About

Tod Kippin is a principal investigator at the Laboratory of Psychological & Brain Sciences at the University of California, Santa Barbara. His research focuses on using electrochemical aptamer-based (EAB) sensors to understand neuropharmacology and individual variability in pharmacokinetics. His work aims to improve biosensors for application in clinical use and animal models, contributing to the understanding of drug pharmacokinetics and addiction.

Research topics

• Chemistry
• Pharmacology
• Biology
• Computer Science
• Medicine
• Anesthesia
• Optics
• Biochemistry
• Surgery
• Biological system
• Biophysics
• Biomedical engineering
• Biotechnology
• Physics
• Materials science
• Nanotechnology

Selected publications

• Pilot phase clinical trial of a wearable, electrochemical aptamer-based patch for continuous drug concentration measurement

  Nature Biotechnology · 2026-02-04 · 3 citations

  article
  PublisherDOI

• Seconds-Resolved Measurements of Vancomycin Transport from the Plasma to the Interstitial Fluid Highlight a Path Towards Real-Time Therapeutic Drug Monitoring

  Sensors · 2026-04-04

  articleOpen accessSenior author

  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.

  PublisherDOI

• Inactivation of NMDAR and CaMKII signaling within the prelimbic cortex blocks incubated cocaine- and sucrose-craving

  Neuropsychopharmacology · 2026-01-08

  articleOpen access

  The incubation of craving is a term coined to characterize the behavioral phenomenon wherein cue-elicited craving strengthens over a period of abstinence. Incubated cocaine-craving is mediated, at least in part, by increased glutamate release within the prelimbic cortex (PL). We hypothesized that this glutamate release stimulates NMDA-type glutamate receptors (NMDARs), leading to calcium-dependent activation of CaMKII signaling that drives incubated craving. To test this hypothesis, adult male and female Sprague-Dawley rats were trained to self-administer either intravenous cocaine or sucrose pellets (6 h/day × 10 days) and tested for cue-elicited cocaine- or sucrose-craving in early versus later (i.e., after incubation) withdrawal. Incubated cocaine-seeking was associated with increased CaMKII activity in the PL, but no change in NMDAR subunits. In contrast, incubated sucrose-craving was associated with many sex-dependent changes in both NMDAR subunit expression and CaMKII activation that were subregion-selective. An intra-PL infusion of the NMDA antagonist D-AP5 (2.5 or 7.5 µg/side) or the CaMKII inhibitor myr-AIP (10 pg/side) blocked both incubated cocaine- and sucrose-craving, with no effects detected in early withdrawal. Co-infusion of both D-AP5 and myr-AIP exerted a larger effect on incubated cocaine-craving than either antagonist alone. These data corroborate earlier evidence for distinct biochemical correlates within mPFC between incubated cocaine- and sucrose-craving and, for the first time, demonstrate that both NMDAR and CaMKII activation within the PL are common drivers of incubated craving of potential relevance to the design of anti-craving medications in the contexts of both drug and food reinforcers.

  PublisherOA PDFDOI

• Extending Electrochemical Aptamer-Based Sensing to Microfabricated Sensor Formats

  Journal of Microelectromechanical Systems · 2026-01-01

  article

  Electrochemical aptamer-based (EAB) sensing is a generalizable approach to monitoring a wide range of molecular targets. Selective, dynamically responsive, real-time measurements are possible in complex body fluids while using standard electrochemical methods for read out. To advance miniaturized, wearable EAB sensing formats, 17 candidate materials compatible with microfabrication into 2D and 3D microstructures were investigated as sensor substrates. Since the aptamer attachment chemistry requires a gold surface, adhesion of gold thin films was evaluated followed by compatibility with EAB surface functionalization chemistry and the electrochemical interrogation method. Sensing results for each material were benchmarked against the gold standard solid gold microwire sensor format. Finally, two microneedle-based EAB sensor formats were demonstrated at the benchtop and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i>, by modifying commercially produced microneedles and developing a novel laser-machined polyether ether ketone (PEEK) microneedle array. Multiplexed sensing was enabled by selective functionalization of subgroups of needles within a single array.[2025-0204]

  PublisherDOI

• Continuous, Week-Long, Seconds-Resolved <i>In Vivo</i> Drug Measurements Performed with a Xenonucleic Acid-Employing Electrochemical, Aptamer-Based Sensor

  Journal of the American Chemical Society · 2026-02-26 · 5 citations

  articleOpen access

  The ability to monitor drug and biomarker concentrations in the body continuously and in real time could transform our understanding of physiology, enhance the diagnosis and monitoring of disease, and enable high-precision, truly personalized drug dosing. Toward this goal, we are developing electrochemical aptamer-based (EAB) sensors, the only real-time monitoring technology yet shown able to measure molecules as diverse as small molecule drugs to protein biomarkers in situ in the veins, brains, and peripheral tissues of live subjects. This advance notwithstanding, a significant challenge nevertheless remains: to date, degradation of their target-recognizing aptamer has limited the demonstrated, in vivo operation of EAB sensors to less than 24 h, reducing the platform’s clinical and scientific utility. Notably, for example, the continuous glucose monitor did not come into widespread clinical use until it reached an in vivo duration of 5 days, with current models achieving an operational duration of 2 weeks. Thus motivated, here we use a non-natural, more nuclease-resistant “xenonucleic” acid (XNA) aptamer to extend the continuous, in vivo operation of EAB sensors to 1 week, with the latter encompassing >47,000 real-time, 12.8 s-resolved measurements. Moreover, we have reached this operational duration without employing protective membranes, which can harm sensor performance and complicate sensor fabrication and insertion. The week-long in vivo operation demonstrated here represents a crucial milestone for clinical adoption and experimental flexibility, marking a shift from short-term testing toward robust, long-duration, real-time molecular measurements.

  PublisherOA PDFDOI

• On the Blood Components Contributing to the Drift of Electrochemical Aptamer-Based Biosensors

  ACS Sensors · 2025-07-01 · 11 citations

  article

  Electrochemical aptamer-based (EAB) sensors support the high-frequency, real-time measurement of specific molecules, including metabolites, pharmacological agents, and biomarkers, in situ in the living body. A challenge that complicates their long-term, in vivo deployment, however, is signal drift, which causes a reduction in their signal output over time that is unrelated to the presence of target. Previously, we and others have shown that, when placed in undiluted whole blood at body temperature, EAB sensor drift arises predominantly due to fouling and enzymatic degradation of the DNA aptamer, with the former dominating in vitro in days-old bovine blood, and the latter dominating in vivo in blood flowing through the rat jugular. Building on this background, here we explore the specific blood components that prompt the EAB sensor drift in vitro. Comparison of the drift produced by whole blood, washed blood cells, and plasma demonstrates that this drift is caused by blood proteins rather than blood cells. And studies employing size-fractionated serum and plasma indicate that the proteins causing drift are approximately of molecular weight >100 kDa. The latter observation explains past successes in mitigating drift via the use of molecular-weight-selective films.

  PublisherDOI

• Carboxylate-Terminated Electrode Surfaces Improve the Performance of Electrochemical Aptamer-Based Sensors

  ACS Applied Materials & Interfaces · 2025-01-22 · 14 citations

  articleOpen access

  Electrochemical aptamer-based (EAB) sensors are a molecular measurement platform that enables the continuous, real-time measurement of a wide range of drugs and biomarkers in situ in the living body. EAB sensors are fabricated by depositing a thiol-modified, target-binding aptamer on the surface of a gold electrode, followed by backfilling with an alkanethiol to form a self-assembled monolayer. And while the majority of previously described EAB sensors have employed hydroxyl-terminated monolayers, a handful of studies have shown that altering the monolayer headgroup can strongly affect sensor performance. Here, using 4 different EAB sensors, we show that the mixed monolayers composed of mixtures of 6-carbon hydroxyl-terminated thiols and varying amounts of either 6- or 8-carbon, carboxylate-terminated thiols lead to improved EAB sensor performance. Specifically, the use of such mixed monolayers enhances the signal gain (the relative change in the signal seen upon target addition) for all tested sensors, often by several fold, both in buffer and whole blood at room temperature or physiological temperatures. Moreover, these improvements in gain are achieved without significant changes in the aptamer affinity or the stability of the resulting sensors. In addition to proving a ready means of improving EAB sensor performance, these results suggest that exploration of the chemistry of the electrode surface employed in such sensors could prove to be a fruitful means of advancing this unique in vivo sensing technology.

  PublisherDOI

• Feedback control over plasma drug concentrations achieves rapid and accurate control over solid-tissue drug concentrations  

  Research Square · 2025-01-28 · 1 citations

  preprintOpen access
  PublisherOA PDFDOI

• Methods of Estimating Plasma Pharmacokinetics From Minimally Invasive, High Temporal Resolution Measurements of Interstitial Fluid Drug Concentrations

  Clinical and Translational Science · 2025-07-01 · 2 citations

  articleOpen access

  In therapeutic drug monitoring, plasma drug concentrations are used to guide dosing decisions, significantly improving outcomes for many therapeutic interventions. Due to the cumbersome, laboratory-based approaches used to measure such drug concentrations, however, such monitoring is slow to return actionable information to the clinician and is performed far less frequently than would be optimal. In response, approaches are being developed by which in vivo drug concentrations can be monitored in real time and at high frequency in the subcutaneous or intradermal interstitial fluid-measurements that are safe, convenient, and minimally invasive. In the furtherance of this approach, here, we explore theoretically the ability to use such high-frequency sub- or intradermal measurements to estimate the corresponding plasma concentration-time courses, as the latter remain the basis of effectively all clinical decision making. Doing so, we find that, given various physiologically and technologically plausible assumptions, it is possible to accurately estimate plasma concentration-time courses from measurements of interstitial fluid taken at two nonredundant sites in the interstitial fluid. This ability to derive clinically important plasma pharmacokinetics using minimally invasive subcutaneous or intradermal sensor placements has the potential to significantly improve the precision and reach of therapeutic drug monitoring and, with that, the safety and efficacy of drug delivery.

  PublisherOA PDFDOI

• A Wearable System for Wireless and Multiplexed Molecular Sensing Via Solid Microneedles

  2025-01-19 · 1 citations

  article

  Using a microneedle array (MNA) format, the potential for continuous, real-time wearable intracutaneous monitoring of multiple molecules can be achieved via electrochemical aptamer-based (EAB) sensors. Here we demonstrate multiplexed electrochemical detection of endogenous and exogenous molecules using the smallest wireless EAB/MNA system reported to date. The small form factor required for wearability was accomplished using laser-micromachined polyether ether ketone (PEEK) to form a multielectrode MNA having two sets of working electrodes responsive to different targets. Multiplexed MNAs responded selectively to phenylalanine and vancomycin, two model targets. Benchtop and in vivo demonstration in rat were achieved towards realizing a translatable wearable intracutaneous electrochemical sensing system.

  PublisherDOI

Recent grants

• NIH Grant R03DA021161

  NIH · $64k · 2006

• NIH Grant R01DA027525

  NIH · $1.6M · 2016

• Bio-electrochemical detectors for in vivo continuous monitoring

  NIH · $4.6M · 2017–2026

• NIH Grant R21DA027115

  NIH · $411k · 2012

Frequent coauthors

• Karen K. Szumlinski

  University of California, Santa Barbara

  69 shared

• Kevin W. Plaxco

  University of California, Santa Barbara

  49 shared

• Joannalee C. Campbell

  40 shared

• Chris Poland Knight

  37 shared

• F. R. Hall

  Insigneo

  36 shared

• Micaella Panessiti

  Tufts University

  36 shared

• Marco A. Riva

  36 shared

• Atsushi Kamiya

  Johns Hopkins University

  36 shared

Labs

• Tod Kippin LabPI

  Not provided