{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:56:25Z","timestamp":1791197785066,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI145206"],"award-info":[{"award-number":["AI145206"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering &amp;amp; Transla Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The recent availability of a technology providing real\u2010time, seconds\u2010resolved in vivo drug concentration measurements has opened the door to performing fully autonomous, closed\u2010loop feedback control over drug dosing. The controllers employed in prior demonstrations of such dosing, however, were designed and optimized using population\u2010based pharmacokinetic models. In the face of individual pharmacokinetic variation (between subjects or even within a single subject over time as their physiology varies), these controllers must be set rather conservatively so as to avoid potentially dangerous overshooting. This, however, slows the speed with which they achieve the desired set point and opening the possibility of their nevertheless still overshooting if the response of a subject differs too much from that of the \u201caverage\u201d subject. To address these issues, here we have developed an adaptive feedback\u2010control system that, rather than employing population\u2010pharmacokinetic information, instead uses real\u2010time drug concentration measurements to individualize drug delivery to the specific subject, \u201con the fly.\u201d To achieve this, the system estimates the pharmacokinetics of the individual subject during the initial stages of the infusion, and then continuously updates this subject\u2010specific pharmacokinetic model to maintain effective controller performance even in the face of physiological variations brought on, for example, by changing health status. Using this approach, we then demonstrate a feedback controller that rapidly (20\u201330\u2009min) achieves and accurately (5%\u201312% root\u2010mean\u2010squared deviations, though this also includes sensor noise) maintains pre\u2010defined concentrations of the anesthetic procaine in the ventricles of live rats, an application that, due to the delays associated with intracranial drug transport, represents a particular challenge for feedback\u2010controlled intravenous drug delivery. Given the precision and accuracy it achieves in our rat animal model, we believe that the use of adaptive feedback control will ultimately enable safer, more precise drug dosing in humans.<\/jats:p>","DOI":"10.1002\/btm2.70146","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:06:17Z","timestamp":1780491977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adaptive feedback control for the high\u2010precision management of in\u2010tissue drug concentrations"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6073-2380","authenticated-orcid":false,"given":"Murat Kaan","family":"Erdal","sequence":"first","affiliation":[{"name":"Department of Electrical and Computer Engineering University of California, Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Gerson","sequence":"additional","affiliation":[{"name":"Department of Psychological &amp; Brain Sciences University of California, Santa Barbara  Santa Barbara California USA"},{"name":"Department of Chemistry and Biochemistry University of California, Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tod E.","family":"Kippin","sequence":"additional","affiliation":[{"name":"Department of Psychological &amp; Brain Sciences University of California, Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4772-8771","authenticated-orcid":false,"given":"Kevin W.","family":"Plaxco","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California, Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao P.","family":"Hespanha","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering University of California, Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00483\u201018"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12490"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010198510060\u201000001"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01062211"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2020.03.001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11517\u2010024\u201003042\u2010x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcontrol.2024.100937"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200500989"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1613458114"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adg3254"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16471"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.8b00033"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.9b01616"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.2c01428"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.7b00787"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.2c01894"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c05024"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/mi14020323"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abk2901"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq4539"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.2c00829"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/aic.10489"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.5c00142"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40435\u2010020\u201000665\u20104"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2024.03.020"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01211647"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1109\/CDC45484.2021.9683244"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15756"},{"key":"e_1_2_11_30_1","volume-title":"Model Predictive Control: Theory, Computation, and Design","author":"Rawlings JB","year":"2017"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010control\u2010090419\u2010075625"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.17226\/12910"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcontrol.2021.03.008"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10107\u2010004\u20100559\u2010y"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compchemeng.2008.08.006"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12532\u2010018\u20100139\u20104"}],"container-title":["Bioengineering &amp; 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