A recent article in Small introduces a compact fiber-optic device for rapid, microscope-free detection of disease-related biomarkers.
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Background: Lab-on-Fiber Sensing for Diagnostics
Fiber-optic technologies are widely used across fields ranging from telecommunications to biomedical sensing due to their compact size, affordability, and ability to support high-resolution data acquisition. In diagnostics, they offer a practical alternative to optical microscopy, which can be bulky, expensive, and impractical in clinical or field settings.
This study applies a gliding motility assay, in which kinesin motors transport microtubules across a surface. When microtubules are conjugated with antibodies or biotin, binding events with target analytes alter their motion, typically slowing their speed. These motion changes can be detected optically, enabling real-time monitoring without a microscope.
Device Design and Assay Implementation
The researchers developed a fiber-optic device that integrates gliding motility assays for rapid analyte detection, including clinically relevant biomarkers for heart disease. The system uses fluorescently labeled, antibody-functionalized microtubules that glide along kinesin-coated surfaces at the polished tip of an optical fiber.
The presence of target analytes affects microtubule dynamics, such as gliding speed or bundle formation, which is tracked by changes in fluorescence intensity.
To prepare the sensing surface, the fiber tip was coated with a BRB80-casein buffer, kinesin-1, and a microtubule-containing motility solution. After washing off unbound microtubules, the fiber was immersed in the analyte solution. Motility was powered by ATP, while analyte binding altered microtubule behavior, producing a measurable decrease in fluorescence over time.
Fluorescence signals were recorded using a SOLA light engine, filter wheels, and an avalanche photodiode, with real-time acquisition managed via LabView software. The device successfully detected monomeric streptavidin, neutravidin, and the cardiac biomarker creatine kinase-MB (CK-MB), demonstrating its utility for point-of-care diagnostics.
Key Findings: Detection Mechanisms and Sensitivity
The decay of the fluorescence signal was directly linked to microtubule gliding speed: faster motion led to quicker signal loss, while slower motion resulted in more gradual decay. This relationship enabled analyte quantification based on velocity, supported by a mathematical model showing a linear correlation between the decay constant and gliding speed.
Two detection mechanisms were observed: slowdown and bundling. In slowdown mode, biotinylated-TAMRA microtubules exposed to streptavidin showed a clear reduction in speed compared to controls, with statistically significant results achieved within five minutes. In bundling mode, larger analytes like neutravidin induced aggregation, further impeding gliding and amplifying the fluorescence signal.
The system detected analytes at concentrations as low as 1 nM and distinguished between targets based on size and binding behavior. Additional tests showed that adjusting linker length and antibody size could further improve sensitivity.
Point-of-Care Applications and Clinical Relevance
The fiber-optic device’s compact form factor and rapid detection capabilities make it well-suited for clinical diagnostics, particularly in point-of-care environments. Its sensitivity to analytes at nanomolar concentrations supports the monitoring of various health conditions, including cardiovascular disease.
The integration of fiber-optic technology also enables multiplexing, allowing simultaneous detection of multiple biomarkers and streamlining diagnostic workflows by reducing both time and resource demands.
The device’s compatibility with different biological samples, including blood, highlights its flexibility for clinical applications. Its utility extends beyond laboratory research, offering real-time diagnostic support in acute settings, such as during suspected myocardial infarctions.
The system’s ability to detect markers like Creatine Kinase-MB demonstrates its effectiveness for on-site screening. Its low-cost construction and minimal hardware requirements make it particularly beneficial in emergency care and resource-limited settings. Multiplexing, enabled through the functionalization of microtubules with various antibodies, expands the device’s potential for broad-spectrum disease screening.
Additionally, this platform could be integrated into existing diagnostic systems for expanded applications, including therapeutic monitoring in chronic care. The fiber-optic system presents a practical, scalable solution for rapid and sensitive analyte detection in modern healthcare settings.
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Conclusion: Enhancing Diagnostic Precision
This work demonstrates a compact, microscope-free gliding motility assay integrated with fiber optics for analyte detection. By linking microtubule motion to fluorescence signal decay, the platform offers a simple yet sensitive method for detecting biomolecules, including cardiac biomarkers, in real time.
Future development could focus on enhancing specificity through alternative binders such as aptamers, and expanding the range of detectable targets. The technology also holds promise for integration with broader diagnostic platforms, contributing to the development of next-generation, point-of-care biosensors with real-world clinical impact.
Journal Reference
Carey-Morgan, H., et al. (2025). Microscope-Free Analyte Detection Based on Fiber-Optic Gliding Motility Assays. Small. DOI: 10.1002/smll.202411836, https://onlinelibrary.wiley.com/doi/full/10.1002/smll.202411836
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