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results)</h2></header><div class="c-sortpagination"><div class="c-sort"><div class="o-input__droplist1"><label for="c-sort1">Sort By:</label><select name="sort" id="c-sort1" form="facetForm"><option selected="" value="rel">Relevance</option><option value="a-title">A-Z By Title</option><option value="z-title">Z-A By Title</option><option value="a-author">A-Z By Author</option><option value="z-author">Z-A By Author</option><option value="asc">Date Ascending</option><option value="desc">Date Descending</option></select></div></div><input type="hidden" name="start" form="facetForm" value="0"/></div><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-thesis">Thesis</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/08r1r28z"><div class="c-clientmarkup">Advancing personalized medicine with electrochemical aptamer-based (EAB) sensors</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3AEmmons%2C%20Nicole%20Ann">Emmons, Nicole Ann</a> </li><li class="c-authorlist__begin"><span class="c-authorlist__heading">Advisor(s):</span> <a href="/search/?q=author%3AKippin%2C%20Tod">Kippin, Tod</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsb_etd">UC Santa Barbara Electronic Theses and Dissertations</a> (2024)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup"><p>Personalized medicine, a rapidly evolving field of healthcare, aims to improve therapeuticoutcomes by individualizing patient care. Therapeutic drug monitoring (TDM) presents a vast improvement to personalized medicine, enabling clinicians to optimize dosing regimens to improve therapeutic outcomes while minimizing toxicity. The state of the art of TDM is significantly limited by the current techniques employed to perform it. Existing technologies are limited by reliance on ex vivo quantification that generally results in single time point or low temporal resolution measurements and the inability to measure drug levels in different physiological compartments simultaneously. Electrochemical aptamer-based (EAB) sensors, a novel biosensing platform, present a powerful means of overcoming these limitations, providing seconds-resolved, cross-compartment measurements of drug distribution in real time. Centered around the focus of advancing TDM, this work first utilizes EAB sensors to better elucidate drug transport from blood to solid tissue, with the ultimate goal of improving transport into the brain. Using doxorubicin as a testbed, I first demonstrate that EAB sensors can capture the distribution of chemotherapeutics from the bloodstream to the peripheral subcutaneous tissue. I then utilize these measurements to perform high-precision feedback-controlled drug delivery over plasma drug levels. After careful evaluation of the permeation of drugs into tissue not separated by a physiological barrier, I then demonstrate the in-brain EAB platform can explore how pharmacological manipulations and drug encapsulation methods may improve drug permeation into the brain. Finally, this work utilizes individual, subject-specific measurements to suggest EAB sensors could be used to inform inter-patient pharmacokinetic variability. Collectively, this work argues that EAB sensors could significantly advance both our understanding of drug transport to the brain and peripheral tissues and revolutionize personalized medicine by enabling high-precision therapeutic drug monitoring.</p></div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/08r1r28z"><img src="/cms-assets/7c645e7d07814f1314f3bc5966f7a11e95d9dd0554ef23af739732d142f9cfda" alt="Cover page: Advancing personalized medicine with electrochemical aptamer-based (EAB) sensors"/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/57j4c6bm"><div class="c-clientmarkup">A tight squeeze: geometric effects on the performance of three-electrode electrochemical-aptamer based sensors in constrained, in vivo placements.</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3ALeung%2C%20Kaylyn">Leung, Kaylyn</a>; </li><li><a href="/search/?q=author%3AGerson%2C%20Julian">Gerson, Julian</a>; </li><li><a href="/search/?q=author%3AEmmons%2C%20Nicole">Emmons, Nicole</a>; </li><li><a href="/search/?q=author%3ARoehrich%2C%20Brian">Roehrich, Brian</a>; </li><li><a href="/search/?q=author%3AVerrinder%2C%20Elsi">Verrinder, Elsi</a>; </li><li><a href="/search/?q=author%3AFetter%2C%20Lisa">Fetter, Lisa</a>; </li><li><a href="/search/?q=author%3AKippin%2C%20Tod">Kippin, Tod</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3APlaxco%2C%20Kevin">Plaxco, Kevin</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsb_postprints">UC Santa Barbara Previously Published Works</a> (2023)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Electrochemical, aptamer-based (EAB) sensors are the first molecular monitoring technology that is (1) based on receptor binding and not the reactivity of the target, rendering it fairly general, and (2) able to support high-frequency, real-time measurements in situ in the living body. To date, EAB-derived in vivo measurements have largely been performed using three electrodes (working, reference, counter) bundled together within a catheter for insertion into the rat jugular. Exploring this architecture, here we show that the placement of these electrodes inside or outside of the lumen of the catheter significantly impacts sensor performance. Specifically, we find that retaining the counter electrode within the catheter increases the resistance between it and the working electrode, increasing the capacitive background. In contrast, extending the counter electrode outside the lumen of the catheter reduces this effect, significantly enhancing the signal-to-noise of intravenous molecular measurements. Exploring counter electrode geometries further, we find that they need not be larger than the working electrode. Putting these observations together, we have developed a new intravenous EAB architecture that achieves improved performance while remaining short enough to safely emplace in the rat jugular. These findings, though explored here with EAB sensors may prove important for the design of many electrochemical biosensors.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/57j4c6bm"><img src="/cms-assets/348dfc6b64c96571cef14d245a53bb809b36ed5933dbe5c7c5092530d8432bfa" alt="Cover page: A tight squeeze: geometric effects on the performance of three-electrode electrochemical-aptamer based sensors in constrained, in vivo placements."/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/8rz1k6ss"><div class="c-clientmarkup">The Use of Xenonucleic Acids Significantly Reduces the In Vivo Drift of Electrochemical Aptamer-Based Sensors.</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3ALeung%2C%20Kaylyn">Leung, Kaylyn</a>; </li><li><a href="/search/?q=author%3AGerson%2C%20Julian">Gerson, Julian</a>; </li><li><a href="/search/?q=author%3AEmmons%2C%20Nicole">Emmons, Nicole</a>; </li><li><a href="/search/?q=author%3AHeemstra%2C%20Jennifer">Heemstra, Jennifer</a>; </li><li><a href="/search/?q=author%3AKippin%2C%20Tod">Kippin, Tod</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3APlaxco%2C%20Kevin">Plaxco, Kevin</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsb_postprints">UC Santa Barbara Previously Published Works</a> (2024)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Electrochemical aptamer-based sensors support the high-frequency, real-time monitoring of molecules-of-interest in vivo. Achieving this requires methods for correcting the sensor drift seen during in vivo placements. While this correction ensures EAB sensor measurements remain accurate, as drift progresses it reduces the signal-to-noise ratio and precision. Here, we show that enzymatic cleavage of the sensors target-recognizing DNA aptamer is a major source of this signal loss. To demonstrate this, we deployed a tobramycin-detecting EAB sensor analog fabricated with the DNase-resistant xenonucleic acid 2O-methyl-RNA in a live rat. In contrast to the sensor employing the equivalent DNA aptamer, the 2O-methyl-RNA aptamer sensor lost very little signal and had improved signal-to-noise. We further characterized the EAB sensor drift using unstructured DNA or 2O-methyl-RNA oligonucleotides. While the two devices drift similarly in vitro in whole blood, the in vivo drift of the 2O-methyl-RNA-employing device is less compared to the DNA-employing device. Studies of the electron transfer kinetics suggested that the greater drift of the latter sensor arises due to enzymatic DNA degradation. These findings, coupled with advances in the selection of aptamers employing XNA, suggest a means of improving EAB sensor stability when they are used to perform molecular monitoring in the living body.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/8rz1k6ss"><img src="/cms-assets/a16c6004dfb137e687a9b3bae51b8047626081f267a53b6400bf04ae08c245cf" alt="Cover page: The Use of Xenonucleic Acids Significantly Reduces the In Vivo Drift of Electrochemical Aptamer-Based Sensors."/></a></div></section><section class="c-scholworks"><div class="c-scholworks__main-column"><ul class="c-scholworks__tag-list"><li class="c-scholworks__tag-article">Article</li><li class="c-scholworks__tag-peer">Peer Reviewed</li></ul><div><h3 class="c-scholworks__heading"><a href="/uc/item/4tx2b3rc"><div class="c-clientmarkup">High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats</div></a></h3></div><div class="c-authorlist"><ul class="c-authorlist__list"><li class="c-authorlist__begin"><a href="/search/?q=author%3AGerson%2C%20Julian">Gerson, Julian</a>; </li><li><a href="/search/?q=author%3AErdal%2C%20Murat%20Kaan">Erdal, Murat Kaan</a>; </li><li><a href="/search/?q=author%3AMcDonough%2C%20Matthew%20H">McDonough, Matthew H</a>; </li><li><a href="/search/?q=author%3APloense%2C%20Kyle%20L">Ploense, Kyle L</a>; </li><li><a href="/search/?q=author%3ADauphin-Ducharme%2C%20Philippe">Dauphin-Ducharme, Philippe</a>; </li><li><a href="/search/?q=author%3AHoneywell%2C%20Kevin%20M">Honeywell, Kevin M</a>; </li><li><a href="/search/?q=author%3ALeung%2C%20Kaylyn%20K">Leung, Kaylyn K</a>; </li><li><a href="/search/?q=author%3AArroyo-Curras%2C%20Netzahualcoyotl">Arroyo-Curras, Netzahualcoyotl</a>; </li><li><a href="/search/?q=author%3AGibson%2C%20Jenny%20M">Gibson, Jenny M</a>; </li><li><a href="/search/?q=author%3AEmmons%2C%20Nicole%20A">Emmons, Nicole A</a>; </li><li><a href="/search/?q=author%3AMeiring%2C%20Wendy">Meiring, Wendy</a>; </li><li><a href="/search/?q=author%3AHespanha%2C%20Joao%20P">Hespanha, Joao P</a>; </li><li><a href="/search/?q=author%3APlaxco%2C%20Kevin%20W">Plaxco, Kevin W</a>; </li><li class="c-authorlist__end"><a href="/search/?q=author%3AKippin%2C%20Tod%20E">Kippin, Tod E</a> </li></ul></div><div class="c-scholworks__publication"><a href="/uc/ucsb_postprints">UC Santa Barbara Previously Published Works</a> (2023)</div><div class="c-scholworks__abstract"><div class="c-clientmarkup">Knowledge of drug concentrations in the brains of behaving subjects remains constrained on a number of dimensions, including poor temporal resolution and lack of real-time data. Here, however, we demonstrate the ability of electrochemical aptamer-based sensors to support seconds-resolved, real-time measurements of drug concentrations in the brains of freely moving rats. Specifically, using such sensors, we achieve <4 渭M limits of detection and 10-s resolution in the measurement of procaine in the brains of freely moving rats, permitting the determination of the pharmacokinetics and concentration-behavior relations of the drug with high precision for individual subjects. In parallel, we have used closed-loop feedback-controlled drug delivery to hold intracranial procaine levels constant (卤10%) for >1.5 hours. These results demonstrate the utility of such sensors in (i) the determination of the site-specific, seconds-resolved neuropharmacokinetics, (ii) enabling the study of individual subject neuropharmacokinetics and concentration-response relations, and (iii) performing high-precision control over intracranial drug levels.</div></div><div class="c-scholworks__media"><ul class="c-medialist"></ul></div></div><div class="c-scholworks__ancillary"><a class="c-scholworks__thumbnail" href="/uc/item/4tx2b3rc"><img src="/cms-assets/0eb9e7747661a0aeeaa074f4e0588e75f8e35e8d780c79f9a6a6230907e5de1c" alt="Cover page: High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats"/></a><a href="https://creativecommons.org/licenses/by/4.0/" class="c-scholworks__license"><img class="c-lazyimage" data-src="/images/cc-by-small.svg" alt="Creative Commons 'BY' version 4.0 license"/></a></div></section></section></main></form></div><div><div class="c-toplink"><a href="javascript:window.scrollTo(0, 0)">Top</a></div><footer class="c-footer"><nav class="c-footer__nav"><ul><li><a href="/">Home</a></li><li><a href="/aboutEschol">About eScholarship</a></li><li><a href="/campuses">Campus Sites</a></li><li><a href="/ucoapolicies">UC Open Access Policy</a></li><li><a href="/publishing">eScholarship Publishing</a></li><li><a href="https://www.cdlib.org/about/accessibility.html">Accessibility</a></li><li><a href="/privacypolicy">Privacy Statement</a></li><li><a href="/policies">Site Policies</a></li><li><a href="/terms">Terms of Use</a></li><li><a href="/login"><strong>Admin Login</strong></a></li><li><a href="https://help.escholarship.org"><strong>Help</strong></a></li></ul></nav><div class="c-footer__logo"><a href="/"><img class="c-lazyimage" data-src="/images/logo_footer-eschol.svg" alt="eScholarship, University of California"/></a></div><div class="c-footer__copyright">Powered by the<br/><a href="http://www.cdlib.org">California Digital Library</a><br/>Copyright 漏 2017<br/>The Regents of the University of California</div></footer></div></div></div></div> <script src="/js/vendors~app-bundle-2aefc956e545366a5d4e.js"></script> <script src="/js/app-bundle-4477d7630fb8c6f70662.js"></script> </body> </html>