AC electrokinetics is rapidly becoming a foundational tool for lab-on-a-chip systems due to its versatility and the simplicity of the components capable of generating them. Predicting the behavior of fluids and particles under non-uniform AC electric fields is important for the design of next generation devices. Though there are several important phenomena that contribute to the overall behavior of particles and fluids, current predictive techniques consider special conditions where only a single phenomenon may be considered. We report a 2D numerical simulation, using COMSOL Multiphysics, which incorporates the three major AC electrokinetic phenomena (dielectrophoresis, AC electroosmosis and electrothermal effect) and is valid for a wide range of operational conditions. Corroboration has been performed using experimental conditions that mimic those of the simulation and shows good qualitative agreement. Furthermore, a broad range of experiments has been performed using four of the most widely reported devices under varying conditions in order to show their behavior as it relates to the simulation. The large number of experimental conditions reported, together with the comprehensive numerical simulation, will help provide guidelines for scientists and engineers interested in incorporating AC electrokinetics into their lab-on-a-chip systems.

This paper presents a novel liver model that mimics the liver sinusoid where most liver activities occur. A key aspect of our current liver model is a layered co-culture of primary rat hepatocytes (PRHs) and primary rat liver sinusoidal endothelial cells (LSECs) or bovine aortic endothelial cells (BAECs) on a transwell membrane. When a layered co-culture was attempted with a thin Matrigel layer placed between hepatocytes and endothelial cells to mimic the space of Disse, the cells did not form completely separated monolayers. However, when hepatocytes and endothelial cells were cultured on the opposite sides of a transwell membrane, PRHs co-cultured with LSECs or BAECs maintained their viability and normal morphology for 39 and 57 days, respectively. We assessed the presence of hepatocyte-specific differentiation markers to verify that PRHs remained differentiated in the long-term co-culture and analyzed hepatocyte function by monitoring urea synthesis. We also noted that the expression of cytochrome P-450 remained similar in the co-cultured system from day 1 to day 48. Thus, our novel liver model system demonstrated that primary hepatocytes can be cultured for extended times and retain their hepatocyte-specific functions when layered with endothelial cells.

We have developed a miniature human liver (liver-sinusoid-on-a-chip) model using a dual microchannel separated by a porous membrane. Primary human hepatocytes and immortalized bovine aortic endothelial cells were co-cultured on opposite sides of a microporous membrane in a dual microchannel with continuous perfusion. Primary human hepatocytes in this system retained their polygonal morphology for up to 26 days, while hepatocytes cultured in the absence of bovine aortic endothelial cells lost their morphology within a week. In order to demonstrate the utility of our human-liver-sinusoid-on-a-chip, human hepatocytes in this system were directly infected by Hepatitis B Virus (HBV). Expression of the HBV core antigen was detected in human hepatocytes in the microchannel system. HBV replication, measured by the presence of cell-secreted HBV DNA, was also detected. Importantly, HBV is hepatotropic, and expression of HBV RNA transcripts is dependent upon expression of hepatocyte-specific factors. Moreover, HBV infection requires expression of the human-hepatocyte-specific HBV cell surface receptor. Therefore, the ability to detect HBV replication and Hepatitis B core Antigen (HBcAg) expression in our microfluidic platform confirmed that hepatocyte differentiation and functions were retained throughout the time course of our studies. We believe that our human-liver-sinusoid-on-a-chip could have many applications in liver-related research and drug development.

We present a novel microvalve for the treatment of a pathological condition, i.e., hydrocephalus. This microvalve is made of polydimethylsiloxane/Parylene composite layer which has a 3-D dome petal shape. This geometry enables the microvalve to rectify fluid flow in the forward and backward directions. New microfabrication techniques such as dome-shaped SU-8 mold fabrication and excimer laser machining for valve opening have been investigated to build the proposed microvalve. The pressure drop versus flow rate characteristics of the fabricated microvalve was investigated through in vitro flow tests. The flow test results showed that a 10 × 10 microvalve array with a cross-cut opening shape (200 × 60 μm) was found to be optimal for the treatment of hydrocephalus.