{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:08:11Z","timestamp":1777892891647,"version":"3.51.4"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Primary tumors of patients can release circulating tumor cells (CTCs) to flow inside of their blood. The CTCs have different mechanical properties in comparison with red and white blood cells, and their detection may be employed to study the efficiency of medical treatments against cancer. We present the design of a novel MEMS microgripper with rotatory electrostatic comb-drive actuators for mechanical properties characterization of cells. The microgripper has a compact structural configuration of four polysilicon layers and a simple performance that control the opening and closing displacements of the microgripper tips. The microgripper has a mobile arm, a fixed arm, two different actuators and two serpentine springs, which are designed based on the SUMMiT V surface micromachining process from Sandia National Laboratories. The proposed microgripper operates at its first rotational resonant frequency and its mobile arm has a controlled displacement of 40 \u00b5m at both opening and closing directions using dc and ac bias voltages. Analytical models are developed to predict the stiffness, damping forces and first torsional resonant frequency of the microgripper. In addition, finite element method (FEM) models are obtained to estimate the mechanical behavior of the microgripper. The results of the analytical models agree very well respect to FEM simulations. The microgripper has a first rotational resonant frequency of 463.8 Hz without gripped cell and it can operate up to with maximum dc and ac voltages of 23.4 V and 129.2 V, respectively. Based on the results of the analytical and FEM models about the performance of the proposed microgripper, it could be used as a dispositive for mechanical properties characterization of circulating tumor cells (CTCs).<\/jats:p>","DOI":"10.3390\/s18051664","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T03:14:24Z","timestamp":1527045264000},"page":"1664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Design of a Novel MEMS Microgripper with Rotatory Electrostatic Comb-Drive Actuators for Biomedical Applications"],"prefix":"10.3390","volume":"18","author":[{"given":"Luis A.","family":"Velosa-Moncada","sequence":"first","affiliation":[{"name":"Departamento de Ingenier\u00eda Mec\u00e1nica, DICIS, Universidad de Guanajuato\/Carretera Salamanca-Valle de Santiago km 3.5+1.8, Salamanca 36885, Mexico"},{"name":"Grupo de Investigaci\u00f3n GIDEATIC, Universidad Popular del Cesar Seccional Aguachica, Carrera 40 via al Mar, Aguachica 25010, Colombia"}]},{"given":"Luz Antonio","family":"Aguilera-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Departamento de Ingenier\u00eda Mec\u00e1nica, DICIS, Universidad de Guanajuato\/Carretera Salamanca-Valle de Santiago km 3.5+1.8, Salamanca 36885, Mexico"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9892-5305","authenticated-orcid":false,"given":"Max A.","family":"Gonz\u00e1lez-Palacios","sequence":"additional","affiliation":[{"name":"Departamento de Ingenier\u00eda Mec\u00e1nica, DICIS, Universidad de Guanajuato\/Carretera Salamanca-Valle de Santiago km 3.5+1.8, Salamanca 36885, Mexico"}]},{"given":"Jean-Pierre","family":"Raskin","sequence":"additional","affiliation":[{"name":"Institute of Information and Communication Technologies, Electronics and Applied Mathematics (ICTEAM), Universit\u00e9 catholique de Louvain (UCL), 1348 Louvain-la-Neuve, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7373-9258","authenticated-orcid":false,"given":"Agustin L.","family":"Herrera-May","sequence":"additional","affiliation":[{"name":"Micro and Nanotechnology Research Center, Universidad Veracruzana, Calzada Ru\u00edz Cortines 455, Boca del R\u00edo 94294, Mexico"},{"name":"Maestr\u00eda en Ingenier\u00eda Aplicada, Facultad de Ingenier\u00eda de la Construcci\u00f3n y el H\u00e1bitat, Universidad Veracruzana, Calzada Ru\u00edz Cortines 455, Boca del R\u00edo 94294, Mexico"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,22]]},"reference":[{"key":"ref_1","unstructured":"(2017, December 16). World Health Organization. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs297\/en\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21387","article-title":"Cancer statistics","volume":"67","author":"Siegel","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1373\/clinchem.2011.165068","article-title":"Circulating tumor cells in breast cancer: Detection systems, molecular characterization, and future challenges","volume":"57","author":"Lianidou","year":"2011","journal-title":"Clin. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.gde.2009.12.002","article-title":"Circulating tumor cells: A window into c\u00e1ncer biology and met\u00e1stasis","volume":"20","author":"Maheswaran","year":"2010","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ymeth.2012.07.002","article-title":"Microfluidic: An innovative tool for efficient cell sorting","volume":"57","author":"Autebert","year":"2012","journal-title":"Methods"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1200\/jco.2010.28.15_suppl.1003","article-title":"Use of circulating tumor cells (CTC) in peripheral blood of breast cancer patients before and after adjuvant chemotherapy to predict risk for relapse: The success trial","volume":"28","author":"Rack","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7004","DOI":"10.1158\/1078-0432.CCR-08-0030","article-title":"Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II ramdomized trial","volume":"14","author":"Pierga","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1093\/annonc\/mdp391","article-title":"Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer","volume":"21","author":"Bidard","year":"2010","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1056\/NEJMoa040766","article-title":"Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer","volume":"351","author":"Cristofanilli","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1200\/JCO.2007.15.8923","article-title":"Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal c\u00e1ncer","volume":"26","author":"Cohen","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S1470-2045(08)70340-1","article-title":"Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: A reanalysis of IMMC38 trial data","volume":"10","author":"Scher","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1039\/c2lc90148j","article-title":"Probing circulating tumor cells in microfluidics","volume":"13","author":"Li","year":"2013","journal-title":"Lab Chip"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jmoldx.2012.09.004","article-title":"Microfluidics and circulating tumor cells","volume":"15","author":"Dong","year":"2013","journal-title":"J. Mol. Diagn."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4970","DOI":"10.1073\/pnas.1504484112","article-title":"Acoustic separation of circulating tumor cells","volume":"112","author":"Li","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.molonc.2016.01.007","article-title":"Circulating tumor cell tecnologies","volume":"10","author":"Ferreira","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9322","DOI":"10.1021\/acs.analchem.5b02023","article-title":"Acoustofluidic, label-free separation and simultaneous concentration of rare tumor cells from White bllod cells","volume":"87","author":"Antfolk","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.snb.2017.12.013","article-title":"Sorting of tumor cells in a microfluidic device by multi-stage Surface acoustic waves","volume":"258","author":"Wang","year":"2018","journal-title":"Sens. Actuators B Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.compbiomed.2015.05.024","article-title":"A computational study of circulating large tumor cells traversing microvessels","volume":"63","author":"Sarioglu","year":"2015","journal-title":"Comput. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8152","DOI":"10.1158\/1078-0432.CCR-04-1110","article-title":"Circulating tumor cells in patients with breast cancer dormancy","volume":"10","author":"Meng","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0090-4295(01)01191-8","article-title":"Changes in circulating carcinoma cells in patients with metastatic prostate cancer correlate with disease status","volume":"58","author":"Moreno","year":"2001","journal-title":"Urology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.chroma.2007.05.064","article-title":"Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells","volume":"1162","author":"Zheng","year":"2007","journal-title":"J. Chromatogr. A"},{"key":"ref_22","unstructured":"Lentner, C., Lentner, C., and Wink, A. (1981). Geigy Scientific Tables, CIBA-Geigy."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1177\/24.1.56391","article-title":"Combined blood cell counting and classification with fluorochrome stains and flow instrumentation","volume":"24","author":"Shapiro","year":"1976","journal-title":"J. Histochem. Cytochem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Xu, W., Mezencev, R., Kim, B., Wang, L., McDonald, J., and Sulchek, T. (2012). Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046609"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10555-008-9173-4","article-title":"Mechanics, malignancy, and metastasis: The force journey of a tumor cell","volume":"28","author":"Kumar","year":"2009","journal-title":"Cancer Metastasis Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5075","DOI":"10.1158\/0008-5472.CAN-11-0247","article-title":"Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines","volume":"71","author":"Swaminathan","year":"2011","journal-title":"Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/boc.201600078","article-title":"Are cancer cells really softer than normal cells?","volume":"109","author":"Alibert","year":"2017","journal-title":"Biol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.bbrc.2008.07.078","article-title":"AFM indentation study of breast cancer cells","volume":"374","author":"Li","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1186\/s11671-015-1174-y","article-title":"Discrimination between cervical cancer cells and normal cervical cells based on longitudinal elasticity using atomic force microscopy","volume":"10","author":"Zhao","year":"2015","journal-title":"Nanoscale Res. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1039\/b803355b","article-title":"Measurement of elastic properties of prostate cancer cells using AFM","volume":"133","author":"Faria","year":"2008","journal-title":"Analyst"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.micron.2012.03.023","article-title":"Comparison of mechanical properties of normal and malignant thyroid cells","volume":"43","author":"Prabhune","year":"2012","journal-title":"Micron"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s12668-016-0191-3","article-title":"Discrimination between normal and cancerous cells using AFM","volume":"6","author":"Lekka","year":"2016","journal-title":"Bionanoscience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e120","DOI":"10.1111\/odi.12171","article-title":"Evaluation of single-cell biomechanics as potential marker for oral squamous cell carcinomas: A pilot study","volume":"20","author":"Runge","year":"2014","journal-title":"Oral Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1529\/biophysj.104.045476","article-title":"Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence","volume":"88","author":"Guck","year":"2005","journal-title":"Biophys. J."},{"key":"ref_35","unstructured":"Ameneh, M. (2015). Mechanical Properties of Cancer Cells: A Possible Biomarker for Stemness. [Ph.D. Dissertation, Ohio University]."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.msec.2005.08.022","article-title":"Experimental techniques for single cell and single molecule biomechanics","volume":"26","author":"Lim","year":"2006","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s11340-007-9099-8","article-title":"The potential of MEMS for advancing experiments and modeling in cell mechanics","volume":"49","author":"Loh","year":"2009","journal-title":"Exp. Mech."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Qu, J., Zhang, W., Jung, A., Silva-Da Cruz, S., and Liu, X. (2015, January 24\u201328). A MEMS Microgripper with Two-Axis Actuators and Force Sensors for Microscale Mechanical Characterization of Soft Materials. Proceedings of the 2015 IEEE International Conference on Automation Science and Engineering (CASE), Gothenburg, Sweden.","DOI":"10.1109\/CoASE.2015.7294332"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"055013","DOI":"10.1088\/0960-1317\/18\/5\/055013","article-title":"Nanonewton force-controlled manipulation of biological cells using a monolithic MEMS microgripper with two-axis force feedback","volume":"18","author":"Kim","year":"2008","journal-title":"J. Micromech. Microeng."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s00542-013-1737-8","article-title":"A rotary comb-actuated microgripper with a large displacement range","volume":"20","author":"Chang","year":"2014","journal-title":"Microsyst. Technol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"20140","DOI":"10.3390\/s150820140","article-title":"A microgripper with a post-assembly self-locking mechanism","volume":"15","author":"Yuan","year":"2015","journal-title":"Sensors"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1109\/JMEMS.2006.889532","article-title":"A real pivot structure for MEMS tunable lasers","volume":"16","author":"Zhang","year":"2007","journal-title":"J. Microelectromech. Syst."},{"key":"ref_43","first-page":"65","article-title":"A virtual pivot point MEMS actuator with externally mounted mirror, design, fabrication and characterization","volume":"183","author":"Amin","year":"2014","journal-title":"Sens. Transducers"},{"key":"ref_44","unstructured":"(2017, December 21). Sandia National Laboratories, Available online: http:\/\/www.sandia.gov\/mstc\/mems\/."},{"key":"ref_45","unstructured":"Bao, M. (2005). Analysis and Design Principles of MEMS Devices, Elsevier."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tu, C.-C., Fanchiang, K., and Liu, C.H. (2005). 1 \u00d7 N rotary vertical micromirror for optical switching applications. Proc. SPIE MOEMS Miniat. Syst. V, 5719.","DOI":"10.1117\/12.589810"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1109\/JMEMS.2015.2388539","article-title":"Force-controlled MEMS rotary microgripper","volume":"24","author":"Piriyanont","year":"2015","journal-title":"J. Microelectromech. Syst."},{"key":"ref_48","unstructured":"Budynas, R.G., and Nisbett, J.K. (2008). Shigley\u2019s Mechanical Engineering Design, Mc Graw Hill. [9th ed.]."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Younis, M. (2011). MEMS Linear and Nonlinear Statics and Dynamics, Springer Science Business Media.","DOI":"10.1007\/978-1-4419-6020-7"},{"key":"ref_50","unstructured":"Lobontiu, N., and Ephrahim, G. (2005). Mechanics of Microelectromechanical Systems, Kluwer Academic Publishers."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/jbm.a.32338","article-title":"Investigation of mechanical properties of soft hydrogel microcapsules in relation protein delivery using a MEMS force sensor","volume":"92A","author":"Kim","year":"2010","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_52","first-page":"190","article-title":"Large deformations of a rubber sphere under diametral compression. Part 1: Theoretical analysis of press approach, contact radius and lateral extension","volume":"36","author":"Tatara","year":"1993","journal-title":"JSME Int. J. Ser. A Mech. Mater. Eng."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jbiomech.2004.11.006","article-title":"Determination of the Poisson\u2019s ratio of the cell: Recovery properties of chondrocytes after release from complete micropipette aspiration","volume":"39","author":"Trickey","year":"2006","journal-title":"J. Biomech."},{"key":"ref_54","unstructured":"Nicolae, L. (2010). System Dynamics for Engineering Students, Elsevier."},{"key":"ref_55","unstructured":"Weaver, W., Timoshenko, S.P., and Young, D.H. (1990). Vibration Problems in Engineering, Wiley. [5th ed.]."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/18\/5\/1664\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:05:26Z","timestamp":1760195126000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/18\/5\/1664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,22]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["s18051664"],"URL":"https:\/\/doi.org\/10.3390\/s18051664","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,22]]}}}