Interferometric biosensor on optical fibers

towards in vivo molecular diagnostics
A route towards in vivo molecular diagnostics. Internship at UGA/CEA/CNRS lab Molecular Systems and nanoMaterials for Energy and Health (SyMMES)

Fibres_finalesScientific context and objective

Optical fibers are minimally invasive devices commonly used in medicine to image tissues in vivo by endoscopy. For in vitro analysis, biochips are a fast-growing approach to perform multiparametric diagnostics from biological fluids (blood, urine, saliva). The coupling of these two technologies would give rise to a novel tool capable of performing real-time, remote, in situ, and multiplexed molecular analysis. Such a tool could bring important progress in the medical field. Indeed, when imaging techniques are insufficient to establish a diagnosis, it is necessary to perform biopsies, a long and invasive procedure. The use of fiber-based biosensors would allow faster (real-time) and less invasive analyses directly at the level of the diseased tissue, thus shortening the diagnosis time.
To date, there is no sensor able to perform a biomolecular analysis in situ, label-free, highly multiplexed, and adapted to measurements in complex environments such as in vivo. The objective of this/these internship(s) is to contribute to the development of such a sensor.

Biosensor principle

Based on our experience with fiber-based plasmonic biosensors1,2,3, we have chosen to develop a new sensing strategy based on interferometry. This label-free approach is particularly interesting for in vivo diagnosis. The figure provided below represents a schematic view of the tool we wish to develop. The detection principle is based on the interference between a light wave reflected by an internal reference layer and a second wave reflected by the probe layer immobilized at the end of the fiber. The optical path of the second wave will be modulated by the recognition of the targeted molecules by the corresponding probes. This will result in a real-time quantification of the interaction. Using a multifiber assembly, each fiber will act as an individual sensor, and the measurement of the intensity of the light retro-reflected by the functionalized side will allow monitoring of biological interactions occurring on this surface.

Trainee's work

Thanks to the modeling of the interference phenomenon occurring at the end of the fiber, we have determined geometrical parameters (thickness) and optical parameters (indices) to maximize the sensitivity of the fibers to optical index variations. Surface treatments have been applied on different samples (single fiber, multicore fibers, multifiber assemblies...) selected to produce interferences.
The M1 trainee will participate in the optical characterization of the different samples. He/she will determine the sensitivities and resolutions of the fibers to optical index variations from the analysis of data collected and image processing. The obtained results will help us to specify the optical and geometric parameters necessary to achieve the highest sensitivity and may lead to the production of new samples.
Thereafter, once the sensitivities are evaluated and optimized, and depending on the project’s progress (M2 internship), the detection limits for biological targets will be evaluated. To reach this objective, the trainee will participate in the functionalization of the sensors. He/she will carry out these functionalizations by deposition using micro-levers2 and/or using optical methods developed in the team4. Then, he/she will participate in the implementation of biosensors to detect biological target, first using model probes and targets, secondly using targets of biological interest. The detection will be gradually done in more and more complex environments (serum, blood).

Background expected: master student in the Soft Nanosciences track, or student from Phelma Biomedical Engineering.

References

[1] Vindas, K., et al. Enhanced sensitivity of plasmonic optical fiber sensors by analyzing the distribution of the optical modes intensity. (2020) Optics Express Vol. 28, Issue 20, pp. 28740-28749. doi.org/10.1364/OE.399856
[2] Desmet, C., et al. Multiplexed Remote SPR Detection of Biological Interactions through Optical Fiber Bundles. (2020) Sensors, MDPI, Vol 20 (2), p.511. doi.org/10.3390/s20020511
[3] Vindas, K., et al. Highly-Parallel Remote SPR Detection of DNA Hybridization by Micropillar Optical Arrays. (2019) Analytical and Bioanalytical Chemistry, Vol 411, p2249-2259 doi.org/10.1007/s00216-019-01689-2
[4] Alvarado Meza, R., et al. Optically Assisted Surface Functionalization for Protein Arraying in Aqueous Media. (2017) Langmuir 33, 10511-10516
 
Published on March 14, 2022
Updated onMarch 14, 2022