{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T03:00:18Z","timestamp":1775703618877,"version":"3.50.1"},"reference-count":23,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T00:00:00Z","timestamp":1433289600000},"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>We propose a method to characterize the mechanical properties of cells using a robot-integrated microfluidic chip (robochip) and microscopy. The microfluidic chip is designed to apply the specified deformations to a single detached cell using an on-chip actuator probe. The reaction force is simultaneously measured using an on-chip force sensor composed of a hollow folded beam and probe structure. In order to measure the cellular characteristics in further detail, a sub-pixel level of resolution of probe position is required. Therefore, we utilize the phase detection of moir\u00e9 fringe. Using this method, the experimental resolution of the probe position reaches 42 nm. This is approximately ten times smaller than the optical wavelength, which is the limit of sharp imaging with a microscope. Calibration of the force sensor is also important in accurately measuring cellular reaction forces. We calibrated the spring constant from the frequency response, by the proposed sensing method of the probe position. As a representative of mechanical characteristics, we measured the elastic modulus of Madin-Darby Cannie Kidney (MDCK) cells. In spite of the rigid spring constant, the resolution and sensitivity were twice that achieved in our previous study. Unique cellular characteristics can be elucidated by the improvements in sensing resolution and accuracy.<\/jats:p>","DOI":"10.3390\/mi6060660","type":"journal-article","created":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T11:29:39Z","timestamp":1433330979000},"page":"660-673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["On-Chip Method to Measure Mechanical Characteristics of a Single Cell by Using Moir\u00e9 Fringe"],"prefix":"10.3390","volume":"6","author":[{"given":"Hirotaka","family":"Sugiura","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya 464-8603, Japan"}]},{"given":"Shinya","family":"Sakuma","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya 464-8603, Japan"}]},{"given":"Makoto","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Osaka University, Yamadaoka 2-1, Suita 565-0871, Japan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2508-1615","authenticated-orcid":false,"given":"Fumihito","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya 464-8603, Japan"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1088\/0960-1317\/21\/5\/054003","article-title":"Microsystems for cellular force measurement: A review","volume":"21","author":"Zheng","year":"2011","journal-title":"J. Micromech. Microeng."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.bioeng.9.060906.151927","article-title":"Cell mechanics: Integrating cell responses to mechanical stimuli","volume":"9","author":"Janmey","year":"2007","journal-title":"Annu. Biomed. Eng."},{"key":"ref_3","first-page":"1514","article-title":"Tissue elasticity imaging for diagnosis of prostate cancer: A preliminary report","volume":"13","author":"Miyanaga","year":"2004","journal-title":"J. Urol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/ncb1037","article-title":"Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells","volume":"5","author":"Beil","year":"2003","journal-title":"Nat. Cell Bio."},{"key":"ref_5","first-page":"3689","article-title":"Cancer cell stiffness: Integrated roles of three-dimensional matrix stiffness and transforming potential","volume":"99","author":"Erin","year":"2005","journal-title":"J Biophys."},{"key":"ref_6","first-page":"47","article-title":"Measuring the elastic properties of biological samples with the AFM","volume":"16","author":"Manfred","year":"1997","journal-title":"IEEE J. Transl. Eng. Health Med. Mag."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/S0006-3495(02)75434-9","article-title":"The effects of osmotic stress on the viscoelastic and physical roperties of articular chondrocytes","volume":"82","author":"Guilak","year":"2002","journal-title":"J Biophys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1080\/01691864.2013.876933","article-title":"Atomic force microscopy measurements of mechanical properties of single cells patterned by microcontact printing","volume":"28","author":"Takahashia","year":"2014","journal-title":"J. Adv. Robot."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/BF00164421","article-title":"A novel micromanipulation technique for measuring the bursting strength of single mammalian cells","volume":"36","author":"Zhang","year":"1991","journal-title":"Appl. Microbiol. Biotech."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1115\/1.2895716","article-title":"Numerical simulation of the flow of highly viscous drops down a tapered tube","volume":"116","author":"Kirk","year":"1994","journal-title":"J. Biomech. Eng."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"277","DOI":"10.20965\/jrm.2013.p0277","article-title":"Cellular force measurement using a nanometric-probe-integrated microfluidic chip with a displacement reduction mechanism","volume":"25","author":"Sakuma","year":"2013","journal-title":"J. Mech. Robot."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kakio, T., Bilal, T., Sakuma, S., Kaneko, M., and Arai, F. (2013, January 10\u201313). On-chip cellular force measurement using direct outer drive mechanism. Proceedings of 2013 International Symposium on Micro-Nano Mechatronics and Human Science, Nagoya, Japan.","DOI":"10.1109\/MHS.2013.6710424"},{"key":"ref_13","first-page":"145","article-title":"Hard and soft micromachining for BioMEMS: Review of techniques and examples of applications in microfluidics and drug delivery","volume":"56","author":"Ziaie","year":"2004","journal-title":"Biosens. Drug Deliv. Microscale"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5056","DOI":"10.3390\/s140305056","article-title":"Subpixelic measurement of large 1D displacements: Principle, processing algorithms, performances and software","volume":"14","author":"Guelpa","year":"2014","journal-title":"Sensors"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1364\/AO.24.003049","article-title":"Phase shifter calibration in phase-shifting interferometry","volume":"24","author":"Cheng","year":"1985","journal-title":"Appl. Opt."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s11340-009-9239-4","article-title":"Sampling moir\u00e9 method for accurate small deformation distribution measurement","volume":"50","author":"Ri","year":"2010","journal-title":"Exp. Mech."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1364\/AO.26.001112","article-title":"Effect of piezoelectric transducer nonlinearity on phase shifted interferometry","volume":"26","author":"Ai","year":"1987","journal-title":"Appl. Opt."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.snb.2005.06.009","article-title":"Re-usable multi-inlet, PDMS fluidic connector","volume":"114","author":"Saarela","year":"2006","journal-title":"Sens. Actuators B Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1115\/1.1538190","article-title":"A Semi-Analytical Solution for the Sliding Inception of a Spherical Contact","volume":"125","author":"Kogut","year":"2003","journal-title":"J. Tribol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/smll.200600018","article-title":"Membrane stiffness of animal cells challenged by osmotic stress","volume":"2","author":"Steletenkmap","year":"2006","journal-title":"Small"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jbiomech.2004.12.008","article-title":"Mechanical models for living cells","volume":"39","author":"Lima","year":"2006","journal-title":"J. Biomech."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1109\/TBME.2013.2258155","article-title":"Micro-to-nano biomechanical modeling for assisted biological cell injection","volume":"60","author":"Ladjal","year":"2013","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/BF02510753","article-title":"Rheological modelling of leukocytes","volume":"36","author":"Kan","year":"1998","journal-title":"Med. Biol. Eng. Comput."}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/6\/6\/660\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:47:25Z","timestamp":1760215645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/6\/6\/660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,3]]},"references-count":23,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6]]}},"alternative-id":["mi6060660"],"URL":"https:\/\/doi.org\/10.3390\/mi6060660","relation":{},"ISSN":["2072-666X"],"issn-type":[{"value":"2072-666X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,3]]}}}