L’objectif de cette thèse est l’élaboration de sondes à base de lanthanide pour la microscopie optique biphotonique. Cette technique d’imagerie complémentaire à l’IRM et au scanner permet une analyse rapide et facile de tissus épais. Afin de permettre l’observation en profondeur, l’absorption et l’émission de la sonde doit se situer dans la zone de transparence biologique [700 – 1200 nm]. L’absorption à deux photons (ADP) est un phénomène d’optique linéaire de troisième ordre par lequel l’état excité est atteint par absorption simultanée de deux photons. De fait, l’excitation à énergie moitié se situe dans la zone de transparence biologique. Les sondes envisagées combineraient les propriétés optiques uniques des lanthanides, telles que des bandes d’émission très étroites allant du visible à l’infrarouge et des durées de vie de luminescence longues, et les avantages de l’ADP, permettant une excitation dans l’IR et une résolution tridimensionnelle. Dans ce contexte, cette thèse décrit l’élaboration de complexes d’europium et d’ytterbium à ligands macrocycliques stables en milieu aqueux et dont la luminescence peut être sensibilisée à deux photons. Ces complexes ont permis l’imagerie de la vascularisation de cerveaux de souris par microscopie biphotonique dans le proche infrarouge. La seconde approche consiste à encapsuler un complexe luminescent dans des nanoparticules desilice formées par la technique sol-gel (collaboration A. Ibanez, institut Néel, Grenoble) afin de protéger le complexe du milieu biologique. Enfin la dernière approche consiste à greffer des complexes de lanthanides à la surface d’une particule de silice par chimie organométallique de surface. Ces travaux ont conduit à la formation de nano-objet très brillants dans le rouge et le proche infrarouge, détectables à l’échelle de l’objet unique par microscopie à deux photons. / Two Photon Scanning Laser Microscopy (TPSLM) has evolved as an emerging bio-imaging technique widely used in academic research and in medical diagnosis. This technique requires the design of bioprobes specially optimized for such purpose. A particular attention is actually devoted bio-probes featuring both two-photon absorption (TPA) and emission in the near infra-red (NIR) spectral range [700 – 1200 nm], also called biological window that is particularly promising for thick tissues imaging. In this context, europium complexes emitting in the red (615 nm) has been recently sensitized by two photon antenna effect and used for TPSLM in cells combining the advantages of lanthanide emission (sharp line and long lived) and those of TPA. Based on this preliminary results, this thesis describe the design of europium and ytterbium complexes which have an improved stability in water and good emission properties sensitized by TPA. Theses complexes allow the imaging of mice’s brain vascularisation in the NIR. An another approach to stabilize lanthanide complexes was also used by encapsulating theses fluorophores in silica nanoparticle (collaboration with A. Ibanez, Institut Néel, Grenoble). Then the last approach consists on the grafting of the chromophores on silica sphere using surface organometallic chemistry methods. The nanoparticles obtained by both way are really luminescent in the red or infrared and can be imaged as single nanoparticle by TPSLM.

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.

Lymph is primarily composed of fluid and proteins from the blood circulatory system that drain into the space surrounding cells, interstitial space. From the interstitial space, the fluid enters and circulates in the lymphatic system until it is delivered into the venous system. In contrast to the blood circulatory system, the lymphatic system lacks a central pumping organ dictating the predominant driving pressure and velocity of lymph. Transport of lymph via capillaries, pre-collecting and collecting lymphatic vessels relies on the synergy between pressure gradients, local tissue motion, valves and lymphatic vessel contractility. The direction of lymph transport is regulated by bicuspid valves distributed throughout pre-collecting and collecting lymphatic vessels. Effective transport of lymph into the venous system is of prime importance. Disruption of lymph transport, because of impaired lymphatic function, reduced numbers of vessels or valvular insufficiencies can have severe health consequences, including lymphedema for which current clinical therapies are not curative. The lymphatic valves are usually bicuspid, however, congenital malformations in the valve such as single leaflet valve formation and arrested lymphatic valve development are observed and can cause lymphedema. Here we employ 4-week-old mice to study the effects of valves and malformed valves on lymph transport shedding light into some of the potentially underlying consequences of lymphedema. Polyethylene glycol (PEG) coated latex particles were injected into the inguinal lymph node of anesthetized mice. Particle displacement measurements through efferent lymphatic vessels yielded velocity, wall shear stress, vorticity and strain of the efferent lymph flow field carrying lymph from subdermal inguinal lymph nodes. Lymphatic vessel endothelial Prox1 green fluorescent protein (GFP) marker enabled the detection of lymphatic vessel walls and valves. Flow field, flow velocity, flow rate, velocity profiles, wall shear stress, vorticity and strain values were compared in regions downstream of normal and malformed valves in two wild type mice. A Clec2-deficient mouse, which experiences lymphatic development defects and is used as a lymphedema model, was employed to further elucidate the lymphatic valves on transport. The absence of centralized pumping yields highly variable lymphatic flow cycles varying from one to fifteen seconds. The presence of lymphatic valves introduces boundary conditions that yield spatial and temporal flow gradients increasing the degree of complexity of lymph transport. The valves dictate the trajectory of the particles and promote the formation of recirculation zones. Even in the presence of valves, lymph flow commonly reverses. Congenital defects like a single leaflet valve lowers the lymph flow efficiency and promotes higher wall shear stress regions. Furthermore, the absence of functional valves in the Clec2-deficient mouse not displaying lymphedema yielded lymph flow lacking the pulsatility that characterizes normal lymphatic flow.

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5.4pt;mso-para-margin-top:0cm;mso-para-margin-right:0cm;mso-para-margin-bottom:8.0pt;mso-para-margin-left:0cm;line-height:107%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri","sans-serif";mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-ansi-language:EN-US;mso-fareast-language:EN-US;}</style><![endif]--></p><p>Luminescentni nanokristali (nanofosfori) na bazi fluorapatita (FAP-a) dopirani elementima retkih zemalja idealni su kontrastni agenti za bio-medicinske primene, kao &scaron;to su detekcije, snimanja, praćenja i terapije ćelija kancera. Kancer je jedna od najče&scaron;ćih bolesti modernog doba čiji uspeh lečenja zavisi od rane dijagnostike i neinvazivnog tretmana. Luminescentne nanočestice mogu uneti inovativnu paradigmu u lečenje kancera kombinovanjem biosnimanja, dijagnostike i tretmana. Za studije fluorescentnih biosnimanja nanokristali fluorapatita dopirani retkim zemljama kao kontrastni agenti pružaju značajne prednosti u vidu velikih kontrasta i dugotrajnosti luminescencije, i &scaron;to je jo&scaron; važnije visoke biokompatibilnosti, netoksičnosti i bioaktivnosti. Glavni ciljevi ove doktorske disertacije su sinteza novih luminescentnih multifotonskih bionanomaterijala na bazi fluorapatita dopiranih jonima prazeodimijuma (Pr³⁺), njihova karakterizacija i evaluacija&nbsp; primene za fluorescentna biosnimanja kancera. Sintezom nanoprahova u umerenim uslovima metodom ko-precipitacije, a potom su&scaron;enjem na 110 ^oC i kalcinacijom na temperaturama od 700 i 1000 ^oC očekuje se pronalaženje najboljih uslova za dobijanje novih nanofosfora koji bi na&scaron;li i različite bio-medicinske primene u oblasti fluorescentnih biosnimanja. Proučavane su tri vrste PrFAP nanokristala, sa 0,1%, 0,5% i 1% atomskih procenta Pr³⁺, zajedno sa nedopiranim FAP kontrolnim uzorkom. Nivoi energije aktivator jona Pr³⁺ sadrže metastabilna multipletna stanja koja nude mogućnosti efikasnih emisionih linija u vi&scaron;e boja u FAP nanokristalima, kao i u infracrvenoj i ultravioletnoj oblasti spektra. Metodom ko-precipitacije na sobnoj temperaturi (25 ^oC), a potom su&scaron;enjem na 110 ^oC, sintetisani su monofazni heksagonalni nanokristali PrFAPs nepravilnog sfernog oblika. Termičkom analizom sintetisanih uzoraka, na&nbsp;osnovu detektovanih temperaturnih opsega procesa dekarbonacije i dehidroksilacije, utvrđene su temperature kalcinacije od 700 i 1000 oC. Termička analiza i karakterizacija uzoraka su pokazale da Pr³⁺ joni dovode do stabilizacije FAP strukture na vi&scaron;im temperaturama, &scaron;to je pripisano unosu lantanoidnih jona sa specifičnim magnetnim osobinama u sistem i stvaranju jačih privlačnih sila sa O^2-anjonima. Nanokristali su&scaron;eni na 100 ^oC i kalcinisani na 1000 ^oC, zbog prisustva defekata kristalne re&scaron;etke koji zadržavaju emisiju Pr³⁺ jona, nisu pokazali luminescentne karakteristike od značaja za primene u medicinskim fluorescentnim biosnimanjima. Kalcinacijom uzoraka na 700 ^oC izrađen je novi tip aktiviranih fluorapatitnih nanokristala dopira / <p>Luminescent nanocrystals (nanophosphorus) based on fluorapatite (FAP) doped with rare earth elements are ideal contrast agents for biomedical applications such as cancer cell detection, imaging, tracking and therapy. Cancer is one of the most common diseases of the modern times whose success of the cure depends on early diagnosis and non-invasive treatment. Luminescent nanoparticles can bring an innovative paradigm into the treatment of cancer by combining bioimaging, diagnostics and treatment. Rare earth doped fluorapatite nanocrystals as contrast agents for studies of fluorescence bioimaging, offer significant advantages in terms of high contrasts and long-term luminescence, and more importantly high biocompatibility, non-toxicity and bioactivity. The main objectives of this doctoral dissertation are the synthesis of novel luminescent multiphoton bionanomaterials based on fluorapatites doped with praseodymium ions (Pr³⁺), their characterization and evaluation of their application for cancer fluorescence bioimaging. Synthesis of nanopowders under moderate conditions by the co-precipitation method, followed by dried at 110 &deg;C and calcination at 700 and 1000 &deg;C, is expected to find the best conditions for obtaining new nanophosphors that would find different bio-<br />medical applications in the field of fluorescence bioimaging. Three types of PrFAP nanocrystals were studied, with 0,1%, 0,5%, and 1% atomic percentages of Pr³⁺, together with an undoped FAP control sample. Energy levels of the Pr³⁺ ion activator contain metastable multiplet states that offer the possibility of efficient multi-color emission lines in FAP nanocrystals as well as in the infrared and ultraviolet regions of the spectrum. Single-phase hexagonal nanocrystals PrFAPs of irregular spherical shape were synthesized by the method of co-precipitation at room temperature (25 ^oC) and then drying at 110 ^oC. Thermal analysis of the synthesized samples, based on the detected temperature ranges of the decarbonation and dehydroxylation processes, determined calcination temperatures of 700 and 1000 ^oC. Thermal analysis with characterization showed that Pr³⁺ ions lead to stabilization of the FAP structure at higher temperatures,&nbsp;which was attributed to the entry of lanthanoid ions with specific magnetic properties into the system and the creation of stronger attractive forces with O^2- anions. Nanocrystals dried at 100 ^oC and calcined at 1000 ^oC, due to the presence of crystal lattice defects that quench the emission of Pr³⁺ ions, did not show luminescent characteristics of significance for applications in medical fluorescence imaging. Calcination of the samples at 700 ^oC produced a new type of activated praseodymium doped fluorapatite nanocrystals (PrFAPa) with excitation-emission profiles in the visible part of the spectrum. Physicochemical characterization confirmed spherical crystals of hexagonal structure up to a nanometer size of about 20 nm. Quantum-chemical calculations predicted that Pr³⁺ ions would be embedded in the crystal lattice of FAP nanocrystals at the Ca2 position (6h), which was followed by deformations of the F^- ion position. The assumed substitution mechanism is one Pr3+ ion for one Ca²⁺, with partial substitution of F^&ndash;anions with O^2&ndash; and OH^&ndash; and creation of vacancies due to achieving system neutrality. The results of in vitro biocompatibility and hemocompatibility showed that PrFAP nanocrystals were not toxic to living cells. In addition, the internalization of PrFAPa nanocrystals by skin (A431) and lung (A549) cancer cells was studied using fluorescence-based confocal microscopy and wide-field microscopy. The nanocrystals show characteristic green emission at 545 nm (³P₀&rarr;³H₅ transition of Pr³⁺ ion) and orange emission at 600 nm (¹D₂&rarr;³H₄), which we use to discriminate from cell autofluorescence. Studies of the images obtained by confocal microscopy in the blue, green, and red channels revealed that nanocrystals could recognize the cell surface and adhere to it, but they did not confirm the entry of nanocrystals into the cells. The wide-field microscopy detected emission transitions in green and orange color, and confirmed that the luminescent signal was coming from inside the cells. Using resonant excitation of PrFAP nanocrystals at 488 nm and emission of 600 nm, confocal microscopy extracted the fluorescence signal from inside the cancer cells. Orthogonal projections across 3D confocal stacks show that the nanocrystals are able to enter the cells positioning themselves within the cytoplasm. Overall, the obtained PrFAPa nanocrystals are biocompatible and of the tested types, the 0,5% Pr³⁺ doped nanocrystals show the highest promise as a tracking nanoparticle probe for bioimaging applications.</p>

Zero-dimensional graphene (carbon) quantum dots have been drawing attention in bio-related applications since their discovery, especially for their optical properties, chemical stability, and easily modifiable surface.  This thesis focuses on the green synthesis of nitrogen-doped graphene quantum dots (GQDs) for dual-mode bioimaging with X-ray fluorescence (XRF) and optical fluorescence. Both conventional and microwave- (MW-)assisted solvothermal methods were followed to investigate the precursors’ effect on the synthesized GQDs. The MW-assisted method permitted the synthesis of uniform GQDs with an excitation-independent behavior, due to highly controllable reaction conditions. It was demonstrated that the molecular structure of the precursors influenced the optical fluorescence properties of the GQDs. Thus, both blue- (BQDs) and red-emitting (RQDs) GQDs were obtained by selecting specific precursors, leading to emission maxima at 438 and 605 nm under the excitation wavelengths of 390 and 585 nm, respectively.  Amine-functionalized Rh nanoparticles (NPs) were chosen as the X-ray fluorescence (XRF) active core, synthesized via MW-assisted hydrothermal method with a custom designed sugar ligand as the reducing agent. These NPs were conjugated with BQDs using EDC-NHS treatment. The hybrid Rh-GQDs NPs exhibited green emission (520 nm) under 490 nm excitation and led to a reduced cytotoxicity with respect to bare Rh NPs, highlighting the passivation role of the GQDs via the real-time cell analysis (RTCA) assay. The hybrid complex constituted a multimodal bioimaging contrastagent, tested with confocal microscopy (in vitro) and XRF phantom experiments. / Sedan deras upptäckt har nolldimensionella kvantprickar av grafen (kol) uppmärksammats inom biorelaterade applikationer, särskilt för deras optiska egenskaper, kemiska stabilitet och enkelt modifierbara yta. Denna avhandling fokuserar på en grön syntesmetod av kvävedopade grafen-kvantprickar för bimodal bioavbildning med röntgenfluorescens och optisk fluorescens. Både konventionella och mikrovågs-assisterade solvotermiska syntesmetoder användes för att undersöka metodernas effekt på de syntetiserade kvantprickarna. Den mikrovågs-assisterade metoden möjliggjorde syntes av uniforma kvantprickar med exciteringsoberoende egenskaper på grund av mycket kontrollerbara reaktionsförhållanden. Det demonstrerades att den molekylära strukturen hos prekursorerna påverkade de optiska fluorescensegenskaperna hos grafen-kvantprickarna. Genom att välja specifika prekursorer erhölls kvantprickar som emitterar i både blått och rött ljus, motsvarande emissionsmaxima vid 438 respektive 605 nm under excitering vid 390 respektive 585 nm. Amin-funktionaliserade Rh-nanopartiklar valdes som en aktiv kärna för röntgenfluorescens, syntetiserad genom en mikrovågs-assisterad hydrotermisk metod med en specialdesignad sockerligand som reduktionsmedel. Dessa nanopartiklar konjugerades med blåemitterande kvantprickar genom EDC-NHS-behandling. De hybrida nanopartiklarna uppvisade grön emission (520 nm) under 490 nm excitation och ledde till en minskad cytotoxicitet uppmätt genom cellanalys i realtid (RTCA) jämfört med endast Rh-nanopartiklar, vilket framhävde passiveringsrollen som kvantprickarna spelar. Hybridkomplexet utgjorde ett multimodalt kontrastmedel för bioavbildning, vilket demonstrerades med konfokalmikroskopi (in vitro) och fantomexperiment med röntgenfluorescens.

This project evaluates the ability of terahertz (THz) radiation to differentiate cancerous from non-cancerous human breast lumpectomy and mastectomy tissue. This is done by aiming a narrow-band THz beam at medical samples and measuring reflected power. THz images of specimens from Breast Conservation Surgery (BCS) were created using a gas laser source and mechanical scanning. The design and characterization of this system is discussed in detail. The images were correlated with optical histological micrographs of the same specimens and discrimination values of more than 70% were found for five of the six samples using Receiver Operating Characteristic (ROC) analysis.

?-Conjugated systems have been the focus of study in recent years in order to understand their charge transport and optical properties for use in organic electronic devices, fluorescence bioimaging, sensors, and 3D optical data storage (ODS), among others. As a result, several molecular building blocks have been designed, allowing new frontiers to be realized. While various successful building blocks have been fine-tuned at both the electronic and molecular structure level to provide advanced photophysical and optoelectronic characteristics, the azulene framework has been under-appreciated despite its unique electronic and optical properties. Among several attributes, azulenes are vibrant blue naturally occurring hydrocarbons that exhibit large dipolar character, coupled with stimuli-responsive behavior in acidic environments. Additionally, the non-toxic nature and the accompanying eco-friendly feature of some azulenes, namely guaiazulene, may set the stage to further explore a more "green" route towards photonic and conductive materials. The first part of this dissertation focuses on exploiting guaiazulene as a natural building block for the synthesis of chromophores with varying stimuli-responsiveness. Results described in Chapter 1 show that extending the conjugation of guaiazulene through its seven-membered ring methyl group with aromatic substituents dramatically impacts the optical properties of the guaiazulenium carbocation. Study of these ?–stabilized tropilium ions enabled establishing photophysical structure-property trends for guaiazulene-terminated ?-conjugated analogs under acidic conditions, including absorption, emission, quantum yield, and optical band gap patterns. These results were exploited in the design of a photosensitive polymeric system with potential application in the field of three dimensional (3D) optical data storage (ODS). Chapter 2 describes the use of guaiazulene reactive sites (C-3 and C-4 methyl group) to generate a series of cyclopenta[ef]heptalenes that exhibit strong stimuli-responsive behavior. The approach presents a versatile route that allows for various substrates to be incorporated into the resulting cyclopenta[ef]heptalenes, especially after optimization that led to devising a one-pot reaction toward such tricyclic systems. Examining the UV-vis absorption profiles in neutral and acidic media showed that the extension of conjugation at C(4) of the cyclopenta[ef]heptalene skeleton results in longer absorption maxima and smaller optical energy gaps. Additionally, it was concluded that these systems act as sensitizers of a UV-activated (< 300 nm) photoacid generator (PAG), via intermolecular photoinduced electron transfer (PeT), upon which the PAG undergoes photodecomposition resulting in the generation of acid. In a related study, the guaiazulene methyl group at C-4 was employed to study the linear and nonlinear optical properties of 4-styrylguaiazulenes, having the same ?–donor with varying ?-spacer. It was realized that the conjugation length correlates with the extent of bathochromic shift of the protonated species. On the other hand, a trend of decreasing quantum yield was established for this set of 4-styrylguaiazulenes, which can be explained by the increasingly higher degree of flexibility. The second part of this dissertation presents a comprehensive investigation of the linear photophysical, photochemical, and nonlinear optical properties of diketopyrrolopyrrole (DPP)-based derivatives, including two-photon absorption (2PA), femtosecond transient absorption, stimulated emission spectroscopy, and superfluorescence phenomena. The synthetic feasibility, ease of modification, outstanding robustness, and attractive spectroscopic properties of DPPs have motivated their study for fluorescence microscopy applications, concluding that the prepared DPP's are potentially suitable chromophores for high resolution stimulated emission depletion (STED) microscopy.

In this work, hydrophilic fluorene-based derivatives that contain ethylene oxide substituents, have been synthesized and characterized for potential use as new fluorophores for bioimaging applications and for fluorescence sensing of heavy metals. Symmetrical and unsymmetrical fluorene derivatives based on structural types of acceptor-pi-acceptor, acceptor-pi-donor, and donor-pi-donor were characterized by TGA, UV-vis absorption, fluorescence emission, lifetime, anisotropy, and two-photon absorption (2PA) cross section. They were found to possess high thermal stability, high photostability, high fluorescence quantum yields, and generally large two-photon absorption cross sections, making them quite suitable for new probes in single-photon absorption and two-photon absorption fluorescence microscopy imaging. Novel hydrophilic fluorene derivatives were synthesized from fluorene in multiple steps employing the metal-catalyzed Heck coupling reaction, the Stille reaction, the Sonogashira reaction, the Ullmann condensation reaction, and "click" chemistry. To increase the hydrophilicity of the new compounds, ethylene oxide substituents were utilized for to impart water solubility. An alternative alkylation methodology using ethyleneoxy tosylates was introduced for the synthesis of ethylene oxide-containing fluorene derivatives. Several of these hydrophilic derivatives were incubated into various cell lines as new probes for both conventional and two-photon absorption fluorescence bioimaging. These compounds were biocompatible, exhibiting low cytotoxicity as determined by cell viability studies, and displayed colocalization for selected cellular organelles. In addition, hydrophilic bis(1,2,3-triazolyl)fluorene derivatives were found to exhibit sensitive fluorescence responses in the presence of certain heavy metal, and were selective for sensing zinc and mercury over other a number of other metal ions relevant to living cells or other biological environments. The UV-vis absorption and fluorescence emission spectra of the complexes exhibited a blue-shifted absorption and emission for selective metal chelation upon binding to zinc and mercury(II) ions, resulting in an approximately two-fold enhanced fluorescence response. Fluorescence titration studies revealed that the complexes of 1:2 and 1:3 ligand to metal formed with binding constant values of 108 and 1014 for zinc and mercury ions, respectively. Finally, preliminary experiments were performed to explore the possibility of employing select hydrophilic fluorene-based derivatives in the synthesis of hydrophilic fluorescent gold nanoparticles. Although results are very preliminary, the aim is to use such materials for other biomedical applications, such as surface enhanced scattering resonance and noninvasive photothermal therapy to diagnose and to treat cancers. Thus, this research had led to the discovery of alternative methodologies for synthesis of hydrophilic fluorene derivatives by alkylation with alkyl tosylates and synthesis of hydrophilic fluorescent molecule capped gold nanoparticles. Furthermore, several novel hydrophilic fluorene-based derivatives were synthesized and characterized for their linear and nonlinear photophysical properties, and are now available for further examination of their bioimaging and sensing applications.

This thesis discusses the research, experimental methods, and data gathered for the investigation of a novel method for the diagnosis of melanoma skin cancer. First, a background about human skin tissue is presented. Then, a detailed description of melanoma along with current diagnosis techniques and treatment options are presented. In the experimental methods, the electrical properties of several types of tissue were analyzed, the purpose of which was to discover if a tissue type can be distinguished by its electrical properties alone. This would allow for the diagnosis of melanoma to be done by examining the electrical properties of the suspected tumor and comparing the results to known values of healthy and cancerous skin. After analyzing the data, it was concluded that tissue types can be identified by their electrical properties and it may be possible to diagnose melanoma through this method. Finally, the possibility of using a similar technology and radiofrequency tissue ablation to treat melanoma is presented.

Insight Photonic Solutions Inc. has continued to develop their patented VT-DBR laser design; these wavelength tunable lasers promise marked image-quality and acquisition time improvements in SS-OCT applications. To be well suited for SS-OCT, tunable lasers must be capable of producing a highly linear wavelength sweep across a tuning range well-matched to the medium being imaged; many different tunable lasers used in SS-OCT are compared to identify the optimal solution. This work electrically and spectrally characterizes two completely new all-semiconductor VT-DBR designs to compare, as well. The Neptune VT-DBR, an O-band laser, operates around the 1310 nm range and is a robust solution for many OCT applications. The VTL-2 is the first 1060 nm VT-DBR laser to be demonstrated. It offers improved penetration through water over earlier designs which operate at longer wavelengths (e.g. - 1550 nm and 1310 nm), making it an optimal solution for the relatively deep imaging requirements of the human eye; the non-invasive nature of OCT makes it the ideal imaging technology for ophthalmology. Each laser has five semiconductor P-N junction segments that collectively enable precise akinetic wavelength-tuning (i.e. - the tuning mechanism has no moving parts). In an SS-OCT system utilizing one of these laser packages, the segments are synchronously driven with high speed current signals that achieve the desired wavelength, power, and sweep pattern of the optical output. To validate the laser’s fast tuning response time necessary for its use in SS-OCT, a circuit model of each tuning section is created; each laser section is modeled as a diode with a significant lead inductance. The dynamic resistance, effective capacitance, and lead inductance of this model are measured as a function of bias current and the response time corresponding to each bias condition is determined. Tuning maps, spectral linewidths, and side-mode suppression ratio (SMSR) measurements important to SS-OCT performance are also collected. Measured response times vary from 700 ps to 2 ns for the Neptune and 1.2 to 2.3 ns for the VTL-2. Linewidth measurements range from 9 MHz to 124 MHz for the Neptune and 300 kHz to 2 MHz for the VTL-2. SMSR measurements greater than 38 dB and 40 dB were observed for the Neptune and VTL-2, respectively. Collectively, these results implicate the VT-DBR lasers as ideal tunable sources for use in SS-OCT applications.