Οπτικά χαρακτηριστικά κβαντικών τελειών ενσωματωμένων σε υμένια πολυμερούς για χρήση στην ιατρική απεικόνιση
Authors: Σαατσάκης Γεώργιος 
Published: September 2021

Today it has become a reality that quantum dots have great potential for applications in medicine and biology, both in vivo and in vitro, in areas such as pharmacokinetics, biosensors, and bio-imaging. For quantum dots to be realistically used in clinical applications, several issues, such as overall toxicity, must be addressed. The problem with toxicity is mainly related to their chemical composition, especially if they contain heavy metal ions such as Cd and Hg. In order to use quantum dots in clinical applications, they must have little or no toxicity. As a result, the potential risk of quantum biosafety and their ever-increasing potential for use in biomedical applications has raised significant concerns about their toxic effects on living organisms and the environment. However, there are quantum dots with low or even non-toxic compounds in their composition, such as ZnS/Mn2+ and ZnCuInS/ZnS. These quantum dots do not contain Cd, Hg, Pb, Se, Te, As, or any other high toxic compound, thus overcoming the inherent toxicity of other well-studied quantum dots such as CdSe/ZnS. The latter removes a significant barrier towards their clinical use. For the purposes of this doctoral dissertation, quantum dots were studied both in solution form and embedded in thin films. Polymethacrylate methyl (PMMA) was chosen as the primary substrate material for the fabrication of thin films. PMMA is a well-known biocompatible resin widely used in dentistry, ophthalmology and orthopedic surgery. It also has some key features particularly conducive to the current research, such as almost zero scattering and transparency across the visible spectral range. Compared to inorganic glass, PMMA has a higher light transmission, is much lighter, has higher impact resistance, and even more important, it does not filter ultraviolet (UV) radiation. The latter is of great importance as the experimental process for evaluating the optical properties of QDs involves, among other things, the irradiation of prepared samples with ultraviolet radiation. A simple method for the fabrication of thin films was designed. This method included dissolving the QDs in toluene, producing the PMMA in a liquid form by mixing PMMA and MMA, incorporating the QDs into the final PMMA mixture, placing the final mixture in specialized molds and further treating them for removal of residual air, and solidification. During the sample’s fabrication process, care was taken for the proper stirring of the mixture but also for the dissolution of possible aggregations by using sonication and vortex. The assessment of the volume homogeneity and the quality of the final samples were evaluated both by the use of X-rays and scanning electron microscope (SEM). A total of four compound thin films (screens) were prepared with a thickness of 1 mm, with different concentrations of QDs, 1.0, 4.0, 6.0, and 10.0% w/v. For convenience and better understanding, the names QD25, QD100, QD150, and QD250 were given, with the numbers representing the mg of QDs used in each sample. The QDs used in the fabrication of the four samples were ZnCuInS/ZnS, with a particle size of 4-5 nm, and a transmission wavelength of 530±15nm. In order to systematically study the optical properties of the ZnCuInS/ZnS nanoparticles, the prepared thin films of the QD-PMMA compounds were exposed to X-ray and ultraviolet (UV) radiation. Absolute Efficiency (AE) was measured using X-ray radiation, while Energy Quantum Efficiency (EQE) was measured with ultraviolet radiation. The QDs-PMMA samples were exposed to X-rays, with energy ranging from 50 to 130 kVp. An additional 20 mm aluminum filter was inserted into the beam to simulate the changes in the X-ray beam quality when it passes through a human body. An integrating sphere collected the light produced by the samples. A suitable photomultiplier coupled to the integrating sphere converted the produced light into an electrical signal in order to be measured and displayed. Absolute Efficiency (AE) was calculated through the mathematical processing of the produced signal. Absolute Luminescence Efficiency (AE) of ZnCuInS/ZnS tends to decrease when exposed to X-rays with energies from 50 to 130 kVp. Different mechanisms and phenomena justify this behavior, like the intrinsic X-ray to light conversion efficiency, X-ray absorption mechanisms, and the light transmission efficiency, that have been previously analyzed. By increasing the concentration of QDs, the AE tends to increase abruptly up to QD100, while after that point, it seems to reach a plateau where the rise is almost negligible. Different light attenuation mechanisms are responsible for such performance, which among other self-absorption, plays the most significant role.Besides, the spectral compatibility of the fabricated ZnCuInS/ZnS thin films with various contemporary optical detectors used in modern medical imaging modalities has been investigated. Results showed excellent compatibility with various types of photocathodes, CMOS, CCDs, and photocathodes used in flat-panel detectors.The PMMA/QD thin films were studied by X-ray stimulation, both experimentally and theoretically. Assuming that the samples consist of several similar layers of material, a modified mathematical model was used to calculate the fraction of the produced optical photons that passed through these different layers. In order to accurately calculate the produced visible photons, the intrinsic conversion efficiency for the specific QDs was calculated. The calculation of the number of visible photons that reach the output of the thin films (screens) was based on the two following assumptions. First, that half of the photons produced by X-rays are directed forward while the other half backwards, and second, the number of reflections in each transition of visible photons from the exit of one layer of material to the entrance of the next. Having already measured the Absolute Luminescence Efficiency (AE) experimentally, the theoretical and experimental results were directly compared. The results showed an excellent correlation. The accuracy of the predicted values reached 99.5% with the QD250 sample. To accurately determine Energy Quantum Efficiency (EQE), thin films were exposed to ultraviolet radiation. Through two different experimental configurations, it was possible to measure both the forward luminescent light and the backward luminescent light. A UV radiation source with the capability to produce UV photon beams of different intensities was used. The latter was necessary in order to study not only the optical properties of QDs in relation to QD concentration but also in relation to the intensity of the incident UV radiation. Results have shown that in the examined UV energy range, the power of the forward luminescent light is linearly increased by increasing the power of the incident UV radiation. Also, the forward luminescent light production rate is increasing almost linearly up to the concentration of QD150, while after that point, it tends to reach a plateau. UV radiation that penetrated the samples, as well as the reflected UV radiation, were also measured, both for different concentrations of QDs but also for different intensities of the incident UV radiation. UV radiation passed through, only by the QD25 film, by a percentage of approximately 9%. QD100, QD150, and QD250 films were practically impermeable to UV radiation. The percentage of the transmitted UV radiation, i.e., the UV radiation that is ultimately pass through the compound films, is not affected by the power increase of the incident UV radiation. Regarding the intensity of the reflected UV radiation, it ranges from about 2% to approximately 6% of the incident UV radiation, as the quantum dot concentration ranges from 25 mg to 250 mg. Moreover, the intensity of the reflected UV radiation is increasing up to the concentration of QD150, while after that point, it remains virtually unchanged. In order to calculate EQE more accurately, both the reflected UV radiation and the UV radiation that penetrated the samples were subtracted from the incident UV radiation, as they did not contribute to the production of visible photons. Provided that the energy losses are constant and the same for all samples, EQE reached a maximum of 45.52% with the QD250 sample, while beyond the concentration of QD150, EQE saturates. X-ray imaging was incorporated in order to assess the volume homogeneity of the samples macroscopically. For this purpose, a digital mammography system was used with radiation settings of 32 kV and 8 mAs. Scanning Electron Microscopy (SEM) was also incorporated for the corresponding microscopic assessment. From the produced images and by measuring the coefficient variation using a software, it was possible to evaluate the quality of the fabricated thin films, as a measure of the dispersion of QDs. Significant conclusions have been drawn both about the degree of dispersion of QDs in relation to their concentration per sample, but also about the existence of aggregations. Sample images from SEM and X-rays showed an almost uniform distribution and dispersion of nanoparticles. However, the aggregations of QDs, although significantly reduced in the sample with the QD250 due to sonication, were still enough, which means that further optimization of the fabrication method is required. These aggregations can adversely affect the fluorescence efficiency of thin films. Optimizing specific parameters of the fabrication method could lead to QD thin films of any size and shape that could be used for medical imaging applications. Concluding, •The Energy Quantum Efficiency of the ZnCuInS / ZnS quantum dots was found to be greater than 45.52%. This percentage makes this particular quantum dot a high-level UV detector laying the groundwork for future hybrid imaging systems. •ZnCuInS / ZnS quantum dots have excellent compatibility with various types of photocathodes, CMOS, CCD and Flat panels used in modern medical applications. •As for the X-rays, the measurements of the Absolute Luminescence Efficiency of the ZnCuInS / ZnS quantum dots, at the specific concentrations, allow us to assume that it will be very difficult to compete with the existing fluorescent materials used for the detection of X-rays, in the area of classical radiodiagnostics. •On the contrary, with X-ray energies used in mammography, the QD250 thin film has been shown to absorb almost all X-ray photons, indicating that these quantum dots have an excellent absorption profile in this energy range (K-edge peak absorption of nanomaterials within mammographic energy range), thus making it an ideal candidate material for use as a contrast medium in mammography.