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      Multilayer Scaling of a Biomimetic Microfluidic Oxygenator

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          Abstract

          Extracorporeal membrane oxygenation (ECMO) has been advancing rapidly due to a combination of rising rates of acute and chronic lung diseases as well as significant improvements in the safety and efficacy of this therapeutic modality. However, the complexity of the ECMO blood circuit, and challenges with regard to clotting and bleeding, remain as barriers to further expansion of the technology. Recent advances in microfluidic fabrication techniques, devices, and systems present an opportunity to develop new solutions stemming from the ability to precisely maintain critical dimensions such as gas transfer membrane thickness and blood channel geometries, and to control levels of fluid shear within narrow ranges throughout the cartridge. Here, we present a physiologically inspired multilayer microfluidic oxygenator device that mimics physiologic blood flow patterns not only within individual layers but throughout a stacked device. Multiple layers of this microchannel device are integrated with a three-dimensional physiologically inspired distribution manifold that ensures smooth flow throughout the entire stacked device, including the critical entry and exit regions. We then demonstrate blood flows up to 200 ml/min in a multilayer device, with oxygen transfer rates capable of saturating venous blood, the highest of any microfluidic oxygenator, and a maximum blood flow rate of 480 ml/min in an eight-layer device, higher than any yet reported in a microfluidic device. Hemocompatibility and large animal studies utilizing these prototype devices are planned.

          Supplemental Visual Abstract, http://links.lww.com/ASAIO/A769.

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          Most cited references29

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          Myocardial localization of coronavirus in COVID‐19 cardiogenic shock

          Abstract We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a 69‐year‐old patient with flu‐like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous‐arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low‐grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.
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            Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1).

            Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic. To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO. A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching). Survival to hospital discharge analyzed according to the intention-to-treat principle. Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated. For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.
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              Extracorporeal membrane oxygenation for ARDS in adults.

              A 41-year-old woman presents with severe community-acquired pneumococcal pneumonia. Chest radiography reveals diffuse bilateral infiltrates, and hypoxemic respiratory failure develops despite appropriate antibiotic therapy. She is intubated and mechanical ventilation is initiated with a volume- and pressure-limited approach for the acute respiratory distress syndrome (ARDS). Over the ensuing 24 hours, her partial pressure of arterial oxygen (Pao2) decreases to 40 mm Hg, despite ventilatory support with a fraction of inspired oxygen (Fio2) of 1.0 and a positive end-expiratory pressure (PEEP) of 20 cm of water. She is placed in the prone position and a neuromuscular blocking agent is administered, without improvement in her Pao2. An intensive care specialist recommends the initiation of extracorporeal membrane oxygenation (ECMO).
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                Author and article information

                Contributors
                Journal
                ASAIO J
                ASAIO J
                MAT
                Asaio Journal
                Lippincott Williams & Wilkins (Hagerstown, MD )
                1058-2916
                1538-943X
                12 January 2022
                October 2022
                : 68
                : 10
                : 1312-1319
                Affiliations
                From the [* ]Draper, Cambridge, Massachusetts
                []Autonomous Reanimation and Evacuation (AREVA) Research Program, The Geneva Foundation, San Antonio, Texas
                []Thrombodyne, Inc., Salt Lake City, Utah
                [§ ]Uniformed Services University of the Health Sciences, Bethesda, Maryland.
                Author notes
                Correspondence: Jeffrey T. Borenstein, PhD, Bioengineering Division, Draper, 555 Technology Square, MS 32, Cambridge MA 02139. Email: jborenstein@ 123456draper.com .
                Author information
                https://orcid.org/0000-0001-7208-8804
                https://orcid.org/0000-0002-1268-4492
                https://orcid.org/0000-0002-9557-5813
                https://orcid.org/0000-0002-2460-6432
                https://orcid.org/0000-0002-4887-3471
                https://orcid.org/0000-0002-2781-3787
                https://orcid.org/0000-0002-4482-3274
                Article
                00015
                10.1097/MAT.0000000000001647
                9521578
                502a0640-992f-4974-861a-08531930f417
                Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : June 2021
                : November 2021
                Categories
                Pulmonary
                Custom metadata
                TRUE
                T

                microfluidics,oxygenator,transfer,scaling,multilayer
                microfluidics, oxygenator, transfer, scaling, multilayer

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