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The Gas Electron Multiplier (GEM) was introduced by Fabio Sauli in 1997. This technology is broadly used in current and planned High-Energy Physics (HEP) experiments. One of the key components of these detectors is a readout board, which collects charges amplified by GEM foils and transfers them to readout electronics. The commonly used Cartesian XY readout boards are manufactured from the same type of polyamide film used to produce the GEM foils. The manufacturing process utilizes a deep polyimide etching, similar to the Micro Chemical Vias (MCV) etching process, which is protected by patent. The material prepared in this way is glued onto a rigid substrate and mounted in a detector. The production process was developed at CERN, and the technology has been commercialized to a small extent. Consequently, only a few research centers have the ability to make dedicated readout strips readouts. GEM detectors are characterized by a segmented structure that allows the separation of an electron-multiplying structure from a readout. This feature enables the implementation of a new type of charge reading system without the need to interfere with the GEM foil system. A new approach is proposed to simplify production and reduce the costs of GEM detector readout boards. It is based on the concept of segmental readout structures that are manufactured in standard Printed Circuit Board (PCB) technology. The interconnectors and mountings are located on the back of the bottom, so it is possible to place the readout electronics behind the readout plate. The boards are designed in such a way that they can be panelized into a readout with a more extensive active area. The margin between PCBs is minimalized to approximately 200 µm, which is less than 1% of the 70 × 70 mm2 board area, so the active area is as big as possible. Therefore, this solution gives us the ability to further increase the size of a readout by adding additional segments, which reduces the cost of scaling up the detector size. A few research groups have suggested similar solutions that utilize PCB technology, but currently, only detectors with 1D zigzag readouts have been validated and used. The measurement results of other 2D (XY) redouts using PCB technology have not been presented. The measurements shown and discussed in this paper validated the proposed technology. X-ray radiographs were obtained, validating the ability to use this technology to manufacture readout boards for GEM detectors. In opposition to state-of-the-art readouts, the proposed solution can be manufactured by any PCB manufacturer without using MCV-patented technology. This gives the users flexibility in designing and ordering low-cost custom readouts.
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This paper presents the manufacturing procedure and electrical properties of a microstrip line on flexible printed circuit boards (FPCBs) fabricated using the micro pattern transfer printing (MPTP) method for millimeter wave band application. The MPTP method presented herein is compared to the conventional FPCB process based on the degree of insertion loss as it pertains to the cross-sectional shape of the formed microstrip line. Electromagnetic field simulations were performed to confirm that the cross-sectional arch shape fabricated by the MPTP process reduces insertion loss in the high-frequency band. Based on the simulation, the microstrip transmission line was optimized to a width of 217 µm and a length of 30 cm, fabricated on a 50 µm thick poly-cyclohexylene dimethylene terephthalate (PCT) substrate to measure the insertion loss. The insertion loss fabricated using the MPTP method is measured as 0.37 dB/cm at 10 GHz, while the conventional FPCB is measured as 0.66 dB/cm. Through the analysis, it was confirmed that the FPCBs manufactured by the MPTP process show lower insertion loss compared to the conventional FPCBs.
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The Low Temperature Cofired Ceramic (LTCC) technology has proven to be highly suitable for 3D microstructures manufacturing in electronic devices due to its excellent electrical and mechanical properties. In this paper, a novel idea of implementing the LTCC structures into high-energy particle detectors technology is proposed. It can be applied in High Energy Physics (HEP) laboratories, where such sophisticated sensors are constantly exposed to particles of the TeV energy range for many years. The most advanced applications of the concept are based on dedicated gas amplifier systems coupled with readout microstructures. Typically, the readout microstructures are made in the Printed Circuit Boards (PCB) technology and processed in a sophisticated and patent-protected way. This article presents the manufacturing process and parameters of the novel microstructures made in the LTCC technology. The structures were implemented into the high-energy particle detector, and the first results are presented.
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Surface topography has become a powerful tool to control cell behaviors, however, it's still difficult to monitor cellular microenvironment changes during topography-induced cell responses. Here, a dual-functional platform integrating cell alignment with extracellular pH (pHe) measurement is proposed. The platform is fabricated by assembling gold nanorods (AuNRs) into micro pattern via wettability difference interface method, which provides topographical cues and surface-enhanced Raman scattering (SERS) effect for cell alignment and biochemical detection respectively. Results demonstrate that contact guidance and cell morphology changes are achieved by the AuNRs micro pattern, and pHe are also obtained by the changes of SERS spectra during cell alignment, where the pHe near cytoplasm is lower than nucleus, revealing the heterogeneity of extracellular microenvironment. Moreover, a correlation between lower extracellular pH and higher cell migration ability is revealed, and AuNRs micro pattern can differentiate cells with different migration ability, which may be an inheritable character during cell division. Furthermore, mesenchymal stem cells response dramatically to AuNRs micro pattern, showing different morphology and increased pHe level, offering the potential of impacting stem cell differentiation. This approach provides a new idea for the research of cell regulation and response mechanism.
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Ouro , Nanotubos , Análise Espectral Raman/métodos , Microambiente CelularRESUMO
Posterior capsular opacification (PCO) is the most common complication resulting from cataract surgery and limits the long-term postoperative visual outcome. Using Nd:YAG laser-assisted posterior capsulotomy for the clinical treatment of symptomatic PCO increases the risks of complications, such as glaucoma, retinal diseases, uveitis, and intraocular lens (IOL) pitting. Therefore, finding how to prevent PCO development is the subject of active investigations. As a replacement organ, the IOL is implanted into the lens capsule after cataract surgery, but it is also associated with the occurrence of PCO. Using IOL as a medium for PCO prophylaxis is a more facile and efficient method that has demonstrated various clinical application prospects. Thus, scientists have conducted a lot of research on new intraocular lens fabrication methods, such as optimizing IOL materials and design, and IOL surface modification (including plasma/ultraviolet/ozone treatment, chemical grafting, drug loading, coating modification, and layer-by-layer self-assembly methods). This paper summarizes the research progress for different types of intraocular lenses prepared by different surface modifications, including anti-biofouling IOLs, enhanced-adhesion IOLs, micro-patterned IOLs, photothermal IOLs, photodynamic IOLs, and drug-loading IOLs. These modified intraocular lenses inhibit PCO development by reducing the residual intraoperative lens epithelial cells or by regulating the cellular behavior of lens epithelial cells. In the future, more works are needed to improve the biosecurity and therapeutic efficacy of these modified IOLs.
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Human cells are both advanced pharmaceutical drugs and 'drug deliverers'. However, functional control prior to or after cell implantation remains challenging. Micro-patterning cells through geometrically defined adhesion sites allows controlling morphogenesis, polarity, cellular mechanics, proliferation, migration, differentiation, stemness, cell-cell interactions, collective cell behavior, and likely immuno-modulatory properties. Consequently, generating micro-patterned therapeutic cells is a promising idea that has not yet been realized and few if any steps have been undertaken in this direction. This review highlights potential therapeutic applications, summarizes comprehensively the many cell functions that have been successfully controlled through micro-patterning, details the established micro-pattern designs, introduces the available fabrication technologies to the non-specialized reader, and suggests a quality evaluation score. Such a broad review is not yet available but would facilitate the manufacturing of therapeutically patterned cell populations using micro-patterned cell-instructive biomaterials for improved functional control as drug delivery systems in the context of cells as pharmaceutical products.
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Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Diferenciação Celular , Humanos , Preparações FarmacêuticasRESUMO
The production of energetic crystalized micro-patterns by using one-step printing has become a recent trend in energetic materials engineering. We report a direct ink writing (DIW) approach in which micro-scale energetic composites composed of 1,3,5-trinitro-1,3,5-triazinane (RDX) crystals in selected ink formulations of a cellulose acetate butyrate (CAB) matrix are produced based on a direct phase transformation from organic, solvent-based, all-liquid ink. Using the formulated RDX ink and the DIW method, we printed crystalized RDX micro-patterns of various sizes and shapes on silicon wafers. The crystalized RDX micro-patterns contained single crystals on pristine Si wafers while the micro-patterns containing dendrite crystals were produced on UV-ozone (UVO)-treated Si wafers. The printing method and the formulated all-liquid ink make up a simple route for designing and printing energetic micro-patterns for micro-electromechanical systems.
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Body implants and implantable medical devices have dramatically improved and prolonged the life of countless patients. However, our body repair mechanisms have evolved to isolate, reject, or destroy any object that is recognized as foreign to the organism and inevitably mounts a foreign body reaction (FBR). Depending on its severity and chronicity, the FBR can impair implant performance or create severe clinical complications that will require surgical removal and/or replacement of the faulty device. The number of review articles discussing the FBR seems to be proportional to the number of different implant materials and clinical applications and one wonders, what else is there to tell? We will here take the position of a fibrosis researcher (which, coincidentally, we are) to elaborate similarities and differences between the FBR, normal wound healing, and chronic healing conditions that result in the development of peri-implant fibrosis. After giving credit to macrophages in the inflammatory phase of the FBR, we will mainly focus on the activation of fibroblastic cells into matrix-producing and highly contractile myofibroblasts. While fibrosis has been discussed to be a consequence of the disturbed and chronic inflammatory milieu in the FBR, direct activation of myofibroblasts at the implant surface is less commonly considered. Thus, we will provide a perspective how physical properties of the implant surface control myofibroblast actions and accumulation of stiff scar tissue. Because formation of scar tissue at the surface and around implant materials is a major reason for device failure and extraction surgeries, providing implant surfaces with myofibroblast-suppressing features is a first step to enhance implant acceptance and functional lifetime. Alternative therapeutic targets are elements of the myofibroblast mechanotransduction and contractile machinery and we will end with a brief overview on such targets that are considered for the treatment of other organ fibroses.
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Fibroblastos/transplante , Reação a Corpo Estranho/imunologia , Miofibroblastos/citologia , Próteses e Implantes , Reação a Corpo Estranho/metabolismo , Humanos , Macrófagos/metabolismo , Mecanotransdução Celular/imunologia , Miofibroblastos/imunologiaRESUMO
Titanium dioxide (TiO2) is a widely used biomaterial. It is a great challenge to confer antibacterial and antithrombotic properties to TiO2 while maintaining its cell affinity. Here, we developed a new strategy to achieve the above goal by comprehensively controlling the chemical cues and geometrical cues of the surface of TiO2. Using colloidal etching technology and UV irradiation treatment, we obtained the photofunctionalized nano-micro-honeycomb structured TiO2. The honeycomb structured increased the photocatalytic activity of TiO2, which endowed TiO2 with photo-induced superhydrophilicity to inhibit bacterial adhesion. The high photocatalytic activity also induced the strong photocatalytic oxidation of TiO2 surface organic adsorbates to suppress fibrinogen and platelet attachment. In addition, owing to the micropore trapping-isolation effect on the bacteria and the nano-frames' contact guidance effect on the growth and spreading of platelet pseudopods, the honeycomb structure also shows a considerable inhibiting effect on bacterial and platelet adhesion. Therefore, due to the controlled chemical and geometrical cues' synergistic effect, the photo-functionalized TiO2 honeycomb structure shows excellent bacterial-adhesion resistance and antithrombotic properties. More importantly, the photo-functionalized TiO2 honeycomb did not inhibit the adhesion and growth of endothelial cells (ECs) after culturing for 3 d, indicating a good cell affinity that the traditional antifouling surfaces do not possess.
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Células Endoteliais , Titânio , Bactérias , Materiais Biocompatíveis , Titânio/farmacologiaRESUMO
Endothelial extracellular matrix (EC-ECM) modification by decellularization is generally recognized as an effective method for cardiovascular biomaterials to enhance their biocompatibility. However, the now available EC-ECM was mainly secreted by the in vitro cultured endothelial cells which lacked a physiological growth environment in vivo, such as blood flow shear stress (BFSS) acting, thus had a serious defect of biocompatibility. Our previous work markedly improved the biocompatibility of the EC-ECM modified materials by simulating the BFSS acting to control the endothelial cells with hyaluronic acid (HA) micro-pattern. In this contribution, the EC-ECM was further enriched onto the HA micro-pattern via a novel layer-by-layer decellularizatio method. In vitro platelets adhesion/activation, macrophages attachment test and ex vivo blood experiment of New Zealand White Rabbits suggested better blood compatibility and anti-inflammation property of this novel biomimetic ECM surface. The endothelial cells culture tests and in vivo rat subcutaneous implantation also proved its good pro-endothelialization function and tissue compatibility. In summary, the present study demonstrated better biocompatibility of the novel biomimetic ECM surface and its potential application for cardiovascular biomaterials modification.
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Materiais Biomiméticos , Matriz Extracelular/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Teste de Materiais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Plaquetas/citologia , Plaquetas/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/metabolismo , Adesividade Plaquetária/efeitos dos fármacosRESUMO
In this study, two kinds of copper micro-patterned surfaces with different heights were fabricated by using a powder injection molding (PIM) process. The micro-pattern's size was 100 µm, and the gap size was 50 µm. The short micro-pattern's height was 100 µm, and the height of the tall one was 380 µm. A copper powder and wax-polymer-based binder system was used to fabricate the micro-patterned surfaces. The critical heat flux (CHF) and heat transfer coefficient (HTC) during pool-boiling tests were measured with the micro-patterned surfaces and a reference plain copper surface. The CHF of short and tall micro-patterned surfaces were 1434 and 1444 kW/m², respectively, and the plain copper surface's CHF was 1191 kW/m². The HTC of the plain copper surface and the PIM surface with short and tall micro-patterned surfaces were similar in value up to a heat flux 1000 kW/m². Beyond that value, the plain surface quickly reached its CHF, while the HTC of the short micro-patterned surface achieved higher values than that of the tall micro-patterned surface. At CHF, the maximum values of HTC for the short micro-pattern, tall micro-pattern, and the plain copper surface were 68, 58, and 57 kW/m² K.
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A micro pattern is a key component of various functional devices. In the present study, using the poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) mixed material as the direct-writing solution and photographic paper as the flexible insulating substrate, the organic micro patterns of various shapes, such as the curve of the second-order self-similar structure, the helical curve, and the wave curve, were fabricated on the flexible insulating substrate by using the near-field electrohydrodynamic direct-writing method. The effects of process parameters, such as the applied voltage, direct-writing height, flow rate of the injection system, and moving velocity of the substrate, on the width and the conductivity of the organic micro patterns were studied in the near-field electrohydrodynamic direct-writing process. The results show that the width of an organic micro pattern increases with the increase of the applied voltage of the high-voltage power supplier and the flow rate of the injection system under the condition where the three other process parameters remained constant, respectively, while the width of an organic micro pattern decreases with the increase of the direct-writing height and the moving velocity of the flexible substrate, respectively. The fabricated organic microcircuit patterns of the natural drying in air at room temperature were tested by a thin film thermoelectric tester at a detection temperature. The results show that the conductivity of a fabricated organic micro pattern decreases with the increase of the electric field intensity, while the effect of moving velocity and the flow rate on the conductivity is small under the condition where the three other process parameters remained constant.
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Autophagy failure is implicated in age-related human disease. A decrease in the rate of protein degradation through the entire autophagy pathway, i.e., autophagic flux, has been associated with the onset of cellular proteotoxity and cell death. Although the precision control of autophagy as a pharmacological intervention has received major attention, mammalian model systems that enable a dissection of the relationship between autophagic flux and pathway intermediate pool sizes remain largely underexplored. Here, we make use of a micropattern-based fluorescence life cell imaging approach, allowing a high degree of experimental control and cellular geometry constraints. By assessing two autophagy modulators in a system that achieves a similarly raised autophagic flux, we measure their impact on the pathway intermediate pool size, autophagosome velocity, and motion. Our results reveal a differential effect of autophagic flux enhancement on pathway intermediate pool sizes, velocities, and directionality of autophagosome motion, suggesting distinct control over autophagy function. These findings may be of importance for better understanding the fine-tuning autophagic activity and protein degradation proficiency in different cell and tissue types of age-associated pathologies.
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BACKGROUND: Ventilator-associated pneumonia (VAP) is a leading hospital acquired infection in intensive care units despite improved patient care practices and advancements in endotracheal tube (ETT) designs. The ETT provides a conduit for bacterial access to the lower respiratory tract and a substratum for biofilm formation, both of which lead to VAP. A novel microscopic ordered surface topography, the Sharklet micro-pattern, has been shown to decrease surface attachment of numerous microorganisms, and may provide an alternative strategy for VAP prevention if included on the surface of an ETT. To evaluate the feasibility of this micro-pattern for this application, the microbial range of performance was investigated in addition to biofilm studies with and without a mucin-rich medium to simulate the tracheal environment in vitro. METHODS: The top five pathogens associated with ETT-related pneumonia, Methicillin-Resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Klebsiella pneumonia, Acinetobacter baumannii, and Escherichia coli, were evaluated for attachment to micro-patterned and un-patterned silicone surfaces in a short-term colonization assay. Two key pathogens, MRSA and Pseudomonas aeruginosa, were evaluated for biofilm formation in a nutrient rich broth for four days and minimal media for 24 hours, respectively, on each surface type. P. aeruginosa was further evaluated for biofilm formation on each surface type in a mucin-modified medium mimicking tracheal mucosal secretions. Results are reported as percent reductions and significance is based on t-tests and ANOVA models of log reductions. All experiments were replicated at least three times. RESULTS: Micro-patterned surfaces demonstrated reductions in microbial colonization for a broad range of species, with up to 99.9% (p < 0.05) reduction compared to un-patterned controls. Biofilm formation was also reduced, with 67% (p = 0.12) and 52% (p = 0.05) reductions in MRSA and P. aeruginosa biofilm formation, respectively. Further, a 58% (p < 0.01) reduction was demonstrated on micro-patterned surfaces for P. aeruginosa biofilms under clinically-simulated conditions when compared to un-patterned controls. CONCLUSIONS: This engineered micro-pattern reduces the colonization and biofilm formation of key VAP-associated pathogens in vitro. Future application of this micro-pattern on endotracheal tubes may prevent or prolong the onset of VAP without the need for antimicrobial agents.