Electrochemical aptamer-based (EAB) sensors are the first technology supporting high-frequency, real-time, in vivo molecular measurements that is independent of the chemical reactivity of its targets, rendering it easily generalizable. As is true for all biosensors, however, EAB sensor performance is affected by the measurement environment, potentially reducing accuracy when this environment deviates from the conditions under which the sensor was calibrated. Here, we address this question by measuring the extent to which physiological-scale environmental fluctuations reduce the accuracy of a representative set of EAB sensors and explore the means of correcting these effects. To do so, we first calibrated sensors against vancomycin, phenylalanine, and tryptophan under conditions that match the average ionic strength, cation composition, pH, and temperature of healthy human plasma. We then assessed their accuracy in samples for which the ionic composition, pH, and temperature were at the lower and upper ends of their physiological ranges. Doing so, we find that physiologically relevant fluctuations in ionic strength, cation composition, and pH do not significantly harm EAB sensor accuracy. Specifically, all 3 of our test-bed sensors achieve clinically significant mean relative accuracy (i.e., better than 20%) over the clinically or physiologically relevant concentration ranges of their target molecules. In contrast, physiologically plausible variations away from the temperature used for calibration induce more substantial errors. With knowledge of the temperature in hand, however, these errors are easily ameliorated. It thus appears that physiologically induced changes in the sensing environment are likely not a major impediment to clinical application of this in vivo molecular monitoring technology.

中文翻译：

---

阳离子、pH 值和温度的生理尺度变化对基于电化学适子体的传感器校准的影响


基于电化学适配体 （EAB） 的传感器是第一个支持高频、实时、体内分子测量的技术，它独立于其靶标的化学反应性，使其易于推广。然而，与所有生物传感器一样，EAB 传感器性能会受到测量环境的影响，当该环境偏离传感器校准的条件时，可能会降低精度。在这里，我们通过测量生理尺度环境波动在多大程度上降低一组具有代表性的 EAB 传感器的精度来解决这个问题，并探索纠正这些影响的方法。为此，我们首先在与健康人血浆的平均离子强度、阳离子组成、pH 值和温度相匹配的条件下校准了针对万古霉素、苯丙氨酸和色氨酸的传感器。然后，我们在离子组成、pH 值和温度处于其生理范围的下限和上限的样品中评估了它们的准确性。这样做，我们发现离子强度、阳离子组成和 pH 值的生理相关波动不会显著损害 EAB 传感器的精度。具体来说，我们的所有 3 种测试台传感器在其目标分子的临床或生理相关浓度范围内都实现了具有临床意义的平均相对准确度（即优于 20%）。相比之下，远离用于校准的温度的生理上合理的变化会引起更大的误差。然而，只要知道温度，这些误差就很容易得到改善。 因此，传感环境的生理诱导变化似乎不是这种体内分子监测技术临床应用的主要障碍。