Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, California 93106, United States.
Center for Bioengineering, University of California Santa Barbara, Santa Barbara, California 93106, United States.
ACS Sens. 2021 Sep 24;6(9):3340-3347. doi: 10.1021/acssensors.1c01183. Epub 2021 Sep 7.
The ability to monitor drugs, metabolites, hormones, and other biomarkers in situ in the body would greatly advance both clinical practice and biomedical research. To this end, we are developing electrochemical aptamer-based (EAB) sensors, a platform technology able to perform real-time, in vivo monitoring of specific molecules irrespective of their chemical or enzymatic reactivity. An important obstacle to the deployment of EAB sensors in the challenging environments found in the living body is signal drift, whereby the sensor signal decreases over time. To date, we have demonstrated a number of approaches by which this drift can be corrected sufficiently well to achieve good measurement precision over multihour in vivo deployments. To achieve a much longer in vivo measurement duration, however, will likely require that we understand and address the sources of this effect. In response, here, we have systematically examined the mechanisms underlying the drift seen when EAB sensors and simpler, EAB-like devices are challenged in vitro at 37 °C in whole blood as a proxy for in vivo conditions. Our results demonstrate that electrochemically driven desorption of a self-assembled monolayer and fouling by blood components are the two primary sources of signal loss under these conditions, suggesting targeted approaches to remediating this degradation and thus improving the stability of EAB sensors and other, similar electrochemical biosensor technologies when deployed in the body.
能够在体内原位监测药物、代谢物、激素和其他生物标志物，将极大地促进临床实践和生物医学研究。为此，我们正在开发基于电化学适体的（EAB）传感器，这是一种能够实时、体内监测特定分子的平台技术，而不受其化学或酶反应性的限制。将 EAB 传感器部署在活体中具有挑战性的环境中面临的一个重要障碍是信号漂移，即传感器信号随时间的推移而降低。迄今为止，我们已经证明了许多方法可以很好地纠正这种漂移，从而在多小时的体内部署中实现良好的测量精度。然而，要实现更长的体内测量时间，可能需要我们了解并解决这种效应的来源。有鉴于此，在这里，我们系统地研究了当 EAB 传感器和更简单的 EAB 样设备在 37°C 的全血中作为体内条件的替代物进行体外挑战时，所观察到的漂移的机制。我们的研究结果表明，电化学驱动的自组装单层的解吸和血液成分的污染是这些条件下信号损失的两个主要来源，这表明可以采取有针对性的方法来修复这种降解，从而提高 EAB 传感器和其他类似电化学生物传感器技术在体内部署时的稳定性。
