{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:37:18Z","timestamp":1760243838981,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2011,10,12]],"date-time":"2011-10-12T00:00:00Z","timestamp":1318377600000},"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 demonstrates a novel cell manipulation microdevice for cell docking, culturing, cell-cell contact and interaction by microfluidic manipulation of heterogeneous cell suspensions. Heterogeneous cell suspensions include disparate blood cells of natural killer cells and leukemia cancer cells for immune cell transplantation therapy. However, NK cell alloreactivity from different healthy donors present various recovery response levels. Little is still known about the interactions and cytotoxicity effects between donor NK cells and recipient cancer cells. The cell-based micro device first showed the capability of cell docking, movement, contact and cell-cell interaction with respect to cell cytotoxicity of NK cells against cancer cells. With various flow tests for live cell loading, flow rates of 10 \u03bcL\/h were chosen for injection in the central and side flows such that both types of suspension cells could be gently docked at the gap structure in a reaction zone. The trapping number of particles and cells was linearly proportional to the gap length. Finally, the cytotoxicity of around 40% was found to be similar in the case of dilute cells and a large cell population. As a result, the cell manipulation microdevice has been validated for live suspensions of natural killer and cancer cells, and exhibited the capability to measure the cytotoxicity of dilute cell suspensions.<\/jats:p>","DOI":"10.3390\/s111009613","type":"journal-article","created":{"date-parts":[[2011,10,12]],"date-time":"2011-10-12T10:41:24Z","timestamp":1318416084000},"page":"9613-9627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cell Docking, Movement and Cell-Cell Interactions of Heterogeneous Cell Suspensions in a Cell Manipulation Microdevice"],"prefix":"10.3390","volume":"11","author":[{"given":"Fei-Lung","family":"Lai","sequence":"first","affiliation":[{"name":"Institute of Applied Mechanics, National Taiwan University, 1 Sec. 4 Roosevelt Road, Taipei 10617, Taiwan"}]},{"given":"Yu-Hung","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Applied Mechanics, National Taiwan University, 1 Sec. 4 Roosevelt Road, Taipei 10617, Taiwan"}]},{"given":"Yu-Wei","family":"Chung","sequence":"additional","affiliation":[{"name":"Institute of Applied Mechanics, National Taiwan University, 1 Sec. 4 Roosevelt Road, Taipei 10617, Taiwan"}]},{"given":"Shiaw-Min","family":"Hwang","sequence":"additional","affiliation":[{"name":"Bioresources Collection and Research Center, Food Industry Research and Development Institute, 331 Shih-Pin Road, Hsinchu 300, Taiwan"}]},{"given":"Long-Sun","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Applied Mechanics, National Taiwan University, 1 Sec. 4 Roosevelt Road, Taipei 10617, Taiwan"}]}],"member":"1968","published-online":{"date-parts":[[2011,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1182\/blood-2006-07-038687","article-title":"Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value","volume":"110","author":"Ruggeri","year":"2007","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1200\/JCO.2009.24.4590","article-title":"NKAML: A pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia","volume":"28","author":"Rubnitz","year":"2010","journal-title":"J. Clin. Oncol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1126\/science.1068440","article-title":"Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants","volume":"295","author":"Ruggeri","year":"2002","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1182\/blood-2007-04-084293","article-title":"Outcomes in CCG-2961, a Children\u2019s Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: A report from the Children\u2019s Oncology Group","volume":"111","author":"Lange","year":"2008","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1200\/JCO.2006.06.5037","article-title":"Less toxicity by optimizing chemotherapy, but not by addition of granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: Results of AML-BFM 98","volume":"24","author":"Creutzig","year":"2006","journal-title":"J. Clin. Oncol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.molimm.2004.07.034","article-title":"Activation of NK cell cytotoxicity","volume":"42","author":"Smyth","year":"2005","journal-title":"Mol. Immunol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1038\/leu.2010.19","article-title":"Identifying candidate allogeneic NK-cell donors for hematopoietic stem-cell transplantation based on functional phenotype","volume":"24","author":"Hurton","year":"2010","journal-title":"Leukemia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1182\/blood-2010-07-294041","article-title":"Donor selection for AML: Do the KIR","volume":"116","author":"Handgretinger","year":"2010","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1182\/blood-2010-05-283051","article-title":"Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia","volume":"116","author":"Cooley","year":"2010","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1007\/s10544-009-9304-x","article-title":"The culture and differentiation of amniotic stem cells using a microfluidic system","volume":"11","author":"Wu","year":"2009","journal-title":"Biomed. Microdevices"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1039\/b803598a","article-title":"An integrated optofluidic platform for Raman-activated cell sorting","volume":"8","author":"Lau","year":"2008","journal-title":"Lab Chip"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1039\/b507575k","article-title":"Micromachined electrochemical T-switches for cell sorting applications","volume":"5","author":"Ho","year":"2005","journal-title":"Lab Chip"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6623","DOI":"10.3390\/s100706623","article-title":"Microfluidic systems for biosensing","volume":"10","author":"Liu","year":"2010","journal-title":"Sensors"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1023\/A:1024467417471","article-title":"Optical manipulation of objects and biological cells in microfluidic devices","volume":"5","author":"Ozkan","year":"2003","journal-title":"Biomed. Microdevices"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1039\/b605937f","article-title":"Dynamic single cell culture array","volume":"6","author":"Carlo","year":"2006","journal-title":"Lab Chip"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1039\/b201021f","article-title":"Generation of concentration gradient by controlled flow distribution and diffusive mixing in a microfluidic chip","volume":"2","author":"Yang","year":"2002","journal-title":"Lab Chip"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1039\/c0lc00620c","article-title":"Integrated ionic liquid-based electrofluidic circuits for pressure sensing within polydimethylsiloxane microfluidic systems","volume":"11","author":"Wu","year":"2011","journal-title":"Lab Chip"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.1021\/ac0340758","article-title":"Microfluidic device for single-cell analysis","volume":"75","author":"Wheeler","year":"2003","journal-title":"Anal. Chem"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1021\/ac025536c","article-title":"Cell docking and on-chip monitoring of cellular reactions with a controlled concentration gradient on a microfluidic device","volume":"74","author":"Yang","year":"2002","journal-title":"Anal. Chem"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1039\/b712897p","article-title":"Sonoporation of suspension cells with a single cavitation bubble in a microfluidic confinement","volume":"7","author":"Gac","year":"2007","journal-title":"Lab Chip"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1039\/B613344D","article-title":"Continuous dielectrophoretic cell separation microfluidic device","volume":"7","author":"Li","year":"2007","journal-title":"Lab Chip"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e15453:1","DOI":"10.1371\/journal.pone.0015453","article-title":"Imaging immune surveillance of individual natural killer cells confined in microwell arrays","volume":"5","author":"Guldevall","year":"2010","journal-title":"PLoS One"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"223902:1","DOI":"10.1063\/1.1938253","article-title":"Microfluidic application-specific integrated device for monitoring direct cell-cell communication via gap junctions between individual cell pairs","volume":"86","author":"Lee","year":"2005","journal-title":"Appl Phys Lett"},{"key":"ref_24","unstructured":"Fox, RW, McDonald, AT, and Pritchard, PJ (2003). Introduction to Fluid Mechanics, John Wiley & Sons. [6th Edition]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S0006-3495(98)77562-9","article-title":"A theoretical model study of the influence of fluid stresses on a cell adhering to a microchannel wall","volume":"75","author":"Gaver","year":"1998","journal-title":"Biophys. J"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1158\/1078-0432.CCR-10-0735","article-title":"Cytotoxicity of activated natural killer cells against pediatric solid tumors","volume":"16","author":"Cho","year":"2010","journal-title":"Clin. Cancer Res"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/j.actamat.2003.12.028","article-title":"Large deformation of living cells using laser traps","volume":"52","author":"Lim","year":"2004","journal-title":"Acta Mater"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/11\/10\/9613\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:57:39Z","timestamp":1760219859000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/11\/10\/9613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,12]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2011,10]]}},"alternative-id":["s111009613"],"URL":"https:\/\/doi.org\/10.3390\/s111009613","relation":{},"ISSN":["1424-8220"],"issn-type":[{"type":"electronic","value":"1424-8220"}],"subject":[],"published":{"date-parts":[[2011,10,12]]}}}