Label-free multiplexed detection of diabetic retinopathy biomarkers using fiber optic biosensors: Towards lab-in-the-tear
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Label-free multiplexed detection of diabetic retinopathy biomarkers using fiber optic biosensors: Towards lab-in-the-tear


Detecting disease signals in tears

Tear fluid is emerging as an attractive source of diagnostic information because it can be collected easily and non-invasively. Changes in tear composition often reflect underlying physiological conditions, making tears a valuable medium for monitoring eye diseases.

The newly developed biosensor targets two proteins associated with diabetic retinopathy:

  • Lipocalin-1 (LCN1) — linked to inflammation and changes in tear composition

  • Vascular endothelial growth factor (VEGF) — a key driver of abnormal blood vessel growth in advanced stages of the disease

By detecting both biomarkers simultaneously, the system provides a more comprehensive picture of retinal health compared with conventional single-target tests.

A miniature fiber-optic sensing platform

The technology is based on semi-distributed interferometer (SDI) sensors fabricated from optical fibers. These miniature devices are lightweight, resistant to electromagnetic interference, and suitable for in-situ monitoring.

After fabrication, the researchers functionalized the fiber tips with specific antibodies, enabling selective binding to the target biomarkers. When proteins attach to the sensor surface, the optical signal changes — allowing real-time monitoring without fluorescent labels or complex sample preparation.

Laboratory tests demonstrated strong performance:

  • Detection of LCN1 down to 5.98 ng/mL

  • Detection of VEGF as low as 26.6 fg/mL

Importantly, the system was evaluated not only in static laboratory conditions but also in dynamic experiments simulating natural tear flow — an essential step toward real-world clinical applications.

Multiplex sensing for improved diagnostics

A key innovation of the study is the use of a three-sensor configuration: two biosensors for LCN1 and VEGF detection, and a reference sensor monitoring background signals. This design improves measurement stability and reduces the risk of false readings.

Simultaneous measurement of multiple biomarkers, known as multiplexed detection. May help clinicians assess disease progression more accurately while reducing analysis time and costs.

Toward accessible and personalized eye care

Current diagnostic tools for diabetic retinopathy, such as retinal imaging and optical coherence tomography, require specialized equipment and trained personnel. The research team believes that compact fiber-optic biosensors could complement these methods by enabling rapid screening and personalized monitoring, particularly in settings with limited resources.

Because the sensing element is small and inexpensive, future versions could be integrated into wearable devices or point-of-care systems, potentially supporting continuous monitoring of tear biomarkers.

Next steps

While the present work demonstrates proof-of-concept performance in artificial tear fluid, future research will focus on testing diluted clinical samples and exploring practical clinical deployment.

The study was funded by the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan and Nazarbayev University.

Sabira Seipetdenova, Toheeb O. Oladejo, Aliya Bekmurzayeva, Christabel K.L. Tan, Minghong Yang, Wilfried Blanc, Daniele Tosi,
Label-free multiplexed detection of diabetic retinopathy biomarkers using fiber optic biosensors: Towards lab-in-the-tear,
Optics and Lasers in Engineering,
Volume 189,
2025,
108943,
ISSN 0143-8166,
https://doi.org/10.1016/j.optlaseng.2025.108943.
(https://www.sciencedirect.com/science/article/pii/S0143816625001307)
Abstract: Diabetic retinopathy is a common disease in diabetic patients accompanied by such complications as edema, formation of hard exudates, hemorrhages, and eventually vision loss. Detection of the disease at an early stage could increase the effectiveness of therapy and preserve the patient's vision. Measuring the levels of diabetic retinopathy-associated biomarkers using more reliable methods is an alternative and promising way of diagnosis. Optical fiber biosensors have gained rising popularity in providing affordable platforms due to their high-performance capabilities, miniature size, and label-free nature of detection. These properties made them a sensor of choice for developing biosensors for a multiplexed in situ detection of biomarkers in this study. Here, we report an optical fiber-based biosensor that is based on simply fabricated semi-distributed interferometry sensors. After fabrication, sensitive sensors were chosen for further functionalization with two antibodies against biomarkers relevant to diabetic retinopathy to produce biosensors. The detection of the biomarkers was evaluated in artificial tear fluid in static conditions and most importantly in dynamic conditions simulating natural tear flow. This method allowed label-free monitoring of the intensity change with the increasing concentrations of analytes specifically binding on the biosensor surface. Namely, it was possible to detect lipocalin 1 protein with a limit of detection of 5.98 ng/mL and vascular endothelial growth factor down to 26.6 fg/mL. The designed biosensors can become the basis for developing a new method for a clinical diagnosis of eye diseases at early stages of development.
Keywords: Diabetic retinopathy; Biomarker; Lipocalin 1; Vascular endothelial growth factor; Multiplexed detection; Optical fiber biosensor; Semi-distributed interferometer
Attached files
  • wfer.jpg
Regions: Asia, Kazakhstan
Keywords: Applied science, Engineering, Technology, Health, Medical

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