. Our goal is the development and validation of a technology that can measure a wide range of drugs, metabolites, and biomarkers in the blood, urine, and interstitial fluids of living subjects continuously and in real time, an ability that would revolutionize many aspects of biomedical research and healthcare. To achieve this goal we will combine electrochemical aptamer-based sensors (which are reagentless and wash-free and can operate directly in complex samples without fouling) with biocompatible anti-coagulation membranes and advanced drift correction methods to achieve continuous, real-time, multi-day measurements directly in vivo. As preliminary results supporting this goal we demonstrate the continuous, real-time measurement of four different drugs directly in the jugulars of anesthetized rats for periods of more than five hours with 20-second time resolution and sub-micromolar precision. Leveraging these initial results we propose here three further advancements: First, we will expand the platform to the in vivo measurement of nine additional drugs and metabolites, which will demonstrate the platform's versatility. Second, we will improve the platform's stability such that we can perform high-precision in vivo measurements over the course of days, which will enable continuous measurements of long-lived drugs and capture clinically important circadian metabolic variations. Finally, we will expand the platform to the simultaneous measurement of multiple molecules and/or across multiple body compartments (e.g., blood, tissues, brain, bladder), rendering it a powerful new tool for understanding pharmacokinetics and physiology. By creating an unprecedented window into a patient's molecular-level physiological state, the proposed technology would enable many transformative clinical applications, including the high-precision measurement of patient-specific pharmacokinetics, the continuous monitoring of health status via the real-time measurement of specific biomarkers, and, ultimately, feedback- controlled drug delivery.

Public Health Relevance

Health relevance. The goal of the proposed research program is the development of a technology for the continuous, real-time, multi-day measurement of specific molecules directly in the body. By creating an unprecedented window into a subject's molecular physiological state, such an advance would vastly improve our knowledge of pharmacokinetics and metabolism, would provide a valuable new tool for following health status in real-time, would offer the promise of personalized pharmacokinetics, in which drug doses are determined using high-precision, patient-specific measurements, and would enable unprecedented, feedback- controlled drug delivery in which drugs with narrow therapeutic windows or complex optimal dosing regimes can be delivered safely and efficiently. In short, such a technology could revolutionize many aspects of our ability to understand, detect, monitor, and treat disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB022015-03
Application #
9730466
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Selimovic, Seila
Project Start
2017-09-01
Project End
2021-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Santa Barbara
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
094878394
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106