Ming Tao, Lan Tingting, Yu Mingxing, Wang Hong, Deng Juan, Kong Deling, Yang Shuang, Shen Zhongyang
Research Institute of Transplant Medicine, Tianjin First Central Hospital, Nankai University, Tianjin 300190, China.
Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
Polymers (Basel). 2023 Jun 23;15(13):2796. doi: 10.3390/polym15132796.
Continuous in vivo monitoring (CIVM) of pH value is essential for personalized medicine, as many diseases are closely related to acid-base imbalances. However, conventional pH meters are limited in their ability to perform CIVM due to excessive blood consumption, large device volume, frequent calibration, and inadequate real-time monitoring. There is thus an urgent need for a portable method for CIVM of pH value. To address this need, we propose a minimally invasive, continuous monitoring solution in the form of an implantable pH microneedle sensor (MNS) in this study. The MNS is based on the integration of an acupuncture needle (AN) and a Ag/AgCl reference electrode. We fabricate the sensor by electrochemically depositing platinum black and gold nanoparticles onto the AN and further modifying it with polyaniline to increase its sensitivity to hydrogen ions. The pH value is obtained by calculating the open circuit voltage between the modified AN and the reference electrode. The resulting MNS demonstrates excellent selectivity and a high nernstian response to pH (-57.4 mV per pH) over a broad range (pH = 4.0 to pH = 9.0). Both in vitro and in vivo experiments have verified the performance of the sensor, showcasing its potential for biomedical research and clinical practice. The MNS provides an alternative to conventional pH meters, offering a less invasive and more convenient way to perform CIVM of pH value. Moreover, this electrochemical implantable sensor based on AN and silver wires provides a simple and sensitive method for continuous in vivo detection of other biomarkers.
体内pH值的连续监测（CIVM）对于个性化医疗至关重要，因为许多疾病都与酸碱失衡密切相关。然而，传统pH计由于耗血量过多、设备体积大、频繁校准以及实时监测不足，在进行CIVM方面能力有限。因此，迫切需要一种用于pH值CIVM的便携式方法。为满足这一需求，我们在本研究中提出了一种以可植入pH微针传感器（MNS）形式存在的微创连续监测解决方案。该MNS基于针灸针（AN）和Ag/AgCl参比电极的集成。我们通过将铂黑和金纳米颗粒电化学沉积到AN上并进一步用聚苯胺对其进行修饰来制造传感器，以提高其对氢离子的敏感性。通过计算修饰后的AN与参比电极之间的开路电压来获得pH值。所得的MNS在较宽的pH范围（pH = 4.0至pH = 9.0）内表现出优异的选择性和对pH的高能斯特响应（每pH变化-57.4 mV）。体外和体内实验均验证了该传感器的性能，展示了其在生物医学研究和临床实践中的潜力。MNS为传统pH计提供了一种替代方案，提供了一种侵入性较小且更方便的方法来进行pH值的CIVM。此外，这种基于AN和银线的电化学可植入传感器为连续体内检测其他生物标志物提供了一种简单而灵敏的方法。
