Alkanethiol Monolayer End Groups Affect the Long-Term Operational Stability and Signaling of Electrochemical, Aptamer-Based Sensors in Biological Fluids
Alkanethiol Monolayer End Groups Affect the Long-Term Operational Stability and Signaling of Electrochemical, Aptamer-Based Sensors in Biological Fluids
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DOI：
10.1021/acsami.9b22385
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发表时间：
2020-03-04
影响因子：
9.5
通讯作者：
Arroyo-Curras, Netzahualcoyotl
中科院分区：
文献类型：
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作者：
Shaver, Alexander;Curtis, Samuel D.;Arroyo-Curras, Netzahualcoyotl
基于电化学适体（E-AB）的传感器实现了对未处理生物液体中特定分子目标的高精度测量。这种独特的能力，加上他们的测量。秒或更快的频率，使得能够以前所未有的时间分辨率实时监测活体动物中的药物药代动力学。然而，E-AB传感器的一个重要弱点是，它们的生物电子界面在连续的电化学询问时降解，这一过程通常被视为法拉第下降和充电电流随时间的增加。这种渐进性降解将其体内使用寿命限制在最多12小时，这一时间比人体中绝大多数药物的消除半衰期短得多。因此，迫切需要开发新的E-AB界面，其在生物流体中长时间抵抗连续的电化学询问。作为回应，我们的团队正在开发更好的包装，更稳定的自组装单分子层（SAM），以改善信号传导，并将体内E-AB传感器的使用寿命从数小时延长到数天。通过调用疏水性参数，我们已经创建了在水性生理溶液和生物流体中不从电极表面解吸的自组装膜。这些自组装膜，从1-己基乙醇溶液形成，降低了3倍，相对于6-巯基-1-己醇的标准单层的伏安充电电流的E-AB传感器，增加总法拉第电流，并改变平台的电子转移动力学。此外，我们的新型SAMs的稳定性使得在37摄氏度的生理温度下，在生物液体（如未稀释的血清）中连续数天不间断地进行E-AB询问。
Electrochemical aptamer-based (E-AB) sensors achieve highly precise measurements of specific molecular targets in untreated biological fluids. This unique ability, together with their measurement. frequency of seconds or faster, has enabled the real-time monitoring of drug pharmacokinetics in live animals with unprecedented temporal resolution. However, one important weakness of E-AB sensors is that their bioelectronic interface degrades upon continuous electrochemical interrogation-a process typically seen as a drop in faradaic and an increase in charging currents over time. This progressive degradation limits their in vivo operational life to 12 h at best, a period that is much shorter than the elimination half-life of the vast majority of drugs in humans. Thus, there is a critical need to develop novel E-AB interfaces that resist continuous electrochemical interrogation in biological fluids for prolonged periods. In response, our group is pursuing the development of better packed, more stable self-assembled monolayers (SAMs) to improve the signaling and extend the operational life of in vivo E-AB sensors from hours to days. By invoking hydrophobicity arguments, we have created SAMs that do not desorb from the electrode surface in aqueous physiological solutions and biological fluids. These SAMs, formed from 1-hexanethiol solutions, decrease the voltammetric charging currents of E-AB sensors by 3-fold relative to standard monolayers of 6-mercapto-1-hexanol, increase the total faradaic current, and alter the electron transfer kinetics of the platform. Moreover, the stability of our new SAMs enables uninterrupted, continuous E-AB interrogation for several days in biological fluids, like undiluted serum, at a physiological temperature of 37 degrees C.