A Microfluidic Device for Real-time On-demand Intravenous Oxygen Delivery

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Mar 21

PMID 35312360

Authors

Ashwin Kumar Vutha

Ryan Patenaude

Alexis Cole

Rajesh Kumar

John N Kheir

Brian D Polizzotti

Affiliations

Soon will be listed here.

Abstract

SignificanceThe treatment of hypoxemia that is refractory to the current standard of care is time-sensitive and requires skilled caregivers and use of specialized equipment (e.g., extracorporeal membrane oxygenation). Most patients experiencing refractory hypoxemia will suffer organ dysfunction, and death is common in this cohort. Here, we describe a new strategy to stabilize and support patients using a microfluidic device that administers oxygen gas directly to the bloodstream in real time and on demand using a process that we call sequential shear-induced bubble breakup. If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxemia.

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References

Pu G, Borden M, Longo M . Collapse and shedding transitions in binary lipid monolayers coating microbubbles. Langmuir. 2006; 22(7):2993-9. DOI: 10.1021/la0530337. View

Sarkar K, Katiyar A, Jain P . Growth and dissolution of an encapsulated contrast microbubble: effects of encapsulation permeability. Ultrasound Med Biol. 2009; 35(8):1385-96. PMC: 2713870. DOI: 10.1016/j.ultrasmedbio.2009.04.010. View

Seekell R, Lock A, Peng Y, Cole A, Perry D, Kheir J . Oxygen delivery using engineered microparticles. Proc Natl Acad Sci U S A. 2016; 113(44):12380-12385. PMC: 5098671. DOI: 10.1073/pnas.1608438113. View

Katiyar A, Sarkar K . Stability analysis of an encapsulated microbubble against gas diffusion. J Colloid Interface Sci. 2009; 343(1):42-7. PMC: 2821677. DOI: 10.1016/j.jcis.2009.11.030. View

Li Z, Leshansky A, Metais S, Pismen L, Tabeling P . Step-emulsification in a microfluidic device. Lab Chip. 2014; 15(4):1023-31. DOI: 10.1039/c4lc01289e. View

Kheir J, Polizzotti B, Thomson L, OConnell D, Black K, Lee R . Bulk manufacture of concentrated oxygen gas-filled microparticles for intravenous oxygen delivery. Adv Healthc Mater. 2013; 2(8):1131-41. DOI: 10.1002/adhm.201200350. View

Kheir J, Scharp L, Borden M, Swanson E, Loxley A, Reese J . Oxygen gas-filled microparticles provide intravenous oxygen delivery. Sci Transl Med. 2012; 4(140):140ra88. DOI: 10.1126/scitranslmed.3003679. View

Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L . COVID-19 pneumonia: different respiratory treatments for different phenotypes?. Intensive Care Med. 2020; 46(6):1099-1102. PMC: 7154064. DOI: 10.1007/s00134-020-06033-2. View

Peyman S, Abou-Saleh R, McLaughlan J, Ingram N, Johnson B, Critchley K . Expanding 3D geometry for enhanced on-chip microbubble production and single step formation of liposome modified microbubbles. Lab Chip. 2012; 12(21):4544-52. DOI: 10.1039/c2lc40634a. View

10.

Peng Y, Kheir J, Polizzotti B . Injectable Oxygen: Interfacing Materials Chemistry with Resuscitative Science. Chemistry. 2018; 24(71):18820-18829. DOI: 10.1002/chem.201802054. View

11.

Thomson L, Polizzotti B, McGowan F, Kheir J . Manufacture of concentrated, lipid-based oxygen microbubble emulsions by high shear homogenization and serial concentration. J Vis Exp. 2014; (87). PMC: 4207250. DOI: 10.3791/51467. View

12.

Seekell R, Peng Y, Lock A, Kheir J, Polizzotti B . Tunable Polymer Microcapsules for Controlled Release of Therapeutic Gases. Langmuir. 2018; 34(31):9175-9183. DOI: 10.1021/acs.langmuir.8b01328. View

13.

Peng Y, Seekell R, Cole A, Lamothe J, Lock A, van den Bosch S . Interfacial Nanoprecipitation toward Stable and Responsive Microbubbles and Their Use as a Resuscitative Fluid. Angew Chem Int Ed Engl. 2017; 57(5):1271-1276. DOI: 10.1002/anie.201711839. View

14.

Black K, Lock A, Thomson L, Cole A, Tang X, Polizzotti B . Hemodynamic Effects of Lipid-Based Oxygen Microbubbles via Rapid Intravenous Injection in Rodents. Pharm Res. 2017; 34(10):2156-2162. DOI: 10.1007/s11095-017-2222-3. View

15.

Watanabe H, Suzuki M, Inaoka H, Ito N . Ostwald ripening in multiple-bubble nuclei. J Chem Phys. 2014; 141(23):234703. DOI: 10.1063/1.4903811. View

16.

Hippalgaonkar K, Majumdar S, Kansara V . Injectable lipid emulsions-advancements, opportunities and challenges. AAPS PharmSciTech. 2010; 11(4):1526-40. PMC: 3011075. DOI: 10.1208/s12249-010-9526-5. View

17.

Polizzotti B, Thomson L, OConnell D, McGowan F, Kheir J . Optimization and characterization of stable lipid-based, oxygen-filled microbubbles by mixture design. J Biomed Mater Res B Appl Biomater. 2014; 102(6):1148-56. DOI: 10.1002/jbm.b.33096. View