{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:56:49Z","timestamp":1776779809586,"version":"3.51.2"},"reference-count":32,"publisher":"AIP Publishing","issue":"4","funder":[{"name":"Medical Science and Technology Key Research and Development Program of Henan","award":["SBGJ202402054"],"award-info":[{"award-number":["SBGJ202402054"]}]},{"DOI":"10.13039\/501100015956","name":"Special Project for Research and Development in Key Areas of Guangdong Province","doi-asserted-by":"publisher","award":["2023B0909020003"],"award-info":[{"award-number":["2023B0909020003"]}],"id":[{"id":"10.13039\/501100015956","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82341019"],"award-info":[{"award-number":["82341019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["WDZC20231129232931001"],"award-info":[{"award-number":["WDZC20231129232931001"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016804","name":"Natural Science Foundation of Shenzhen Municipality","doi-asserted-by":"publisher","award":["RCYX20200714114736146"],"award-info":[{"award-number":["RCYX20200714114736146"]}],"id":[{"id":"10.13039\/100016804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFA0919800"],"award-info":[{"award-number":["2024YFA0919800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:p>Stem cell-derived organoid development typically involves an initial gel-free embryoid body (EB) formation step followed by a gel-embedded differentiation phase. Although high-throughput EB formation technologies are well established, the manual gel-embedding step remains a major bottleneck that limits overall throughput. In this study, we introduce OrgDense, a droplet-confined high-throughput centrifugal cell condensation method that operates within nanoliter volumes. OrgDense efficiently aggregates stem cells into compact cell pellets within a gel matrix, processing over 1000 organoid precursors per batch. The cell-occupied projected area was reduced to \u223c50% of that in controls, thus enhancing paracrine signaling. Condensed droplet-engineered organoids reliably developed into organoids from single colonies with accelerated developmental timelines. In gel-free conditions, OrgDense enabled rapid cell aggregation within 1\u00a0h without compromising cell viability. Moreover, centrifuge-based condensation demonstrated robust compatibility across multiple cell lines and primary cells.<\/jats:p>","DOI":"10.1063\/5.0319625","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:49:17Z","timestamp":1776775757000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["OrgDense: An automatic microfluidic centrifugal device for 3D cell condensation"],"prefix":"10.1063","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5259-3133","authenticated-orcid":false,"given":"Jiawei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Zhengzhou University 1 , Zhengzhou,","place":["China"]},{"name":"Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University 2 , Shenzhen 518055,","place":["China"]},{"name":"Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University 3 , Beijing 100084,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongde","family":"Cai","sequence":"additional","affiliation":[{"name":"Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University 2 , Shenzhen 518055,","place":["China"]},{"name":"Synorg Biotechnology (Shenzhen) Co. Ltd. 4 , Shenzhen 518107,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9503-7775","authenticated-orcid":false,"given":"Ziqi","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Zhengzhou University 1 , Zhengzhou,","place":["China"]},{"name":"Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University 2 , Shenzhen 518055,","place":["China"]},{"name":"Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University 3 , Beijing 100084,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingshi","family":"Su","sequence":"additional","affiliation":[{"name":"Synorg Biotechnology (Shenzhen) Co. Ltd. 4 , Shenzhen 518107,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Synorg Biotechnology (Shenzhen) Co. Ltd. 4 , Shenzhen 518107,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyu","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Zhengzhou University 1 , Zhengzhou,","place":["China"]},{"name":"Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University 2 , Shenzhen 518055,","place":["China"]},{"name":"Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University 3 , Beijing 100084,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haowei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Zhengzhou University 1 , Zhengzhou,","place":["China"]},{"name":"Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University 2 , Shenzhen 518055,","place":["China"]},{"name":"Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University 3 , Beijing 100084,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Zhengzhou University 1 , Zhengzhou,","place":["China"]},{"name":"Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University 2 , Shenzhen 518055,","place":["China"]},{"name":"Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University 3 , Beijing 100084,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Zhengzhou University 1 , Zhengzhou,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4995-2032","authenticated-orcid":false,"given":"Shaohua","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Zhengzhou University 1 , Zhengzhou,","place":["China"]},{"name":"Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University 2 , Shenzhen 518055,","place":["China"]},{"name":"Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University 3 , Beijing 100084,","place":["China"]},{"name":"Key Lab of Active Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education Institutes, Tsinghua Shenzhen International Graduate School 5 , Shenzhen 518055,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"317","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"2026042108491458300_c1","doi-asserted-by":"publisher","first-page":"eadu9375","DOI":"10.1126\/science.adu9375","article-title":"Gastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization","volume":"388","year":"2025","journal-title":"Science"},{"key":"2026042108491458300_c2","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/s41586-024-07330-2","article-title":"Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo","volume":"629","year":"2024","journal-title":"Nature"},{"key":"2026042108491458300_c3","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41421-024-00662-3","article-title":"Treating a type 2 diabetic patient with impaired pancreatic islet function by personalized endoderm stem cell-derived islet tissue","volume":"10","year":"2024","journal-title":"Cell Discovery"},{"key":"2026042108491458300_c4","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nature12517","article-title":"Cerebral organoids model human brain development and microcephaly","volume":"501","year":"2013","journal-title":"Nature"},{"key":"2026042108491458300_c5","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.3390\/cells9102270","article-title":"Cell mechanics in embryoid bodies","volume":"9","year":"2020","journal-title":"Cells"},{"key":"2026042108491458300_c6","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1242\/dev.142794","article-title":"Paracrine signals regulate human liver organoid maturation from induced pluripotent stem cells","volume":"144","year":"2017","journal-title":"Development"},{"key":"2026042108491458300_c7","doi-asserted-by":"publisher","first-page":"12258","DOI":"10.1073\/pnas.94.23.12258","article-title":"Effective intercellular communication distances are determined by the relative time constants for cyto\/chemokine secretion and diffusion","volume":"94","year":"1997","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026042108491458300_c8","doi-asserted-by":"publisher","first-page":"e09652","DOI":"10.7554\/elife.09652","article-title":"Paracrine communication maximizes cellular response fidelity in wound signaling","volume":"4","year":"2015","journal-title":"Elife"},{"key":"2026042108491458300_c9","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41592-018-0255-0","article-title":"Reliability of human cortical organoid generation","volume":"16","year":"2019","journal-title":"Nat. Methods"},{"key":"2026042108491458300_c10","doi-asserted-by":"publisher","first-page":"9420","DOI":"10.1038\/s41467-024-53073-z","article-title":"Scalable production of uniform and mature organoids in a 3D geometrically-engineered permeable membrane","volume":"15","year":"2024","journal-title":"Nat. Commun."},{"key":"2026042108491458300_c11","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1038\/s41551-021-00757-2","article-title":"Single-cell-resolved differentiation of human induced pluripotent stem cells into pancreatic duct-like organoids on a microwell chip","volume":"5","year":"2021","journal-title":"Nat. Biomed. Eng."},{"issue":"13","key":"2026042108491458300_c12","doi-asserted-by":"publisher","first-page":"692","DOI":"10.3791\/692","article-title":"Shrinky-Dink hanging drops: A simple way to form and culture embryoid bodies","volume":"2008","journal-title":"JoVE"},{"key":"2026042108491458300_c13","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1248\/bpb.35.308","article-title":"Stirred suspension culture improves embryoid body formation and cardiogenic differentiation of genetically modified embryonic stem cells","volume":"35","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"2026042108491458300_c14","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1089\/cell.2012.0082","article-title":"Slow turning lateral vessel bioreactor improves embryoid body formation and cardiogenic differentiation of mouse embryonic stem cells","volume":"15","year":"2013","journal-title":"Cell. Reprogram."},{"key":"2026042108491458300_c15","doi-asserted-by":"publisher","first-page":"6685","DOI":"10.1038\/s41467-023-42297-0","article-title":"Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules","volume":"14","year":"2023","journal-title":"Nat. Commun."},{"key":"2026042108491458300_c16","doi-asserted-by":"publisher","first-page":"3082","DOI":"10.1038\/s41596-019-0213-z","article-title":"Generation of blood vessel organoids from human pluripotent stem cells","volume":"14","year":"2019","journal-title":"Nat. Protoc."},{"key":"2026042108491458300_c17","doi-asserted-by":"publisher","first-page":"100161","DOI":"10.1016\/j.xcrm.2020.100161","article-title":"An automated organoid platform with inter-organoid homogeneity and inter-patient heterogeneity","volume":"1","year":"2020","journal-title":"Cell Rep. Med."},{"key":"2026042108491458300_c18","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.stem.2022.04.006","article-title":"Patient-derived micro-organospheres enable clinical precision oncology","volume":"29","year":"2022","journal-title":"Cell Stem Cell"},{"key":"2026042108491458300_c19","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/s1673-8527(09)60064-3","article-title":"Embryoid bodies formation and differentiation from mouse embryonic stem cells in collagen\/Matrigel scaffolds","volume":"37","year":"2010","journal-title":"J.\u00a0Genet. Genomics"},{"key":"2026042108491458300_c20","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/embor.2011.88","article-title":"E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming","volume":"12","year":"2011","journal-title":"EMBO Rep."},{"key":"2026042108491458300_c21","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/s0092-8674(04)00255-7","article-title":"Socializing with the neighbors: Stem cells and their niche","volume":"116","year":"2004","journal-title":"Cell"},{"key":"2026042108491458300_c22","doi-asserted-by":"publisher","first-page":"E267","DOI":"10.1152\/ajpendo.00151.2002","article-title":"Magnitude and variation of fat-free mass density: A cellular-level body composition modeling study","volume":"284","year":"2003","journal-title":"Am. J. Physiol.: Endocrinol. Metab."},{"key":"2026042108491458300_c23","doi-asserted-by":"publisher","first-page":"116257","DOI":"10.1016\/j.cma.2023.116257","article-title":"Diffuse interface model for cell interaction and aggregation with Lennard-Jones type potential","volume":"415","year":"2023","journal-title":"Comput. Methods Appl. Mech. Eng."},{"key":"2026042108491458300_c24","doi-asserted-by":"publisher","first-page":"100420","DOI":"10.1016\/j.device.2024.100420","article-title":"Ultra-small tissue-compatible organoid printer for rapid and controllable modeling of respiratory organoids","volume":"2","year":"2024","journal-title":"Device"},{"key":"2026042108491458300_c25","doi-asserted-by":"publisher","first-page":"0699","DOI":"10.34133\/research.0699","article-title":"Microdroplet-engineered skeletal muscle organoids from primary tissue recapitulate parental physiology with high reproducibility","volume":"8","year":"2025","journal-title":"Research"},{"key":"2026042108491458300_c26","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1038\/nprot.2014.158","article-title":"Generation of cerebral organoids from human pluripotent stem cells","volume":"9","year":"2014","journal-title":"Nat. Protoc."},{"key":"2026042108491458300_c27","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.scr.2013.07.011","article-title":"Scalable expansion of human induced pluripotent stem cells in the defined xeno-free E8 medium under adherent and suspension culture conditions","volume":"11","year":"2013","journal-title":"Stem Cell Res."},{"key":"2026042108491458300_c28","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s12079-021-00643-1","article-title":"Matrigel: History\/background, uses, and future applications","volume":"16","year":"2022","journal-title":"J.\u00a0Cell Commun. Signal."},{"key":"2026042108491458300_c29","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-025-01550-1","article-title":"Nonexpansive biodegradable matrix promotes blood vessel organoid development for neurovascular repair and functional recovery in ischaemic stroke","year":"2025","journal-title":"Nat. Biomed. Eng."},{"key":"2026042108491458300_c30","doi-asserted-by":"publisher","first-page":"5829","DOI":"10.1111\/jcmm.16578","article-title":"Organoid models of the tumor microenvironment and their applications","volume":"25","year":"2021","journal-title":"J.\u00a0Cell. Mol. Med."},{"key":"2026042108491458300_c31","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/s41578-020-0199-8","article-title":"Synthetic alternatives to Matrigel","volume":"5","year":"2020","journal-title":"Nat. Rev. Mater."},{"key":"2026042108491458300_c32","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth","volume":"41","year":"2023","journal-title":"Cancer Cell"}],"container-title":["Review of Scientific Instruments"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.aip.org\/aip\/rsi\/article-pdf\/doi\/10.1063\/5.0319625\/20980372\/045208_1_5.0319625.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.aip.org\/aip\/rsi\/article-pdf\/doi\/10.1063\/5.0319625\/20980372\/045208_1_5.0319625.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:49:19Z","timestamp":1776775759000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.aip.org\/rsi\/article\/97\/4\/045208\/3387480\/OrgDense-An-automatic-microfluidic-centrifugal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1063\/5.0319625","relation":{},"ISSN":["0034-6748","1089-7623"],"issn-type":[{"value":"0034-6748","type":"print"},{"value":"1089-7623","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,4,1]]},"article-number":"045208"}}