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Electrochemical Aptamer-Based Sensors for Improved Therapeutic Drug Monitoring and High-Precision, Feedback-Controlled Drug Delivery.
ACS Sensors ( IF 8.2 ) Pub Date : 2019-10-15 , DOI: 10.1021/acssensors.9b01616 Philippe Dauphin-Ducharme , Kyungae Yang , Netzahualcóyotl Arroyo-Currás 1 , Kyle L Ploense , Yameng Zhang , Julian Gerson , Martin Kurnik , Tod E Kippin , Milan N Stojanovic , Kevin W Plaxco
ACS Sensors ( IF 8.2 ) Pub Date : 2019-10-15 , DOI: 10.1021/acssensors.9b01616 Philippe Dauphin-Ducharme , Kyungae Yang , Netzahualcóyotl Arroyo-Currás 1 , Kyle L Ploense , Yameng Zhang , Julian Gerson , Martin Kurnik , Tod E Kippin , Milan N Stojanovic , Kevin W Plaxco
Affiliation
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The electrochemical aptamer-based (E-AB) sensing platform appears to be a convenient (rapid, single-step, and calibration-free) and modular approach to measure concentrations of specific molecules (irrespective of their chemical reactivity) directly in blood and even in situ in the living body. Given these attributes, the platform may thus provide significant opportunities to render therapeutic drug monitoring (the clinical practice in which dosing is adjusted in response to plasma drug measurements) as frequent and convenient as the measurement of blood sugar has become for diabetics. The ability to measure arbitrary molecules in the body in real time could even enable closed-loop feedback control over plasma drug levels in a manner analogous to the recently commercialized controlled blood sugar systems. As initial exploration of this, we describe here the selection of an aptamer against vancomycin, a narrow therapeutic window antibiotic for which therapeutic monitoring is a critical part of the standard of care, and its adaptation into an electrochemical aptamer-based (E-AB) sensor. Using this sensor, we then demonstrate: (i) rapid (seconds) and convenient (single-step and calibration-free) measurement of plasma vancomycin in finger-prick-scale samples of whole blood, (ii) high-precision measurement of subject-specific vancomycin pharmacokinetics (in a rat animal model), and (iii) high-precision, closed-loop feedback control over plasma levels of the drug (in a rat animal model). The ability to not only track (with continuous-glucose-monitor-like measurement frequency and convenience) but also actively control plasma drug levels provides an unprecedented route toward improving therapeutic drug monitoring and, more generally, the personalized, high-precision delivery of pharmacological interventions.
中文翻译：
基于电化学适体的传感器，用于改善治疗药物监测和高精度，反馈控制的药物输送。
基于电化学适体（E-AB）的传感平台似乎是一种便捷的（快速，单步操作且无需校准）模块化方法，可直接在血液中甚至在血液中直接测量特定分子的浓度（无论其化学反应性如何）在生物体内原位。考虑到这些属性，该平台可能会提供大量机会，使糖尿病患者的血糖测量变得既频繁又方便，从而使治疗药物监测（临床实践中根据血浆药物的测量调整剂量）成为可能。实时测量体内任意分子的能力甚至可以以类似于最近商业化的受控血糖系统的方式实现对血浆药物水平的闭环反馈控制。作为对此的初步探索，我们在此描述针对万古霉素的适体的选择，万古霉素是一种狭窄的治疗窗抗生素，对其进行治疗监测是护理标准的关键部分，并将其适应于基于电化学适体的（E-AB）传感器。然后，使用这种传感器，我们证明：（i）快速（秒）便捷（单步和无标定）全血手指刺血样中血浆万古霉素的测定，（ii）受试者的高精度测定特异性万古霉素药代动力学（在大鼠模型中），以及（iii）对药物血浆水平的高精度，闭环反馈控制（在大鼠模型中）。
更新日期：2019-10-16
中文翻译：
基于电化学适体的传感器，用于改善治疗药物监测和高精度，反馈控制的药物输送。
基于电化学适体（E-AB）的传感平台似乎是一种便捷的（快速，单步操作且无需校准）模块化方法，可直接在血液中甚至在血液中直接测量特定分子的浓度（无论其化学反应性如何）在生物体内原位。考虑到这些属性，该平台可能会提供大量机会，使糖尿病患者的血糖测量变得既频繁又方便，从而使治疗药物监测（临床实践中根据血浆药物的测量调整剂量）成为可能。实时测量体内任意分子的能力甚至可以以类似于最近商业化的受控血糖系统的方式实现对血浆药物水平的闭环反馈控制。作为对此的初步探索，我们在此描述针对万古霉素的适体的选择，万古霉素是一种狭窄的治疗窗抗生素，对其进行治疗监测是护理标准的关键部分，并将其适应于基于电化学适体的（E-AB）传感器。然后，使用这种传感器，我们证明：（i）快速（秒）便捷（单步和无标定）全血手指刺血样中血浆万古霉素的测定，（ii）受试者的高精度测定特异性万古霉素药代动力学（在大鼠模型中），以及（iii）对药物血浆水平的高精度，闭环反馈控制（在大鼠模型中）。
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