{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:59:10Z","timestamp":1775933950414,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya","award":["2017 SGR 1079"],"award-info":[{"award-number":["2017 SGR 1079"]}]},{"DOI":"10.13039\/501100005053","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina","doi-asserted-by":"publisher","award":["CIBER Actions"],"award-info":[{"award-number":["CIBER Actions"]}],"id":[{"id":"10.13039\/501100005053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Catalonia Trade and Investment; Generalitat de Catalunya","award":["AdvanceCat and Base3D"],"award-info":[{"award-number":["AdvanceCat and Base3D"]}]},{"name":"Spanish Ministry of Economy and Competitiveness","award":["TEC2015-70104-P, CTQ2016-75870-P"],"award-info":[{"award-number":["TEC2015-70104-P, CTQ2016-75870-P"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Microfabrication and Polydimethylsiloxane (PDMS) soft-lithography techniques became popular for microfluidic prototyping at the lab, but even after protocol optimization, fabrication is yet a long, laborious process and partly user-dependent. Furthermore, the time and money required for the master fabrication process, necessary at any design upgrade, is still elevated. Digital Manufacturing (DM) and Rapid-Prototyping (RP) for microfluidics applications arise as a solution to this and other limitations of photo and soft-lithography fabrication techniques. Particularly for this paper, we will focus on the use of subtractive DM techniques for Organ-on-a-Chip (OoC) applications. Main available thermoplastics for microfluidics are suggested as material choices for device fabrication. The aim of this review is to explore DM and RP technologies for fabrication of an OoC with an embedded membrane after the evaluation of the main limitations of PDMS soft-lithography strategy. Different material options are also reviewed, as well as various bonding strategies. Finally, a new functional OoC device is showed, defining protocols for its fabrication in Cyclic Olefin Polymer (COP) using two different RP technologies. Different cells are seeded in both sides of the membrane as a proof of concept to test the optical and fluidic properties of the device.<\/jats:p>","DOI":"10.3390\/s21041382","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T22:13:38Z","timestamp":1613513618000},"page":"1382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Rapid Manufacturing of Multilayered Microfluidic Devices for Organ on a Chip Applications"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1062-0401","authenticated-orcid":false,"given":"Roberto","family":"Paoli","sequence":"first","affiliation":[{"name":"Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15\u201321, 08028 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), Monforte de Lemos 3\u20135, Pabell\u00f3n 11, 28029 Madrid, Spain"},{"name":"Department of Electronics and Biomedical Engineering, University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1731-8678","authenticated-orcid":false,"given":"Davide","family":"Di Giuseppe","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Interdisciplinary Center for Advanced Studies on Lab-on-Chip and Organ-on-Chip Applications (IC-LOC), University of Rome Tor Vergata, 00133 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3745-149X","authenticated-orcid":false,"given":"Maider","family":"Badiola-Mateos","sequence":"additional","affiliation":[{"name":"Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15\u201321, 08028 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), Monforte de Lemos 3\u20135, Pabell\u00f3n 11, 28029 Madrid, Spain"},{"name":"Department of Electronics and Biomedical Engineering, University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6673-2066","authenticated-orcid":false,"given":"Eugenio","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Interdisciplinary Center for Advanced Studies on Lab-on-Chip and Organ-on-Chip Applications (IC-LOC), University of Rome Tor Vergata, 00133 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4009-6206","authenticated-orcid":false,"given":"Maria Jose","family":"Lopez-Martinez","sequence":"additional","affiliation":[{"name":"Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15\u201321, 08028 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), Monforte de Lemos 3\u20135, Pabell\u00f3n 11, 28029 Madrid, Spain"},{"name":"Department of Electronics and Biomedical Engineering, University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-3679","authenticated-orcid":false,"given":"Josep","family":"Samitier","sequence":"additional","affiliation":[{"name":"Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15\u201321, 08028 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), Monforte de Lemos 3\u20135, Pabell\u00f3n 11, 28029 Madrid, Spain"},{"name":"Department of Electronics and Biomedical Engineering, University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1039\/C6LC00163G","article-title":"The upcoming 3D-printing revolution in microfluidics","volume":"16","author":"Bhattacharjee","year":"2016","journal-title":"Lab Chip"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1039\/b903043c","article-title":"Biological implications of polydimethylsiloxane-based microfluidic cell culture","volume":"9","author":"Regehr","year":"2009","journal-title":"Lab 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