Towards a catheter-based impedimetric sensor for the assessment of intestinal histamine levels in IBS patients.
Towards a catheter-based impedimetric sensor for the assessment of intestinal histamine levels in IBS patients.
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DOI：
10.1016/j.bios.2020.112152
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发表时间：
2020-03
影响因子：
12.6
通讯作者：
Gideon Wackers;T. Putzeys;M. Peeters;Lori Van de Cauter;P. Cornelis;M. Wübbenhorst;J. Tack;F. Troost;N. Verhaert;T. Doll;P. Wagner
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作者：
Gideon Wackers;T. Putzeys;M. Peeters;Lori Van de Cauter;P. Cornelis;M. Wübbenhorst;J. Tack;F. Troost;N. Verhaert;T. Doll;P. Wagner
在这项工作中，我们报告了一种基于导管的传感器的开发，该传感器设计用于测量人类十二指肠中组胺的浓度。某些肠道疾病，例如肠易激综合症（IBS），与慢性免疫激活导致的肠道组胺水平升高有关。由于仍然无法确定体内组胺浓度，因此具有组胺传感功能的鼻肠导管有可能成为一种有价值的诊断仪器。关于传感原理，我们选择使用与分子印迹聚合物（MIP）作为识别元件的体内应用兼容的电压的阻抗谱。 MIP 是合成受体，具有对组胺作为靶标的稳健性、高特异性和选择性的优点。在本例中，MIP 是由丙烯酸单体合成的，这保证了在肠液 pH 范围内具有均匀的结合能力。我们在模拟十二指肠内环境的测试装置中对掺有组胺的人体肠道液体验证了导管传感器。剂量反应曲线显示组胺的分析范围在 5 至 200 nM 之间，对应于生理正常条件，而较高浓度则与疾病相关。传感器的关键输出信号是 MIP 功能化钛电极的电阻分量，该分量源自全范围阻抗谱的等效电路建模。未来的应用可能是针对心血管、泌尿、胃肠和神经血管应用定制的导管。这与 MIP 的多功能性相结合，将使该传感器平台成为多功能诊断工具。
In this work, we report on the development of a catheter-based sensor designed for measuring the concentration of histamine in the human duodenum. Certain gut disorders, such as the irritable bowel syndrome (IBS), are associated with elevated levels of intestinal histamine due to chronic immune activation. As it is still impossible to determine histamine concentrationsin vivo, a nasointestinal catheter with histamine-sensing capabilities has the potential to become a valuable diagnostic instrument. Regarding the sensing principle, we selected impedance spectroscopy using voltages that are compatible with intra-body applications with molecularly imprinted polymers (MIPs) as recognition elements. MIPs are synthetic receptors that offer the advantages of robustness, high specificity and selectivity for histamine as a target. In this specific case, the MIPs were synthesized from acryclic acid monomers, which guarantees a uniform binding capacity within the pH range of intestinal fluid. We have validated the catheter sensor on human intestinal liquids spiked with histamine in a testing setup that mimics the environment inside the duodenum. The dose-response curves show an analytical range between 5 and 200 nM of histamine, corresponding to physiologically normal conditions while higher concentrations correlate with disease. The key output signal of the sensor is the resistive component of the MIP-functionalized titanium electrodes as derived from the equivalent-circuit modelling of full-range impedance spectra. Future applications could be catheters tailored to cardiovascular, urological, gastrointestinal, and neurovascular applications. This, in combination with the versatility of the MIPs, will make this sensor platform a versatile diagnostic tool.