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一种用于实时和炎症部位检测多种促炎细胞因子的免疫传感器。

An immunosensor for the near real-time and site of inflammation detections of multiple proinflammatory cytokines.

机构信息

Jiangzhong Cancer Research Center & Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, China.

Jiangzhong Cancer Research Center & Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, China; Dept. of Rehabilitation, Nanchang Hongdu Hospital, 1399 Diezihu Road, Honggutan, Nanchang, Jiangxi, 330008, China.

出版信息

Biosens Bioelectron. 2024 Nov 1;263:116618. doi: 10.1016/j.bios.2024.116618. Epub 2024 Jul 30.

DOI:10.1016/j.bios.2024.116618
PMID:39106691
Abstract

Diseases mediated by cytokine storms are often characterized by an overexuberant pace of pathogenesis accompanied by significant morbidity and mortality. Thus, near real-time (NRT) detections via a site-of-inflammation (SOI) sampling of proinflammatory cytokines are essential to ensure a timely and effective treatment of acute inflammations, which up to now, has not been fully possible. In this work, we proposed a novel NRT and SOI immunosensor using ZIF-8 signal amplification together with an off-on strategy. To achieve NRT detections via a SOI sampling, the body fluid of choice is the dermal interstitial fluid (ISF). The significant merits of ISF over blood are the quality, quantity and diversity of ISF-based biomarkers; the fluid is non-coagulating, making it feasible to perform multiple or continuous samplings and the sampling is minimally invasive. Our immunosensor requires only 5 μL of ISF to achieve a simultaneous detection of five highly potent proinflammatory cytokines: IL-6, IFN-γ, IL-1β, TNF-α, IP-10. We employed a microneedle array patch (MAP) together with a trifurcated nozzle pump to extract a mean volume of between 30 and 60 μL of ISF in 20 min. Under optimal conditions, the biosensor is capable of high-quality performance that exhibits a lower limit of detection (LOD) of 5.761 pg/mL over a wide linear range of 5.761 ‒ 20.00 ng/mL. We believe our immunosensor for NRT detections via a SOI sampling of ISF-biomarkers offers new theranostic opportunities that may not be possible with blood-based biomarkers.

摘要

由细胞因子风暴介导的疾病通常表现为发病过程过于旺盛,并伴有显著的发病率和死亡率。因此,通过炎症部位(SOI)对促炎细胞因子进行实时(NRT)检测对于确保急性炎症的及时有效治疗至关重要,但迄今为止,这还不完全可行。在这项工作中,我们提出了一种使用 ZIF-8 信号放大和开-关策略的新型 NRT 和 SOI 免疫传感器。为了通过 SOI 采样进行 NRT 检测,首选的体液是皮肤间质液(ISF)。ISF 优于血液的显著优点是 ISF 中生物标志物的质量、数量和多样性;该流体不凝固,可进行多次或连续采样,采样微创。我们的免疫传感器仅需 5 μL 的 ISF 即可同时检测五种强效促炎细胞因子:IL-6、IFN-γ、IL-1β、TNF-α、IP-10。我们采用微针阵列贴片(MAP)和三叉分叉喷嘴泵在 20 分钟内提取 30 至 60 μL 的平均 ISF 体积。在最佳条件下,该生物传感器能够实现高质量的性能,在 5.761 pg/mL 至 20.00 ng/mL 的宽线性范围内,检测限(LOD)低至 5.761 pg/mL。我们相信,我们的用于通过 SOI 采样 ISF-生物标志物进行 NRT 检测的免疫传感器提供了新的治疗机会,这可能是基于血液的生物标志物所不可能实现的。

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