{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:44:55Z","timestamp":1783079095870,"version":"3.54.6"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2011,12,30]],"date-time":"2011-12-30T00:00:00Z","timestamp":1325203200000},"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>Many conventional biochemical assays are performed using populations of cells to determine their quantitative biomolecular profiles. However, population averages do not reflect actual physiological processes in individual cells, which occur either on short time scales or nonsynchronously. Therefore, accurate analysis at the single-cell level has become a highly attractive tool for investigating cellular content. Microfluidic chips with arrays of microwells were developed for single-cell chemical lysis in the present study. The cellular occupancy in 30-mm-diameter microwells (91.45%) was higher than that in 20-mm-diameter microwells (83.19%) at an injection flow rate of 2.8 mL\/min. However, most of the occupied 20-mm-diameter microwells contained individual cells. The results of chemical lysis experiments at the single-cell level indicate that cell membranes were gradually lysed as the lysis buffer was injected; they were fully lysed after 12 s. Single-cell chemical lysis was demonstrated in the proposed microfluidic chip, which is suitable for high-throughput cell lysis.<\/jats:p>","DOI":"10.3390\/s120100347","type":"journal-article","created":{"date-parts":[[2011,12,30]],"date-time":"2011-12-30T08:44:36Z","timestamp":1325234676000},"page":"347-358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Single-Cell Chemical Lysis on Microfluidic Chips with Arrays of Microwells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5558-5817","authenticated-orcid":false,"given":"Chun-Ping","family":"Jen","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering and Advanced Institute of Manufacturing with High-Tech Innovation, National Chung Cheng University, Chia Yi 62102, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Hsiu","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Advanced Institute of Manufacturing with High-Tech Innovation, National Chung Cheng University, Chia Yi 62102, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay A.","family":"Maslov","sequence":"additional","affiliation":[{"name":"Khristianovich Institute of Theoretical and Applied Mechanics, Siberian Division, Russian Academy of Science, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2011,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.molonc.2008.09.003","article-title":"A single lysis solution for the analysis of tissue samples by different proteomic technologies","volume":"2","author":"Gromov","year":"2008","journal-title":"Mol. Oncol"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1021\/ac071891x","article-title":"Chemical analysis of single mammalian cells with microfluidics","volume":"79","author":"Price","year":"2007","journal-title":"Anal. Chem"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1039\/b818610n","article-title":"Inverted pattern formation of cell microarrays on poly(ethylene glycol) (PEG) gel patterned surface and construction of hepatocyte spheroids on unmodified PEG gel microdomains","volume":"9","author":"Yoshimoto","year":"2009","journal-title":"Lab Chip"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev.bioeng.2.1.227","article-title":"Microenginggering of cellular interactions","volume":"2","author":"Folch","year":"2000","journal-title":"Annu. Rev. Biomed. Eng"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1021\/bp020143k","article-title":"Integration of cell culture and microfabrication technology","volume":"19","author":"Park","year":"2003","journal-title":"Biotechnol. Prog"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1016\/j.biomaterials.2005.12.024","article-title":"Surface engineering approaches to micropattern surfaces for cell-based assays","volume":"27","author":"Falconnet","year":"2006","journal-title":"Biomaterials"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1089\/ten.2006.0154","article-title":"Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning","volume":"13","author":"Lim","year":"2007","journal-title":"Tissue Eng"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1039\/b405557h","article-title":"Development of a microfabricated cytometry platform for characterization and sorting of individual leukocytes","volume":"5","author":"Revzin","year":"2005","journal-title":"Lab Chip"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.1021\/ac0256235","article-title":"A microfabrication-based dynamic array cytometer","volume":"74","author":"Voldman","year":"2002","journal-title":"Anal. Chem"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1073\/pnas.94.10.4853","article-title":"Optical trapping and manipulation of neutral particles using lasers","volume":"94","author":"Ashkin","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1016\/S0006-3495(03)74606-2","article-title":"Stimulation of single isolated adult ventricular myocytes within a low volume using a planar microelectrode array","volume":"85","author":"Klauke","year":"2003","journal-title":"Biophys. J"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S139","DOI":"10.1098\/rsif.2008.0233.focus","article-title":"Microfluidic single-cell analysis of intracellular compounds","volume":"5","author":"Chao","year":"2008","journal-title":"J. R. Soc. Interface"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1039\/b905844c","article-title":"Microfluidic sample preparation: Cell lysis and nucleic acid purification","volume":"1","author":"Kim","year":"2009","journal-title":"Integr. Biol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24109:1","DOI":"10.1063\/1.3596394","article-title":"Analysis of gene expression at the single-cell level using microdroplet-based microfluidic technology","volume":"5","author":"Mary","year":"2011","journal-title":"Biomicrofluidics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1039\/b605937f","article-title":"Dynamic single cell culture array","volume":"6","author":"Wu","year":"2006","journal-title":"Lab Chip"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1002\/elps.201100413","article-title":"Parallel single-cell analysis microfluidic platform","volume":"32","author":"Gool","year":"2011","journal-title":"Electrophoresis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7044","DOI":"10.1021\/ac2011153","article-title":"Imaging single-cell signaling dynamics with a deterministic high-density single-cell trap array","volume":"83","author":"Chung","year":"2011","journal-title":"Anal. Chem"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1039\/b615235j","article-title":"Analysis of single mammalian cells on-chip","volume":"7","author":"Sims","year":"2007","journal-title":"Lab Chip"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bbagen.2010.04.009","article-title":"Miniaturization of biological assays\u2014Overview on microwell devices for single-cell analyses","volume":"1810","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1006\/abio.1999.4440","article-title":"Application of high-density optical microwell arrays in a live-cell biosensing system","volume":"278","author":"Taylor","year":"2000","journal-title":"Anal. Biochem"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1039\/b603961h","article-title":"A novel miniature cell retainer for correlative high-content analysis of individual untethered nonadherent cells","volume":"6","author":"Deutsch","year":"2006","journal-title":"Lab Chip"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/cyto.a.20478","article-title":"Single lymphocyte analysis with a microwell array chip","volume":"71","author":"Tokimitsu","year":"2007","journal-title":"Cytometry A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.1021\/ac0505977","article-title":"Large-scale single-cell trapping and imaging using microwell arrays","volume":"77","author":"Rettig","year":"2005","journal-title":"Anal. Chem"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/bit.20254","article-title":"Microfabricated platform for studying stem cell fates","volume":"88","author":"Chin","year":"2004","journal-title":"Biotechnol. Bioeng"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10404-009-0503-9","article-title":"Single cell trapping in larger microwells capable of supporting cell spreading and proliferation","volume":"8","author":"Park","year":"2010","journal-title":"Microfluid. Nanofluid"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"123701:1","DOI":"10.1063\/1.3565236","article-title":"Highly-efficient single-cell capture in microfluidic array chips using differential hydrodynamic guiding structures","volume":"98","author":"Chung","year":"2011","journal-title":"Appl. Phys. Lett"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1063\/1.1705728","article-title":"Investigation of laser-induced cell lysis using time-resolved imaging","volume":"84","author":"Rau","year":"2004","journal-title":"Appl. Phys. Lett"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1039\/b305162e","article-title":"Reagentless mechanical cell lysis by nanoscale barbs in microchannels for sample preparation","volume":"3","author":"Jeong","year":"2003","journal-title":"Lab Chip"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5646","DOI":"10.1021\/ac0346510","article-title":"Microfluidic devices for the high-throughput chemical analysis of cells","volume":"75","author":"McClain","year":"2003","journal-title":"Anal. Chem"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6137","DOI":"10.1021\/ac0497508","article-title":"Single-cell chemical lysis in picoliter-scale closed volumes using a microfabricated device","volume":"76","author":"Irimia","year":"2004","journal-title":"Anal. Chem"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.1098\/rsif.2008.0009.focus","article-title":"Current techniques for single-cell lysis","volume":"5","author":"Brown","year":"2008","journal-title":"J. R. Soc. Interface"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1021\/ac0480850","article-title":"Selective encapsulation of single cells and subcellular organelles into picoliter- and femtoliter-volume droplets","volume":"77","author":"He","year":"2005","journal-title":"Anal. Chem"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1039\/c0lc00370k","article-title":"Continuous analysis of dye-loaded, single cells on a microfluidic chip","volume":"11","author":"Phillips","year":"2011","journal-title":"Lab Chip"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.snb.2006.11.054","article-title":"A continuous electrical cell lysis device using a low dc voltage for a cell transport and rupture","volume":"124","author":"Lee","year":"2007","journal-title":"Sens. Actuat. B"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1039\/c000977f","article-title":"Continuous-flow electrical lysis device with integrated control by dielectrophoretic cell sorting","volume":"10","author":"Mernier","year":"2010","journal-title":"Lab Chip"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1126\/science.1133992","article-title":"Counting low-copy number proteins in a single cell","volume":"315","author":"Huang","year":"2007","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9054","DOI":"10.1021\/ac7017519","article-title":"Coaxial flow system for chemical cytometry","volume":"79","author":"Marc","year":"2007","journal-title":"Anal. Chem"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9141","DOI":"10.1021\/ac8016423","article-title":"Single-cell chemical lysis method for analyses of intracellular molecules using an array of picoliter-scale microwells","volume":"80","author":"Sasuga","year":"2008","journal-title":"Anal. Chem"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/12\/1\/347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:58:33Z","timestamp":1760219913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/12\/1\/347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,30]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,1]]}},"alternative-id":["s120100347"],"URL":"https:\/\/doi.org\/10.3390\/s120100347","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,30]]}}}