{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:42:49Z","timestamp":1785426169601,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EB022015"],"award-info":[{"award-number":["R01EB022015"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R01EB022015"],"award-info":[{"award-number":["R01EB022015"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000006","name":"Office of Naval Research","doi-asserted-by":"crossref","award":["N00014-20-1-2164"],"award-info":[{"award-number":["N00014-20-1-2164"]}],"id":[{"id":"10.13039\/100000006","id-type":"DOI","asserted-by":"crossref"}]},{"award":["N00014-20-1-2164"],"award-info":[{"award-number":["N00014-20-1-2164"]}],"id":[{"id":"https:\/\/ror.org\/00rk2pe57","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Continuous, in vivo drug and biomarker measurements could transform healthcare, enabling both the high-precision personalization of drug dosing and the real-time monitoring of health status. A practical realization of this vision, however, requires an improved understanding of the relationship between concentrations measured in the easily accessible dermal interstitial fluid (ISF) that correlate with the plasma concentrations that guide clinical decision making. As a preliminary step towards this goal, here we have used electrochemical, aptamer-based (EAB) sensors to perform seconds-resolved vancomycin measurements in the plasma and subcutaneous ISF of live rats. Concentrations of the antibiotic in the ISF vary rather little between different subcutaneous sites and, after the very rapid initial distribution phase is complete, they are well correlated with the plasma concentrations (mean R2 = 0.88). Likewise, a simple, two-compartment, two-parameter model describes our six paired plasma and ISF drug time courses quantitatively. Together, these findings provide further evidence of the viability of the drug concentration measurements performed in the subcutaneous or dermal ISF as a less invasive approach to real-time drug monitoring in individual patients.<\/jats:p>","DOI":"10.3390\/s26072233","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T01:12:33Z","timestamp":1775437953000},"page":"2233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Seconds-Resolved Measurements of Vancomycin Transport from the Plasma to the Interstitial Fluid Highlight a Path Towards Real-Time Therapeutic Drug Monitoring"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5922-4477","authenticated-orcid":false,"given":"Julian","family":"Gerson","sequence":"first","affiliation":[{"name":"Department of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"},{"name":"Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"},{"name":"Department of Bioengineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6073-2380","authenticated-orcid":false,"given":"Murat Kaan","family":"Erdal","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1492-9449","authenticated-orcid":false,"given":"Lisa C.","family":"Fetter","sequence":"additional","affiliation":[{"name":"Biomolecular Sciences and Engineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-801X","authenticated-orcid":false,"given":"Kaylyn K.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A.","family":"Emmons","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"},{"name":"Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2809-4718","authenticated-orcid":false,"given":"Joao","family":"Hespanha","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl M.","family":"Kirkpatrick","sequence":"additional","affiliation":[{"name":"Monash Institute for Pharmaceutical Sciences, Monash University, Melbourne 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Plaxco","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"},{"name":"Biomolecular Sciences and Engineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"},{"name":"Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tod E.","family":"Kippin","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"},{"name":"Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"},{"name":"Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.4093\/dmj.2019.0121","article-title":"Continuous Glucose Monitoring Sensors for Diabetes Management: A Review of Technologies and Applications","volume":"43","author":"Cappon","year":"2019","journal-title":"Diabetes Metab. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e14528","DOI":"10.1111\/dme.14528","article-title":"Continuous glucose monitoring: A review of the evidence in type 1 and 2 diabetes mellitus","volume":"38","author":"Lin","year":"2021","journal-title":"Diabet. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1021\/acssensors.9b01616","article-title":"Electrochemical Aptamer-Based Sensors for Improved Therapeutic Drug Monitoring and High-Precision, Feedback-Controlled Drug Delivery","volume":"4","author":"Yang","year":"2019","journal-title":"ACS Sens."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"eadg3254","DOI":"10.1126\/sciadv.adg3254","article-title":"High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats","volume":"9","author":"Gerson","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/aic.10489","article-title":"Integrated medical feedback systems for drug delivery","volume":"51","author":"Heller","year":"2005","journal-title":"AIChE J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e335","DOI":"10.1016\/S2589-7500(19)30131-1","article-title":"Microneedle biosensors for real-time, minimally invasive drug monitoring of phenoxymethylpenicillin: A first-in-human evaluation in healthy volunteers","volume":"1","author":"Rawson","year":"2019","journal-title":"Lancet Digit. Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"eadr5493","DOI":"10.1126\/scitranslmed.adr5493","article-title":"Resilient nanostructured bioanalytic microneedle longitudinally monitors preclinical renal and hepatic drug clearance and dysfunction","volume":"843","author":"Zhu","year":"2026","journal-title":"Sci. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8335","DOI":"10.1021\/acs.analchem.2c00829","article-title":"Microneedle Aptamer-Based Sensors for Continuous, Real-Time Therapeutic Drug Monitoring","volume":"94","author":"Wu","year":"2022","journal-title":"Anal. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"eabk2901","DOI":"10.1126\/sciadv.abk2901","article-title":"Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals","volume":"8","author":"Seo","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1073\/pnas.1613458114","article-title":"Real-time measurement of small molecules directly in awake, ambulatory animals","volume":"114","author":"Somerson","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8164","DOI":"10.1039\/C9SC01495K","article-title":"Seconds-resolved pharmacokinetic measurements of the chemotherapeutic irinotecan in situ in the living body","volume":"10","author":"Idili","year":"2019","journal-title":"Chem. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1021\/acs.analchem.0c05024","article-title":"Seconds-Resolved, In Situ Measurements of Plasma Phenylalanine Disposition Kinetics in Living Rats","volume":"93","author":"Idili","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_13","first-page":"150","article-title":"Real-Time, Seconds-Resolved Measurements of Plasma Methotrexate In Situ in the Living Body","volume":"8","author":"Gerson","year":"2022","journal-title":"ACS Sens."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1021\/acsptsci.8b00033","article-title":"High-Precision Control of Plasma Drug Levels Using Feedback-Controlled Dosing","volume":"1","author":"Ortega","year":"2018","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1039\/D2AN02096C","article-title":"A tight squeeze: Geometric effects on the performance of three-electrode electrochemical-aptamer based sensors in constrained, in vivo placements","volume":"148","author":"Leung","year":"2023","journal-title":"Analyst"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s10544-019-0363-3","article-title":"Monitoring drug pharmacokinetics and immunologic biomarkers in dermal interstitial fluid using a microneedle patch","volume":"21","author":"Kolluru","year":"2019","journal-title":"Biomed. Microdevices"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"271","DOI":"10.7150\/ijms.13601","article-title":"Therapeutic Drug Monitoring of Vancomycin in Dermal Interstitial Fluid Using Dissolving Microneedles","volume":"13","author":"Ito","year":"2016","journal-title":"Int. J. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, X., Wu, Y., and Wang, D. (2024). Clinical application of vancomycin TDM in ventilated patients with gastrointestinal cancer: A propensity-matched analysis. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-023-08885-7"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"eabq4539","DOI":"10.1126\/sciadv.abq4539","article-title":"Wearable microneedle-based electrochemical aptamer biosensing for precision dosing of drugs with narrow therapeutic windows","volume":"8","author":"Lin","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1021\/acsptsci.5c00062","article-title":"Simultaneous, Seconds-Resolved Doxorubicin Measurements in the Blood and Subcutaneous Interstitial Fluid Identify Quantitative Pharmacokinetic Relationships between the Two","volume":"8","author":"Emmons","year":"2025","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Macheras, P., and Iliadis, A. (2016). Modeling in Biopharmaceutics, Pharmacokinetics and Pharmacodynamics: Homogeneous and Heterogeneous Approaches, Springer International Publishing.","DOI":"10.1007\/978-3-319-27598-7"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1214\/aos\/1176344136","article-title":"Estimating the Dimension of a Model","volume":"6","author":"Schwarz","year":"1978","journal-title":"Ann. Stat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1038\/s41551-022-00998-9","article-title":"Opportunities and challenges in the diagnostic utility of dermal interstitial fluid","volume":"7","author":"Friedel","year":"2023","journal-title":"Nat. Biomed. Eng."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sprunger, Y., Capua, L., Ernst, T., Barraud, S., Locca, D., Ionescu, A., and Saeidi, A. (2023). pH Quantification in Human Dermal Interstitial Fluid Using Ultra-Thin SOI Silicon Nanowire ISFETs and a High-Sensitivity Constant-Current Approach. Biosensors, 13.","DOI":"10.20944\/preprints202308.1010.v1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"125","DOI":"10.4239\/wjd.v6.i1.125","article-title":"Roles of interstitial fluid pH in diabetes mellitus: Glycolysis and mitochondrial function","volume":"6","author":"Marunaka","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1042\/BST20200667","article-title":"Roles of interstitial fluid pH and weak organic acids in development and amelioration of insulin resistance","volume":"49","author":"Marunaka","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1038\/s41598-022-09070-7","article-title":"Improved calibration of electrochemical aptamer-based sensors","volume":"12","author":"Downs","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"35S","DOI":"10.1111\/j.1365-2125.2001.00377.x","article-title":"The therapeutic monitoring of antimicrobial agents","volume":"52","author":"Begg","year":"2001","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1046\/j.1365-2125.1998.00770.x","article-title":"Best practice in therapeutic drug monitoring","volume":"46","author":"Gross","year":"1998","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Booth, M.A., Erdal, M.K., Larson, M., Birthisel, E., Friedel, M., Gon\u00e7ales, V.R., Alinezhad, A., Morawski, F., Li, J., and Hogan, N. (2026). Pilot phase clinical trial of a wearable, electrochemical aptamer-based patch for continuous drug concentration measurement. Nat. Biotechnol., Epub ahead of printing.","DOI":"10.1038\/s41587-026-03010-w"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: Fundamental algorithms for scientific computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.1111\/bph.16471","article-title":"A high-precision view of intercompartmental drug transport via simultaneous, seconds-resolved, in situ measurements in the vein and brain","volume":"181","author":"Gerson","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12532-018-0139-4","article-title":"CasADi\u2014A software framework for nonlinear optimization and optimal control","volume":"11","author":"Andersson","year":"2018","journal-title":"Math. Program. Comput."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10107-004-0559-y","article-title":"On the implementation of an interior-point filter line-search algorithm for large-scale nonlinear programming","volume":"106","author":"Biegler","year":"2006","journal-title":"Math. Program."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/26\/7\/2233\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:17:13Z","timestamp":1775449033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/26\/7\/2233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,4]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["s26072233"],"URL":"https:\/\/doi.org\/10.3390\/s26072233","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,4]]}}}