An artificial placenta type microfluidic blood oxygenator with double-sided gas transfer microchannels and its integration as a neonatal lung assist device

Dabaghi, Mohammadhossein; Fusch, Gerhard; Saraei, Neda; Rochow, Niels; Brash, John L.; Fusch, Christoph; Selvaganapathy, P. Ravi

doi:10.1063/1.5034791

Cited by 44 publications

(53 citation statements)

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“…Therefore, a pumpless device, capable of being operated solely by the baby's heart (20-60 mm Hg) and with the ability of oxygenation in ambient air would be the best solution to minimize post-treatment side effects 3,5,6 (such a concept is known as an artificial placenta). Over the last years, several microfluidic-based devices have been introduced for blood oxygenation, 5,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] but only few of them 5,11,12,20 could be operated without any pump and have sufficient gas exchange capability in room air. Therefore, an ideal device for artificial placenta application should have (1) an ability to operate at a pressure differential of 20-60 mm Hg; (2) an ability to be oxygenated in ambient air; (3) a priming volume of <10 ml/kg of the body weight and the ability to process 20-30 ml/min/kg of blood and increase oxygen saturation of ∼30%, thereby an oxygen transfer of 1.3-1.9 mL/min/kg of body weight.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, an ideal device for artificial placenta application should have (1) an ability to operate at a pressure differential of 20-60 mm Hg; (2) an ability to be oxygenated in ambient air; (3) a priming volume of <10 ml/kg of the body weight and the ability to process 20-30 ml/min/kg of blood and increase oxygen saturation of ∼30%, thereby an oxygen transfer of 1.3-1.9 mL/min/kg of body weight. [3][4][5]11,12,20 Fabrication of microfluidic blood oxygenators with double-sided gas exchange 12,21 has led to promising improvement in performance lately. Two different approaches have been taken to fabricate such oxygenators, namely, (1) the use of gas perfusion channels on each side of the microfluidic blood network microchannels which provide mechanical support during the operation 21 or (2) the use of a stiffer material such as stainless-steel mesh to reinforce the PDMS gas exchange membrane 12 such that they could be directly exposed to the ambient atmosphere.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5]11,12,20 Fabrication of microfluidic blood oxygenators with double-sided gas exchange 12,21 has led to promising improvement in performance lately. Two different approaches have been taken to fabricate such oxygenators, namely, (1) the use of gas perfusion channels on each side of the microfluidic blood network microchannels which provide mechanical support during the operation 21 or (2) the use of a stiffer material such as stainless-steel mesh to reinforce the PDMS gas exchange membrane 12 such that they could be directly exposed to the ambient atmosphere. 4 The first approach needs an external gas supply and pumps to perfuse the gases which is not desired, while the second approach reduces the effective gas exchange surface area due to the reinforcement that does not have the same permeation characteristics as PDMS.…”

Section: Introductionmentioning

confidence: 99%

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An ultra-thin, all PDMS-based microfluidic lung assist device with high oxygenation capacity

et al. 2019

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Preterm neonates with immature lungs require a lung assist device (LAD) to maintain oxygen saturation at normal levels. Over the last decade, microfluidic blood oxygenators have attracted considerable interest due to their ability to incorporate unique biomimetic design and to oxygenate in a physiologically relevant manner. Polydimethylsiloxane (PDMS) has become the main material choice for these kinds of devices due to its high gas permeability. However, fabrication of large area ultrathin microfluidic devices that can oxygenate sufficient blood volumes at clinically relevant flow rates, entirely made of PDMS, have been difficult to achieve primarily due to failure associated with stiction of thin PDMS membranes to each other at undesired locations during assembly. Here, we demonstrate the use of a modified fabrication process to produce large area ultrathin oxygenators entirely made of PDMS and robust enough to withstand the hydraulic conditions that are encountered physiologically. We also demonstrate that a LAD assembled from these ultrathin double-sided microfluidic blood oxygenators can increase the oxygen saturation level by 30% at a flow rate of 30 ml/min and a pressure drop of 21 mm Hg in room air which is adequate for 1 kg preterm neonates. In addition, we demonstrated that our LAD could withstand high blood flow rate of 150 ml/min and increase oxygen saturation by 26.7% in enriched oxygen environment which is the highest gas exchange reported so far by any microfluidic-based blood oxygenators. Such performance makes this LAD suitable to provide support to 1 kg neonate suffering from respiratory distress syndrome.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An ultra-thin, all PDMS-based microfluidic lung assist device with high oxygenation capacity

et al. 2019

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“…This study was the first to systematically quantify umbilical vessel damage as the result of expansion by catheters. Dabaghi et al [71] performed microfabrication for microfluidic blood oxygenators using double-sided gas delivery to improve gas exchange. Oxygen uptake increased to 343% in comparison Fig.…”

Section: Lung-on-a-chipmentioning

confidence: 99%

Organ-on-a-chip: recent breakthroughs and future prospects

et al. 2020

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BackgroundMicrofluidics is a science and technology that precisely manipulates and processes microscale fluids. It is commonly used to precisely control microfluidic (10 −9 to 10 −18 L) fluids using channels that range in size from tens to hundreds of microns and is known as a "lab-on-a-chip" [1][2][3][4]. The microchannel is small, but has a large surface area and high mass transfer, favoring its use in microfluidic technology applications including low regent usage, controllable volumes, fast mixing speeds, rapid responses, and precision control of physical and chemical properties [1,5,6]. Microfluidics integrate sample preparation, reactions, separation, detection, and basic operating units such as cell culture, sorting and cell lysis [7]. For these reasons, interest in OOAC has intensified [8]. OOAC combines a range of chemical, biological and material science disciplines [9] and was selected as one of the "Top Ten Emerging Technologies" in the World Economic Forum [10].OOAC is a biomimetic system that can mimic the environment of a physiological organ, with the ability to regulate key parameters including AbstractThe organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on a microfluidic chip. Through a combination of cell biology, engineering, and biomaterial technology, the microenvironment of the chip simulates that of the organ in terms of tissue interfaces and mechanical stimulation. This reflects the structural and functional characteristics of human tissue and can predict response to an array of stimuli including drug responses and environmental effects. OOAC has broad applications in precision medicine and biological defense strategies. Here, we introduce the concepts of OOAC and review its application to the construction of physiological models, drug development, and toxicology from the perspective of different organs. We further discuss existing challenges and provide future perspectives for its application.

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“…31Small volume oxygenation of blood for neonatal application can be addressed by microfluidic 32 oxygenators, where it is vital to keep the oxygenator volume appropriately small due to the low 33 blood volume of the neonatal patient. Furthermore, the associated decrease in membrane surface 34 area and blood-contacting artificial materials reduces complications and blood damage[5], [6]. 35…”

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confidence: 99%

Empirical and Computational Evaluation of Hemolysis in a Microfluidic Extracorporeal Membrane Oxygenator (ECMO) Prototype

Poskus

2020

Preprint

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3Microfluidic devices may overcome the limitations of conventional hemodialysis and 4 oxygenation technology to improve patient outcomes. Namely, the small form of this technology 5 and parallel development of highly permeable membranes may facilitate the development of 6 portable, low-volume, and efficient alternatives to conventional membrane-based equipment. 7However, the characteristically small dimensions of these devices may also inhibit transport and 8 may also induce flow-mediated nonphysiologic shear stresses that may damage red blood cells 9 (RBCs). In vitro testing is commonly used to quantify these phenomenon, but is costly and only 10 characterizes bulk device performance. Here we developed a computational model that predicts 11 the blood damage and solute transport for an abitrary microfluidic geometry. We challenged the 12 predictiveness of the model with three geometric variants of a prototype design and validated 13 hemolysis predictions with in vitro blood damge of prototype devices in a recirculating loop. We 14 found that six of the nine tested damage models statistically agree with the experimental data for 15 at least one geometric variant. Additionally, we found that one geometrical variant, the 16 herringbone design, improved toxin (urea) transport to the dialysate by 38% in silico at the 17 expense of a 50% increase in hemolysis. Our work demonstrates that computational modeling 18 may supplement in vitro testing of prototype microdialyzer/micro-oxygenators to expedite the 19 design optimization of these devices. Furthermore, the low device-induced blood damage 20 measured in our study at physiologically relevant flow rates is promising for the future 21 development of microfluidic dialyzers and oxygenators. 22 reduce the required device size and thus blood volume, a critical parameter for smaller patients. 31Small volume oxygenation of blood for neonatal application can be addressed by microfluidic 32 oxygenators, where it is vital to keep the oxygenator volume appropriately small due to the low 33 blood volume of the neonatal patient. Furthermore, the associated decrease in membrane surface 34 area and blood-contacting artificial materials reduces complications and blood damage[5], [6]. 35

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An artificial placenta type microfluidic blood oxygenator with double-sided gas transfer microchannels and its integration as a neonatal lung assist device

Cited by 44 publications

References 36 publications

An ultra-thin, all PDMS-based microfluidic lung assist device with high oxygenation capacity

An ultra-thin, all PDMS-based microfluidic lung assist device with high oxygenation capacity

Organ-on-a-chip: recent breakthroughs and future prospects

Empirical and Computational Evaluation of Hemolysis in a Microfluidic Extracorporeal Membrane Oxygenator (ECMO) Prototype

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