Biokompatibilni mikro laserji kot senzorji koncentracije glukoze in temperature

Dobravec, Anja (author), Humar, Matjaž (mentor)

V zadnjih letih se vedno več študij ukvarja z bio laserji, ki so namenjeni uporabi znotraj bioloških sistemov. Sipanje in absorpcija svetlobe znotraj tkiv sta glavni problem pri detekciji svetlobe. Zato imajo laserji v primerjavi s fluorescenco veliko prednosti; glavne lastnosti laserske svetlobe so ozke emisijske črte, visoka koherenca in velika intenziteta. Glavna motivacija tega magistrskega dela je bila študija potencialno možnih aplikacij biokompatibilnih mikro laserjev za namen biosenzorike. Mikro laserje lahko vgradimo v biološko tkivo in merimo fiziološke parametre, kot sta koncentracija glukoze in temperatura, v realnem času. Za namene biosenzorike znotraj bioloških tkiv je potrebno razviti laserje iz biokompatibilnih snovi, ki so tudi biorazgradljive. Biokompatibilna snov ne povzroči imunskih reakcij in omogoča nemoteno delovanje telesa. Hkrati morajo biti laserji dovolj občutljivi na zunanje spremembe, ki so v območju fizioloških vrednosti. Razvili smo postopek izdelave mikro laserjev iz biokompatibilnih materialov, ki so tudi biorazgradljivi in dovoljeni za uporabo v medicinske namene. Vsak laser ima tri glavne sestavne dele: optični resonator, ki ujame svetlobo, ojačevalni medij, ki ojačuje svetlobo v resonatorju in črpalni mehanizem, ki ustvarja obrnjeno zasedenost v ojačevalnem mediju. Izdelali smo dva tipa mikro laserjev glede na način delovanja. Prvi tip je Whispering Gallery Mode (WGM) mikro laser. Izdelan je iz biokompatibilnega polimera Poly(L-lactic acid) (PLLA), dopiranega s fluorescentnim barvilom. Drugi tip mikro laserja je Braggov mikro laser, izdelan iz holesteričnih tekočih kristalov, estrov holesterola, ki so že naravno prisotni v človeškem telesu, in dopiran s fluorescentnim barvilom. Najprej smo predstavili lastnosti delovanja klasičnih laserjev, ključne lastnosti WGM in Braggovih resonatorjev ter princip njihovega delovanja. WGM mikro laserji temeljijo na večkratnem popolnem odboju svetlobe znotraj resonatorja, ki je dielektrična sfera, katere lomni količnik je večji od lomnega količnika v okoliškem mediju. Braggovi mikro laserji se zaradi samo urejene periodične strukture obnašajo kot fotonski kristali s prepovedanim pasom za fotone. Svetloba se selektivno odbija na periodični strukturi v skladu z Braggovim zakonom. V drugem delu smo natančno opisali materiale in postopke izdelave mikro laserjev ter eksperimentalne metode, ki smo jih uporabili. V tretjem delu so predstavljeni rezultati in diskusija. Demonstrirali smo lasersko delovanje WGM mikro laserja znotraj biološkega tkiva na globini $\mathrm{\sim 100\ \mu m}$. Testirali smo možnosti uporabe biokompatibilnih WGM mikro laserjev kot senzorjev spremembe lomnega količnika okoliškega medija in posledično koncentracije glukoze. Pri tem smo naleteli na težave in eksperimentalne omejitve, ki smo jih predstavili. Rezultati so dokaj obetavni, vendar bo potrebno razrešiti še nekaj eksperimentalnih problemov. Holesterične mikro laserje smo uporabili kot senzorje temperature. Izkazali so se kot zelo stabilen senzor temperature, saj so ti mikro laserji manj občutljivi na ostale zunanje dejavnike.

• Language: Slovenian
• Keywords: laser, Whispering Gallery Mode, Braggov uklon, fotonski kristal, holesterični tekoči kristali, fluorescenca, senzor, glukoza, temperatura
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: FMF - Faculty of Mathematics and Physics
• Year: 2018
• PID: 20.500.12556/RUL-104001
• COBISS.SI-ID: 3259748
• Publication date in RUL: 30.09.2018

Secondary language

• Language: English
• Title: Biocompatible microlasers as sensors of glucose concentration and temperature

Abstract

In the past few years there has been an increasing number of studies focusing on biolasers, which are used in biological systems. Scattering and absorption of light inside tissues are two main problems of light detection. This is why lasers have many benefits compared to only fluorescence; laser light has high coherence, high intensity and narrow emission spectrum. The main motivation of this master thesis was the study of potential applications of biocompatible microlasers as biosensors. Microlasers can be implanted in a biological tissue where we can measure physiological parameters such as concentration of glucose and temperature in real time. If we want to use microlasers inside a biological tissue, they must be made of biocompatible materials which are also biodegradable. Biocompatible material does not cause any immune reactions and allow body to function normally. At the same time it is important that lasers are sensitive enough to environmental changes in the range of physiological values. We developed a procedure for production of microlasers from biocompatible and biodegradable materials which have already been used for medical applications. There are three main components of every laser system: optical resonator that confines light, gain medium and pumping system which provides an inverted population. We produced two different types of biocompatible microlasers regarding the principle of how it works. The first type is Whispering Gallery Mode (WGM) microlaser. It is made of a biocompatible polymer Poly(L-lactic acid) (PLLA), doped with a fluorescent dye. The second type of a microlaser is so called Bragg microlaser, made of a cholesteric liquid crystals which are cholesterol-derivatives, naturally presented in the body. They are also doped with a fluorescent dye. In the first part we present the characteristic of a classical laser, the main features of WGM and Bragg resonators and their principle of how they work. WGM microlasers are based on a multiple total internal reflections inside a resonator which is a dielectric sphere with a refractive index greater than the surrounding medium. If the circulating light circles the resonator with an integer number of wavelengths and returns to the same point, a constructive interference occurs. Bragg microlasers have self-assembled periodical structure which acts as a photonic crystal with a photonic band gap. Light is selectively reflected on a periodic structure in accordance with Bragg law. In the second part we describe in details materials and procedures for production of both kinds of microlasers and the used experimental methods. In the third part our results and discussion are shown. We demonstrated lasing of a WGM microlaser inside a biological tissue at a depth of approximately $\mathrm{\sim 100\ \mu m}$. We tested possibilities of using WGM microlasers as sensors of changing refractive index of the surrounding medium and consequently glucose concentration. We found many experimental limitations and problems which we discuss. We used Bragg microlasers as sensors of temperature. They are an accurate temperature sensor, mainly due to lower sensitivity to other external factors.

• Keywords: laser, Whispering Gallery Mode, Bragg diffraction, photonic crystal, cholesteric liquid crystal, fluorescence, sensor, glucose, temperature