Animals are commonly used for pharmacokinetic studies which are the most frequent events tested during ocular drug development and preclinical evaluation. Inaccuracy, cost, and ethical criticism in these tests have created a need to construct an in vitro model for studying corneal constraints. In this work, a porous membrane embedded microfluidic platform is fabricated that separates a chip into an apical and basal side. After functionalizing the membrane surface with fibronectin, the membrane's mechanical and surface properties are measured to ensure correct modeling of in vivo characteristics. Immortalized human corneal epithelial cells are cultured on the membrane to create a microengineered corneal epithelium-on-a-chip (cornea chip) that is validated with experiments designed to test the barrier properties of the human corneal epithelium construct using model drugs. A pulsatile flow model is used that closely mimics the ocular precorneal constraints and is reasonable for permeability analysis that models in vivo conditions. This model can be used for preclinical evaluations of potential therapeutic drugs and to mimic the environment of the human cornea.

To precisely investigate the mechanobiological responses of valvular endothelial cells, we developed a microfluidic flow profile generator using a pneumatically-actuated micropump consisting of microvalves of various sizes. By controlling the closing pressures and the actuation times of these microvalves, we modulated the magnitude and frequency of the shear stress to mimic mitral and aortic inflow profiles with frequencies in the range of 0.8–2 Hz and shear stresses up to 20 dyn cm⁻². To demonstrate this flow profile generator, aortic inflow with an average of 5.9 dyn cm⁻² shear stress at a frequency of 1.2 Hz with a Reynolds number of 2.75, a Womersley number of 0.27, and an oscillatory shear index (OSI) value of 0.2 was applied to porcine aortic valvular endothelial cells (PAVECs) for mechanobiological studies. The cell alignment, cell elongation, and alpha-smooth muscle actin (αSMA) expression of PAVECs under perfusion, steady flow, and aortic inflow conditions were analyzed to determine their shear-induced cell migration and trans-differentiation. In this morphological and immunocytochemical study, we found that the PAVECs elongated and aligned themselves perpendicular to the directions of the steady flow and the aortic inflow. In contrast, under perfusion with a fluidic shear stress of 0.47 dyn cm⁻², the PAVECs elongated and aligned themselves parallel to the direction of flow. The PAVECs exposed to the aortic inflow upregulated their αSMA-protein expression to a greater degree than those exposed to perfusion and steady flow. By comparing these results to those of previous studies of pulsatile flow, we also found that the ratio of positive to negative shear stress plays an important role in determining PAVECs' trans-differentiation and adaptation to flow. This microfluidic cardiac flow profile generator will enable future valvular mechanobiological studies to determine the roles of magnitude and frequency of shear stresses.

Current ophthalmological drug discovery and testing methods have limitations and concerns regarding reliability, ethicality, and applicability. These drawbacks can be mitigated by developing biomimetic eye models through mathematical and experimental methods which are often referred to as “eye-on-a-chip” or “eye chip”. These eye chip technologies emulate ocular physiology, anatomy, and microenvironmental conditions. Such models enable understanding of the fundamental biology, pharmacology, and toxicology mechanisms by investigating the pharmacokinetics and pharmacodynamics of various candidate drugs under ocular anatomical and physiological conditions without animal models. This review provides a comprehensive overview of the latest advances in theoretical and in vitro experimental models of the anterior segment of the eye and its microenvironment, including eye motions and tear film dynamics. The current state of ocular modeling and simulation from predictive models to experimental models is discussed in detail with their advantages and limitations. The potential for future eye chip models to expedite new ophthalmic drug discoveries is also discussed.

A pulsatile microfluidic pump transports discrete volume to specific target locations. However, backflow in the pulsatile microfluidic pump often decreases the pumping efficiency and causes unwanted sample mixing due to unsteady boundaries. Employing the concept of a transistor, we developed a pneumatically controlled microfluidic rectifier (PCMR) that prevents backflow in the pulsatile flow regime. This PCMR was interconnected with a microfluidic pulsatile pumping system to characterize the functions of PCMR under continuous pumping sequences (CPS) and discrete pumping sequences (DPS) with various gate pressures on the PCMR. In the passive mode (zero gate pressure), 1.07% backflow for a DPS and 0.12% for a CPS were achieved. However, by adjusting the gate pressure on PCMR actively, we were able to achieve zero backflow for both pumping sequences at the cost of pumping efficiency. Interestingly, when the flow passes through the PCMR under the controlled gate-pressure, a fluidic oscillation was observed due to the force balance between the fluidic pressure and the gate-pressure. This microfluidic system successfully demonstrated half-rectification from various pulsatile flow profiles. By incorporating multiple three-microvalve systems in parallel with frequency modulation, a fully rectified flow pattern can be realized to enable steady laminar flow from pulsatile micropumps.

The exploration of our solar system to characterize the molecular organic inventory will enable the identification of potentially habitable regions and initiate the search for biosignatures of extraterrestrial life. However, it is challenging to perform the required high-resolution, high-sensitivity chemical analyses in space and in planetary environments. To address this challenge, we have developed a microfluidic organic analyzer (MOA) instrument that consists of a multilayer programmable microfluidic analyzer (PMA) for fluidic processing at the microliter scale coupled with a microfabricated glass capillary electrophoresis (CE) wafer for separation and analysis of the sample components. Organic analytes are labeled with a functional group-specific (e.g. amine, organic acid, aldehyde) fluorescent dye, separated according to charge and hydrodynamic size by capillary electrophoresis (CE), and detected with picomolar limit of detection (LOD) using laser-induced fluorescence (LIF). Our goal is a sensitive automated instrument and autonomous process that enables sample-in to data-out performance in a flight capable format. We present here the design, fabrication, and operation of a technology development unit (TDU) that meets these design goals with a core mass of 3 kg and a volume of <5 L. MOA has a demonstrated resolution of 2 × 10⁵ theoretical plates for relevant amino acids using a 15 cm long CE channel and 467 V cm⁻¹. The LOD of LIF surpasses 100 pM (0.01 ppb), enabling biosignature detection in harsh environments on Earth. MOA is ideally suited for probing biosignatures in potentially habitable destinations on icy moons such as Europa and Enceladus, and on Mars.