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Short-Wave Infrared Fluorescence Chemical Sensor for Detection of Otitis Media
Joshua J Yim1, Surya Pratap Singh2,3, Anping Xia2
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, United States.
Abstract:
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.
Insights
A new short-wave infrared (SWIR) otoscope and biosensor, 6QC-ICG, improve middle ear infection (otitis media) diagnosis by detecting inflammatory markers. This technology offers greater diagnostic certainty for middle ear infections in children.
Area of Science:
- Biomedical Engineering
- Otolaryngology
- Medical Imaging
Background:
- Otitis media (OM) is a common childhood infection.
- Current otoscopy lacks visualization across the tympanic membrane and fluid sampling capabilities, leading to diagnostic uncertainty.
- Inflammatory proteases are elevated in middle ear infections.
Purpose of the Study:
- To develop an improved diagnostic tool for otitis media.
- To utilize a novel short-wave infrared (SWIR) otoscope combined with a protease-cleavable biosensor (6QC-ICG).
- To enhance the detection of inflammatory proteases in the middle ear.
Main Methods:
- Development of a custom-built SWIR otomicroscope.
- Utilized a protease-cleavable fluorescent probe, 6QC-ICG, activated by cysteine cathepsin proteases.
- Tested the system in a preclinical model of otitis media.
Main Results:
- Successfully distinguished inflamed ears from control ears with high statistical significance (p = 0.0006).
- Inflamed ears showed a signal-to-background ratio of 2.0 and mean fluorescence of 81 ± 17 AU.
- Control ears exhibited a mean fluorescence of 41 ± 11 AU.
Conclusions:
- The combination of SWIR imaging and 6QC-ICG biosensor shows feasibility for objective otitis media diagnosis.
- This approach has the potential to serve as an adjunct or alternative to conventional otoscopy.
- Offers improved diagnostic accuracy for middle ear infections.
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