Pilot phase clinical trial of a wearable, electrochemical aptamer-based patch for continuous drug concentration measurement
Abdel Jalil, M. H. et al. Vancomycin prescribing and therapeutic drug monitoring: challenges of real clinical practice. PLoS ONE 18, e0285717 (2023).
Google Scholar
Chan, J. O. S. et al. Barriers and facilitators of appropriate vancomycin use: prescribing context is key. Eur. J. Clin. Pharmacol. 74, 1523–1529 (2018).
Google Scholar
Reuter, S. E. et al. Optimal practice for vancomycin therapeutic drug monitoring: position statement from the anti-infectives committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Ther. Drug Monit. 44, 121–132 (2022).
Google Scholar
Yi, Z.-M. et al. Status and quality of guidelines for therapeutic drug monitoring based on AGREE II instrument. Clin. Pharmacokinet. 62, 1201–1217 (2023).
Google Scholar
Pai Mangalore, R. et al. Beta-lactam antibiotic therapeutic drug monitoring in critically ill patients: a systematic review and meta-analysis. Clin. Infect. Dis. 75, 1848–1860 (2022).
Google Scholar
Sanz-Codina, M., Bozkir, H. Ö, Jorda, A. & Zeitlinger, M. Individualized antimicrobial dose optimization: a systematic review and meta-analysis of randomized controlled trials. Clin. Microbiol. Infect. 29, 845–857 (2023).
Google Scholar
Takahashi, N. et al. Efficacy of therapeutic drug monitoring-based antibiotic regimen in critically ill patients: a systematic review and meta-analysis of randomized controlled trials. J. Intensive Care 11, 48 (2023).
Google Scholar
Begg, E. J., Barclay, M. L. & Kirkpatrick, C. M. J. The therapeutic monitoring of antimicrobial agents. Br. J. Clin. Pharmacol. 52, 35–43 (2001).
Google Scholar
Xiao, Y., Lubin, A. A., Heeger, A. J. & Plaxco, K. W. Label-free electronic detection of thrombin in blood serum by using an aptamer-based sensor. Angew. Chem. Int. Ed. 44, 5456–5459 (2005).
Google Scholar
Alkhamis, O. et al. High-affinity aptamers for in vitro and in vivo cocaine sensing. J. Am. Chem. Soc. 146, 3230–3240 (2024).
Google Scholar
Arroyo-Currás, N. et al. Real-time measurement of small molecules directly in awake, ambulatory animals. Proc. Natl Acad. Sci. USA 114, 645–650 (2017).
Google Scholar
Arroyo-Currás, N. et al. Subsecond-resolved molecular measurements in the living body using chronoamperometrically interrogated aptamer-based sensors. ACS Sens. 3, 360–366 (2018).
Google Scholar
Arroyo-Currás, N. et al. High-precision control of plasma drug levels using feedback-controlled dosing. ACS Pharmacol. Transl. Sci. 1, 110–118 (2018).
Google Scholar
Chamorro-Garcia, A. et al. Real-time, seconds-resolved measurements of plasma methotrexate in situ in the living body. ACS Sens. 8, 150–157 (2023).
Google Scholar
Dauphin-Ducharme, P. et al. Electrochemical aptamer-based sensors for improved therapeutic drug monitoring and high-precision, feedback-controlled drug delivery. ACS Sens. 4, 2832–2837 (2019).
Google Scholar
Gerson, J. et al. High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats. Sci. Adv. 9, eadg3254 (2023).
Google Scholar
Gerson, J. et al. A high-precision view of intercompartmental drug transport via simultaneous, seconds-resolved, in situ measurements in the vein and brain. Br. J. Pharmacol. 181, 3869–3885 (2024).
Google Scholar
Idili, A. et al. Seconds-resolved pharmacokinetic measurements of the chemotherapeutic irinotecan in situ in the living body. Chem. Sci. 10, 8164–8170 (2019).
Google Scholar
Idili, A., Gerson, J., Kippin, T. & Plaxco, K. W. Seconds-resolved, in situ measurements of plasma phenylalanine disposition kinetics in living rats. Anal. Chem. 93, 4023–4032 (2021).
Google Scholar
Li, S. et al. Implantable hydrogel-protective DNA aptamer-based sensor supports accurate, continuous electrochemical analysis of drugs at multiple sites in living rats. ACS Nano 17, 18525–18538 (2023).
Google Scholar
Li, H. et al. High frequency, calibration-free molecular measurements in situ in the living body. Chem. Sci. 10, 10843–10848 (2019).
Google Scholar
Lin, S. et al. Wearable microneedle-based electrochemical aptamer biosensing for precision dosing of drugs with narrow therapeutic windows. Sci. Adv. 8, eabq4539 (2022).
Google Scholar
Qin, S.-N. et al. Real-time monitoring of daunorubicin pharmacokinetics with nanoporous electrochemical aptamer-based sensors in vivo. Sens. Actuators B Chem. 411, 135710 (2024).
Google Scholar
Roehrich, B. et al. Calibration-free, seconds-resolved in vivo molecular measurements using Fourier-transform impedance spectroscopy interrogation of electrochemical aptamer sensors. ACS Sens. 8, 3051–3059 (2023).
Google Scholar
Seo, J.-W. et al. Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals. Sci. Adv. 8, eabk2901 (2022).
Google Scholar
Shaver, A. et al. Optimization of vancomycin aptamer sequence length increases the sensitivity of electrochemical, aptamer-based sensors in vivo. ACS Sens. 7, 3895–3905 (2022).
Google Scholar
Vieira, P. A. et al. Ultra-high-precision, in-vivo pharmacokinetic measurements highlight the need for and a route toward more highly personalized medicine. Front. Mol. Biosci. 16, 6 (2019).
Bakhshandeh, F. et al. Wearable Aptalyzer integrates microneedle and electrochemical sensing for in vivo monitoring of glucose and lactate in live animals. Adv. Mater. 36, 2313743 (2024).
Google Scholar
Emmons, N. A. et al. Feedback control over plasma drug concentrations achieves rapid and accurate control over solid-tissue drug concentrations. ACS Pharmacol. Transl. Sci. 8, 1416−1423 (2025).
Kiang, T. K. L., Schmitt, V., Ensom, M. H. H., Chua, B. & Häfeli, U. O. Therapeutic drug monitoring in interstitial fluid: a feasibility study using a comprehensive panel of drugs. J. Pharm. Sci. 101, 4642–4652 (2012).
Google Scholar
Tran, B. Q. et al. Proteomic characterization of dermal interstitial fluid extracted using a novel microneedle-assisted technique. J. Proteome Res. 17, 479–485 (2018).
Google Scholar
Sprunger, Y., Longo, J., Saeidi, A. & Ionescu, A. M. Bridging blood and skin: biomarker profiling in dermal interstitial fluid (dISF) for minimally invasive diagnostics. Biosensors 15, 301 (2025).
Google Scholar
Samant, P. P. et al. Sampling interstitial fluid from human skin using a microneedle patch. Sci. Transl. Med. 12, eaaw0285 (2020).
Google Scholar
Wu, Z. et al. Interstitial fluid-based wearable biosensors for minimally invasive healthcare and biomedical applications. Commun. Mater. 5, 33 (2024).
Google Scholar
U.S. Food and Drug Administration. Device Classification Under Section 513(f)(2) (De Novo): Biolinq Shine Autonomous Time-in-Range Microsensor. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?id=DEN240080 (2025).
Zhu, J. et al. Gelatin methacryloyl microneedle patches for minimally invasive extraction of skin interstitial fluid. Small 16, 1905910 (2020).
Google Scholar
Friedel, M. et al. Continuous molecular monitoring of human dermal interstitial fluid with microneedle-enabled electrochemical aptamer sensors. Lab. Chip 23, 3289–3299 (2023).
Google Scholar
Keyvani, F. et al. Integrated electrochemical aptamer biosensing and colorimetric pH monitoring via hydrogel microneedle assays for assessing antibiotic treatment. Adv. Sci. 11, 2309027 (2024).
Google Scholar
Ranamukhaarachchi, S. A. et al. Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes. Sci. Rep. 6, 29075 (2016).
Google Scholar
Yuan, R. et al. Integrated microneedle aptasensing platform toward point-of-care monitoring of bacterial infections and treatment. ACS Sens. 10, 5684–5693 (2025).
Google Scholar
Reynoso, M. et al. 3D-printed, aptamer-based microneedle sensor arrays using magnetic placement on live rats for pharmacokinetic measurements in interstitial fluid. Biosens. Bioelectron. 244, 115802 (2024).
Google Scholar
Rybak, M. J. et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am. J. Health Syst. Pharm. 77, 835–864 (2020).
Google Scholar
D’Amico, H. et al. Acute kidney injury associated with area under the curve versus trough monitoring of vancomycin in obese patients. Antimicrob. Agents Chemother. 66, e00886–21 (2022).
Google Scholar
Neely, M. N. et al. Prospective trial on the use of trough concentration versus area under the curve to determine therapeutic vancomycin dosing. Antimicrob. Agents Chemother. 62, e02042-17 (2018).
Pai, M. P., Neely, M., Rodvold, K. A. & Lodise, T. P. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Adv. Drug Deliv. Rev. 77, 50–57 (2014).
Google Scholar
Stewart, J. J. et al. A Canadian perspective on the revised 2020 ASHP–IDSA–PIDS–SIDP guidelines for vancomycin AUC-based therapeutic drug monitoring for serious MRSA infections. J. Assoc. Med. Microbiol. Infect. Dis. Can. 6, 3–9 (2021).
Google Scholar
Stocker, S. L. et al. Evaluation of a pilot vancomycin precision dosing advisory service on target exposure attainment using an interrupted time series analysis. Clin. Pharmacol. Ther. 109, 212–221 (2021).
Google Scholar
Aljefri, D. M. et al. Vancomycin area under the curve and acute kidney injury: a meta-analysis. Clin. Infect. Dis. 69, 1881–1887 (2019).
Google Scholar
Drennan, P. G., Begg, E. J., Gardiner, S. J., Kirkpatrick, C. M. J. & Chambers, S. T. The dosing and monitoring of vancomycin: what is the best way forward? Int. J. Antimicrob. Agents 53, 401–407 (2019).
Google Scholar
Bradley, N., Lee, Y. & Sadeia, M. Assessment of the implementation of AUC dosing and monitoring practices with vancomycin at hospitals across the United States. J. Pharm. Pract. 35, 864–869 (2022).
Google Scholar
Dauphin-Ducharme, P., Ploense, K. L., Arroyo-Currás, N., Kippin, T. E. & Plaxco, K. W. Electrochemical aptamer-based sensors: a platform approach to high-frequency molecular monitoring in situ in the living body. in Biomedical Engineering Technologies: Volume 1 (eds Ossandon, M. R., Baker, H. & Rasooly, A.) 479–492 (Springer, 2022).
U.S. Food and Drug Administration. Bioanalytical method validation: guidance for industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioanalytical-method-validation-guidance-industry (2018).
Rüsch, D., Koch, T., Spies, M. & Eberhart, L. H. J. Pain during venous cannulation. Dtsch. Arztebl. Int. 114, 605–611 (2017).
Google Scholar
Leung, K. K., Downs, A. M., Ortega, G., Kurnik, M. & Plaxco, K. W. Elucidating the mechanisms underlying the signal drift of electrochemical aptamer-based sensors in whole blood. ACS Sens. 6, 3340–3347 (2021).
Google Scholar
Leung, K. K. et al. The use of xenonucleic acids significantly reduces the in vivo drift of electrochemical aptamer-based sensors. Angew. Chem. Int. Ed. 63, e202316678 (2024).
Google Scholar
Pham, J. D. et al. On the blood components contributing to the drift of electrochemical aptamer-based biosensors. ACS Sens. 10, 5160–5165 (2025).
Google Scholar
Ningrum, V. D. A., Amalia, S. P. & Wibowo, A. Vancomycin bioanalysis for TDM services by using immunoassay and HPLC: a scoping review. Pharm. Educ. 24, 197–203 (2024).
Google Scholar
Abraham, J. et al. Plasma and interstitial fluid population pharmacokinetics of vancomycin in critically ill patients with sepsis. Int. J. Antimicrob. Agents 53, 137–142 (2019).
Google Scholar
Kolluru, C. et al. Monitoring drug pharmacokinetics and immunologic biomarkers in dermal interstitial fluid using a microneedle patch. Biomed. Microdevices 21, 14 (2019).
Google Scholar
Ito, Y., Inagaki, Y., Kobuchi, S., Takada, K. & Sakaeda, T. Therapeutic drug monitoring of vancomycin in dermal interstitial fluid using dissolving microneedles. Int. J. Med. Sci. 13, 271–276 (2016).
Google Scholar
Hariri, G. et al. Narrative review: clinical assessment of peripheral tissue perfusion in septic shock. Ann. Intensive Care 9, 37 (2019).
Google Scholar
Heller, A. Integrated medical feedback systems for drug delivery. AIChE J. 51, 1054–1066 (2005).
Google Scholar
D’Souza, D., Thaivalappil Padmanabhan, P., Batchelor, R. & Yin, W. Aptamer sequences and uses thereof. International patent, WO2025123084 (2025).
Bakestani, R. M. et al. Carboxylate-terminated electrode surfaces improve the performance of electrochemical aptamer-based sensors. ACS Appl. Mater. Interfaces 17, 8706–8714 (2025).
Google Scholar
Groenendaal, W., von Basum, G., Schmidt, K. A., Hilbers, P. A. J. & van Riel, N. A. W. Quantifying the composition of human skin for glucose sensor development. J. Diabetes Sci. Technol 4, 1032–1040 (2010).
Google Scholar
Friedel, M. et al. Opportunities and challenges in the diagnostic utility of dermal interstitial fluid. Nat. Biomed. Eng. 7, 1541–1555 (2023).
Google Scholar
Oyaert, M. et al. Factors impacting unbound vancomycin concentrations in different patient populations. Antimicrob. Agents Chemother. 59, 7073–7079 (2015).
Google Scholar
Butterfield, J. M. et al. Refining vancomycin protein binding estimates: identification of clinical factors that influence protein binding. Antimicrob. Agents Chemother. 55, 4277–4282 (2011).
Google Scholar
Urakami, T., Oka, Y., Matono, T. & Aoki, Y. Factors affecting free vancomycin concentration and target attainment of free area under the concentration-time curve. J. Pharm. Health Care Sci. 11, 13 (2025).
Google Scholar
Fetter, L. C., McDonough, M. H., Kippin, T. E. & Plaxco, K. W. Effects of physiological-scale variation in cations, pH, and temperature on the calibration of electrochemical aptamer-based sensors. ACS Sens. 9, 6675–6684 (2024).
Google Scholar
Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261–272 (2020).
Google Scholar
Ljung, L. System Identification: Theory for the User 2nd edn (Prentice Hall, 1999).
Ogata, K. Modern Control Engineering 5th edn (Prentice Hall, 2010).
Wächter, A. & Biegler, L. T. On the implementation of an interior-point filter line-search algorithm for large-scale nonlinear programming. Math. Program. 106, 25–57 (2006).
Google Scholar
Andersson, J. A. E., Gillis, J., Horn, G., Rawlings, J. B. &Diehl, M. CasADi: a software framework for nonlinear optimization and optimal control. Math. Program. Comput. https://doi.org/10.1007/s12532-018-0139-4 (2018).
Erdal, M. K. Custom code for “Pilot-phase clinical trial of wearable electrochemical-aptamer-based patches for continuous drug concentration measurement” by MA Booth, MK Erdal, SL Stocker, KW Plaxco et. al. Zenodo https://doi.org/10.5281/zenodo.17931397 (2025).
:max_bytes(150000):strip_icc()/a-wild-jaguar-in-the-pantanal-is-watchful-while-laying-in-thick-vegetation-along-the-river-bank-of-t-520391160-30409cae6a054ef2b5142dad8c232487.jpg?w=390&resize=390,220&ssl=1 "12 Fierce Facts About Jaguars")
