{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:51:00Z","timestamp":1774590660808,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>This study presents the development of a robust aluminum-based microfluidic chip fabricated by conventional mechanical micromachining (computer numerical control-based micro-milling process). It applied the aluminum-based microfluidic chip to form poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating CdSe\/ZnS quantum dots (QDs). A cross-flow design and flow-focusing system were employed to control the oil-in-water (o\/w) emulsification to ensure the generation of uniformly-sized droplets. The size of the droplets could be tuned by adjusting the flow rates of the water and oil phases. The proposed microfluidic platform is easy to fabricate, set up, organize as well as program, and is valuable for further applications under harsh reaction conditions (high temperature and\/or strong organic solvent systems). The proposed method has the advantages of actively controlling the droplet diameter, with a narrow size distribution, good sphericity, as well as being a simple process with a high throughput. In addition to the fluorescent PLGA microparticles in this study, this approach can also be applied to many applications in the pharmaceutical and biomedical area.<\/jats:p>","DOI":"10.3390\/s120201455","type":"journal-article","created":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T12:23:15Z","timestamp":1328098995000},"page":"1455-1467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["An Aluminum Microfluidic Chip Fabrication Using a Convenient Micromilling Process for Fluorescent Poly(DL-lactide-co-glycolide) Microparticle Generation"],"prefix":"10.3390","volume":"12","author":[{"given":"Yung-Sheng","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Biological Science & Technology, I-Shou University, Kaohsiung 84001, Taiwan"},{"name":"Department of Applied Cosmetology and Master Program of Cosmetic Science, Hung-Kuang University, Taichung 43302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biological Science & Technology, I-Shou University, Kaohsiung 84001, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-4193","authenticated-orcid":false,"given":"Fang-Rong","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keng-Shiang","family":"Huang","sequence":"additional","affiliation":[{"name":"The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Chen","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Biological Science & Technology, I-Shou University, Kaohsiung 84001, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2012,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cej.2010.07.021","article-title":"Development of micro chemical, biological and thermal systems in China: A review","volume":"163","author":"Tu","year":"2010","journal-title":"Chem. Eng. J"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4163","DOI":"10.1103\/PhysRevLett.86.4163","article-title":"Dynamic pattern formation in a vesicle-generating microfluidic device","volume":"86","author":"Thorsen","year":"2001","journal-title":"Phys. Rev. Lett"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0169-409X(02)00223-5","article-title":"Lab-on-a-chip for drug development","volume":"55","author":"Weigl","year":"2003","journal-title":"Adv. Drug. Deliv. Rev"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1088\/0960-1317\/18\/2\/025012","article-title":"Rapid fabrication of tooling for microfluidic devices via laser micromachining and hot embossing","volume":"18","author":"Shiu","year":"2008","journal-title":"J. Micromech. Microeng"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1088\/0960-1317\/17\/5\/R01","article-title":"Lab-on-chip technologies: Making a microfluidic network and coupling it into a complete microsystem\u2014A review","volume":"17","author":"Abgrall","year":"2007","journal-title":"J. Micromech. Microeng"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nature05058","article-title":"The origins and the future of microfluidics","volume":"442","author":"Whitesides","year":"2006","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1146\/annurev.fluid.36.050802.122124","article-title":"Engineering flows in small devices: Microfluidics toward a lab-on-a-chip","volume":"36","author":"Stone","year":"2004","journal-title":"Annu. Rev. Fluid Mech"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5897","DOI":"10.1021\/ac020396s","article-title":"An electrospray ionization source for integration with microfluidics","volume":"74","author":"Kameoka","year":"2002","journal-title":"Anal. Chem"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1021\/ac0202435","article-title":"Micrototal analysis systems. 1. Introduction, theory, and technology","volume":"74","author":"Reyes","year":"2002","journal-title":"Anal. Chem"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1021\/ac011111z","article-title":"Continuous-flow chemical processing on a microchip by combining microunit operations and a multiphase flow network","volume":"74","author":"Tokeshi","year":"2002","journal-title":"Anal. Chem"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.jconrel.2005.11.018","article-title":"Fabrication and characterization of microfluidic probes for convection enhanced drug delivery","volume":"111","author":"Neeves","year":"2006","journal-title":"J. Control. Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/(SICI)1522-2683(20000101)21:1<12::AID-ELPS12>3.0.CO;2-7","article-title":"Polymer microfabrication methods for microfluidic analytical applications","volume":"21","author":"Becker","year":"2000","journal-title":"Electrophoresis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0039-9140(01)00594-X","article-title":"Polymer microfluidic devices","volume":"56","author":"Becker","year":"2002","journal-title":"Talanta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1243\/09544062JMES220","article-title":"Comparison between microfabrication technologies for metal tooling","volume":"220","author":"Uriarte","year":"2006","journal-title":"Proc. Inst. Mech. Eng. Part C J. Eng. Mech. Eng. Sci"},{"key":"ref_15","unstructured":"Nguyen, N.T., and Wereley, S.T. (2002). Fabrication Techniques for Microfluidics, Artech House."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0141-6359(00)00064-7","article-title":"Micromilling of metal alloys with focused ion beam-fabricated tools","volume":"25","author":"Adams","year":"2001","journal-title":"Precis. Eng"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1088\/0960-1317\/17\/8\/016","article-title":"Fabrication of round channels using the surface tension of PDMS and its application to a 3D serpentine mixer","volume":"17","author":"Lee","year":"2007","journal-title":"J. Micromech. Microeng"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1006\/jcis.2001.7461","article-title":"Production of oil-in-water microspheres using a stainless steel microchannel","volume":"237","author":"Tong","year":"2001","journal-title":"J. Colloid Interf. Sci"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10404-008-0278-4","article-title":"Generation of uniform drops via through-hole arrays micromachined in stainless-steel plates","volume":"5","author":"Kobayashi","year":"2008","journal-title":"Microfluid. Nanofluid"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9279","DOI":"10.1021\/ie1005228","article-title":"De-emulsification of kerosene\/water emulsions with plate-type microchannels","volume":"49","author":"Chen","year":"2010","journal-title":"Ind. Eng. Chem. Res"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1039\/b606424h","article-title":"Manipulating the generation of Ca-alginate microspheres using microfluidic channels as a carrier of gold nanoparticles","volume":"6","author":"Huang","year":"2006","journal-title":"Lab Chip"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1002\/elps.201100343","article-title":"Synthesis of agar microparticles using temperature-controlled microfluidic devices for Cordyceps Militaris cultivation","volume":"32","author":"Lin","year":"2011","journal-title":"Electrophoresis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6713","DOI":"10.1039\/c0sm01361g","article-title":"In situ synthesis of twin monodispersed alginate microparticles","volume":"7","author":"Huang","year":"2011","journal-title":"Soft Matter"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1039\/B807454B","article-title":"Microfluidic emulsification and sorting assisted preparation of monodisperse chitosan microparticles","volume":"9","author":"Yang","year":"2009","journal-title":"Lab Chip"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1039\/B814952F","article-title":"Microfluidic assisted synthesis of multi-functional polycaprolactone microspheres: Incorporation of CdTe quantum Dots, Fe3O4 superparamagnetic nanoparticles, and tamoxifen","volume":"9","author":"Yang","year":"2009","journal-title":"Lab Chip"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jconrel.2009.02.019","article-title":"Microfluidic controlling monodisperse microdroplet for 5-fluorouracil loaded genipin-gelatin microcapsules","volume":"127","author":"Huang","year":"2009","journal-title":"J. Control. Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s13346-011-0020-8","article-title":"Electrostatic droplets assisted synthesis of alginate microcapsules","volume":"1","author":"Huang","year":"2011","journal-title":"Drug Deliv. Transl. Res"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0168-3659(95)00010-6","article-title":"Preparation of porous and nonporous biodegradable polymeric hollow microspheres","volume":"35","author":"Crotts","year":"1995","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.3390\/s8021308","article-title":"Fabrication of biochips with micro fluidic channels by micro end-milling and powder blasting","volume":"8","author":"Yun","year":"2008","journal-title":"Sensors"},{"key":"ref_30","unstructured":"Clift, R., Grace, J.R., and Weber, M.E. (1978). Bubbles, Drops, and Particles, Academic Press."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/S0009-2509(99)00027-5","article-title":"Dynamics of drop formation in viscous flows","volume":"54","author":"Zhang","year":"1999","journal-title":"Chem. Eng. Sci"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1039\/b715524g","article-title":"Droplet microfluidics","volume":"8","author":"Teh","year":"2008","journal-title":"Lab Chip"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0378-5173(00)00574-3","article-title":"Effects of the rate of solvent evaporation on the characteristics of drug loaded PLLA and PDLLA microspheres","volume":"212","author":"Chung","year":"2001","journal-title":"Int. J. Pharm"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jconrel.2011.02.012","article-title":"Altering the drug release profiles of double-layered ternary-phase microparticles","volume":"151","author":"Lee","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1016\/j.biomaterials.2008.01.010","article-title":"Stabilizer-free poly(lactide-co-glycolide) nanoparticles for multimodal biomedical probes","volume":"29","author":"Cheng","year":"2008","journal-title":"Biomaterials"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/aic.690140105","article-title":"Drop formation at low velocities in liquid-liquid systems: Part I. Prediction of drop volume","volume":"14","author":"Scheele","year":"1968","journal-title":"AIChE J"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/aic.690180326","article-title":"Prediction of drop volumes in liquid-liduid systems","volume":"18","author":"Izard","year":"1972","journal-title":"AIChE J"},{"key":"ref_38","first-page":"514","article-title":"Drop size with drop-type flow conditions out of nozzles in liquid\/liquid systems","volume":"7","author":"Kagan","year":"1973","journal-title":"Theor. Found. Chem. Eng"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chang, J.Y., Yang, C.H., and Huang, K.S. (2007). Microfluidic assisted preparation of CdSe\/ZnS nanocrystals encapsulated into poly(DL-lactide-co-glycolide) microcapsules. Nanotechnology.","DOI":"10.1088\/0957-4484\/18\/30\/305305"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/12\/2\/1455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:48:42Z","timestamp":1760219322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/12\/2\/1455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,1]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2012,2]]}},"alternative-id":["s120201455"],"URL":"https:\/\/doi.org\/10.3390\/s120201455","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,1]]}}}