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Short-Wave Infrared Fluorescence Chemical Sensor for Detection of Otitis Media
ACS Sensors ( IF 8.2 ) Pub Date : 2020-11-11 , DOI: 10.1021/acssensors.0c01272 Joshua J. Yim 1 , Surya Pratap Singh 2, 3 , Anping Xia 2 , Raana Kashfi-Sadabad 2 , Martina Tholen 4 , David M. Huland 5 , David Zarabanda 2 , Zhixin Cao 2, 6 , Paola Solis-Pazmino 2 , Matthew Bogyo 1, 4, 7 , Tulio A. Valdez 2
ACS Sensors ( IF 8.2 ) Pub Date : 2020-11-11 , DOI: 10.1021/acssensors.0c01272 Joshua J. Yim 1 , Surya Pratap Singh 2, 3 , Anping Xia 2 , Raana Kashfi-Sadabad 2 , Martina Tholen 4 , David M. Huland 5 , David Zarabanda 2 , Zhixin Cao 2, 6 , Paola Solis-Pazmino 2 , Matthew Bogyo 1, 4, 7 , Tulio A. Valdez 2
Affiliation
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Otitis media (OM) or middle ear infection is one of the most common diseases in young children around the world. The diagnosis of OM is currently performed using an otoscope to detect middle ear fluid and inflammatory changes manifested in the tympanic membrane. However, conventional otoscopy cannot visualize across the tympanic membrane or sample middle ear fluid. This can lead to low diagnostic certainty and overdiagnoses of OM. To improve the diagnosis of OM, we have developed a short-wave infrared (SWIR) otoscope in combination with a protease-cleavable biosensor, 6QC-ICG, which can facilitate the detection of inflammatory proteases in the middle ear with an increase in contrast. 6QC-ICG is a fluorescently quenched probe, which is activated in the presence of cysteine cathepsin proteases that are up-regulated in inflammatory immune cells. Using a preclinical model and custom-built SWIR otomicroscope in this proof-of-concept study, we successfully demonstrated the feasibility of robustly distinguishing inflamed ears from controls (p = 0.0006). The inflamed ears showed an overall signal-to-background ratio of 2.0 with a mean fluorescence of 81 ± 17 AU, while the control ear exhibited a mean fluorescence of 41 ± 11 AU. We envision that these fluorescently quenched probes in conjunction with SWIR imaging tools have the potential to be used as an alternate/adjunct tool for objective diagnosis of OM.
中文翻译：
短波红外荧光化学传感器检测中耳炎
中耳炎（OM）或中耳感染是全世界幼儿中最常见的疾病之一。目前，OM的诊断是使用耳镜来检测中耳液和鼓膜中表现出的炎症变化。但是，传统的耳镜无法在鼓膜或样本中耳液中看到。这可能会导致OM的低诊断确定性和过度诊断。为了改善OM的诊断，我们开发了短波红外（SWIR）耳镜结合蛋白酶可裂解的生物传感器6QC-ICG，可以促进中耳炎性蛋白酶的检测，而对比度却有所提高。6QC-ICG是一种荧光淬灭探针，在存在于炎症性免疫细胞中的半胱氨酸组织蛋白酶中被激活。在此概念验证研究中，使用临床前模型和定制的SWIR耳镜，我们成功地证明了从对照中可靠地区分发炎的耳朵的可行性（p = 0.0006）。发炎的耳朵的总信号与背景之比为2.0，平均荧光为81±17 AU，而对照耳朵的平均荧光为41±11 AU。我们设想这些荧光淬灭探针与SWIR成像工具结合在一起，有可能被用作OM客观诊断的替代/辅助工具。
更新日期：2020-11-25
中文翻译：
短波红外荧光化学传感器检测中耳炎
中耳炎（OM）或中耳感染是全世界幼儿中最常见的疾病之一。目前，OM的诊断是使用耳镜来检测中耳液和鼓膜中表现出的炎症变化。但是，传统的耳镜无法在鼓膜或样本中耳液中看到。这可能会导致OM的低诊断确定性和过度诊断。为了改善OM的诊断，我们开发了短波红外（SWIR）耳镜结合蛋白酶可裂解的生物传感器6QC-ICG，可以促进中耳炎性蛋白酶的检测，而对比度却有所提高。6QC-ICG是一种荧光淬灭探针，在存在于炎症性免疫细胞中的半胱氨酸组织蛋白酶中被激活。在此概念验证研究中，使用临床前模型和定制的SWIR耳镜，我们成功地证明了从对照中可靠地区分发炎的耳朵的可行性（p = 0.0006）。发炎的耳朵的总信号与背景之比为2.0，平均荧光为81±17 AU，而对照耳朵的平均荧光为41±11 AU。我们设想这些荧光淬灭探针与SWIR成像工具结合在一起，有可能被用作OM客观诊断的替代/辅助工具。
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