{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T20:04:29Z","timestamp":1776888269673,"version":"3.51.2"},"reference-count":32,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP15H05761"],"award-info":[{"award-number":["JP15H05761"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16K14197"],"award-info":[{"award-number":["JP16K14197"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16K18051"],"award-info":[{"award-number":["JP16K18051"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>An on-chip deformability checker is proposed to improve the velocity\u2013deformation correlation for red blood cell (RBC) evaluation. RBC deformability has been found related to human diseases, and can be evaluated based on RBC velocity through a microfluidic constriction as in conventional approaches. The correlation between transit velocity and amount of deformation provides statistical information of RBC deformability. However, such correlations are usually only moderate, or even weak, in practical evaluations due to limited range of RBC deformation. To solve this issue, we implemented three constrictions of different width in the proposed checker, so that three different deformation regions can be applied to RBCs. By considering cell responses from the three regions as a whole, we practically extend the range of cell deformation in the evaluation, and could resolve the issue about the limited range of RBC deformation. RBCs from five volunteer subjects were tested using the proposed checker. The results show that the correlation between cell deformation and transit velocity is significantly improved by the proposed deformability checker. The absolute values of the correlation coefficients are increased from an average of 0.54 to 0.92. The effects of cell size, shape and orientation to the evaluation are discussed according to the experimental results. The proposed checker is expected to be useful for RBC evaluation in medical practices.<\/jats:p>","DOI":"10.3390\/mi7100176","type":"journal-article","created":{"date-parts":[[2016,10,3]],"date-time":"2016-10-03T10:17:01Z","timestamp":1475489821000},"page":"176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["An On-Chip RBC Deformability Checker Significantly Improves Velocity-Deformation Correlation"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8840-3984","authenticated-orcid":false,"given":"Chia-Hung","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering, Osaka University, Suita 565-0871, Japan"}]},{"given":"Junichi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Osaka University, Suita 565-0871, Japan"}]},{"given":"Makoto","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Osaka University, Suita 565-0871, Japan"}]},{"given":"Mitsuhiro","family":"Horade","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Osaka University, Suita 565-0871, Japan"}]},{"given":"Hiroaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Osaka University, Suita 565-0871, Japan"}]},{"given":"Tatsunori","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University the Graduate School of Medicine, Suita 565-0871, Japan"}]},{"given":"Tomohito","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University the Graduate School of Medicine, Suita 565-0871, Japan"}]},{"given":"Yasushi","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka University the Graduate School of Medicine, Suita 565-0871, Japan"}]}],"member":"1968","published-online":{"date-parts":[[2016,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jbiomech.2004.12.008","article-title":"Mechanical models for living cells\u2014A review","volume":"39","author":"Lim","year":"2006","journal-title":"J. Biomech."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1182\/blood.V99.3.1060","article-title":"Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells","volume":"99","author":"Glenister","year":"2002","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/jor.1100180607","article-title":"Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage","volume":"18","author":"Trickey","year":"2000","journal-title":"J. Orthop. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1182\/blood.V74.2.855.855","article-title":"Abnormalities in the mechanical properties of red blood cells caused by Plasmodium falciparum","volume":"74","author":"Nash","year":"1989","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/S0140-6736(76)92778-1","article-title":"Impaired red cell deformability in peripheral vascular disease","volume":"307","author":"Reid","year":"1976","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1039\/c2lc21210b","article-title":"High-throughput biophysical measurement of human red blood cells","volume":"12","author":"Zheng","year":"2012","journal-title":"Lab Chip"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1109\/TBME.2013.2296624","article-title":"A new dimensionless index for evaluating cell stiffness-based deformability in microchannel","volume":"61","author":"Tsai","year":"2014","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hirose, Y., Tadakuma, K., Higashimori, M., Arai, T., Kaneko, M., Iitsuka, R., Yamanishi, Y., and Arai, F. (2010, January 3\u20137). A new stiffness evaluation toward high speed cell sorter. Proceedings of the 2010 IEEE International Conference on Robotics and Automation (ICRA), Anchorage, AK, USA.","DOI":"10.1109\/ROBOT.2010.5509970"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.3390\/mi6111457","article-title":"Constriction channel based single-cell mechanical property characterization","volume":"6","author":"Xue","year":"2015","journal-title":"Micromachines"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tsai, C.D., Mizoue, K., Kaneko, M., Sakuma, S., and Arai, F. (2015, January 2\u20135). Novel microfluidic chip for extracting cell deformability. Proceedings of the 2015 IEEE International Conference on Mechatronics and Automation, Beijing, China.","DOI":"10.1109\/ICMA.2015.7237817"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1103\/PhysRevLett.56.930","article-title":"Atomic force microscope","volume":"56","author":"Binnig","year":"1986","journal-title":"Phys. Rev. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.tibtech.2007.01.005","article-title":"Biomechanics approaches to studying human diseases","volume":"25","author":"Lee","year":"2007","journal-title":"Trends Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1006\/mvre.2001.2307","article-title":"Direct measurement of erythrocyte deformability in diabetes mellitus with a transparent microchannel capillary model and high-speed video camera system","volume":"61","author":"Tsukada","year":"2001","journal-title":"Microvasc. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1109\/TBME.2010.2042448","article-title":"Mechanical characterization of human red blood cells under different osmotic conditions by robotic manipulation with optical tweezers","volume":"57","author":"Tan","year":"2010","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S0006-3495(96)79602-9","article-title":"Measuring the viscoelastic properties of human platelets with the atomic force microscope","volume":"70","author":"Radmacher","year":"1996","journal-title":"Biophys. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1034\/j.1600-0609.2003.00027.x","article-title":"Optical tweezers for measuring red blood cell elasticity: Application to the study of drug response in sickle cell disease","volume":"70","author":"Brandao","year":"2003","journal-title":"Eur. J. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1039\/c3lc50355k","article-title":"Recent advances in microfluidic techniques for single-cell biophysical characterization","volume":"13","author":"Zheng","year":"2013","journal-title":"Lab Chip"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.1039\/c1lc20473d","article-title":"Classification of cell types using a microfluidic device for mechanical and electrical measurement on single cells","volume":"11","author":"Chen","year":"2011","journal-title":"Lab Chip"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45050","DOI":"10.1039\/C4RA08276A","article-title":"Geometrical alignment for improving cell evaluation in a microchannel with application on multiple myeloma red blood cells","volume":"4","author":"Tsai","year":"2014","journal-title":"RSC Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1039\/c3lc51003d","article-title":"Red blood cell fatigue evaluation based on close-encountering point between extensibility and recoverability","volume":"14","author":"Sakuma","year":"2014","journal-title":"Lab Chip"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"36079","DOI":"10.1039\/C4RA04229H","article-title":"Erythrocyte deformation in a microfluidic cross-slot channel","volume":"4","author":"Henon","year":"2014","journal-title":"RSC Adv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101319","DOI":"10.1039\/C5RA17864A","article-title":"Atomic force microscopy for dynamic observation of human erythrocytes in a microfluidic system","volume":"5","author":"Kuo","year":"2015","journal-title":"RSC Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nmeth.3281","article-title":"Real-time deformability cytometry: On-the-fly cell mechanical phenotyping","volume":"12","author":"Otto","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7630","DOI":"10.1073\/pnas.1200107109","article-title":"Hydrodynamic stretching of single cells for large population mechanical phenotyping","volume":"109","author":"Gossett","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1002\/elps.200600553","article-title":"Parallel separation of multiple samples with negative pressure sample injection on a 3-D microfluidic array chip","volume":"28","author":"Zhang","year":"2007","journal-title":"Electrophoresis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s10544-012-9643-x","article-title":"Improvement in cell capture throughput using parallel bioactivated microfluidic channels","volume":"14","author":"Javanmard","year":"2012","journal-title":"Biomed. Microdevices"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S0006-3495(03)74882-6","article-title":"Parallel microchannel-based measurements of individual erythrocyte areas and volumes","volume":"84","author":"Gifford","year":"2003","journal-title":"Biophys. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1039\/b712486d","article-title":"Matrix-dependent adhesion of vascular and valvular endothelial cells in microfluidic channels","volume":"7","author":"Young","year":"2007","journal-title":"Lab Chip"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1039\/C4LC01100G","article-title":"Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability","volume":"15","author":"Deng","year":"2015","journal-title":"Lab Chip"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1039\/C2LC20799K","article-title":"Design of pressure-driven microfluidic networks using electric circuit analogy","volume":"12","author":"Oh","year":"2012","journal-title":"Lab Chip"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1039\/C5SM02933C","article-title":"Deformation and internal stress in a red blood cell as it is driven through a slit by an incoming flow","volume":"12","author":"Salehyar","year":"2016","journal-title":"Soft Matter"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Yoshikawa, S., Tsai, C.H.D., Sakuma, S., Arai, F., and Kaneko, M. (November, January 30). Realtime cell tracking in a microchannel. Proceedings of the 2013 10th International Conference on Ubiquitous Robots and Ambient Intelligence, Jeju, Korea.","DOI":"10.1109\/URAI.2013.6677498"}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/7\/10\/176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:32:17Z","timestamp":1760211137000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/7\/10\/176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,1]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2016,10]]}},"alternative-id":["mi7100176"],"URL":"https:\/\/doi.org\/10.3390\/mi7100176","relation":{},"ISSN":["2072-666X"],"issn-type":[{"value":"2072-666X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,1]]}}}