Akif Ibraguimov

A review of chemical gradient systems for cell analysis.

Microfluidic spatial and temporal gradient generators have played an important role in many biological assays such as in the analysis of wound healing, inflammation, and cancer metastasis. Chemical gradient systems can also be applied to other fields such as drug design, chemical synthesis, chemotaxis, etc. Microfluidic systems are particularly amenable to gradient formation, as the length scales used in chips enable fluid processes that cannot be conducted in bulk scale. In this review we discuss new microfluidic devices for gradient generation and applications of those systems in cell analysis.

A computational model of fibroblast and macrophage spatial/temporal dynamics in foreign body reactions.

The implantation of medical devices often triggers several immune responses, one kind of which is categorized as foreign body reactions. It is well established that macrophages and many other cells participate in the complex processes of foreign body reactions, and cause severe inflammations and fibrotic capsule formation in surrounding tissues. However, the detailed mechanisms of macrophage responses, recruitment and activation, in foreign body reactions are not totally understood. In the meantime, mathematical models have been proposed to systematically decipher the behavior of this complex system of multiple cells, proteins and biochemical processes in wound healing responses. Based on these early works, this study introduces a mathematical model in two spatial dimensions to investigate the transient behavior of macrophages, fibroblasts and their interactions during the formation of fibrotic tissue. We find that the simulation results are consistent with the experimental observations. These findings support that the model can reveal quantitative insights for studying foreign body reaction processes.

Stability Analysis of a Model for Foreign Body Fibrotic Reactions

Implanted medical devices often trigger immunological and inflammatory reactions from surrounding tissues. The foreign body-mediated tissue responses may result in varying degrees of fibrotic tissue formation. There is an intensive research interest in the area of wound healing modeling, and quantitative methods are proposed to systematically study the behavior of this complex system of multiple cells, proteins, and enzymes. This paper introduces a kinetics-based model for analyzing reactions of various cells/proteins and biochemical processes as well as their transient behavior during the implant healing in 2-dimensional space. In particular, we provide a detailed modeling study of different roles of macrophages (MΦ) and their effects on fibrotic reactions. The main mathematical result indicates that the stability of the inflamed steady state depends primarily on the reaction dynamics of the system. However, if the said equilibrium is unstable by its reaction-only system, the spatial diffusion and chemotactic effects can help to stabilize when the model is dominated by classical and regulatory macrophages over the inflammatory macrophages. The mathematical proof and counter examples are given for these conclusions.

A ONE-DIMENSIONAL MODEL CAPTURING SELECTIVE ION TRANSPORT EFFECTS IN NANOFLUIDIC DEVICES

This paper presents a numerical model of one-dimensional, steady-state, multi-species, ion transport along a channel of variable width and depth. It is intended for computationally efficient simulation of devices with large variations in characteristic length scale—for example those incorporating both micro- and nanochannels. The model represents both volume charge in the fluid and surface charge on the channel walls as equivalent linear charge densities. The relative importance of the surface terms is captured by a so-called “overlap parameter” that accounts for electric double-layer effects, such as selective ion transport. Scale transitions are implemented using position-dependent area and perimeter functions. The model is validated against experimental results previously reported in the literature. In particular, model predictions are compared to measurements of fluorescent tracer species in nanochannels, of nanochannel conductivity, and of the relative enhancement and depletion of negatively and positively charged tracer species in a device combining microand nanochannels. Surface charge density is a critical model parameter, but in practice it is often poorly known. Therefore it is also shown how the model may be used to estimate surface charge density based on measurements. In two of the three experiments studied the externally applied voltage is low, and excellent results are achieved with electroosmotic terms neglected. In the remaining case a large external potential (~ 1 kV) is applied, necessitating an additional adjustable parameter to capture convective transport. With this addition, model performance is excellent.