School of Materials Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Birck Nanotechnology Center, Purdue University, West Lafayette, IN, 47907, USA.
Lab Chip. 2021 Dec 21;22(1):57-70. doi: 10.1039/d1lc00451d.
Although serum and fecal biomarkers (, lactoferrin, and calprotectin) have been used in management and distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), none are proven to be a differential diagnostic tool between Crohn's disease (CD) and ulcerative colitis (UC). The main challenge with laboratory-based biomarkers in the stool test is the inability to indicate the location of the disease/inflammation in the gastrointestinal (GI) tract due to the homogenous nature of the collected fecal sample. For the first time, we have designed and developed a battery-free smart capsule that will allow targeted sampling of inflammatory biomarkers inside the gut lumen of the small intestine. The capsule is designed to provide a simple and non-invasive complementary tool to fecal biomarker analysis to differentiate the type of IBD by pinpointing the site of inflammatory biomarkers secretion (, small or large bowel) throughout the GI tract. The capsule takes advantage of the rapid change from an acidic environment in the stomach to higher pH levels in the small intestine to dissolve a pH-sensitive polymeric coating as a means to activate the sampling process of the capsule within the small intestine. A swelling polyacrylamide hydrogel is placed inside the capsule as a milieu to collect the sampled GI fluid while also providing the required mechanical actuation to close the capsule once the sampling is completed. The hydrogel component along with the collected GI fluid can be easily obtained from the capsule through the screw-cap design for further extraction and analysis. As a proof of concept, the capsule's performance in sampling and extraction of bovine serum albumin (BSA) and calprotectin - a key biomarker of inflammation - was assessed within the physiologically relevant ranges. The ratio of extracted biomarkers relative to that in the initial sampling environment remained constant (∼3%) and independent of the sampling matrix in both and studies. It is believed that the demonstrated technology will provide immediate impact in more effective IBD type differential diagnostic and treatment strategies by providing a non-invasive assessment of inflammation biomarkers profile throughout the digestive tract.
虽然血清和粪便生物标志物（乳铁蛋白和钙卫蛋白）已被用于炎症性肠病（IBD）和肠易激综合征（IBS）的管理和鉴别，但没有一种被证明是克罗恩病（CD）和溃疡性结肠炎（UC）之间的鉴别诊断工具。粪便检测中基于实验室的生物标志物的主要挑战是由于收集的粪便样本具有均匀性质，因此无法指示胃肠道（GI）道中疾病/炎症的位置。我们首次设计并开发了一种无电池的智能胶囊，该胶囊将允许在小肠肠腔内部靶向采样炎症生物标志物。该胶囊旨在提供一种简单、非侵入性的粪便生物标志物分析补充工具，通过精确定位炎症生物标志物分泌的部位（小肠或大肠）来区分 IBD 的类型。该胶囊利用胃中酸性环境到小肠中较高 pH 值的快速变化来溶解 pH 敏感的聚合物涂层，作为在小肠内激活胶囊采样过程的一种手段。在胶囊内放置一种可溶胀的聚丙烯酰胺水凝胶作为收集被采样的 GI 液的环境，同时还提供完成采样后关闭胶囊所需的机械致动。水凝胶组件以及收集到的 GI 液可以通过螺旋盖设计轻松从胶囊中获得，以便进一步提取和分析。作为概念验证，评估了胶囊在采样和提取牛血清白蛋白（BSA）和钙卫蛋白（炎症的关键生物标志物）方面的性能，这些生物标志物的提取在生理相关范围内进行。在 研究和 研究中，提取的生物标志物与初始采样环境中的生物标志物的比值保持恒定（约 3%）且与采样基质无关。据信，所展示的技术将通过在整个消化道提供对炎症生物标志物谱的非侵入性评估，为更有效的 IBD 型鉴别诊断和治疗策略提供直接影响。
