{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:47:46Z","timestamp":1760237266828,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T00:00:00Z","timestamp":1585180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>Air inside of blood vessels is a phenomenon known as gas embolism. During the past years, studies have been performed to assess the influence of air bubbles in microcirculation. In this study, we investigated the flow of bubbles in a microchannel network with several bifurcations, mimicking part of a capillary system. Thus, two working fluids were used, composed by sheep red blood cells (RBCs) suspended in a Dextran 40 solution with different hematocrits (5% and 10%). The experiments were carried out in a polydimethylsiloxane (PDMS) microchannel network fabricated by a soft lithography. A high-speed video microscopy system was used to obtain the results for a blood flow rate of 10 \u00b5L\/min. This system enables the visualization of bubble formation and flow along the network. The results showed that the passage of air bubbles strongly influences the cell\u2019s local concentration, since a higher concentration of cells was observed upstream of the bubble, whereas a lower local hematocrit was visualized at the region downstream of the bubble. In bifurcations, bubbles may split asymmetrically, leading to an uneven distribution of RBCs between the outflow branches.<\/jats:p>","DOI":"10.3390\/mi11040344","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T10:29:38Z","timestamp":1585650578000},"page":"344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Bubbles Moving in Blood Flow in a Microchannel Network: The Effect on the Local Hematocrit"],"prefix":"10.3390","volume":"11","author":[{"given":"David","family":"Bento","sequence":"first","affiliation":[{"name":"CEFT, Faculdade de Engenharia da Universidade do Porto (FEUP) Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"Polytechnic Institute of Bragan\u00e7a, ESTiG\/IPB, C. Sta. Apol\u00f3nia, 5300-857 Bragan\u00e7a, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7986-8934","authenticated-orcid":false,"given":"Sara","family":"Lopes","sequence":"additional","affiliation":[{"name":"Polytechnic Institute of Bragan\u00e7a, ESTiG\/IPB, C. Sta. Apol\u00f3nia, 5300-857 Bragan\u00e7a, Portugal"}]},{"given":"In\u00eas","family":"Maia","sequence":"additional","affiliation":[{"name":"Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-637X","authenticated-orcid":false,"given":"Rui","family":"Lima","sequence":"additional","affiliation":[{"name":"CEFT, Faculdade de Engenharia da Universidade do Porto (FEUP) Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"MEtRICS, Mechanical Eng. Dep., University of Minho, Campus de Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1830-0525","authenticated-orcid":false,"given":"Jo\u00e3o M.","family":"Miranda","sequence":"additional","affiliation":[{"name":"CEFT, Faculdade de Engenharia da Universidade do Porto (FEUP) Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cis.2013.02.002","article-title":"A critical review of physiological bubble formation in hyperbaric decompression","volume":"191","author":"Papadopoulou","year":"2013","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S59","DOI":"10.1016\/j.resp.2009.04.003","article-title":"Venous gas emboli and exhaled nitric oxide with simulated and actual extravehicular activity","volume":"169","author":"Karlsson","year":"2009","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1152\/japplphysiol.91099.2008","article-title":"Decompression to altitude: Assumptions, experimental evidence, and future directions","volume":"106","author":"Foster","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1161\/01.STR.29.9.1821","article-title":"Microemboli in cerebral circulation and alteration of cognitive abilities in patients with mechanical prosthetic heart valves","volume":"29","author":"Deklunder","year":"1998","journal-title":"Stroke"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S1010-7940(03)00379-8","article-title":"Mitral mechanical heart valves: In vitro studies of their closure, vortex and microbubble formation with possible medical implications","volume":"24","author":"Milo","year":"2003","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1067\/mtc.2001.112526","article-title":"Neuropsychologic impairment after coronary bypass surgery: Effect of gaseous microemboli during perfusionist interventions","volume":"121","author":"Borger","year":"2001","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.jtcvs.2003.09.048","article-title":"Solid and gaseous cerebral microembolization during off-pump, on-pump, and open cardiac surgery procedures","volume":"127","author":"Balacumaraswami","year":"2004","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1378\/chest.67.3.335","article-title":"Evidence for pulmonary microembolization during hemodialysis","volume":"67","author":"Bischel","year":"1975","journal-title":"Chest"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/j.1549-8719.2012.00176.x","article-title":"In vivo microscopy of targeted vessel occlusion employing acoustic droplet vaporization","volume":"19","author":"Samuel","year":"2012","journal-title":"Microcirculation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1056\/NEJM200002173420706","article-title":"Gas embolism","volume":"342","author":"Muth","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.3390\/mi6091249","article-title":"Recent advances in applications of droplet microfluidics","volume":"6","author":"Chou","year":"2015","journal-title":"Micromachines"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5700","DOI":"10.1016\/j.ijheatmasstransfer.2008.04.050","article-title":"A boundary element model of microbubble sticking and sliding in the microcirculation","volume":"51","author":"Eshpuniyani","year":"2008","journal-title":"Int. J. Heat Mass Transf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1517\/17425247.4.5.475","article-title":"The application of microbubbles for targeted drug delivery","volume":"4","author":"Bull","year":"2007","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.cis.2014.01.017","article-title":"Circulatory bubble dynamics: From physical to biological aspects","volume":"206","author":"Papadopoulou","year":"2014","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1097\/00000542-200204000-00027","article-title":"Accelerated arteriolar gas embolism reabsorption by an exogenous surfactant","volume":"96","author":"Branger","year":"2002","journal-title":"Anesthesiology: J. Am. Soc. Anesthesiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.jbiomech.2003.09.032","article-title":"MRI and CFD studies of pulsatile flow in healthy and stenosed carotid bifurcation models","volume":"37","author":"Marshall","year":"2004","journal-title":"J. Biomechan."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1549-8719.2011.00099.x","article-title":"Bifurcations: Focal points of particle adhesion in microvascular networks","volume":"18","author":"Prabhakarpandian","year":"2011","journal-title":"Microcirculation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109847","DOI":"10.1016\/j.expthermflusci.2019.109847","article-title":"In vitro blood flow visualizations and cell-free layer (CFL) measurements in a microchannel network","volume":"109","author":"Bento","year":"2019","journal-title":"Exp. Therm. Fluid Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s13206-016-0102-2","article-title":"In Vitro Blood flow and cell-free layer in hyperbolic microchannels: Visualizations and measurements","volume":"10","author":"Rodrigues","year":"2016","journal-title":"BioChip J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.jbiomech.2009.01.026","article-title":"Red blood cell motions in high-hematocrit blood flowing through a stenosed microchannel","volume":"42","author":"Fujiwara","year":"2009","journal-title":"J. Biomech."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s10544-016-0138-z","article-title":"Microbubble moving in blood flow in microchannels: Effect on the cell-free layer and cell local concentration","volume":"19","author":"Bento","year":"2017","journal-title":"Biomed. Microdevices"},{"key":"ref_22","first-page":"629","article-title":"Cell-free layer measurements of in vitro blood flow in a microfluidic network: An automatic and manual approach","volume":"6","author":"Bento","year":"2018","journal-title":"Comput. Methods Biomech. Biomed. Eng. Imaging Vis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bento, D., Rodrigues, R.O., Faustino, V., Pinho, D., Fernandes, C.S., Pereira, A.I., Garcia, V., Miranda, J.M., and Lima, R. (2018). Deformation of red blood cells, air bubbles, and droplets in microfluidic devices: Flow visualizations and measurements. Micromachines, 9.","DOI":"10.3390\/mi9040151"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Catarino, S.O., Rodrigues, R.O., Pinho, D., Miranda, J.M., Minas, G., and Lima, R. (2019). Blood cells separation and sorting techniques of passive microfluidic devices: From fabrication to applications. Micromachines, 10.","DOI":"10.3390\/mi10090593"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1039\/C4LC01246A","article-title":"Microfluidic cell sorting: A review of the advances in the separation of cells from debulking to rare cell isolation","volume":"15","author":"Shields","year":"2015","journal-title":"Lab A Chip"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"44120","DOI":"10.1063\/1.3672689","article-title":"Asymmetry of red blood cell motions in a microchannel with a diverging and converging bifurcation","volume":"5","author":"Leble","year":"2011","journal-title":"Biomicrofluidics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1039\/C5LC01159K","article-title":"Fundamentals and applications of inertial microfluidics: A review","volume":"16","author":"Zhang","year":"2016","journal-title":"Lab A Chip"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rocha, L.A., Miranda, J.M., and Campos, J.B. (2017). Wide range simulation study of taylor bubbles in circular milli and microchannels. Micromachines, 8.","DOI":"10.3390\/mi8050154"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Moreira, A.I., Rocha, L.A.M., Carneiro, J., Ara\u00fajo, J.D.P., Campos, J.B.L.M., and Miranda, J.M. (2020). Isolated taylor bubbles in co-current with shear thinning cmc solutions in microchannels\u2014A numerical study. Processes, 8.","DOI":"10.3390\/pr8020242"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Calejo, J., Pinho, D., Galindo-Rosales, F.J., Lima, R., and Campo-Dea\u00f1o, L. (2016). Particulate blood analogues reproducing the erythrocytes cell-free layer in a microfluidic device containing a hyperbolic contraction. Micromachines, 7.","DOI":"10.3390\/mi7010004"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"026502","DOI":"10.1063\/1.3259624","article-title":"Fabrication of microfluidic devices using polydimethylsiloxane","volume":"4","author":"Friend","year":"2010","journal-title":"Biomicrofluidics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"R81","DOI":"10.1088\/0960-1317\/17\/6\/R01","article-title":"SU-8: A photoresist for high-aspect-ratio and 3D submicron lithography","volume":"17","author":"Greiner","year":"2007","journal-title":"J. Micromech. Microeng."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1088\/0960-1317\/7\/3\/010","article-title":"SU-8: A low-cost negative resist for MEMS","volume":"7","author":"Lorenz","year":"1997","journal-title":"J. Micromech. Microeng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"045021","DOI":"10.1088\/0960-1317\/18\/4\/045021","article-title":"Large-area, high-aspect-ratio SU-8 molds for the fabrication of PDMS microfluidic devices","volume":"18","author":"Natarajan","year":"2008","journal-title":"J. Micromech. Microeng."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1549-8719.2011.00114.x","article-title":"Cell-free layer formation in small arterioles at pathological levels of erythrocyte aggregation","volume":"18","author":"Ong","year":"2011","journal-title":"Microcirculation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s10237-012-0449-9","article-title":"Hematocrit, viscosity and velocity distributions of aggregating and non-aggregating blood in a bifurcating microchannel","volume":"13","author":"Sherwood","year":"2014","journal-title":"Biomech. Model. Mechanobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s10544-015-0014-2","article-title":"A simple microfluidic device for the deformability assessment of blood cells in a continuous flow","volume":"17","author":"Rodrigues","year":"2015","journal-title":"Biomed Microdevices"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/s11051-016-3498-7","article-title":"Haemocompatibility of iron oxide nanoparticles synthesized for theranostic applications: A high-sensitivity microfluidic tool","volume":"18","author":"Rodrigues","year":"2016","journal-title":"J. Nanopart. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/10739680590894966","article-title":"Microvascular rheology and hemodynamics","volume":"12","author":"Lipowsky","year":"2005","journal-title":"Microcirculation"},{"key":"ref_40","first-page":"9","article-title":"Vascular wall shear stress: Basic principles and methods","volume":"46","author":"Papaioannou","year":"2005","journal-title":"Hell. J. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1146\/annurev.fluid.37.042604.133933","article-title":"Microcirculation and hemorheology","volume":"37","author":"Popel","year":"2005","journal-title":"Annu. Rev. Fluid Mech."},{"key":"ref_42","first-page":"H1005","article-title":"Robin Fahraeus: Evolution of his concepts in cardiovascular physiology","volume":"257","author":"Goldsmith","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_43","first-page":"H1770","article-title":"Blood viscosity in tube flow: Dependence on diameter and hematocrit","volume":"263","author":"Pries","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1088\/0957-0233\/17\/4\/026","article-title":"Confocal micro-PIV measurements of three-dimensional profiles of cell suspension flow in a square microchannel","volume":"17","author":"Lima","year":"2006","journal-title":"Meas. Sci. Technol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1016\/j.jbiomech.2015.11.037","article-title":"Red blood cells radial dispersion in blood flowing through microchannels: The role of temperature","volume":"49","author":"Pinho","year":"2016","journal-title":"J. Biomech."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1146\/annurev-fluid-121108-145427","article-title":"Recent advances in micro-particle image velocimetry","volume":"42","author":"Wereley","year":"2010","journal-title":"Annu. Rev. Fluid Mech."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Faustino, V., Catarino, S.O., Pinho, D., Lima, R., and Minas, G. (2018). A passive microfluidic device based on crossflow filtration for cell separation measurements: A spectrophotometric characterization. Biosensors, 8.","DOI":"10.3390\/bios8040125"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Cerdeira, A.T.S., Campos, J., Miranda, J.M., and Araujo, J.D.P. (2020). Review on microbubbles and microdroplets flowing through microfluidic geometrical elements. Micromachines, 11.","DOI":"10.3390\/mi11020201"}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/11\/4\/344\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:11:56Z","timestamp":1760173916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/11\/4\/344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,26]]},"references-count":48,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["mi11040344"],"URL":"https:\/\/doi.org\/10.3390\/mi11040344","relation":{},"ISSN":["2072-666X"],"issn-type":[{"type":"electronic","value":"2072-666X"}],"subject":[],"published":{"date-parts":[[2020,3,26]]}}}