Publicação
Optical microsystem for spectroscopy signals extraction applied to gastrointestinal dysplasia detection
| Resumo: | The early detection of gastrointestinal cancer, in the dysplastic stage, is essential to increase the patient survival rate. Spectroscopic techniques, particularly diffuse reflectance and fluorescence, can improve the gastrointestinal dysplasia detection, since these techniques can be used to extract biochemical and morphologic information related with the status of a gastrointestinal tissue. Several research groups have developed prototypes for the extraction of diffuse reflectance and fluorescence signals applied to gastrointestinal cancer detection. Despite their advantages associated with the gastrointestinal cancer identification, they have several disadvantages related with the use of complex, high-cost and sophisticate components such as xenon lamps, lasers, monochromators, optical fibers and high quantum efficiency detectors, which may hamper their wide use as well as their huge clinical value. Therefore, it is of utmost importance to develop a low-cost, miniaturized and minimal invasive microsystem for spectroscopic signals extraction. As a result, in this work it is proposed the implementation of a microsystem, which comprises in a single chip, an optical filter system for selection and extraction of the diffuse reflectance and fluorescence signals in relevant spectral bands, a silicon photodiodes matrix (4×4) and its readout electronics, and miniaturized light emitting diodes. The main applications of this microsystem are: its use as a portable device in a surgery room for inspection of total removing of the cancerous or dysplastic tissue; and its integration with the standard endoscopes and colonoscopes using it as an auxiliary, to the physician, in early gastrointestinal cancer detection. Along this thesis, important steps towards that microsystem implementation were achieved. In a first step experimental measurements were performed, with phantoms representative of the main absorbing, scattering and fluorescence properties of gastrointestinal tissues (containing hemoglobin, polystyrene microspheres to represent collagen fibers, and the fluorophores NADH and Carbostyril 124, the latter representing collagen), in order to study the diffuse reflectance and fluorescence typical spectra and their temperature dependence. Moreover, the viability of using only 16 spectral bands (between 350 and 750 nm) for signals extraction was discussed, proving the feasibility of an optical filter system implementation in the final microsystem. Therefore, it were designed, fabricated and characterized 16 MgO/TiO2 and SiO2/TiO2 based thin-film optical filters. Their characterization performed through optical transmittance, selectivity, profilometry and scanning electron microscopy, allowed understanding the deviations between the simulated characteristics and the ones experimentally obtained. Moreover, the optical filters results showed transmittances ranging from 50% to 90% approximately, and a full width half maximum (FWHM) averaging from 11 nm to 20 nm, which fits the required application. The fabricated optical filters had some deviations considering their simulated characteristics, which can be explained by the complexity of the optical filters design, for example, the materials refractive index dependence with wavelength and thin-film thickness. The diffuse reflectance and fluorescence signals that pass through the optical filters can be measured with an on-chip silicon photodetectors matrix (4×4), based on n+/p-epilayer junction photodiodes with an active area of 100 × 100 µm2, and a light-to-frequency converter, per each photodiode, that enables producing a digital signal with a frequency proportional to the photodiode current. As a result, the design and implementation of a CMOS microsystem comprising these components were performed. The photodiodes characterization showed a responsivity of 200 mA/W at 550 nm, approximately, and the light-to-frequency converter connected to the photodiode showed a linear response (R2>0.99) with a sensitivity of 25 Hz/nA at 550 nm, approximately. The behavior of the current-to-frequency converter, with an external current source directly injected in its input, was also studied allowing to confirm its linearity in the range of currents produced in this application, its power consumption of 1 mW, and its maximum input current, approximately 300 µA. This CMOS approach avoids the need of an expensive readout optical microsystem, since it is possible to integrate the photodiodes and the readout electronics in a small silicon area (275 × 100 µm2 per photodiode and its respective converter). The performance of the implemented microsystem and the fabricated optical filters was evaluated, using phantoms (also containing hemoglobin, polystyrene microspheres, NADH and Carbostyril 124). The obtained results have shown the viability of the microsystem (including the optical filter system) to extract diffuse reflectance and fluorescence signals. Some issues were noted on the sensitivity of the implemented optical setups for the on-chip measurements. However, some solutions were proposed for the remaining problems, specifically the future use of miniaturized light emitting diodes and the direct deposition of the optical filters on the top of the photodetection system. Finally, the direct integration of optical filters on top of the photodiodes was discussed and a new approach was tested. |
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| Autores principais: | Pimenta, Sara Filomena Ribeiro |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | The early detection of gastrointestinal cancer, in the dysplastic stage, is essential to increase the patient survival rate. Spectroscopic techniques, particularly diffuse reflectance and fluorescence, can improve the gastrointestinal dysplasia detection, since these techniques can be used to extract biochemical and morphologic information related with the status of a gastrointestinal tissue. Several research groups have developed prototypes for the extraction of diffuse reflectance and fluorescence signals applied to gastrointestinal cancer detection. Despite their advantages associated with the gastrointestinal cancer identification, they have several disadvantages related with the use of complex, high-cost and sophisticate components such as xenon lamps, lasers, monochromators, optical fibers and high quantum efficiency detectors, which may hamper their wide use as well as their huge clinical value. Therefore, it is of utmost importance to develop a low-cost, miniaturized and minimal invasive microsystem for spectroscopic signals extraction. As a result, in this work it is proposed the implementation of a microsystem, which comprises in a single chip, an optical filter system for selection and extraction of the diffuse reflectance and fluorescence signals in relevant spectral bands, a silicon photodiodes matrix (4×4) and its readout electronics, and miniaturized light emitting diodes. The main applications of this microsystem are: its use as a portable device in a surgery room for inspection of total removing of the cancerous or dysplastic tissue; and its integration with the standard endoscopes and colonoscopes using it as an auxiliary, to the physician, in early gastrointestinal cancer detection. Along this thesis, important steps towards that microsystem implementation were achieved. In a first step experimental measurements were performed, with phantoms representative of the main absorbing, scattering and fluorescence properties of gastrointestinal tissues (containing hemoglobin, polystyrene microspheres to represent collagen fibers, and the fluorophores NADH and Carbostyril 124, the latter representing collagen), in order to study the diffuse reflectance and fluorescence typical spectra and their temperature dependence. Moreover, the viability of using only 16 spectral bands (between 350 and 750 nm) for signals extraction was discussed, proving the feasibility of an optical filter system implementation in the final microsystem. Therefore, it were designed, fabricated and characterized 16 MgO/TiO2 and SiO2/TiO2 based thin-film optical filters. Their characterization performed through optical transmittance, selectivity, profilometry and scanning electron microscopy, allowed understanding the deviations between the simulated characteristics and the ones experimentally obtained. Moreover, the optical filters results showed transmittances ranging from 50% to 90% approximately, and a full width half maximum (FWHM) averaging from 11 nm to 20 nm, which fits the required application. The fabricated optical filters had some deviations considering their simulated characteristics, which can be explained by the complexity of the optical filters design, for example, the materials refractive index dependence with wavelength and thin-film thickness. The diffuse reflectance and fluorescence signals that pass through the optical filters can be measured with an on-chip silicon photodetectors matrix (4×4), based on n+/p-epilayer junction photodiodes with an active area of 100 × 100 µm2, and a light-to-frequency converter, per each photodiode, that enables producing a digital signal with a frequency proportional to the photodiode current. As a result, the design and implementation of a CMOS microsystem comprising these components were performed. The photodiodes characterization showed a responsivity of 200 mA/W at 550 nm, approximately, and the light-to-frequency converter connected to the photodiode showed a linear response (R2>0.99) with a sensitivity of 25 Hz/nA at 550 nm, approximately. The behavior of the current-to-frequency converter, with an external current source directly injected in its input, was also studied allowing to confirm its linearity in the range of currents produced in this application, its power consumption of 1 mW, and its maximum input current, approximately 300 µA. This CMOS approach avoids the need of an expensive readout optical microsystem, since it is possible to integrate the photodiodes and the readout electronics in a small silicon area (275 × 100 µm2 per photodiode and its respective converter). The performance of the implemented microsystem and the fabricated optical filters was evaluated, using phantoms (also containing hemoglobin, polystyrene microspheres, NADH and Carbostyril 124). The obtained results have shown the viability of the microsystem (including the optical filter system) to extract diffuse reflectance and fluorescence signals. Some issues were noted on the sensitivity of the implemented optical setups for the on-chip measurements. However, some solutions were proposed for the remaining problems, specifically the future use of miniaturized light emitting diodes and the direct deposition of the optical filters on the top of the photodetection system. Finally, the direct integration of optical filters on top of the photodiodes was discussed and a new approach was tested. |
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