{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T22:11:14Z","timestamp":1769724674805,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R44HL140739"],"award-info":[{"award-number":["R44HL140739"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R41HL151015"],"award-info":[{"award-number":["R41HL151015"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["R21TW010610"],"award-info":[{"award-number":["R21TW010610"]}]},{"name":"National Institute of Health","award":["T32HL134622"],"award-info":[{"award-number":["T32HL134622"]}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["U54HL143541"],"award-info":[{"award-number":["U54HL143541"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>Paper-based microchip electrophoresis has the potential to bring laboratory electrophoresis tests to the point of need. However, high electric potential and current values induce pH and temperature shifts, which may affect biomolecule electrophoretic mobility thus decrease test reproducibility and accuracy of paper-based microfluidic electrophoresis. We have previously developed a microchip electrophoresis system, HemeChip, which has the capability of providing low-cost, rapid, reproducible, and accurate point-of-care (POC) electrophoresis tests for hemoglobin analysis. Here, we report the methodologies we implemented for characterizing HemeChip system pH and temperature during the development process, including utilizing commercially available universal pH indicator and digital camera pH shift characterization, and infrared camera characterizing temperature shift characterization. The characterization results demonstrated that pH shifts up to 1.1 units, a pH gradient up to 0.11 units\/mm, temperature shifts up to 40 \u00b0C, and a temperature gradient up to 0.5 \u00b0C\/mm existed in the system. Finally, we report an acid pre-treatment of the separation media, a cellulose acetate paper, mitigated both pH and temperature shifts and provided a stable environment for reproducible HemeChip hemoglobin electrophoresis separation.<\/jats:p>","DOI":"10.3390\/mi12111433","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T05:42:10Z","timestamp":1638250930000},"page":"1433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Dynamic pH and Thermal Analysis of Paper-Based Microchip Electrophoresis"],"prefix":"10.3390","volume":"12","author":[{"given":"Muhammad Noman","family":"Hasan","sequence":"first","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"An","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asya","family":"Akkus","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6269-4795","authenticated-orcid":false,"given":"Derya","family":"Akkaynak","sequence":"additional","affiliation":[{"name":"Department of Ecology & Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2382-7831","authenticated-orcid":false,"given":"Adrienne R.","family":"Minerick","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Michigan Technological University, Houghton, MI 49931, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7636-7296","authenticated-orcid":false,"given":"Chirag R.","family":"Kharangate","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0331-9960","authenticated-orcid":false,"given":"Umut A.","family":"Gurkan","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8447","DOI":"10.1021\/acs.chemrev.7b00024","article-title":"Turning the Page: Advancing Paper-Based Microfluidics for Broad Diagnostic Application","volume":"117","author":"Gong","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"011301","DOI":"10.1063\/1.3687398","article-title":"A perspective on paper-based microfluidics: Current status and future trends","volume":"6","author":"Li","year":"2012","journal-title":"Biomicrofluidics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1801084","DOI":"10.1002\/adhm.201801084","article-title":"Paper Microfluidics for Cell Analysis","volume":"8","author":"Ma","year":"2018","journal-title":"Adv. Heal. Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1039\/c3cc49770d","article-title":"Electrophoretic separation in a microfluidic paper-based analytical device with an on-column wireless electrogenerated chemiluminescence detector","volume":"50","author":"Ge","year":"2014","journal-title":"Chem. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12390","DOI":"10.1021\/ac503976c","article-title":"Low-Voltage Origami-Paper-Based Electrophoretic Device for Rapid Protein Separation","volume":"86","author":"Luo","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4011","DOI":"10.1039\/C6RA26500F","article-title":"Simultaneous electrokinetic concentration and separation of proteins on a paper-based analytical device","volume":"7","author":"Wu","year":"2017","journal-title":"RSC Adv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1182\/blood-2020-142548","article-title":"Computer Vision and Deep Learning Assisted Microchip Electrophoresis for Integrated Anemia and Sickle Cell Disease Screening","volume":"136","author":"An","year":"2020","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1002\/elps.200700601","article-title":"Effect of Joule heating on electrokinetic transport","volume":"29","author":"Cetin","year":"2008","journal-title":"Electrophoresis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/elps.1150170123","article-title":"Variation of the pH of the background electrolyte due to electrode reactions in capillary electropho-resis: Theoretical approach and in situ measurement","volume":"17","author":"Corstjens","year":"1996","journal-title":"Electrophoresis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S1044-0305(98)00155-X","article-title":"Electrochemical properties of capillary electrophoresis-nanoelectrospray mass spectrometry","volume":"10","author":"Bateman","year":"1999","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1021\/ac0007940","article-title":"Control of Electrochemical Reactions at the Capillary Electrophoresis Outlet\/Electrospray Emitter Electrode under CE\/ESI-MS through the Application of Redox Buffers","volume":"73","author":"Smith","year":"2001","journal-title":"Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bengtsson, K., Nilsson, S., and Robinson, N.D. (2014). Conducting Polymer Electrodes for Gel Electrophoresis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089416"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1002\/elps.201000617","article-title":"Electrolysis-reducing electrodes for electrokinetic devices","volume":"32","author":"Erlandsson","year":"2011","journal-title":"Electrophoresis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1002\/1522-2683(200107)22:12<2526::AID-ELPS2526>3.0.CO;2-K","article-title":"Microchip capillary electrophoresis\/electrochemistry","volume":"22","author":"Lacher","year":"2001","journal-title":"Electrophoresis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/elps.200800643","article-title":"Joule heating effects and the experimental determination of temperature during CE","volume":"30","author":"Evenhuis","year":"2009","journal-title":"Electrophoresis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.chroma.2003.12.062","article-title":"Joule heating and determination of temperature in capillary electrophoresis and capillary electrochromatography columns","volume":"1037","author":"Rathore","year":"2004","journal-title":"J. Chromatogr. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1182\/blood-2019-126096","article-title":"Integrated Anemia Detection and Hemoglobin Variant Identification Using Point-of-Care Microchip Electrophoresis","volume":"134","author":"An","year":"2019","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1039\/C9AN02250C","article-title":"Paper-based microchip electrophoresis for point-of-care hemoglobin testing","volume":"145","author":"Hasan","year":"2020","journal-title":"Analyst"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1182\/blood-2019-129336","article-title":"International Multi-Site Clinical Validation of Point-of-Care Microchip Electrophoresis Test for Hemoglobin Variant Identification","volume":"134","author":"Fraiwan","year":"2019","journal-title":"Blood"},{"key":"ref_20","first-page":"3519","article-title":"Hemechip: An Automated Portable Microchip Electrophoresis Platform for Point-of-Care Sickle Cell Disease Screening","volume":"130","author":"Hasan","year":"2017","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hasan, M.N., Fraiwan, A., Gurkan, U.A., and Little, J.A. (2018, January 17\u201319). Live Demonstration: HemeChip\u2014A Portable Microchip Electrophoresis Technology for Point-of-Care Sickle Cell Disease Screening. Proceedings of the 2018 IEEE Biomedical Circuits and Systems Conference (BioCAS), Cleveland, OH, USA.","DOI":"10.1109\/BIOCAS.2018.8584795"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1182\/blood-2018-99-115355","article-title":"Clinical Testing of Hemechip in Nigeria for Point-of-Care Screening of Sickle Cell Disease","volume":"132","author":"Hasan","year":"2018","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1182\/blood.V126.23.3379.3379","article-title":"Point-of-Care Screening for Sickle Cell Disease By a Mobile Micro-Electrophoresis Platform","volume":"126","author":"Ung","year":"2015","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e12662","DOI":"10.1111\/micc.12662","article-title":"Standardized microfluidic assessment of red blood cell\u2013mediated microcapillary occlusion: Association with clinical phenotype and hydroxyurea responsiveness in sickle cell disease","volume":"28","author":"Man","year":"2021","journal-title":"Microcirculation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1039\/D0LC00112K","article-title":"Microfluidic assessment of red blood cell mediated microvascular occlusion","volume":"20","author":"Man","year":"2020","journal-title":"Lab. Chip"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102424","DOI":"10.1016\/j.bcmd.2020.102424","article-title":"Leukocyte adhesion to P-selectin and the inhibitory role of Crizanlizumab in sickle cell disease: A stand-ardized microfluidic assessment","volume":"83","author":"Man","year":"2020","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1002\/ajh.25933","article-title":"Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease","volume":"95","author":"Kucukal","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/bjh.16671","article-title":"Inhibition of Band 3 tyrosine phosphorylation: A new mechanism for treatment of sickle cell disease","volume":"190","author":"Noomuna","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"064126","DOI":"10.1063\/1.4904059","article-title":"Solution pH change in non-uniform alternating current electric fields at frequencies above the electrode charging frequency","volume":"8","author":"An","year":"2014","journal-title":"Biomicrofluidics"},{"key":"ref_30","unstructured":"Scheinberg, H.I. (2019, September 30). The Structural Basis of Differences in Electrophoretic Behavior of Human Hemoglobins. In Proceedings of the Conference on Hemoglobin, Washington, DC, USA, 2\u20133 May 1957, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK224284\/."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3390\/diagnostics3010033","article-title":"A Review of Heating and Temperature Control in Microfluidic Systems: Techniques and Applications","volume":"3","author":"Miralles","year":"2013","journal-title":"Diagnostics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.rser.2010.11.031","article-title":"Heat transfer and fluid flow characteristics in microchannels heat exchanger using nanofluids: A review","volume":"15","author":"Mohammed","year":"2011","journal-title":"Renew. Sustain. Energy Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1002\/elps.201600565","article-title":"Surface isoelectric focusing (sIEF) with carrier ampholyte pH gradient","volume":"38","author":"Wang","year":"2017","journal-title":"Electrophoresis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.1021\/ac400447k","article-title":"Temperature Effects on Electrophoresis","volume":"85","author":"Rogacs","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1063\/1.555581","article-title":"Viscosity of liquid water in the range \u22128 \u00b0C to 150 \u00b0C","volume":"7","author":"Kestin","year":"1978","journal-title":"J. Phys. Chem. Ref. Data"}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/12\/11\/1433\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:34:05Z","timestamp":1760168045000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/12\/11\/1433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,22]]},"references-count":35,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["mi12111433"],"URL":"https:\/\/doi.org\/10.3390\/mi12111433","relation":{},"ISSN":["2072-666X"],"issn-type":[{"value":"2072-666X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,22]]}}}