Experimental characterization and modelling of specialty optical fibres for bio-medical applications

Abstract

Specialty optical fibers (SOF) which have at least one property different from standard ones are gaining more and more attention in bio-medical applications. These fibers include a wide group of liquid core fibers, photonic crystal fibers (PCFs), and active fibers. Particularly during the last years, employing the PCFs as optical biosensors has received much attention in the scientific community. Generally speaking, optical biosensors are of special interest because of the increasing demand for biological and chemical analyte detection in a wide range of applications including clinical analysis \cite{haes2005detection}, food quality control \cite{khansili2018label}, defense and security \cite{kumar2013development}, and environmental monitoring \cite{giardi2009optical}. Briefly, a biosensor device is made of three main elements: the biorecognition element, the transducer, and the receiver. There are different kinds of biosensors named electrochemical, thermometric, piezoelectric, and magnetic sensors \cite{andrews2015photonics, newman1992biosensors}. Among them, especially, optical biosensors look promising for point-of-care-based diagnosis \cite{haes2005detection} and food quality control \cite{khansili2018label}. These biosensors are modern analytical devices that employ light-guiding technologies as their transducer part and exploit the properties of light for bio/analyte detection. Changes in the optical properties of the light in contact with the bio/chemical analytes lead to changes in the output spectrum or the electrical signal recorded by the photodetector. Some of the advantages of optical biosensors compared with other sensors are the immunity of EM fields to electrical noises, higher sensitivity, simpler mechanism and detection protocol, more reliability, more flexibility, lower cost, and more compactness \cite{andrews2015photonics}. Regarding the pros of being simple, compact, and usability with untrained personnel, particularly label-free optical biosensors are attracting more attention~\cite{andrews2015photonics}. In this scheme of detection, the bio/chemical analytes are directly detected without the laborious process of analyte molecule labeling \cite{zanchetta2017emerging,morales2019graphene, chamorro2022asymmetric}. Regarding their transducer part, optical biosensors are categorized into different groups resonator-based \cite{khozeymeh2018cylindrical,khozeymeh2019parallel, khozeymeh2019crystalline}, waveguide-based \cite{khozeymeh2018fast,khozeymeh2018sensitivity}, and interferometric-devices based \cite{nguyen2015interferometric, jiang2014high}. Although these optical sensors have demonstrated high sensitivities for both bulk and surface sensing measurements~\cite{cunningham2002enhancing, khozeymeh2019characteristics, talebifard2017optimized}, they still suffer from a critical issue. Indeed, the integration need of photonic and fluidic technologies \cite{gonzalez2016trends, ricciardi2015lab} envisages unified sensor devices. PCF-based biosensors are a group of optical biosensors that meet the need for effective integration between fluidics and photonics \cite{yang2011hollow, nasirifar2020hollow}. The integration of fluidics and photonics in these miniaturized structures may pave the way for lab-in-fiber technologies employing in vivo biosensing \cite{ricciardi2015lab}. PCFs can be referred to the structures that confine the light inside a core surrounded by a microstructured cladding composed of air holes running along the length of the fiber \cite{yang2011hollow}. Thus, gas or liquid solutions can be infiltrated inside these air holes leading to the creation of biological layers on the dielectric inner walls of the fiber \cite{coscelli2009toward}. This advantage can be further exploited if HC-PCFs are considered thanks to the possibility of having a strong interaction between the sample and the light guided by the fiber. HC-PCFs can rely on two different transmission mechanisms: Photonic Band-gap (PBG) or inhibited coupling (IC) \cite{giovanardi2017inhibited}. The former presents disadvantages in terms of bandwidth and, moreover, this mechanism requires complicated microstructured cladding, while the latter allows covering a wider range of wavelengths. The transmission spectra of this kind of fiber are characterized by an alternating sequence of high and low transmission bands. In particular, there is high transmission when the coupling between the fundamental core mode and the cladding modes is prevented \cite{vincetti2010waveguiding}. The position of the transmission bands is defined by the thickness of the microstructured cladding which can be composed of much simpler structures and larger pitches with respect to PBG fibers, allowing easier infiltration of solutions. So, HC-IC specialty fibers represent a promising platform for the development of label-free sensors for biological molecule detection \cite{giovanardi2017inhibited,giovanardi2019hollow}. The formation of a biological layer due to the molecular interaction of the target analyte with the suitably functionalized glass core surface is exploited for detection because it changes the thickness of cladding that is directly translated into a red shift in the transmission spectrum of the fiber without the use of additional transducers. In the first part of this thesis, we aim to demonstrate, as a proof of concept, the suitability of the HC-IC specialty fibers as a platform for DNA detection. For this purpose, two different kinds of HC-IC specialty fibers, tube-lattice (TL), and Kagome-lattice (KL) HC-IC fibers have been selected for DNA detection. Then precise functionalization process of the inner surface of the fiber has been performed. In the functionalization process, new steps have been added to increase the possibility of DNA detection. The experimental setup including optical and chemical parts, the methods, and the material are explained in Chapter 1, and the obtained results, their analysis, and reliability will be discussed in Chapter 2. \par In Chapter 3, we will deal with another kind of specialty fiber used to develop yellow lasers for ophthalmology applications. These lasers have proven to be effective in treating a variety of retinal diseases. Recently, visible lasers with applications in medicine, biology, metrology, optical storage, and display technology have been interesting subjects for many research worldwide groups \cite{luke2019lasers}. For visible laser generation, there are several techniques based on gas lasers, Dye lasers, second harmonic generation (SHG), or optical parametric oscillator (OPO) techniques that can be adapted for visible laser development \cite{omatsu2009passively,fujimoto2011575, okamoto2010fundamentals}. Nevertheless, in general, these techniques suffer from low efficiency, complexity, and high costs. On the other hand, fiber lasers have the advantages of high beam quality, stability, excellent excitation efficiency, and an alignment-free design which enables low-cost and high-quality lasers. Particularly yellow fiber-based lasers emitting around 565-590 nm are of particular interest for their existing and potential applications in sodium laser guide star \cite{lavinsky2016nondamaging}, optical clock \cite{hong2005observation}, ophthalmology \cite{zhang2014versatile}, and in particular medical treatment for diabetic retinopathy (DR) \cite{aflalo2020theoretical}. DR is the most common eye disease among diabetic patients which causes vision impairment and blindness. In the treatment of DR, experimental investigations on animals and humans, but also numerical analysis, have confirmed that yellow laser emission is the most suitable candidate, because it is effective with low power, and presents good clinical results with minimal collateral effects \cite{kapany1963retinal, aflalo2020theoretical, verdina2020role}. So far yellow emission has been possible with several techniques from copper bromide laser \cite {coutts1990efficient}, Yb$-$doped fiber \cite{ota2006high}, bi$-$fiber lasers \cite{dianov2007high}, optically pumped semiconductor lasers \cite{fallahi20085}. However, these techniques demand bulky structures with several free-space alignments, high maintenance, and tight limitations on the pump conditions. For accessing high-efficiency and simple direct yellow laser emission, particularly dysprosium Dy$-$doped ZBLAN fiber lasers exploiting transition from $^4F_{9/2}$ to $^6H_{13/2}$ level, is a desirable candidate. Therefore, the design, modeling, and fabrication of compact and efficient Dy$-$doped yellow fiber lasers are of critical importance. In 2001 \cite{limpert2001laser}, the first CW yellow emission in a Dy$-$doped ZBLAN fiber laser was demonstrated. Although Dy$-$doped yellow fiber lasers have been analyzed in some other research works \cite{fujimoto2011575, bowman2012diode, bolognesi2014yellow}, still the reported slope efficiencies were less than 13.2$\%$. Indeed, in a considerable time, due to the lack of high-performance gain fibers and high-power GaN blue lasers as the pumping sources, no significant research progress has been observed in Dy$-$doped fiber yellow lasers. In 2020, thanks to the breakthroughs of both Dy$-$doped fluoride fibers and high-power blue GaN laser diodes, the first Dy$-$doped ZBLAN fiber laser pumped by GaN laser diode, emitting at 445 nm, was reported \cite{amin2020yellow}. In that experiment, the maximum laser slope efficiency of 2.3$\%$ and 0.9$\%$ was reported for absorbed pump power in a Dy$-$doped fiber with lengths of 0.6 m and 5.95 m. In 2021, the same researchers investigated the potential causes of the low experimental slope efficiency and found contributions from the background loss of the fiber and excited-state absorption (ESA) of the intracavity yellow light \cite{amin2021experimental}. They measured a maximum slope efficiency of 33$\%$ \cite{amin2021experimental}, which is still less than half of the Stokes limit which is about 78$\%$. Recently, Dy$-$doped multi-component phosphate glass was examined and showed a strong yellow emission which was due to the high asymmetry and covalency of the local field and the high phonon energy \cite{tian2022silicate}. In that work, Dy$-$doped multi-component phosphate core glass fiber was successfully drawn by using a rod-in-tube method. Furthermore in \cite{chen2023efficient}, another Dy$-$doped NaLa(WO$_4$)$_2$ glass ceramic fiber with good uniformity was fabricated using the molten core method, showing that it can be a very promising material candidate for tunable yellow lasers \cite{chen2023efficient}. Despite these positive results in the fabrication technology of new glasses, the most promising commercially available Dy$-$doped fiber is the ZBLAN one produced by Le Verre Fluoré, France \cite{https}. Interesting results have been obtained so far with this fiber \cite{amin2021experimental, amin2020yellow, zou2021direct}, even if the maximum reported slope efficiency is still quite low. Until now, few research works have dealt fully with the causes of the low slope efficiency in Dy$-$doped fiber yellow lasers. Therefore, it is necessary to propose more numerical and analytical methods for further improvements in the performance of Dy$-$doped ZBLAN fiber lasers.\\ In my thesis activity, it is proposed to use a Forward Time Centered Space (FTCS) method \cite{meyer2022fiber} and analytical methods for deep analysis and further understanding of Dy$-$doped ZBLAN fiber laser properties. In this way, a suitable and comprehensive model is obtained that figures out the impact of different physical parameters, such as pump and signal overlap integrals with the doped region, as well as cavity parameters (active fiber length and mirror's reflectivity), on laser output performance. On the other hand, the developed numerical method asses the impact of both ESA and amplified spontaneous emission (ASE) on the output power of the laser. Finally, the optimization criteria providing high slope efficiency (more than half of the Stokes limit) for yellow lasers, have been found. This in turn will pave the way for design, modeling, and employing the high slope efficiency Dy$-$doped ZBLAN fiber lasers in DR treatments. The modeling and simulation of the yellow-fiber laser will be represented in Chapter 4. Towards the final application of the yellow fiber lasers studied with numerical simulations, in Chapter 5, cell irradiation experiments are carried out, which obtain preliminary results. Finally, in Chapter 6, we conclude our research studies.