Arroyo-Currás Netzahualcóyotl, Somerson Jacob, Vieira Philip A, Ploense Kyle L, Kippin Tod E, Plaxco Kevin W
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106.
Center for Bioengineering, University of California, Santa Barbara, CA 93106.
Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):645-650. doi: 10.1073/pnas.1613458114. Epub 2017 Jan 9.
The development of a technology capable of tracking the levels of drugs, metabolites, and biomarkers in the body continuously and in real time would advance our understanding of health and our ability to detect and treat disease. It would, for example, enable therapies guided by high-resolution, patient-specific pharmacokinetics (including feedback-controlled drug delivery), opening new dimensions in personalized medicine. In response, we demonstrate here the ability of electrochemical aptamer-based (E-AB) sensors to support continuous, real-time, multihour measurements when emplaced directly in the circulatory systems of living animals. Specifically, we have used E-AB sensors to perform the multihour, real-time measurement of four drugs in the bloodstream of even awake, ambulatory rats, achieving precise molecular measurements at clinically relevant detection limits and high (3 s) temporal resolution, attributes suggesting that the approach could provide an important window into the study of physiology and pharmacokinetics.
开发一种能够持续实时追踪体内药物、代谢物和生物标志物水平的技术,将推动我们对健康的理解以及疾病检测和治疗能力的提升。例如,它将使基于高分辨率、患者特异性药代动力学的治疗成为可能(包括反馈控制给药),为个性化医疗开辟新的维度。作为回应,我们在此展示了基于电化学适配体(E-AB)的传感器在直接植入活体动物循环系统时支持连续、实时、数小时测量的能力。具体而言,我们已使用E-AB传感器对清醒、活动的大鼠血液中的四种药物进行了数小时的实时测量,在临床相关检测限和高(3秒)时间分辨率下实现了精确的分子测量,这些特性表明该方法可为生理学和药代动力学研究提供重要窗口。