Zargartalebi H, Mirzaie S, GhavamiNejad A, Ahmed S U, Esmaeili F, Geraili A, Flynn C D, Chang D, Das J, Abdrabou A, Sargent E H, Kelley S O
Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
Department of Chemistry, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, USA.
Science. 2024 Dec 6;386(6726):1146-1153. doi: 10.1126/science.adn2600. Epub 2024 Dec 5.
Continuous measurement of proteins in vivo is important for real-time disease management and prevention. Implantable sensors for monitoring small molecules such as glucose have been available for more than a decade. However, analysis of proteins remains an unmet need because the lower physiological levels require that sensors have high affinities, which are linked to long complexation half-lives ( ~20 hours) and slow equilibration when concentrations decrease. We report active-reset sensors by use of high-frequency oscillations to accelerate dissociation, which enables regeneration of the unbound form of the sensor within 1 minute. When implemented within implanted devices, these sensors allow for real-time, in vivo monitoring of proteins within interstitial fluid. Active-reset protein sensors track biomarker levels on a physiological timescale for inflammation monitoring in living animals.
体内蛋白质的连续测量对于实时疾病管理和预防至关重要。用于监测葡萄糖等小分子的可植入传感器已经问世十多年了。然而,蛋白质分析仍然是一个未满足的需求,因为较低的生理水平要求传感器具有高亲和力,这与长的络合半衰期(约20小时)以及浓度降低时缓慢的平衡有关。我们报告了通过使用高频振荡来加速解离的主动重置传感器,这使得传感器的未结合形式能够在1分钟内再生。当在植入设备中实施时,这些传感器能够实时、在体内监测组织间液中的蛋白质。主动重置蛋白质传感器在生理时间尺度上跟踪生物标志物水平,用于活体动物的炎症监测。