{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:26:38Z","timestamp":1787505998760,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["19H04495"],"award-info":[{"award-number":["19H04495"]}]},{"name":"JSPS KAKENHI","award":["22K04893"],"award-info":[{"award-number":["22K04893"]}]},{"name":"JSPS KAKENHI","award":["JPMJTR 24U9"],"award-info":[{"award-number":["JPMJTR 24U9"]}]},{"DOI":"10.13039\/501100002241","name":"Adaptable and Seamless Technology Transfer Program","doi-asserted-by":"publisher","award":["19H04495"],"award-info":[{"award-number":["19H04495"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Adaptable and Seamless Technology Transfer Program","doi-asserted-by":"publisher","award":["22K04893"],"award-info":[{"award-number":["22K04893"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Adaptable and Seamless Technology Transfer Program","doi-asserted-by":"publisher","award":["JPMJTR 24U9"],"award-info":[{"award-number":["JPMJTR 24U9"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>The mechanisms underlying reduced deformability of red blood cells (RBCs) in Plasmodium falciparum remain unclear. The decrease in RBC deformability associated with malarial infection was measured using ektacytometry, and only mean values were evaluated. In this study, we report the development of a microfluidic sensing device that can evaluate decreased RBC deformability at the single-cell level by measuring ionic current waveforms through micropores. Using an in vitro culture system, we found that when RBC deformability was reduced by P. falciparum infection, ionic current waveforms changed. As RBC deformability decreased, waveforms became asymmetric. Computer simulations suggested that these waveform parameters are largely independent of RBC size and may represent a reliable indicator of diminished deformability. This novel microfluidic RBC deformability sensor allows for detailed single-cell analysis of malaria-associated deformability reduction, potentially aiding in elucidating its pathology.<\/jats:p>","DOI":"10.3390\/s25154722","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T16:41:54Z","timestamp":1754325714000},"page":"4722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Measuring Asymmetric Ionic Current Waveform Through Micropores for Detecting Reduced Red Blood Cell Deformability Due to Plasmodium falciparum Infection"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8590-2737","authenticated-orcid":false,"given":"Kazumichi","family":"Yokota","sequence":"first","affiliation":[{"name":"Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14, Hayashi-cho, Takamatsu 761-0301, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9696-5066","authenticated-orcid":false,"given":"Ken","family":"Hirano","sequence":"additional","affiliation":[{"name":"Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14, Hayashi-cho, Takamatsu 761-0301, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Kajimoto","sequence":"additional","affiliation":[{"name":"Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14, Hayashi-cho, Takamatsu 761-0301, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneaki","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14, Hayashi-cho, Takamatsu 761-0301, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","first-page":"H2145","article-title":"Capillary recruitment in response to tissue hypoxia and its dependence on red blood cell deformability","volume":"277","author":"Parthasarathi","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_2","first-page":"315","article-title":"Disturbed blood flow structuring as critical factor of hemorheological disorders in microcirculation","volume":"19","author":"McHedlishvili","year":"1998","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1586\/14779072.5.4.743","article-title":"Role of red blood cell flow behavior in hemodynamics and hemostasis","volume":"5","author":"Barshtein","year":"2007","journal-title":"Expert. Rev. Cardiovasc. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1164\/ajrccm.157.2.9611103","article-title":"Red blood cell deformability in sepsis","volume":"157","author":"Baskurt","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0950-3536(87)80023-9","article-title":"Rheology of the sickle cell disorders","volume":"1","author":"Stuart","year":"1987","journal-title":"Baillieres Clin. Haematol."},{"key":"ref_6","first-page":"407","article-title":"Rheological changes in diabetic microangiopathy","volume":"42","author":"Negrean","year":"2004","journal-title":"Rom. J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jns.2007.03.011","article-title":"Hemorheological changes dependent on the time from the onset of ischemic stroke","volume":"258","author":"Kowal","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"507","DOI":"10.4269\/ajtmh.1997.57.507","article-title":"Prognostic significance of reduced red blood cell deformability in severe falciparum malaria","volume":"57","author":"Dondorp","year":"1997","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1126\/science.6362007","article-title":"Plasmodium falciparum maturation abolishes physiologic red cell deformability","volume":"223","author":"Cranston","year":"1984","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1182\/bloodadvances.2017013730","article-title":"Reduced red blood cell deformability in Plasmodium knowlesi malaria","volume":"2","author":"Barber","year":"2018","journal-title":"Blood Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0014-5793(91)80842-Q","article-title":"A Plasmodium falciparum exo-antigen alters erythrocyte membrane deformability","volume":"292","author":"Naumann","year":"1991","journal-title":"FEBS Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1093\/infdis\/jiv502","article-title":"Sequestration and Red Cell Deformability as Determinants of Hyperlactatemia in Falciparum Malaria","volume":"213","author":"Ishioka","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e566","DOI":"10.1093\/infdis\/jiae490","article-title":"Reduced Red Blood Cell Deformability in Vivax Malaria","volume":"231","author":"Rathnam","year":"2025","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rey, J., Buffet, P.A., Ciceron, L., Milon, G., Mercereau-Puijalon, O., and Safeukui, I. (2014). Reduced erythrocyte deformability associated with hypoargininemia during Plasmodium falciparum malaria. Sci. Rep., 4.","DOI":"10.1038\/srep03767"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3109\/00365510903266069","article-title":"Parameterization of red blood cell elongation index--shear stress curves obtained by ektacytometry","volume":"69","author":"Baskurt","year":"2009","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1039\/D1LC01058A","article-title":"Technologies for measuring red blood cell deformability","volume":"22","author":"Matthews","year":"2022","journal-title":"Lab. Chip"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Song, Y., Zhang, J., and Li, D. (2017). Microfluidic and Nanofluidic Resistive Pulse Sensing: A Review. Micromachines, 8.","DOI":"10.3390\/mi8070204"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tsutsui, M., Yoshida, T., Yokota, K., Yasaki, H., Yasui, T., Arima, A., Tonomura, W., Nagashima, K., Yanagida, T., and Kaji, N. (2017). Discriminating single-bacterial shape using low-aspect-ratio pores. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-17443-6"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nnano.2016.267","article-title":"Real-time shape approximation and fingerprinting of single proteins using a nanopore","volume":"12","author":"Yusko","year":"2017","journal-title":"Nat. Nanotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"155501","DOI":"10.1088\/1361-6528\/aa5e66","article-title":"Rapid structural analysis of nanomaterials in aqueous solutions","volume":"28","author":"Ryuzaki","year":"2017","journal-title":"Nanotechnology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8490","DOI":"10.1021\/ac300705z","article-title":"Measuring the electric charge and zeta potential of nanometer-sized objects using pyramidal-shaped nanopores","volume":"84","author":"Arjmandi","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1039\/c3lc50427a","article-title":"Electrical measurement of red blood cell deformability on a microfluidic device","volume":"13","author":"Zheng","year":"2013","journal-title":"Lab. Chip"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14420","DOI":"10.1039\/C6NR03371G","article-title":"Nanoparticle mechanics: Deformation detection via nanopore resistive pulse sensing","volume":"8","author":"Darvish","year":"2016","journal-title":"Nanoscale"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.bios.2019.02.064","article-title":"Development of a highly sensitive, quantitative, and rapid detection system for Plasmodium falciparum-infected red blood cells using a fluorescent blue-ray optical system","volume":"132","author":"Yamamoto","year":"2019","journal-title":"Biosens. Bioelectron."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nm.3622","article-title":"Micromagnetic resonance relaxometry for rapid label-free malaria diagnosis","volume":"20","author":"Peng","year":"2014","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yokota, K., Hashimoto, M., Kajimoto, K., Tanaka, M., Murayama, S., Tsutsui, M., Nakajima, Y., Taniguchi, M., and Kataoka, M. (2021). Effect of Electrolyte Concentration on Cell Sensing by Measuring Ionic Current Waveform through Micropores. Biosensors, 11.","DOI":"10.3390\/bios11030078"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1039\/D3CP05565E","article-title":"Multivariate analysis of nanoparticle translocation through a nanopore to improve the accuracy of resistive pulse sensing","volume":"26","author":"Jodeyri","year":"2024","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_28","first-page":"665","article-title":"Red blood cell morphology in falciparum malaria","volume":"47","author":"Kruatrachue","year":"1972","journal-title":"Bull. World Health Organ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17030","DOI":"10.1039\/C5NR03145A","article-title":"Mapping viscoelastic properties of healthy and pathological red blood cells at the nanoscale level","volume":"7","author":"Ciasca","year":"2015","journal-title":"Nanoscale"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1182\/blood-2008-03-146779","article-title":"Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen","volume":"112","author":"Safeukui","year":"2008","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.bios.2017.07.019","article-title":"High-throughput and label-free parasitemia quantification and stage differentiation for malaria-infected red blood cells","volume":"98","author":"Yang","year":"2017","journal-title":"Biosens. Bioelectron."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/25\/15\/4722\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:19:51Z","timestamp":1760033991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/25\/15\/4722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":31,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["s25154722"],"URL":"https:\/\/doi.org\/10.3390\/s25154722","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]}}}