{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:31:57Z","timestamp":1790685117044,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"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>Spheroids are recognized for resembling the important characteristics of natural tumors in cancer research. However, the lack of controllability of the spheroid size, form, and density in conventional spheroid culture methods reduces the reproducibility and precision of bioassay results and the assessment of drug-dose responses in spheroids. Nonetheless, the accurate prediction of cellular responses to drug compounds is crucial for developing new efficient therapeutic agents and optimizing existing therapeutic strategies for personalized medicine. We developed a surface-optimized PDMS microfluidic biochip to produce uniform and homogenous multicellular spheroids in a reproducible manner. This platform is surface optimized with 10% bovine serum albumin (BSA) to provide cell-repellent properties. Therefore, weak cell-surface interactions lead to the promotion of cell self-aggregations and the production of compact and uniform spheroids. We used a lung cancer cell line (A549), a co-culture model of lung cancer cells (A549) with (primary human osteoblasts, and patient-derived spine metastases cells (BML, bone metastasis secondary to lung). We observed that the behavior of cells cultured in three-dimensional (3D) spheroids within this biochip platform more closely reflects in vivo-like cellular responses to a chemotherapeutic drug, Doxorubicin, rather than on 24-well plates (two-dimensional (2D) model). It was also observed that the co-culture and patient-derived spheroids exhibited resistance to anti-cancer drugs more than the mono-culture spheroids. The repeatability of drug test results in this optimized platform is the hallmark of the reproducibility of uniform spheroids on a chip. This surface-optimized biochip can be a reliable platform to generate homogenous and uniform spheroids to study and monitor the tumor microenvironment and for drug screening.<\/jats:p>","DOI":"10.3390\/mi13040587","type":"journal-article","created":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T06:02:54Z","timestamp":1649570574000},"page":"587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Uniform Tumor Spheroids on Surface-Optimized Microfluidic Biochips for Reproducible Drug Screening and Personalized Medicine"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6836-4797","authenticated-orcid":false,"given":"Neda","family":"Azizipour","sequence":"first","affiliation":[{"name":"Institut de G\u00e9nie Biom\u00e9dical, Polytechnique Montr\u00e9al, Montr\u00e9al, QC H3C 3A7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2522-2692","authenticated-orcid":false,"given":"Rahi","family":"Avazpour","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Polytechnique Montr\u00e9al, Montr\u00e9al, QC H3C 3A7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Orthopaedic Surgery, McGill University, Montr\u00e9al, QC H3G 1A4, Canada"},{"name":"Injury, Repair and Recovery Program, Research Institute of McGill University Health Centre, Montr\u00e9al, QC H3H 2R9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4137-7272","authenticated-orcid":false,"given":"Mohamad","family":"Sawan","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9nie Biom\u00e9dical, Polytechnique Montr\u00e9al, Montr\u00e9al, QC H3C 3A7, Canada"},{"name":"Polystim Neurotech Laboratory, Electrical Engineering Department, Polytechnique Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"},{"name":"CenBRAIN Laboratory, School of Engineering, Westlake Institute for Advanced Study, Westlake University, Hangzhou 310024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9944-4538","authenticated-orcid":false,"given":"Abdellah","family":"Ajji","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9nie Biom\u00e9dical, Polytechnique Montr\u00e9al, Montr\u00e9al, QC H3C 3A7, Canada"},{"name":"NSERC-Industry Chair, CREPEC, Chemical Engineering Department, Polytechnique Montr\u00e9al, Montr\u00e9al, QC H3C 3A7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-8177","authenticated-orcid":false,"given":"Derek H.","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Orthopaedic Surgery, McGill University, Montr\u00e9al, QC H3G 1A4, Canada"},{"name":"Injury, Repair and Recovery Program, Research Institute of McGill University Health Centre, Montr\u00e9al, QC H3H 2R9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-89352-8","article-title":"A combined microfluidic deep learning approach for lung cancer cell high throughput screening toward automatic cancer screening applications","volume":"11","author":"Hashemzadeh","year":"2021","journal-title":"Sci. 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