Holt Brian M, Stine Justin M, Beardslee Luke A, Ayansola Hammed, Jin Younggeon, Pasricha Pankaj J, Ghodssi Reza
Department of Electrical and Computer Engineering, University of Maryland, College Park, MD, 20742, USA.
Institute for Systems Research, University of Maryland, College Park, MD, 20742, USA.
Microsyst Nanoeng. 2025 Feb 7;11(1):24. doi: 10.1038/s41378-025-00877-8.
Existing gastrointestinal (GI) diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus. In the GI tract, local inflammatory processes induce alterations in tight junction proteins, enhancing paracellular ion permeability. Although transepithelial electrical resistance (TEER) may be used in the laboratory to assess mucosal barrier integrity, there are no existing methodologies for characterizing tight junction dilation in vivo. Addressing this technology gap, intraluminal bioimpedance sensing may be employed as a localized, non-invasive surrogate to TEER electrodes used in cell cultures. Thus far, bioimpedance has only been implemented in esophagogastroduodenoscopy (EGD) due to the need for external electronics connections. In this work, we develop a novel, noise-resilient Bluetooth-enabled ingestible device for the continuous, non-invasive measurement of intestinal mucosal "leakiness." As a proof-of-concept, we validate wireless impedance readout on excised porcine tissues in motion. Through an animal study, we demonstrate how the device exhibits altered impedance response to tight junction dilation induced on mice colonic tissue through calcium-chelator exposure. Device measurements are validated using standard benchtop methods for assessing mucosal permeability.
现有的胃肠道(GI)诊断工具无法在体内非侵入性地监测食管以外部位的粘膜紧密连接完整性。在胃肠道中,局部炎症过程会导致紧密连接蛋白发生改变,增加细胞旁离子通透性。虽然在实验室中可以使用跨上皮电阻(TEER)来评估粘膜屏障完整性,但目前尚无用于在体内表征紧密连接扩张的方法。为了填补这一技术空白,可以采用腔内生物阻抗传感作为细胞培养中使用的TEER电极的局部非侵入性替代方法。到目前为止,由于需要外部电子连接,生物阻抗仅在食管胃十二指肠镜检查(EGD)中得以应用。在这项工作中,我们开发了一种新型的、具有抗噪声功能的蓝牙可吞咽设备,用于连续、非侵入性地测量肠道粘膜的“渗漏性”。作为概念验证,我们在运动的离体猪组织上验证了无线阻抗读数。通过一项动物研究,我们展示了该设备如何对通过钙螯合剂暴露在小鼠结肠组织上诱导的紧密连接扩张表现出改变的阻抗反应。使用评估粘膜通透性的标准台式方法对设备测量结果进行了验证。
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