Chip CMOS para deteção de hemozoína por refletância ótica

Dissertação de mestrado integrado em Engenharia FísicaAtualmente, a doença da malária provoca ainda a morte de milhares de pessoas em países de baixo poder económico, onde o acesso a técnicas de diagnóstico adequadas é escasso. O projeto apresentado nesta dissertação pretende ultrapassar as limitações dos métodos de diagnóstico atuais, através do desenvolvimento de um dispositivo ótico não invasivo, capaz de detetar a presença do parasita da malária abaixo dos 20 parasitas/μL de glóbulos vermelhos, com melhor desempenho que os métodos disponíveis comercialmente, e sem necessidade de amostras de sangue. A sua operação baseia-se na medida, direcionada para a pele do paciente, de sinais de refletância ótica, na gama espectral entre os 400-800 nm. Assim, propõe-se o desenvolvimento de um sistema em CMOS para deteção e leitura dos sinais de refletância ótica, que possa ser integrado no dispositivo ótico. O sistema desenvolvido inclui uma matriz de dezasseis (4×4) fotodíodos, que convertem a intensidade de luz refletida em corrente elétrica, assim como dezasseis conversores corrente-frequência (IF), um por cada fotodíodo da matriz. As três estruturas de fotodíodos de junção permitidas num processo CMOS (n+/substrato, p+/n-well e n-well/p-substrato) foram simuladas utilizando diferentes tecnologias CMOS (0,18 µm, 0,35 µm e 0,7 µm) através do software COMSOL Multiphysics. De acordo com as simulações efetuadas, o fotodíodo n+/p-substrato é o que apresenta uma maior eficiência quântica na gama espectral de interesse (400 - 800 nm), tendo a tecnologia 0,18 µm apresentado o melhor desempenho. O conversor IF foi projetado na mesma tecnologia 0,18 μm, e os resultados da sua simulação, recorrendo ao software Cadence (Virtuoso) permitiram concluir que cada conversor tem uma escala de conversão linear entre 0,6 pA até aproximadamente 1800 nA, com uma linearidade de R2 = 0,999. Além disso apresenta uma sensibilidade de 4560 Hz/nA, uma resolução de 0,01 nA e uma potência de consumo de 0,94 mW, apresentando ainda uma baixa influência da temperatura no desempenho do circuito. O layout do chip CMOS completo, com cada fotodíodo com uma área ativa de 100 × 100 μm e cada IF com uma área de 1500 µm2, comporta uma área total de 2,25 mm2. As máscaras, Exportadas do layout, foram enviadas para uma fundição de silício para fabrico. Uma vez fabricado, o chip permitirá a integração total do dispositivo proposto, esperando-se que possa contribuir significativamente para o avanço do estado da arte do diagnóstico de malária.Nowadays, malaria still causes the death of thousands of people in countries with low economic power, where the access to adequate diagnostic techniques is scarce. The project presented in this dissertation intends to overcome the limitations of current diagnostic methods, through the development of a non invasive optical device, capable of detecting the presence of the malaria parasite below 20 parasites/μL of red blood cells, with better performance than the methods commercially available, and without the need for blood samples. Its operation is based on the measurement of optical reflectance signals, in the spectral range between 400-800 nm, directly in the patient's skin. Thus, it is proposed the development of a CMOS system for detecting and reading optical reflectance signals, which can be integrated into the targeted optical device. The developed system includes an array of sixteen (4×4) photodiodes, which convert the reflected light intensity into electrical current, as well as sixteen current-frequency (IF) converters, one for each photodiode of the array. The three junction photodiode structures allowed in a CMOS process (n+/substrate, p+/n-well and n well/p-substrate) were simulated using different CMOS technologies (0.18 µm, 0.35 µm and 0.7 µm) via COMSOL Multiphysics software. According to the simulations, the n+/p-substrate photodiode is the one with the highest quantum efficiency in the spectral range of interest (400 - 800 nm), with the 0.18 µm technology showing the best performance. The IF converter was designed using the same 0.18 μm technology. The results of its simulation, using Cadence’s Virtuoso software, allowed to conclude that each converter has a linear conversion scale from 0.6 pA to approximately 1800 nA, with a linearity of R2 = 0.999. Furthermore, it has a sensitivity of 4560 Hz/nA, a resolution of 0.01 nA and a power consumption of 0.94 mW, with a low influence of temperature on the circuit performance. The complete CMOS chip layout, where each photodiode has an active area of 100 × 100 µm, and each IF converter has an area of 1500 µm2 , holds a total area of 2.25 mm2 . The masks, exported from the layout, were sent to a silicon foundry for fabrication. Once manufactured, the chip will allow for the full integration of the proposed device, hoping it will significantly contribute to advancing the state of the art in malaria diagnosis.O trabalho desenvolvido teve o apoio do projeto MalariaChip, NORTE-01-0145-FEDER-028178, financiado pelo Programa Operacional Regional do Norte (NORTE 2020), sob o Acordo de Parceria PORTUGAL 2020, através do Fundo Europeu de Desenvolvimento Regional (FEDER) e pela Fundação para a Ciência e Tecnologia (FCT), IP

Multilayer thin-film optical filters for reflectance-based malaria diagnostics

Malaria diagnosis relies on optical microscopy and/or rapid diagnostic tests based on detecting specific malaria antigens. The clinical sensitivity of these methods is highly dependent on parasite density, with low levels of detection at low parasite density, challenging the worldwide malaria elimination efforts. Therefore, there is a need for diagnostic methods with higher sensitivity, demanding innovative diagnostics devices able to detect malaria at low parasite density and at early stages of the disease. We propose an innovative optical device for malaria diagnosis, based on optical reflectance spectrophotometry, for the detection of parasites through the quantification of haemozoin. For this purpose, a set of eight thin-film optical filters, based on multilayer stacks of MgO/TiO2 and SiO2/TiO2 thin-films, with high transmittance and low full width at half maximum (FWHM) at specific wavelengths, was designed and fully characterized (both numerically and experimentally). A preliminary assessment of its potential to reconstruct the original spectra of red blood cells was performed, both in uninfected and Plasmodium falciparum-infected samples. The obtained results show that, although the experimental filters have a non-ideal performance characteristic, they allow us to distinguish, based on only 8 discrete points in the optical spectrum, between healthy and malaria infected samples, up to a detection limit of 12 parasites/μL of red blood cells. Those results enhance the potential of using such a device for malaria diagnostics, aiming for non-invasiveness.Project NORTE-01-0145-FEDER-028178 funded by NORTE 2020 Portugal Regional Operational Program under PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund and the Fundação para a Ciência e Tecnologia (FCT), IP. This work was also supported by national funds, through the Portuguese FCT, under the reference projects UIDB/04436/2020, UIDP/04436/2020, UIDB/50026/2020 and UIDP/50026/2020, and by the ICVS Scientific Microscopy Platform, member of the national infrastructure PPBIPortuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122). V. Baptista thanks FCT for the SFRH/BD/145427/2019 grant. Maria Isabel Veiga thanks FCT for her contract funding provided through 2020.03113.CEECIND. Susana Catarino thanks FCT for her contract funding provided through 2020.00215.CEECIN

CMOS spectrophotometric microsystem for malaria detection

Objectives: Optical spectrophotometry has been explored to quantify Plasmodium falciparum malaria parasites at low parasitemia, with potential to overcome the limitations of detection in the current diagnostic methods. This work presents the design, simulation and fabrication of a CMOS microelectronic detection system to automatically quantify the presence of malaria parasites in a blood sample. Methods: The designed system is composed by an array of 16 n+/p-substrate silicon junction photodiodes as photodetectors and 16 current to frequency (IF) converters. An optical setup was used to individually and jointly characterize the entire system. Results: The IF converter was simulated and characterized in Cadence Tools using UMC 1180 MM/RF technology rules, featuring a resolution of 0.01 nA, a linearity up to 1800 nA and a sensitivity of 4430 Hz/nA. After fabrication in a silicon foundry, the photodiodes' characterization presented a responsivity peak of 120 mA/W (λ = 570 nm) and a dark current of 7.15 pA at 0 V. Regarding the IF converter, it exhibited high linearity (R2 ≈ 0.999) up to 30 nA, with a sensitivity of 4840 Hz/nA. Furthermore, the microsystem performance was validated using RBCs (Red Blood Cells) infected with P. falciparum and diluted at different parasitemia (12, 25 and 50 parasites/μL). Conclusion: The microsystem was able to distinguish between healthy and infected RBCs, with a sensitivity of 4.5 Hz/parasites.μL -1 . Significance: The developed microsystem presents a competitive result, when compared to the gold standard diagnosis methods, with increased potential for malaria in field diagnosis

A numerical study of the heat distribution generated by a microheater in an organ-on-a-chip chamber

In an organ-on-a-chip (OoC), temperature must be kept stable for a well-controlled and human representative microenvironment. This work presents the numerical simulation of a microheater to be integrated in a polydimethylsiloxane chamber that will comprise an OoC. Numerical simulations were performed to evaluate the heat distribution, considering the fluid flow and its direction, the microheater and substrate materials, and the thickness of the oxide layer (electric insulator), on top of the microheater. Silicon (Si) and glass for the substrate, and platinum (Pt) and aluminium (Al) for the microheater materials were evaluated. Results showed that the Si substrate assured better heat uniformity than glass, although reaching lower temperature values, for the same input power. For the microheater, although Al achieved better heat uniformity than Pt, it needed higher current to reach the same temperatures (ranging from 35-45°C). The oxide layer thickness did not affect the achieved temperature. The Si substrate/Pt microheater microsystem was able to heat the fluid chamber up to the 35-45°C range, with current consumption from 0.06 A to 0.1 A, respectively, showing good heat uniformity and low power consumption. Regarding the fluid flow, the domain temperature decreases as the flow rate increases, for the same actuation conditions. It was also analysed the effect of the flux direction and it was observed that, at 120 μL/min , it did not affect the heat distribution in the chamber.This work has been supported by the project PTDC/EEI-EEE/2846/2021 and partially by 2022.02165.PTDC, through national funds (OE), within the scope of the Scientific Research and Technological Development Projects (IC&DT) program in all scientific domains (PTDC), through the Foundation for Science and Technology, I.P. (FCT, I.P). The authors also acknowledge the partial financial support within the R&D Unit Project Scope: UIDB/04436/2020. Gabriel M. Ferreira thanks FCT for his Ph.D. grant with reference 2022.10519.BD. Paulo Sousa, Vânia Pinto and Susana Catarino thank FCT for their contracts funding provided through 2021.01086.CEECIND, 2021.01087.CEECIND and 2020.00215.CEECIND, respectively

Numerical simulation, fabrication, and characterization of a heating system for integration into an Organ-on-a-Chip

In an organ-on-a-chip (OoC) device, temperature control is essential for a well-controlled and human representative microenvironment. This work presents the design, numerical simulation, fabrication and characterization of three aluminium microheater geometries for temperature control into an OoC device. Two of them are circular-based, with different curvature filleting angles and different line widths, and the third is a Hilbert-based geometry. Numerical simulations in COMSOL Multiphysics were performed to evaluate the heat distribution and power consumption of each resistive microheater, by Joule effect, according to target temperature range needed: 35 ºC (physiological) to 45 ºC (hyperthermia). Those simulated microheaters were fabricated on top of a glass substrate, using standard microfabrication technologies and bonded to a polydimethylsiloxane chamber that will contain the cultured organ model. An infrared thermal camera was used for the experimental heating tests and a proportional–integral–derivative (PID) controller, implemented on a printed circuit board, was used for monitoring and controlling the chamber temperature around its target range. Despite the observed differences between the numerical and experimental power consumption, needed for reaching the target temperatures, the obtained heating distribution and the temperature variations showed a good match for all geometries. Both the numerical and experimental results of the Hilbert-based geometry showed an ellipsoidal heat distribution in the circular culture chamber, which allowed to conclude an impair in the chamber temperature uniformity. Regarding the PID controller of the heating system, it was tested for long periods of time (>12 h) without loss of performance or overheating and the results showed a variation of 0.05 ºC/s during the cooling and 0.02 ºC/s during the heating phases, with a resolution of 1 ºC for temperatures up to 42 ºC, and ~0.5 ºC for temperatures below 38 ºC. Thus, the developed numerical approach enabled to qualitatively predict the performance of different microheater geometries, allowing to optimize the heating system performance, required for integration into an OoCThis work has been supported by the project PTDC/EEI-EEE/2846/ 2021 and partially by 2022.02165. PTDC, through national funds (OE), within the scope of the Scientific Research and Technological Development Projects (IC&DT) program in all scientific domains (PTDC), through the Foundation for Science and Technology, I.P. (FCT, I.P). The authors also acknowledge the partial financial support within the R&D Unit Project Scope: UIDB/04436/2020. Gabriel M. Ferreira thanks FCT for his Ph.D. grant with reference 2022.10519. BD. Paulo Sousa, Vania ˆ Pinto and Susana Catarino thank FCT for their contracts funding provided through 2021.01086. CEECIND, 2021.01087. CEECIND and 2020.00215. CEECIND, respectively. The authors would like to thank Dr. Paulo Mendes for access to the IR camera

Reconfigurable and Ergonomic Smart Desk – An EPS@ISEP 2021 Project

The European Project Semester (EPS) offered by the Instituto Superior de Engenharia do Porto (ISEP) provides engineering, business and product design undergraduates with a project-based learning experience in a multicultural and multidisciplinary teamwork environment. This paper reports the research and development of a reconfigurable and ergonomic three-level desk, for people who live in small spaces, by a multicultural and multidisciplinary team of five students. The main objective of the project was to integrate ethics- and sustainability-driven practices in the design, simulation and test of an ergonomic, transformable desk. The FREE desk proposal aims to create a comfortable and dynamic working environment for people while providing a transformable space for different daily activities. This goal was pursued by designing a reconfigurable product, a smart desk that offers the user three levels of adjustability: bench level, sitting desk level, and standing desk level. The desk includes a folding light-sensor lamp into the table top and an integrated battery, in order to create a proper working space. The selected materials have a low environmental impact. The solution comes with different options regarding the table top lifting mechanism. This paper describes the state-of-the-art research, the ethics, sustainability, and marketing analyses, the design and simulation of the FREE desk as well as the obtained results.This work was partially financed by National Funds through the Portuguese funding agency, FCT - Fundação para a Ciência e a Tecnologia, within project UIDB/50014/2020.info:eu-repo/semantics/publishedVersio

Núcleos de Ensino da Unesp: artigos 2010: volume 4: as disciplinas escolares, os temas transversais e o processo de educação

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved