Silicon Micropore-Based Parallel Plate Membrane Oxygenator

PloS one, 2016

Hemodialysis using hollow-fiber membranes provides life-sustaining treatment for nearly 2 million patients worldwide with end stage renal disease (ESRD). However, patients on hemodialysis have worse long-term outcomes compared to kidney transplant or other chronic illnesses. Additionally, the underlying membrane technology of polymer hollow-fiber membranes has not fundamentally changed in over four decades. Therefore, we have proposed a fundamentally different approach using microelectromechanical systems (MEMS) fabrication techniques to create thin-flat sheets of silicon-based membranes for implantable or portable hemodialysis applications. The silicon nanopore membranes (SNM) have biomimetic slit-pore geometry and uniform pores size distribution that allow for exceptional permeability and selectivity. A quantitative diffusion model identified structural limits to diffusive solute transport and motivated a new microfabrication technique to create SNM with enhanced diffusive transpo...

The journal of medical investigation : JMI, 2002

Currently in United States, there are no clinically-applicable hollow fiber extracorporeal membrane oxygenation (ECMO) oxygenators available. Therefore, our laboratory is in the process of developing a silicone hollow fiber membrane oxygenator for long-term ECMO usage. This oxygenator incorporates an ultrathin silicone hollow fiber. At this time, a specially-modified blood flow distributor (one chamber distributor) is centered in the module to prevent blood stagnation. An ex vivo long-term durability test for ECMO was performed using a healthy miniature calf for 2 weeks. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3 centrifugal blood pump. A successful 2-week ex vivo experiment was performed. The O2 and CO2 gas transfer rates were maintained at the same value of 40 m/min at a blood flow rate of 1 L/min flow and V/Q=3 (V=gas flow rate; Q=blood flow rate). The plasma free hemoglob...

AIChE Journal, 2005

Extracorporeal blood oxygenators are used to oxygenate blood during open-heart surgery. Hydrophobic microporous flat-sheet or hollow-fiber membranes are used to separate blood and gas phases. Oxygen diffuses from the gas phase through the gas-filled membrane pores into the blood. Mass-transfer and friction-factor correlations have been developed for flat-sheet and hollow-fiber blood oxygenators. Generalized Graetz, Reynolds, and Schmidt numbers are used in these correlations to account for the shearthinning behavior of blood. Because oxygen not only dissolves in plasma but also binds to hemoglobin, a mass-transfer enhancement factor based on film theory has been developed to account for oxygen binding to hemoglobin. Experimental results for oxygen transfer to bovine blood and both non-Newtonian and Newtonian blood analogue fluids indicate that the correlations developed may be used to predict the performance of a blood oxygenator based on results for an experimentally simple system such as the oxygenation of deionized water.

MRS Advances

In the last decade, organ-on-a-chip technology has been researched as an alternative to animal and cell culture models (Buhidma et al. in NPJ Parkinson’s Dis, 2020; Pearce et al. in Eur Cells Mater 13:1–10, 2007; Huh et al. in Nat Protoc 8:2135–2157, 2013). While extensive research has focused on the biological functions of these chips, there has been limited exploration of functional materials that can accurately replicate the biological environment. Our group concentrated on a lung-on-a-chip featuring a newly fabricated porous silicon bio-membrane. This bio-membrane mimics the interstitial space found between epithelial and endothelial cells in vivo, with a thickness of approximately 1 μm (Ingber in Cell 164:1105–1109, 2016). This study aims to establish a fabrication method for producing a thin, uniform porous silicon membrane with a predictable reduced modulus. We conducted mechanical and morphological characterization using scanning electron microscopy and nanoindentation. A sm...

Frontiers in Bioengineering and Biotechnology, 2020

resistance to breakthrough; the presence of surfactants in the patient's blood (e.g., lipids, alcohol, etc.) may significantly modify the intrinsic membrane resistance to breakthrough, more so the higher the surfactant concentration. We conclude that the requirements of ECMO devices in terms of resistance to plasma breakthrough ought to account for all these factors and not rely only on membrane maximal pore size.

Annals of Surgery, 1977

Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia, 2002

Based on the results of many experimental models, a hollow fiber silicone membrane oxygenator applicable for long-term extracorporeal membrane oxygenation (ECMO) was developed. For further high performance and antithrombogenicity, this preclinical model was modified, and a new improved oxygenator was successfully developed. In addition to ECMO application, the superior biocompatibility of silicone must be advantageous for pediatric cardiopulmonary bypass (CPB). An ex vivo short-term durability test for pediatric CPB was performed using a healthy miniature calf for six hours. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3 centrifugal pump. For six hours, the O2 and CO2 gas transfer rates were maintained around 90 and 80 ml/min at a blood flow rate of 2 L/min and V/Q=3, respectively. The plasma free hemoglobin was maintained around 5 mg/dl. These data suggest that this newly improv...

Biomicrofluidics, 2017

Artificial lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic artificial lungs (lAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the ll/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic artificial lung in which the structure is assembled via a continuous "rolling" and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10 lm tall artificial capillaries, and a 66 lm thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1-1.25 ml/min) for two different sweep gases (pure O 2 , atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO 2 removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic artificial lungs. Although designed for microfluidic artificial lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS. [

Annals of Biomedical Engineering, 1977

A new membrane oxygenator capable of effective and efficient arterialization of venous blood flowing through etched microchannels has been developed. The design flow capacity can be regulated up to 1.4 liters per minute with a priming volume of 80 cm 3. The characteristics of oxygen and carbon dioxide exchange are correlated to the effective channel depth and compared with theoretical predictions. An analysis of the resistance coefficient of blood flowing through the etched microchannels shows a significant reduction (50-65 %) of the apparent viscosity of blood, indicating the peripheral plasma layer effect on the microflow processes. The particulate flow results in an anomalous oxygen and carbon dioxide exchange above theoretical predictions for homogeneous fluids.

Lab on a Chip, 2012

Microfluidic fabrication technologies are emerging as viable platforms for extracorporeal lung assist devices and oxygenators for cardiac surgical support and critical care medicine, based in part on their ability to more closely mimic the architecture of the human vasculature than existing technologies. In comparison with current hollow fiber oxygenator technologies, microfluidic systems have more physiologically-representative blood flow paths, smaller cross section blood conduits and thinner gas transfer membranes. These features can enable smaller device sizes and a reduced blood volume in the oxygenator, enhanced gas transfer efficiencies, and may also reduce the tendency for clotting in the system. Several critical issues need to be addressed in order to advance this technology from its current state and implement it in an organ-scale device for clinical use. Here we report on the design, fabrication and characterization of multilayer microfluidic oxygenators, investigating scaling effects associated with fluid mechanical resistance, oxygen transfer efficiencies, and other parameters in multilayer devices. Important parameters such as the fluidic resistance of interconnects are shown to become more predominant as devices are scaled towards many layers, while other effects such as membrane distensibility become less significant. The present study also probes the relationship between blood channel depth and membrane thickness on oxygen transfer, as well as the rate of oxygen transfer on the number of layers in the device. These results contribute to our understanding of the complexity involved in designing three-dimensional microfluidic oxygenators for clinical applications.

Artificial Organs, 2003

Silicone rubber hollow fiber membrane produces an ideal gas exchange for long-term ECMO due to nonporous characteristics. The extracapillary type silicone rubber ECMO oxygenator having an ultrathin hollow fiber membrane was developed for pediatric application. The test modules were compared to conventional silicone coiltype ECMO modules. In vitro experiments demonstrated a higher O 2 and CO 2 transfer rate, lower blood flow resistance, and less hemolysis than the conventional silicone coil-type modules. This oxygenator was combined with the Gyro C1E3 centrifugal pump, and three ex vivo experiments were conducted to simulate pediatric V-A ECMO condition. Four day and 6 day experiments were conducted in cases 1 and 2, respectively. Case 3 was a long-term experiment up to 2 weeks. No plasma leakage and stable gas performances were achieved. The plasma free hemoglobin was maintained within a normal range. This compact pump-oxygenator system in conjunction with the Gyro C1E3 centrifugal pump has potential for a hybrid total ECMO system.

Nature communications, 2013

In a gas membrane, gas is transferred between a liquid and a gas through a microporous membrane. The main challenge is to achieve a high gas transfer while preventing wetting and clogging. With respect to the oxygenation of blood, haemocompatibility is also required. Here we coat macroporous meshes with a superamphiphobic-or liquid repellent-layer to meet this challenge. The superamphiphobic layer consists of a fractal-like network of fluorinated silicon oxide nanospheres; gas trapped between the nanospheres keeps the liquid from contacting the wall of the membrane. We demonstrate the capabilities of the membrane by capturing carbon dioxide gas into a basic aqueous solution and in addition use it to oxygenate blood. Usually, blood tends to clog membranes because of the abundance of blood cells, platelets, proteins and lipids. We show that human blood stored in a superamphiphobic well for 24 h can be poured off without leaving cells or adsorbed protein behind.

Materials Science and Engineering: C, 2019

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Interactive cardiovascular and thoracic surgery, 2015

Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature ...