Wen-I Wu

An Integrated Array of Microfluidic Oxygenators as a Neonatal Lung Assist Device: In Vitro Characterization and In Vivo Demonstration

A miniaturized oxygenator device that is perfused like an artificial placenta via the umbilical vessels may have significant potential to save the lives of newborns with respiratory insufficiency. Recently we presented the concept of an integrated modular lung assist device (LAD) that consists of stacked microfluidic single oxygenator units (SOUs) and demonstrated the technical details and operation of SOU prototypes. In this article, we present a LAD prototype that is designed to accommodate the different needs of term and preterm infants by permitting changing of the number of parallel-stacked microfluidic SOUs according to the actual body weight. The SOUs are made of polydimethylsiloxane, arranged in parallel, and connected though 3D-printed polymeric interconnects to form the LAD. The flow characteristics and the gas exchange properties were tested in vitro using human blood. We found that the pressure drop of the LAD increased linearly with flow rate. Gas exchange rates of 2.4-3.8 μL/min/cm(2) (0.3-0.5 mL/kg/min) and 6.4-10.1 μL/min/cm(2) (0.8-1.3 mL/kg/min) for O2 and CO2 , respectively, were achieved. We also investigated protein adsorption to provide preliminary information on the need for application of anticoagulant coating of LAD materials. Albumin adsorption, as measured by gold staining, showed that surface uptake was evenly distributed and occurred at the monolayer level (>0.2 μg/cm(2) ). Finally, we also tested the LAD under in vivo conditions using a newborn piglet model (body weight 1.65-2.0 kg). First, the effect of an arteriovenous bypass via a carotid artery-to-jugular vein shortcut on heart rate and blood pressure was investigated. Heart rate and mean arterial blood pressure remained stable for extracorporeal flow rates of up to 61 mL/kg/min (101 mL/min). Next, the LAD was connected to umbilical vessels (maximum flow rate of 24 mL/min [10.4 mL/kg/min]), and O2 gas exchange was measured under hypoxic conditions (Fi O2  = 0.15) and was found to be 3.0 μL/min/cm(2) . These results are encouraging and support the feasibility of an artificial placental design for an LAD.

Fluid Dynamics and Biofilm Removal Generated by Syringe-delivered and 2 Ultrasonic-assisted Irrigation Methods: A Novel Experimental Approach

INTRODUCTION Thorough understanding of fluid dynamics in root canal irrigation and corresponding antibiofilm capacity will support improved disinfection strategies. This study aimed to develop a standardized, simulated root canal model that allows real-time analysis of fluid/irrigation dynamics and its correlation with biofilm elimination. METHODS A maxillary incisor with an instrumented root canal was imaged with micro-computed tomography. The canal volume was reconstructed in 3 dimensions and replicated in soft lithography-based models microfabricated from polyethylene glycol-modified polydimethylsiloxane. Canals were irrigated by using a syringe (SI) and 2 ultrasonic-assisted methods, intermittent (IUAI) and continuous (CUAI). Real-time fluid movement within the apical 3 mm of canals was imaged by using microparticle image velocimetry. In similar models, canals were inoculated with Enterococcus faecalis to grow 3-week-old biofilms. Biofilm reduction by irrigation with SI, CUAI, and IUAI was assessed by using a crystal violet assay and compared with an untreated control. RESULTS SI generated higher velocity and shear stress in the apical 1-2 mm than 0-1 and 2-3 mm. IUAI generated consistently low shear stress in the apical 3 mm. CUAI generated consistently high levels of velocity and shear stress; it was the highest of the groups in the apical 0-1 and 2-3 mm. Biofilm was significantly reduced compared with the control only by CUAI (two-sample permutation test, P = .005). CONCLUSIONS CUAI exhibited the highest mechanical effects of fluid flow in the apical 3 mm, which correlated with significant biofilm reduction. The soft lithography-based models provided a novel model/method for study of correlations between fluid dynamics and the antibiofilm capacity of root canal irrigation methods.

Transport of particles and microorganisms in microfluidic channels using rectified ac electro-osmotic flow.

A new method is demonstrated to transport particles, cells, and other microorganisms using rectified ac electro-osmotic flows in open microchannels. The rectified flow is obtained by synchronous zeta potential modulation with the driving potential in the microchannel. Experiments were conducted to transport both neutral, charged particles, and microorganisms of various sizes. A maximum speed of 50 μm∕s was obtained for 8 μm polystyrene beads, without any electrolysis, using a symmetrical square waveform driving electric field of 5 V∕mm at 10 Hz and a 360 V gate potential with its polarity synchronized with the driving potential (phase lag=0°).

Artificial placenta--lung assist devices for term and preterm newborns with respiratory failure.

Respiratory insufficiency is a major cause of neonatal mortality and long-term morbidity, especially in very low birth weight infants. Today, non-invasive and mechanical ventilation are commonly accepted procedures to provide respiratory support to newborns, but they can reach their limit of efficacy. To overcome this technological plateau and further reduce mortality rates, the technology of an “artificial placenta”, which is a pumpless lung assist device connected to the umbilical vessels, would serve to expand the therapeutic spectrum when mechanical ventilation becomes inadequate to treat neonates with severe respiratory insufficiency. The first attempts to create such an artificial placenta took place more than 60 years ago. However, there has been a recent renaissance of this concept, including developments of its major components like the oxygenator, vascular access via umbilical vessels, flow control, as well as methods to achieve hemocompatibility in extracorporeal circuits. This paper gives a review of past and current development, animal experiments and human case studies of artificial placenta technology.

Integrated microfluidic oxygenator bundles for blood gas exchange in premature infants

This paper reports the development of a low volume pumpless lung assist device (LAD) composed of a stack of microfluidic single oxygenators units (SOUs) connected in parallel. SOUs are comprised of a microfluidic vascular network (polydimethylsiloxane) and a gas-permeable polycarbonate (PC) membrane to enhance gas exchange between blood and ambient air. We report results from an in vitro test and the first performance test of the LAD in hypoxic newborn piglet in which we show an increase of up to 40% in peripheral oxygen saturation.

Materials and methods for the microfabrication of microfluidic biomedical devices

Abstract: The materials that have been employed for the construction of microfluidic devices have been diverse, ranging from traditional materials, such as silicon and glass, to newer polymeric materials. Similarly, the methods for microfabrication have included lithography, casting, injection molding and hot embossing, to name a few. In this chapter, we provide an overview of the various materials and methods that have been used in a diverse range of microfluidic applications. Details on the physical and chemical properties of the materials, as well as the performance characteristics of the microfabrication methods, are provided.