactions in large polymers can be systematically coarse-grained to substantially reduce the computational cost of the simulation. Finally, we examine the effects of confinement and flow on the polymer distribution and diffusion constant in a narrow channel. Our results support the qualitative conclusions of recent Brownian dynamics simulations of confined polymers [Jendrejack et al., J. Chem. Phys. 119, 1165 (2003) and Jendrejack et al., J. Chem. Phys. 120, 2513 (2004)].