Ivezic, Nenad; Potok, Thomas E.
2003-09-30
A method for automatically evaluating a manufacturing technique comprises the steps of: receiving from a user manufacturing process step parameters characterizing a manufacturing process; accepting from the user a selection for an analysis of a particular lean manufacturing technique; automatically compiling process step data for each process step in the manufacturing process; automatically calculating process metrics from a summation of the compiled process step data for each process step; and, presenting the automatically calculated process metrics to the user. A method for evaluating a transition from a batch manufacturing technique to a lean manufacturing technique can comprise the steps of: collecting manufacturing process step characterization parameters; selecting a lean manufacturing technique for analysis; communicating the selected lean manufacturing technique and the manufacturing process step characterization parameters to an automatic manufacturing technique evaluation engine having a mathematical model for generating manufacturing technique evaluation data; and, using the lean manufacturing technique evaluation data to determine whether to transition from an existing manufacturing technique to the selected lean manufacturing technique.
Method for distributed agent-based non-expert simulation of manufacturing process behavior
Ivezic, Nenad; Potok, Thomas E.
2004-11-30
A method for distributed agent based non-expert simulation of manufacturing process behavior on a single-processor computer comprises the steps of: object modeling a manufacturing technique having a plurality of processes; associating a distributed agent with each the process; and, programming each the agent to respond to discrete events corresponding to the manufacturing technique, wherein each discrete event triggers a programmed response. The method can further comprise the step of transmitting the discrete events to each agent in a message loop. In addition, the programming step comprises the step of conditioning each agent to respond to a discrete event selected from the group consisting of a clock tick message, a resources received message, and a request for output production message.
NASA Astrophysics Data System (ADS)
Iwamura, Koji; Kuwahara, Shinya; Tanimizu, Yoshitaka; Sugimura, Nobuhiro
Recently, new distributed architectures of manufacturing systems are proposed, aiming at realizing more flexible control structures of the manufacturing systems. Many researches have been carried out to deal with the distributed architectures for planning and control of the manufacturing systems. However, the human operators have not yet been discussed for the autonomous components of the distributed manufacturing systems. A real-time scheduling method is proposed, in this research, to select suitable combinations of the human operators, the resources and the jobs for the manufacturing processes. The proposed scheduling method consists of following three steps. In the first step, the human operators select their favorite manufacturing processes which they will carry out in the next time period, based on their preferences. In the second step, the machine tools and the jobs select suitable combinations for the next machining processes. In the third step, the automated guided vehicles and the jobs select suitable combinations for the next transportation processes. The second and third steps are carried out by using the utility value based method and the dispatching rule-based method proposed in the previous researches. Some case studies have been carried out to verify the effectiveness of the proposed method.
Lively, Brooks; Kumar, Sandeep; Tian, Liu; Li, Bin; Zhong, Wei-Hong
2011-05-01
In this study we report the advantages of a 2-step method that incorporates an additional process pre-conditioning step for rapid and precise blending of the constituents prior to the commonly used melt compounding method for preparing polycarbonate/oxidized carbon nanofiber composites. This additional step (equivalent to a manufacturing cell) involves the formation of a highly concentrated solid nano-nectar of polycarbonate/carbon nanofiber composite using a solution mixing process followed by melt mixing with pure polycarbonate. This combined method yields excellent dispersion and improved mechanical and thermal properties as compared to the 1-step melt mixing method. The test results indicated that inclusion of carbon nanofibers into composites via the 2-step method resulted in dramatically reduced ( 48% lower) coefficient of thermal expansion compared to that of pure polycarbonate and 30% lower than that from the 1-step processing, at the same loading of 1.0 wt%. Improvements were also found in dynamic mechanical analysis and flexural mechanical properties. The 2-step approach is more precise and leads to better dispersion, higher quality, consistency, and improved performance in critical application areas. It is also consistent with Lean Manufacturing principles in which manufacturing cells are linked together using less of the key resources and creates a smoother production flow. Therefore, this 2-step process can be more attractive for industry.
Wang, Chen; Lv, Shidong; Wu, Yuanshuang; Lian, Ming; Gao, Xuemei; Meng, Qingxiong
2016-10-01
Biluochun is a typical non-fermented tea and is also famous for its unique aroma in China. Few studies have been performed to evaluate the effect of the manufacturing process on the formation and content of its aroma. The volatile components were extracted at different manufacturing process steps of Biluochun green tea using fully automated headspace solid-phase microextraction (HS-SPME) and further characterised by gas chromatography-mass spectrometry (GC-MS). Among 67 volatile components collected, the fractions of linalool oxides, β-ionone, phenylacetaldehyde, aldehydes, ketones, and nitrogen compounds were increased while alcohols and hydrocarbons declined during the manufacturing process. The aroma compounds decreased the most during the drying steps. We identified a number of significantly changed components that can be used as markers and quality control during the producing process of Biluochun. The drying step played a major role in the aroma formation of green tea products and should be the most important step for quality control. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.
Byrn, Stephen; Futran, Maricio; Thomas, Hayden; Jayjock, Eric; Maron, Nicola; Meyer, Robert F; Myerson, Allan S; Thien, Michael P; Trout, Bernhardt L
2015-03-01
We describe the key issues and possibilities for continuous final dosage formation, otherwise known as downstream processing or drug product manufacturing. A distinction is made between heterogeneous processing and homogeneous processing, the latter of which is expected to add more value to continuous manufacturing. We also give the key motivations for moving to continuous manufacturing, some of the exciting new technologies, and the barriers to implementation of continuous manufacturing. Continuous processing of heterogeneous blends is the natural first step in converting existing batch processes to continuous. In heterogeneous processing, there are discrete particles that can segregate, versus in homogeneous processing, components are blended and homogenized such that they do not segregate. Heterogeneous processing can incorporate technologies that are closer to existing technologies, where homogeneous processing necessitates the development and incorporation of new technologies. Homogeneous processing has the greatest potential for reaping the full rewards of continuous manufacturing, but it takes long-term vision and a more significant change in process development than heterogeneous processing. Heterogeneous processing has the detriment that, as the technologies are adopted rather than developed, there is a strong tendency to incorporate correction steps, what we call below "The Rube Goldberg Problem." Thus, although heterogeneous processing will likely play a major role in the near-term transformation of heterogeneous to continuous processing, it is expected that homogeneous processing is the next step that will follow. Specific action items for industry leaders are. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-15
... appropriate steps during the manufacturing process to prevent cross-contamination of finished pharmaceuticals... implementing appropriate steps during the manufacturing process to prevent cross-contamination of finished... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0104...
Optimum processing of mammographic film.
Sprawls, P; Kitts, E L
1996-03-01
Underprocessing of mammographic film can result in reduced contrast and visibility of breast structures and an unnecessary increase in radiation dose to the patient. Underprocessing can be caused by physical factors (low developer temperature, inadequate development time, insufficient developer agitation) or chemical factors (developer not optimized for film type; overdiluted, underreplenished, contaminated, or frequently changed developer). Conventional quality control programs are designed to produce consistent processing but do not address the issue of optimum processing. Optimum processing is defined as the level of processing that produces the film performance characteristics (contrast and sensitivity) specified by the film manufacturer. Optimum processing of mammographic film can be achieved by following a two-step protocol. The first step is to set up the processing conditions according to recommendations from the film and developer chemistry manufacturers. The second step is to verify the processing results by comparing them with sensitometric data provided by the film manufacturer.
NASA Astrophysics Data System (ADS)
Korshunov, G. I.; Petrushevskaya, A. A.; Lipatnikov, V. A.; Smirnova, M. S.
2018-03-01
The strategy of quality of electronics insurance is represented as most important. To provide quality, the processes sequence is considered and modeled by Markov chain. The improvement is distinguished by simple database means of design for manufacturing for future step-by-step development. Phased automation of design and digital manufacturing electronics is supposed. The MatLab modelling results showed effectiveness increase. New tools and software should be more effective. The primary digital model is proposed to represent product in the processes sequence from several processes till the whole life circle.
Byrn, Stephen; Futran, Maricio; Thomas, Hayden; Jayjock, Eric; Maron, Nicola; Meyer, Robert F; Myerson, Allan S; Thien, Michael P; Trout, Bernhardt L
2015-03-01
We describe the key issues and possibilities for continuous final dosage formation, otherwise known as downstream processing or drug product manufacturing. A distinction is made between heterogeneous processing and homogeneous processing, the latter of which is expected to add more value to continuous manufacturing. We also give the key motivations for moving to continuous manufacturing, some of the exciting new technologies, and the barriers to implementation of continuous manufacturing. Continuous processing of heterogeneous blends is the natural first step in converting existing batch processes to continuous. In heterogeneous processing, there are discrete particles that can segregate, versus in homogeneous processing, components are blended and homogenized such that they do not segregate. Heterogeneous processing can incorporate technologies that are closer to existing technologies, where homogeneous processing necessitates the development and incorporation of new technologies. Homogeneous processing has the greatest potential for reaping the full rewards of continuous manufacturing, but it takes long-term vision and a more significant change in process development than heterogeneous processing. Heterogeneous processing has the detriment that, as the technologies are adopted rather than developed, there is a strong tendency to incorporate correction steps, what we call below "The Rube Goldberg Problem." Thus, although heterogeneous processing will likely play a major role in the near-term transformation of heterogeneous to continuous processing, it is expected that homogeneous processing is the next step that will follow. Specific action items for industry leaders are: Form precompetitive partnerships, including industry (pharmaceutical companies and equipment manufacturers), government, and universities. These precompetitive partnerships would develop case studies of continuous manufacturing and ideally perform joint-technology development, including development of small-scale equipment and processes. Develop ways to invest internally in continuous manufacturing. How best to do this will depend on the specifics of a given organization, in particular the current development projects. Upper managers will need to energize their process developers to incorporate continuous manufacturing in at least part of their processes to gain experience and demonstrate directly the benefits. Training of continuous manufacturing technologies, organizational approaches, and regulatory approaches is a key area that industrial leaders should pursue together. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
Kim, Sumin
2010-04-15
This paper assesses the reproducibility of testing formaldehyde and TVOC emission behavior from wood flooring composites bonded by urea-formaldehyde resin at various manufacturing steps for surface finishing materials. The surface adhesion step of laminate flooring for this research was divided into two steps; HDF only and HDF with LPMs. In the case of engineered flooring, the manufacturing steps were divided into three steps; plywood only, fancy veneer bonded on plywood and UV coated on fancy veneer with plywood. Formaldehyde and VOCs emission decreased at the process of final surface finishing materials; LPMs were applied on the surface of HDF for laminate flooring. Although emissions increased when fancy veneer was bonded onto plywood in the case of engineered flooring, emission was dramatically reduced up to similar level with plywood only when final surface finishing; UV-curable coating was applied on fancy veneer. This study suggests that formaldehyde and VOCs emission from floorings can be controlled at manufacturing steps for surface finishing. 2009 Elsevier B.V. All rights reserved.
Manufacturing challenges in the commercial production of recombinant coagulation factor VIII.
Jiang, R; Monroe, T; McRogers, R; Larson, P J
2002-03-01
Advances in gene technology have led to the development of a method to manufacture recombinant coagulation Factor VIII (rFVIII) for haemophilia A. Because rFVIII is a large and complex protein, its commercialization has required that many challenges in manufacturing, purification and processing be overcome. In order to license the first generation of rFVIII (Kogenate) in 1993, Bayer Corporation invested over 10 years in research and manufacturing development. Seven additional years were subsequently devoted to research and manufacturing improvements in order to accomplish the recent licensing of a second rFVIII product (KOGENATE Bayer or Kogenate FS). This product differs from its predecessor, in that human albumin is removed from the purification and the formulation steps. In addition, fewer chromatography steps are involved resulting in greater yields per mL of conditioned medium, and a solvent-detergent viral inactivation step replaces the heat-processing step used for the previous product. Despite these changes in the manufacturing, the protein backbone and carbohydrate structure of the final rFVIII molecule are identical. The complexity of the production processes is reflected by over 100 000 manufacturing data entries and by 600 quality control tests for each batch of rFVIII. Manufacturers are continuing to develop the next generation of rFVIII, which will be produced without the addition of any human or animal proteins or byproducts. Investments in research, development and manufacturing technology are expected to result in the development of new products with enhanced safety profiles, and in an increase in the production capacity for products that are chronically in short supply.
New Nomenclatures for Heat Treatments of Additively Manufactured Titanium Alloys
NASA Astrophysics Data System (ADS)
Baker, Andrew H.; Collins, Peter C.; Williams, James C.
2017-07-01
The heat-treatment designations and microstructure nomenclatures for many structural metallic alloys were established for traditional metals processing, such as casting, hot rolling or forging. These terms do not necessarily apply for additively manufactured (i.e., three-dimensionally printed or "3D printed") metallic structures. The heat-treatment terminology for titanium alloys generally implies the heat-treatment temperatures and their sequence relative to a thermomechanical processing step (e.g., forging, rolling). These designations include: β-processing, α + β-processing, β-annealing, duplex annealing and mill annealing. Owing to the absence of a thermomechanical processing step, these traditional designations can pose a problem when titanium alloys are first produced via additive manufacturing, and then heat-treated. This communication proposes new nomenclatures for heat treatments of additively manufactured titanium alloys, and uses the distinct microstructural features to provide a correlation between traditional nomenclature and the proposed nomenclature.
UOE Pipe Manufacturing Process Simulation: Equipment Designing and Construction
NASA Astrophysics Data System (ADS)
Delistoian, Dmitri; Chirchor, Mihael
2017-12-01
UOE pipe manufacturing process influence directly on pipeline resilience and operation capacity. At present most spreaded pipe manufacturing method is UOE. This method is based on cold forming. After each technological step appears a certain stress and strain level. For pipe stress strain study is designed and constructed special equipment that simulate entire technological process.UOE pipe equipment is dedicated for manufacturing of longitudinally submerged arc welded DN 400 (16 inch) steel pipe.
Perfusion mammalian cell culture for recombinant protein manufacturing - A critical review.
Bielser, Jean-Marc; Wolf, Moritz; Souquet, Jonathan; Broly, Hervé; Morbidelli, Massimo
The manufacturing of recombinant protein is traditionally divided in two main steps: upstream (cell culture and synthesis of the target protein) and downstream (purification and formulation of the protein into a drug substance or drug product). Today, cost pressure, market uncertainty and market growth, challenge the existing manufacturing technologies. Leaders in the field are active in designing the process of the future and continuous manufacturing is recurrently mentioned as a potential solution to address some of the current limitations. This review focuses on the application of continuous processing to the first step of the manufacturing process. Enabling technologies and operation modes are described in the first part. In the second part, recent advances in the field that have the potential to support its successful future development are critically discussed. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Reducing the stair step effect of layer manufactured surfaces by ball burnishing
NASA Astrophysics Data System (ADS)
Hiegemann, Lars; Agarwal, Chiranshu; Weddeling, Christian; Tekkaya, A. Erman
2016-10-01
The layer technology enables fast and flexible additive manufacturing of forming tools. The disadvantages of this system is the formation of stair steps in the range of tool radii. Within this work a new method to smooth this stair steps by ball burnishing is introduced. This includes studies on the general feasibility of the process and the determination of the influence of the rolling parameters. The investigations are carried out experimentally and numerically. Ultimately, the gained knowledge is applied to finish a deep drawing tool which is manufactured by layer technology.
Comparability of automated human induced pluripotent stem cell culture: a pilot study.
Archibald, Peter R T; Chandra, Amit; Thomas, Dave; Chose, Olivier; Massouridès, Emmanuelle; Laâbi, Yacine; Williams, David J
2016-12-01
Consistent and robust manufacturing is essential for the translation of cell therapies, and the utilisation automation throughout the manufacturing process may allow for improvements in quality control, scalability, reproducibility and economics of the process. The aim of this study was to measure and establish the comparability between alternative process steps for the culture of hiPSCs. Consequently, the effects of manual centrifugation and automated non-centrifugation process steps, performed using TAP Biosystems' CompacT SelecT automated cell culture platform, upon the culture of a human induced pluripotent stem cell (hiPSC) line (VAX001024c07) were compared. This study, has demonstrated that comparable morphologies and cell diameters were observed in hiPSCs cultured using either manual or automated process steps. However, non-centrifugation hiPSC populations exhibited greater cell yields, greater aggregate rates, increased pluripotency marker expression, and decreased differentiation marker expression compared to centrifugation hiPSCs. A trend for decreased variability in cell yield was also observed after the utilisation of the automated process step. This study also highlights the detrimental effect of the cryopreservation and thawing processes upon the growth and characteristics of hiPSC cultures, and demonstrates that automated hiPSC manufacturing protocols can be successfully transferred between independent laboratories.
Eon-duval, Alex; Valax, Pascal; Solacroup, Thomas; Broly, Hervé; Gleixner, Ralf; Strat, Claire L E; Sutter, James
2012-10-01
The article describes how Quality by Design principles can be applied to the drug substance manufacturing process of an Fc fusion protein. First, the quality attributes of the product were evaluated for their potential impact on safety and efficacy using risk management tools. Similarly, process parameters that have a potential impact on critical quality attributes (CQAs) were also identified through a risk assessment. Critical process parameters were then evaluated for their impact on CQAs, individually and in interaction with each other, using multivariate design of experiment techniques during the process characterisation phase. The global multi-step Design Space, defining operational limits for the entire drug substance manufacturing process so as to ensure that the drug substance quality targets are met, was devised using predictive statistical models developed during the characterisation study. The validity of the global multi-step Design Space was then confirmed by performing the entire process, from cell bank thawing to final drug substance, at its limits during the robustness study: the quality of the final drug substance produced under different conditions was verified against predefined targets. An adaptive strategy was devised whereby the Design Space can be adjusted to the quality of the input material to ensure reliable drug substance quality. Finally, all the data obtained during the process described above, together with data generated during additional validation studies as well as manufacturing data, were used to define the control strategy for the drug substance manufacturing process using a risk assessment methodology. Copyright © 2012 Wiley-Liss, Inc.
NASA Astrophysics Data System (ADS)
Harkrider, Curtis Jason
2000-08-01
The incorporation of gradient-index (GRIN) material into optical systems offers novel and practical solutions to lens design problems. However, widespread use of gradient-index optics has been limited by poor correlation between gradient-index designs and the refractive index profiles produced by ion exchange between glass and molten salt. Previously, a design-for- manufacture model was introduced that connected the design and fabrication processes through use of diffusion modeling linked with lens design software. This project extends the design-for-manufacture model into a time- varying boundary condition (TVBC) diffusion model. TVBC incorporates the time-dependent phenomenon of melt poisoning and introduces a new index profile control method, multiple-step diffusion. The ions displaced from the glass during the ion exchange fabrication process can reduce the total change in refractive index (Δn). Chemical equilibrium is used to model this melt poisoning process. Equilibrium experiments are performed in a titania silicate glass and chemically analyzed. The equilibrium model is fit to ion concentration data that is used to calculate ion exchange boundary conditions. The boundary conditions are changed purposely to control the refractive index profile in multiple-step TVBC diffusion. The glass sample is alternated between ion exchange with a molten salt bath and annealing. The time of each diffusion step can be used to exert control on the index profile. The TVBC computer model is experimentally verified and incorporated into the design- for-manufacture subroutine that runs in lens design software. The TVBC design-for-manufacture model is useful for fabrication-based tolerance analysis of gradient-index lenses and for the design of manufactureable GRIN lenses. Several optical elements are designed and fabricated using multiple-step diffusion, verifying the accuracy of the model. The strength of multiple-step diffusion process lies in its versatility. An axicon, imaging lens, and curved radial lens, all with different index profile requirements, are designed out of a single glass composition.
21 CFR 111.80 - What representative samples must you collect?
Code of Federal Regulations, 2010 CFR
2010-04-01
... Process Control System § 111.80 What representative samples must you collect? The representative samples... unique lot within each unique shipment); (b) Representative samples of in-process materials for each manufactured batch at points, steps, or stages, in the manufacturing process as specified in the master...
Diode step stress program for JANTX1N5615
NASA Technical Reports Server (NTRS)
1979-01-01
The effect of power/temperature step stress when applied to the switching diode JANTX1N5615 manufactured by Semtech and Micro semiconductor was examined. A total of 48 samples from each manufacturer were submitted to the process. In addition, two control sample units were maintained for verification of the electrical parametric testing. All test samples were subjected to the electrical tests after completing the prior power/temperature step stress point. Results are presented.
Transistor step stress testing program for JANTX2N2905A
NASA Technical Reports Server (NTRS)
1979-01-01
The effect of power/temperature step stress when applied to the transistor JANTX2N2905A manufactured by Texas Instruments and Motorola is reported. A total of 48 samples from each manufacturer was submitted to the process outlined. In addition, two control sample units were maintained for verification of the electrical parametric testing. All test samples were subjected to the electrical tests outlined in Table 2 after completing the prior power/temperature step stress point.
Rapid prototype extruded conductive pathways
Bobbitt, III, John T.
2016-06-21
A process of producing electrically conductive pathways within additively manufactured parts and similar parts made by plastic extrusion nozzles. The process allows for a three-dimensional part having both conductive and non-conductive portions and allows for such parts to be manufactured in a single production step.
Transistor step stress testing program for JANTX2N2484
NASA Technical Reports Server (NTRS)
1979-01-01
The effect of power/temperature step stress when applied to the transistor JANTX2N2484, manufactured by Raytheon and Teledyne was evaluated. Forty-eight samples from each manufacturer were divided equally (16 per group) into three groups and submitted to the processes outlined. In addition, two control sample units were maintained for verification of the electrical parametric testing.
Additive Manufacturing Design Considerations for Liquid Engine Components
NASA Technical Reports Server (NTRS)
Whitten, Dave; Hissam, Andy; Baker, Kevin; Rice, Darron
2014-01-01
The Marshall Space Flight Center's Propulsion Systems Department has gained significant experience in the last year designing, building, and testing liquid engine components using additive manufacturing. The department has developed valve, duct, turbo-machinery, and combustion device components using this technology. Many valuable lessons were learned during this process. These lessons will be the focus of this presentation. We will present criteria for selecting part candidates for additive manufacturing. Some part characteristics are 'tailor made' for this process. Selecting the right parts for the process is the first step to maximizing productivity gains. We will also present specific lessons we learned about feature geometry that can and cannot be produced using additive manufacturing machines. Most liquid engine components were made using a two-step process. The base part was made using additive manufacturing and then traditional machining processes were used to produce the final part. The presentation will describe design accommodations needed to make the base part and lessons we learned about which features could be built directly and which require the final machine process. Tolerance capabilities, surface finish, and material thickness allowances will also be covered. Additive Manufacturing can produce internal passages that cannot be made using traditional approaches. It can also eliminate a significant amount of manpower by reducing part count and leveraging model-based design and analysis techniques. Information will be shared about performance enhancements and design efficiencies we experienced for certain categories of engine parts.
McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D
2014-01-01
Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. PMID:24811361
DOE Office of Scientific and Technical Information (OSTI.GOV)
Popova, Evdokia; Rodgers, Theron M.; Gong, Xinyi
A novel data science workflow is developed and demonstrated to extract process-structure linkages (i.e., reduced-order model) for microstructure evolution problems when the final microstructure depends on (simulation or experimental) processing parameters. Our workflow consists of four main steps: data pre-processing, microstructure quantification, dimensionality reduction, and extraction/validation of process-structure linkages. These methods that can be employed within each step vary based on the type and amount of available data. In this paper, this data-driven workflow is applied to a set of synthetic additive manufacturing microstructures obtained using the Potts-kinetic Monte Carlo (kMC) approach. Additive manufacturing techniques inherently produce complex microstructures thatmore » can vary significantly with processing conditions. Using the developed workflow, a low-dimensional data-driven model was established to correlate process parameters with the predicted final microstructure. In addition, the modular workflows developed and presented in this work facilitate easy dissemination and curation by the broader community.« less
Popova, Evdokia; Rodgers, Theron M.; Gong, Xinyi; ...
2017-03-13
A novel data science workflow is developed and demonstrated to extract process-structure linkages (i.e., reduced-order model) for microstructure evolution problems when the final microstructure depends on (simulation or experimental) processing parameters. Our workflow consists of four main steps: data pre-processing, microstructure quantification, dimensionality reduction, and extraction/validation of process-structure linkages. These methods that can be employed within each step vary based on the type and amount of available data. In this paper, this data-driven workflow is applied to a set of synthetic additive manufacturing microstructures obtained using the Potts-kinetic Monte Carlo (kMC) approach. Additive manufacturing techniques inherently produce complex microstructures thatmore » can vary significantly with processing conditions. Using the developed workflow, a low-dimensional data-driven model was established to correlate process parameters with the predicted final microstructure. In addition, the modular workflows developed and presented in this work facilitate easy dissemination and curation by the broader community.« less
Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing.
Burcham, Christopher L; Florence, Alastair J; Johnson, Martin D
2018-06-07
The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new chemistries not practical in batch, improved safety, flexible manufacturing platforms, and improved product quality assurance. The transformation from batch to continuous manufacturing processing is the focus of this review. The review is limited to small, chemically synthesized organic molecules and encompasses the manufacture of both active pharmaceutical ingredients (APIs) and the subsequent drug product. Continuous drug product is currently used in approved processes. A few examples of production of APIs under current good manufacturing practice conditions using continuous processing steps have been published in the past five years, but they are lagging behind continuous drug product with respect to regulatory filings.
An Overview of Cloud Implementation in the Manufacturing Process Life Cycle
NASA Astrophysics Data System (ADS)
Kassim, Noordiana; Yusof, Yusri; Hakim Mohamad, Mahmod Abd; Omar, Abdul Halim; Roslan, Rosfuzah; Aryanie Bahrudin, Ida; Ali, Mohd Hatta Mohamed
2017-08-01
The advancement of information and communication technology (ICT) has changed the structure and functions of various sectors and it has also started to play a significant role in modern manufacturing in terms of computerized machining and cloud manufacturing. It is important for industries to keep up with the current trend of ICT for them to be able survive and be competitive. Cloud manufacturing is an approach that wanted to realize a real-world manufacturing processes that will apply the basic concept from the field of Cloud computing to the manufacturing domain called Cloud-based manufacturing (CBM) or cloud manufacturing (CM). Cloud manufacturing has been recognized as a new paradigm for manufacturing businesses. In cloud manufacturing, manufacturing companies need to support flexible and scalable business processes in the shop floor as well as the software itself. This paper provides an insight or overview on the implementation of cloud manufacturing in the modern manufacturing processes and at the same times analyses the requirements needed regarding process enactment for Cloud manufacturing and at the same time proposing a STEP-NC concept that can function as a tool to support the cloud manufacturing concept.
Atomic Step Formation on Sapphire Surface in Ultra-precision Manufacturing
Wang, Rongrong; Guo, Dan; Xie, Guoxin; Pan, Guoshun
2016-01-01
Surfaces with controlled atomic step structures as substrates are highly relevant to desirable performances of materials grown on them, such as light emitting diode (LED) epitaxial layers, nanotubes and nanoribbons. However, very limited attention has been paid to the step formation in manufacturing process. In the present work, investigations have been conducted into this step formation mechanism on the sapphire c (0001) surface by using both experiments and simulations. The step evolutions at different stages in the polishing process were investigated with atomic force microscopy (AFM) and high resolution transmission electron microscopy (HRTEM). The simulation of idealized steps was constructed theoretically on the basis of experimental results. It was found that (1) the subtle atomic structures (e.g., steps with different sawteeth, as well as steps with straight and zigzag edges), (2) the periodicity and (3) the degree of order of the steps were all dependent on surface composition and miscut direction (step edge direction). A comparison between experimental results and idealized step models of different surface compositions has been made. It has been found that the structure on the polished surface was in accordance with some surface compositions (the model of single-atom steps: Al steps or O steps). PMID:27444267
Atomic Step Formation on Sapphire Surface in Ultra-precision Manufacturing
NASA Astrophysics Data System (ADS)
Wang, Rongrong; Guo, Dan; Xie, Guoxin; Pan, Guoshun
2016-07-01
Surfaces with controlled atomic step structures as substrates are highly relevant to desirable performances of materials grown on them, such as light emitting diode (LED) epitaxial layers, nanotubes and nanoribbons. However, very limited attention has been paid to the step formation in manufacturing process. In the present work, investigations have been conducted into this step formation mechanism on the sapphire c (0001) surface by using both experiments and simulations. The step evolutions at different stages in the polishing process were investigated with atomic force microscopy (AFM) and high resolution transmission electron microscopy (HRTEM). The simulation of idealized steps was constructed theoretically on the basis of experimental results. It was found that (1) the subtle atomic structures (e.g., steps with different sawteeth, as well as steps with straight and zigzag edges), (2) the periodicity and (3) the degree of order of the steps were all dependent on surface composition and miscut direction (step edge direction). A comparison between experimental results and idealized step models of different surface compositions has been made. It has been found that the structure on the polished surface was in accordance with some surface compositions (the model of single-atom steps: Al steps or O steps).
Development of a Launch Vehicle Manufacturing Process. Chapter 4
NASA Technical Reports Server (NTRS)
Vickers, John; Munafo, Paul M. (Technical Monitor)
2002-01-01
One of the goals of this chapter is to provide sufficient information so that you can develop a manufacturing process for a potential launch vehicle. With the variety of manufacturing options available, you might ask how this can possibly be done in the span of a single chapter. Actually, it will be quite simple because a basic manufacturing process is nothing more than a set of logical steps that are iterated until they produce a desired product. Although these statements seem simple and logical, don't let this simplicity fool you. Manufacturing problems with launch vehicles and their subassemblies have been the primary cause of project failures because the vehicle concept delivered to the manufacturing floor could not be built as designed.
NASA Astrophysics Data System (ADS)
Luqman, M.; Rosli, M. U.; Khor, C. Y.; Zambree, Shayfull; Jahidi, H.
2018-03-01
Crank arm is one of the important parts in a bicycle that is an expensive product due to the high cost of material and production process. This research is aimed to investigate the potential type of manufacturing process to fabricate composite bicycle crank arm and to describe an approach based on analytical hierarchy process (AHP) that assists decision makers or manufacturing engineers in determining the most suitable process to be employed in manufacturing of composite bicycle crank arm at the early stage of the product development process to reduce the production cost. There are four types of processes were considered, namely resin transfer molding (RTM), compression molding (CM), vacuum bag molding and filament winding (FW). The analysis ranks these four types of process for its suitability in the manufacturing of bicycle crank arm based on five main selection factors and 10 sub factors. Determining the right manufacturing process was performed based on AHP process steps. Consistency test was performed to make sure the judgements are consistent during the comparison. The results indicated that the compression molding was the most appropriate manufacturing process because it has the highest value (33.6%) among the other manufacturing processes.
NASA Astrophysics Data System (ADS)
Delistoian, Dmitri; Chirchor, Mihael
2017-12-01
Fluid transportation from production areas to final customer is effectuated by pipelines. For oil and gas industry, pipeline safety and reliability represents a priority. From this reason, pipe quality guarantee directly influence pipeline designed life, but first of all protects environment. A significant number of longitudinally welded pipes, for onshore/offshore pipelines, are manufactured by UOE method. This method is based on cold forming. In present study, using finite element method is modeled UOE pipe manufacturing process and is obtained von Mises stresses for each step. Numerical simulation is performed for L415 MB (X60) steel plate with 7,9 mm thickness, length 30 mm and width 1250mm, as result it is obtained a DN 400 pipe.
Technology of welding aluminum alloys-II
NASA Technical Reports Server (NTRS)
1978-01-01
Step-by-step procedures were developed for high integrity manual and machine welding of aluminum alloys. Detailed instructions are given for each step with tables and graphs to specify materials and dimensions. Throughout work sequence, processing procedure designates manufacturing verification points and inspection points.
Transistor step stress program for JANTX2N2945A
NASA Technical Reports Server (NTRS)
1979-01-01
Data compiled for the purpose of evaluating the effect of power/temperature step stress when applied to the transistor JANTX2N2945A manufactured by Raytheon and Teledyne is presented. A total of 48 samples from each manufacturer was divided equally (16 per group) into three groups and submitted to the processes outlined. In addition, two control units were maintained for verification of the electrical parametric testing.
McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D
2014-07-01
Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. © 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.
Remote Collaborative 3D Printing - Process Investigation
2016-04-01
transferring, receiving, manipulating, and printing a digital 3D model into an additively manufactured component. Several digital models were...into an additively manufactured component. Several digital models were exchanged, and the steps, barriers, workarounds, and results have been...ABBREVIATIONS ABS Acrylonitrile Butadiene Styrene AM Additive Manufacturing AMRDEC SAFE Aviation and Missile Research Development and Engineering
On-site manufacture of propellant oxygen from lunar resources
NASA Technical Reports Server (NTRS)
Rosenberg, Sanders D.
1992-01-01
The Aerojet Carbothermal Process for the manufacture of oxygen from lunar resources has three essential steps: the reduction of silicate with methane to form carbon monoxide and hydrogen; the reduction of carbon monoxide with hydrogen to form methane and water; and the electrolysis of water to form oxygen and hydrogen. This cyclic process does not depend upon the presence of water or water precursors in the lunar materials; it will produce oxygen from silicates regardless of their precise composition and fine structure. Research on the first step of the process was initiated by determining some of the operating conditions required to reduce igneous rock with carbon and silicon carbide. The initial phase of research on the second step is completed; quantitative conversion of carbon monoxide and hydrogen to methane and water was achieved with a nickel-on-kieselguhr catalyst. The equipment used in and the results obtained from these process studies are reported in detail.
Palmero, Paola; Kern, Frank; Sommer, Frank; Lombardi, Mariangela; Gadow, Rainer; Montanaro, Laura
2014-12-30
Ceramic nanocomposites, containing at least one phase in the nanometric dimension, have received special interest in recent years. They have, in fact, demonstrated increased performance, reliability and lifetime with respect to monolithic ceramics. However, a successful approach to the production of tailored composite nanostructures requires the development of innovative concepts at each step of manufacturing, from the synthesis of composite nanopowders, to their processing and sintering.This review aims to deepen understanding of some of the critical issues associated with the manufacturing of nanocomposite ceramics, focusing on alumina-based composite systems. Two case studies are presented and briefly discussed. The former illustrates the benefits, in terms of sintered microstructure and related mechanical properties, resulting from the application of an engineering approach to a laboratory-scale protocol for the elaboration of nanocomposites in the system alumina-ZrO2-YAG (yttrium aluminium garnet). The latter illustrates the manufacturing of alumina-based composites for large-scale applications such as cutting tools, carried out by an injection molding process. The need for an engineering approach to be applied in all processing steps is demonstrated also in this second case study, where a tailored manufacturing process is required to obtain the desired results.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liddell, Heather; Brueske, Sabine; Carpenter, Alberta
With their high strength-to-weight ratios, fiber-reinforced polymer (FRP) composites are important materials for lightweighting in structural applications; however, manufacturing challenges such as low process throughput and poor quality control can lead to high costs and variable performance, limiting their use in commercial applications. One of the most significant challenges for advanced composite materials is their high manufacturing energy intensity. This study explored the energy intensities of two lightweight FRP composite materials (glass- and carbon-fiber-reinforced polymers), with three lightweight metals (aluminum, magnesium, and titanium) and structural steel (as a reference material) included for comparison. Energy consumption for current typical and state-of-the-artmore » manufacturing processes were estimated for each material, deconstructing manufacturing process energy use by sub-process and manufacturing pathway in order to better understand the most energy intensive steps. Energy saving opportunities were identified and quantified for each production step based on a review of applied R&D technologies currently under development in order to estimate the practical minimum energy intensity. Results demonstrate that while carbon fiber reinforced polymer (CFRP) composites have the highest current manufacturing energy intensity of all materials considered, the large differences between current typical and state-of-the-art energy intensity levels (the 'current opportunity') and between state-of-the-art and practical minimum energy intensity levels (the 'R&D opportunity') suggest that large-scale energy savings are within reach.« less
An update on coating/manufacturing techniques of microneedles.
Tarbox, Tamara N; Watts, Alan B; Cui, Zhengrong; Williams, Robert O
2017-12-29
Recently, results have been published for the first successful phase I human clinical trial investigating the use of dissolving polymeric microneedles… Even so, further clinical development represents an important hurdle that remains in the translation of microneedle technology to approved products. Specifically, the potential for accumulation of polymer within the skin upon repeated application of dissolving and coated microneedles, combined with a lack of safety data in humans, predicates a need for further clinical investigation. Polymers are an important consideration for microneedle technology-from both manufacturing and drug delivery perspectives. The use of polymers enables a tunable delivery strategy, but the scalability of conventional manufacturing techniques could arguably benefit from further optimization. Micromolding has been suggested in the literature as a commercially viable means to mass production of both dissolving and swellable microneedles. However, the reliance on master molds, which are commonly manufactured using resource intensive microelectronics industry-derived processes, imparts notable material and design limitations. Further, the inherently multi-step filling and handling processes associated with micromolding are typically batch processes, which can be challenging to scale up. Similarly, conventional microneedle coating processes often follow step-wise batch processing. Recent developments in microneedle coating and manufacturing techniques are highlighted, including micromilling, atomized spraying, inkjet printing, drawing lithography, droplet-born air blowing, electro-drawing, continuous liquid interface production, 3D printing, and polyelectrolyte multilayer coating. This review provides an analysis of papers reporting on potentially scalable production techniques for the coating and manufacturing of microneedles.
Splendidly blended: a machine learning set up for CDU control
NASA Astrophysics Data System (ADS)
Utzny, Clemens
2017-06-01
As the concepts of machine learning and artificial intelligence continue to grow in importance in the context of internet related applications it is still in its infancy when it comes to process control within the semiconductor industry. Especially the branch of mask manufacturing presents a challenge to the concepts of machine learning since the business process intrinsically induces pronounced product variability on the background of small plate numbers. In this paper we present the architectural set up of a machine learning algorithm which successfully deals with the demands and pitfalls of mask manufacturing. A detailed motivation of this basic set up followed by an analysis of its statistical properties is given. The machine learning set up for mask manufacturing involves two learning steps: an initial step which identifies and classifies the basic global CD patterns of a process. These results form the basis for the extraction of an optimized training set via balanced sampling. A second learning step uses this training set to obtain the local as well as global CD relationships induced by the manufacturing process. Using two production motivated examples we show how this approach is flexible and powerful enough to deal with the exacting demands of mask manufacturing. In one example we show how dedicated covariates can be used in conjunction with increased spatial resolution of the CD map model in order to deal with pathological CD effects at the mask boundary. The other example shows how the model set up enables strategies for dealing tool specific CD signature differences. In this case the balanced sampling enables a process control scheme which allows usage of the full tool park within the specified tight tolerance budget. Overall, this paper shows that the current rapid developments off the machine learning algorithms can be successfully used within the context of semiconductor manufacturing.
Ma, Chengying; Li, Junxing; Chen, Wei; Wang, Wenwen; Qi, Dandan; Pang, Shi; Miao, Aiqing
2018-06-01
Oolong tea is a typical semi-fermented tea and is famous for its unique aroma. The aim of this study was to compare the volatile compounds during manufacturing process to reveal the formation of aroma. In this paper, a method was developed based on head-space solid phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS) combined with chemometrics to assess volatile profiles during manufacturing process (fresh leaves, sun-withered leaves, rocked leaves and leaves after de-enzyming). A total of 24 aroma compounds showing significant differences during manufacturing process were identified. Subsequently, according to these aroma compounds, principal component analysis and hierarchical cluster analysis showed that the four samples were clearly distinguished from each other, which suggested that the 24 identified volatile compounds can represent the changes of volatile compounds during the four steps. Additionally, sun-withering, rocking and de-enzyming can influence the variations of volatile compounds in different degree, and we found the changes of volatile compounds in withering step were less than other two manufacturing process, indicating that the characteristic volatile compounds of oolong tea might be mainly formed in rocking stage by biological reactions and de-enzyming stage through thermal chemical transformations rather than withering stage. This study suggested that HS-SPME/GC-MS combined with chemometrics methods is accurate, sensitive, fast and ideal for rapid routine analysis of the aroma compounds changes in oolong teas during manufacturing processing. Copyright © 2018 Elsevier Ltd. All rights reserved.
A Virtual Environment for Process Management. A Step by Step Implementation
ERIC Educational Resources Information Center
Mayer, Sergio Valenzuela
2003-01-01
In this paper it is presented a virtual organizational environment, conceived with the integration of three computer programs: a manufacturing simulation package, an automation of businesses processes (workflows), and business intelligence (Balanced Scorecard) software. It was created as a supporting tool for teaching IE, its purpose is to give…
Hierarchical modeling of professional skills in the field of castings manufacture engineering
NASA Astrophysics Data System (ADS)
Samuilă, V.; Soporan, V. F.; Conțiu, G.; Pădurețu, S.; Lehene, T. R.; Vescan, M. M.
2017-06-01
The paper presents a method of hierarchizing professional skills in the manufacturing of molded parts (castings) by using and adapting the FAHP algorithm (Fuzzy Analitical Hierarchy Process). Assessments are made regarding the peculiarities of the professional training process, specifying the activities to be carried out and the competences necessary for their development. The contribution of the design of the method extends to the design of the hierarchy system architecture, the linguistic determination of the importance of each characteristic, the construction of the fuzzy ordering matrices for each stage of the process, the determination of the share of the characteristics for each hierarchy step and establishing the hierarchy of the characteristics taking into account the influences of the others, grouped at the level of the steps and within the global matrix. The research carried out represents the support for generating an instrument of hierarchy of professional competencies that can be used in various professional and institutional contexts. Case study on the hierarchy of professional skills in the manufacturing of molded parts engineering. Keywords: Materials engineering, castings manufacture professional skills, hierarchy, AHP method, standard occupational curriculum.
Hümmer, Christiane; Poppe, Carolin; Bunos, Milica; Stock, Belinda; Wingenfeld, Eva; Huppert, Volker; Stuth, Juliane; Reck, Kristina; Essl, Mike; Seifried, Erhard; Bonig, Halvard
2016-03-16
Automation of cell therapy manufacturing promises higher productivity of cell factories, more economical use of highly-trained (and costly) manufacturing staff, facilitation of processes requiring manufacturing steps at inconvenient hours, improved consistency of processing steps and other benefits. One of the most broadly disseminated engineered cell therapy products is immunomagnetically selected CD34+ hematopoietic "stem" cells (HSCs). As the clinical GMP-compliant automat CliniMACS Prodigy is being programmed to perform ever more complex sequential manufacturing steps, we developed a CD34+ selection module for comparison with the standard semi-automatic CD34 "normal scale" selection process on CliniMACS Plus, applicable for 600 × 10(6) target cells out of 60 × 10(9) total cells. Three split-validation processings with healthy donor G-CSF-mobilized apheresis products were performed; feasibility, time consumption and product quality were assessed. All processes proceeded uneventfully. Prodigy runs took about 1 h longer than CliniMACS Plus runs, albeit with markedly less hands-on operator time and therefore also suitable for less experienced operators. Recovery of target cells was the same for both technologies. Although impurities, specifically T- and B-cells, were 5 ± 1.6-fold and 4 ± 0.4-fold higher in the Prodigy products (p = ns and p = 0.013 for T and B cell depletion, respectively), T cell contents per kg of a virtual recipient receiving 4 × 10(6) CD34+ cells/kg was below 10 × 10(3)/kg even in the worst Prodigy product and thus more than fivefold below the specification of CD34+ selected mismatched-donor stem cell products. The products' theoretical clinical usability is thus confirmed. This split validation exercise of a relatively short and simple process exemplifies the potential of automatic cell manufacturing. Automation will further gain in attractiveness when applied to more complex processes, requiring frequent interventions or handling at unfavourable working hours, such as re-targeting of T-cells.
Overview of the production of sintered SiC optics and optical sub-assemblies
NASA Astrophysics Data System (ADS)
Williams, S.; Deny, P.
2005-08-01
The following is an overview on sintered silicon carbide (SSiC) material properties and processing requirements for the manufacturing of components for advanced technology optical systems. The overview will compare SSiC material properties to typical materials used for optics and optical structures. In addition, it will review manufacturing processes required to produce optical components in detail by process step. The process overview will illustrate current manufacturing process and concepts to expand the process size capability. The overview will include information on the substantial capital equipment employed in the manufacturing of SSIC. This paper will also review common in-process inspection methodology and design rules. The design rules are used to improve production yield, minimize cost, and maximize the inherent benefits of SSiC for optical systems. Optimizing optical system designs for a SSiC manufacturing process will allow systems designers to utilize SSiC as a low risk, cost competitive, and fast cycle time technology for next generation optical systems.
Heger, A; Svae, T-E; Neisser-Svae, A; Jordan, S; Behizad, M; Römisch, J
2009-10-01
A new chromatographic step for the selective binding of pathological prion proteins (PrP(Sc)) to an affinity ligand, developed and optimized for PrP(Sc) capture and attached to synthetic resin particles (PRDT, USA; ProMetic BioSciences Ltd, Isle of Man, UK) was implemented into the manufacturing process of the solvent/detergent (S/D) treated biopharmaceutical quality plasma Octaplas. Pilot batches of Octaplas with the implemented chromatographic step [labelled as OctaplasLG (ligand gel)] were manufactured by Octapharma PPGmbH, Vienna, Austria. The biochemical quality was compared directly after manufacturing as well as after 18 months storage. All samples were tested on global coagulation parameters, fibrinogen levels, activities of coagulation factors and protease inhibitors, ADAMTS13 levels, as well as markers of activated coagulation and fibrinolysis. In addition, von Willebrand factor multimeric analysis was performed. The incorporation of this novel chromatography into the large-scale routine manufacturing process was shown to be technically feasible and the performance of the column was assessed to be excellent. The biochemical studies showed that Octaplas and OctaplasLG produced without and with the new column, respectively, demonstrate an identical biochemical quality. OctaplasLG remained stable over a period of 18 months stored frozen. A parallel reduction of the S/D virus inactivation step from 4-4.5 to 1-1.5 h led to significantly higher activities of plasmin inhibitor. The studies confirmed that the affinity ligand chromatography under the developed conditions can be introduced into the Octaplas manufacturing process, as a mean to reduce potentially present PrP(Sc), without hampering the proven quality of this product.
Code of Federal Regulations, 2010 CFR
2010-10-01
..., or other organization that designs, manufactures, assembles, or controls the assembly of a respirator... source of production and at each step of the manufacturing process, so that departures from... respirator component designed to provide a gas-tight or dust-tight fit with the face and may include...
New high-precision deep concave optical surface manufacturing capability
NASA Astrophysics Data System (ADS)
Piché, François; Maloney, Chris; VanKerkhove, Steve; Supranowicz, Chris; Dumas, Paul; Donohue, Keith
2017-10-01
This paper describes the manufacturing steps necessary to manufacture hemispherical concave aspheric mirrors for high- NA systems. The process chain is considered from generation to final figuring and includes metrology testing during the various manufacturing steps. Corning Incorporated has developed this process by taking advantage of recent advances in commercially available Satisloh and QED Technologies equipment. Results are presented on a 100 mm concave radius nearly hemispherical (NA = 0.94) fused silica sphere with a better than 5 nm RMS figure. Part interferometric metrology was obtained on a QED stitching interferometer. Final figure was made possible by the implementation of a high-NA rotational MRF mode recently developed by QED Technologies which is used at Corning Incorporated for production. We also present results from a 75 mm concave radius (NA = 0.88) Corning ULE sphere that was produced using sub-aperture tools from generation to final figuring. This part demonstrates the production chain from blank to finished optics for high-NA concave asphere.
Quality control in the development of coagulation factor concentrates.
Snape, T J
1987-01-01
Limitation of process change is a major factor contributing to assurance of quality in pharmaceutical manufacturing. This is particularly true in the manufacture of coagulation factor concentrates, for which presumptive testing for poorly defined product characteristics is an integral feature of finished product quality control. The development of new or modified preparations requires that this comfortable position be abandoned, and that the effect on finished product characteristics of changes to individual process steps (and components) be assessed. The degree of confidence in the safety and efficacy of the new product will be determined by, amongst other things, the complexity of the process alteration and the extent to which the results of finished product tests can be considered predictive. The introduction of a heat-treatment step for inactivation of potential viral contaminants in coagulation factor concentrates presents a significant challenge in both respects, quite independent of any consideration of assessment of the effectiveness of the viral inactivation step. These interactions are illustrated by some of the problems encountered with terminal dry heat-treatment (72 h. at 80 degrees C) of factor VIII and prothrombin complex concentrates manufactured by the Blood Products Laboratory.
Economic assessment of single-walled carbon nanotube processes
NASA Astrophysics Data System (ADS)
Isaacs, J. A.; Tanwani, A.; Healy, M. L.; Dahlben, L. J.
2010-02-01
The carbon nanotube market is steadily growing and projected to reach 1.9 billion by 2010. This study examines the economics of manufacturing single-walled carbon nanotubes (SWNT) using process-based cost models developed for arc, CVD, and HiPco processes. Using assumed input parameters, manufacturing costs are calculated for 1 g SWNT for arc, CVD, and HiPco, totaling 1,906, 1,706, and 485, respectively. For each SWNT process, the synthesis and filtration steps showed the highest costs, with direct labor as a primary cost driver. Reductions in production costs are calculated for increased working hours per day and for increased synthesis reaction yield (SRY) in each process. The process-based cost models offer a means for exploring opportunities for cost reductions, and provide a structured system for comparisons among alternative SWNT manufacturing processes. Further, the models can be used to comprehensively evaluate additional scenarios on the economics of environmental, health, and safety best manufacturing practices.
One-step manufacturing of innovative flat-knitted 3D net-shape preforms for composite applications
NASA Astrophysics Data System (ADS)
Bollengier, Quentin; Wieczorek, Florian; Hellmann, Sven; Trümper, Wolfgang; Cherif, Chokri
2017-10-01
Mostly due to the cost-intensive manually performed processing operations, the production of complex-shaped fibre reinforced plastic composites (FRPC) is currently very expensive and therefore either restricted to sectors with high added value or for small batch applications (e.g. in the aerospace or automotive industry). Previous works suggest that the successful integration of conventional textile manufacturing processes in the FRPC-process chain is the key to a cost-efficient manufacturing of complex three-dimensional (3D) FRPC-components with stress-oriented fibre arrangement. Therefore, this work focuses on the development of the multilayer weft knitting technology for the one-step manufacturing of complex 3D net-shaped preforms for high performance FRPC applications. In order to highlight the advantages of net-shaped multilayer weft knitted fabrics for the production of complex FRPC parts, seamless preforms such as 3D skin-stringer structures and tubular fabrics with load oriented fibre arrangement are realised. In this paper, the development of the textile bindings and performed technical modifications on flat knitting machines are presented. The results show that the multilayer weft knitting technology meets perfectly the requirements for a fully automated and reproducible manufacturing of complex 3D textile preforms with stress-oriented fibre arrangement.
Recent progress in continuous and semi-continuous processing of solid oral dosage forms: a review.
Teżyk, Michał; Milanowski, Bartłomiej; Ernst, Andrzej; Lulek, Janina
2016-08-01
Continuous processing is an innovative production concept well known and successfully used in other industries for many years. The modern pharmaceutical industry is facing the challenge of transition from a traditional manufacturing approach based on batch-wise production to a continuous manufacturing model. The aim of this article is to present technological progress in manufacturing based on continuous and semi-continuous processing of the solid oral dosage forms. Single unit processes possessing an alternative processing pathway to batch-wise technology or, with some modification, an altered approach that may run continuously, and are thus able to seamlessly switch to continuous manufacturing are briefly presented. Furthermore, the concept of semi-continuous processing is discussed. Subsequently, more sophisticated production systems created by coupling single unit processes and comprising all the steps of production, from powder to final dosage form, were reviewed. Finally, attempts of end-to-end production approach, meaning the linking of continuous synthesis of API from intermediates with the production of final dosage form, are described. There are a growing number of scientific articles showing an increasing interest in changing the approach to the production of pharmaceuticals in recent years. Numerous scientific publications are a source of information on the progress of knowledge and achievements of continuous processing. These works often deal with issues of how to modify or replace the unit processes in order to enable seamlessly switching them into continuous processing. A growing number of research papers concentrate on integrated continuous manufacturing lines in which the production concept of "from powder to tablet" is realized. Four main domains are under investigation: influence of process parameters on intermediates or final dosage forms properties, implementation of process analytical tools, control-managing system responsible for keeping continuous materials flow through the whole manufacturing process and the development of new computational methods to assess or simulate these new manufacturing techniques. The attempt to connect the primary and secondary production steps proves that development of continuously operating lines is possible. A mind-set change is needed to be able to face, and fully assess, the advantages and disadvantages of switching from batch to continuous mode production.
Analysis of residual stress state in sheet metal parts processed by single point incremental forming
NASA Astrophysics Data System (ADS)
Maaß, F.; Gies, S.; Dobecki, M.; Brömmelhoff, K.; Tekkaya, A. E.; Reimers, W.
2018-05-01
The mechanical properties of formed metal components are highly affected by the prevailing residual stress state. A selective induction of residual compressive stresses in the component, can improve the product properties such as the fatigue strength. By means of single point incremental forming (SPIF), the residual stress state can be influenced by adjusting the process parameters during the manufacturing process. To achieve a fundamental understanding of the residual stress formation caused by the SPIF process, a valid numerical process model is essential. Within the scope of this paper the significance of kinematic hardening effects on the determined residual stress state is presented based on numerical simulations. The effect of the unclamping step after the manufacturing process is also analyzed. An average deviation of the residual stress amplitudes in the clamped and unclamped condition of 18 % reveals, that the unclamping step needs to be considered to reach a high numerical prediction quality.
Demonstration of the feasibility of automated silicon solar cell fabrication
NASA Technical Reports Server (NTRS)
Taylor, W. E.; Schwartz, F. M.
1975-01-01
A study effort was undertaken to determine the process, steps and design requirements of an automated silicon solar cell production facility. Identification of the key process steps was made and a laboratory model was conceptually designed to demonstrate the feasibility of automating the silicon solar cell fabrication process. A detailed laboratory model was designed to demonstrate those functions most critical to the question of solar cell fabrication process automating feasibility. The study and conceptual design have established the technical feasibility of automating the solar cell manufacturing process to produce low cost solar cells with improved performance. Estimates predict an automated process throughput of 21,973 kilograms of silicon a year on a three shift 49-week basis, producing 4,747,000 hexagonal cells (38mm/side), a total of 3,373 kilowatts at an estimated manufacturing cost of $0.866 per cell or $1.22 per watt.
Pharmaceutical 3D printing: Design and qualification of a single step print and fill capsule.
Smith, Derrick M; Kapoor, Yash; Klinzing, Gerard R; Procopio, Adam T
2018-06-10
Fused deposition modeling (FDM) 3D printing (3DP) has a potential to change how we envision manufacturing in the pharmaceutical industry. A more common utilization for FDM 3DP is to build upon existing hot melt extrusion (HME) technology where the drug is dispersed in the polymer matrix. However, reliable manufacturing of drug-containing filaments remains a challenge along with the limitation of active ingredients which can sustain the processing risks involved in the HME process. To circumvent this obstacle, a single step FDM 3DP process was developed to manufacture thin-walled drug-free capsules which can be filled with dry or liquid drug product formulations. Drug release from these systems is governed by the combined dissolution of the FDM capsule 'shell' and the dosage form encapsulated in these shells. To prepare the shells, the 3D printer files (extension '.gcode') were modified by creating discrete zones, so-called 'zoning process', with individual print parameters. Capsules printed without the zoning process resulted in macroscopic print defects and holes. X-ray computed tomography, finite element analysis and mechanical testing were used to guide the zoning process and printing parameters in order to manufacture consistent and robust capsule shell geometries. Additionally, dose consistencies of drug containing liquid formulations were investigated in this work. Copyright © 2018 Elsevier B.V. All rights reserved.
Bring Your Next Film or Videotape in on Time--And within Budget.
ERIC Educational Resources Information Center
Hampe, Barry
1980-01-01
Seventeen steps are presented for the successful production of training films and video tapes. The steps include concept, script preparation, budget, filming and recording, laboratory processing, editing, titles and narration, sound mix, corrections, manufacture of prints, and distribution. (CT)
Six-sigma application in tire-manufacturing company: a case study
NASA Astrophysics Data System (ADS)
Gupta, Vikash; Jain, Rahul; Meena, M. L.; Dangayach, G. S.
2017-09-01
Globalization, advancement of technologies, and increment in the demand of the customer change the way of doing business in the companies. To overcome these barriers, the six-sigma define-measure-analyze-improve-control (DMAIC) method is most popular and useful. This method helps to trim down the wastes and generating the potential ways of improvement in the process as well as service industries. In the current research, the DMAIC method was used for decreasing the process variations of bead splice causing wastage of material. This six-sigma DMAIC research was initiated by problem identification through voice of customer in the define step. The subsequent step constitutes of gathering the specification data of existing tire bead. This step was followed by the analysis and improvement steps, where the six-sigma quality tools such as cause-effect diagram, statistical process control, and substantial analysis of existing system were implemented for root cause identification and reduction in process variation. The process control charts were used for systematic observation and control the process. Utilizing DMAIC methodology, the standard deviation was decreased from 2.17 to 1.69. The process capability index (C p) value was enhanced from 1.65 to 2.95 and the process performance capability index (C pk) value was enhanced from 0.94 to 2.66. A DMAIC methodology was established that can play a key role for reducing defects in the tire-manufacturing process in India.
Quality cell therapy manufacturing by design.
Lipsitz, Yonatan Y; Timmins, Nicholas E; Zandstra, Peter W
2016-04-01
Transplantation of live cells as therapeutic agents is poised to offer new treatment options for a wide range of acute and chronic diseases. However, the biological complexity of cells has hampered the translation of laboratory-scale experiments into industrial processes for reliable, cost-effective manufacturing of cell-based therapies. We argue here that a solution to this challenge is to design cell manufacturing processes according to quality-by-design (QbD) principles. QbD integrates scientific knowledge and risk analysis into manufacturing process development and is already being adopted by the biopharmaceutical industry. Many opportunities to incorporate QbD into cell therapy manufacturing exist, although further technology development is required for full implementation. Linking measurable molecular and cellular characteristics of a cell population to final product quality through QbD is a crucial step in realizing the potential for cell therapies to transform healthcare.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ko, Young Ho; Han, Myoung Soo; Han, Jong Man
2007-05-17
Doubly curved thick plate forming in shipbuilding industries is currently performed by a thermal forming process, called as Line Heating by using gas flame torches. Due to the empirical manual work of it, the industries are eager for an alternative way to manufacture curved thick plates for ships. It was envisaged in this study to manufacture doubly curved thick plates by the multi-punch die forming. Experiments and finite element analyses were conducted to evaluate the feasibility of the reconfigurable discrete die forming to the thick plates. Single and segmented multiple step forming procedures were considered from both forming efficiency andmore » accuracy. Configuration of the multi-punch dies suitable for the segmented multiple step forming was also explored. As a result, Segmented multiple step forming with matched dies had a limited formability when the objective shapes become complicate, while a unmatched die configuration provided better possibility to manufacture large curved plates for ships.« less
Economics of polysilicon process: A view from Japan
NASA Technical Reports Server (NTRS)
Shimizu, Y.
1986-01-01
The production process of solar grade silicon (SOG-Si) through trichlorosilane (TCS) was researched in a program sponsored by New Energy Development Organization (NEDO). The NEDO process consists of the following two steps: TCS production from by-product silicon tetrachloride (STC) and SOG-Si formation from TCS using a fluidized bed reactor. Based on the data obtained during the research program, the manufacturing cost of the NEDO process and other polysilicon manufacturing processes were compared. The manufacturing cost was calculated on the basis of 1000 tons/year production. The cost estimate showed that the cost of producing silicon by all of the new processes is less than the cost by the conventional Siemens process. Using a new process, the cost of producing semiconductor grade silicon was found to be virtually the same with any to the TCS, diclorosilane, and monosilane processes when by-products were recycled. The SOG-Si manufacturing processes using the fluidized bed reactor, which needs further development, shows a greater probablility of cost reduction than the filament processes.
Analytical method for promoting process capability of shock absorption steel.
Sung, Wen-Pei; Shih, Ming-Hsiang; Chen, Kuen-Suan
2003-01-01
Mechanical properties and low cycle fatigue are two factors that must be considered in developing new type steel for shock absorption. Process capability and process control are significant factors in achieving the purpose of research and development programs. Often-used evaluation methods failed to measure process yield and process centering; so this paper uses Taguchi loss function as basis to establish an evaluation method and the steps for assessing the quality of mechanical properties and process control of an iron and steel manufacturer. The establishment of this method can serve the research and development and manufacturing industry and lay a foundation in enhancing its process control ability to select better manufacturing processes that are more reliable than decision making by using the other commonly used methods.
Sethi, Rajiv; Yanamadala, Vijay; Burton, Douglas C; Bess, Robert Shay
2017-11-01
Lean methodology was developed in the manufacturing industry to increase output and decrease costs. These labor organization methods have become the mainstay of major manufacturing companies worldwide. Lean methods involve continuous process improvement through the systematic elimination of waste, prevention of mistakes, and empowerment of workers to make changes. Because of the profit and productivity gains made in the manufacturing arena using lean methods, several healthcare organizations have adopted lean methodologies for patient care. Lean methods have now been implemented in many areas of health care. In orthopaedic surgery, lean methods have been applied to reduce complication rates and create a culture of continuous improvement. A step-by-step guide based on our experience can help surgeons use lean methods in practice. Surgeons and hospital centers well versed in lean methodology will be poised to reduce complications, improve patient outcomes, and optimize cost/benefit ratios for patient care.
Real World of Industrial Chemistry: The SHOP Process: An Example of Industrial Creativity.
ERIC Educational Resources Information Center
Reuben, Bryan; Wittcoff, Harold
1988-01-01
Discusses the Shell Higher Olefins Process (SHOP) in the manufacture of primary C11-C15 fatty alcohols. Offers examples and explanations of the four-step process. Gives uses for reaction products. (ML)
Panzitta, Michele; Ponti, Mauro; Bruno, Giorgio; Cois, Giancarlo; D'Arpino, Alessandro; Minghetti, Paola; Mendicino, Francesca Romana; Perioli, Luana; Ricci, Maurizio
2017-01-10
Manufacturing is the bridge between research and patient: without product, there is no clinical outcome. Shortage has a variety of causes, in this paper we analyse only causes related to manufacturing technology and we use shortage as a paradigm highliting the relevance of Pharmaceutical Technology. Product and process complexity and capacity issues are the main challenge for the Pharmaceutical Industry Supply chain. Manufacturing Technology should be acknowledged as a R&D step and as a very important matter during University degree in Pharmacy and related disciplines, promoting collaboration between Academia and Industry, measured during HTA step and rewarded in terms of price and reimbursement. The above elements are not yet properly recognised, and manufacturing technology is taken in to consideration only when a shortage is in place. In a previous work, Panzitta et al. proposed to perform a full technology assessment at the Health Technological Assessment stage, evaluating three main technical aspects of a medicine: manufacturing process, physicochemical properties, and formulation characteristics. In this paper, we develop the concept of manufacturing appraisal, providing a technical overview of upcoming challenges, a risk based approach and an economic picture of shortage costs. We develop also an overall quality concept, not limited to GMP factors but broaden to all elements leading to a robust supply and promoting technical innovation. Copyright © 2016 Elsevier B.V. All rights reserved.
Development of metallization process. FSA project, cell and module formation research area
NASA Technical Reports Server (NTRS)
Garcia, A., III
1984-01-01
New pastes were evaluated that contained additives to aid in the silicon-to-metallization contact. None were completely successful. A reevaluation of the molybdenum oxide paste and the two-step screen printing process was done. The oxide paste did not show promise. The two-step process enabled soldering of the cells but the cells still had a high series resistance. Pastes are on order from a different manufacturer.
2006-05-01
dies. This process uses a laser beam to melt a controlled amount of injected powder on a base plate to deposit the first layer and on previous passes...Consolidation” to build functional net-shape components directly from metallic powder in one step [1-3]. The laser consolidation is a one-step computer-aided...A focused laser beam is irradiated on the substrate to create a molten pool, while metallic powder is injected simultaneously into the pool. A
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
2017-06-22
The starting point for many consumer products is the industrial manufacture of platform chemicals. The recent boom in domestic shale gas production makes it possible to envision a new resource for chemical manufacturing. Catalysts are the accelerants behind most industrial chemical reactions. A sophisticated research technique using a Temporal Analysis of Products (or TAP) reactor can now help. By shedding light on a catalyst’s fundamental step-by-step process, a TAP reactor can help chemists and chemical engineers understand why a new catalyst works better in the lab than in the chemical plant.
Kelley, Brian D; Tannatt, Molly; Magnusson, Robert; Hagelberg, Sigrid; Booth, James
2004-08-05
An affinity chromatography step was developed for purification of recombinant B-Domain Deleted Factor VIII (BDDrFVIII) using a peptide ligand selected from a phage display library. The peptide library had variegated residues, contained both within a disulfide bond-constrained ring and flanking the ring. The peptide ligand binds to BDDrFVIII with a dissociation constant of approximately 1 microM both in free solution and when immobilized on a chromatographic resin. The peptide is chemically synthesized and the affinity resin is produced by coupling the peptide to an agarose matrix preactivated with N-hydroxysuccinimide. Coupling conditions were optimized to give consistent and complete ligand incorporation and validated with a robustness study that tested various combinations of processing limits. The peptide affinity chromatographic operation employs conditions very similar to an immunoaffinity chromatography step currently in use for BDDrFVIII manufacture. The process step provides excellent recovery of BDDrFVIII from a complex feed stream and reduces host cell protein and DNA by 3-4 logs. Process validation studies established resin reuse over 26 cycles without changes in product recovery or purity. A robustness study using a factorial design was performed and showed that the step was insensitive to small changes in process conditions that represent normal variation in commercial manufacturing. A scaled-down model of the process step was qualified and used for virus removal studies. A validation package addressing the safety of the leached peptide included leaching rate measurements under process conditions, testing of peptide levels in product pools, demonstration of robust removal downstream by spiking studies, end product testing, and toxicological profiling of the ligand. The peptide ligand affinity step was scaled up for cGMP production of BDDrFVIII for clinical trials.
Method of manufacturing carbon nanotubes
NASA Technical Reports Server (NTRS)
Benavides, Jeanette M. (Inventor); Leidecker, Henning W. (Inventor); Frazier, Jeffrey (Inventor)
2004-01-01
A process for manufacturing carbon nanotubes, including a step of inducing electrical current through a carbon anode and a carbon cathode under conditions effective to produce the carbon nanotubes, wherein the carbon cathode is larger than the carbon anode. Preferably, a welder is used to induce the electrical current via an arc welding process. Preferably, an exhaust hood is placed on the anode, and the process does not require a closed or pressurized chamber. The process provides high-quality, single-walled carbon nanotubes, while eliminating the need for a metal catalyst.
Integrated coal liquefaction process
Effron, Edward
1978-01-01
In a process for the liquefaction of coal in which coal liquids containing phenols and other oxygenated compounds are produced during the liquefaction step and later hydrogenated, oxygenated compounds are removed from at least part of the coal liquids in the naphtha and gas oil boiling range prior to the hydrogenation step and employed as a feed stream for the manufacture of a synthesis gas or for other purposes.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Creasy, John T
2015-05-12
This project has the objective to reduce and/or eliminate the use of HEU in commerce. Steps in the process include developing a target testing methodology that is bounding for all Mo-99 target irradiators, establishing a maximum target LEU-foil mass, developing a LEU-foil target qualification document, developing a bounding target failure analysis methodology (failure in reactor containment), optimizing safety vs. economics (goal is to manufacture a safe, but relatively inexpensive target to offset the inherent economic disadvantage of using LEU in place of HEU), and developing target material specifications and manufacturing QC test criteria. The slide presentation is organized under themore » following topics: Objective, Process Overview, Background, Team Structure, Key Achievements, Experiment and Activity Descriptions, and Conclusions. The High Density Target project has demonstrated: approx. 50 targets irradiated through domestic and international partners; proof of concept for two front end processing methods; fabrication of uranium foils for target manufacture; quality control procedures and steps for manufacture; multiple target assembly techniques; multiple target disassembly devices; welding of targets; thermal, hydraulic, and mechanical modeling; robust target assembly parametric studies; and target qualification analysis for insertion into very high flux environment. The High Density Target project has tested and proven several technologies that will benefit current and future Mo-99 producers.« less
Jiang, Canping; Flansburg, Lisa; Ghose, Sanchayita; Jorjorian, Paul; Shukla, Abhinav A
2010-12-15
The concept of design space has been taking root under the quality by design paradigm as a foundation of in-process control strategies for biopharmaceutical manufacturing processes. This paper outlines the development of a design space for a hydrophobic interaction chromatography (HIC) process step. The design space included the impact of raw material lot-to-lot variability and variations in the feed stream from cell culture. A failure modes and effects analysis was employed as the basis for the process characterization exercise. During mapping of the process design space, the multi-dimensional combination of operational variables were studied to quantify the impact on process performance in terms of yield and product quality. Variability in resin hydrophobicity was found to have a significant influence on step yield and high-molecular weight aggregate clearance through the HIC step. A robust operating window was identified for this process step that enabled a higher step yield while ensuring acceptable product quality. © 2010 Wiley Periodicals, Inc.
Pohlscheidt, Michael; Charaniya, Salim; Kulenovic, Fikret; Corrales, Mahalia; Shiratori, Masaru; Bourret, Justin; Meier, Steven; Fallon, Eric; Kiss, Robert
2014-04-01
The production of therapeutic proteins by mammalian cell culture is complex and sets high requirements for process, facility, and equipment design, as well as rigorous regulatory and quality standards. One particular point of concern and significant risk to supply chain is the susceptibility to contamination such as bacteria, fungi, mycoplasma, and viruses. Several technologies have been developed to create barriers for these agents to enter the process, e.g. filtration, UV inactivation, and temperature inactivation. However, if not implemented during development of the manufacturing process, these types of process changes can have significant impact on process performance if not managed appropriately. This article describes the implementation of the high-temperature short-time (HTST) treatment of cell culture media as an additional safety barrier against adventitious agents during the transfer of a large-scale commercial cell culture manufacturing process. The necessary steps and experiments, as well as subsequent results during qualification runs and routine manufacturing, are shown.
21 CFR 211.188 - Batch production and control records.
Code of Federal Regulations, 2012 CFR
2012-04-01
... that each significant step in the manufacture, processing, packing, or holding of the batch was... automated equipment under § 211.68, the identification of the person checking the significant step performed by the automated equipment. (12) Any investigation made according to § 211.192. (13) Results of...
21 CFR 211.188 - Batch production and control records.
Code of Federal Regulations, 2013 CFR
2013-04-01
... that each significant step in the manufacture, processing, packing, or holding of the batch was... automated equipment under § 211.68, the identification of the person checking the significant step performed by the automated equipment. (12) Any investigation made according to § 211.192. (13) Results of...
21 CFR 211.188 - Batch production and control records.
Code of Federal Regulations, 2014 CFR
2014-04-01
... that each significant step in the manufacture, processing, packing, or holding of the batch was... automated equipment under § 211.68, the identification of the person checking the significant step performed by the automated equipment. (12) Any investigation made according to § 211.192. (13) Results of...
NASA Astrophysics Data System (ADS)
de Buttet, Côme; Prevost, Emilie; Campo, Alain; Garnier, Philippe; Zoll, Stephane; Vallier, Laurent; Cunge, Gilles; Maury, Patrick; Massin, Thomas; Chhun, Sonarith
2017-03-01
Today the IC manufacturing faces lots of problematics linked to the continuous down scaling of printed structures. Some of those issues are related to wet processing, which are often used in the IC manufacturing flow for wafer cleaning, material etching and surface preparation. In the current work we summarize the limitations for the next nodes of wet processing such as metallic contaminations, wafer charging, corrosion and pattern collapse. As a replacement, we promoted the isotropic chemical dry etching (CDE) which is supposed to fix all the above drawbacks. Etching steps of SI3N4 layers were evaluated in order to prove the interest of such technique.
To repair or not to repair: with FAVOR there is no question
NASA Astrophysics Data System (ADS)
Garetto, Anthony; Schulz, Kristian; Tabbone, Gilles; Himmelhaus, Michael; Scheruebl, Thomas
2016-10-01
In the mask shop the challenges associated with today's advanced technology nodes, both technical and economic, are becoming increasingly difficult. The constant drive to continue shrinking features means more masks per device, smaller manufacturing tolerances and more complexity along the manufacturing line with respect to the number of manufacturing steps required. Furthermore, the extremely competitive nature of the industry makes it critical for mask shops to optimize asset utilization and processes in order to maximize their competitive advantage and, in the end, profitability. Full maximization of profitability in such a complex and technologically sophisticated environment simply cannot be achieved without the use of smart automation. Smart automation allows productivity to be maximized through better asset utilization and process optimization. Reliability is improved through the minimization of manual interactions leading to fewer human error contributions and a more efficient manufacturing line. In addition to these improvements in productivity and reliability, extra value can be added through the collection and cross-verification of data from multiple sources which provides more information about our products and processes. When it comes to handling mask defects, for instance, the process consists largely of time consuming manual interactions that are error prone and often require quick decisions from operators and engineers who are under pressure. The handling of defects itself is a multiple step process consisting of several iterations of inspection, disposition, repair, review and cleaning steps. Smaller manufacturing tolerances and features with higher complexity contribute to a higher number of defects which must be handled as well as a higher level of complexity. In this paper the recent efforts undertaken by ZEISS to provide solutions which address these challenges, particularly those associated with defectivity, will be presented. From automation of aerial image analysis to the use of data driven decision making to predict and propose the optimized back end of line process flow, productivity and reliability improvements are targeted by smart automation. Additionally the generation of the ideal aerial image from the design and several repair enhancement features offer additional capabilities to improve the efficiency and yield associated with defect handling.
Ötes, Ozan; Flato, Hendrik; Winderl, Johannes; Hubbuch, Jürgen; Capito, Florian
2017-10-10
The protein A capture step is the main cost-driver in downstream processing, with high attrition costs especially when using protein A resin not until end of resin lifetime. Here we describe a feasibility study, transferring a batch downstream process to a hybrid process, aimed at replacing batch protein A capture chromatography with a continuous capture step, while leaving the polishing steps unchanged to minimize required process adaptations compared to a batch process. 35g of antibody were purified using the hybrid approach, resulting in comparable product quality and step yield compared to the batch process. Productivity for the protein A step could be increased up to 420%, reducing buffer amounts by 30-40% and showing robustness for at least 48h continuous run time. Additionally, to enable its potential application in a clinical trial manufacturing environment cost of goods were compared for the protein A step between hybrid process and batch process, showing a 300% cost reduction, depending on processed volumes and batch cycles. Copyright © 2017 Elsevier B.V. All rights reserved.
All-solid-state lithium-ion and lithium metal batteries - paving the way to large-scale production
NASA Astrophysics Data System (ADS)
Schnell, Joscha; Günther, Till; Knoche, Thomas; Vieider, Christoph; Köhler, Larissa; Just, Alexander; Keller, Marlou; Passerini, Stefano; Reinhart, Gunther
2018-04-01
Challenges and requirements for the large-scale production of all-solid-state lithium-ion and lithium metal batteries are herein evaluated via workshops with experts from renowned research institutes, material suppliers, and automotive manufacturers. Aiming to bridge the gap between materials research and industrial mass production, possible solutions for the production chains of sulfide and oxide based all-solid-state batteries from electrode fabrication to cell assembly and quality control are presented. Based on these findings, a detailed comparison of the production processes for a sulfide based all-solid-state battery with conventional lithium-ion cell production is given, showing that processes for composite electrode fabrication can be adapted with some effort, while the fabrication of the solid electrolyte separator layer and the integration of a lithium metal anode will require completely new processes. This work identifies the major steps towards mass production of all-solid-state batteries, giving insight into promising manufacturing technologies and helping stakeholders, such as machine engineering, cell producers, and original equipment manufacturers, to plan the next steps towards safer batteries with increased storage capacity.
Billoir, Elise; Denis, Jean-Baptiste; Cammeau, Natalie; Cornu, Marie; Zuliani, Veronique
2011-02-01
To assess the impact of the manufacturing process on the fate of Listeria monocytogenes, we built a generic probabilistic model intended to simulate the successive steps in the process. Contamination evolution was modeled in the appropriate units (breasts, dice, and then packaging units through the successive steps in the process). To calibrate the model, parameter values were estimated from industrial data, from the literature, and based on expert opinion. By means of simulations, the model was explored using a baseline calibration and alternative scenarios, in order to assess the impact of changes in the process and of accidental events. The results are reported as contamination distributions and as the probability that the product will be acceptable with regards to the European regulatory safety criterion. Our results are consistent with data provided by industrial partners and highlight that tumbling is a key step for the distribution of the contamination at the end of the process. Process chain models could provide an important added value for risk assessment models that basically consider only the outputs of the process in their risk mitigation strategies. Moreover, a model calibrated to correspond to a specific plant could be used to optimize surveillance. © 2010 Society for Risk Analysis.
Integrated flexible manufacturing program for manufacturing automation and rapid prototyping
NASA Technical Reports Server (NTRS)
Brooks, S. L.; Brown, C. W.; King, M. S.; Simons, W. R.; Zimmerman, J. J.
1993-01-01
The Kansas City Division of Allied Signal Inc., as part of the Integrated Flexible Manufacturing Program (IFMP), is developing an integrated manufacturing environment. Several systems are being developed to produce standards and automation tools for specific activities within the manufacturing environment. The Advanced Manufacturing Development System (AMDS) is concentrating on information standards (STEP) and product data transfer; the Expert Cut Planner system (XCUT) is concentrating on machining operation process planning standards and automation capabilities; the Advanced Numerical Control system (ANC) is concentrating on NC data preparation standards and NC data generation tools; the Inspection Planning and Programming Expert system (IPPEX) is concentrating on inspection process planning, coordinate measuring machine (CMM) inspection standards and CMM part program generation tools; and the Intelligent Scheduling and Planning System (ISAPS) is concentrating on planning and scheduling tools for a flexible manufacturing system environment. All of these projects are working together to address information exchange, standardization, and information sharing to support rapid prototyping in a Flexible Manufacturing System (FMS) environment.
Advanced metal lift-off process using electron-beam flood exposure of single-layer photoresist
NASA Astrophysics Data System (ADS)
Minter, Jason P.; Ross, Matthew F.; Livesay, William R.; Wong, Selmer S.; Narcy, Mark E.; Marlowe, Trey
1999-06-01
In the manufacture of many types of integrated circuit and thin film devices, it is desirable to use a lift-of process for the metallization step to avoid manufacturing problems encountered when creating metal interconnect structures using plasma etch. These problems include both metal adhesion and plasma etch difficulties. Key to the success of the lift-off process is the creation of a retrograde or undercut profile in the photoresists before the metal deposition step. Until now, lift-off processing has relied on costly multi-layer photoresists schemes, image reversal, and non-repeatable photoresist processes to obtain the desired lift-off profiles in patterned photoresist. This paper present a simple, repeatable process for creating robust, user-defined lift-off profiles in single layer photoresist using a non-thermal electron beam flood exposure. For this investigation, lift-off profiles created using electron beam flood exposure of many popular photoresists were evaluated. Results of lift-off profiles created in positive tone AZ7209 and ip3250 are presented here.
A prototype scanning system for optimal edging and trimming of rough hardwood lumber
Sang-Mook Lee; A. Lynn Abbott; Philip A. Araman; Daniel L. Schmoldt
2003-01-01
This paper is concerned with scanning and assessment of hardwood lumber early in the manufacturing process. Scanning operations that take place immediately after the headrig have significantly greater potential to reduce loss and improve economic value, as compared to scanning that is performed during subsequent manufacturing steps. In spite of this, the scanning of...
Dynamic control of moisture during hot pressing of wood composites
Cheng Piao; Todd F. Shupe; Chung Y. Hse
2006-01-01
Hot pressing is an important step in the manufacture of wood composites. In the conventional pressing system, hot press output often acts as a constraint to increased production. Severe drying of the furnish (e.g., particles, flakes, or fibers) required by this process substantially increases the manufacturing cost and creates air-polluting emissions of volatile...
Achieving world class performance step by step.
Kerr, L J
1992-02-01
Bridgestone of Japan acquired Firestone, a United States corporation, in early 1988. This article describes the integration process of the two organizations' cultures. There are many lessons in the approach that should apply to a variety of organizations. The Strategic Improvement Process, a rather highly structured approach, harnesses the strengths of both the Japanese and American organizations and starts the manufacturing and technical departments on the road to excellence.
Pollution prevention in the pulp and paper industry
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jenkins, P.G.
1995-09-01
Probably no other industry has made as much progress as the kraft pulp and paper industry in reclaiming waste products. About half of the wood used in making pulp is cellulose; the reclamation of the other ingredients in the wood constitutes a continuing evolution of pollution prevention and economic success. The by-products of chemical pulping include turpentine used in the paint industry, lignosulfonates used as surfactants and dispersants, ``tall oil`` used in chemical manufacturing, yeast, vanillin, acetic acid, activated carbon, and alcohol. Sulfamic turpentine recovered in the kraft process is used to manufacture pine oil, dimethyl sulfoxide (DMSO), and othermore » useful chemical products. In addition, the noncellulose portion of the wood is used to provide energy for the pulping process through the combustion of concentrated black liquor. Over 75% of the pulp produced in the US is manufactured using the kraft process. Because of the predominance of the kraft process, the remainder of this section will address pollution prevention methods for kraft pulp and paper mills. Some of these techniques may be applicable or adaptable to other pulping processes, especially sulfite mills. The major steps in the kraft process are described, followed by a discussion of major wastestreams, and proven pollution prevention methods for each of these steps.« less
Solid State Lighting Program (Falcon)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meeks, Steven
2012-06-30
Over the past two years, KLA-Tencor and partners successfully developed and deployed software and hardware tools that increase product yield for High Brightness LED (HBLED) manufacturing and reduce product development and factory ramp times. This report summarizes our development effort and details of how the results of the Solid State Light Program (Falcon) have started to help HBLED manufacturers optimize process control by enabling them to flag and correct identified killer defect conditions at any point of origin in the process manufacturing flow. This constitutes a quantum leap in yield management over current practice. Current practice consists of die dispositioningmore » which is just rejection of bad die at end of process based upon probe tests, loosely assisted by optical in-line monitoring for gross process deficiencies. For the first time, and as a result of our Solid State Lighting Program, our LED manufacturing partners have obtained the software and hardware tools that optimize individual process steps to control killer defects at the point in the processes where they originate. Products developed during our two year program enable optimized inspection strategies for many product lines to minimize cost and maximize yield. The Solid State Lighting Program was structured in three phases: i) the development of advanced imaging modes that achieve clear separation between LED defect types, improves signal to noise and scan rates, and minimizes nuisance defects for both front end and back end inspection tools, ii) the creation of defect source analysis (DSA) software that connect the defect maps from back-end and front-end HBLED manufacturing tools to permit the automatic overlay and traceability of defects between tools and process steps, suppress nuisance defects, and identify the origin of killer defects with process step and conditions, and iii) working with partners (Philips Lumileds) on product wafers, obtain a detailed statistical correlation of automated defect and DSA map overlay to failed die identified using end product probe test results. Results from our two year effort have led to “automated end-to-end defect detection” with full defect traceability and the ability to unambiguously correlate device killer defects to optically detected features and their point of origin within the process. Success of the program can be measured by yield improvements at our partner’s facilities and new product orders.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Graham, Mark W.
2015-07-28
In a manufacturing process, a need is identified and a product is created to fill this need. While design and engineering of the final product is important, the tools and fixtures that aid in the creation of the final product are just as important, if not more so. Power supplies assembled at the TA-55 PF-5 have been designed by an excellent engineering team. The task in PF-5 now is to ensure that all steps of the assembly and manufacturing process can be completed safely, reliably, and in a quality repeatable manner. One of these process steps involves soldering fine wiresmore » to an electrical connector. During the process development phase, the method of soldering included placing the power supply in a vice in order to manipulate it into a position conducive to soldering. This method is unacceptable from a reliability, repeatability, and ergonomic standpoint. To combat these issues, a fixture was designed to replace the current method. To do so, a twelve step engineering design process was used to create the fixture that would provide a solution to a multitude of problems, and increase the safety and efficiency of production.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Guest, Daniel A.; Cairns, Douglas S.
2014-02-01
The increased use and interest in wind energy over the last few years has necessitated an increase in the manufacturing of wind turbine blades. This increase in manufacturing has in many ways out stepped the current understanding of not only the materials used but also the manufacturing methods used to construct composite laminates. The goal of this study is to develop a list of process parameters which influence the quality of composite laminates manufactured using vacuum assisted resin transfer molding and to evaluate how they influence laminate quality. Known to be primary factors for the manufacturing process are resin flowmore » rate and vacuum pressure. An incorrect balance of these parameters will often cause porosity or voids in laminates that ultimately degrade the strength of the composite. Fiber waviness has also been seen as a major contributor to failures in wind turbine blades and is often the effect of mishandling during the lay-up process. Based on laboratory tests conducted, a relationship between these parameters and laminate quality has been established which will be a valuable tool in developing best practices and standard procedures for the manufacture of wind turbine blade composites.« less
Caredda, Marco; Addis, Margherita; Pes, Massimo; Fois, Nicola; Sanna, Gabriele; Piredda, Giovanni; Sanna, Gavino
2018-06-01
The aim of this work was to measure the physico-chemical and the colorimetric parameters of ovaries from Mugil cephalus caught in the Tortolì lagoon (South-East coast of Sardinia) along the steps of the manufacturing process of Bottarga, together with the rheological parameters of the final product. A lowering of all CIELab coordinates (lightness, redness and yellowness) was observed during the manufacture process. All CIELab parameters were used to build a Linear Discriminant Analysis (LDA) predictive model able to determine in real time if the roes had been subdued to a freezing process, with a success in prediction of 100%. This model could be used to identify the origin of the roes, since only the imported ones are frozen. The major changes of all the studied parameters (p < 0.05) were noted in the drying step rather than in the salting step. After processing, Bottarga was characterized by a pH value of 5.46 (CV = 2.8) and a moisture content of 25% (CV = 8), whereas the typical per cent amounts of proteins, fat and NaCl, calculated as a percentage on the dried weight, were 56 (CV = 2), 34 (CV = 3) and 3.6 (CV = 17), respectively. The physical chemical changes of the roes during the manufacturing process were consistent for moisture, which decreased by 28%, whereas the protein and the fat contents on the dried weight got respectively lower of 3% and 2%. NaCl content increased by 3.1%. Principal Component Analyses (PCA) were also performed on all data to establish trends and relationships among all parameters. Hardness and consistency of Bottarga were negatively correlated with the moisture content (r = -0.87 and r = -0.88, respectively), while its adhesiveness was negatively correlated with the fat content (r = -0.68). Copyright © 2018. Published by Elsevier Ltd.
Materials Characterization of Additively Manufactured Components for Rocket Propulsion
NASA Technical Reports Server (NTRS)
Carter, Robert; Draper, Susan; Locci, Ivan; Lerch, Bradley; Ellis, David; Senick, Paul; Meyer, Michael; Free, James; Cooper, Ken; Jones, Zachary
2015-01-01
To advance Additive Manufacturing (AM) technologies for production of rocket propulsion components the NASA Glenn Research Center (GRC) is applying state of the art characterization techniques to interrogate microstructure and mechanical properties of AM materials and components at various steps in their processing. The materials being investigated for upper stage rocket engines include titanium, copper, and nickel alloys. Additive manufacturing processes include laser powder bed, electron beam powder bed, and electron beam wire fed processes. Various post build thermal treatments, including Hot Isostatic Pressure (HIP), have been studied to understand their influence on microstructure, mechanical properties, and build density. Micro-computed tomography, electron microscopy, and mechanical testing in relevant temperature environments has been performed to develop relationships between build quality, microstructure, and mechanical performance at temperature. A summary of GRC's Additive Manufacturing roles and experimental findings will be presented.
Material Characterization of Additively Manufactured Components for Rocket Propulsion
NASA Technical Reports Server (NTRS)
Carter, Robert; Draper, Susan; Locci, Ivan; Lerch, Bradley; Ellis, David; Senick, Paul; Meyer, Michael; Free, James; Cooper, Ken; Jones, Zachary
2015-01-01
To advance Additive Manufacturing (AM) technologies for production of rocket propulsion components the NASA Glenn Research Center (GRC) is applying state of the art characterization techniques to interrogate microstructure and mechanical properties of AM materials and components at various steps in their processing. The materials being investigated for upper stage rocket engines include titanium, copper, and nickel alloys. Additive manufacturing processes include laser powder bed, electron beam powder bed, and electron beam wire fed processes. Various post build thermal treatments, including Hot Isostatic Pressure (HIP), have been studied to understand their influence on microstructure, mechanical properties, and build density. Micro-computed tomography, electron microscopy, and mechanical testing in relevant temperature environments has been performed to develop relationships between build quality, microstructure, and mechanical performance at temperature. A summary of GRCs Additive Manufacturing roles and experimental findings will be presented.
A review on recent technologies for the manufacture of pulmonary drugs.
Hadiwinoto, Gabriela Daisy; Lip Kwok, Philip Chi; Lakerveld, Richard
2018-01-01
This review discusses recent developments in the manufacture of inhalable dry powder formulations. Pulmonary drugs have distinct advantages compared with other drug administration routes. However, requirements of drugs properties complicate the manufacture. Control over crystallization to make particles with the desired properties in a single step is often infeasible, which calls for micronization techniques. Although spray drying produces particles in the desired size range, a stable solid state may not be attainable. Supercritical fluids may be used as a solvent or antisolvent, which significantly reduces solvent waste. Future directions include application areas such as biopharmaceuticals for dry powder inhalers and new processing strategies to improve the control over particle formation such as continuous manufacturing with in-line process analytical technologies.
NASA Astrophysics Data System (ADS)
Nichols, Leannah M.
Commercially pure titanium can take up to six months to successfully manufacture a six-inch in diameter ingot in which can be shipped to be melted and shaped into other useful components. The applications to the corrosion-resistant, light weight, strong metal are endless, yet so is the manufacturing processing time. At a cost of around $80 per pound of certain grades of titanium powder, the everyday consumer cannot afford to use titanium in the many ways it is beneficial simply because the number of processing steps it takes to manufacture consumes too much time, energy, and labor. In this research, the steps it takes from the raw powder form to the final part are proposed to be reduced from 4-8 steps to only 2 steps utilizing a new technology that may even improve upon the titanium properties at the same time as it is reducing the number of steps of manufacture. The two-step procedure involves selecting a cylindrical or rectangular die and punch to compress a small amount of commercially pure titanium to a strong-enough compact for transportation to the friction stir welder to be consolidated. Friction stir welding invented in 1991 in the United Kingdom uses a tool, similar to a drill bit, to approach a sample and gradually plunge into the material at a certain rotation rate of between 100 to 2,100 RPM. In the second step, the friction stir welder is used to process the titanium powder held in a tight holder to consolidate into a harder titanium form. The resulting samples are cut to expose the cross section and then grinded, polished, and cleaned to be observed and tested using scanning electron microscopy (SEM), electron dispersive spectroscopy (EDS), and a Vickers microhardness tester. The results were that the thicker the sample, the harder the resulting consolidated sample peaking at 2 to 3 times harder than that of the original commercially pure titanium in solid form at a peak value of 435.9 hardness and overall average of 251.13 hardness. The combined results of the SEM and EDS have shown that the mixing of the sample holder material, titanium, and tool material were not of a large amount and therefore proves the feasibility of this study. This study should be continued to lessen the labor, energy, and cost of the production of titanium to therefore allow titanium to be improved upon and be more efficient for many applications across many industries.
Perspectives on the manufacture of combination vaccines.
Vose, J R
2001-12-15
Evolving regulatory requirements in the United States and Europe create major challenges for manufacturers tasked with production of vaccines that contain > or =9 separate antigens capable of protecting against infectious diseases, such as diphtheria, tetanus, pertussis, polio, hepatitis B, and Haemophilus influenza b, in a single shot. This article describes 10 steps that can facilitate the process of licensing these complex vaccines. It also points out problems associated with the use of animal tests for the crucial step of potency testing for batch release caused by the inherent variability of such tests and the difficulties of interpreting their results.
NASA Astrophysics Data System (ADS)
Piqué, Alberto; Auyeung, Raymond C. Y.; Kim, Heungsoo; Charipar, Nicholas A.; Mathews, Scott A.
2016-06-01
Laser-based materials processing techniques are gaining widespread use in micro-manufacturing applications. The use of laser microfabrication techniques enables the processing of micro- and nanostructures from a wide range of materials and geometries without the need for masking and etching steps commonly associated with photolithography. This review aims to describe the broad applications space covered by laser-based micro- and nanoprocessing techniques and the benefits offered by the use of lasers in micro-manufacturing processes. Given their non-lithographic nature, these processes are also referred to as laser direct-write and constitute some of the earliest demonstrations of 3D printing or additive manufacturing at the microscale. As this review will show, the use of lasers enables precise control of the various types of processing steps—from subtractive to additive—over a wide range of scales with an extensive materials palette. Overall, laser-based direct-write techniques offer multiple modes of operation including the removal (via ablative processes) and addition (via photopolymerization or printing) of most classes of materials using the same equipment in many cases. The versatility provided by these multi-function, multi-material and multi-scale laser micro-manufacturing processes cannot be matched by photolithography nor with other direct-write microfabrication techniques and offer unique opportunities for current and future 3D micro-manufacturing applications.
Consolidation modelling for thermoplastic composites forming simulation
NASA Astrophysics Data System (ADS)
Xiong, H.; Rusanov, A.; Hamila, N.; Boisse, P.
2016-10-01
Pre-impregnated thermoplastic composites are widely used in the aerospace industry for their excellent mechanical properties, Thermoforming thermoplastic prepregs is a fast manufacturing process, the automotive industry has shown increasing interest in this manufacturing processes, in which the reconsolidation is an essential stage. The model of intimate contact is investigated as the consolidation model, compression experiments have been launched to identify the material parameters, several numerical tests show the influents of the temperature and pressure applied during processing. Finally, a new solid-shell prismatic element has been presented for the simulation of consolidation step in the thermoplastic composites forming process.
Code of Federal Regulations, 2010 CFR
2010-07-01
... Hazardous Air Pollutants for Epoxy Resins Production and Non-Nylon Polyamides Production § 63.522... that are related to the production of BLR or WSR, including process vents, storage tanks, wastewater... process involving the bulk movement of material through sequential manufacturing steps. Mass, temperature...
Boedeker, Berthold; Goldstein, Adam; Mahajan, Ekta
2017-11-04
The availability and use of pre-sterilized disposables has greatly changed the methods used in biopharmaceuticals development and production, particularly from mammalian cell culture. Nowadays, almost all process steps from cell expansion, fermentation, cell removal, and purification to formulation and storage of drug substances can be carried out in disposables, although there are still limitations with single-use technologies, particularly in the areas of pretesting and quality control of disposables, bag and connections standardization and qualification, extractables and leachables (E/L) validation, and dependency on individual vendors. The current status of single-use technologies is summarized for all process unit operations using a standard mAb process as an example. In addition, current pros and cons of using disposables are addressed in a comparative way, including quality control and E/L validation.The continuing progress in developing single-use technologies has an important impact on manufacturing facilities, resulting in much faster, less expensive and simpler plant design, start-up, and operation, because cell culture process steps are no longer performed in hard-piped unit operations. This leads to simpler operations in a lab-like environment. Overall it enriches the current landscape of available facilities from standard hard-piped to hard-piped/disposables hybrid to completely single-use-based production plants using the current segregation and containment concept. At the top, disposables in combination with completely and functionally closed systems facilitate a new, revolutionary design of ballroom facilities without or with much less segregation, which enables us to perform good manufacturing practice manufacturing of different products simultaneously in unclassified but controlled areas.Finally, single-use processing in lab-like shell facilities is a big enabler of transferring and establishing production in emergent countries, and this is described in more detail in 7. Graphical Abstract.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ulsh, M.; Wheeler, D.; Protopappas, P.
The U.S. Department of Energy (DOE) is interested in supporting manufacturing research and development (R&D) for fuel cell systems in the 10-1,000 kilowatt (kW) power range relevant to stationary and distributed combined heat and power applications, with the intent to reduce manufacturing costs and increase production throughput. To assist in future decision-making, DOE requested that the National Renewable Energy Laboratory (NREL) provide a baseline understanding of the current levels of adoption of automation in manufacturing processes and flow, as well as of continuous processes. NREL identified and visited or interviewed key manufacturers, universities, and laboratories relevant to the study usingmore » a standard questionnaire. The questionnaire covered the current level of vertical integration, the importance of quality control developments for automation, the current level of automation and source of automation design, critical balance of plant issues, potential for continuous cell manufacturing, key manufacturing steps or processes that would benefit from DOE support for manufacturing R&D, the potential for cell or stack design changes to support automation, and the relationship between production volume and decisions on automation.« less
Freeform Optics: current challenges for future serial production
NASA Astrophysics Data System (ADS)
Schindler, C.; Köhler, T.; Roth, E.
2017-10-01
One of the major developments in optics industry recently is the commercial manufacturing of freeform surfaces for optical mid- and high performance systems. The loss of limitation on rotational symmetry enables completely new optical design solutions - but causes completely new challenges for the manufacturer too. Adapting the serial production from radial-symmetric to freeform optics cannot be done just by the extension of machine capabilities and software for every process step. New solutions for conventional optics productions or completely new process chains are necessary.
Potential Dimension Yields From Direct Processing
Wenjie Lin; D. Earl Kline; Philip A. Araman
1994-01-01
As the price of timber increases and environmental leigslation limits harvestable log volumes, the process of converting logs directly into dimension parts needs further exploration. Direct processing converts logs directly into rough green dimension parts without the intermediate steps of lumber manufacturing, grading, trading, shipping and drying. A major attraction...
Nepveux, Kevin; Sherlock, Jon-Paul; Futran, Mauricio; Thien, Michael; Krumme, Markus
2015-03-01
Continuous manufacturing (CM) is a process technology that has been used in the chemical industry for large-scale mass production of chemicals in single-purpose plants with benefit for many years. Recent interest has been raised to expand CM into the low-volume, high-value pharmaceutical business with its unique requirements regarding readiness for human use and the required quality, supply chain, and liability constraints in this business context. Using a fairly abstract set of definitions, this paper derives technical consequences of CM in different scenarios along the development-launch-supply axis in different business models and how they compare to batch processes. Impact of CM on functions in development is discussed and several operational models suitable for originators and other business models are discussed and specific aspects of CM are deduced from CM's technical characteristics. Organizational structures of current operations typically can support CM implementations with just minor refinements if the CM technology is limited to single steps or small sequences (bin-to-bin approach) and if the appropriate technical skill set is available. In such cases, a small, dedicated group focused on CM is recommended. The manufacturing strategy, as centralized versus decentralized in light of CM processes, is discussed and the potential impact of significantly shortened supply lead times on the organization that runs these processes. The ultimate CM implementation may be seen by some as a totally integrated monolithic plant, one that unifies chemistry and pharmaceutical operations into one plant. The organization supporting this approach will have to reflect this change in scope and responsibility. The other extreme, admittedly futuristic at this point, would be a highly decentralized approach with multiple smaller hubs; this would require a new and different organizational structure. This processing approach would open up new opportunities for products that, because of stability constraints or individualization to patients, do not allow centralized manufacturing approaches at all. Again, the entire enterprise needs to be restructured accordingly. The situation of CM in an outsourced operation business model is discussed. Next steps for the industry are recommended. In summary, opportunistic implementation of isolated steps in existing portfolios can be implemented with minimal organizational changes; the availability of the appropriate skills is the determining factor. The implementation of more substantial sequences requires business processes that consider the portfolio, not just single products. Exploration and implementation of complete process chains with consequences for quality decisions do require appropriate organizational support. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
NASA Astrophysics Data System (ADS)
Lhomé, Emilie; Agócs, Tibor; Abrams, Don Carlos; Dee, Kevin M.; Middleton, Kevin F.; Tosh, Ian A.; Jaskó, Attila; Connor, Peter; Cochrane, Dave; Gers, Luke; Jonas, Graeme; Rakich, Andrew; Benn, Chris R.; Balcells, Marc; Trager, Scott C.; Dalton, Gavin B.; Carrasco, Esperanza; Vallenari, Antonella; Bonifacio, Piercarlo; Aguerri, J. Alfonso L.
2016-07-01
In this paper, we detail the manufacturing process for the lenses that will constitute the new two-degree field-of-view Prime Focus Corrector (PFC) for the 4.2m William Herschel Telescope (WHT) optimised for the upcoming WEAVE Multi-Object Spectroscopy (MOS) facility. The corrector, including an Atmospheric Dispersion Corrector (ADC), is made of six large lenses, the largest being 1.1-meter diameter. We describe how the prescriptions of the optical design were translated into manufacturing specifications for the blanks and lenses. We explain how the as-built glass blank parameters were fed back into the optical design and how the specifications for the lenses were subsequently modified. We review the critical issues for the challenging manufacturing process and discuss the trade-offs that were necessary to deliver the lenses while maintaining the optimal optical performance. A short description of the lens optical testing is also presented. Finally, the subsequent manufacturing steps, including assembly, integration, and alignment are outlined.
NASA Astrophysics Data System (ADS)
Shahriar, Bakrani Balani; Arthur, Cantarel; France, Chabert; Valérie, Nassiet
2018-05-01
Extrusion is one of the oldest manufacturing processes; it is widely used for manufacturing finished and semi-finished products. Moreover, extrusion is also the main process in additive manufacturing technologies such as Fused Filament Fabrication (FFF). In FFF process, the parts are manufactured layer by layer using thermoplastic material. The latter in form of filament, is melted in the liquefier and then it is extruded and deposited on the previous layer. The mechanical properties of the printed parts rely on the coalescence of each extrudate with another one. The coalescence phenomenon is driven by the flow properties of the melted polymer when it comes out the nozzle just before the deposition step. This study aims to master the quality of the printed parts by controlling the effect of the parameters of the extruder on the flow properties in the FFF process. In the current study, numerical simulation of the polymer coming out of the extruder was carried out using Computational Fluid Dynamics (CFD) and two phase flow (TPF) simulation Level Set (LS) method by 2D axisymmetric module of COMSOL Multiphysics software. In order to pair the heat transfer with the flow simulation, an advection-diffusion equation was used. Advection-diffusion equation was implemented as a Partial Differential Equation (PDE) in the software. In order to define the variation of viscosity of the polymer with temperature, the rheological behaviors of two thermoplastics were measured by extensional rheometer and using a parallel-plate configuration of an oscillatory rheometer. The results highlight the influence of the environment temperature and the cooling rate on the temperature and viscosity of the extrudate exiting from the nozzle. Moreover, the temperature and its corresponding viscosity at different times have been determined using numerical simulation. At highest shear rates, the extrudate undergoes deformation from typical cylindrical shape. These results are required to predict the coalescence of filaments, a step towards understanding the mechanical properties of the printed parts.
Incorporating exposure science into life-cycle assessment
Life-cycle assessment (LCA) is used to estimate the potential for environmental damage that may be caused by a product or process, ideally before the product or process begins. LCA includes all of the steps from extracting natural resources through manufacturing through product u...
Pollock, James; Bolton, Glen; Coffman, Jon; Ho, Sa V; Bracewell, Daniel G; Farid, Suzanne S
2013-04-05
This paper presents an integrated experimental and modelling approach to evaluate the potential of semi-continuous chromatography for the capture of monoclonal antibodies (mAb) in clinical and commercial manufacture. Small-scale single-column experimental breakthrough studies were used to derive design equations for the semi-continuous affinity chromatography system. Verification runs with the semi-continuous 3-column and 4-column periodic counter current (PCC) chromatography system indicated the robustness of the design approach. The product quality profiles and step yields (after wash step optimisation) achieved were comparable to the standard batch process. The experimentally-derived design equations were incorporated into a decisional tool comprising dynamic simulation, process economics and sizing optimisation. The decisional tool was used to evaluate the economic and operational feasibility of whole mAb bioprocesses employing PCC affinity capture chromatography versus standard batch chromatography across a product's lifecycle from clinical to commercial manufacture. The tool predicted that PCC capture chromatography would offer more significant savings in direct costs for early-stage clinical manufacture (proof-of-concept) (∼30%) than for late-stage clinical (∼10-15%) or commercial (∼5%) manufacture. The evaluation also highlighted the potential facility fit issues that could arise with a capture resin (MabSelect) that experiences losses in binding capacity when operated in continuous mode over lengthy commercial campaigns. Consequently, the analysis explored the scenario of adopting the PCC system for clinical manufacture and switching to the standard batch process following product launch. The tool determined the PCC system design required to operate at commercial scale without facility fit issues and with similar costs to the standard batch process whilst pursuing a process change application. A retrofitting analysis established that the direct cost savings obtained by 8 proof-of-concept batches would be sufficient to pay back the investment cost of the pilot-scale semi-continuous chromatography system. Copyright © 2013 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Koenig, Jan D.
2018-04-01
Thermoelectric devices convert heat flows into electricity. Researchers recently demonstrated that thermoelectric materials can be produced in good quality by 3D printing, enabling a low-cost production process in the near future.
Hot working behavior of selective laser melted and laser metal deposited Inconel 718
NASA Astrophysics Data System (ADS)
Bambach, Markus; Sizova, Irina
2018-05-01
The production of Nickel-based high-temperature components is of great importance for the transport and energy sector. Forging of high-temperature alloys often requires expensive dies, multiple forming steps and leads to forged parts with tolerances that require machining to create the final shape and a large amount of scrap. Additive manufacturing offers the possibility to print the desired shapes directly as net-shape components, requiring only little additional effort in machining. Especially for high-temperature alloys carrying a large amount of energy per unit mass, additive manufacturing could be more energy-efficient than forging if the energy contained in the machining scrap exceeds the energy needed for powder production and laser processing. However, the microstructure and performance of 3d-printed parts will not reach the level of forged material unless further expensive processes such as hot-isostatic pressing are used. Using the design freedom and possibilities to locally engineer material, additive manufacturing could be combined with forging operations to novel process chains, offering the possibility to reduce the number of forging steps and to create near-net shape forgings with desired local properties. Some innovative process chains combining additive manufacturing and forging have been patented recently, but almost no scientific knowledge on the workability of 3D printed preforms exists. The present study investigates the flow stress and microstructure evolution during hot working of pre-forms produced by laser powder deposition and selective laser melting (Figure 1) and puts forward a model for the flow stress.
Influence of type of muscle on volatile compounds throughout the manufacture of Celta dry-cured ham.
Bermúdez, Roberto; Franco, Daniel; Carballo, Javier; Lorenzo, José M
2015-12-01
The effect of muscle type on volatile compounds throughout the manufacture of Celta dry-cured ham was studied. Thirty Celta ham were taken from the fresh pieces, after the end of the salting stage, after 120 days of post-salting, after the end of drying-ripening stage, and after 165 and 330 days of "bodega" step. The volatile compounds from semimembranosus (SM) and biceps femoris (BF) muscles were extracted by using headspace-solid phase microextraction (SPME) and analysed by gas chromatographic/mass spectrometry (GC/MS). Fifty-five volatile compounds were identified and quantified. The number of volatile compounds increased during the different steps of the process, reaching at 550 days of process 39 and 40 volatile compounds in SM and BF muscles, respectively. Results indicated that the most abundant chemical family in flavour at the end of the manufacturing process were esters in the two muscles studied, followed by aliphatic hydrocarbons and aldehydes. During the manufacturing process, an increase in the total amount of volatile compounds was observed, being this increase more marked in samples from BF muscle (from 550.7 to 1118.9 × 10(6) area units) than in samples from SM muscle (from 459.3 to 760.4 × 10(6) area units). Finally, muscle type displayed significant (P < 0.05) differences for four esters, two alcohols, one aldehyde, one ketone and four aliphatic hydrocarbons. © The Author(s) 2014.
One size fits all electronics for insole-based activity monitoring.
Hegde, Nagaraj; Bries, Matthew; Melanson, Edward; Sazonov, Edward
2017-07-01
Footwear based wearable sensors are becoming prominent in many areas of monitoring health and wellness, such as gait and activity monitoring. In our previous research we introduced an insole based wearable system SmartStep, which is completely integrated in a socially acceptable package. From a manufacturing perspective, SmartStep's electronics had to be custom made for each shoe size, greatly complicating the manufacturing process. In this work we explore the possibility of making a universal electronics platform for SmartStep - SmartStep 3.0, which can be used in the most common insole sizes without modifications. A pilot human subject experiments were run to compare the accuracy between the one-size fits all (SmartStep 3.0) and custom size SmartStep 2.0. A total of ~10 hours of data was collected in the pilot study involving three participants performing different activities of daily living while wearing SmartStep 2.0 and SmartStep 3.0. Leave one out cross validation resulted in a 98.5% average accuracy from SmartStep 2.0, while SmartStep 3.0 resulted in 98.3% accuracy, suggesting that the SmartStep 3.0 can be as accurate as SmartStep 2.0, while fitting most common shoe sizes.
Addressable-Matrix Integrated-Circuit Test Structure
NASA Technical Reports Server (NTRS)
Sayah, Hoshyar R.; Buehler, Martin G.
1991-01-01
Method of quality control based on use of row- and column-addressable test structure speeds collection of data on widths of resistor lines and coverage of steps in integrated circuits. By use of straightforward mathematical model, line widths and step coverages deduced from measurements of electrical resistances in each of various combinations of lines, steps, and bridges addressable in test structure. Intended for use in evaluating processes and equipment used in manufacture of application-specific integrated circuits.
Intelligent monitoring and control of semiconductor manufacturing equipment
NASA Technical Reports Server (NTRS)
Murdock, Janet L.; Hayes-Roth, Barbara
1991-01-01
The use of AI methods to monitor and control semiconductor fabrication in a state-of-the-art manufacturing environment called the Rapid Thermal Multiprocessor is described. Semiconductor fabrication involves many complex processing steps with limited opportunities to measure process and product properties. By applying additional process and product knowledge to that limited data, AI methods augment classical control methods by detecting abnormalities and trends, predicting failures, diagnosing, planning corrective action sequences, explaining diagnoses or predictions, and reacting to anomalous conditions that classical control systems typically would not correct. Research methodology and issues are discussed, and two diagnosis scenarios are examined.
Method for indexing and retrieving manufacturing-specific digital imagery based on image content
Ferrell, Regina K.; Karnowski, Thomas P.; Tobin, Jr., Kenneth W.
2004-06-15
A method for indexing and retrieving manufacturing-specific digital images based on image content comprises three steps. First, at least one feature vector can be extracted from a manufacturing-specific digital image stored in an image database. In particular, each extracted feature vector corresponds to a particular characteristic of the manufacturing-specific digital image, for instance, a digital image modality and overall characteristic, a substrate/background characteristic, and an anomaly/defect characteristic. Notably, the extracting step includes generating a defect mask using a detection process. Second, using an unsupervised clustering method, each extracted feature vector can be indexed in a hierarchical search tree. Third, a manufacturing-specific digital image associated with a feature vector stored in the hierarchicial search tree can be retrieved, wherein the manufacturing-specific digital image has image content comparably related to the image content of the query image. More particularly, can include two data reductions, the first performed based upon a query vector extracted from a query image. Subsequently, a user can select relevant images resulting from the first data reduction. From the selection, a prototype vector can be calculated, from which a second-level data reduction can be performed. The second-level data reduction can result in a subset of feature vectors comparable to the prototype vector, and further comparable to the query vector. An additional fourth step can include managing the hierarchical search tree by substituting a vector average for several redundant feature vectors encapsulated by nodes in the hierarchical search tree.
Energy impact of cathode drying and solvent recovery during lithium-ion battery manufacturing
NASA Astrophysics Data System (ADS)
Ahmed, Shabbir; Nelson, Paul A.; Gallagher, Kevin G.; Dees, Dennis W.
2016-08-01
Successful deployment of electric vehicles requires maturity of the manufacturing process to reduce the cost of the lithium ion battery (LIB) pack. Drying the coated cathode layer and subsequent recovery of the solvent for recycle is a vital step in the lithium ion battery manufacturing plant and offers significant potential for cost reduction. A spreadsheet model of the drying and recovery of the solvent, is used to study the energy demand of this step and its contribution towards the cost of the battery pack. The base case scenario indicates that the drying and recovery process imposes an energy demand of ∼10 kWh per kg of the solvent n-methyl pyrrolidone (NMP), and is almost 45 times the heat needed to vaporize the NMP. For a plant producing 100 K battery packs per year for 10 kWh plug-in hybrid vehicles (PHEV), the energy demand is ∼5900 kW and the process contributes 107 or 3.4% to the cost of the battery pack. The cost of drying and recovery is equivalent to 1.12 per kg of NMP recovered, saving 2.08 per kg in replacement purchase.
Manufacturing considerations for AMLCD cockpit displays
NASA Astrophysics Data System (ADS)
Luo, Fang-Chen
1995-06-01
AMLCD cockpit displays need to meet more stringent requirements compared with AMLCD commercial displays in areas such as environmental conditions, optical performance and device reliability. Special considerations are required for the manufacturing of AMLCD cockpit displays in each process step to address these issues. Some examples are: UV stable polarizers, wide-temperature LC material, strong LC glue seal, ESS test system, gray scale voltage EEPROM, etc.
Equilibrium moisture content during storage, manufacturing, and shipping of Bolivian wood products
Omar A. Espinoza; Brian H. Bond; Joseph R. Loferski
2007-01-01
After lumber is kiln-dried it is important to keep its moisture content (MC) as close as possible to its target value during all stages of production to assure final product quality. Knowledge of climate conditions at all stages of the manufacturing process is essential to provide a good control of lumber MC. This study is the first step to provide Bolivian companies...
Steinebach, Fabian; Müller-Späth, Thomas; Morbidelli, Massimo
2016-09-01
The economic advantages of continuous processing of biopharmaceuticals, which include smaller equipment and faster, efficient processes, have increased interest in this technology over the past decade. Continuous processes can also improve quality assurance and enable greater controllability, consistent with the quality initiatives of the FDA. Here, we discuss different continuous multi-column chromatography processes. Differences in the capture and polishing steps result in two different types of continuous processes that employ counter-current column movement. Continuous-capture processes are associated with increased productivity per cycle and decreased buffer consumption, whereas the typical purity-yield trade-off of classical batch chromatography can be surmounted by continuous processes for polishing applications. In the context of continuous manufacturing, different but complementary chromatographic columns or devices are typically combined to improve overall process performance and avoid unnecessary product storage. In the following, these various processes, their performances compared with batch processing and resulting product quality are discussed based on a review of the literature. Based on various examples of applications, primarily monoclonal antibody production processes, conclusions are drawn about the future of these continuous-manufacturing technologies. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
A guide to manufacturing CAR T cell therapies.
Vormittag, Philipp; Gunn, Rebecca; Ghorashian, Sara; Veraitch, Farlan S
2018-02-17
In recent years, chimeric antigen receptor (CAR) modified T cells have been used as a treatment for haematological malignancies in several phase I and II trials and with Kymriah of Novartis and Yescarta of KITE Pharma, the first CAR T cell therapy products have been approved. Promising clinical outcomes have yet been tempered by the fact that many therapies may be prohibitively expensive to manufacture. The process is not yet defined, far from being standardised and often requires extensive manual handling steps. For academia, big pharma and contract manufacturers it is difficult to obtain an overview over the process strategies and their respective advantages and disadvantages. This review details current production processes being used for CAR T cells with a particular focus on efficacy, reproducibility, manufacturing costs and release testing. By undertaking a systematic analysis of the manufacture of CAR T cells from reported clinical trial data to date, we have been able to quantify recent trends and track the uptake of new process technology. Delivering new processing options will be key to the success of the CAR-T cells ensuring that excessive manufacturing costs do not disrupt the delivery of exciting new therapies to the wide possible patient cohort. Copyright © 2018 Elsevier Ltd. All rights reserved.
LSA: Low-cost Solar Array project
NASA Technical Reports Server (NTRS)
1978-01-01
Topics discussed include silicon material processing; large-area silicon sheet development; encapsulation materials testing and development; project engineering and operations activities, and manufacturing techniques. The steps taken to integrate these efforts, are described.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bates, Robert; McConnell, Elizabeth
Machining methods across many industries generally require multiple operations to machine and process advanced materials, features with micron precision, and complex shapes. The resulting multiple machining platforms can significantly affect manufacturing cycle time and the precision of the final parts, with a resultant increase in cost and energy consumption. Ultrafast lasers represent a transformative and disruptive technology that removes material with micron precision and in a single step manufacturing process. Such precision results from athermal ablation without modification or damage to the remaining material which is the key differentiator between ultrafast laser technologies and traditional laser technologies or mechanical processes.more » Athermal ablation without modification or damage to the material eliminates post-processing or multiple manufacturing steps. Combined with the appropriate technology to control the motion of the work piece, ultrafast lasers are excellent candidates to provide breakthrough machining capability for difficult-to-machine materials. At the project onset in early 2012, the project team recognized that substantial effort was necessary to improve the application of ultrafast laser and precise motion control technologies (for micromachining difficult-to-machine materials) to further the aggregate throughput and yield improvements over conventional machining methods. The project described in this report advanced these leading-edge technologies thru the development and verification of two platforms: a hybrid enhanced laser chassis and a multi-application testbed.« less
Koziel, David; Michaelis, Uwe; Kruse, Tobias
2018-08-01
Endotoxins contaminate proteins that are produced in E. coli. High levels of endotoxins can influence cellular assays and cause severe adverse effects when administered to humans. Thus, endotoxin removal is important in protein purification for academic research and in GMP manufacturing of biopharmaceuticals. Several methods exist to remove endotoxin, but often require additional downstream-processing steps, decrease protein yield and are costly. These disadvantages can be avoided by using an integrated endotoxin depletion (iED) wash-step that utilizes Triton X-114 (TX114). In this paper, we show that the iED wash-step is broadly applicable in most commonly used chromatographies: it reduces endotoxin by a factor of 10 3 to 10 6 during NiNTA-, MBP-, SAC-, GST-, Protein A and CEX-chromatography but not during AEX or HIC-chromatography. We characterized the iED wash-step using Design of Experiments (DoE) and identified optimal experimental conditions for application scenarios that are relevant to academic research or industrial GMP manufacturing. A single iED wash-step with 0.75% (v/v) TX114 added to the feed and wash buffer can reduce endotoxin levels to below 2 EU/ml or deplete most endotoxin while keeping the manufacturing costs as low as possible. The comprehensive characterization enables academia and industry to widely adopt the iED wash-step for a routine, efficient and cost-effective depletion of endotoxin during protein purification at any scale. Copyright © 2018. Published by Elsevier B.V.
Simulation of dynamic processes when machining transition surfaces of stepped shafts
NASA Astrophysics Data System (ADS)
Maksarov, V. V.; Krasnyy, V. A.; Viushin, R. V.
2018-03-01
The paper addresses the characteristics of stepped surfaces of parts categorized as "solids of revolution". It is noted that in the conditions of transition modes during the switch to end surface machining, there is cutting with varied load intensity in the section of the cut layer, which leads to change in cutting force, onset of vibrations, an increase in surface layer roughness, a decrease of size precision, and increased wear of a tool's cutting edge. This work proposes a method that consists in developing a CNC program output code that allows one to process complex forms of stepped shafts with only one machine setup. The authors developed and justified a mathematical model of a technological system for mechanical processing with consideration for the resolution of tool movement at the stages of transition processes to assess the dynamical stability of a system in the process of manufacturing stepped surfaces of parts of “solid of revolution” type.
Neisser-Svae, A; Bailey, A; Gregori, L; Heger, A; Jordan, S; Behizad, M; Reichl, H; Römisch, J; Svae, T-E
2009-10-01
A new chromatographic step for the selective binding of abnormal prion protein (PrP(Sc)) was developed, and optimization for PrP(Sc) capture was achieved by binding to an affinity ligand attached to synthetic resin particles. This step was implemented into the manufacturing process of the solvent/detergent (S/D)-treated biopharmaceutical quality plasma Octaplas to further improve the safety margin in terms of risk for variant Creutzfeldt-Jakob disease (vCJD) transmission. Intermediates and Octaplas final container material, spiked with hamster brain-derived PrP(Sc)-containing fractions, were used for experiments to establish the feasibility of introducing this novel chromatography step. The binding capacity per millilitre of ligand gel was determined under the selected manufacturing conditions. In addition, the specificity of the ligand gel to bind PrP(Sc) from human sources was investigated. A validated Western blot test was used for the identification and quantification of PrP(Sc). A reduction factor of > or = 3.0 log(10) could be demonstrated by Western blotting, utilizing the relevant Octaplas matrix from manufacturing. In this particular cell-free plasma solution, the PrP(Sc) binding capacity of the selected gel was very high (> or = 6 log(10) ID(50)/ml, equivalent to roughly 10 log(10) ID(50)/column at manufacturing scale). The gel binds specifically PrP(Sc) from both animal (hamster and mouse) and human (sporadic and variant CJD) sources. This new single-use, disposable PrP(Sc)-harvesting gel ensures a very high capacity in terms of removing the pathogenic agent causing vCJD from the new generation OctaplasLG, in the event that prions can be found in plasma from donors incubating the disease and thereby contaminating the raw material plasma used for manufacturing.
Context-based virtual metrology
NASA Astrophysics Data System (ADS)
Ebersbach, Peter; Urbanowicz, Adam M.; Likhachev, Dmitriy; Hartig, Carsten; Shifrin, Michael
2018-03-01
Hybrid and data feed forward methodologies are well established for advanced optical process control solutions in highvolume semiconductor manufacturing. Appropriate information from previous measurements, transferred into advanced optical model(s) at following step(s), provides enhanced accuracy and exactness of the measured topographic (thicknesses, critical dimensions, etc.) and material parameters. In some cases, hybrid or feed-forward data are missed or invalid for dies or for a whole wafer. We focus on approaches of virtual metrology to re-create hybrid or feed-forward data inputs in high-volume manufacturing. We discuss missing data inputs reconstruction which is based on various interpolation and extrapolation schemes and uses information about wafer's process history. Moreover, we demonstrate data reconstruction approach based on machine learning techniques utilizing optical model and measured spectra. And finally, we investigate metrics that allow one to assess error margin of virtual data input.
Soares, Filipa A.C.; Chandra, Amit; Thomas, Robert J.; Pedersen, Roger A.; Vallier, Ludovic; Williams, David J.
2014-01-01
The transfer of a laboratory process into a manufacturing facility is one of the most critical steps required for the large scale production of cell-based therapy products. This study describes the first published protocol for scalable automated expansion of human induced pluripotent stem cell lines growing in aggregates in feeder-free and chemically defined medium. Cells were successfully transferred between different sites representative of research and manufacturing settings; and passaged manually and using the CompacT SelecT automation platform. Modified protocols were developed for the automated system and the management of cells aggregates (clumps) was identified as the critical step. Cellular morphology, pluripotency gene expression and differentiation into the three germ layers have been used compare the outcomes of manual and automated processes. PMID:24440272
Process for manufacture of inertial confinement fusion targets and resulting product
Masnari, Nino A.; Rensel, Walter B.; Robinson, Merrill G.; Solomon, David E.; Wise, Kensall D.; Wuttke, Gilbert H.
1982-01-01
An ICF target comprising a spherical pellet of fusion fuel surrounded by a concentric shell; and a process for manufacturing the same which includes the steps of forming hemispheric shells of a silicon or other substrate material, adhering the shell segments to each other with a fuel pellet contained concentrically therein, then separating the individual targets from the parent substrate. Formation of hemispheric cavities by deposition or coating of a mold substrate is also described. Coatings or membranes may also be applied to the interior of the hemispheric segments prior to joining.
Mining manufacturing data for discovery of high productivity process characteristics.
Charaniya, Salim; Le, Huong; Rangwala, Huzefa; Mills, Keri; Johnson, Kevin; Karypis, George; Hu, Wei-Shou
2010-06-01
Modern manufacturing facilities for bioproducts are highly automated with advanced process monitoring and data archiving systems. The time dynamics of hundreds of process parameters and outcome variables over a large number of production runs are archived in the data warehouse. This vast amount of data is a vital resource to comprehend the complex characteristics of bioprocesses and enhance production robustness. Cell culture process data from 108 'trains' comprising production as well as inoculum bioreactors from Genentech's manufacturing facility were investigated. Each run constitutes over one-hundred on-line and off-line temporal parameters. A kernel-based approach combined with a maximum margin-based support vector regression algorithm was used to integrate all the process parameters and develop predictive models for a key cell culture performance parameter. The model was also used to identify and rank process parameters according to their relevance in predicting process outcome. Evaluation of cell culture stage-specific models indicates that production performance can be reliably predicted days prior to harvest. Strong associations between several temporal parameters at various manufacturing stages and final process outcome were uncovered. This model-based data mining represents an important step forward in establishing a process data-driven knowledge discovery in bioprocesses. Implementation of this methodology on the manufacturing floor can facilitate a real-time decision making process and thereby improve the robustness of large scale bioprocesses. 2010 Elsevier B.V. All rights reserved.
User's guide to resin infusion simulation program in the FORTRAN language
NASA Technical Reports Server (NTRS)
Weideman, Mark H.; Hammond, Vince H.; Loos, Alfred C.
1992-01-01
RTMCL is a user friendly computer code which simulates the manufacture of fabric composites by the resin infusion process. The computer code is based on the process simulation model described in reference 1. Included in the user's guide is a detailed step by step description of how to run the program and enter and modify the input data set. Sample input and output files are included along with an explanation of the results. Finally, a complete listing of the program is provided.
Ono, Daiki; Bamba, Takeshi; Oku, Yuichi; Yonetani, Tsutomu; Fukusaki, Eiichiro
2011-09-01
In this study, we constructed prediction models by metabolic fingerprinting of fresh green tea leaves using Fourier transform near-infrared (FT-NIR) spectroscopy and partial least squares (PLS) regression analysis to objectively optimize of the steaming process conditions in green tea manufacture. The steaming process is the most important step for manufacturing high quality green tea products. However, the parameter setting of the steamer is currently determined subjectively by the manufacturer. Therefore, a simple and robust system that can be used to objectively set the steaming process parameters is necessary. We focused on FT-NIR spectroscopy because of its simple operation, quick measurement, and low running costs. After removal of noise in the spectral data by principal component analysis (PCA), PLS regression analysis was performed using spectral information as independent variables, and the steaming parameters set by experienced manufacturers as dependent variables. The prediction models were successfully constructed with satisfactory accuracy. Moreover, the results of the demonstrated experiment suggested that the green tea steaming process parameters could be predicted on a larger manufacturing scale. This technique will contribute to improvement of the quality and productivity of green tea because it can objectively optimize the complicated green tea steaming process and will be suitable for practical use in green tea manufacture. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
Tracking the course of the manufacturing process in selective laser melting
NASA Astrophysics Data System (ADS)
Thombansen, U.; Gatej, A.; Pereira, M.
2014-02-01
An innovative optical train for a selective laser melting based manufacturing system (SLM) has been designed under the objective to track the course of the SLM process. In this, the thermal emission from the melt pool and the geometric properties of the interaction zone are addressed by applying a pyrometer and a camera system respectively. The optical system is designed such that all three radiations from processing laser, thermal emission and camera image are coupled coaxially and that they propagate on the same optical axis. As standard f-theta lenses for high power applications inevitably lead to aberrations and divergent optical axes for increasing deflection angles in combination with multiple wavelengths, a pre-focus system is used to implement a focusing unit which shapes the beam prior to passing the scanner. The sensor system records synchronously the current position of the laser beam, the current emission from the melt pool and an image of the interaction zone. Acquired data of the thermal emission is being visualized after processing which allows an instant evaluation of the course of the process at any position of each layer. As such, it provides a fully detailed history of the product This basic work realizes a first step towards self-optimization of the manufacturing process by providing information about quality relevant events during manufacture. The deviation from the planned course of the manufacturing process to the actual course of the manufacturing process can be used to adapt the manufacturing strategy from one layer to the next. In the current state, the system can be used to facilitate the setup of the manufacturing system as it allows identification of false machine settings without having to analyze the work piece.
Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review.
Blackshields, Caroline A; Crean, Abina M
2018-07-01
There has been a noticeable shift from pharmaceutical batch processing towards a more continuous mode of manufacture for solid oral dosage forms. Continuous solid oral dose processes would not be possible in the absence of a highly accurate feeding system. The performance of feeders defines the content of formulations and is therefore a critical operation in continuous manufacturing of solid dosage forms. It was the purpose of this review to review the role of the initial powder feeding step in a continuous manufacturing process. Different feeding mechanisms are discussed with a particular emphasis on screw controlled loss in weight (LIW) feeding. The importance of understanding the physical properties of the raw materials and its impact on the feeding process is reviewed. Prior knowledge of materials provides an initial indication of how the powders will behave through processing and facilitates in the selection of the most suitable (i) feeder (capacity), (ii) feeding mechanism, and (iii) in the case of screw feeder - screw type. The studies identified in this review focus on the impact of material on powder feeding performance.
Very large scale monoclonal antibody purification: the case for conventional unit operations.
Kelley, Brian
2007-01-01
Technology development initiatives targeted for monoclonal antibody purification may be motivated by manufacturing limitations and are often aimed at solving current and future process bottlenecks. A subject under debate in many biotechnology companies is whether conventional unit operations such as chromatography will eventually become limiting for the production of recombinant protein therapeutics. An evaluation of the potential limitations of process chromatography and filtration using today's commercially available resins and membranes was conducted for a conceptual process scaled to produce 10 tons of monoclonal antibody per year from a single manufacturing plant, a scale representing one of the world's largest single-plant capacities for cGMP protein production. The process employs a simple, efficient purification train using only two chromatographic and two ultrafiltration steps, modeled after a platform antibody purification train that has generated 10 kg batches in clinical production. Based on analyses of cost of goods and the production capacity of this very large scale purification process, it is unlikely that non-conventional downstream unit operations would be needed to replace conventional chromatographic and filtration separation steps, at least for recombinant antibodies.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-21
... knowledge transfer, technology transition, and technology diffusion steps, along with numerous... promising research discoveries and ideas for advanced, high-value-added products and processes with existing...
The onsite manufacture of propellant oxygen from lunar resources
NASA Technical Reports Server (NTRS)
Rosenberg, Sanders D.; Beegle, Robert L., Jr.; Guter, Gerald A.; Miller, Frederick E.; Rothenberg, Michael
1992-01-01
The Aerojet carbothermal process for the manufacture of oxygen from lunar materials has three essential steps: the reduction of silicate with methane to form carbon monoxide and hydrogen; the reduction of carbon monoxide with hydrogen to form methane and water; and the electrolysis of water to form hydrogen and oxygen. The reactions and the overall process are shown. It is shown with laboratory experimentation that the carbothermal process is feasible. Natural silicates can be reduced with carbon or methane. The important products are carbon monoxide, metal, and slag. The carbon monoxide can be completely reduced to form methane and water. The water can be electrolyzed to produce hydrogen and oxygen. A preliminary engineering study shows that the operation of plants using this process for the manufacture of propellant oxygen has a large economic advantage when the cost of the plant and its operation is compared to the cost of delivering oxygen from Earth.
Laminated Object Manufacturing of 3D-Printed Laser-Induced Graphene Foams.
Luong, Duy Xuan; Subramanian, Ajay K; Silva, Gladys A Lopez; Yoon, Jongwon; Cofer, Savannah; Yang, Kaichun; Owuor, Peter Samora; Wang, Tuo; Wang, Zhe; Lou, Jun; Ajayan, Pulickel M; Tour, James M
2018-05-29
Laser-induced graphene (LIG), a graphene structure synthesized by a one-step process through laser treatment of commercial polyimide (PI) film in an ambient atmosphere, has been shown to be a versatile material in applications ranging from energy storage to water treatment. However, the process as developed produces only a 2D product on the PI substrate. Here, a 3D LIG foam printing process is developed on the basis of laminated object manufacturing, a widely used additive-manufacturing technique. A subtractive laser-milling process to yield further refinements to the 3D structures is also developed and shown here. By combining both techniques, various 3D graphene objects are printed. The LIG foams show good electrical conductivity and mechanical strength, as well as viability in various energy storage and flexible electronic sensor applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Nicolette, C A; Healey, D; Tcherepanova, I; Whelton, P; Monesmith, T; Coombs, L; Finke, L H; Whiteside, T; Miesowicz, F
2007-09-27
Dendritic cell (DC) active immunotherapy is potentially efficacious in a broad array of malignant disease settings. However, challenges remain in optimizing DC-based therapy for maximum clinical efficacy within manufacturing processes that permit quality control and scale-up of consistent products. In this review we discuss the critical issues that must be addressed in order to optimize DC-based product design and manufacture, and highlight the DC based platforms currently addressing these issues. Variables in DC-based product design include the type of antigenic payload used, DC maturation steps and activation processes, and functional assays. Issues to consider in development include: (a) minimizing the invasiveness of patient biological material collection; (b) minimizing handling and manipulations of tissue at the clinical site; (c) centralized product manufacturing and standardized processing and capacity for commercial-scale production; (d) rapid product release turnaround time; (e) the ability to manufacture sufficient product from limited starting material; and (f) standardized release criteria for DC phenotype and function. Improvements in the design and manufacture of DC products have resulted in a handful of promising leads currently in clinical development.
Thermodynamic analysis of resources used in manufacturing processes.
Gutowski, Timothy G; Branham, Matthew S; Dahmus, Jeffrey B; Jones, Alissa J; Thiriez, Alexandre
2009-03-01
In this study we use a thermodynamic framework to characterize the material and energy resources used in manufacturing processes. The analysis and data span a wide range of processes from "conventional" processes such as machining, casting, and injection molding, to the so-called "advanced machining" processes such as electrical discharge machining and abrasive waterjet machining, and to the vapor-phase processes used in semiconductor and nanomaterials fabrication. In all, 20 processes are analyzed. The results show that the intensity of materials and energy used per unit of mass of material processed (measured either as specific energy or exergy) has increased by at least 6 orders of magnitude over the past several decades. The increase of material/energy intensity use has been primarily a consequence of the introduction of new manufacturing processes, rather than changes in traditional technologies. This phenomenon has been driven by the desire for precise small-scale devices and product features and enabled by stable and declining material and energy prices over this period. We illustrate the relevance of thermodynamics (including exergy analysis) for all processes in spite of the fact that long-lasting focus in manufacturing has been on product quality--not necessarily energy/material conversion efficiency. We promote the use of thermodynamics tools for analysis of manufacturing processes within the context of rapidly increasing relevance of sustainable human enterprises. We confirm that exergy analysis can be used to identify where resources are lost in these processes, which is the first step in proposing and/or redesigning new more efficient processes.
Development of STEP-NC Adaptor for Advanced Web Manufacturing System
NASA Astrophysics Data System (ADS)
Ajay Konapala, Mr.; Koona, Ramji, Dr.
2017-08-01
Information systems play a key role in the modern era of Information Technology. Rapid developments in IT & global competition calls for many changes in basic CAD/CAM/CAPP/CNC manufacturing chain of operations. ‘STEP-NC’ an enhancement to STEP for operating CNC machines, creating new opportunities for collaborative, concurrent, adaptive works across the manufacturing chain of operations. Schemas and data models defined by ISO14649 in liaison with ISO10303 standards made STEP-NC file rich with feature based, rather than mere point to point information of G/M Code format. But one needs to have a suitable information system to understand and modify these files. Various STEP-NC information systems are reviewed to understand the suitability of STEP-NC for web manufacturing. Present work also deals with the development of an adaptor which imports STEP-NC file, organizes its information, allowing modifications to entity values and finally generates a new STEP-NC file to export. The system is designed and developed to work on web to avail additional benefits through the web and also to be part of a proposed ‘Web based STEP-NC manufacturing platform’ which is under development and explained as future scope.
Nepveux, Kevin; Sherlock, Jon-Paul; Futran, Mauricio; Thien, Michael; Krumme, Markus
2015-03-01
Continuous manufacturing (CM) is a process technology that has been used in the chemical industry for large-scale mass production of chemicals in single-purpose plants with benefit for many years. Recent interest has been raised to expand CM into the low-volume, high-value pharmaceutical business with its unique requirements regarding readiness for human use and the required quality, supply chain, and liability constraints in this business context. Using a fairly abstract set of definitions, this paper derives technical consequences of CM in different scenarios along the development-launch-supply axis in different business models and how they compare to batch processes. Impact of CM on functions in development is discussed and several operational models suitable for originators and other business models are discussed and specific aspects of CM are deduced from CM's technical characteristics. Organizational structures of current operations typically can support CM implementations with just minor refinements if the CM technology is limited to single steps or small sequences (bin-to-bin approach) and if the appropriate technical skill set is available. In such cases, a small, dedicated group focused on CM is recommended. The manufacturing strategy, as centralized versus decentralized in light of CM processes, is discussed and the potential impact of significantly shortened supply lead times on the organization that runs these processes. The ultimate CM implementation may be seen by some as a totally integrated monolithic plant, one that unifies chemistry and pharmaceutical operations into one plant. The organization supporting this approach will have to reflect this change in scope and responsibility. The other extreme, admittedly futuristic at this point, would be a highly decentralized approach with multiple smaller hubs; this would require a new and different organizational structure. This processing approach would open up new opportunities for products that, because of stability constraints or individualization to patients, do not allow centralized manufacturing approaches at all. Again, the entire enterprise needs to be restructured accordingly. The situation of CM in an outsourced operation business model is discussed. Next steps for the industry are recommended. In summary, opportunistic implementation of isolated steps in existing portfolios can be implemented with minimal organizational changes; the availability of the appropriate skills is the determining factor. The implementation of more substantial sequences requires business processes that consider the portfolio, not just single products. Exploration and implementation of complete process chains with consequences for quality decisions do require appropriate organizational support. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
Processing and problems in manufacturing a Ti-modified Nb/sub 3/Sn MJR billet. Volume 2
DOE Office of Scientific and Technical Information (OSTI.GOV)
McDonald, W.K.; Smathers, D.; Geno, J.D.
1985-06-18
This report is submitted to complete Task II of University of California Order Number 4321405. Task I had Teledyne Wah Chang Albany (TWCA) assemble and process by the Modified Jelly Roll (MJR) method a Ti-modified Nb/sub 3/Sn superconductor billet. This billet was identified as M103 by TWCA. The billet matrix is nominally composed of copper 13.5 wt % tin bronze sheet and niobium 1.2 wt % titanium expanded metal with a volume ratio of three parts bronze to one part niobium alloy. All processing steps and problems encountered in manufacturing billet M103 are described in this report.
NASA Astrophysics Data System (ADS)
Klein, M.; Eifler, D.
2010-07-01
To analyse interactions between single steps of process chains, variations in material properties, especially the microstructure and the resulting mechanical properties, specimens with tension screw geometry were manufactured with five process chains. The different process chains as well as their parameters influence the near surface condition and consequently the fatigue behaviour in a characteristic manner. The cyclic deformation behaviour of these specimens can be benchmarked equivalently with conventional strain measurements as well as with high-precision temperature and electrical resistance measurements. The development of temperature-values provides substantial information on cyclic load dependent changes in the microstructure.
NASA Astrophysics Data System (ADS)
El-Wardany, Tahany; Lynch, Mathew; Gu, Wenjiong; Hsu, Arthur; Klecka, Michael; Nardi, Aaron; Viens, Daniel
This paper proposes an optimization framework enabling the integration of multi-scale / multi-physics simulation codes to perform structural optimization design for additively manufactured components. Cold spray was selected as the additive manufacturing (AM) process and its constraints were identified and included in the optimization scheme. The developed framework first utilizes topology optimization to maximize stiffness for conceptual design. The subsequent step applies shape optimization to refine the design for stress-life fatigue. The component weight was reduced by 20% while stresses were reduced by 75% and the rigidity was improved by 37%. The framework and analysis codes were implemented using Altair software as well as an in-house loading code. The optimized design was subsequently produced by the cold spray process.
Ramp Technology and Intelligent Processing in Small Manufacturing
NASA Technical Reports Server (NTRS)
Rentz, Richard E.
1992-01-01
To address the issues of excessive inventories and increasing procurement lead times, the Navy is actively pursuing flexible computer integrated manufacturing (FCIM) technologies, integrated by communication networks to respond rapidly to its requirements for parts. The Rapid Acquisition of Manufactured Parts (RAMP) program, initiated in 1986, is an integral part of this effort. The RAMP program's goal is to reduce the current average production lead times experienced by the Navy's inventory control points by a factor of 90 percent. The manufacturing engineering component of the RAMP architecture utilizes an intelligent processing technology built around a knowledge-based shell provided by ICAD, Inc. Rules and data bases in the software simulate an expert manufacturing planner's knowledge of shop processes and equipment. This expert system can use Product Data Exchange using STEP (PDES) data to determine what features the required part has, what material is required to manufacture it, what machines and tools are needed, and how the part should be held (fixtured) for machining, among other factors. The program's rule base then indicates, for example, how to make each feature, in what order to make it, and to which machines on the shop floor the part should be routed for processing. This information becomes part of the shop work order. The process planning function under RAMP greatly reduces the time and effort required to complete a process plan. Since the PDES file that drives the intelligent processing is 100 percent complete and accurate to start with, the potential for costly errors is greatly diminished.
Ramp technology and intelligent processing in small manufacturing
NASA Astrophysics Data System (ADS)
Rentz, Richard E.
1992-04-01
To address the issues of excessive inventories and increasing procurement lead times, the Navy is actively pursuing flexible computer integrated manufacturing (FCIM) technologies, integrated by communication networks to respond rapidly to its requirements for parts. The Rapid Acquisition of Manufactured Parts (RAMP) program, initiated in 1986, is an integral part of this effort. The RAMP program's goal is to reduce the current average production lead times experienced by the Navy's inventory control points by a factor of 90 percent. The manufacturing engineering component of the RAMP architecture utilizes an intelligent processing technology built around a knowledge-based shell provided by ICAD, Inc. Rules and data bases in the software simulate an expert manufacturing planner's knowledge of shop processes and equipment. This expert system can use Product Data Exchange using STEP (PDES) data to determine what features the required part has, what material is required to manufacture it, what machines and tools are needed, and how the part should be held (fixtured) for machining, among other factors. The program's rule base then indicates, for example, how to make each feature, in what order to make it, and to which machines on the shop floor the part should be routed for processing. This information becomes part of the shop work order. The process planning function under RAMP greatly reduces the time and effort required to complete a process plan. Since the PDES file that drives the intelligent processing is 100 percent complete and accurate to start with, the potential for costly errors is greatly diminished.
The vital role of manufacturing quality in the reliability of PV modules
NASA Astrophysics Data System (ADS)
Rusch, Peter
2014-10-01
The influence of manufacturing quality on the reliability of PV modules coming out of today's factories has been, and is still, under estimated among investors and buyers. The main reason is perception. Contrary to popular belief, PV modules are not a commodity. Module quality does differ among module brands. Certification alone does not guarantee the quality or reliability of a module. Cost reductions in manufacturing have unequivocally affected module quality. And the use of new, cheaper materials has had a measureable impact on module reliability. The need for meaningful manufacturing quality standards has been understood by the leading technical institutions and important industry players. The fact that most leading PV panel manufacturers have been certified according to ISO 9001 has led to some level of improvement and higher effectiveness. The new ISO 9001 PV QMS standards will be a major step in providing a tool to assess PV manufacturers' quality management systems. The current lack of sufficient standards has still got a negative influence on the quality of modules being installed today. Today every manufacturer builds their modules in their own way with little standardization or adherence to quality processes and methods, which are commonplace in other manufacturing industries. Although photovoltaic technology is to a great extent mature, the way modules are being produced has changed significantly over the past few years and it continues to change at a rapid pace. Investors, financiers and lenders stand the most to gain from PV systems over the long-term, but also the most to lose. Investors, developers, EPC, O&M and solar asset management companies must all manage manufacturing quality more proactively or they will face unexpected risks and failures down the road. Manufacturing quality deserves more transparency and attention, as it is a major driver of module performance and reliability. This paper will explain the benefits of good manufacturing quality and the dangers in poor manufacturing quality. The paper also explains why buyers and long-term investors need to pay close attention to the day-to-day manufacturing quality of module manufacturers. We demonstrate how these quality risks can be assessed and mitigated by independent diligence, professional contracting and smart quality assurance processes that can be easily built into any module procurement process. We highlight the steps to ensure that every module used in a PV system is built to quality standards that support the long-term reliability of a PV system.
A Roadmap for the Implementation of Continued Process Verification.
Boyer, Marcus; Gampfer, Joerg; Zamamiri, Abdel; Payne, Robin
2016-01-01
In 2014, the members of the BioPhorum Operations Group (BPOG) produced a 100-page continued process verification case study, entitled "Continued Process Verification: An Industry Position Paper with Example Protocol". This case study captures the thought processes involved in creating a continued process verification plan for a new product in response to the U.S. Food and Drug Administration's guidance on the subject introduced in 2011. In so doing, it provided the specific example of a plan developed for a new molecular antibody product based on the "A MAb Case Study" that preceded it in 2009.This document provides a roadmap that draws on the content of the continued process verification case study to provide a step-by-step guide in a more accessible form, with reference to a process map of the product life cycle. It could be used as a basis for continued process verification implementation in a number of different scenarios: For a single product and process;For a single site;To assist in the sharing of data monitoring responsibilities among sites;To assist in establishing data monitoring agreements between a customer company and a contract manufacturing organization. The U.S. Food and Drug Administration issued guidance on the management of manufacturing processes designed to improve quality and control of drug products. This involved increased focus on regular monitoring of manufacturing processes, reporting of the results, and the taking of opportunities to improve. The guidance and practice associated with it is known as continued process verification This paper summarizes good practice in responding to continued process verification guidance, gathered from subject matter experts in the biopharmaceutical industry. © PDA, Inc. 2016.
NASA Astrophysics Data System (ADS)
Wang, Fenglin; Li, Yunping; Xu, Xiandong; Koizumi, Yuichiro; Yamanaka, Kenta; Bian, Huakang; Chiba, Akihiko
2015-12-01
A Cu-TiC alloy, with nanoscale TiC particles highly dispersed in the submicron-grained Cu matrix, was manufactured by a self-developed two-step ball-milling process on Cu, Ti and C powders. The thermostability of the composite was evaluated by high-temperature isothermal annealing treatments, with temperatures ranging from 727 to 1273 K. The semicoherent nanoscale TiC particles with Cu matrix, mainly located along the grain boundaries, were found to exhibit the promising trait of blocking grain boundary migrations, which leads to a super-stabilized microstructures up to approximately the melting point of copper (1223 K). Furthermore, the Cu-TiC alloys after annealing at 1323 K showed a slight decrease in Vickers hardness as well as the duplex microstructure due to selective grain growth, which were discussed in terms of hardness contributions from various mechanisms.
Compaction behavior of out-of-autoclave prepreg materials
NASA Astrophysics Data System (ADS)
Serrano, Léonard; Olivier, Philippe; Cinquin, Jacques
2017-10-01
The main challenges with composite parts manufacturing are related to the curing means, mainly autoclaves, the length of their cycles and their operating costs. In order to decrease this dependency, out of autoclave materials have been considered as a solution for high production rate parts such as spars, flaps, etc… However, most out-of-autoclave process do not possess the same maturity as their counterpart, especially concerning part quality1. Some pre-cure processes such as compaction and ply lay-up are usually less of a concern for autoclave manufacturing: the pressure applied during the cycle participates to reduce the potential defects (porosity caused by a poor quality lay-up, bad compaction, entrapped air or humidity…). For out-of-autoclave parts, those are crucial steps which may have many consequences on the final quality of the laminate2. In order to avoid this quality loss, those steps must be well understood.
Process for manufacture of thick film hydrogen sensors
Perdieu, Louisa H.
2000-09-09
A thick film process for producing hydrogen sensors capable of sensing down to a one percent concentration of hydrogen in carrier gasses such as argon, nitrogen, and air. The sensor is also suitable to detect hydrogen gas while immersed in transformer oil. The sensor includes a palladium resistance network thick film printed on a substrate, a portion of which network is coated with a protective hydrogen barrier. The process utilizes a sequence of printing of the requisite materials on a non-conductive substrate with firing temperatures at each step which are less than or equal to the temperature at the previous step.
Advances in polycrystalline thin-film photovoltaics for space applications
NASA Technical Reports Server (NTRS)
Lanning, Bruce R.; Armstrong, Joseph H.; Misra, Mohan S.
1994-01-01
Polycrystalline, thin-film photovoltaics represent one of the few (if not the only) renewable power sources which has the potential to satisfy the demanding technical requirements for future space applications. The demand in space is for deployable, flexible arrays with high power-to-weight ratios and long-term stability (15-20 years). In addition, there is also the demand that these arrays be produced by scalable, low-cost, high yield, processes. An approach to significantly reduce costs and increase reliability is to interconnect individual cells series via monolithic integration. Both CIS and CdTe semiconductor films are optimum absorber materials for thin-film n-p heterojunction solar cells, having band gaps between 0.9-1.5 ev and demonstrated small area efficiencies, with cadmium sulfide window layers, above 16.5 percent. Both CIS and CdTe polycrystalline thin-film cells have been produced on a laboratory scale by a variety of physical and chemical deposition methods, including evaporation, sputtering, and electrodeposition. Translating laboratory processes which yield these high efficiency, small area cells into the design of a manufacturing process capable of producing 1-sq ft modules, however, requires a quantitative understanding of each individual step in the process and its (each step) effect on overall module performance. With a proper quantification and understanding of material transport and reactivity for each individual step, manufacturing process can be designed that is not 'reactor-specific' and can be controlled intelligently with the design parameters of the process. The objective of this paper is to present an overview of the current efforts at MMC to develop large-scale manufacturing processes for both CIS and CdTe thin-film polycrystalline modules. CIS cells/modules are fabricated in a 'substrate configuration' by physical vapor deposition techniques and CdTe cells/modules are fabricated in a 'superstrate configuration' by wet chemical methods. Both laser and mechanical scribing operations are used to monolithically integrate (series interconnect) the individual cells into modules. Results will be presented at the cell and module development levels with a brief description of the test methods used to qualify these devices for space applications. The approach and development efforts are directed towards large-scale manufacturability of established thin-film, polycrystalline processing methods for large area modules with less emphasis on maximizing small area efficiencies.
NASA Astrophysics Data System (ADS)
Ghasemi Nejhad, M. N.
1993-04-01
The on-line consolidation of thermoplastic composites is a relatively new technology that can be used to manufacture composite parts with complex geometries. The localized melting/solidification technique employed in this process can reduce the residual stresses and allow for improved dimensional stability and performance. An additional advantage of this technique is the elimination of the curing steps which are necessary in the processing of thermoset-matrix composites. This article presents the effects of processing parameters on processability in on-line consolidation of thermoplastic composites for tape-laying and filament-winding processes employing anisotropic thermal analyses. The results show that the heater size, preheating conditions, and tow thickness can significantly affect the processing window which, in turn, affects the production rate and the quality of the parts.
Taylor, Rod S; Hutton, John; Culyer, Anthony J
2002-01-01
One of the principal roles of the National Institute for Clinical Excellence (NICE) is to appraise selected existing and emerging healthcare technologies and, as a result, produce guidance for the National Health Service (NHS) in England and Wales. A central part of this appraisal is the potential for manufacturers and sponsors to make a data submission. This paper describes the process of development of the second edition of technical guidance to manufacturers and sponsors for submission to NICE. The revision process took place during the period May 2000 and January 2001 and involved a number of key steps -- establishment of a guidance steering committee, review of current international guidelines of clinical and cost effectiveness, drafting of the guidance, detailed consultation with stakeholders, revision of the guidance and, finally, publication. The lessons learnt from revision of the NICE guidance for manufacturers and sponsors and some main issues for its future development are discussed.
Mass production of silicon pore optics for ATHENA
NASA Astrophysics Data System (ADS)
Wille, Eric; Bavdaz, Marcos; Collon, Maximilien
2016-07-01
Silicon Pore Optics (SPO) provide high angular resolution with low effective area density as required for the Advanced Telescope for High Energy Astrophysics (Athena). The x-ray telescope consists of several hundreds of SPO mirror modules. During the development of the process steps of the SPO technology, specific requirements of a future mass production have been considered right from the beginning. The manufacturing methods heavily utilise off-the-shelf equipment from the semiconductor industry, robotic automation and parallel processing. This allows to upscale the present production flow in a cost effective way, to produce hundreds of mirror modules per year. Considering manufacturing predictions based on the current technology status, we present an analysis of the time and resources required for the Athena flight programme. This includes the full production process starting with Si wafers up to the integration of the mirror modules. We present the times required for the individual process steps and identify the equipment required to produce two mirror modules per day. A preliminary timeline for building and commissioning the required infrastructure, and for flight model production of about 1000 mirror modules, is presented.
Additive manufacturing of optical components
NASA Astrophysics Data System (ADS)
Heinrich, Andreas; Rank, Manuel; Maillard, Philippe; Suckow, Anne; Bauckhage, Yannick; Rößler, Patrick; Lang, Johannes; Shariff, Fatin; Pekrul, Sven
2016-08-01
The development of additive manufacturing methods has enlarged rapidly in recent years. Thereby, the work mainly focuses on the realization of mechanical components, but the additive manufacturing technology offers a high potential in the field of optics as well. Owing to new design possibilities, completely new solutions are possible. This article briefly reviews and compares the most important additive manufacturing methods for polymer optics. Additionally, it points out the characteristics of additive manufactured polymer optics. Thereby, surface quality is of crucial importance. In order to improve it, appropriate post-processing steps are necessary (e.g. robot polishing or coating), which will be discussed. An essential part of this paper deals with various additive manufactured optical components and their use, especially in optical systems for shape metrology (e.g. borehole sensor, tilt sensor, freeform surface sensor, fisheye lens). The examples should demonstrate the potentials and limitations of optical components produced by additive manufacturing.
Looby, Mairead; Ibarra, Neysi; Pierce, James J; Buckley, Kevin; O'Donovan, Eimear; Heenan, Mary; Moran, Enda; Farid, Suzanne S; Baganz, Frank
2011-01-01
This study describes the application of quality by design (QbD) principles to the development and implementation of a major manufacturing process improvement for a commercially distributed therapeutic protein produced in Chinese hamster ovary cell culture. The intent of this article is to focus on QbD concepts, and provide guidance and understanding on how the various components combine together to deliver a robust process in keeping with the principles of QbD. A fed-batch production culture and a virus inactivation step are described as representative examples of upstream and downstream unit operations that were characterized. A systematic approach incorporating QbD principles was applied to both unit operations, involving risk assessment of potential process failure points, small-scale model qualification, design and execution of experiments, definition of operating parameter ranges and process validation acceptance criteria followed by manufacturing-scale implementation and process validation. Statistical experimental designs were applied to the execution of process characterization studies evaluating the impact of operating parameters on product quality attributes and process performance parameters. Data from process characterization experiments were used to define the proven acceptable range and classification of operating parameters for each unit operation. Analysis of variance and Monte Carlo simulation methods were used to assess the appropriateness of process design spaces. Successful implementation and validation of the process in the manufacturing facility and the subsequent manufacture of hundreds of batches of this therapeutic protein verifies the approaches taken as a suitable model for the development, scale-up and operation of any biopharmaceutical manufacturing process. Copyright © 2011 American Institute of Chemical Engineers (AIChE).
Process for fabrication of large titanium diboride ceramic bodies
Moorhead, Arthur J.; Bomar, E. S.; Becher, Paul F.
1989-01-01
A process for manufacturing large, fully dense, high purity TiB.sub.2 articles by pressing powders with a sintering aid at relatively low temperatures to reduce grain growth. The process requires stringent temperature and pressure applications in the hot-pressing step to ensure maximum removal of sintering aid and to avoid damage to the fabricated article or the die.
Automated aray assembly, phase 2
NASA Technical Reports Server (NTRS)
Daiello, R. V.
1979-01-01
A manufacturing process suitable for the large-scale production of silicon solar array modules at a cost of less than $500/peak kW is described. Factors which control the efficiency of ion implanted silicon solar cells, screen-printed thick film metallization, spray-on antireflection coating process, and panel assembly are discussed. Conclusions regarding technological readiness or cost effectiveness of individual process steps are presented.
Development of Process Analytical Technology (PAT) methods for controlled release pellet coating.
Avalle, P; Pollitt, M J; Bradley, K; Cooper, B; Pearce, G; Djemai, A; Fitzpatrick, S
2014-07-01
This work focused on the control of the manufacturing process for a controlled release (CR) pellet product, within a Quality by Design (QbD) framework. The manufacturing process was Wurster coating: firstly layering active pharmaceutical ingredient (API) onto sugar pellet cores and secondly a controlled release (CR) coating. For each of these two steps, development of a Process Analytical Technology (PAT) method is discussed and also a novel application of automated microscopy as the reference method. Ultimately, PAT methods should link to product performance and the two key Critical Quality Attributes (CQAs) for this CR product are assay and release rate, linked to the API and CR coating steps respectively. In this work, the link between near infra-red (NIR) spectra and those attributes was explored by chemometrics over the course of the coating process in a pilot scale industrial environment. Correlations were built between the NIR spectra and coating weight (for API amount), CR coating thickness and dissolution performance. These correlations allow the coating process to be monitored at-line and so better control of the product performance in line with QbD requirements. Copyright © 2014 Elsevier B.V. All rights reserved.
Hunt, Gavin R; Corballis, Michael C; Gray, Russell D
2006-01-01
Population-level laterality is generally considered to reflect functional brain specialization. Consequently, the strength of population-level laterality in manipulatory tasks is predicted to positively correlate with task complexity. This relationship has not been investigated in tool manufacture. Here, we report the correlation between strength of laterality and design complexity in the manufacture of New Caledonian crows' three pandanus tool designs: wide, narrow and stepped designs. We documented indirect evidence of over 5800 tool manufactures on 1232 pandanus trees at 23 sites. We found that the strength of laterality in tool manufacture was correlated with design complexity in three ways: (i) the strongest effect size among the population-level edge biases for each design was for the more complex, stepped design, (ii) the strength of laterality at individual sites was on average greater for the stepped design than it was for the simpler wide and narrow, non-stepped designs, and (iii) there was a positive, but non-significant, trend for a correlation between the strength of laterality and the number of steps on a stepped tool. These three aspects together indicate that greater design complexity generally elicits stronger lateralization of crows' pandanus tool manufacture. PMID:16600891
Hunt, Gavin R; Corballis, Michael C; Gray, Russell D
2006-05-07
Population-level laterality is generally considered to reflect functional brain specialization. Consequently, the strength of population-level laterality in manipulatory tasks is predicted to positively correlate with task complexity. This relationship has not been investigated in tool manufacture. Here, we report the correlation between strength of laterality and design complexity in the manufacture of New Caledonian crows' three pandanus tool designs: wide, narrow and stepped designs. We documented indirect evidence of over 5,800 tool manufactures on 1,232 pandanus trees at 23 sites. We found that the strength of laterality in tool manufacture was correlated with design complexity in three ways: (i) the strongest effect size among the population-level edge biases for each design was for the more complex, stepped design, (ii) the strength of laterality at individual sites was on average greater for the stepped design than it was for the simpler wide and narrow, non-stepped designs, and (iii) there was a positive, but non-significant, trend for a correlation between the strength of laterality and the number of steps on a stepped tool. These three aspects together indicate that greater design complexity generally elicits stronger lateralization of crows' pandanus tool manufacture.
Clinical manufacturing of CAR T cells: foundation of a promising therapy
Wang, Xiuyan; Rivière, Isabelle
2016-01-01
The treatment of cancer patients with autologous T cells expressing a chimeric antigen receptor (CAR) is one of the most promising adoptive cellular therapy approaches. Reproducible manufacturing of high-quality, clinical-grade CAR-T cell products is a prerequisite for the wide application of this technology. Product quality needs to be built-in within every step of the manufacturing process. We summarize herein the requirements and logistics to be considered, as well as the state of the art manufacturing platforms available. CAR-T cell therapy may be on the verge of becoming standard of care for a few clinical indications. Yet, many challenges pertaining to manufacturing standardization and product characterization remain to be overcome in order to achieve broad usage and eventual commercialization of this therapeutic modality. PMID:27347557
NASA Astrophysics Data System (ADS)
Maier, A.; Schledjewski, R.
2016-07-01
For continuous manufacturing processes mechanical preloading of the fibers occurs during the delivery of the fibers from the spool creel to the actual manufacturing process step. Moreover preloading of the dry roving bundles might be mandatory, e.g. during winding, to be able to produce high quality components. On the one hand too high tensile loads within dry roving bundles might result in a catastrophic failure and on the other hand the part produced under too low pre-tension might have low quality and mechanical properties. In this work, load conditions influencing mechanical properties of dry glass fiber bundles during continuous composite manufacturing processes were analyzed. Load conditions, i.e. fiber delivery speed, necessary pre-tension and other effects of the delivery system during continuous fiber winding, were chosen in process typical ranges. First, the strain rate dependency under static tensile load conditions was investigated. Furthermore different free gauge lengths up to 1.2 m, interactions between fiber points of contact regarding influence of sizing as well as impregnation were tested and the effect of twisting on the mechanical behavior of dry glass fiber bundles during the fiber delivery was studied.
Study on contaminants on flight and other critical surfaces
NASA Technical Reports Server (NTRS)
Workman, Gary L.; Hughes, Charles; Arendale, William F.
1994-01-01
The control of surface contamination in the manufacture of space hardware can become a critical step in the production process. Bonded surfaces have been shown to be affected markedly by contamination. It is important to insure surface cleanliness by preventing contamination prior to bonding. In this vein techniques are needed in which the contamination which may affect bonding are easily found and removed. Likewise, if materials which are detrimental to bonding are not easily removed, then they should not be used in the manufacturing process. This study will address the development of techniques to locate and quantify contamination levels of particular contaminants. With other data becoming available from MSFC and its contractors, this study will also quantify how certain contaminants affect bondlines and how easily they are removed in manufacturing.
Approaches to eliminating chlorofluorocarbon use in manufacturing.
Boyhan, W S
1992-01-01
Until quite recently, chlorofluorocarbons (CFCs) had been considered the safest and most benign of industrial chemicals. Their physical and chemical properties made them an integral part of manufacturing processes for electronics products. The recognition that CFCs destroy the stratospheric ozone layer, with consequent enormous consequences to all forms of life on earth, has led to international agreements which will end virtually all possibly before. This impending phaseout of CFCs has caused electronics manufacturers to examine alternative chemicals and processing methods. This manuscript documents the steps AT&T has taken to reach its goal of 100% phaseout of CFCs by years-end 1994. These actions include top-down management support with combined bottom-up thrusts, an internal information gathering and dissemination center, internal technology transfer, and external corporate activism. Images PMID:11607258
Verification of the Skorohod-Olevsky Viscous Sintering (SOVS) Model
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lester, Brian T.
2017-11-16
Sintering refers to a manufacturing process through which mechanically pressed bodies of ceramic (and sometimes metal) powders are heated to drive densification thereby removing the inherit porosity of green bodies. As the body densifies through the sintering process, the ensuing material flow leads to macroscopic deformations of the specimen and as such the final configuration differs form the initial. Therefore, as with any manufacturing step, there is substantial interest in understanding and being able to model the sintering process to predict deformation and residual stress. Efforts in this regard have been pursued for face seals, gear wheels, and consumer productsmore » like wash-basins. To understand the sintering process, a variety of modeling approaches have been pursued at different scales.« less
Industrializing Autologous Adoptive Immunotherapies: Manufacturing Advances and Challenges
Iyer, Rohin K.; Bowles, Paul A.; Kim, Howard; Dulgar-Tulloch, Aaron
2018-01-01
Cell therapy has proven to be a burgeoning field of investigation, evidenced by hundreds of clinical trials being conducted worldwide across a variety of cell types and indications. Many cell therapies have been shown to be efficacious in humans, such as modified T-cells and natural killer (NK) cells. Adoptive immunotherapy has shown the most promise in recent years, with particular emphasis on autologous cell sources. Chimeric Antigen Receptor (CAR)-based T-cell therapy targeting CD19-expressing B-cell leukemias has shown remarkable efficacy and reproducibility in numerous clinical trials. Recent marketing approval of Novartis' Kymriah™ (tisagenlecleucel) and Gilead/Kite's Yescarta™ (axicabtagene ciloleucel) by the FDA further underscores both the promise and legwork to be done if manufacturing processes are to become widely accessible. Further work is needed to standardize, automate, close, and scale production to bring down costs and democratize these and other cell therapies. Given the multiple processing steps involved, commercial-scale manufacturing of these therapies necessitates tighter control over process parameters. This focused review highlights some of the most recent advances used in the manufacturing of therapeutic immune cells, with a focus on T-cells. We summarize key unit operations and pain points around current manufacturing solutions. We also review emerging technologies, approaches and reagents used in cell isolation, activation, transduction, expansion, in-process analytics, harvest, cryopreservation and thaw, and conclude with a forward-look at future directions in the manufacture of adoptive immunotherapies.
Industrializing Autologous Adoptive Immunotherapies: Manufacturing Advances and Challenges.
Iyer, Rohin K; Bowles, Paul A; Kim, Howard; Dulgar-Tulloch, Aaron
2018-01-01
Cell therapy has proven to be a burgeoning field of investigation, evidenced by hundreds of clinical trials being conducted worldwide across a variety of cell types and indications. Many cell therapies have been shown to be efficacious in humans, such as modified T-cells and natural killer (NK) cells. Adoptive immunotherapy has shown the most promise in recent years, with particular emphasis on autologous cell sources. Chimeric Antigen Receptor (CAR)-based T-cell therapy targeting CD19-expressing B-cell leukemias has shown remarkable efficacy and reproducibility in numerous clinical trials. Recent marketing approval of Novartis' Kymriah™ (tisagenlecleucel) and Gilead/Kite's Yescarta™ (axicabtagene ciloleucel) by the FDA further underscores both the promise and legwork to be done if manufacturing processes are to become widely accessible. Further work is needed to standardize, automate, close, and scale production to bring down costs and democratize these and other cell therapies. Given the multiple processing steps involved, commercial-scale manufacturing of these therapies necessitates tighter control over process parameters. This focused review highlights some of the most recent advances used in the manufacturing of therapeutic immune cells, with a focus on T-cells. We summarize key unit operations and pain points around current manufacturing solutions. We also review emerging technologies, approaches and reagents used in cell isolation, activation, transduction, expansion, in-process analytics, harvest, cryopreservation and thaw, and conclude with a forward-look at future directions in the manufacture of adoptive immunotherapies.
Bidding-based autonomous process planning and scheduling
NASA Astrophysics Data System (ADS)
Gu, Peihua; Balasubramanian, Sivaram; Norrie, Douglas H.
1995-08-01
Improving productivity through computer integrated manufacturing systems (CIMS) and concurrent engineering requires that the islands of automation in an enterprise be completely integrated. The first step in this direction is to integrate design, process planning, and scheduling. This can be achieved through a bidding-based process planning approach. The product is represented in a STEP model with detailed design and administrative information including design specifications, batch size, and due dates. Upon arrival at the manufacturing facility, the product registered in the shop floor manager which is essentially a coordinating agent. The shop floor manager broadcasts the product's requirements to the machines. The shop contains autonomous machines that have knowledge about their functionality, capabilities, tooling, and schedule. Each machine has its own process planner and responds to the product's request in a different way that is consistent with its capabilities and capacities. When more than one machine offers certain process(es) for the same requirements, they enter into negotiation. Based on processing time, due date, and cost, one of the machines wins the contract. The successful machine updates its schedule and advises the product to request raw material for processing. The concept was implemented using a multi-agent system with the task decomposition and planning achieved through contract nets. The examples are included to illustrate the approach.
Dizon-Maspat, Jemelle; Bourret, Justin; D'Agostini, Anna; Li, Feng
2012-04-01
As the therapeutic monoclonal antibody (mAb) market continues to grow, optimizing production processes is becoming more critical in improving efficiencies and reducing cost-of-goods in large-scale production. With the recent trends of increasing cell culture titers from upstream process improvements, downstream capacity has become the bottleneck in many existing manufacturing facilities. Single Pass Tangential Flow Filtration (SPTFF) is an emerging technology, which is potentially useful in debottlenecking downstream capacity, especially when the pool tank size is a limiting factor. It can be integrated as part of an existing purification process, after a column chromatography step or a filtration step, without introducing a new unit operation. In this study, SPTFF technology was systematically evaluated for reducing process intermediate volumes from 2× to 10× with multiple mAbs and the impact of SPTFF on product quality, and process yield was analyzed. Finally, the potential fit into the typical 3-column industry platform antibody purification process and its implementation in a commercial scale manufacturing facility were also evaluated. Our data indicate that using SPTFF to concentrate protein pools is a simple, flexible, and robust operation, which can be implemented at various scales to improve antibody purification process capacity. Copyright © 2011 Wiley Periodicals, Inc.
High pressure as an alternative processing step for ham production.
Pingen, Sylvia; Sudhaus, Nadine; Becker, André; Krischek, Carsten; Klein, Günter
2016-08-01
As high pressure processing (HPP) is becoming more and more important in the food industry, this study examined the application of HPP (500 and 600MPa) as a manufacturing step during simulated ham production. By replacing conventional heating with HPP steps, ham-like texture or color attributes could not be achieved. HPP products showed a less pale, less red appearance, softer texture and higher yields. However, a combination of mild temperature (53°C) and 500MPa resulted in parameters more comparable to cooked ham. We conclude that HPP can be used for novel food development, providing novel textures and colors. However, when it comes to ham production, a heating step seems to be unavoidable to obtain characteristic ham properties. Copyright © 2016 Elsevier Ltd. All rights reserved.
Automated assembling of single fuel cell units for use in a fuel cell stack
NASA Astrophysics Data System (ADS)
Jalba, C. K.; Muminovic, A.; Barz, C.; Nasui, V.
2017-05-01
The manufacturing of PEMFC stacks (POLYMER ELEKTROLYT MEMBRAN Fuel Cell) is nowadays still done by hand. Over hundreds of identical single components have to be placed accurate together for the construction of a fuel cell stack. Beside logistic problems, higher total costs and disadvantages in weight the high number of components produce a higher statistic interference because of faulty erection or material defects and summation of manufacturing tolerances. The saving of costs is about 20 - 25 %. Furthermore, the total weight of the fuel cells will be reduced because of a new sealing technology. Overall a one minute cycle time has to be aimed per cell at the manufacturing of these single components. The change of the existing sealing concept to a bonded sealing is one of the important requisites to get an automated manufacturing of single cell units. One of the important steps for an automated gluing process is the checking of the glue application by using of an image processing system. After bonding the single fuel cell the sealing and electrical function can be checked, so that only functional and high qualitative cells can get into further manufacturing processes.
NASA Technical Reports Server (NTRS)
Stachulla, M.; Pernpeinter, R.; Brewster J.; Curreri, P.; Hoffman, E.
2010-01-01
Improving structural efficiency while reducing manufacturing costs are key objectives when making future heavy-lift launchers more performing and cost efficient. The main enabling technologies are the application of advanced high performance materials as well as cost effective manufacture processes. This paper presents the status and main results of a joint industrial research & development effort to demonstrate TRL 6 of a novel manufacturing process for large liquid propellant tanks for launcher applications. Using high strength aluminium-lithium alloy combined with the spin forming manufacturing technique, this development aims at thinner wall thickness and weight savings up to 25% as well as a significant reduction in manufacturing effort. In this program, the concave spin forming process is used to manufacture tank domes from a single flat plate. Applied to aluminium alloy, this process allows reaching the highest possible material strength status T8, eliminating numerous welding steps which are typically necessary to assemble tank domes from 3D-curved panels. To minimize raw material costs for large diameter tank domes for launchers, the dome blank has been composed from standard plates welded together prior to spin forming by friction stir welding. After welding, the dome blank is contoured in order to meet the required wall thickness distribution. For achieving a material state of T8, also in the welding seams, the applied spin forming process allows the required cold stretching of the 3D-curved dome, with a subsequent ageing in a furnace. This combined manufacturing process has been demonstrated up to TRL 6 for tank domes with a 5.4 m diameter. In this paper, the manufacturing process as well as test results are presented. Plans are shown how this process could be applied to future heavy-lift launch vehicles developments, also for larger dome diameters.
Manufacturing Ethyl Acetate From Fermentation Ethanol
NASA Technical Reports Server (NTRS)
Rohatgi, Naresh K.; Ingham, John D.
1991-01-01
Conceptual process uses dilute product of fermentation instead of concentrated ethanol. Low-concentration ethanol, extracted by vacuum from fermentation tank, and acetic acid constitutes feedstock for catalytic reaction. Product of reaction goes through steps that increases ethyl acetate content to 93 percent by weight. To conserve energy, heat exchangers recycle waste heat to preheat process streams at various points.
NASA Astrophysics Data System (ADS)
Hu, Di; Dolganov, Aleksei; Ma, Mingchan; Bhattacharya, Biyash; Bishop, Matthew T.; Chen, George Z.
2018-02-01
The Kroll process has been employed for titanium extraction since the 1950s. It is a labour and energy intensive multi-step semi-batch process. The post-extraction processes for making the raw titanium into alloys and products are also excessive, including multiple remelting steps. Invented in the late 1990s, the Fray-Farthing-Chen (FFC) Cambridge process extracts titanium from solid oxides at lower energy consumption via electrochemical reduction in molten salts. Its ability to produce alloys and powders, while retaining the cathode shape also promises energy and material efficient manufacturing. Focusing on titanium and its alloys, this article reviews the recent development of the FFC-Cambridge process in two aspects, (1) resource and process sustainability and (2) advanced post-extraction processing.
Lithographic chip identification: meeting the failure analysis challenge
NASA Astrophysics Data System (ADS)
Perkins, Lynn; Riddell, Kevin G.; Flack, Warren W.
1992-06-01
This paper describes a novel method using stepper photolithography to uniquely identify individual chips for permanent traceability. A commercially available 1X stepper is used to mark chips with an identifier or `serial number' which can be encoded with relevant information for the integrated circuit manufacturer. The permanent identification of individual chips can improve current methods of quality control, failure analysis, and inventory control. The need for this technology is escalating as manufacturers seek to provide six sigma quality control for their products and trace fabrication problems to their source. This need is especially acute for parts that fail after packaging and are returned to the manufacturer for analysis. Using this novel approach, failure analysis data can be tied back to a particular batch, wafer, or even a position within a wafer. Process control can be enhanced by identifying the root cause of chip failures. Chip identification also addresses manufacturers concerns with increasing incidences of chip theft. Since chips currently carry no identification other than the manufacturer's name and part number, recovery efforts are hampered by the inability to determine the sales history of a specific packaged chip. A definitive identifier or serial number for each chip would address this concern. The results of chip identification (patent pending) are easily viewed through a low power microscope. Batch number, wafer number, exposure step, and chip location within the exposure step can be recorded, as can dates and other items of interest. An explanation of the chip identification procedure and processing requirements are described. Experimental testing and results are presented, and potential applications are discussed.
USDA-ARS?s Scientific Manuscript database
The purpose of the cotton ginning process is to separate a field crop into its salable components. It is a necessary step between the farmer and the textile manufacturer. The original gin was a simple manually operated device that took hand harvested cotton and separated fiber from the cottonseed. T...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ewsuk, K.G.; Cochran, R.J.; Blackwell, B.F.
The properties and performance of a ceramic component is determined by a combination of the materials from which it was fabricated and how it was processed. Most ceramic components are manufactured by dry pressing a powder/binder system in which the organic binder provides formability and green compact strength. A key step in this manufacturing process is the removal of the binder from the powder compact after pressing. The organic binder is typically removed by a thermal decomposition process in which heating rate, temperature, and time are the key process parameters. Empirical approaches are generally used to design the burnout time-temperaturemore » cycle, often resulting in excessive processing times and energy usage, and higher overall manufacturing costs. Ideally, binder burnout should be completed as quickly as possible without damaging the compact, while using a minimum of energy. Process and computational modeling offer one means to achieve this end. The objective of this study is to develop an experimentally validated computer model that can be used to better understand, control, and optimize binder burnout from green ceramic compacts.« less
NASA Astrophysics Data System (ADS)
Bechtler, Laurie; Velidandla, Vamsi
2003-04-01
In response to demand for higher volumes and greater product capability, integrated optoelectronic device processing is rapidly increasing in complexity, benefiting from techniques developed for conventional silicon integrated circuit processing. The needs for high product yield and low manufacturing cost are also similar to the silicon wafer processing industry. This paper discusses the design and use of an automated inspection instrument called the Optical Surface Analyzer (OSA) to evaluate two critical production issues in optoelectronic device manufacturing: (1) film thickness uniformity, and (2) defectivity at various process steps. The OSA measurement instrument is better suited to photonics process development than most equipment developed for conventional silicon wafer processing in two important ways: it can handle both transparent and opaque substrates (unlike most inspection and metrology tools), and it is a full-wafer inspection method that captures defects and film variations over the entire substrate surface (unlike most film thickness measurement tools). Measurement examples will be provided in the paper for a variety of films and substrates used for optoelectronics manufacturing.
Ratcliffe, Elizabeth; Hourd, Paul; Guijarro-Leach, Juan; Rayment, Erin; Williams, David J; Thomas, Robert J
2013-01-01
Commercial regenerative medicine will require large quantities of clinical-specification human cells. The cost and quality of manufacture is notoriously difficult to control due to highly complex processes with poorly defined tolerances. As a step to overcome this, we aimed to demonstrate the use of 'quality-by-design' tools to define the operating space for economic passage of a scalable human embryonic stem cell production method with minimal cell loss. Design of experiments response surface methodology was applied to generate empirical models to predict optimal operating conditions for a unit of manufacture of a previously developed automatable and scalable human embryonic stem cell production method. Two models were defined to predict cell yield and cell recovery rate postpassage, in terms of the predictor variables of media volume, cell seeding density, media exchange and length of passage. Predicted operating conditions for maximized productivity were successfully validated. Such 'quality-by-design' type approaches to process design and optimization will be essential to reduce the risk of product failure and patient harm, and to build regulatory confidence in cell therapy manufacturing processes.
How to unlock the benefits of MRP (materiel requirements planning) II and Just-in-Time.
Jacobi, M A
1994-05-01
Manufacturing companies need to use the best and most applicable parts of MRP II and JIT to run their businesses effectively. MRP II provides the methodology to plan and control the total resources of the company and focuses on the processes that add value to their customers' products. It is the cornerstone of total quality management, as it reduces the variability and costly activities in the communication and subsequent execution of the required steps from customer order to shipment. JIT focuses on simplifying the total business operation and execution of business processes. MRP II and JIT are the foundations for successful manufacturing businesses.
NASA Astrophysics Data System (ADS)
Qu, Zilian; Meng, Yonggang; Zhao, Qian
2015-03-01
This paper proposes a new eddy current method, named equivalent unit method (EUM), for the thickness measurement of the top copper film of multilayer interconnects in the chemical mechanical polishing (CMP) process, which is an important step in the integrated circuit (IC) manufacturing. The influence of the underneath circuit layers on the eddy current is modeled and treated as an equivalent film thickness. By subtracting this equivalent film component, the accuracy of the thickness measurement of the top copper layer with an eddy current sensor is improved and the absolute error is 3 nm for sampler measurement.
Producing optical (contact) lenses by a novel low cost process
NASA Astrophysics Data System (ADS)
Skipper, Richard S.; Spencer, Ian D.
2005-09-01
The rapid and impressive growth of China has been achieved on the back of highly labour intensive industries, often in manufacturing, and at the cost of companies and jobs in Europe and America. Approaches that worked well in the 1990's to reduce production costs in the developed countries are no longer effective when confronted with the low labour costs of China and India. We have looked at contact lenses as a product that has become highly available to consumers here but as an industry that has reduced costs by moving to low labour cost countries. The question to be answered was, "Do we have the skill to still make the product in the UK, and can we make it cheap enough to export to China?" if we do not, then contact lens manufacture will move to China sooner or later. The challenge to enter the markets of the BRIC (Brazil, Russia, India and China) countries is extremely exciting as here is the new money, high growth and here is a product that sells to those with disposable incomes. To succeed we knew we had to be radical in our approach; the radical step was very simple: to devise a process in which each step added value to the customer and not cost to the product. The presentation examines the processes used by the major producers and how, by applying good manufacturing practice sound scientific principles to them, the opportunity to design a new low cost patented process was identified.
Global Manufacturing of CAR T Cell Therapy.
Levine, Bruce L; Miskin, James; Wonnacott, Keith; Keir, Christopher
2017-03-17
Immunotherapy using chimeric antigen receptor-modified T cells has demonstrated high response rates in patients with B cell malignancies, and chimeric antigen receptor T cell therapy is now being investigated in several hematologic and solid tumor types. Chimeric antigen receptor T cells are generated by removing T cells from a patient's blood and engineering the cells to express the chimeric antigen receptor, which reprograms the T cells to target tumor cells. As chimeric antigen receptor T cell therapy moves into later-phase clinical trials and becomes an option for more patients, compliance of the chimeric antigen receptor T cell manufacturing process with global regulatory requirements becomes a topic for extensive discussion. Additionally, the challenges of taking a chimeric antigen receptor T cell manufacturing process from a single institution to a large-scale multi-site manufacturing center must be addressed. We have anticipated such concerns in our experience with the CD19 chimeric antigen receptor T cell therapy CTL019. In this review, we discuss steps involved in the cell processing of the technology, including the use of an optimal vector for consistent cell processing, along with addressing the challenges of expanding chimeric antigen receptor T cell therapy to a global patient population.
Surface-specific additive manufacturing test artefacts
NASA Astrophysics Data System (ADS)
Townsend, Andrew; Racasan, Radu; Blunt, Liam
2018-06-01
Many test artefact designs have been proposed for use with additive manufacturing (AM) systems. These test artefacts have primarily been designed for the evaluation of AM form and dimensional performance. A series of surface-specific measurement test artefacts designed for use in the verification of AM manufacturing processes are proposed here. Surface-specific test artefacts can be made more compact because they do not require the large dimensions needed for accurate dimensional and form measurements. The series of three test artefacts are designed to provide comprehensive information pertaining to the manufactured surface. Measurement possibilities include deviation analysis, surface texture parameter data generation, sub-surface analysis, layer step analysis and build resolution comparison. The test artefacts are designed to provide easy access for measurement using conventional surface measurement techniques, for example, focus variation microscopy, stylus profilometry, confocal microscopy and scanning electron microscopy. Additionally, the test artefacts may be simply visually inspected as a comparative tool, giving a fast indication of process variation between builds. The three test artefacts are small enough to be included in every build and include built-in manufacturing traceability information, making them a convenient physical record of the build.
NASA Astrophysics Data System (ADS)
Nadimpalli, Venkata K.; Nagy, Peter B.
2018-04-01
Ultrasonic Additive Manufacturing (UAM) is a solid-state layer by layer manufacturing process that utilizes vibration induced plastic deformation to form a metallurgical bond between a thin layer and an existing base structure. Due to the vibration based bonding mechanism, the quality of components at each layer depends on the geometry of the structure. In-situ monitoring during and between UAM manufacturing steps offers the potential for closed-loop control to optimize process parameters and to repair existing defects. One interface that is most prone to delamination is the base/build interface and often UAM component height and quality are limited by failure at the base/build interface. Low manufacturing temperatures and favorable orientation of typical interface defects in UAM make ultrasonic NDE an attractive candidate for online monitoring. Two approaches for in-situ NDE are discussed and the design of the monitoring system optimized so that the quality of UAM components is not affected by the addition of the NDE setup. Preliminary results from in-situ ultrasonic NDE indicate the potential to be utilized for online qualification, closed-loop control and offline certification of UAM components.
Application of Additive Manufacturing in Oral and Maxillofacial Surgery.
Farré-Guasch, Elisabet; Wolff, Jan; Helder, Marco N; Schulten, Engelbert A J M; Forouzanfar, Tim; Klein-Nulend, Jenneke
2015-12-01
Additive manufacturing is the process of joining materials to create objects from digital 3-dimensional (3D) model data, which is a promising technology in oral and maxillofacial surgery. The management of lost craniofacial tissues owing to congenital abnormalities, trauma, or cancer treatment poses a challenge to oral and maxillofacial surgeons. Many strategies have been proposed for the management of such defects, but autogenous bone grafts remain the gold standard for reconstructive bone surgery. Nevertheless, cell-based treatments using adipose stem cells combined with osteoconductive biomaterials or scaffolds have become a promising alternative to autogenous bone grafts. Such treatment protocols often require customized 3D scaffolds that fulfill functional and esthetic requirements, provide adequate blood supply, and meet the load-bearing requirements of the head. Currently, such customized 3D scaffolds are being manufactured using additive manufacturing technology. In this review, 2 of the current and emerging modalities for reconstruction of oral and maxillofacial bone defects are highlighted and discussed, namely human maxillary sinus floor elevation as a valid model to test bone tissue-engineering approaches enabling the application of 1-step surgical procedures and seeding of Good Manufacturing Practice-level adipose stem cells on computer-aided manufactured scaffolds to reconstruct large bone defects in a 2-step surgical procedure, in which cells are expanded ex vivo and seeded on resorbable scaffolds before implantation. Furthermore, imaging-guided tissue-engineering technologies to predetermine the surgical location and to facilitate the manufacturing of custom-made implants that meet the specific patient's demands are discussed. The potential of tissue-engineered constructs designed for the repair of large oral and maxillofacial bone defects in load-bearing situations in a 1-step surgical procedure combining these 2 innovative approaches is particularly emphasized. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
Process Development for Automated Solar Cell and Module Production. Task 4: Automated Array Assembly
NASA Technical Reports Server (NTRS)
1979-01-01
A baseline sequence for the manufacture of solar cell modules was specified. Starting with silicon wafers, the process goes through damage etching, texture etching, junction formation, plasma edge etch, aluminum back surface field formation, and screen printed metallization to produce finished solar cells. The cells were then series connected on a ribbon and bonded into a finished glass tedlar module. A number of steps required additional developmental effort to verify technical and economic feasibility. These steps include texture etching, plasma edge etch, aluminum back surface field formation, array layup and interconnect, and module edge sealing and framing.
Manufacture of high aspect ratio micro-pillar wall shear stress sensor arrays
NASA Astrophysics Data System (ADS)
Gnanamanickam, Ebenezer P.; Sullivan, John P.
2012-12-01
In the field of experimental fluid mechanics the measurement of unsteady, distributed wall shear stress has proved historically challenging. Recently, sensors based on an array of flexible micro-pillars have shown promise in carrying out such measurements. Similar sensors find use in other applications such as cellular mechanics. This work presents a manufacturing technique that can manufacture micro-pillar arrays of high aspect ratio. An electric discharge machine (EDM) is used to manufacture a micro-drilling tool. This micro-drilling tool is used to form holes in a wax sheet which acts as the mold for the micro-pillar array. Silicone rubber is cast in these molds to yield a micro-pillar array. Using this technique, micro-pillar arrays with a maximum aspect ratio of about 10 have been manufactured. Manufacturing issues encountered, steps to alleviate them and the potential of the process to manufacture similar micro-pillar arrays in a time-efficient manner are also discussed.
Semi-solid state bioremediation of CCA-treated wood using malted barley as a nutrient source
Carol A. Clausen
2002-01-01
Bioremediation processes for recovery and reuse of CCA-treated wood invariably increase the cost of any secondary products manufactured from the remediated fiber. Microbial remediation using either bacteria or fungi has been shown to remove heavy metals from CCA-treated southern yellow pine (SYP). In a two-step remediation process utilizing oxalic acid extraction and...
NASA Technical Reports Server (NTRS)
Metschan, Stephen L.; Wilden, Kurtis S.; Sharpless, Garrett C.; Andelman, Rich M.
1993-01-01
Textile manufacturing processes offer potential cost and weight advantages over traditional composite materials and processes for transport fuselage elements. In the current study, design cost modeling relationships between textile processes and element design details were developed. Such relationships are expected to help future aircraft designers to make timely decisions on the effect of design details and overall configurations on textile fabrication costs. The fundamental advantage of a design cost model is to insure that the element design is cost effective for the intended process. Trade studies on the effects of processing parameters also help to optimize the manufacturing steps for a particular structural element. Two methods of analyzing design detail/process cost relationships developed for the design cost model were pursued in the current study. The first makes use of existing databases and alternative cost modeling methods (e.g. detailed estimating). The second compares design cost model predictions with data collected during the fabrication of seven foot circumferential frames for ATCAS crown test panels. The process used in this case involves 2D dry braiding and resin transfer molding of curved 'J' cross section frame members having design details characteristic of the baseline ATCAS crown design.
RTD-based Material Tracking in a Fully-Continuous Dry Granulation Tableting Line.
Martinetz, M C; Karttunen, A-P; Sacher, S; Wahl, P; Ketolainen, J; Khinast, J G; Korhonen, O
2018-06-06
Continuous manufacturing (CM) offers quality and cost-effectiveness benefits over currently dominating batch processing. One challenge that needs to be addressed when implementing CM is traceability of materials through the process, which is needed for the batch/lot definition and control strategy. In this work the residence time distributions (RTD) of single unit operations (blender, roller compactor and tablet press) of a continuous dry granulation tableting line were captured with NIR based methods at selected mass flow rates to create training data. RTD models for continuous operated unit operations and the entire line were developed based on transfer functions. For semi-continuously operated bucket conveyor and pneumatic transport an assumption based the operation frequency was used. For validation of the parametrized process model, a pre-defined API step change and its propagation through the manufacturing line was computed and compared to multi-scale experimental runs conducted with the fully assembled continuous operated manufacturing line. This novel approach showed a very good prediction power at the selected mass flow rates for a complete continuous dry granulation line. Furthermore, it shows and proves the capabilities of process simulation as a tool to support development and control of pharmaceutical manufacturing processes. Copyright © 2018. Published by Elsevier B.V.
Additive direct-write microfabrication for MEMS: A review
NASA Astrophysics Data System (ADS)
Teh, Kwok Siong
2017-12-01
Direct-write additive manufacturing refers to a rich and growing repertoire of well-established fabrication techniques that builds solid objects directly from computer- generated solid models without elaborate intermediate fabrication steps. At the macroscale, direct-write techniques such as stereolithography, selective laser sintering, fused deposition modeling ink-jet printing, and laminated object manufacturing have significantly reduced concept-to-product lead time, enabled complex geometries, and importantly, has led to the renaissance in fabrication known as the maker movement. The technological premises of all direct-write additive manufacturing are identical—converting computer generated three-dimensional models into layers of two-dimensional planes or slices, which are then reconstructed sequentially into threedimensional solid objects in a layer-by-layer format. The key differences between the various additive manufacturing techniques are the means of creating the finished layers and the ancillary processes that accompany them. While still at its infancy, direct-write additive manufacturing techniques at the microscale have the potential to significantly lower the barrier-of-entry—in terms of cost, time and training—for the prototyping and fabrication of MEMS parts that have larger dimensions, high aspect ratios, and complex shapes. In recent years, significant advancements in materials chemistry, laser technology, heat and fluid modeling, and control systems have enabled additive manufacturing to achieve higher resolutions at the micrometer and nanometer length scales to be a viable technology for MEMS fabrication. Compared to traditional MEMS processes that rely heavily on expensive equipment and time-consuming steps, direct-write additive manufacturing techniques allow for rapid design-to-prototype realization by limiting or circumventing the need for cleanrooms, photolithography and extensive training. With current direct-write additive manufacturing technologies, it is possible to fabricate unsophisticated micrometer scale structures at adequate resolutions and precisions using materials that range from polymers, metals, ceramics, to composites. In both academia and industry, direct-write additive manufacturing offers extraordinary promises to revolutionize research and development in microfabrication and MEMS technologies. Importantly, direct-write additive manufacturing could appreciably augment current MEMS fabrication technologies, enable faster design-to-product cycle, empower new paradigms in MEMS designs, and critically, encourage wider participation in MEMS research at institutions or for individuals with limited or no access to cleanroom facilities. This article aims to provide a limited review of the current landscape of direct-write additive manufacturing techniques that are potentially applicable for MEMS microfabrication.
Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.
McCue, Justin; Kshirsagar, Rashmi; Selvitelli, Keith; Lu, Qi; Zhang, Mingxuan; Mei, Baisong; Peters, Robert; Pierce, Glenn F; Dumont, Jennifer; Raso, Stephen; Reichert, Heidi
2015-07-01
Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc. Copyright © 2015 Biogen. Published by Elsevier Ltd.. All rights reserved.
Quality by Design (QbD)-Based Process Development for Purification of a Biotherapeutic.
Rathore, Anurag S
2016-05-01
Quality by Design (QbD) is currently receiving increased attention from the pharmaceutical community. As a result, most major biotech manufacturers are in varying stages of implementing QbD. Here, I present a case study that illustrates the step-by-step development using QbD of a purification process for the production of a biosimilar product: granulocyte colony-stimulating factor (GCSF). I also highlight and discuss the advantages that QbD-based process development offers over traditional approaches. The case study is intended to help those who wish to implement QbD towards the development and commercialization of biotech products. Copyright © 2016 Elsevier Ltd. All rights reserved.
MOLECULES TO MOZZARELLA: THE CHEMISTRY OF CHEESE
USDA-ARS?s Scientific Manuscript database
Almost ten billion pounds of cheese are produced in the US each year, and chemistry is involved in every step of the manufacturing process. The milk coagulates into a curd when starter culture bacteria digest lactose and rennet enzyme destabilizes casein micelles. Cooking and piling the curd force...
Production of polyol oils from soybean oil through bioprocess
USDA-ARS?s Scientific Manuscript database
Soy-polyol oils (oxygenated acylglycerols) are important starting materials for the manufacture of polymers such as polyurethane. Currently, they are produced by a two-step chemical process involving epoxidation and then the subsequent opening of the oxirane ring. The objective of this study is to d...
Lam, Carl W; Lim, Seong-Rin; Schoenung, Julie M
2011-05-15
Modern manufacturing of printed wiring boards (PWBs) involves extensive use of various hazardous chemicals in different manufacturing steps such as board preparation, circuit design transfer, etching and plating processes. Two complementary environmental screening methods developed by the U.S. EPA, namely: (i) the Tool for the Reduction and Assessment of Chemical and Other Environmental Impacts (TRACI) and (ii) Risk-Screening Environmental Indicators (RSEI), are used to quantify geographic and chemical environmental impacts in the U.S. PWB manufacturing industry based on Toxics Release Inventory (TRI) data. Although the release weight percentages of industrial chemicals such as methanol, glycol ethers and dimethylformamide comprise the larger fraction of reported air and water emissions, results indicate that lead, copper and their compounds' releases correspond to the highest environmental impact from toxicity potentials and risk-screening scores. Combining these results with further knowledge of PWB manufacturing, select alternative chemical processes and materials for pollution prevention are discussed. Examples of effective pollution prevention options in the PWB industry include spent etchant recovery technologies, and process and material substitutions. In addition, geographic assessment of environmental burden highlights states where promotion of pollution prevention strategies and emissions regulations can have the greatest effect to curb the PWB industry's toxic release impacts. Copyright © 2011 Elsevier B.V. All rights reserved.
Study of a dry room in a battery manufacturing plant using a process model
NASA Astrophysics Data System (ADS)
Ahmed, Shabbir; Nelson, Paul A.; Dees, Dennis W.
2016-09-01
The manufacture of lithium ion batteries requires some processing steps to be carried out in a dry room, where the moisture content should remain below 100 parts per million. The design and operation of such a dry room adds to the cost of the battery. This paper studied the humidity management of the air to and from the dry room to understand the impact of design and operating parameters on the energy demand and the cost contribution towards the battery manufacturing cost. The study was conducted with the help of a process model for a dry room with a volume of 16,000 cubic meters. For a defined base case scenario it was found that the dry room operation has an energy demand of approximately 400 kW. The paper explores some tradeoffs in design and operating parameters by looking at the humidity reduction by quenching the make-up air vs. at the desiccant wheel, and the impact of the heat recovery from the desiccant regeneration cycle.
Trainer, Asa; Hedberg, Thomas; Feeney, Allison Barnard; Fischer, Kevin; Rosche, Phil
2016-01-01
Advances in information technology triggered a digital revolution that holds promise of reduced costs, improved productivity, and higher quality. To ride this wave of innovation, manufacturing enterprises are changing how product definitions are communicated - from paper to models. To achieve industry's vision of the Model-Based Enterprise (MBE), the MBE strategy must include model-based data interoperability from design to manufacturing and quality in the supply chain. The Model-Based Definition (MBD) is created by the original equipment manufacturer (OEM) using Computer-Aided Design (CAD) tools. This information is then shared with the supplier so that they can manufacture and inspect the physical parts. Today, suppliers predominantly use Computer-Aided Manufacturing (CAM) and Coordinate Measuring Machine (CMM) models for these tasks. Traditionally, the OEM has provided design data to the supplier in the form of two-dimensional (2D) drawings, but may also include a three-dimensional (3D)-shape-geometry model, often in a standards-based format such as ISO 10303-203:2011 (STEP AP203). The supplier then creates the respective CAM and CMM models and machine programs to produce and inspect the parts. In the MBE vision for model-based data exchange, the CAD model must include product-and-manufacturing information (PMI) in addition to the shape geometry. Today's CAD tools can generate models with embedded PMI. And, with the emergence of STEP AP242, a standards-based model with embedded PMI can now be shared downstream. The on-going research detailed in this paper seeks to investigate three concepts. First, that the ability to utilize a STEP AP242 model with embedded PMI for CAD-to-CAM and CAD-to-CMM data exchange is possible and valuable to the overall goal of a more efficient process. Second, the research identifies gaps in tools, standards, and processes that inhibit industry's ability to cost-effectively achieve model-based-data interoperability in the pursuit of the MBE vision. Finally, it also seeks to explore the interaction between CAD and CMM processes and determine if the concept of feedback from CAM and CMM back to CAD is feasible. The main goal of our study is to test the hypothesis that model-based-data interoperability from CAD-to-CAM and CAD-to-CMM is feasible through standards-based integration. This paper presents several barriers to model-based-data interoperability. Overall, the project team demonstrated the exchange of product definition data between CAD, CAM, and CMM systems using standards-based methods. While gaps in standards coverage were identified, the gaps should not stop industry's progress toward MBE. The results of our study provide evidence in support of an open-standards method to model-based-data interoperability, which would provide maximum value and impact to industry.
New numerical approach for the modelling of machining applied to aeronautical structural parts
NASA Astrophysics Data System (ADS)
Rambaud, Pierrick; Mocellin, Katia
2018-05-01
The manufacturing of aluminium alloy structural aerospace parts involves several steps: forming (rolling, forging …etc), heat treatments and machining. Before machining, the manufacturing processes have embedded residual stresses into the workpiece. The final geometry is obtained during this last step, when up to 90% of the raw material volume is removed by machining. During this operation, the mechanical equilibrium of the part is in constant evolution due to the redistribution of the initial stresses. This redistribution is the main cause for workpiece deflections during machining and for distortions - after unclamping. Both may lead to non-conformity of the part regarding the geometrical and dimensional specifications and therefore to rejection of the part or additional conforming steps. In order to improve the machining accuracy and the robustness of the process, the effect of the residual stresses has to be considered for the definition of the machining process plan and even in the geometrical definition of the part. In this paper, the authors present two new numerical approaches concerning the modelling of machining of aeronautical structural parts. The first deals with the use of an immersed volume framework to model the cutting step, improving the robustness and the quality of the resulting mesh compared to the previous version. The second is about the mechanical modelling of the machining problem. The authors thus show that in the framework of rolled aluminium parts the use of a linear elasticity model is functional in the finite element formulation and promising regarding the reduction of computation times.
USDA-ARS?s Scientific Manuscript database
Clay and plant materials such as wood are the raw materials used in manufacture of ceramic water filtration devices around the world. A step by step manufacturing procedure which includes initial mixing, molding and sintering is used. The manufactured ceramic filters have numerous pores which help i...
Low-cost Solar Array (LSA) project
NASA Technical Reports Server (NTRS)
1978-01-01
Progress made by the Low-Cost Silicon Solar Array Project during the period January through March 1978 is reported. It includes task reports on silicon material processing, large-area silicon sheet development, encapsulation materials testing and development, project engineering and operations, and manufacturing techniques, plus the steps taken to integrate these efforts.
Making Stronger Twine With Matched Strands
NASA Technical Reports Server (NTRS)
Kirkland, W. L.
1985-01-01
Higher tensil strength achieved with same production equipment. Strong twine made by using spools in one of two-step manufacturing process. Three primary strands twisted together in opposite direction to form threeply twine. Technique used successfully in manufacture of safety netting with 600- to 700-lb (2,700-to 3,100-N) tensil strength and 60-ton (54 x 10 to third power kg) tuna seine with area of 86 acres (3.5 x 10 to fifth power m2). Increase in tensil strength of completed twine found experimentally 10 to 12 percent.
NASA Technical Reports Server (NTRS)
1984-01-01
The electroepitaxial process and the Very Large Scale Integration (VLSI) circuits (chips) facilities were chosen because each requires a very high degree of automation, and therefore involved extensive use of teleoperators, robotics, process mechanization, and artificial intelligence. Both cover a raw materials process and a sophisticated multi-step process and are therfore highly representative of the kinds of difficult operation, maintenance, and repair challenges which can be expected for any type of space manufacturing facility. Generic areas were identified which will require significant further study. The initial design will be based on terrestrial state-of-the-art hard automation. One hundred candidate missions were evaluated on the basis of automation portential and availability of meaning ful knowldege. The design requirements and unconstrained design concepts developed for the two missions are presented.
Digitalization in roll forming manufacturing
NASA Astrophysics Data System (ADS)
Sedlmaier, A.; Dietl, T.; Ferreira, P.
2017-09-01
Roll formed profiles are used in automotive chassis production as building blocks for the body-in-white. The ability to produce profiles with discontinuous cross sections, both in width and in depth, allows weight savings in the final automotive chassis through the use of load optimized cross sections. This has been the target of the 3D Roll Forming process. A machine concept is presented where a new forming concept for roll formed parts in combination with advanced robotics allowing freely positioned roll forming tooling in 3D space enables the production of complex shapes by roll forming. This is a step forward into the digitalization of roll forming manufacturing by making the process flexible and capable of rapid prototyping and production of small series of parts. Moreover, data collection in a large scale through the control system and integrated sensors lead to an increased understanding of the process and provide the basis to develop self-optimizing roll forming machines, increasing the productivity, quality and predictability of the roll-forming process. The first parts successfully manufactured with this new forming concept are presented.
Fischer, M; Laheurte, P; Acquier, P; Joguet, D; Peltier, L; Petithory, T; Anselme, K; Mille, P
2017-06-01
Biocompatible beta-titanium alloys such as Ti-27.5(at.%)Nb are good candidates for implantology and arthroplasty applications as their particular mechanical properties, including low Young's modulus, could significantly reduce the stress-shielding phenomenon usually occurring after surgery. The CLAD® process is a powder blown additive manufacturing process that allows the manufacture of patient specific (i.e. custom) implants. Thus, the use of Ti-27.5(at.%)Nb alloy formed by CLAD® process for biomedical applications as a mean to increase cytocompatibility and mechanical biocompatibility was investigated in this study. The microstructural properties of the CLAD-deposited alloy were studied with optical microscopy and electron back-scattered diffraction (EBSD) analysis. The conservation of the mechanical properties of the Ti-27.5Nb material after the transformation steps (ingot-powder atomisation-CLAD) were verified with tensile tests and appear to remain close to those of reference material. Cytocompatibility of the material and subsequent cell viability tests showed that no cytotoxic elements are released in the medium and that viable cells proliferated well. Copyright © 2017 Elsevier B.V. All rights reserved.
Leroy, Sabine; Giammarinaro, Philippe; Chacornac, Jean-Paul; Lebert, Isabelle; Talon, Régine
2010-04-01
The staphylococcal community of the environments of nine French small-scale processing units and their naturally fermented meat products was identified by analyzing 676 isolates. Fifteen species were accurately identified using validated molecular methods. The three prevalent species were Staphylococcus equorum (58.4%), Staphylococcus saprophyticus (15.7%) and Staphylococcus xylosus (9.3%). S. equorum was isolated in all the processing units in similar proportion in meat and environmental samples. S. saprophyticus was also isolated in all the processing units with a higher percentage in environmental samples. S. xylosus was present sporadically in the processing units and its prevalence was higher in meat samples. The genetic diversity of the strains within the three species isolated from one processing unit was studied by PFGE and revealed a high diversity for S. equorum and S. saprophyticus both in the environment and the meat isolates. The genetic diversity remained high through the manufacturing steps. A small percentage of the strains of the two species share the two ecological niches. These results highlight that some strains, probably introduced by the meat, will persist in the manufacturing environment, while other strains are more adapted to the meat products.
Perspective: Optical measurement of feature dimensions and shapes by scatterometry
NASA Astrophysics Data System (ADS)
Diebold, Alain C.; Antonelli, Andy; Keller, Nick
2018-05-01
The use of optical scattering to measure feature shape and dimensions, scatterometry, is now routine during semiconductor manufacturing. Scatterometry iteratively improves an optical model structure using simulations that are compared to experimental data from an ellipsometer. These simulations are done using the rigorous coupled wave analysis for solving Maxwell's equations. In this article, we describe the Mueller matrix spectroscopic ellipsometry based scatterometry. Next, the rigorous coupled wave analysis for Maxwell's equations is presented. Following this, several example measurements are described as they apply to specific process steps in the fabrication of gate-all-around (GAA) transistor structures. First, simulations of measurement sensitivity for the inner spacer etch back step of horizontal GAA transistor processing are described. Next, the simulated metrology sensitivity for sacrificial (dummy) amorphous silicon etch back step of vertical GAA transistor processing is discussed. Finally, we present the application of plasmonically active test structures for improving the sensitivity of the measurement of metal linewidths.
Integration of fluidic jet actuators in composite structures
NASA Astrophysics Data System (ADS)
Schueller, Martin; Lipowski, Mathias; Schirmer, Eckart; Walther, Marco; Otto, Thomas; Geßner, Thomas; Kroll, Lothar
2015-04-01
Fluidic Actuated Flow Control (FAFC) has been introduced as a technology that influences the boundary layer by actively blowing air through slots or holes in the aircraft skin or wind turbine rotor blade. Modern wing structures are or will be manufactured using composite materials. In these state of the art systems, AFC actuators are integrated in a hybrid approach. The new idea is to directly integrate the active fluidic elements (such as SJAs and PJAs) and their components in the structure of the airfoil. Consequently, the integration of such fluidic devices must fit the manufacturing process and the material properties of the composite structure. The challenge is to integrate temperature-sensitive active elements and to realize fluidic cavities at the same time. The transducer elements will be provided for the manufacturing steps using roll-to-roll processes. The fluidic parts of the actuators will be manufactured using the MuCell® process that provides on the one hand the defined reproduction of the fluidic structures and, on the other hand, a high light weight index. Based on the first design concept, a demonstrator was developed in order to proof the design approach. The output velocity on the exit was measured using a hot-wire anemometer.
Aktan, Ali Murat; Çiftçi, Mehmet Ertuğrul; Akgünlü, Faruk
2012-01-01
Objective. The purpose of this study was to analyze two phosphor plate systems (PSPs) (Dürr Dental, Digora Optime) according to their scanning delay and protective plastic case performances. Methods. Two PSPs using an aluminum step wedge were exposed. These plates were placed in three different protective plastic cases (manufacturers' original cases, black case, and white case) before obtaining the radiographs and were then processed immediately and 1, 5, 10, 30, 60, 120, 240, and 480 min after exposure. Mean gray values (MGVs) of the 3rd, 5th, 7th, and 9th steps of the wedges were compared using ANOVA. Results. Statistically significant differences were found between the two PSPs (P < 0.001). ANOVA revealed that the MGVs of four steps of the wedges were significantly different from each other for all scan delays (P < 0.001). MGVs increased with increasing scanning delay, except the group with Dürr plates in their original cases. Reduction in image quality began 5 min after exposure in the other Dürr plate groups. Conclusions. Within the limitations of the current study, it can be concluded that scanning delay causes a reduction in image quality, and using the manufacturer's original protective case will result in better performance of PSPs. PMID:23213301
Aktan, Ali Murat; Ciftçi, Mehmet Ertuğrul; Akgünlü, Faruk
2012-01-01
The purpose of this study was to analyze two phosphor plate systems (PSPs) (Dürr Dental, Digora Optime) according to their scanning delay and protective plastic case performances. Two PSPs using an aluminum step wedge were exposed. These plates were placed in three different protective plastic cases (manufacturers' original cases, black case, and white case) before obtaining the radiographs and were then processed immediately and 1, 5, 10, 30, 60, 120, 240, and 480 min after exposure. Mean gray values (MGVs) of the 3rd, 5th, 7th, and 9th steps of the wedges were compared using ANOVA. Statistically significant differences were found between the two PSPs (P < 0.001). ANOVA revealed that the MGVs of four steps of the wedges were significantly different from each other for all scan delays (P < 0.001). MGVs increased with increasing scanning delay, except the group with Dürr plates in their original cases. Reduction in image quality began 5 min after exposure in the other Dürr plate groups. Within the limitations of the current study, it can be concluded that scanning delay causes a reduction in image quality, and using the manufacturer's original protective case will result in better performance of PSPs.
Rapid Thermal Processing (RTP) of semiconductors in space
NASA Technical Reports Server (NTRS)
Anderson, T. J.; Jones, K. S.
1993-01-01
The progress achieved on the project entitled 'Rapid Thermal Processing of Semiconductors in Space' for a 12 month period of activity ending March 31, 1993 is summarized. The activity of this group is being performed under the direct auspices of the ROMPS program. The main objective of this program is to develop and demonstrate the use of advanced robotics in space with rapid thermal process (RTP) of semiconductors providing the test technology. Rapid thermal processing is an ideal processing step for demonstration purposes since it encompasses many of the characteristics of other processes used in solid state device manufacturing. Furthermore, a low thermal budget is becoming more important in existing manufacturing practice, while a low thermal budget is critical to successful processing in space. A secondary objective of this project is to determine the influence of microgravity on the rapid thermal process for a variety of operating modes. In many instances, this involves one or more fluid phases. The advancement of microgravity processing science is an important ancillary objective.
Toward precision manufacturing of immunogene T-cell therapies.
Xu, Jun; Melenhorst, J Joseph; Fraietta, Joseph A
2018-05-01
Cancer can be effectively targeted using a patient's own T cells equipped with synthetic receptors, including chimeric antigen receptors (CARs) that redirect and reprogram these lymphocytes to mediate tumor rejection. Over the past two decades, several strategies to manufacture genetically engineered T cells have been proposed, with the goal of generating optimally functional cellular products for adoptive transfer. Based on this work, protocols for manufacturing clinical-grade CAR T cells have been established, but these complex methods have been used to treat only a few hundred individuals. As CAR T-cell therapy progresses into later-phase clinical trials and becomes an option for more patients, a major consideration for academic institutions and industry is developing robust manufacturing processes that will permit scaling-out production of immunogene T-cell therapies in a reproducible and efficient manner. In this review, we will discuss the steps involved in cell processing, the major obstacles surrounding T-cell manufacturing platforms and the approaches for improving cellular product potency. Finally, we will address the challenges of expanding CAR T-cell therapy to a global patient population. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Virtual manufacturing in reality
NASA Astrophysics Data System (ADS)
Papstel, Jyri; Saks, Alo
2000-10-01
SMEs play an important role in manufacturing industry. But from time to time there is a shortage in resources to complete the particular order in time. Number of systems is introduced to produce digital information in order to support product and process development activities. Main problem is lack of opportunity for direct data transition within design system modules when needed temporary extension of design capacity (virtuality) or to implement integrated concurrent product development principles. The planning experience in the field is weakly used as well. The concept of virtual manufacturing is a supporting idea to solve this problem. At the same time a number of practical problems should be solved like information conformity, data transfer, unified technological concepts acceptation etc. In the present paper the proposed ways to solve the practical problems of virtual manufacturing are described. General objective is to introduce the knowledge-based CAPP system as missing module for Virtual Manufacturing in the selected product domain. Surface-centered planning concept based on STEP- based modeling principles, and knowledge-based process planning methodology will be used to gain the objectives. As a result the planning module supplied by design data with direct access, and supporting advising environment is expected. Mould producing SME would be as test basis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Johnston, S.; Yan, F.; Dorn, D.
2012-06-01
Photoluminescence (PL) imaging techniques can be applied to multicrystalline silicon wafers throughout the manufacturing process. Both band-to-band PL and defect-band emissions, which are longer-wavelength emissions from sub-bandgap transitions, are used to characterize wafer quality and defect content on starting multicrystalline silicon wafers and neighboring wafers processed at each step through completion of finished cells. Both PL imaging techniques spatially highlight defect regions that represent dislocations and defect clusters. The relative intensities of these imaged defect regions change with processing. Band-to-band PL on wafers in the later steps of processing shows good correlation to cell quality and performance. The defect bandmore » images show regions that change relative intensity through processing, and better correlation to cell efficiency and reverse-bias breakdown is more evident at the starting wafer stage as opposed to later process steps. We show that thermal processing in the 200 degrees - 400 degrees C range causes impurities to diffuse to different defect regions, changing their relative defect band emissions.« less
Phase 1 of the automated array assembly task of the low cost silicon solar array project
NASA Technical Reports Server (NTRS)
Coleman, M. G.; Pryor, R. A.; Grenon, L. A.; Lesk, I. A.
1977-01-01
The state of technology readiness for the automated production of solar cells and modules is reviewed. Individual process steps and process sequences for making solar cells and modules were evaluated both technically and economically. High efficiency with a suggested cell goal of 15% was stressed. It is concluded that the technology exists to manufacture solar cells which will meet program goals.
Dutot, Camille; Mercier, Grégoire; Borget, Isabelle; de Sauvebeuf, Côme; Martelli, Nicolas
2017-01-01
Within French university hospitals, some internal committees are in charge of conducting hospital-based health technology assessment (Hb-HTA) to support managerial decisions regarding the adoption of innovations. For manufacturers, hospitals are usually the entry point for new and innovative medical devices, which cannot be accessed without the Hb-HTA committees' approval. Thus, the main objective of this pilot survey was to explore manufacturers' insights into Hb-HTA processes. A two-step pilot survey was conducted in 2014. First, semi-structured phone interviews were carried out to capture manufacturers' feedback on the Hb-HTA procedure. Second, a prospective and iterative questionnaire designed to explore manufacturers' market access strategies was administered. Eight manufacturers from the medical device industry completed the retrospective phone interviews, and five of them participated in the prospective survey. According to the overall feedback, the Hb-HTA process timeline and transparency are major issues, and the expectations of internal committees, especially in terms of clinical evidence, remain difficult to understand. However, despite this and due to the complexity of reimbursement processes at the national level, manufacturers are increasingly considering hospital adoption through Hb-HTA submission as a viable market access and coverage opportunity. Our study reaffirms the primary role of hospitals in the diffusion of innovative medical devices. However, to ensure efficient and broad access to innovation, cooperation between local and national HTA bodies is critical and should be promoted.
NASA Astrophysics Data System (ADS)
Altenbach, H.; Naumenko, K.; L'vov, G. I.; Pilipenko, S. N.
2003-05-01
A model which allows us to estimate the elastic properties of thin-walled structures manufactured by injection molding is presented. The starting step is the numerical prediction of the microstructure of a short-fiber-reinforced composite developed during the filling stage of the manufacturing process. For this purpose, the Moldflow Plastic Insight® commercial program is used. As a result of simulating the filling process, a second-rank orientation tensor characterizing the microstructure of the material is obtained. The elastic properties of the prepared material locally depend on the orientational distribution of fibers. The constitutive equation is formulated by means of orientational averaging for a given orientation tensor. The tensor of elastic material properties is computed and translated into the format for a stress-strain analysis based on the ANSYSÒ finite-element code. The numerical procedure and the convergence of results are discussed for a thin strip, a rectangular plate, and a shell of revolution. The influence of manufacturing conditions on the stress-strain state of statically loaded thin-walled elements is illustrated.
Controlling high-throughput manufacturing at the nano-scale
NASA Astrophysics Data System (ADS)
Cooper, Khershed P.
2013-09-01
Interest in nano-scale manufacturing research and development is growing. The reason is to accelerate the translation of discoveries and inventions of nanoscience and nanotechnology into products that would benefit industry, economy and society. Ongoing research in nanomanufacturing is focused primarily on developing novel nanofabrication techniques for a variety of applications—materials, energy, electronics, photonics, biomedical, etc. Our goal is to foster the development of high-throughput methods of fabricating nano-enabled products. Large-area parallel processing and highspeed continuous processing are high-throughput means for mass production. An example of large-area processing is step-and-repeat nanoimprinting, by which nanostructures are reproduced again and again over a large area, such as a 12 in wafer. Roll-to-roll processing is an example of continuous processing, by which it is possible to print and imprint multi-level nanostructures and nanodevices on a moving flexible substrate. The big pay-off is high-volume production and low unit cost. However, the anticipated cost benefits can only be realized if the increased production rate is accompanied by high yields of high quality products. To ensure product quality, we need to design and construct manufacturing systems such that the processes can be closely monitored and controlled. One approach is to bring cyber-physical systems (CPS) concepts to nanomanufacturing. CPS involves the control of a physical system such as manufacturing through modeling, computation, communication and control. Such a closely coupled system will involve in-situ metrology and closed-loop control of the physical processes guided by physics-based models and driven by appropriate instrumentation, sensing and actuation. This paper will discuss these ideas in the context of controlling high-throughput manufacturing at the nano-scale.
Status of the secondary mirrors (M2) for the Gemini 8-m telescopes
NASA Astrophysics Data System (ADS)
Knohl, Ernst-Dieter; Schoeppach, Armin; Pickering, Michael A.
1998-08-01
The 1-m diameter lightweight secondary mirrors (M2) for the Gemini 8-m telescopes will be the largest CVD-SiC mirrors ever produced. The design and manufacture of these mirrors is a very challenging task. In this paper we will discuss the mirror design, structural and mechanical analysis, and the CVD manufacturing process used to produce the mirror blanks. The lightweight design consist of a thin faceplate (4-mm) and triangular backstructure cells with ribs of varying heights. The main drivers in the design were weight (40 kg) and manufacturing limitations imposed on the backstructure cells and mirror mounts. Finite element modeling predicts that the mirror design will meet all of the Gemini M2 requirements for weight, mechanical integrity, resonances, and optical performance. Special design considerations were necessary to avoid stress concentration in the mounting areas and to meet the requirement that the mirror survive an 8-g earthquake. The highest risk step in the mirror blank manufacturing process is the near-net-shape CVD deposition of the thin, curved faceplate. Special tooling and procedures had to be developed to produce faceplates free of fractures, cracks, and stress during the cool-down from deposition temperature (1350 C) to room temperature. Due to time delay with the CVD manufacturing process in the meantime a backup solution from Zerodur has been started. This mirror is now in the advanced polishing process. Because the design of both mirrors is very similar an excellent comparison of both solutions is possible.
ERIC Educational Resources Information Center
Kaiser, Adrian; Stark, Wendelin J.; Grass, Robert N.
2017-01-01
A chemistry laboratory experiment using everyday items and readily available chemicals is described to introduce advanced high school students and undergraduate college students to porous polymer membranes. In a three-step manufacturing process, a membrane is produced at room temperature. The filtration principle of the membrane is then…
Towards quality by design in pharmaceutical manufacturing: modelling and control of air jet mills
NASA Astrophysics Data System (ADS)
Bhonsale, Satyajeet; Telen, Dries; Stokbroekx, Bard; Van Impe, Jan
2017-06-01
Milling is an important step in pharmaceutical manufacturing as it not only determines the final formulation of the drug product, but also influences the bioavailability and dissolution rate of the active pharmaceutical ingredient (API). In this respect, the air jet mill (AJM) is most commonly used in the pharmaceutical industry as it is a non-contaminating and non-degrading self-classifying process capable of delivering narrow particle size distributions (PSD). Keeping the principles of Quality by Design in mind, the Critical Process Parameters (CPPs) of the AJM have been identified to be the pressures at the grinding nozzles, and the feed rate which affect the PSD, surface charge and the morphology of the product (i.e. the Critical Material Attributes (CMAs)). For the purpose of this research, the PSD is considered to be the only relevant CMA. A population balance based model is proposed to simulate the dynamics milling operation by utilizing the concept of breakage functions. This model agrees qualitatively with experimental observations of the air jet mill unit present at Janssen Pharmaceutica but further steps for model validation need to be carried out.
The Automated Array Assembly Task of the Low-cost Silicon Solar Array Project, Phase 2
NASA Technical Reports Server (NTRS)
Coleman, M. G.; Grenon, L.; Pastirik, E. M.; Pryor, R. A.; Sparks, T. G.
1978-01-01
An advanced process sequence for manufacturing high efficiency solar cells and modules in a cost-effective manner is discussed. Emphasis is on process simplicity and minimizing consumed materials. The process sequence incorporates texture etching, plasma processes for damage removal and patterning, ion implantation, low pressure silicon nitride deposition, and plated metal. A reliable module design is presented. Specific process step developments are given. A detailed cost analysis was performed to indicate future areas of fruitful cost reduction effort. Recommendations for advanced investigations are included.
Robotic Processing Of Rocket-Engine Nozzles
NASA Technical Reports Server (NTRS)
Gilbert, Jeffrey L.; Maslakowski, John E.; Gutow, David A.; Deily, David C.
1994-01-01
Automated manufacturing cell containing computer-controlled robotic processing system developed to implement some important related steps in fabrication of rocket-engine nozzles. Performs several tedious and repetitive fabrication, measurement, adjustment, and inspection processes and subprocesses now performed manually. Offers advantages of reduced processing time, greater consistency, excellent collection of data, objective inspections, greater productivity, and simplified fixturing. Also affords flexibility: by making suitable changes in hardware and software, possible to modify process and subprocesses. Flexibility makes work cell adaptable to fabrication of heat exchangers and other items structured similarly to rocket nozzles.
How smart is your BEOL? productivity improvement through intelligent automation
NASA Astrophysics Data System (ADS)
Schulz, Kristian; Egodage, Kokila; Tabbone, Gilles; Garetto, Anthony
2017-07-01
The back end of line (BEOL) workflow in the mask shop still has crucial issues throughout all standard steps which are inspection, disposition, photomask repair and verification of repair success. All involved tools are typically run by highly trained operators or engineers who setup jobs and recipes, execute tasks, analyze data and make decisions based on the results. No matter how experienced operators are and how good the systems perform, there is one aspect that always limits the productivity and effectiveness of the operation: the human aspect. Human errors can range from seemingly rather harmless slip-ups to mistakes with serious and direct economic impact including mask rejects, customer returns and line stops in the wafer fab. Even with the introduction of quality control mechanisms that help to reduce these critical but unavoidable faults, they can never be completely eliminated. Therefore the mask shop BEOL cannot run in the most efficient manner as unnecessary time and money are spent on processes that still remain labor intensive. The best way to address this issue is to automate critical segments of the workflow that are prone to human errors. In fact, manufacturing errors can occur for each BEOL step where operators intervene. These processes comprise of image evaluation, setting up tool recipes, data handling and all other tedious but required steps. With the help of smart solutions, operators can work more efficiently and dedicate their time to less mundane tasks. Smart solutions connect tools, taking over the data handling and analysis typically performed by operators and engineers. These solutions not only eliminate the human error factor in the manufacturing process but can provide benefits in terms of shorter cycle times, reduced bottlenecks and prediction of an optimized workflow. In addition such software solutions consist of building blocks that seamlessly integrate applications and allow the customers to use tailored solutions. To accommodate for the variability and complexity in mask shops today, individual workflows can be supported according to the needs of any particular manufacturing line with respect to necessary measurement and production steps. At the same time the efficiency of assets is increased by avoiding unneeded cycle time and waste of resources due to the presence of process steps that are very crucial for a given technology. In this paper we present details of which areas of the BEOL can benefit most from intelligent automation, what solutions exist and the quantification of benefits to a mask shop with full automation by the use of a back end of line model.
NASA Astrophysics Data System (ADS)
Schmitt, R.; Niggemann, C.; Mersmann, C.
2008-04-01
Fibre-reinforced plastics (FRP) are particularly suitable for components where light-weight structures with advanced mechanical properties are required, e.g. for aerospace parts. Nevertheless, many manufacturing processes for FRP include manual production steps without an integrated quality control. A vital step in the process chain is the lay-up of the textile preform, as it greatly affects the geometry and the mechanical performance of the final part. In order to automate the FRP production, an inline machine vision system is needed for a closed-loop control of the preform lay-up. This work describes the development of a novel laser light-section sensor for optical inspection of textile preforms and its integration and validation in a machine vision prototype. The proposed method aims at the determination of the contour position of each textile layer through edge scanning. The scanning route is automatically derived by using texture analysis algorithms in a preliminary step. As sensor output a distinct stage profile is computed from the acquired greyscale image. The contour position is determined with sub-pixel accuracy using a novel algorithm based on a non-linear least-square fitting to a sigmoid function. The whole contour position is generated through data fusion of the measured edge points. The proposed method provides robust process automation for the FRP production improving the process quality and reducing the scrap quota. Hence, the range of economically feasible FRP products can be increased and new market segments with cost sensitive products can be addressed.
Lee, Sunmin; Lee, Sarah; Singh, Digar; Oh, Ji Young; Jeon, Eun Jung; Ryu, Hyung SeoK; Lee, Dong Wan; Kim, Beom Seok; Lee, Choong Hwan
2017-04-15
Two different doenjang manufacturing processes, the industrial process (IP) and the modified industrial process (mIP) with specific microbial assortments, were subjected to metabolite profiling using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). The multivariate analyses indicated that both primary and secondary metabolites exhibited distinct patterns according to the fermentation processes (IP and mIP). Microbial community analysis for doenjang using denaturing gradient gel electrophoresis (DGGE), exhibited that both bacteria and fungi contributed proportionally for each step in the process viz., soybean, steaming, drying, meju fermentation, cooling, brining, and aging. Further, correlation analysis indicated that Aspergillus population was linked to sugar metabolism, Bacillus spp. with that of fatty acids, whereas Tetragenococcus and Zygosaccharomyces were found associated with amino acids. These results suggest that the components and quality of doenjang are critically influenced by the microbial assortments in each process. Copyright © 2016 Elsevier Ltd. All rights reserved.
Simulation research on the process of large scale ship plane segmentation intelligent workshop
NASA Astrophysics Data System (ADS)
Xu, Peng; Liao, Liangchuang; Zhou, Chao; Xue, Rui; Fu, Wei
2017-04-01
Large scale ship plane segmentation intelligent workshop is a new thing, and there is no research work in related fields at home and abroad. The mode of production should be transformed by the existing industry 2.0 or part of industry 3.0, also transformed from "human brain analysis and judgment + machine manufacturing" to "machine analysis and judgment + machine manufacturing". In this transforming process, there are a great deal of tasks need to be determined on the aspects of management and technology, such as workshop structure evolution, development of intelligent equipment and changes in business model. Along with them is the reformation of the whole workshop. Process simulation in this project would verify general layout and process flow of large scale ship plane section intelligent workshop, also would analyze intelligent workshop working efficiency, which is significant to the next step of the transformation of plane segmentation intelligent workshop.
NASA Astrophysics Data System (ADS)
Cullen, Andrew T.; Price, Aaron D.
2017-04-01
Electropolymerization of pyrrole is commonly employed to fabricate intrinsically conductive polymer films that exhibit desirable electromechanical properties. Due to their monolithic nature, electroactive polypyrrole films produced via this process are typically limited to simple linear or bending actuation modes, which has hindered their application in complex actuation tasks. This initiative aims to develop the specialized fabrication methods and polymer formulations required to realize three-dimensional conductive polymer structures capable of more elaborate actuation modes. Our group has previously reported the application of the digital light processing additive manufacturing process for the fabrication of three-dimensional conductive polymer structures using ultraviolet radiation. In this investigation, we further expand upon this initial work and present an improved polymer formulation designed for digital light processing additive manufacturing using visible light. This technology enables the design of novel electroactive polymer sensors and actuators with enhanced capabilities and brings us one step closer to realizing more advanced electroactive polymer enabled devices.
Quantifying Reliability - The Next Step for a Rapidly Maturing PV Industry and China's Role
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kurtz, Sarah
2015-10-14
PV customers wish to know how long their PV modules will last, but quantitatively predicting service life is difficult because of the large number of ways that a module can fail, the variability of the use environment, the cost of the testing, and the short product development time, especially when compared with the long desired lifetime. China should play a key role in developing international standards because China manufactures most of the world's PV modules. The presentation will describe the steps that need to be taken to create a service life prediction within the context of a defined bill ofmore » materials, process window and use environment. Worldwide standards for cost-effective approaches to service-life predictions will be beneficial to both PV customers and manufacturers since the consequences of premature module failure can be disastrous for both.« less
More steps towards process automation for optical fabrication
NASA Astrophysics Data System (ADS)
Walker, David; Yu, Guoyu; Beaucamp, Anthony; Bibby, Matt; Li, Hongyu; McCluskey, Lee; Petrovic, Sanja; Reynolds, Christina
2017-06-01
In the context of Industrie 4.0, we have previously described the roles of robots in optical processing, and their complementarity with classical CNC machines, providing both processing and automation functions. After having demonstrated robotic moving of parts between a CNC polisher and metrology station, and auto-fringe-acquisition, we have moved on to automate the wash-down operation. This is part of a wider strategy we describe in this paper, leading towards automating the decision-making operations required before and throughout an optical manufacturing cycle.
Precision glass molding: Toward an optimal fabrication of optical lenses
NASA Astrophysics Data System (ADS)
Zhang, Liangchi; Liu, Weidong
2017-03-01
It is costly and time consuming to use machining processes, such as grinding, polishing and lapping, to produce optical glass lenses with complex features. Precision glass molding (PGM) has thus been developed to realize an efficient manufacture of such optical components in a single step. However, PGM faces various technical challenges. For example, a PGM process must be carried out within the super-cooled region of optical glass above its glass transition temperature, in which the material has an unstable non-equilibrium structure. Within a narrow window of allowable temperature variation, the glass viscosity can change from 105 to 1012 Pas due to the kinetic fragility of the super-cooled liquid. This makes a PGM process sensitive to its molding temperature. In addition, because of the structural relaxation in this temperature window, the atomic structure that governs the material properties is strongly dependent on time and thermal history. Such complexity often leads to residual stresses and shape distortion in a lens molded, causing unexpected changes in density and refractive index. This review will discuss some of the central issues in PGM processes and provide a method based on a manufacturing chain consideration from mold material selection, property and deformation characterization of optical glass to process optimization. The realization of such optimization is a necessary step for the Industry 4.0 of PGM.
Integration of Machining and Inspection in Aerospace Manufacturing
NASA Astrophysics Data System (ADS)
Simpson, Bart; Dicken, Peter J.
2011-12-01
The main challenge for aerospace manufacturers today is to develop the ability to produce high-quality products on a consistent basis as quickly as possible and at the lowest-possible cost. At the same time, rising material prices are making the cost of scrap higher than ever so making it more important to minimise waste. Proper inspection and quality control methods are no longer a luxury; they are an essential part of every manufacturing operation that wants to grow and be successful. However, simply bolting on some quality control procedures to the existing manufacturing processes is not enough. Inspection must be fully-integrated with manufacturing for the investment to really produce significant improvements. The traditional relationship between manufacturing and inspection is that machining is completed first on the company's machine tools and the components are then transferred to dedicated inspection equipment to be approved or rejected. However, as machining techniques become more sophisticated, and as components become larger and more complex, there are a growing number of cases where closer integration is required to give the highest productivity and the biggest reductions in wastage. Instead of a simple linear progression from CAD to CAM to machining to inspection, a more complicated series of steps is needed, with extra data needed to fill any gaps in the information available at the various stages. These new processes can be grouped under the heading of "adaptive machining". The programming of most machining operations is based around knowing three things: the position of the workpiece on the machine, the starting shape of the material to be machined, and the final shape that needs to be achieved at the end of the operation. Adaptive machining techniques allow successful machining when at least one of those elements is unknown, by using in-process measurement to close the information gaps in the process chain. It also allows any errors to be spotted earlier in the manufacturing process, so helping the problems to be resolved more quickly and at lower cost.
NASA Astrophysics Data System (ADS)
Li, Ning; Habuka, Hitoshi; Ikeda, Shin-ichi; Hara, Shiro
A chemical vapor deposition reactor for producing thin silicon films was designed and developed for achieving a new electronic device production system, the Minimal Manufacturing, using a half-inch wafer. This system requires a rapid process by a small footprint reactor. This was designed and verified by employing the technical issues, such as (i) vertical gas flow, (ii) thermal operation using a highly concentrated infrared flux, and (iii) reactor cleaning by chlorine trifluoride gas. The combination of (i) and (ii) could achieve a low heating power and a fast cooling designed by the heat balance of the small wafer placed at a position outside of the reflector. The cleaning process could be rapid by (iii). The heating step could be skipped because chlorine trifluoride gas was reactive at any temperature higher than room temperature.
Reinholz, Emilee L.; Roberts, Scott A.; Apblett, Christopher A.; ...
2016-06-11
The electrical conductivity is key to the performance of thermal battery cathodes. In this work we present the effects of manufacturing and processing conditions on the electrical conductivity of Li/FeS2 thermal battery cathodes. Finite element simulations were used to compute the conductivity of three-dimensional microcomputed tomography cathode microstructures and compare results to experimental impedance spectroscopy measurements. A regression analysis reveals a predictive relationship between composition, processing conditions, and electrical conductivity; a trend which is largely erased after thermally-induced deformation. Moreover, the trend applies to both experimental and simulation results, although is not as apparent in simulations. This research is amore » step toward a more fundamental understanding of the effects of processing and composition on thermal battery component microstructure, properties, and performance.« less
1366 Project Silicon: Reclaiming US Silicon PV Leadership
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lorenz, Adam
1366 Technologies’ Project Silicon addresses two of the major goals of the DOE’s PV Manufacturing Initiative Part 2 program: 1) How to reclaim a strong silicon PV manufacturing presence and; 2) How to lower the levelized cost of electricity (“LCOE”) for solar to $0.05-$0.07/kWh, enabling wide-scale U.S. market adoption. To achieve these two goals, US companies must commercialize disruptive, high-value technologies that are capable of rapid scaling, defensible from foreign competition, and suited for US manufacturing. These are the aims of 1366 Technologies Direct Wafer ™ process. The research conducted during Project Silicon led to the first industrial scaling ofmore » 1366’s Direct Wafer™ process – an innovative, US-friendly (efficient, low-labor content) manufacturing process that destroys the main cost barrier limiting silicon PV cost-reductions: the 35-year-old grand challenge of making quality wafers (40% of the cost of modules) without the cost and waste of sawing. The SunPath program made it possible for 1366 Technologies to build its demonstration factory, a key and critical step in the Company’s evolution. The demonstration factory allowed 1366 to build every step of the process flow at production size, eliminating potential risk and ensuring the success of the Company’s subsequent scaling for a 1 GW factory to be constructed in Western New York in 2016 and 2017. Moreover, the commercial viability of the Direct Wafer process and its resulting wafers were established as 1366 formed key strategic partnerships, gained entry into the $8B/year multi-Si wafer market, and installed modules featuring Direct Wafer products – the veritable proving grounds for the technology. The program also contributed to the development of three Generation 3 Direct Wafer furnaces. These furnaces are the platform for copying intelligently and preparing our supply chain – large-scale expansion will not require a bigger machine but more machines. SunPath filled the crucial development step between the original research effort in Lexington and the GW factory scheduled to be online before the end of the decade. At the conclusion of the project, it is clear that the Direct Wafer™ technology will have a dramatic impact on the entire silicon photovoltaic supply chain by effectively doubling existing silicon capacity (by reducing silicon usage by 50%) and reducing supply chain capital costs by 35%. The technology, when fully-scaled in the US, will also lead to significant job growth, with the eventual creation of 1,000 jobs in Western New York.« less
One-step catalytic conversion of biomass-derived carbohydrates to liquid fuels
Sen, Ayusman; Yang, Weiran
2014-03-18
The invention relates to a method for manufacture of hydrocarbon fuels and oxygenated hydrocarbon fuels such as alkyl substituted tetrahydrofurans such as 2,5-dimethyltetrahydrofuran, 2-methyltetrahydrofuran, 5-methylfurfural and mixtures thereof. The method generally entails forming a mixture of reactants that includes carbonaceous material, water, a metal catalyst and an acid reacting that mixture in the presence of hydrogen. The reaction is performed at a temperature and for a time sufficient to produce a furan type hydrocarbon fuel. The process may be adapted to provide continuous manufacture of hydrocarbon fuels such as a furan type fuel.
A novel design solution to the fraenal notch of maxillary dentures.
White, J A P; Bond, I P; Jagger, D C
2013-09-01
This study investigates a novel design feature for the fraenal notch of maxillary dentures, using computational and experimental methods, and shows that its use could significantly increase the longevity of the prosthesis. A two-step process can be used to create the design feature with current denture base materials, but would be highly dependent on the individual skill of the dental technician. Therefore, an alternative form of manufacture, multi-material additive layer manufacture (or '3D printing'), has been proposed as a future method for the direct production of complete dentures with multi-material design features.
Trainer, Asa; Hedberg, Thomas; Feeney, Allison Barnard; Fischer, Kevin; Rosche, Phil
2017-01-01
Advances in information technology triggered a digital revolution that holds promise of reduced costs, improved productivity, and higher quality. To ride this wave of innovation, manufacturing enterprises are changing how product definitions are communicated – from paper to models. To achieve industry's vision of the Model-Based Enterprise (MBE), the MBE strategy must include model-based data interoperability from design to manufacturing and quality in the supply chain. The Model-Based Definition (MBD) is created by the original equipment manufacturer (OEM) using Computer-Aided Design (CAD) tools. This information is then shared with the supplier so that they can manufacture and inspect the physical parts. Today, suppliers predominantly use Computer-Aided Manufacturing (CAM) and Coordinate Measuring Machine (CMM) models for these tasks. Traditionally, the OEM has provided design data to the supplier in the form of two-dimensional (2D) drawings, but may also include a three-dimensional (3D)-shape-geometry model, often in a standards-based format such as ISO 10303-203:2011 (STEP AP203). The supplier then creates the respective CAM and CMM models and machine programs to produce and inspect the parts. In the MBE vision for model-based data exchange, the CAD model must include product-and-manufacturing information (PMI) in addition to the shape geometry. Today's CAD tools can generate models with embedded PMI. And, with the emergence of STEP AP242, a standards-based model with embedded PMI can now be shared downstream. The on-going research detailed in this paper seeks to investigate three concepts. First, that the ability to utilize a STEP AP242 model with embedded PMI for CAD-to-CAM and CAD-to-CMM data exchange is possible and valuable to the overall goal of a more efficient process. Second, the research identifies gaps in tools, standards, and processes that inhibit industry's ability to cost-effectively achieve model-based-data interoperability in the pursuit of the MBE vision. Finally, it also seeks to explore the interaction between CAD and CMM processes and determine if the concept of feedback from CAM and CMM back to CAD is feasible. The main goal of our study is to test the hypothesis that model-based-data interoperability from CAD-to-CAM and CAD-to-CMM is feasible through standards-based integration. This paper presents several barriers to model-based-data interoperability. Overall, the project team demonstrated the exchange of product definition data between CAD, CAM, and CMM systems using standards-based methods. While gaps in standards coverage were identified, the gaps should not stop industry's progress toward MBE. The results of our study provide evidence in support of an open-standards method to model-based-data interoperability, which would provide maximum value and impact to industry. PMID:28691120
Practical Framework: Implementing OEE Method in Manufacturing Process Environment
NASA Astrophysics Data System (ADS)
Maideen, N. C.; Sahudin, S.; Mohd Yahya, N. H.; Norliawati, A. O.
2016-02-01
Manufacturing process environment requires reliable machineries in order to be able to satisfy the market demand. Ideally, a reliable machine is expected to be operated and produce a quality product at its maximum designed capability. However, due to some reason, the machine usually unable to achieved the desired performance. Since the performance will affect the productivity of the system, a measurement technique should be applied. Overall Equipment Effectiveness (OEE) is a good method to measure the performance of the machine. The reliable result produced from OEE can then be used to propose a suitable corrective action. There are a lot of published paper mentioned about the purpose and benefit of OEE that covers what and why factors. However, the how factor not yet been revealed especially the implementation of OEE in manufacturing process environment. Thus, this paper presents a practical framework to implement OEE and a case study has been discussed to explain in detail each steps proposed. The proposed framework is beneficial to the engineer especially the beginner to start measure their machine performance and later improve the performance of the machine.
Interferometric surface mapping with variable sensitivity.
Jaerisch, W; Makosch, G
1978-03-01
In the photolithographic process, presently employed for the production of integrated circuits, sets of correlated masks are used for exposing the photoresist on silicon wafers. Various sets of masks which are printed in different printing tools must be aligned correctly with respect to the structures produced on the wafer in previous process steps. Even when perfect alignment is considered, displacements and distortions of the printed wafer patterns occur. They are caused by imperfections of the printing tools or/and wafer deformations resulting from high temperature processes. Since the electrical properties of the final integrated circuits and therefore the manufacturing yield depend to a great extent on the precision at which such patterns are superimposed, simple and fast overlay measurements and flatness measurements as well are very important in IC-manufacturing. A simple optical interference method for flatness measurements will be described which can be used under manufacturing conditions. This method permits testing of surface height variations by nearly grazing light incidence by absence of a physical reference plane. It can be applied to polished surfaces and rough surfaces as well.
Study of a dry room in a battery manufacturing plant using a process model
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ahmed, Shabbir; Nelson, Paul A.; Dees, Dennis W.
The manufacture of lithium ion batteries requires some processing steps to be carried out in a dry room, where the moisture content should remain below 100 parts per million. The design and operation of such a dry room adds to the cost of the battery. This paper studies the humidity management of the air to and from the dry room to understand the impact of design and operating parameters on the energy demand and the cost contribution towards the battery manufacturing cost. The study is conducted with the help of a process model for a dry room with a volumemore » of 16000 cubic meters. For a defined base case scenario it is found that the dry room operation has an energy demand of approximately 400 kW. The paper explores some tradeoffs in design and operating parameters by looking at the humidity reduction by quenching the make-up air vs. at the desiccant wheel, and the impact of the heat recovery from the desiccant regeneration cycle.« less
Cervera-Padrell, Albert E; Skovby, Tommy; Kiil, Søren; Gani, Rafiqul; Gernaey, Krist V
2012-10-01
A systematic framework is proposed for the design of continuous pharmaceutical manufacturing processes. Specifically, the design framework focuses on organic chemistry based, active pharmaceutical ingredient (API) synthetic processes, but could potentially be extended to biocatalytic and fermentation-based products. The method exploits the synergic combination of continuous flow technologies (e.g., microfluidic techniques) and process systems engineering (PSE) methods and tools for faster process design and increased process understanding throughout the whole drug product and process development cycle. The design framework structures the many different and challenging design problems (e.g., solvent selection, reactor design, and design of separation and purification operations), driving the user from the initial drug discovery steps--where process knowledge is very limited--toward the detailed design and analysis. Examples from the literature of PSE methods and tools applied to pharmaceutical process design and novel pharmaceutical production technologies are provided along the text, assisting in the accumulation and interpretation of process knowledge. Different criteria are suggested for the selection of batch and continuous processes so that the whole design results in low capital and operational costs as well as low environmental footprint. The design framework has been applied to the retrofit of an existing batch-wise process used by H. Lundbeck A/S to produce an API: zuclopenthixol. Some of its batch operations were successfully converted into continuous mode, obtaining higher yields that allowed a significant simplification of the whole process. The material and environmental footprint of the process--evaluated through the process mass intensity index, that is, kg of material used per kg of product--was reduced to half of its initial value, with potential for further reduction. The case-study includes reaction steps typically used by the pharmaceutical industry featuring different characteristic reaction times, as well as L-L separation and distillation-based solvent exchange steps, and thus constitutes a good example of how the design framework can be useful to efficiently design novel or already existing API manufacturing processes taking advantage of continuous processes. Copyright © 2012 Elsevier B.V. All rights reserved.
In Situ Fringe Projection Profilometry for Laser Power Bed Fusion Process
NASA Astrophysics Data System (ADS)
Zhang, Bin
Additive manufacturing (AM) offers an industrial solution to produce parts with complex geometries and internal structures that conventional manufacturing techniques cannot produce. However, current metal additive process, particularly the laser powder bed fusion (LPBF) process, suffers from poor surface finish and various material defects which hinder its wide applications. One way to solve this problem is by adding in situ metrology sensor onto the machine chamber. Matured manufacturing processes are tightly monitored and controlled, and instrumentation advances are needed to realize this same advantage for metal additive process. This encourages us to develop an in situ fringe projection system for the LPBF process. The development of such a system and the measurement capability are demonstrated in this dissertation. We show that this system can measure various powder bed signatures including powder layer variations, the average height drop between fused metal and unfused powder, and the height variations on the fused surfaces. The ability to measure textured surface is also evaluated through the instrument transfer function (ITF). We analyze the mathematical model of the proposed fringe projection system, and prove the linearity of the system through simulations. A practical ITF measurement technique using a stepped surface is also demonstrated. The measurement results are compared with theoretical predictions generated through the ITF simulations.
Papantoniou Ir, Ioannis; Chai, Yoke Chin; Luyten, Frank P; Schrooten Ir, Jan
2013-08-01
The incorporation of Quality-by-Design (QbD) principles in tissue-engineering bioprocess development toward clinical use will ensure that manufactured constructs possess prerequisite quality characteristics addressing emerging regulatory requirements and ensuring the functional in vivo behavior. In this work, the QbD principles were applied on a manufacturing process step for the in vitro production of osteogenic three-dimensional (3D) hybrid scaffolds that involves cell matrix deposition on a 3D titanium (Ti) alloy scaffold. An osteogenic cell source (human periosteum-derived cells) cultured in a bioinstructive medium was used to functionalize regular Ti scaffolds in a perfusion bioreactor, resulting in an osteogenic hybrid carrier. A two-level three-factor fractional factorial design of experiments was employed to explore a range of production-relevant process conditions by simultaneously changing value levels of the following parameters: flow rate (0.5-2 mL/min), cell culture duration (7-21 days), and cell-seeding density (1.5×10(3)-3×10(3) cells/cm(2)). This approach allowed to evaluate the individual impact of the aforementioned process parameters upon key quality attributes of the produced hybrids, such as collagen production, mineralization level, and cell number. The use of a fractional factorial design approach helped create a design space in which hybrid scaffolds of predefined quality attributes may be robustly manufactured while minimizing the number of required experiments.
Residual stress prediction in a powder bed fusion manufactured Ti6Al4V hip stem
NASA Astrophysics Data System (ADS)
Barrett, Richard A.; Etienne, Titouan; Duddy, Cormac; Harrison, Noel M.
2017-10-01
Powder bed fusion (PBF) is a category of additive manufacturing (AM) that is particularly suitable for the production of 3D metallic components. In PBF, only material in the current build layer is at the required melt temperature, with the previously melted and solidified layers reducing in temperature, thus generating a significant thermal gradient within the metallic component, particularly for laser based PBF components. The internal thermal stresses are subsequently relieved in a post-processing heat-treatment step. Failure to adequately remove these stresses can result in cracking and component failure. A prototype hip stem was manufactured from Ti6Al4V via laser PBF but was found to have fractured during over-seas shipping. This study examines the evolution of thermal stresses during the laser PBF manufacturing and heat treatment processes of the hip stem in a 2D finite element analysis (FEA) and compares it to an electron beam PBF process. A custom written script for the automatic conversion of a gross geometry finite element model into a thin layer- by-layer finite element model was developed. The build process, heat treatment (for laser PBF) and the subsequent cooling were simulated at the component level. The results demonstrate the effectiveness of the heat treatment in reducing PBF induced thermal stresses, and the concentration of stresses in the region that fractured.
Sharp, J R
1994-12-01
Drucker writes that the emerging theory of manufacturing includes four principles and practices: statistical quality control, manufacturing accounting, modular organization, and systems approach. SQC is a rigorous, scientific method of identifying variation in the quality and productivity of a given production process, with an emphasis on improvement. The new manufacturing economics intends to integrate the production strategy with the business strategy in order to account for the biggest portions of costs that the old methods did not assess: time and automation. Production operations that are both standardized and flexible will allow the organization to keep up with changes in design, technology, and the market. The return on innovation in this environment is predicated on a modular arrangement of flexible steps in the process. Finally, the systems approach sees the entire process as being integrated in converting goods or services into economic satisfaction. There is now a major restructuring of the U.S. health care industry, and the incorporation of these four theories into health care reform would appear to be essential. This two-part article will address two problems: Will Drucker's theories relate to health care (Part I)? Will the "new manufacturing" in health care (practice guidelines) demonstrate cost, quality, and access changes that reform demands (Part II)?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Havasy, C.K.; Quach, T.K.; Bozada, C.A.
1995-12-31
This work is the development of a single-layer integrated-metal field effect transistor (SLIMFET) process for a high performance 0.2 {mu}m AlGaAs/InGaAs pseudomorphic high electron mobility transistor (PHEMT). This process is compatible with MMIC fabrication and minimizes process variations, cycle time, and cost. This process uses non-alloyed ohmic contacts, a selective gate-recess etching process, and a single gate/source/drain metal deposition step to form both Schottky and ohmic contacts at the same time.
Developing weighted criteria to evaluate lean reverse logistics through analytical network process
NASA Astrophysics Data System (ADS)
Zagloel, Teuku Yuri M.; Hakim, Inaki Maulida; Krisnawardhani, Rike Adyartie
2017-11-01
Reverse logistics is a part of supply chain that bring materials from consumers back to manufacturer in order to gain added value or do a proper disposal. Nowadays, most companies are still facing several problems on reverse logistics implementation which leads to high waste along reverse logistics processes. In order to overcome this problem, Madsen [Framework for Reverse Lean Logistics to Enable Green Manufacturing, Eco Design 2009: 6th International Symposium on Environmentally Conscious Design and Inverse Manufacturing, Sapporo, 2009] has developed a lean reverse logistics framework as a step to eliminate waste by implementing lean on reverse logistics. However, the resulted framework sets aside criteria used to evaluate its performance. This research aims to determine weighted criteria that can be used as a base on reverse logistics evaluation by considering lean principles. The resulted criteria will ensure reverse logistics are kept off from waste, thus implemented efficiently. Analytical Network Process (ANP) is used in this research to determine the weighted criteria. The result shows that criteria used for evaluation lean reverse logistics are Innovation and Learning (35%), Economic (30%), Process Flow Management (14%), Customer Relationship Management (13%), Environment (6%), and Social (2%).
USDA-ARS?s Scientific Manuscript database
To develop a better understanding of compositional changes occurring during the production of commercial teas, we determined by high-performance liquid chromatography (HPLC) changes in ingredient levels during each of several manufacturing steps used to produce Kamairi-cha, a premium green tea. We ...
Thin film solar cell configuration and fabrication method
Menezes, Shalini
2009-07-14
A new photovoltaic device configuration based on an n-copper indium selenide absorber and a p-type window is disclosed. A fabrication method to produce this device on flexible or rigid substrates is described that reduces the number of cell components, avoids hazardous materials, simplifies the process steps and hence the costs for high volume solar cell manufacturing.
Design and operation of a continuous integrated monoclonal antibody production process.
Steinebach, Fabian; Ulmer, Nicole; Wolf, Moritz; Decker, Lara; Schneider, Veronika; Wälchli, Ruben; Karst, Daniel; Souquet, Jonathan; Morbidelli, Massimo
2017-09-01
The realization of an end-to-end integrated continuous lab-scale process for monoclonal antibody manufacturing is described. For this, a continuous cultivation with filter-based cell-retention, a continuous two column capture process, a virus inactivation step, a semi-continuous polishing step (twin-column MCSGP), and a batch-wise flow-through polishing step were integrated and operated together. In each unit, the implementation of internal recycle loops allows to improve the performance: (a) in the bioreactor, to simultaneously increase the cell density and volumetric productivity, (b) in the capture process, to achieve improved capacity utilization at high productivity and yield, and (c) in the MCSGP process, to overcome the purity-yield trade-off of classical batch-wise bind-elute polishing steps. Furthermore, the design principles, which allow the direct connection of these steps, some at steady state and some at cyclic steady state, as well as straight-through processing, are discussed. The setup was operated for the continuous production of a commercial monoclonal antibody, resulting in stable operation and uniform product quality over the 17 cycles of the end-to-end integration. The steady-state operation was fully characterized by analyzing at the outlet of each unit at steady state the product titer as well as the process (HCP, DNA, leached Protein A) and product (aggregates, fragments) related impurities. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1303-1313, 2017. © 2017 American Institute of Chemical Engineers.
Breathe easy with proper respiratory protection
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bidwell, J.
1996-05-01
Evaluating the need for respiratory protection in chemical process industries (CPI) plants and selecting the appropriate respirator involves several steps. The Occupational Safety and Health Administration (OSHA) general industry standard for respiratory protection (29 CFR 1910.134(b)) requires the employer to establish a program to help reduce exposures to occupational contaminants. When feasible, employers must eliminate contaminants by using engineering controls (such as general and local ventilation, enclosure or isolation, or substitution of a less-hazardous process or material). Establishing a respiratory protection program consists of four steps: (1) Identify respiratory hazards and concentrations; (2) Understand the contaminants` effects on workers` health;more » (3) Select appropriate respiratory protection; and (4) Train in proper respirator use and maintenance. Consult applicable state and OSHA requirements to ensure that your program satisfies these steps. Industrial respirator manufacturers can assist with on-site training and fit testing. The paper discusses these four steps, program guidelines, determination of the hazard, and styles of respirators.« less
Chhatre, Sunil; Jones, Carl; Francis, Richard; O'Donovan, Kieran; Titchener-Hooker, Nigel; Newcombe, Anthony; Keshavarz-Moore, Eli
2006-01-01
Growing commercial pressures in the pharmaceutical industry are establishing a need for robust computer simulations of whole bioprocesses to allow rapid prediction of the effects of changes made to manufacturing operations. This paper presents an integrated process simulation that models the cGMP manufacture of the FDA-approved biotherapeutic CroFab, an IgG fragment used to treat rattlesnake envenomation (Protherics U.K. Limited, Blaenwaun, Ffostrasol, Llandysul, Wales, U.K.). Initially, the product is isolated from ovine serum by precipitation and centrifugation, before enzymatic digestion of the IgG to produce FAB and FC fragments. These are purified by ion exchange and affinity chromatography to remove the FC and non-specific FAB fragments from the final venom-specific FAB product. The model was constructed in a discrete event simulation environment and used to determine the potential impact of a series of changes to the process, such as increasing the step efficiencies or volumes of chromatographic matrices, upon product yields and process times. The study indicated that the overall FAB yield was particularly sensitive to changes in the digestive and affinity chromatographic step efficiencies, which have a predicted 30% greater impact on process FAB yield than do the precipitation or centrifugation stages. The study showed that increasing the volume of affinity matrix has a negligible impact upon total process time. Although results such as these would require experimental verification within the physical constraints of the process and the facility, the model predictions are still useful in allowing rapid "what-if" scenario analysis of the likely impacts of process changes within such an integrated production process.
Process development and tooling design for intrinsic hybrid composites
NASA Astrophysics Data System (ADS)
Riemer, M.; Müller, R.; Drossel, W. G.; Landgrebe, D.
2017-09-01
Hybrid parts, which combine the advantages of different material classes, are moving into the focus of lightweight applications. This development is amplified by their high potential for usage in the field of crash relevant structures. By the current state of the art, hybrid parts are mainly made in separate, subsequent forming and joining processes. By using the concept of an intrinsic hybrid, the shaping of the part and the joining of the different materials are performed in a single process step for shortening the overall processing time and thereby the manufacturing costs. The investigated hybrid part is made from continuous fibre reinforced plastic (FRP), in which a metallic reinforcement structure is integrated. The connection between these layered components is realized by a combination of adhesive bonding and a geometrical form fit. The form fit elements are intrinsically generated during the forming process. This contribution regards the development of the forming process and the design of the forming tool for the single step production of a hybrid part. To this end a forming tool, which combines the thermo-forming and the metal forming process, is developed. The main challenge by designing the tool is the temperature management of the tool elements for the variothermal forming process. The process parameters are determined in basic tests and finite element (FE) simulation studies. On the basis of these investigations a control concept for the steering of the motion axes and the tool temperature is developed. Forming tests are carried out with the developed tool and the manufactured parts are analysed by computer assisted tomography (CT) scans.
Joda, Tim; Brägger, Urs
2015-01-01
To compare time-efficiency in the production of implant crowns using a digital workflow versus the conventional pathway. This prospective clinical study used a crossover design that included 20 study participants receiving single-tooth replacements in posterior sites. Each patient received a customized titanium abutment plus a computer-aided design/computer-assisted manufacture (CAD/CAM) zirconia suprastructure (for those in the test group, using digital workflow) and a standardized titanium abutment plus a porcelain-fused-to-metal crown (for those in the control group, using a conventional pathway). The start of the implant prosthetic treatment was established as the baseline. Time-efficiency analysis was defined as the primary outcome, and was measured for every single clinical and laboratory work step in minutes. Statistical analysis was calculated with the Wilcoxon rank sum test. All crowns could be provided within two clinical appointments, independent of the manufacturing process. The mean total production time, as the sum of clinical plus laboratory work steps, was significantly different. The mean ± standard deviation (SD) time was 185.4 ± 17.9 minutes for the digital workflow process and 223.0 ± 26.2 minutes for the conventional pathway (P = .0001). Therefore, digital processing for overall treatment was 16% faster. Detailed analysis for the clinical treatment revealed a significantly reduced mean ± SD chair time of 27.3 ± 3.4 minutes for the test group compared with 33.2 ± 4.9 minutes for the control group (P = .0001). Similar results were found for the mean laboratory work time, with a significant decrease of 158.1 ± 17.2 minutes for the test group vs 189.8 ± 25.3 minutes for the control group (P = .0001). Only a few studies have investigated efficiency parameters of digital workflows compared with conventional pathways in implant dental medicine. This investigation shows that the digital workflow seems to be more time-efficient than the established conventional production pathway for fixed implant-supported crowns. Both clinical chair time and laboratory manufacturing steps could be effectively shortened with the digital process of intraoral scanning plus CAD/CAM technology.
3D Printing In Zero-G ISS Technology Demonstration
NASA Technical Reports Server (NTRS)
Werkheiser, Niki; Cooper, Kenneth; Edmunson, Jennifer; Dunn, Jason; Snyder, Michael
2014-01-01
The National Aeronautics and Space Administration (NASA) has a long term strategy to fabricate components and equipment on-demand for manned missions to the Moon, Mars, and beyond. To support this strategy, NASA and Made in Space, Inc. are developing the 3D Printing In Zero-G payload as a Technology Demonstration for the International Space Station (ISS). The 3D Printing In Zero-G experiment ('3D Print') will be the first machine to perform 3D printing in space. The greater the distance from Earth and the longer the mission duration, the more difficult resupply becomes; this requires a change from the current spares, maintenance, repair, and hardware design model that has been used on the International Space Station (ISS) up until now. Given the extension of the ISS Program, which will inevitably result in replacement parts being required, the ISS is an ideal platform to begin changing the current model for resupply and repair to one that is more suitable for all exploration missions. 3D Printing, more formally known as Additive Manufacturing, is the method of building parts/objects/tools layer-by-layer. The 3D Print experiment will use extrusion-based additive manufacturing, which involves building an object out of plastic deposited by a wire-feed via an extruder head. Parts can be printed from data files loaded on the device at launch, as well as additional files uplinked to the device while on-orbit. The plastic extrusion additive manufacturing process is a low-energy, low-mass solution to many common needs on board the ISS. The 3D Print payload will serve as the ideal first step to proving that process in space. It is unreasonable to expect NASA to launch large blocks of material from which parts or tools can be traditionally machined, and even more unreasonable to fly up multiple drill bits that would be required to machine parts from aerospace-grade materials such as titanium 6-4 alloy and Inconel. The technology to produce parts on demand, in space, offers unique design options that are not possible through traditional manufacturing methods while offering cost-effective, high-precision, low-unit on-demand manufacturing. Thus, Additive Manufacturing capabilities are the foundation of an advanced manufacturing in space roadmap. The 3D Printing In Zero-G experiment will demonstrate the capability of utilizing Additive Manufacturing technology in space. This will serve as the enabling first step to realizing an additive manufacturing, print-on-demand "machine shop" for long-duration missions and sustaining human exploration of other planets, where there is extremely limited ability and availability of Earth-based logistics support. Simply put, Additive Manufacturing in space is a critical enabling technology for NASA. It will provide the capability to produce hardware on-demand, directly lowering cost and decreasing risk by having the exact part or tool needed in the time it takes to print. This capability will also provide the much-needed solution to the cost, volume, and up-mass constraints that prohibit launching everything needed for long-duration or long-distance missions from Earth, including spare parts and replacement systems. A successful mission for the 3D Printing In Zero-G payload is the first step to demonstrate the capability of printing on orbit. The data gathered and lessons learned from this demonstration will be applied to the next generation of additive manufacturing technology on orbit. It is expected that Additive Manufacturing technology will quickly become a critical part of any mission's infrastructure.
Local Structure Fixation in the Composite Manufacturing Chain
NASA Astrophysics Data System (ADS)
Girdauskaite, Lina; Krzywinski, Sybille; Rödel, Hartmut; Wildasin-Werner, Andrea; Böhme, Ralf; Jansen, Irene
2010-12-01
Compared to metal materials, textile reinforced composites show interesting features, but also higher production costs because of low automation rate in the manufacturing chain at this time. Their applicability is also limited due to quality problems, which restrict the production of complex shaped dry textile preforms. New technologies, design concepts, and cost-effective manufacturing methods are needed in order to establish further fields of application. This paper deals with possible ways to improve the textile deformation process by locally applying a fixative to the structure parallel to the cut. This hinders unwanted deformation in the textile stock during the subsequent stacking and formation steps. It is found that suitable thermoplastic binders, applied in the appropriate manner do not restrict formation of the textile and have no negative influence on the mechanical properties of the composite.
Technical manual for manufacturing autologous fibrin tissue adhesive.
Park, J J; Cintron, J R; Siedentop, K H; Orsay, C P; Pearl, R K; Nelson, R L; Abcarian, H
1999-10-01
The aim of this article is to provide a concise and simple technical manual for manufacturing autologous fibrin tissue adhesive derived from the precipitation of fibrinogen using a combination of ethanol and freezing for surgery. All materials and equipment needed to manufacture ethanol-based autologous fibrin tissue adhesive are listed. In addition, step-by-step instructions are provided to allow for easy and rapid fibrin adhesive production. Ethanol-based autologous fibrin tissue adhesive can be manufactured in under 60 minutes. Furthermore, at our institution the startup cost for manufacturing ethanol-based autologous fibrin tissue adhesive was under $2,500.00. Ethanol-based autologous fibrin tissue adhesive is a safe, reliable, and easily manufactured autologous fibrin tissue adhesive that can be made by a trained technician in any blood bank, pharmacy, or surgical laboratory.
Additive manufactured x-ray optics for astronomy
NASA Astrophysics Data System (ADS)
Atkins, Carolyn; Feldman, Charlotte; Brooks, David; Watson, Stephen; Cochrane, William; Roulet, Melanie; Doel, Peter; Willingale, Richard; Hugot, Emmanuel
2017-08-01
Additive manufacturing, more commonly known as 3D printing, has become a commercially established technology for rapid prototyping and the fabrication of bespoke intricate parts. Optical components, such as mirrors and lenses, are now being fabricated via additive manufacturing, where the printed substrate is polished in a post-processing step. One application of additively manufactured optics could be within the astronomical X-ray community, where there is a growing need to demonstrate thin, lightweight, high precision optics for a beyond Chandra style mission. This paper will follow a proof-of-concept investigation, sponsored by the UK Space Agency's National Space Technology Programme, into the feasibility of applying additive manufacturing in the production of thin, lightweight, precision X-ray optics for astronomy. One of the benefits of additive manufacturing is the ability to construct intricate lightweighting, which can be optimised to minimise weight while ensuring rigidity. This concept of optimised lightweighting will be applied to a series of polished additively manufactured test samples and experimental data from these samples, including an assessment of the optical quality and the magnitude of any print-through, will be presented. In addition, the finite element analysis optimisations of the lightweighting development will be discussed.
Rouiller, Yolande; Solacroup, Thomas; Deparis, Véronique; Barbafieri, Marco; Gleixner, Ralf; Broly, Hervé; Eon-Duval, Alex
2012-06-01
The production bioreactor step of an Fc-Fusion protein manufacturing cell culture process was characterized following Quality by Design principles. Using scientific knowledge derived from the literature and process knowledge gathered during development studies and manufacturing to support clinical trials, potential critical and key process parameters with a possible impact on product quality and process performance, respectively, were determined during a risk assessment exercise. The identified process parameters were evaluated using a design of experiment approach. The regression models generated from the data allowed characterizing the impact of the identified process parameters on quality attributes. The main parameters having an impact on product titer were pH and dissolved oxygen, while those having the highest impact on process- and product-related impurities and variants were pH and culture duration. The models derived from characterization studies were used to define the cell culture process design space. The design space limits were set in such a way as to ensure that the drug substance material would consistently have the desired quality. Copyright © 2012 Elsevier B.V. All rights reserved.
3D printing and milling a real-time PCR device for infectious disease diagnostics.
Mulberry, Geoffrey; White, Kevin A; Vaidya, Manjusha; Sugaya, Kiminobu; Kim, Brian N
2017-01-01
Diagnosing infectious diseases using quantitative polymerase chain reaction (qPCR) offers a conclusive result in determining the infection, the strain or type of pathogen, and the level of infection. However, due to the high-cost instrumentation involved and the complexity in maintenance, it is rarely used in the field to make a quick turnaround diagnosis. In order to provide a higher level of accessibility than current qPCR devices, a set of 3D manufacturing methods is explored as a possible option to fabricate a low-cost and portable qPCR device. The key advantage of this approach is the ability to upload the digital format of the design files on the internet for wide distribution so that people at any location can simply download and feed into their 3D printers for quick manufacturing. The material and design are carefully selected to minimize the number of custom parts that depend on advanced manufacturing processes which lower accessibility. The presented 3D manufactured qPCR device is tested with 20-μL samples that contain various concentrations of lentivirus, the same type as HIV. A reverse-transcription step is a part of the device's operation, which takes place prior to the qPCR step to reverse transcribe the target RNA from the lentivirus into complementary DNA (cDNA). This is immediately followed by qPCR which quantifies the target sequence molecules in the sample during the PCR amplification process. The entire process of thermal control and time-coordinated fluorescence reading is automated by closed-loop feedback and a microcontroller. The resulting device is portable and battery-operated, with a size of 12 × 7 × 6 cm3 and mass of only 214 g. By uploading and sharing the design files online, the presented low-cost qPCR device may provide easier access to a robust diagnosis protocol for various infectious diseases, such as HIV and malaria.
3D printing and milling a real-time PCR device for infectious disease diagnostics
Mulberry, Geoffrey; White, Kevin A.; Vaidya, Manjusha; Sugaya, Kiminobu
2017-01-01
Diagnosing infectious diseases using quantitative polymerase chain reaction (qPCR) offers a conclusive result in determining the infection, the strain or type of pathogen, and the level of infection. However, due to the high-cost instrumentation involved and the complexity in maintenance, it is rarely used in the field to make a quick turnaround diagnosis. In order to provide a higher level of accessibility than current qPCR devices, a set of 3D manufacturing methods is explored as a possible option to fabricate a low-cost and portable qPCR device. The key advantage of this approach is the ability to upload the digital format of the design files on the internet for wide distribution so that people at any location can simply download and feed into their 3D printers for quick manufacturing. The material and design are carefully selected to minimize the number of custom parts that depend on advanced manufacturing processes which lower accessibility. The presented 3D manufactured qPCR device is tested with 20-μL samples that contain various concentrations of lentivirus, the same type as HIV. A reverse-transcription step is a part of the device’s operation, which takes place prior to the qPCR step to reverse transcribe the target RNA from the lentivirus into complementary DNA (cDNA). This is immediately followed by qPCR which quantifies the target sequence molecules in the sample during the PCR amplification process. The entire process of thermal control and time-coordinated fluorescence reading is automated by closed-loop feedback and a microcontroller. The resulting device is portable and battery-operated, with a size of 12 × 7 × 6 cm3 and mass of only 214 g. By uploading and sharing the design files online, the presented low-cost qPCR device may provide easier access to a robust diagnosis protocol for various infectious diseases, such as HIV and malaria. PMID:28586401
NASA Technical Reports Server (NTRS)
Vosteen, Louis F.; Hadcock, Richard N.
1994-01-01
A study of past composite aircraft structures programs was conducted to determine the lessons learned during the programs. The study focused on finding major underlying principles and practices that experience showed have significant effects on the development process and should be recognized and understood by those responsible for using of composites. Published information on programs was reviewed and interviews were conducted with personnel associated with current and past major development programs. In all, interviews were conducted with about 56 people representing 32 organizations. Most of the people interviewed have been involved in the engineering and manufacturing development of composites for the past 20 to 25 years. Although composites technology has made great advances over the past 30 years, the effective application of composites to aircraft is still a complex problem that requires experienced personnel with special knowledge. All disciplines involved in the development process must work together in real time to minimize risk and assure total product quality and performance at acceptable costs. The most successful programs have made effective use of integrated, collocated, concurrent engineering teams, and most often used well-planned, systematic development efforts wherein the design and manufacturing processes are validated in a step-by-step or 'building block' approach. Such approaches reduce program risk and are cost effective.
Precision reconstruction of manufactured free-form components
NASA Astrophysics Data System (ADS)
Ristic, Mihailo; Brujic, Djordje; Ainsworth, Iain
2000-03-01
Manufacturing needs in many industries, especially the aerospace and the automotive, involve CAD remodeling of manufactured free-form parts using NURBS. This is typically performed as part of 'first article inspection' or 'closing the design loop.' The reconstructed model must satisfy requirements such as accuracy, compatibility with the original CAD model and adherence to various constraints. The paper outlines a methodology for realizing this task. Efficiency and quality of the results are achieved by utilizing the nominal CAD model. It is argued that measurement and remodeling steps are equally important. We explain how the measurement was optimized in terms of accuracy, point distribution and measuring speed using a CMM. Remodeling steps include registration, data segmentation, parameterization and surface fitting. Enforcement of constraints such as continuity was performed as part of the surface fitting process. It was found necessary that the relevant algorithms are able to perform in the presence of measurement noise, while making no special assumptions about regularity of data distribution. In order to deal with real life situations, a number of supporting functions for geometric modeling were required and these are described. The presented methodology was applied using real aeroengine parts and the experimental results are presented.
Propellant for the NASA Standard Initiator
NASA Technical Reports Server (NTRS)
Hohmann, Carl; Tipton, Bill, Jr.; Dutton, Maureen
2000-01-01
This paper discusses processes employed in manufacturing zirconium-potassium perchlorate propellant for the NASA standard initiator. It provides both a historical background on the NSI device-detailing problem areas and their resolution--and on propellant blending techniques. Emphasis is placed on the precipitation blending method. The findings on mixing equipment, processing, and raw materials are described. Also detailed are findings on the bridgewire slurry operation, one of the critical steps in the production of the NASA standard initiator.
NASA Astrophysics Data System (ADS)
Biermann, D.; Gausemeier, J.; Heim, H.-P.; Hess, S.; Petersen, M.; Ries, A.; Wagner, T.
2014-05-01
In this contribution a framework for the computer-aided planning and optimisation of functional graded components is presented. The framework is divided into three modules - the "Component Description", the "Expert System" for the synthetisation of several process chains and the "Modelling and Process Chain Optimisation". The Component Description module enhances a standard computer-aided design (CAD) model by a voxel-based representation of the graded properties. The Expert System synthesises process steps stored in the knowledge base to generate several alternative process chains. Each process chain is capable of producing components according to the enhanced CAD model and usually consists of a sequence of heating-, cooling-, and forming processes. The dependencies between the component and the applied manufacturing processes as well as between the processes themselves need to be considered. The Expert System utilises an ontology for that purpose. The ontology represents all dependencies in a structured way and connects the information of the knowledge base via relations. The third module performs the evaluation of the generated process chains. To accomplish this, the parameters of each process are optimised with respect to the component specification, whereby the result of the best parameterisation is used as representative value. Finally, the process chain which is capable of manufacturing a functionally graded component in an optimal way regarding to the property distributions of the component description is presented by means of a dedicated specification technique.
Modelization of three-layered polymer coated steel-strip ironing process using a neural network
NASA Astrophysics Data System (ADS)
Sellés, M. A.; Schmid, S. R.; Sánchez-Caballero, S.; Seguí, V. J.; Reig, M. J.; Pla, R.
2012-04-01
An alternative to the traditional can manufacturing process is to use plastic laminated rolled steels as base stocks. This material consist of pre-heated steel coils that are sandwiched between one or two sheets of polymer. The heated sheets are then immediately quenched, which yields a strong bond between the layers. Such polymer-coated steels were investigated by Jaworski [1,2] and Sellés [3], and found to be suitable for ironing with carefully controlled conditions. A novel multi-layer polymer coated steel has been developed for container applications. This material presents an interesting extension to previous research on polymer laminated steel in ironing, and offers several advantages over the previous material (Sellés [3]). This document shows a modelization for the ironing process (the most crucial step in can manufacturing) done by using a neural network
NASA Astrophysics Data System (ADS)
Hosseini, S. M. A.; Baran, I.; Akkerman, R.
2018-05-01
The laser-assisted tape winding (LATW) is an automated process for manufacturing fiber-reinforced thermoplastic tubular products, such as pipes and pressure vessels. Multi-physical phenomena such as heat transfer, mechanical bonding, phase changes and solid mechanics take place during the process. These phenomena need to be understood and described well for an improved product reliability. Temperature is one of the important parameters in this process to control and optimize the product quality which can be employed in an intelligent model-based inline control system. The incoming tape can overlap with the already wounded layer during the process based on the lay-up configuration. In this situation, the incoming tape can step-on or step-off to an already deposited layer/laminate. During the overlapping, the part temperature changes due to the variation of the geometry caused by previously deposited layer, i.e. a bump geometry. In order to qualify the temperature behavior at the bump regions, an experimental set up is designed on a flat laminate. Artificial bumps/steps are formed on the laminate with various thicknesses and fiber orientations. As the laser head experiences the step-on and step-off, the IR (Infra-Red) camera and the embedded thermocouples measure the temperature on the surface and inside the laminate, respectively. During the step-on, a small drop in temperature is observed while in step-off a higher peak in temperature is observed. It can be concluded that the change in the temperature during overlapping is due to the change in laser incident angle made by the bump geometry. The effect of the step thickness on the temperature peak is quantified and found to be significant.
Caballero, Santiago; Nieto, Sandra; Gajardo, Rodrigo; Jorquera, Juan I
2010-07-01
A new human liquid intravenous immunoglobulin product, Flebogamma DIF, has been developed. This IgG is purified from human plasma by cold ethanol fractionation, PEG precipitation and ion exchange chromatography. The manufacturing process includes three different specific pathogen clearance (inactivation/removal) steps: pasteurization, solvent/detergent treatment and Planova nanofiltration with a pore size of 20 nm. This study evaluates the pathogen clearance capacity of seven steps in the production process for a wide range of viruses through spiking experiments: the three specific steps mentioned above and also four more production steps. Infectivity of samples was measured using a Tissue Culture Infectious Dose assay (log(10) TCID(50)) or Plaque Forming Units assay (log(10) PFU). Validation studies demonstrated that each specific step cleared more than 4 log(10) for all viruses assayed. An overall viral clearance between > or =13.33 log(10) and > or =25.21 log(10), was achieved depending on the virus and the number of steps studied for each virus. It can be concluded that Flebogamma DIF has a very high viral safety profile. 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.
Advantages offered by high average power picosecond lasers
NASA Astrophysics Data System (ADS)
Moorhouse, C.
2011-03-01
As electronic devices shrink in size to reduce material costs, device size and weight, thinner material thicknesses are also utilized. Feature sizes are also decreasing, which is pushing manufacturers towards single step laser direct write process as an attractive alternative to conventional, multiple step photolithography processes by eliminating process steps and the cost of chemicals. The fragile nature of these thin materials makes them difficult to machine either mechanically or with conventional nanosecond pulsewidth, Diode Pumped Solids State (DPSS) lasers. Picosecond laser pulses can cut materials with reduced damage regions and selectively remove thin films due to the reduced thermal effects of the shorter pulsewidth. Also, the high repetition rate allows high speed processing for industrial applications. Selective removal of thin films for OLED patterning, silicon solar cells and flat panel displays is discussed, as well as laser cutting of transparent materials with low melting point such as Polyethylene Terephthalate (PET). For many of these thin film applications, where low pulse energy and high repetition rate are required, throughput can be increased by the use of a novel technique to using multiple beams from a single laser source is outlined.
Almutairy, B K; Alshetaili, A S; Ashour, E A; Patil, H; Tiwari, R V; Alshehri, S M; Repka, M A
2016-03-01
The present study aimed to develop a continuous single-step manufacturing platform to prepare a porous, low-density, and floating multi-particulate system (mini-tablet, 4 mm size). This process involves injecting inert, non-toxic pressurized CO₂gas (P-CO₂) in zone 4 of a 16-mm hot-melt extruder (HME) to continuously generate pores throughout the carrier matrix. Unlike conventional methods for preparing floating drug delivery systems, additional chemical excipients and additives are not needed in this approach to create minute openings on the surface of the matrices. The buoyancy efficiency of the prepared floating system (injection of P-CO₂) in terms of lag time (0 s) significantly improved (P < 0.05), compared to the formulation prepared by adding the excipient sodium bicarbonate (lag time 120 s). The main advantages of this novel manufacturing technique include: (i) no additional chemical excipients need to be incorporated in the formulation, (ii) few manufacturing steps are required, (iii) high buoyancy efficiency is attained, and (iv) the extrudate is free of toxic solvent residues. Floating mini-tablets containing acetaminophen (APAP) as a model drug within the matrix-forming carrier (Eudragit® RL PO) have been successfully processed via this combined technique (P-CO₂/HME). Desired controlled release profile of APAP from the polymer Eudragit® RL PO is attained in the optimized formulation, which remains buoyant on the surface of gastric fluids prior to gastric emptying time (average each 4 h).
Streefland, M; Van Herpen, P F G; Van de Waterbeemd, B; Van der Pol, L A; Beuvery, E C; Tramper, J; Martens, D E; Toft, M
2009-10-15
A licensed pharmaceutical process is required to be executed within the validated ranges throughout the lifetime of product manufacturing. Changes to the process, especially for processes involving biological products, usually require the manufacturer to demonstrate that the safety and efficacy of the product remains unchanged by new or additional clinical testing. Recent changes in the regulations for pharmaceutical processing allow broader ranges of process settings to be submitted for regulatory approval, the so-called process design space, which means that a manufacturer can optimize his process within the submitted ranges after the product has entered the market, which allows flexible processes. In this article, the applicability of this concept of the process design space is investigated for the cultivation process step for a vaccine against whooping cough disease. An experimental design (DoE) is applied to investigate the ranges of critical process parameters that still result in a product that meets specifications. The on-line process data, including near infrared spectroscopy, are used to build a descriptive model of the processes used in the experimental design. Finally, the data of all processes are integrated in a multivariate batch monitoring model that represents the investigated process design space. This article demonstrates how the general principles of PAT and process design space can be applied for an undefined biological product such as a whole cell vaccine. The approach chosen for model development described here, allows on line monitoring and control of cultivation batches in order to assure in real time that a process is running within the process design space.
Additive Technology: Update on Current Materials and Applications in Dentistry.
Barazanchi, Abdullah; Li, Kai Chun; Al-Amleh, Basil; Lyons, Karl; Waddell, J Neil
2017-02-01
Additive manufacturing or 3D printing is becoming an alternative to subtractive manufacturing or milling in the area of computer-aided manufacturing. Research on material for use in additive manufacturing is ongoing, and a wide variety of materials are being used or developed for use in dentistry. Some materials, however, such as cobalt chromium, still lack sufficient research to allow definite conclusions about the suitability of their use in clinical dental practice. Despite this, due to the wide variety of machines that use additive manufacturing, there is much more flexibility in the build material and geometry when building structures compared with subtractive manufacturing. Overall additive manufacturing produces little material waste and is energy efficient when compared to subtractive manufacturing, due to passivity and the additive layering nature of the build process. Such features make the technique suitable to be used with fabricating structures out of hard to handle materials such as cobalt chromium. The main limitations of this technology include the appearance of steps due to layering of material and difficulty in fabricating certain material generally used in dentistry for use in 3D printing such as ceramics. The current pace of technological development, however, promises exciting possibilities. © 2016 by the American College of Prosthodontists.
NASA Astrophysics Data System (ADS)
Slange, T. K.; Warnet, L. L.; Grouve, W. J. B.; Akkerman, R.
2018-05-01
Stamp forming is a rapid manufacturing technology used to shape flat blanks of thermoplastic composite material into three-dimensional components. The combination with rapid AFP as blank manufacturing technology can further extend the applicability of stamp forming by allowing rapid lay-up of tailored blanks and offering partial preconsolidation. In an experimental study it is demonstrated that high quality laminates with good flexural strength can be obtained by following this process route. The consolidation of ply-drop regions is demonstrated by flat laminates with a thickness step. The influence of fiber orientations, blank-tooling misalignments and AFP tolerances is investigated.
The role of robotics in computer controlled polishing of large and small optics
NASA Astrophysics Data System (ADS)
Walker, David; Dunn, Christina; Yu, Guoyu; Bibby, Matt; Zheng, Xiao; Wu, Hsing Yu; Li, Hongyu; Lu, Chunlian
2015-08-01
Following formal acceptance by ESO of three 1.4m hexagonal off-axis prototype mirror segments, one circular segment, and certification of our optical test facility, we turn our attention to the challenge of segment mass-production. In this paper, we focus on the role of industrial robots, highlighting complementarity with Zeeko CNC polishing machines, and presenting results using robots to provide intermediate processing between CNC grinding and polishing. We also describe the marriage of robots and Zeeko machines to automate currently manual operations; steps towards our ultimate vision of fully autonomous manufacturing cells, with impact throughout the optical manufacturing community and beyond.
Merritt, Russell J; Goldsmith, Arthur H
2014-11-01
Many nutrition products and related drugs are unavailable or not consistently available to clinicians despite a body of clinical data and experience supporting their use. Many of these can be related to drug shortages that have increased since 2009. In addition, there are potentially useful products that are not approved for a specific use or are no longer being manufactured. This review broadly examines the product availability gap from the perspectives of a clinician/former nutrition industry medical director and an economist. The process of pediatric nutrition product and related drug innovation, as well as its drivers and the steps involved in bringing a product to market, is first described. This is followed by an assessment of factors influencing product availability beyond the innovation process, including regulatory issues, manufacturing compliance, purchasing practices, and other factors related to drug and nutrition product pricing and reimbursement. Three pediatric case examples are reviewed and placed in the context of the prior review. Last, recent and future possible steps toward closing the product availability gap are discussed. © 2014 American Society for Parenteral and Enteral Nutrition.
Bioprinting: an assessment based on manufacturing readiness levels.
Wu, Changsheng; Wang, Ben; Zhang, Chuck; Wysk, Richard A; Chen, Yi-Wen
2017-05-01
Over the last decade, bioprinting has emerged as a promising technology in the fields of tissue engineering and regenerative medicine. With recent advances in additive manufacturing, bioprinting is poised to provide patient-specific therapies and new approaches for tissue and organ studies, drug discoveries and even food manufacturing. Manufacturing Readiness Level (MRL) is a method that has been applied to assess manufacturing maturity and to identify risks and gaps in technology-manufacturing transitions. Technology Readiness Level (TRL) is used to evaluate the maturity of a technology. This paper reviews recent advances in bioprinting following the MRL scheme and addresses corresponding MRL levels of engineering challenges and gaps associated with the translation of bioprinting from lab-bench experiments to ultimate full-scale manufacturing of tissues and organs. According to our step-by-step TRL and MRL assessment, after years of rigorous investigation by the biotechnology community, bioprinting is on the cusp of entering the translational phase where laboratory research practices can be scaled up into manufacturing products specifically designed for individual patients.
Yang, Yang; Velayudhan, Ajoy; Thornhill, Nina F; Farid, Suzanne S
2017-09-01
The need for high-concentration formulations for subcutaneous delivery of therapeutic monoclonal antibodies (mAbs) can present manufacturability challenges for the final ultrafiltration/diafiltration (UF/DF) step. Viscosity levels and the propensity to aggregate are key considerations for high-concentration formulations. This work presents novel frameworks for deriving a set of manufacturability indices related to viscosity and thermostability to rank high-concentration mAb formulation conditions in terms of their ease of manufacture. This is illustrated by analyzing published high-throughput biophysical screening data that explores the influence of different formulation conditions (pH, ions, and excipients) on the solution viscosity and product thermostability. A decision tree classification method, CART (Classification and Regression Tree) is used to identify the critical formulation conditions that influence the viscosity and thermostability. In this work, three different multi-criteria data analysis frameworks were investigated to derive manufacturability indices from analysis of the stress maps and the process conditions experienced in the final UF/DF step. Polynomial regression techniques were used to transform the experimental data into a set of stress maps that show viscosity and thermostability as functions of the formulation conditions. A mathematical filtrate flux model was used to capture the time profiles of protein concentration and flux decay behavior during UF/DF. Multi-criteria decision-making analysis was used to identify the optimal formulation conditions that minimize the potential for both viscosity and aggregation issues during UF/DF. Biotechnol. Bioeng. 2017;114: 2043-2056. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc.
Velayudhan, Ajoy; Thornhill, Nina F.
2017-01-01
ABSTRACT The need for high‐concentration formulations for subcutaneous delivery of therapeutic monoclonal antibodies (mAbs) can present manufacturability challenges for the final ultrafiltration/diafiltration (UF/DF) step. Viscosity levels and the propensity to aggregate are key considerations for high‐concentration formulations. This work presents novel frameworks for deriving a set of manufacturability indices related to viscosity and thermostability to rank high‐concentration mAb formulation conditions in terms of their ease of manufacture. This is illustrated by analyzing published high‐throughput biophysical screening data that explores the influence of different formulation conditions (pH, ions, and excipients) on the solution viscosity and product thermostability. A decision tree classification method, CART (Classification and Regression Tree) is used to identify the critical formulation conditions that influence the viscosity and thermostability. In this work, three different multi‐criteria data analysis frameworks were investigated to derive manufacturability indices from analysis of the stress maps and the process conditions experienced in the final UF/DF step. Polynomial regression techniques were used to transform the experimental data into a set of stress maps that show viscosity and thermostability as functions of the formulation conditions. A mathematical filtrate flux model was used to capture the time profiles of protein concentration and flux decay behavior during UF/DF. Multi‐criteria decision‐making analysis was used to identify the optimal formulation conditions that minimize the potential for both viscosity and aggregation issues during UF/DF. Biotechnol. Bioeng. 2017;114: 2043–2056. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc. PMID:28464235
NASA Astrophysics Data System (ADS)
Englisch, Andreas; Deuter, Armin
1990-06-01
Integration and automation have gained more and more ground in modern IC-manufacturing. It is difficult to make a direct calculation of the profit these investments yield. On the other hand, the demands to man, machine and technology have increased enormously of late; it is not difficult to see that only by means of integration and automation can these demands be coped with. Here are some salient points: U the complexity and costs incurred by the equipment and processes have got significantly higher . owing to the reduction of all dimensions, the tolerances within which the various process steps have to be carried out have got smaller and smaller and the adherence to these tolerances more and more difficult U the cycle time has become more and more important both for the development and control of new processes and, to a great extent, for a rapid and reliable supply to the customer. In order that the products be competitive under these conditions, all sort of costs have to be reduced and the yield has to be maximized. Therefore, the computer-aided control of the equipment and the process combined with an automatic data collection and a real-time SPC (statistical process control) has become absolutely necessary for successful IC-manufacturing. Human errors must be eliminated from the execution of the various process steps by automation. The work time set free in this way makes it possible for the human creativity to be employed on a larger scale in stabilizing the processes. Besides, a computer-aided equipment control can ensure the optimal utilization of the equipment round the clock.
Fate of Listeria monocytogenes in experimentally contaminated French sausages.
Thévenot, D; Delignette-Muller, M L; Christieans, S; Vernozy-Rozand, C
2005-05-25
Listeria monocytogenes has been recognized as one of the most important foodborne pathogens dealt with by the food. The bacterium has been found in every part along the pork processing industry from the slaughterhouse to the cutting room and the delicatessen factories. During the fermentation and drying of sausages, L. monocytogenes tends to decrease substantially. However, despite the various hurdles in the dry sausage manufacturing process, L. monocytogenes is able to survive and is detected in the final products. The present study has evaluated growth and survival of eight different L. monocytogenes strains (originating from sausage, sausage industry environment and from clinical cases of listeriosis) in experimentally inoculated French sausages with 10(4) cfu g(-1). This study points out the fact that the decrease of L. monocytogenes contamination rate during the manufacturing process of sausages is strain dependent (p < 0.001) and mainly due to the drying and maturation step than to the fermentation itself. Whatever the strains studied, almost no decrease of the contamination rate was noted during the fermentation step. However hurdle-adapted strains (those isolated from sausages or sausage industry environment) were more difficult to cure from sausages (decrease by 1.5 log10) than non-adapted strains (decrease by 3 log10) at the end of the drying period (day 35), when sausages were ready for consumption. These sausages became safe only at the best before date. As a consequence, L. monocytogenes and more particularly those "adapted" strains might represent a very important issue for hygienists since these strains originating from sausages or production environment themselves are likely to contaminate sausages during manufacturing and remain in the final products. However, the high inoculum levels used in the study (10(4) cfu g(-1)) are not representative of the natural contamination of L. monocytogenes commonly encountered in the raw material for sausages. If such contamination happened to be inferior to 100 cfu g(-1), then the manufacturing process used in this study would be able to produce "safe" sausages according to the European regulation requiring the absence of L. monocytogenes in 25 g of food with a tolerance of below 100 cfu g(-1) at the best before date.
Causes and remedies for porosity in composite manufacturing
NASA Astrophysics Data System (ADS)
Fernlund, G.; Wells, J.; Fahrang, L.; Kay, J.; Poursartip, A.
2016-07-01
Porosity is a challenge in virtually all composite processes but in particular in low pressure processes such as out of autoclave processing of prepregs, where the maximum pressure is one atmosphere. This paper discusses the physics behind important transport phenomena that control porosity and how we can use our understanding of the underlying science to develop strategies to achieve low porosity for these materials and processes in an industrial setting. A three step approach is outlined that addresses and discusses: gas evacuation of trapped air, volatiles and off-gassing, and resin infiltration of evacuated void space.
NASA Astrophysics Data System (ADS)
Foughani, Milad; Kolahi, Alireza; Palizdar, Yahya
2018-01-01
Nowadays, Nano structure bainitic steel have attracted attention mostly because of its special mechanical properties such as high tensile strength, hardness, appropriate toughness and low manufacturing cost. The main concern for the mass production of this type of steels is prolong austempering process which increases the production costs as well as time. In this research, in order to accelerate the bainitic transformation and decrease the production time, a medium carbon steel has been prepared and two steps austempering process was employed to prevent the bainite laths thickening. The Samples were austenetized at 1000°C for 15 min and were kept in the salt bath between 1 - 12 hours at 290°C in one step and between 1 - 12 hours at the temperature range of 250°C - 300°C in two steps bainite transformation. The obtained micro structures were studied by the optical and scanning electron microscopy (FESEM) and the mechanical properties were investigated by using tensile and hardness tests. The results show that the two steps austempering process and lower carbon concentration lead to lower austempering time as well as the formation of more stable retained austenite and nanostructured bainite lath which results in higher mechanical properties.
Automated catalyst processing for cloud electrode fabrication for fuel cells
Goller, Glen J.; Breault, Richard D.
1980-01-01
A process for making dry carbon/polytetrafluoroethylene floc material, particularly useful in the manufacture of fuel cell electrodes, comprises of the steps of floccing a co-suspension of carbon particles and polytetrafluoroethylene particles, filtering excess liquids from the co-suspension, molding pellet shapes from the remaining wet floc solids without using significant pressure during the molding, drying the wet floc pellet shapes within the mold at temperatures no greater than about 150.degree. F., and removing the dry pellets from the mold.
Simple construction and performance of a conical plastic cryocooler
NASA Technical Reports Server (NTRS)
Lambert, N.
1985-01-01
Low power cryocoolers with conical displacers offer several advantages over stepped displacers. The described fabrication process allows quick and reproducible manufacturing of plastic conical displacer units. This could be of commercial interest, but it also makes systematic optimization feasible by constructing a number of different models. The process allows for a wide range of displacer profiles. Low temperature performance as dominated by regenerator losses, and several effects are discussed. A simple device is described which controls gas flow during expansion.
NASA Technical Reports Server (NTRS)
Prater, T. J.; Werkheiser, N. J.; Ledbetter, F. E., III
2018-01-01
In-space manufacturing seeks to develop the processes, skill sets, and certification architecture needed to provide a rapid response manufacturing capability on long-duration exploration missions. The first 3D printer on the Space Station was developed by Made in Space, Inc. and completed two rounds of operation on orbit as part of the 3D Printing in Zero-G Technology Demonstration Mission. This Technical Publication provides a comprehensive overview of the technical objections of the mission, the two phases of hardware operation conducted on orbit, and the subsequent detailed analysis of specimens produced. No engineering significant evidence of microgravity effects on material outcomes was noted. This technology demonstration mission represents the first step in developing a suite of manufacturing capabilities to meet future mission needs.
Degradation of Gate Oxide Integrity by Formation of Tiny Holes by Metal Contamination of Raw Wafer
NASA Astrophysics Data System (ADS)
Chen, Po-Ying
2008-12-01
Heavy metal atoms (such as Cu) spontaneously undergo a dissolution reaction when they come into contact with silicon. Most investigations in this extensively studied area begin with a clean, bare wafer and focus on metal contamination during the IC manufacturing stage. In this work, the effect of Fe and Cu contamination on raw wafers was elucidated. When two batches of raw wafers are scheduled, one uncontaminated and one with various degrees of contamination ranging from 0.1 to 10 ppb undergo the typical steps of the 90 nm LOGIC complementary metal-oxide-semiconductor (CMOS) semiconductor manufacturing process. The main contribution of this work is the discovery of a previously unidentified cause of gate oxide leakage: the formation of tiny holes by metal contamination during the wafer manufacturing stage. Because tiny holes are formed, a spontaneous reaction can occur even with at very low metal concentration (0.2 ppb), revealing that the wafer manufacturing stage is more vulnerable to metal contamination than the IC manufacturing stage and therefore requires stricter contamination control.
Milá, Lorely; Valdés, Rodolfo; Tamayo, Andrés; Padilla, Sigifredo; Ferro, Williams
2012-03-01
CB.Hep-1 monoclonal antibody (mAb) is used for a recombinant Hepatitis B vaccine manufacturing, which is included in a worldwide vaccination program against Hepatitis B disease. The use of this mAb as immunoligand has been addressed into one of the most efficient steps of active pharmaceutical ingredient purification process. Regarding this, Quality Risk Management (QRM) provides an excellent framework for the risk management use in pharmaceutical manufacturing and quality decision-making applications. Consequently, this study sought applying a prospective risk analysis methodology Failure Mode Effects Analysis (FMEA) as QRM tool for analyzing different CB.Hep-1 mAb manufacturing technologies. As main conclusions FMEA was successfully used to assess risks associated with potential problems in CB.Hep-1 mAb manufacturing processes. The severity and occurrence of risks analysis evidenced that the percentage of very high severe risks ranged 31.0-38.7% of all risks and the huge majority of risks have a very low occurrence level (61.9-83.3%) in all assessed technologies. Finally, additive Risk Priority Number, was descending ordered as follow: transgenic plants (2636), ascites (2577), transgenic animals (2046) and hollow fiber bioreactors (1654), which also corroborated that in vitro technology, should be the technology of choice for CB.Hep-1 mAb manufacturing in terms of risks and mAb molecule quality. Copyright © 2011 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.
Integrated continuous processing of proteins expressed as inclusion bodies: GCSF as a case study.
Kateja, Nikhil; Agarwal, Harshit; Hebbi, Vishwanath; Rathore, Anurag S
2017-07-01
Affordability of biopharmaceuticals continues to be a challenge, particularly in developing economies. This has fuelled advancements in manufacturing that can offer higher productivity and better economics without sacrificing product quality in the form of an integrated continuous manufacturing platform. While platform processes for monoclonal antibodies have existed for more than a decade, development of an integrated continuous manufacturing process for bacterial proteins has received relatively scant attention. In this study, we propose an end-to-end integrated continuous downstream process (from inclusion bodies to unformulated drug substance) for a therapeutic protein expressed in Escherichia coli as inclusion body. The final process consisted of a continuous refolding in a coiled flow inverter reactor directly coupled to a three-column periodic counter-current chromatography for capture of the product followed by a three-column con-current chromatography for polishing. The continuous bioprocessing train was run uninterrupted for 26 h to demonstrate its capability and the resulting output was analyzed for the various critical quality attributes, namely product purity (>99%), high molecular weight impurities (<0.5%), host cell proteins (<100 ppm), and host cell DNA (<10 ppb). All attributes were found to be consistent over the period of operation. The developed assembly offers smaller facility footprint, higher productivity, fewer hold steps, and significantly higher equipment and resin utilization. The complexities of process integration in the context of continuous processing have been highlighted. We hope that the study presented here will promote development of highly efficient, universal, end-to-end, fully continuous platforms for manufacturing of biotherapeutics. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:998-1009, 2017. © 2016 American Institute of Chemical Engineers.
Performance testing of a prototype Pd-Ag diffuser
DOE Office of Scientific and Technical Information (OSTI.GOV)
Morgan, G. A.; Hodge, B. J.
The fusion fuel cycle has gained significant attention over the last decade as interest in fusion programs has increased. One of the critical components of the fusion process is the tritium fuel cycle. The tritium fuel cycle is designed to supply and recycle process tritium at a specific throughput rate. One of the most important processes within the tritium fuel cycle is the clean-up of the of the process tritium. This step will initially separate the hydrogen isotopes (H2, D2, and T2) from the rest of the process gas using Pd-Ag diffusers or permeators. The Pd-Ag diffuser is an integralmore » component for any tritium purification system; whether part of the United States’ defense mission or fusion programs. Domestic manufacturers of Pd-Ag diffusers are extremely limited and only a few manufacturers exist. Johnson-Matthey (JM) Pd-Ag diffusers (permeators) have previously been evaluated for the separation of hydrogen isotopes from non-hydrogen gas species in the process. JM is no longer manufacturing Pd-Ag diffusers and a replacement vendor needs to be identified to support future needs. A prototype Pd-Ag diffuser has been manufactured by Power and Energy, and is considered a potential replacement for the JM diffuser for tritium service. New diffuser designs for a tritium facility for any fusion energy applications must be characterized by evaluating their operating envelope prior to installation in a tritium processing facility. The prototype Pd-Ag diffuser was characterized to determine the overall performance as a function of the permeation of hydrogen through the membrane. The tests described in this report consider the effects of feed gas compositions, feed flow rates, pump configuration and internal tube pressure on the permeation of H2 through the Pd-Ag tubes.« less
Fused filament 3D printing of ionic polymer-metal composites for soft robotics
NASA Astrophysics Data System (ADS)
Carrico, James D.; Leang, Kam K.
2017-04-01
Additive manufacturing techniques are used to create three-dimensional structures with complex shapes and features from polymer and/or metal materials. For example, fused filament three-dimensional (3D) printing utilizes non-electroactive polymers, such as acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA), to build structures and components in a layer-by-layer fashion for a wide variety of applications. Presented here is a summary of recent work on a fused filament 3D-printing technique to create 3D ionic polymer-metal composite (IPMC) structures for applications in soft robotics. The 3D printing technique overcomes some of the limitations of existing manufacturing processes for creating IPMCs, such as limited shapes and sizes and time-consuming manufacturing steps. In the process described, first a precursor material (non-acid Nafion precursor resin) is extruded into a thermoplastic filament for 3D printing. Then, a custom-designed 3D printer is described that utilizes the precursor filament to manufacture custom-shaped structures. Finally, the 3D-printed samples are functionalized by hydrolyzing them in an aqueous solution of potassium hydroxide and dimethyl sulfoxide, followed by application of platinum electrodes. Presented are example 3D-printed single and multi-degree-of-freedom IPMC actuators and characterization results, as well as example soft-robotic devices to demonstrate the potential of this process.
Relative risk analysis of several manufactured nanomaterials: an insurance industry context.
Robichaud, Christine Ogilvie; Tanzil, Dicksen; Weilenmann, Ulrich; Wiesner, Mark R
2005-11-15
A relative risk assessment is presented for the industrial fabrication of several nanomaterials. The production processes for five nanomaterials were selected for this analysis, based on their current or near-term potential for large-scale production and commercialization: single-walled carbon nanotubes, bucky balls (C60), one variety of quantum dots, alumoxane nanoparticles, and nano-titanium dioxide. The assessment focused on the activities surrounding the fabrication of nanomaterials, exclusive of any impacts or risks with the nanomaterials themselves. A representative synthesis method was selected for each nanomaterial based on its potential for scaleup. A list of input materials, output materials, and waste streams for each step of fabrication was developed and entered into a database that included key process characteristics such as temperature and pressure. The physical-chemical properties and quantities of the inventoried materials were used to assess relative risk based on factors such as volatility, carcinogenicity, flammability, toxicity, and persistence. These factors were first used to qualitatively rank risk, then combined using an actuarial protocol developed by the insurance industry for the purpose of calculating insurance premiums for chemical manufacturers. This protocol ranks three categories of risk relative to a 100 point scale (where 100 represents maximum risk): incident risk, normal operations risk, and latent contamination risk. Results from this analysis determined that relative environmental risk from manufacturing each of these five materials was comparatively low in relation to other common industrial manufacturing processes.
Carbon Nanotube Chopped Fiber for Enhanced Properties in Additive Manufacturing
DOE Office of Scientific and Technical Information (OSTI.GOV)
Menchhofer, Paul A.; Johnson, Joseph E.; Lindahl, John M.
2016-06-06
Nanocomp Technologies, Inc. is working with Oak Ridge National Laboratory to develop carbon nanotube (CNT) composite materials and evaluate their use in additive manufacturing (3D printing). The first phase demonstrated feasibility and improvements for carbon nanotube (CNT)- acrylonitrile butadiene styrene (ABS) composite filaments use in additive manufacturing, with potential future work centering on further improvements. By focusing the initial phase on standard processing methods (developed mainly for the incorporation of carbon fibers in ABS) and characterization techniques, a basis of knowledge for the incorporation of CNTs in ABS was learned. The ability to understand the various processing variables is criticalmore » to the successful development of these composites. From the degradation effects on ABS (caused by excessive temperatures), to the length of time the ABS is in the melt state, to the order of addition of constituents, and also to the many possible mixing approaches, a workable flow sequence that addresses each processing step is critical to the final material properties. Although this initial phase could not deal with each of these variables in-depth, a future study is recommended that will build on the lessons learned for this effort.« less
Impact of Electrostatics on Processing and Product Performance of Pharmaceutical Solids.
Desai, Parind Mahendrakumar; Tan, Bernice Mei Jin; Liew, Celine Valeria; Chan, Lai Wah; Heng, Paul Wan Sia
2015-01-01
Manufacturing of pharmaceutical solids involves different unit operations and processing steps such as powder blending, fluidization, sieving, powder coating, pneumatic conveying and spray drying. During these operations, particles come in contact with other particles, different metallic, glass or polymer surfaces and can become electrically charged. Electrostatic charging often gives a negative connotation as it creates sticking, jamming, segregation or other issues during tablet manufacturing, capsule filling, film packaging and other pharmaceutical operations. A thorough and fundamental appreciation of the current knowledge of mechanisms and the potential outcomes is essential in order to minimize potential risks resulting from this phenomenon. The intent of this review is to discuss the electrostatic properties of pharmaceutical powders, equipment surfaces and devices affecting pharmaceutical processing and product performance. Furthermore, the underlying mechanisms responsible for the electrostatic charging are described and factors affecting electrostatic charging have been reviewed in detail. Feasibility of different methods used in the laboratory and pharmaceutical industry to measure charge propensity and decay has been summarized. Different computational and experimental methods studied have proven that the particle charging is a very complex phenomenon and control of particle charging is extremely important to achieve reliable manufacturing and reproducible product performance.
Multi-material composites prepared by additive manufacturing and melt casting
NASA Astrophysics Data System (ADS)
Murialdo, Maxwell; Sullivan, Kyle; White, Bradley; LLNL MSD Collaboration
2017-06-01
Recent advances in additive manufacturing have disrupted not only means of production, but also have enabled a new parameter space of multiscale materials designs. Understanding the role of architecture to control material response is being investigated for a wide range of applications, from light-weight structural components to energetic materials. In this work, we combine 3D printing of scaffold structures with a subsequent melt-infiltration step to render an architected multi-material composite article. Both the scaffold architecture and material type were investigated. The processing challenges of filling such scaffolds using a melt-infiltration step will be discussed, along with our progress in this area. Using the combined method of printing and casting, we will discuss our path forward for testing the mechanical properties and the high-strain response of our composite architected parts. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. IM release: LLNL-ABS-725497-DRAFT.
Strain hardening behavior during manufacturing of tube shapes by hydroforming
NASA Astrophysics Data System (ADS)
Park, Hyun Kyu; Yi, Hyae Kyung; Van Tyne, Chester J.; Moon, Young Hoon
2009-12-01
Safe and robust process design relies on knowledge of the evolution of the mechanical properties in a tube during hydroforming. The manufacturing of tubular shapes generally consists of three main stages: bending, preforming, and expansion. The latter is usually called hydroforming. As a result of these three steps, the final product's strain hardening history is nonlinear. In the present study, the strain hardening behavior during hydroforming was experimentally investigated. The variation of local flow stress and/or local hardness was used as an index of the strain hardening during the various steps and the local flow stress and/or local hardness were used with respective correlations to determine the effective strain. The strain hardening behavior during hydroforming after preforming has been successfully analyzed by using the relationships between hardness, flow stress, and effective strain for variable pre-strains prior to hydroforming. The comparison of predicted hardness with measured hardness confirms that the methodology used in this study is feasible, and that the strain hardening behavior can be quantitatively estimated with good accuracy.
Identification of a novel structure in heparin generated by potassium permanganate oxidation
Beccati, Daniela; Roy, Sucharita; Yu, Fei; Gunay, Nur Sibel; Capila, Ishan; Lech, Miroslaw; Linhardt, Robert J.; Venkataraman, Ganesh
2012-01-01
The worldwide heparin contamination crisis in 2008 led health authorities to take fundamental steps to better control heparin manufacture, including implementing appropriate analytical and bio-analytical methods to ensure production and release of high quality heparin sodium product. Consequently, there is an increased interest in the identification and structural elucidation of unusually modified structures that may be present in heparin. Our study focuses on the structural elucidation of species that give rise to a signal observed at 2.10 ppm in the N-acetyl region of the 1H NMR spectrum of some pharmaceutical grade heparin preparations. Structural elucidation experiments were carried out using homonuclear (COSY, TOSCY and NOESY) and heteronuclear (HSQC, HSQC-DEPT, HMQC-COSY, HSQC-TOCSY, and HMBC) 2D NMR spectroscopy on both heparin as well as heparin-like model compounds. Our results identify a novel type of oxidative modification of the heparin chain that results from a specific step in the manufacturing process used to prepare heparin. PMID:25147414
Mocellin, J; Mercier, G; Morel, J L; Blais, J F; Simonnot, M O
2015-08-01
In this laboratory study, a process has been developed for selectively leaching zinc and manganese from pyrometallurgical sludge produced in the steel manufacturing industry. In the first part, the yield of Zn extraction was studied using four factors and four levels of the Box-Behnken response surface design. The optimum conditions for the step of Zn leaching were determined to be a sulfuric acid concentration of 0.25 mol/L, a pulp density of 10%, an extraction temperature of 20 °C, and three stages of leaching. Under such conditions, 75% of the Zn should be leached. For Mn leaching, the optimum conditions were determined to be a sulfuric acid concentration of 0.25 mol/L, a Na2S2O5/Mn stoichiometry of 1, a leaching time of 120 min and two leaching steps. In this case, 100% of the Mn should be leached. Copyright © 2015 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Shen, Chien-wen
2009-01-01
During the processes of TFT-LCD manufacturing, steps like visual inspection of panel surface defects still heavily rely on manual operations. As the manual inspection time of TFT-LCD manufacturing could range from 4 hours to 1 day, the reliability of time forecasting is thus important for production planning, scheduling and customer response. This study would like to propose a practical and easy-to-implement prediction model through the approach of Bayesian networks for time estimation of manual operated procedures in TFT-LCD manufacturing. Given the lack of prior knowledge about manual operation time, algorithms of necessary path condition and expectation-maximization are used for structural learning and estimation of conditional probability distributions respectively. This study also applied Bayesian inference to evaluate the relationships between explanatory variables and manual operation time. With the empirical applications of this proposed forecasting model, approach of Bayesian networks demonstrates its practicability and prediction accountability.
Barone, Sandro; Neri, Paolo; Paoli, Alessandro; Razionale, Armando Viviano
2018-01-01
Orthodontic treatments are usually performed using fixed brackets or removable oral appliances, which are traditionally made from alginate impressions and wax registrations. Among removable devices, eruption guidance appliances are used for early orthodontic treatments in order to intercept and prevent malocclusion problems. Commercially available eruption guidance appliances, however, are symmetric devices produced using a few standard sizes. For this reason, they are not able to meet all the specific patient's needs since the actual dental anatomies present various geometries and asymmetric conditions. In this article, a computer-aided design-based methodology for the design and manufacturing of a patient-specific eruption guidance appliances is presented. The proposed approach is based on the digitalization of several steps of the overall process: from the digital reconstruction of patients' anatomies to the manufacturing of customized appliances. A finite element model has been developed to evaluate the temporomandibular joint disks stress level caused by using symmetric eruption guidance appliances with different teeth misalignment conditions. The developed model can then be used to guide the design of a patient-specific appliance with the aim at reducing the patient discomfort. At this purpose, two different customization levels are proposed in order to face both arches and single tooth misalignment issues. A low-cost manufacturing process, based on an additive manufacturing technique, is finally presented and discussed.
Work environment investments: outcomes from three cases.
Rydell, Alexis; Andersson, Ing-Marie
2017-09-27
Work environment investments are important in order to create a healthy and safe workplace. This article presents findings from a seven-step interventions process aimed at examining and following-up work environment investments in small and medium-sized enterprises (SMEs), with a particular focus on air contaminants. Three different cases were analyzed and included in the study: (a) an educational center for welding; (b) a paint station in furniture manufacturing; (c) a joinery in furniture manufacturing. The results show that the work environment investments were highly appreciated by the employees and managers, but at the same time the investment could be optimized through markedly decreased exposure levels for the worker. Factors such as follow-ups of the investment, education and training in how to use the equipment, worker involvement in the process and leadership engagement are important in order to optimize work environment investments.
Multi-Step Ka/Ka Dichroic Plate with Rounded Corners for NASA's 34m Beam Waveguide Antenna
NASA Technical Reports Server (NTRS)
Veruttipong, Watt; Khayatian, Behrouz; Hoppe, Daniel; Long, Ezra
2013-01-01
A multi-step Ka/Ka dichroic plate Frequency Selective Surface (FSS structure) is designed, manufactured and tested for use in NASA's Deep Space Network (DSN) 34m Beam Waveguide (BWG) antennas. The proposed design allows ease of manufacturing and ability to handle the increased transmit power (reflected off the FSS) of the DSN BWG antennas from 20kW to 100 kW. The dichroic is designed using HFSS and results agree well with measured data considering the manufacturing tolerances that could be achieved on the dichroic.
Advanced metrology by offline SEM data processing
NASA Astrophysics Data System (ADS)
Lakcher, Amine; Schneider, Loïc.; Le-Gratiet, Bertrand; Ducoté, Julien; Farys, Vincent; Besacier, Maxime
2017-06-01
Today's technology nodes contain more and more complex designs bringing increasing challenges to chip manufacturing process steps. It is necessary to have an efficient metrology to assess process variability of these complex patterns and thus extract relevant data to generate process aware design rules and to improve OPC models. Today process variability is mostly addressed through the analysis of in-line monitoring features which are often designed to support robust measurements and as a consequence are not always very representative of critical design rules. CD-SEM is the main CD metrology technique used in chip manufacturing process but it is challenged when it comes to measure metrics like tip to tip, tip to line, areas or necking in high quantity and with robustness. CD-SEM images contain a lot of information that is not always used in metrology. Suppliers have provided tools that allow engineers to extract the SEM contours of their features and to convert them into a GDS. Contours can be seen as the signature of the shape as it contains all the dimensional data. Thus the methodology is to use the CD-SEM to take high quality images then generate SEM contours and create a data base out of them. Contours are used to feed an offline metrology tool that will process them to extract different metrics. It was shown in two previous papers that it is possible to perform complex measurements on hotspots at different process steps (lithography, etch, copper CMP) by using SEM contours with an in-house offline metrology tool. In the current paper, the methodology presented previously will be expanded to improve its robustness and combined with the use of phylogeny to classify the SEM images according to their geometrical proximities.
Application of lean manufacturing techniques in the Emergency Department.
Dickson, Eric W; Singh, Sabi; Cheung, Dickson S; Wyatt, Christopher C; Nugent, Andrew S
2009-08-01
"Lean" is a set of principles and techniques that drive organizations to continually add value to the product they deliver by enhancing process steps that are necessary, relevant, and valuable while eliminating those that fail to add value. Lean has been used in manufacturing for decades and has been associated with enhanced product quality and overall corporate success. To evaluate whether the adoption of Lean principles by an Emergency Department (ED) improves the value of emergency care delivered. Beginning in December 2005, we implemented a variety of Lean techniques in an effort to enhance patient and staff satisfaction. The implementation followed a six-step process of Lean education, ED observation, patient flow analysis, process redesign, new process testing, and full implementation. Process redesign focused on generating improvement ideas from frontline workers across all departmental units. Value-based and operational outcome measures, including patient satisfaction, expense per patient, ED length of stay (LOS), and patient volume were compared for calendar year 2005 (pre-Lean) and periodically after 2006 (post-Lean). Patient visits increased by 9.23% in 2006. Despite this increase, LOS decreased slightly and patient satisfaction increased significantly without raising the inflation adjusted cost per patient. Lean improved the value of the care we delivered to our patients. Generating and instituting ideas from our frontline providers have been the key to the success of our Lean program. Although Lean represents a fundamental change in the way we think of delivering care, the specific process changes we employed tended to be simple, small procedure modifications specific to our unique people, process, and place. We, therefore, believe that institutions or departments aspiring to adopt Lean should focus on the core principles of Lean rather than on emulating specific process changes made at other institutions.
NASA Astrophysics Data System (ADS)
Shauly, Eitan; Parag, Allon; Khmaisy, Hafez; Krispil, Uri; Adan, Ofer; Levi, Shimon; Latinski, Sergey; Schwarzband, Ishai; Rotstein, Israel
2011-04-01
A fully automated system for process variability analysis of high density standard cell was developed. The system consists of layout analysis with device mapping: device type, location, configuration and more. The mapping step was created by a simple DRC run-set. This database was then used as an input for choosing locations for SEM images and for specific layout parameter extraction, used by SPICE simulation. This method was used to analyze large arrays of standard cell blocks, manufactured using Tower TS013LV (Low Voltage for high-speed applications) Platforms. Variability of different physical parameters like and like Lgate, Line-width-roughness and more as well as of electrical parameters like drive current (Ion), off current (Ioff) were calculated and statistically analyzed, in order to understand the variability root cause. Comparison between transistors having the same W/L but with different layout configurations and different layout environments (around the transistor) was made in terms of performances as well as process variability. We successfully defined "robust" and "less-robust" transistors configurations, and updated guidelines for Design-for-Manufacturing (DfM).
NASA Astrophysics Data System (ADS)
Prete, Antonio Del; Franchi, Rodolfo; Antermite, Fabrizio; Donatiello, Iolanda
2018-05-01
Residual stresses appear in a component as a consequence of thermo-mechanical processes (e.g. ring rolling process) casting and heat treatments. When machining these kinds of components, distortions arise due to the redistribution of residual stresses due to the foregoing process history inside the material. If distortions are excessive, they can lead to a large number of scrap parts. Since dimensional accuracy can affect directly the engines efficiency, the dimensional control for aerospace components is a non-trivial issue. In this paper, the problem related to the distortions of large thin walled aeroengines components in nickel superalloys has been addressed. In order to estimate distortions on inner diameters after internal turning operations, a 3D Finite Element Method (FEM) analysis has been developed on a real industrial test case. All the process history, has been taken into account by developing FEM models of ring rolling process and heat treatments. Three different strategies of ring rolling process have been studied and the combination of related parameters which allows to obtain the best dimensional accuracy has been found. Furthermore, grain size evolution and recrystallization phenomena during manufacturing process has been numerically investigated using a semi empirical Johnson-Mehl-Avrami-Kohnogorov (JMAK) model. The volume subtractions have been simulated by boolean trimming: a one step and a multi step analysis have been performed. The multi-step procedure has allowed to choose the best material removal sequence in order to reduce machining distortions.
NASA Astrophysics Data System (ADS)
Fuchs, Erica R. H.; Bruce, E. J.; Ram, R. J.; Kirchain, Randolph E.
2006-08-01
The monolithic integration of components holds promise to increase network functionality and reduce packaging expense. Integration also drives down yield due to manufacturing complexity and the compounding of failures across devices. Consensus is lacking on the economically preferred extent of integration. Previous studies on the cost feasibility of integration have used high-level estimation methods. This study instead focuses on accurate-to-industry detail, basing a process-based cost model of device manufacture on data collected from 20 firms across the optoelectronics supply chain. The model presented allows for the definition of process organization, including testing, as well as processing conditions, operational characteristics, and level of automation at each step. This study focuses on the cost implications of integration of a 1550-nm DFB laser with an electroabsorptive modulator on an InP platform. Results show the monolithically integrated design to be more cost competitive over discrete component options regardless of production scale. Dominant cost drivers are packaging, testing, and assembly. Leveraging the technical detail underlying model projections, component alignment, bonding, and metal-organic chemical vapor deposition (MOCVD) are identified as processes where technical improvements are most critical to lowering costs. Such results should encourage exploration of the cost advantages of further integration and focus cost-driven technology development.
Quality By Design: Concept To Applications.
Swain, Suryakanta; Padhy, Rabinarayan; Jena, Bikash Ranjan; Babu, Sitty Manohar
2018-03-08
Quality by Design is associated to the modern, systematic, scientific and novel approach which is concerned with pre-distinct objectives that not only focus on product, process understanding but also leads to process control. It predominantly signifies the design and product improvement and the manufacturing process in order to fulfill the predefined manufactured goods or final products quality characteristics. It is quite essential to identify desire and required product performance report such as Target Product Profile, typical Quality Target Product Profile (QTPP) and Critical Quality attributes (CQA). This review highlighted about the concepts of QbD design space, for critical material attributes (CMAs) as well as the critical process parameters that can totally affect the CQAs within which the process shall be unaffected and consistently manufacture the required product. Risk assessment tools and design of experiments are its prime components. This paper outlines the basic knowledge of QbD, the key elements; steps as well as various tools for QbD implementation in pharmaceutics field are presented briefly. In addition to this, quite a lot of applications of QbD in numerous pharmaceutical related unit operations are discussed and summarized. This article provides a complete data as well as the road map for universal implementation and application of QbD for pharmaceutical products. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Method of manufacturing aluminide sheet by thermomechanical processing of aluminide powders
Hajaligol, Mohammad R.; Scorey, Clive; Sikka, Vinod K.; Deevi, Seetharama C.; Fleishhauer, Grier; Lilly, Jr., A. Clifton; German, Randall M.
2003-12-09
A powder metallurgical process of preparing a sheet from a powder having an intermetallic alloy composition such as an iron, nickel or titanium aluminide. The sheet can be manufactured into electrical resistance heating elements having improved room temperature ductility, electrical resistivity, cyclic fatigue resistance, high temperature oxidation resistance, low and high temperature strength, and/or resistance to high temperature sagging. The iron aluminide has an entirely ferritic microstructure which is free of austenite and can include, in weight %, 4 to 32% Al, and optional additions such as .ltoreq.1% Cr, .gtoreq.0.05% Zr .ltoreq.2% Ti, .ltoreq.2% Mo, .ltoreq.1% Ni, .ltoreq.0.75% C, .ltoreq.0.1% B, .ltoreq.1% submicron oxide particles and/or electrically insulating or electrically conductive covalent ceramic particles, .ltoreq.1% rare earth metal, and/or .ltoreq.3% Cu. The process includes forming a non-densified metal sheet by consolidating a powder having an intermetallic alloy composition such as by roll compaction, tape casting or plasma spraying, forming a cold rolled sheet by cold rolling the non-densified metal sheet so as to increase the density and reduce the thickness thereof and annealing the cold rolled sheet. The powder can be a water, polymer or gas atomized powder which is subjecting to sieving and/or blending with a binder prior to the consolidation step. After the consolidation step, the sheet can be partially sintered. The cold rolling and/or annealing steps can be repeated to achieve the desired sheet thickness and properties. The annealing can be carried out in a vacuum furnace with a vacuum or inert atmosphere. During final annealing, the cold rolled sheet recrystallizes to an average grain size of about 10 to 30 .mu.m. Final stress relief annealing can be carried out in the B2 phase temperature range.
Method of manufacturing aluminide sheet by thermomechanical processing of aluminide powders
Hajaligol, Mohammad R.; Scorey, Clive; Sikka, Vinod K.; Deevi, Seetharama C.; Fleischhauer, Grier; Lilly, Jr., A. Clifton; German, Randall M.
2000-01-01
A powder metallurgical process of preparing a sheet from a powder having an intermetallic alloy composition such as an iron, nickel or titanium aluminide. The sheet can be manufactured into electrical resistance heating elements having improved room temperature ductility, electrical resistivity, cyclic fatigue resistance, high temperature oxidation resistance, low and high temperature strength, and/or resistance to high temperature sagging. The iron aluminide has an entirely ferritic microstructure which is free of austenite and can include, in weight %, 4 to 32% Al, and optional additions such as .ltoreq.1% Cr, .gtoreq.0.05% Zr.ltoreq.2% Ti, .ltoreq.2% Mo, .ltoreq.1% Ni, .ltoreq.0.75% C, .ltoreq.0.1% B, .ltoreq.1% submicron oxide particles and/or electrically insulating or electrically conductive covalent ceramic particles, .ltoreq.1% rare earth metal, and/or .ltoreq.3% Cu. The process includes forming a non-densified metal sheet by consolidating a powder having an intermetallic alloy composition such as by roll compaction, tape casting or plasma spraying, forming a cold rolled sheet by cold rolling the non-densified metal sheet so as to increase the density and reduce the thickness thereof and annealing the cold rolled sheet. The powder can be a water, polymer or gas atomized powder which is subjecting to sieving and/or blending with a binder prior to the consolidation step. After the consolidation step, the sheet can be partially sintered. The cold rolling and/or annealing steps can be repeated to achieve the desired sheet thickness and properties. The annealing can be carried out in a vacuum furnace with a vacuum or inert atmosphere. During final annealing, the cold rolled sheet recrystallizes to an average grain size of about 10 to 30 .mu.m. Final stress relief annealing can be carried out in the B2 phase temperature range.
The automated array assembly task of the low-cost silicon solar array project, phase 2
NASA Technical Reports Server (NTRS)
Coleman, M. G.; Pryor, R. A.; Sparks, T. G.; Legge, R.; Saltzman, D. L.
1980-01-01
Several specific processing steps as part of a total process sequence for manufacturing silicon solar cells were studied. Ion implantation was identified as the preferred process step for impurity doping. Unanalyzed beam ion implantation was shown to have major cost advantages over analyzed beam implantation. Further, high quality cells were fabricated using a high current unanalyzed beam. Mechanically masked plasma patterning of silicon nitride was shown to be capable of forming fine lines on silicon surfaces with spacings between mask and substrate as great as 250 micrometers. Extensive work was performed on advances in plated metallization. The need for the thick electroless palladium layer was eliminated. Further, copper was successfully utilized as a conductor layer utilizing nickel as a barrier to copper diffusion into the silicon. Plasma etching of silicon for texturing and saw damage removal was shown technically feasible but not cost effective compared to wet chemical etching techniques.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sarver, J.M.; Doherty, P.E.; Doyle, D.M.
1995-12-31
Thermally treated Alloy 690 is the tubing material of choice for replacement steam generators in the United States. Throughout the world, it is manufactured using different melting and thermomechanical processing methods. The influence of different processing steps on the intergranular stress corrosion cracking (IGSCC) behavior of Alloy 690 has not been thoroughly evaluated. Evaluations were performed on Alloy 690 steam generator tubing produced using several different melting practices and thermomechanical processing procedures. The evaluations included extensive microstructural examinations as well as constant extension rate (CERT) tests. The CERT test results indicated that the thermally treated Alloy 690 tubing which wasmore » subjected to higher annealing temperatures displayed the highest degree of resistance to stress corrosion cracking (SCC). Examination of the microstructures indicated that the microstructural changes which are produced by increased annealing temperatures are subtle. In an attempt to further elucidate and quantify the effect of manufacturing processes on corrosion behavior, grain boundary character distribution (GBCD) measurements were performed on the same materials which were CERT tested. Analysis of GBCDs of the samples used in this study indicate that Alloy 690 exhibits a significantly larger fraction of special boundaries as compared to Alloy 600 and Alloy 800, regardless of the processing history of the tubing. Preliminary results indicate that a correlation may exist between processing method, GBCD`s and degree of IGSCC exhibited by the thermally treated samples examined in this study.« less
Industrial Photogrammetry - Accepted Metrology Tool or Exotic Niche
NASA Astrophysics Data System (ADS)
Bösemann, Werner
2016-06-01
New production technologies like 3D printing and other adaptive manufacturing technologies have changed the industrial manufacturing process, often referred to as next industrial revolution or short industry 4.0. Such Cyber Physical Production Systems combine virtual and real world through digitization, model building process simulation and optimization. It is commonly understood that measurement technologies are the key to combine the real and virtual worlds (eg. [Schmitt 2014]). This change from measurement as a quality control tool to a fully integrated step in the production process has also changed the requirements for 3D metrology solutions. Key words like MAA (Measurement Assisted Assembly) illustrate that new position of metrology in the industrial production process. At the same time it is obvious that these processes not only require more measurements but also systems to deliver the required information in high density in a short time. Here optical solutions including photogrammetry for 3D measurements have big advantages over traditional mechanical CMM's. The paper describes the relevance of different photogrammetric solutions including state of the art, industry requirements and application examples.
[Establishment of design space for production process of traditional Chinese medicine preparation].
Xu, Bing; Shi, Xin-Yuan; Qiao, Yan-Jiang; Wu, Zhi-Sheng; Lin, Zhao-Zhou
2013-03-01
The philosophy of quality by design (QbD) is now leading the changes in the drug manufacturing mode from the conventional test-based approach to the science and risk based approach focusing on the detailed research and understanding of the production process. Along with the constant deepening of the understanding of the manufacturing process, the design space will be determined, and the emphasis of quality control will be shifted from the quality standards to the design space. Therefore, the establishment of the design space is core step in the implementation of QbD, and it is of great importance to study the methods for building the design space. This essay proposes the concept of design space for the production process of traditional Chinese medicine (TCM) preparations, gives a systematic introduction of the concept of the design space, analyzes the feasibility and significance to build the design space in the production process of traditional Chinese medicine preparations, and proposes study approaches on the basis of examples that comply with the characteristics of traditional Chinese medicine preparations, as well as future study orientations.
Manufacturing Enhancement through Reduction of Cycle Time using Different Lean Techniques
NASA Astrophysics Data System (ADS)
Suganthini Rekha, R.; Periyasamy, P.; Nallusamy, S.
2017-08-01
In recent manufacturing system the most important parameters in production line are work in process, TAKT time and line balancing. In this article lean tools and techniques were implemented to reduce the cycle time. The aim is to enhance the productivity of the water pump pipe by identifying the bottleneck stations and non value added activities. From the initial time study the bottleneck processes were identified and then necessary expanding processes were also identified for the bottleneck process. Subsequently the improvement actions have been established and implemented using different lean tools like value stream mapping, 5S and line balancing. The current state value stream mapping was developed to describe the existing status and to identify various problem areas. 5S was used to implement the steps to reduce the process cycle time and unnecessary movements of man and material. The improvement activities were implemented with required suggested and the future state value stream mapping was developed. From the results it was concluded that the total cycle time was reduced about 290.41 seconds and the customer demand has been increased about 760 units.
NASA Astrophysics Data System (ADS)
Chen, Kai-Hsiung; Huang, Guo-Tsai; Hsieh, Hung-Chih; Ni, Wei-Feng; Chuang, S. M.; Chuang, T. K.; Ke, Chih-Ming; Huang, Jacky; Rao, Shiuan-An; Cumurcu Gysen, Aysegul; d'Alfonso, Maxime; Yueh, Jenny; Izikson, Pavel; Soco, Aileen; Wu, Jon; Nooitgedagt, Tjitte; Ottens, Jeroen; Kim, Yong Ho; Ebert, Martin
2017-03-01
On-product overlay requirements are becoming more challenging with every next technology node due to the continued decrease of the device dimensions and process tolerances. Therefore, current and future technology nodes require demanding metrology capabilities such as target designs that are robust towards process variations and high overlay measurement density (e.g. for higher order process corrections) to enable advanced process control solutions. The impact of advanced control solutions based on YieldStar overlay data is being presented in this paper. Multi patterning techniques are applied for critical layers and leading to additional overlay measurement demands. The use of 1D process steps results in the need of overlay measurements relative to more than one layer. Dealing with the increased number of overlay measurements while keeping the high measurement density and metrology accuracy at the same time presents a challenge for high volume manufacturing (HVM). These challenges are addressed by the capability to measure multi-layer targets with the recently introduced YieldStar metrology tool, YS350. On-product overlay results of such multi-layers and standard targets are presented including measurement stability performance.
Use of Nanofibers to Strengthen Hydrogels of Silica, Other Oxides, and Aerogels
NASA Technical Reports Server (NTRS)
Meador, Mary Ann B.; Capadona, Lynn A.; Hurwitz, Frances; Vivod, Stephanie L.; Lake, Max
2010-01-01
Research has shown that including up to 5 percent w/w carbon nanofibers in a silica backbone of polymer crosslinked aerogels improves its strength, tripling compressive modulus and increasing tensile stress-at-break five-fold with no increase in density or decrease in porosity. In addition, the initial silica hydrogels, which are produced as a first step in manufacturing the aerogels, can be quite fragile and difficult to handle before cross-linking. The addition of the carbon nanofiber also improves the strength of the initial hydrogels before cross-linking, improving the manufacturing process. This can also be extended to other oxide aerogels, such as alumina or aluminosilicates, and other nanofiber types, such as silicon carbide.
Spraying Techniques for Large Scale Manufacturing of PEM-FC Electrodes
NASA Astrophysics Data System (ADS)
Hoffman, Casey J.
Fuel cells are highly efficient energy conversion devices that represent one part of the solution to the world's current energy crisis in the midst of global climate change. When supplied with the necessary reactant gasses, fuel cells produce only electricity, heat, and water. The fuel used, namely hydrogen, is available from many sources including natural gas and the electrolysis of water. If the electricity for electrolysis is generated by renewable energy (e.g., solar and wind power), fuel cells represent a completely 'green' method of producing electricity. The thought of being able to produce electricity to power homes, vehicles, and other portable or stationary equipment with essentially zero environmentally harmful emissions has been driving academic and industrial fuel cell research and development with the goal of successfully commercializing this technology. Unfortunately, fuel cells cannot achieve any appreciable market penetration at their current costs. The author's hypothesis is that: the development of automated, non-contact deposition methods for electrode manufacturing will improve performance and process flexibility, thereby helping to accelerate the commercialization of PEMFC technology. The overarching motivation for this research was to lower the cost of manufacturing fuel cell electrodes and bring the technology one step closer to commercial viability. The author has proven this hypothesis through a detailed study of two non-contact spraying methods. These scalable deposition systems were incorporated into an automated electrode manufacturing system that was designed and built by the author for this research. The electrode manufacturing techniques developed by the author have been shown to produce electrodes that outperform a common lab-scale contact method that was studied as a baseline, as well as several commercially available electrodes. In addition, these scalable, large scale electrode manufacturing processes developed by the author are also flexible and can be used to fabricate almost any fuel cell electrodes on the market today. This dissertation provides a description of the entire electrode manufacturing process as well as an analysis of the accuracy, performance and repeatability of the methods.
Micromachined needles and lancets with design adjustable bevel angles
NASA Astrophysics Data System (ADS)
Sparks, Douglas; Hubbard, Timothy
2004-08-01
A new method of micromachining hollow needles and two-dimensional needle arrays from single crystal silicon is described. The process involves a combination of fusion bonding, photolithography and anisotropic plasma etching. The cannula produced with this process can have design adjustable bevel angles, wall thickness and channel dimensions. A subset of processing steps can be employed to produce silicon blades and lancets with design adjustable bevel angles and shaft dimensions. Applications for this technology include painless drug infusion, blood diagnosis, glucose monitoring, cellular injection and the manufacture of microkeratomes for ocular, vascular and neural microsurgery.
NASA Astrophysics Data System (ADS)
Ness, P. H.; Jacobson, H.
1984-10-01
The thrust of 'group technology' is toward the exploitation of similarities in component design and manufacturing process plans to achieve assembly line flow cost efficiencies for small batch production. The systematic method devised for the identification of similarities in component geometry and processing steps is a coding and classification scheme implemented by interactive CAD/CAM systems. This coding and classification scheme has led to significant increases in computer processing power, allowing rapid searches and retrievals on the basis of a 30-digit code together with user-friendly computer graphics.
Advanced Research Deposition System (ARDS) for processing CdTe solar cells
NASA Astrophysics Data System (ADS)
Barricklow, Keegan Corey
CdTe solar cells have been commercialized at the Gigawatt/year level. The development of volume manufacturing processes for next generation CdTe photovoltaics (PV) with higher efficiencies requires research systems with flexibility, scalability, repeatability and automation. The Advanced Research Deposition Systems (ARDS) developed by the Materials Engineering Laboratory (MEL) provides such a platform for the investigation of materials and manufacturing processes necessary to produce the next generation of CdTe PV. Limited by previous research systems, the ARDS was developed to provide process and hardware flexibility, accommodating advanced processing techniques, and capable of producing device quality films. The ARDS is a unique, in-line process tool with nine processing stations. The system was designed, built and assembled at the Materials Engineering Laboratory. Final assembly, startup, characterization and process development are the focus of this research. Many technical challenges encountered during the startup of the ARDS were addressed in this research. In this study, several hardware modifications needed for the reliable operation of the ARDS were designed, constructed and successfully incorporated into the ARDS. The effect of process condition on film properties for each process step was quantified. Process development to achieve 12% efficient baseline solar cell required investigation of discrete processing steps, troubleshooting process variation, and developing performance correlations. Subsequent to this research, many advances have been demonstrated with the ARDS. The ARDS consistently produces devices of 12% +/-.5% by the process of record (POR). The champion cell produced to date utilizing the ARDS has an efficiency of 16.2% on low cost commercial sodalime glass and utilizes advanced films. The ARDS has enabled investigation of advanced concepts for processing CdTe devices including, Plasma Cleaning, Plasma Enhanced Closed Space Sublimation (PECSS), Electron Reflector (ER) using Cd1-xMgxTe (CMT) structure and alternative device structures. The ARDS has been instrumental in the collaborative research with many institutions.
Harrison, Richard P; Medcalf, Nicholas; Rafiq, Qasim A
2018-03-01
Manufacturing methods for cell-based therapies differ markedly from those established for noncellular pharmaceuticals and biologics. Attempts to 'shoehorn' these into existing frameworks have yielded poor outcomes. Some excellent clinical results have been realized, yet emergence of a 'blockbuster' cell-based therapy has so far proved elusive. The pressure to provide these innovative therapies, even at a smaller scale, remains. In this process, economics research paper, we utilize cell expansion research data combined with operational cost modeling in a case study to demonstrate the alternative ways in which a novel mesenchymal stem cell-based therapy could be provided at small scale. This research outlines the feasibility of cell microfactories but highlighted that there is a strong pressure to automate processes and split the quality control cost-burden over larger production batches. The study explores one potential paradigm of cell-based therapy provisioning as a potential exemplar on which to base manufacturing strategy.
Alternative Approach to Vehicle Element Processing
NASA Technical Reports Server (NTRS)
Huether, Jacob E.; Otto, Albert E.
1995-01-01
The National Space Transportation Policy (NSTP), describes the challenge facing today's aerospace industry. 'Assuring reliable and affordable access to space through U.S. space transportation capabilities is a fundamental goal of the U.S. space program'. Experience from the Space Shuttle Program (SSP) tells us that launch and mission operations are responsible for approximately 45 % of the cost of each shuttle mission. Reducing these costs is critical to NSTP goals in the next generation launch vehicle. Based on this, an innovative alternative approach to vehicle element processing was developed with an emphasis on reduced launch costs. State-of-the-art upgrades to the launch processing system (LPS) will enhance vehicle ground operations. To carry this one step further, these upgrade could be implemented at various vehicle element manufacturing sites to ensure system compatibility between the manufacturing facility and the launch site. Design center vehicle stand alone testing will ensure system integrity resulting in minimized checkout and testing at the launch site. This paper will addresses vehicle test requirements, timelines and ground checkout procedures which enable concept implementation.
Walker, Jason M; Bodamer, Emily; Krebs, Olivia; Luo, Yuanyuan; Kleinfehn, Alex; Becker, Matthew L; Dean, David
2017-04-10
Two distinct molecular masses of poly(propylene fumarate) (PPF) are combined with an additive manufacturing process to fabricate highly complex scaffolds possessing controlled chemical properties and porous architecture. Scaffolds were manufactured with two polymer molecular masses and two architecture styles. Degradation was assessed in an accelerated in vitro environment. The purpose of the degradation study is not to model or mimic in vivo degradation, but to efficiently compare the effect of modulating scaffold properties. This is the first study addressing degradation of chain-growth synthesized PPF, a process that allows for considerably more control over molecular mass distribution. It demonstrates that, with greater process control, not only is scaffold fabrication reproducible, but the mechanical properties and degradation kinetics can be tailored by altering the physical properties of the scaffold. This is a clear step forward in using PPF to address unmet medical needs while meeting regulatory demands and ultimately obtaining clinical relevancy.
NASA Astrophysics Data System (ADS)
Paek, Seung Weon; Kang, Jae Hyun; Ha, Naya; Kim, Byung-Moo; Jang, Dae-Hyun; Jeon, Junsu; Kim, DaeWook; Chung, Kun Young; Yu, Sung-eun; Park, Joo Hyun; Bae, SangMin; Song, DongSup; Noh, WooYoung; Kim, YoungDuck; Song, HyunSeok; Choi, HungBok; Kim, Kee Sup; Choi, Kyu-Myung; Choi, Woonhyuk; Jeon, JoongWon; Lee, JinWoo; Kim, Ki-Su; Park, SeongHo; Chung, No-Young; Lee, KangDuck; Hong, YoungKi; Kim, BongSeok
2012-03-01
A set of design for manufacturing (DFM) techniques have been developed and applied to 45nm, 32nm and 28nm logic process technologies. A noble technology combined a number of potential confliction of DFM techniques into a comprehensive solution. These techniques work in three phases for design optimization and one phase for silicon diagnostics. In the DFM prevention phase, foundation IP such as standard cells, IO, and memory and P&R tech file are optimized. In the DFM solution phase, which happens during ECO step, auto fixing of process weak patterns and advanced RC extraction are performed. In the DFM polishing phase, post-layout tuning is done to improve manufacturability. DFM analysis enables prioritization of random and systematic failures. The DFM technique presented in this paper has been silicon-proven with three successful tape-outs in Samsung 32nm processes; about 5% improvement in yield was achieved without any notable side effects. Visual inspection of silicon also confirmed the positive effect of the DFM techniques.
Fu, Zhibiao; Baker, Daniel; Cheng, Aili; Leighton, Julie; Appelbaum, Edward; Aon, Juan
2016-05-01
The principle of quality by design (QbD) has been widely applied to biopharmaceutical manufacturing processes. Process characterization is an essential step to implement the QbD concept to establish the design space and to define the proven acceptable ranges (PAR) for critical process parameters (CPPs). In this study, we present characterization of a Saccharomyces cerevisiae fermentation process using risk assessment analysis, statistical design of experiments (DoE), and the multivariate Bayesian predictive approach. The critical quality attributes (CQAs) and CPPs were identified with a risk assessment. The statistical model for each attribute was established using the results from the DoE study with consideration given to interactions between CPPs. Both the conventional overlapping contour plot and the multivariate Bayesian predictive approaches were used to establish the region of process operating conditions where all attributes met their specifications simultaneously. The quantitative Bayesian predictive approach was chosen to define the PARs for the CPPs, which apply to the manufacturing control strategy. Experience from the 10,000 L manufacturing scale process validation, including 64 continued process verification batches, indicates that the CPPs remain under a state of control and within the established PARs. The end product quality attributes were within their drug substance specifications. The probability generated with the Bayesian approach was also used as a tool to assess CPP deviations. This approach can be extended to develop other production process characterization and quantify a reliable operating region. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:799-812, 2016. © 2016 American Institute of Chemical Engineers.
Characterization of Long SiAION Ceramic Tubes for Gun Barrel Applications
2006-06-01
sintering kinetics during the sintering of regions with different starting densities can all lead to the production of tubes with gradients in strength and...variations of dimensions. These gradients and deviations from anticipated dimensions all detract from the ability of the manufactured product to be...characteristics of the tubes can be introduced at various steps in the production process. When the powder is initially loaded to be cold
ERIC Educational Resources Information Center
Reifschneider, Louis; Kaufman, Peter; Langrehr, Frederick W.; Kaufman, Kristina
2015-01-01
Marketers are criticized for not understanding the steps in the engineering research and development process and the challenges of manufacturing a new product at a profit. Engineers are criticized for not considering the marketability of and customer interest in such a product during the planning stages. With the development of 3D printing, rapid…
A novel tank for DI water reduction in MEMS manufacturing
NASA Astrophysics Data System (ADS)
Raccurt, O.; Tardif, F.; Kerber, L.; Lardin, T.; Vareine, T.
2003-05-01
A new rinsing process is proposed based on the conclusions obtained by simulations. It consists of a combination of piston flows and internal top-to-bottom recycling steps, which decreases the DI water consumption (and associated cost) for the same rinsing efficiency. This novel concept re-using the DI water in situ in the rinsing tank is demonstrated using an industrial bath recently proposed on the market.
Manufacture of PCDE Prepolymer
1977-10-01
Study ......... .......... 8 B. PBEP Process ................. .................. 10 I. Chemistry ....... ................. 10 2. Operating Conditions...DEPECH made therefrom for evaluation. Two mLthodb of iiproving the PECII were studied . The first method wis to subject "standard" PECH to treatment that...CH2 - CHO.I CI12 CHI2 OC(P 3 groups in this step. 2. Shell Development Study One of Tie objectives of Contract F04611-73-C-0051 was to improve the
Design and manufacture a coconut milk squeezer
NASA Astrophysics Data System (ADS)
Wayan Surata, I.; Gde Tirta Nindhia, Tjokorda; Budyanto, D.; Yulianto, A. E.
2017-05-01
The process of cooking oil production generally is started by grating the ripe coconut meat, then pressing the grated meat to obtain coconut milk, and finally heating the coconut milk to obtain the cooking oil. Pressing mechanism to obtain coconut milk is a very important step and decisive in the process of producing cooking oil. The amount of milk produced depends on the pressure applied at the time of pressing grated coconut. The higher the pressure, the more milk is obtained. Some commercial mechanical pressing tools that available in the market are not efficient due to the working steps too much and take long time per cycle of work. The aims of this study was to design and manufacture a power screw squeezer for the collection of coconut milk. Power screw produces a compressive force in the cylinder to push and press the grated coconut until the end of the cylinder while the coconut milk and coconut dregs flow out simultaneously. Screw press was designed using straight shaft configuration with square profile. Performance test was done to investigate the actual capacity and yield of milk produced. The results showed that squeezer of grated coconut worked well with capacity an average of 13,63 kg/h and coconut milk yield of 58%.
Automated imprint mask cleaning for step-and-flash imprint lithography
NASA Astrophysics Data System (ADS)
Singh, Sherjang; Chen, Ssuwei; Selinidis, Kosta; Fletcher, Brian; McMackin, Ian; Thompson, Ecron; Resnick, Douglas J.; Dress, Peter; Dietze, Uwe
2009-03-01
Step-and-Flash Imprint Lithography (S-FIL) is a promising lithography strategy for semiconductor manufacturing at device nodes below 32nm. The S-FIL 1:1 pattern transfer technology utilizes a field-by-field ink jet dispense of a low viscosity liquid resist to fill the relief pattern of the device layer etched into the glass mask. Compared to other sub 40nm CD lithography methods, the resulting high resolution, high throughput through clustering, 3D patterning capability, low process complexity, and low cost of ownership (CoO) of S-FIL makes it a widely accepted technology for patterned media as well as a promising mainstream option for future CMOS applications. Preservation of mask cleanliness is essential to avoid risk of repeated printing of defects. The development of mask cleaning processes capable of removing particles adhered to the mask surface without damaging the mask is critical to meet high volume manufacturing requirements. In this paper we have presented various methods of residual (cross-linked) resist removal and final imprint mask cleaning demonstrated on the HamaTech MaskTrack automated mask cleaning system. Conventional and non-conventional (acid free) methods of particle removal have been compared and the effect of mask cleaning on pattern damage and CD integrity is also studied.
Clinical benefit and preservation of flavonols in dark chocolate manufacturing.
McShea, Andrew; Ramiro-Puig, Emma; Munro, Sandra B; Casadesus, Gemma; Castell, Margarida; Smith, Mark A
2008-11-01
The consumption of high-cacao-content chocolate has been associated with positive health benefits ascribed to flavanol [corrected] antioxidants derived from the ground, fermented cocoa seeds of Theobroma cacao. However, flavanols [corrected] impart a bitter, astringent flavor to foodstuffs, frequently masked in chocolates and confections by aggressive processing and adulteration with other flavors. Recent reports have implied that not all varieties of dark chocolate are created equally, and significant caveats exist regarding its potential health benefits. It is perhaps not surprising that extensive processing, dilution, and the addition of flavor modifiers may improve the palatability of chocolate, but could have negative nutritional and clinical benefits. This article examines the chemical composition of chocolate and the clinical data associated with the consumption of flavonoid-rich cocoa. We review the steps in chocolate manufacturing that directly affect the antioxidant levels in chocolate products, and the caveats associated with claims of health benefits from the consumption of dark chocolate.
De Vilmorin, Philippe; Slocum, Ashley; Jaber, Tareq; Schaefer, Oliver; Ruppach, Horst; Genest, Paul
2015-01-01
This article describes a four virus panel validation of EMD Millipore's (Bedford, MA) small virus-retentive filter, Viresolve® Pro, using TrueSpike(TM) viruses for a Biogen Idec process intermediate. The study was performed at Charles River Labs in King of Prussia, PA. Greater than 900 L/m(2) filter throughput was achieved with the approximately 8 g/L monoclonal antibody feed. No viruses were detected in any filtrate samples. All virus log reduction values were between ≥3.66 and ≥5.60. The use of TrueSpike(TM) at Charles River Labs allowed Biogen Idec to achieve a more representative scaled-down model and potentially reduce the cost of its virus filtration step and the overall cost of goods. The body of data presented here is an example of the benefits of following the guidance from the PDA Technical Report 47, The Preparation of Virus Spikes Used for Viral Clearance Studies. The safety of biopharmaceuticals is assured through the use of multiple steps in the purification process that are capable of virus clearance, including filtration with virus-retentive filters. The amount of virus present at the downstream stages in the process is expected to be and is typically low. The viral clearance capability of the filtration step is assessed in a validation study. The study utilizes a small version of the larger manufacturing size filter, and a large, known amount of virus is added to the feed prior to filtration. Viral assay before and after filtration allows the virus log reduction value to be quantified. The representativeness of the small-scale model is supported by comparing large-scale filter performance to small-scale filter performance. The large-scale and small-scale filtration runs are performed using the same operating conditions. If the filter performance at both scales is comparable, it supports the applicability of the virus log reduction value obtained with the small-scale filter to the large-scale manufacturing process. However, the virus preparation used to spike the feed material often contains impurities that contribute adversely to virus filter performance in the small-scale model. The added impurities from the virus spike, which are not present at manufacturing scale, compromise the scale-down model and put into question the direct applicability of the virus clearance results. Another consequence of decreased filter performance due to virus spike impurities is the unnecessary over-sizing of the manufacturing system to match the low filter capacity observed in the scale-down model. This article describes how improvements in mammalian virus spike purity ensure the validity of the log reduction value obtained with the scale-down model and support economically optimized filter usage. © PDA, Inc. 2015.
Reduction of spiked porcine circovirus during the manufacture of a Vero cell-derived vaccine.
Lackner, Cornelia; Leydold, Sandra M; Modrof, Jens; Farcet, Maria R; Grillberger, Leopold; Schäfer, Birgit; Anderle, Heinz; Kreil, Thomas R
2014-04-11
Porcine circovirus-1 (PCV1) was recently identified as a contaminant in live Rotavirus vaccines, which was likely caused by contaminated porcine trypsin. The event triggered the development of new regulatory guidance on the use of porcine trypsin which shall ensure that cell lines and porcine trypsin in use are free from PCV1. In addition, manufacturing processes of biologicals other than live vaccines include virus clearance steps that may prevent and mitigate any potential virus contamination of product. In this work, artificial spiking of down-scaled models for the manufacturing process of an inactivated pandemic influenza virus vaccine were used to investigate inactivation of PCV1 and the physico-chemically related porcine parvovirus (PPV) by formalin and ultraviolet-C (UV-C) treatment as well as removal by the purification step sucrose gradient ultracentrifugation. A PCV1 infectivity assay, using a real-time PCR infectivity readout was established. The formalin treatment (0.05% for 48h) showed substantial inactivation for both PCV1 and PPV with reduction factors of 3.0log10 and 6.8log10, respectively, whereas UV-C treatment resulted in complete PPV (≥5.9log10) inactivation already at a dose of 13mJ/cm but merely 1.7log10 at 24mJ/cm(2) for PCV1. The UV-C inactivation results with PPV were confirmed using minute virus of mice (MVM), indicating that parvoviruses are far more sensitive to UV-C than PCV1. The sucrose density gradient ultracentrifugation also contributed to PCV1 clearance with a reduction factor of 2log10. The low pH treatment during the production of procine trypsin was investigated and showed effective inactivation for both PCV1 (4.5log10) and PPV (6.4log10). In conclusion, PCV1 in general appears to be more resistant to virus inactivation than PPV. Still, the inactivated pandemic influenza vaccine manufacturing process provides for robust virus reduction, in addition to the already implemented testing for PCV1 to avoid any contaminations. Copyright © 2014 Elsevier Ltd. All rights reserved.
Ion beam figuring of silicon aspheres
NASA Astrophysics Data System (ADS)
Demmler, Marcel; Zeuner, Michael; Luca, Alfonz; Dunger, Thoralf; Rost, Dirk; Kiontke, Sven; Krüger, Marcus
2011-03-01
Silicon lenses are widely used for infrared applications. Especially for portable devices the size and weight of the optical system are very important factors. The use of aspherical silicon lenses instead of spherical silicon lenses results in a significant reduction of weight and size. The manufacture of silicon lenses is more challenging than the manufacture of standard glass lenses. Typically conventional methods like diamond turning, grinding and polishing are used. However, due to the high hardness of silicon, diamond turning is very difficult and requires a lot of experience. To achieve surfaces of a high quality a polishing step is mandatory within the manufacturing process. Nevertheless, the required surface form accuracy cannot be achieved through the use of conventional polishing methods because of the unpredictable behavior of the polishing tools, which leads to an unstable removal rate. To overcome these disadvantages a method called Ion Beam Figuring can be used to manufacture silicon lenses with high surface form accuracies. The general advantage of the Ion Beam Figuring technology is a contactless polishing process without any aging effects of the tool. Due to this an excellent stability of the removal rate without any mechanical surface damage is achieved. The related physical process - called sputtering - can be applied to any material and is therefore also applicable to materials of high hardness like Silicon (SiC, WC). The process is realized through the commercially available ion beam figuring system IonScan 3D. During the process, the substrate is moved in front of a focused broad ion beam. The local milling rate is controlled via a modulated velocity profile, which is calculated specifically for each surface topology in order to mill the material at the associated positions to the target geometry. The authors will present aspherical silicon lenses with very high surface form accuracies compared to conventionally manufactured lenses.
Campeau, Marc-Antoine; Lortie, Audrey; Tremblay, Pierrick; Béliveau, Marc-Olivier; Dubé, Dominic; Langelier, Ève; Rouleau, Léonie
2017-07-14
Mechanobiological studies allow the characterization of cell response to mechanical stresses. Cells need to be supported by a material with properties similar to the physiological environment. Silicone elastomers have been used to produce various in vitro scaffolds of different geometries for endothelial cell studies given its relevant mechanical, optical and surface properties. However, obtaining defined and repeatable properties is a challenge as depending on the different manufacturing and processing steps, mechanical and surface properties may vary significantly between research groups. The impact of different manufacturing and processing methods on the mechanical and surface properties was assessed by measuring the Young's modulus and the contact angle. Silicone samples were produced using different curing temperatures and processed with different sterilization techniques and hydrophilization conditions. Different curing temperatures were used to obtain materials of different stiffness with a chosen silicone elastomer, i.e. Sylgard 184 ® . Sterilization by boiling had a tendency to stiffen samples cured at lower temperatures whereas UV and ethanol did not alter the material properties. Hydrophilization using sulphuric acid allowed to decrease surface hydrophobicity, however this effect was lost over time as hydrophobic recovery occurred. Extended contact with water maintained decreased hydrophobicity up to 7 days. Mechanobiological studies require complete cell coverage of the scaffolds used prior to mechanical stresses exposure. Different concentrations of fibronectin and collagen were used to coat the scaffolds and cell seeding density was varied to optimize cell coverage. This study highlights the potential bias introduced by manufacturing and processing conditions needed in the preparation of scaffolds used in mechanobiological studies involving endothelial cells. As manufacturing, processing and cell culture conditions are known to influence cell adhesion and function, they should be more thoroughly assessed by research groups that perform such mechanobiological studies using silicone.
Materials and manufacturing processes for increased life/reliability. [of turbine wheels
NASA Technical Reports Server (NTRS)
Duttweiler, R. E.
1977-01-01
Improvements in both quality and durability of disk raw material for both military and commercial engines necessitated an entirely new concept in raw material process control which imposes careful selection, screening and sampling of the basic alloy ingredients, followed by careful monitoring of the melting parameters in all phases of the vacuum melting sequence. Special care is taken to preclude solidification conditions that produce adverse levels of segregation. Melt furnaces are routinely cleaned and inspected for contamination. Ingots are also cleaned and inspected before entering the final melt step.
Toward Magnetorheological Finishing of Magnetic Materials
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shafrir, S.N.; Lambropoulos, J.C.; Jacobs, S.D.
2007-10-24
Magnetorheological finishing (MRF) is a precision finishing process traditionally limited to processing only nonmagnetic materials, e.g., optical glasses, ceramics, polymers, and metals. Here we demonstrate that MRF can be used for material removal from magnetic material surfaces. Our approach is to place an MRF spot on machined surfaces of magnetic WC-Co materials. The resulting surface roughness is comparable to that produced on nonmagnetic materials. This spotting technique may be used to evaluate the depth of subsurface damage, or deformed layer, induced by earlier manufacturing steps, such as grinding and lapping.
Process for obtaining multiple sheet resistances for thin film hybrid microcircuit resistors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Norwood, D.P.
1989-01-31
A standard thin film circuit containing Ta/sub 2/N (100 ohms/square) resistors is fabricated by depositing on a dielectric substrate successive layers of Ta/sub 2/N, Ti and Pd, with a gold layer to provide conductors. The addition of a few simple photoprocessing steps to the standard TFN manufacturing process enables the formation of Ta/sub 2/N + Ti (10 ohms/square) and Ta/sub 2/N + Ti + Pd (1 ohm/square) resistors in the same otherwise standard thin film circuit structure.
NASA Astrophysics Data System (ADS)
Tallian, M.; Pap, A.; Mocsar, K.; Somogyi, A.; Nadudvari, Gy.; Kosztka, D.; Pavelka, T.
2011-01-01
Ultra shallow junctions are becoming widely used in the micro- and nanoelectronic devices, and novel measurement methods are needed to monitor the manufacturing processes. Photomodulated Reflection measurements before anneal and Junction Photovoltage-based sheet resistance measurements after anneal are non-contact, nondestructive techniques suitable for characterizing both the implantation and the annealing process. Tests verify that these methods are consistent with each other and by using them together, defects originating in the implantation and anneal steps can be separated.
Process for obtaining multiple sheet resistances for thin film hybrid microcircuit resistors
Norwood, David P.
1989-01-01
A standard thin film circuit containing Ta.sub.2 N (100 ohms/square) resirs is fabricated by depositing on a dielectric substrate successive layers of Ta.sub.2 N, Ti and Pd, with a gold layer to provide conductors. The addition of a few simple photoprocessing steps to the standeard TFN manufacturing process enables the formation of Ta.sub.2 N+Ti (10 ohms/square) and Ta.sub.2 N+Ti+Pd (1 ohm/square) resistors in the same otherwise standard thin film circuit structure.
Tulsyan, Aditya; Garvin, Christopher; Ündey, Cenk
2018-04-06
Biopharmaceutical manufacturing comprises of multiple distinct processing steps that require effective and efficient monitoring of many variables simultaneously in real-time. The state-of-the-art real-time multivariate statistical batch process monitoring (BPM) platforms have been in use in recent years to ensure comprehensive monitoring is in place as a complementary tool for continued process verification to detect weak signals. This article addresses a longstanding, industry-wide problem in BPM, referred to as the "Low-N" problem, wherein a product has a limited production history. The current best industrial practice to address the Low-N problem is to switch from a multivariate to a univariate BPM, until sufficient product history is available to build and deploy a multivariate BPM platform. Every batch run without a robust multivariate BPM platform poses risk of not detecting potential weak signals developing in the process that might have an impact on process and product performance. In this article, we propose an approach to solve the Low-N problem by generating an arbitrarily large number of in silico batches through a combination of hardware exploitation and machine-learning methods. To the best of authors' knowledge, this is the first article to provide a solution to the Low-N problem in biopharmaceutical manufacturing using machine-learning methods. Several industrial case studies from bulk drug substance manufacturing are presented to demonstrate the efficacy of the proposed approach for BPM under various Low-N scenarios. © 2018 Wiley Periodicals, Inc.
Data handling and representation of freeform surfaces
NASA Astrophysics Data System (ADS)
Steinkopf, Ralf; Dick, Lars; Kopf, Tino; Gebhardt, Andreas; Risse, Stefan; Eberhardt, Ramona
2011-10-01
Freeform surfaces enable innovative optics. They are not limited by axis symmetry and hence they are almost free in design. They are used to reduce the installation space and enhance the performance of optical elements. State of the art optical design tools are computing with powerful algorithms to simulate freeform surfaces. Even new mathematical approaches are under development /1/. In consequence, new optical designs /2/ are pushing the development of manufacturing processes consequently and novel types of datasets have to proceed through the process chain /3/. The complexity of these data is the huge challenge for the data handling. Because of the asymmetrical and 3-dimensional surfaces of freeforms, large data volumes have to be created, trimmed, extended and fitted. All these processes must be performed without losing the accuracy of the original design data. Additionally, manifold types of geometries results in different kinds of mathematical representations of freeform surfaces and furthermore the used CAD/CAM tools are dealing with a set of spatial transport formats. These are all reasons why manufacture-oriented approaches for the freeform data handling are not yet sufficiently developed. This paper suggests a classification of freeform surfaces based on the manufacturing methods which are offered by diamond machining. The different manufacturing technologies, ranging from servo-turning to shaping, require a differentiated approach for the data handling process. The usage of analytical descriptions in form of splines and polynomials as well as the application of discrete descriptions like point clouds is shown in relation to the previously made classification. Advantages and disadvantages of freeform representations are discussed. Aspects of the data handling in between different process steps are pointed out and suitable exchange formats for freeform data are proposed. The described approach offers the possibility for efficient data handling from optical design to systems in novel optics.
Janß, Armin; Thorn, Johannes; Schmitz, Malte; Mildner, Alexander; Dell'Anna-Pudlik, Jasmin; Leucker, Martin; Radermacher, Klaus
2018-02-23
Nowadays, only closed and proprietary integrated operating room systems (IORS) from big manufacturers are available on the market. Hence, the interconnection of components from third-party vendors is only possible with increased time and costs. In the context of the German Federal Ministry of Education and Research (BMBF)-funded project OR.NET (2012-2016), the open integration of medical devices from different manufacturers was addressed. An integrated operating theater based on the open communication standard IEEE 11073 shall give clinical operators the opportunity to choose medical devices independently of the manufacturer. This approach would be advantageous especially for hospital operators and small- and medium-sized enterprises (SME) of medical devices. Actual standards and concepts regarding technical feasibility and the approval process do not cope with the requirements for a modular integration of medical devices in the operating room (OR), based on an open communication standard. Therefore, innovative approval strategies and corresponding certification and test procedures, which cover actual legal and normative standards, have to be developed in order to support the future risk management and the usability engineering process of open integrated medical devices in the OR. The use of standardized device and service profiles and a three-step testing procedure, including conformity, interoperability and integration tests are described in this paper and shall support the manufacturers to integrate their medical devices without disclosing the medical devices' risk analysis and related confidential expertise or proprietary information.
A new polishing process for large-aperture and high-precision aspheric surface
NASA Astrophysics Data System (ADS)
Nie, Xuqing; Li, Shengyi; Dai, Yifan; Song, Ci
2013-07-01
The high-precision aspheric surface is hard to be achieved due to the mid-spatial frequency error in the finishing step. The influence of mid-spatial frequency error is studied through the simulations and experiments. In this paper, a new polishing process based on magnetorheological finishing (MRF), smooth polishing (SP) and ion beam figuring (IBF) is proposed. A 400mm aperture parabolic surface is polished with this new process. The smooth polishing (SP) is applied after rough machining to control the MSF error. In the middle finishing step, most of low-spatial frequency error is removed by MRF rapidly, then the mid-spatial frequency error is restricted by SP, finally ion beam figuring is used to finish the surface. The surface accuracy is improved from the initial 37.691nm (rms, 95% aperture) to the final 4.195nm. The results show that the new polishing process is effective to manufacture large-aperture and high-precision aspheric surface.
Simon, Ross W; Canacari, Elena G
2012-01-01
Manufacturing organizations have used Lean management principles for years to help eliminate waste, streamline processes, and cut costs. This pragmatic approach to structured problem solving can be applied to health care process improvement projects. Health care leaders can use a step-by-step approach to document processes and then identify problems and opportunities for improvement using a value stream process map. Leaders can help a team identify problems and root causes and consider additional problems associated with methods, materials, manpower, machinery, and the environment by using a cause-and-effect diagram. The team then can organize the problems identified into logical groups and prioritize the groups by impact and difficulty. Leaders must manage action items carefully to instill a sense of accountability in those tasked to complete the work. Finally, the team leaders must ensure that a plan is in place to hold the gains. Copyright © 2012 AORN, Inc. Published by Elsevier Inc. All rights reserved.
Conceptual design of a water treatment system to support a manned Mars colony
NASA Technical Reports Server (NTRS)
1988-01-01
The initial tasks addressed by the Prairie View A&M University team were the conceptual design of a breathable-air manufacturing system, a means of drilling for underground water, and a method for storing water for future use. Subsequently, the design objective of the team for the 1987-1988 academic year was the conceptual design of an integrated system for the supply of quality water for biological consumption, farming, residential and industrial use. The source of water for these applications is assumed to be artesian or subsurface. The first step of the project was to establish design criteria and major assumptions. The second step of the effort was to generate a block diagram of the expected treatment system and assign tasks to individual students. The list of processes for water purification and wastewater treatment given above suggests that there will be a need for on-site chemicals manufacturing for ion-exchange regeneration and disinfection. The third step of the project was to establish a basis for the design capacity of the system. A total need of 10,000 gal/day was assumed to be required. It was also assumed that 30,000 gallon raw-water intake volume is needed to produce the desired effluent volume.
NASA Astrophysics Data System (ADS)
Weckenmann, Albert A.; Gall, P.; Gabbia, A.
2005-02-01
Modern forming technology allows the production of highly sophisticated free form sheet material components, affording great flexibility to the design and manufacturing processes across a wide range of industries. This increased design and manufacturing potential places an ever growing demand on the accompanying inspection metrology. As a consequence of their surface shape, these parts underlie a reversible geometrical deformation caused by variations of the material and the manufacturing process, as well as by gravity. This distortion is removed during the assembly process, usually performed in automated robotic processes. For this reason, the part's tolerated parameters have to be inspected in a defined state, simulating the assembly process' boundary conditions. Thus, the inspection process chain consists of six steps: picking the workpiece up, manual fixation of the workpiece, tactile measurement of the surface's coordinates using a defined measurement strategy, manual removal of the fixation and removal of the workpiece from the inspection area. These steps are both laborious and time consuming (for example, the inspection of a car door can take up to a working day to complete). Using optical measuring systems and virtual distortion compensation, this process chain can be dramatically shortened. Optical measuring systems provide as a measurement result a point cloud representing a sample of all nearest surfaces in the measuring range containing the measurand. From this data, a surface model of the measurand can be determined, independent of its position in the measuring range. For thin sheet material parts an approximating finite element model can be deduced from such a surface model. By means of pattern recognition, assembly relevant features of the measurand can be identified and located on this model. Together with the boundary conditions given by the assembly process, the shape of the surface in its assembled state can be calculated using the finite elements method. In application these methods culminate in a shortened inspection process chain (which can now also be automated): picking the workpiece up, placing it in the measuring range, optical measurement, virtual distortion compensation and removal of the workpiece from the inspection area. This work discusses the methodology of our approach in detail and also provides and analyses experimental results. The underlying research was greatfully funded by the German Research Foundation (DFG).
Analysis of form deviation in non-isothermal glass molding
NASA Astrophysics Data System (ADS)
Kreilkamp, H.; Grunwald, T.; Dambon, O.; Klocke, F.
2018-02-01
Especially in the market of sensors, LED lighting and medical technologies, there is a growing demand for precise yet low-cost glass optics. This demand poses a major challenge for glass manufacturers who are confronted with the challenge arising from the trend towards ever-higher levels of precision combined with immense pressure on market prices. Since current manufacturing technologies especially grinding and polishing as well as Precision Glass Molding (PGM) are not able to achieve the desired production costs, glass manufacturers are looking for alternative technologies. Non-isothermal Glass Molding (NGM) has been shown to have a big potential for low-cost mass manufacturing of complex glass optics. However, the biggest drawback of this technology at the moment is the limited accuracy of the manufactured glass optics. This research is addressing the specific challenges of non-isothermal glass molding with respect to form deviation of molded glass optics. Based on empirical models, the influencing factors on form deviation in particular form accuracy, waviness and surface roughness will be discussed. A comparison with traditional isothermal glass molding processes (PGM) will point out the specific challenges of non-isothermal process conditions. Furthermore, the underlying physical principle leading to the formation of form deviations will be analyzed in detail with the help of numerical simulation. In this way, this research contributes to a better understanding of form deviations in non-isothermal glass molding and is an important step towards new applications demanding precise yet low-cost glass optics.
Patterning control strategies for minimum edge placement error in logic devices
NASA Astrophysics Data System (ADS)
Mulkens, Jan; Hanna, Michael; Slachter, Bram; Tel, Wim; Kubis, Michael; Maslow, Mark; Spence, Chris; Timoshkov, Vadim
2017-03-01
In this paper we discuss the edge placement error (EPE) for multi-patterning semiconductor manufacturing. In a multi-patterning scheme the creation of the final pattern is the result of a sequence of lithography and etching steps, and consequently the contour of the final pattern contains error sources of the different process steps. We describe the fidelity of the final pattern in terms of EPE, which is defined as the relative displacement of the edges of two features from their intended target position. We discuss our holistic patterning optimization approach to understand and minimize the EPE of the final pattern. As an experimental test vehicle we use the 7-nm logic device patterning process flow as developed by IMEC. This patterning process is based on Self-Aligned-Quadruple-Patterning (SAQP) using ArF lithography, combined with line cut exposures using EUV lithography. The computational metrology method to determine EPE is explained. It will be shown that ArF to EUV overlay, CDU from the individual process steps, and local CD and placement of the individual pattern features, are the important contributors. Based on the error budget, we developed an optimization strategy for each individual step and for the final pattern. Solutions include overlay and CD metrology based on angle resolved scatterometry, scanner actuator control to enable high order overlay corrections and computational lithography optimization to minimize imaging induced pattern placement errors of devices and metrology targets.
Nanoparticle Selective Laser Processing for a Flexible Display Fabrication
NASA Astrophysics Data System (ADS)
Seung Hwan Ko,; Heng Pan,; Daeho Lee,; Costas P. Grigoropoulos,; Hee K. Park,
2010-05-01
To demonstrate a first step for a novel fabrication method of a flexible display, nanomaterial based laser processing schemes to demonstrate organic light emitting diode (OLED) pixel transfer and organic field effect transistor (OFET) fabrication on a polymer substrate without using any conventional vacuum or photolithography processes were developed. The unique properties of nanomaterials allow laser induced forward transfer of organic light emitting material at low laser energy while maintaining good fluorescence and also allow high resolution transistor electrode patterning at plastic compatible low temperature. These novel processes enable an environmentally friendly and cost effective process as well as a low temperature manufacturing sequence to realize inexpensive, large area, flexible electronics on polymer substrates.
Process development for single-crystal silicon solar cells
NASA Astrophysics Data System (ADS)
Bohra, Mihir H.
Solar energy is a viable, rapidly growing and an important renewable alternative to other sources of energy generation because of its abundant supply and low manufacturing cost. Silicon still remains the major contributor for manufacturing solar cells accounting for 80% of the market share. Of this, single-crystal solar cells account for half of the share. Laboratory cells have demonstrated 25% efficiency; however, commercial cells have efficiencies of 16% - 20% resulting from a focus on implementation processes geared to rapid throughput and low cost, thereby reducing the energy pay-back time. An example would be the use of metal pastes which dissolve the dielectric during the firing process as opposed to lithographically defined contacts. With current trends of single-crystal silicon photovoltaic (PV) module prices down to 0.60/W, almost all other PV technologies are challenged to remain cost competitive. This presents a unique opportunity in revisiting the PV cell fabrication process and incorporating moderately more expensive IC process practices into PV manufacturing. While they may drive the cost toward a 1/W benchmark, there is substantial room to "experiment", leading to higher efficiencies which will help maintain the overall system cost. This work entails a turn-key process designed to provide a platform for rapid evaluation of novel materials and processes. A two-step lithographic process yielding a baseline 11% - 13% efficient cell is described. Results of three studies have shown improvements in solar cell output parameters due to the inclusion of a back-surface field implant, a higher emitter doping and also an additional RCA Clean.
Hu, ChunSheng; Cheng, XiaoChen; Lu, YuXin; Wu, ZuZe; Zhang, QingLin
2016-11-16
The demand of a plasmid encoding human hepatocyte growth factor gene (pUDK-HGF) in large quantities at high purity and concentration has increased for gene therapy of critical limb ischemia (CLI) in clinical trials. In this article, we produced pUDK-HGF in compliance with current good manufacturing practices at gram scale. The process included a 50-L batch fermentation, continuous alkaline lysis, and integrated three-step chromatography on Sepharose 6 Fast Flow, PlasmidSelect Xtra, and Source 15Q. The production process has been scaled up to yield 4.24 ± 0.41 g of pharmaceutical pUDK-HGF from 1.0 kg bacterial cell paste and the overall yield reached range from 58.37 to 66.70%. The final pUDK-HGF product exhibited high purity with supercoiled percentage of > 95.8% and undetectable residual RNA, contaminated protein, and bacterial endotoxin. The phase I clinical study indicates that intramuscular injection of pUDK-HGF is safe, well tolerated, and may provide symptomatic relief to CLI patients. These results show that our manufacturing process of pUDK-HGF is efficient in producing pharmaceutical-grade plasmid DNA and is safe for clinical applications.
Applications of additive manufacturing in dentistry: A review.
Bhargav, Aishwarya; Sanjairaj, Vijayavenkatraman; Rosa, Vinicius; Feng, Lu Wen; Fuh Yh, Jerry
2017-07-24
Additive manufacturing (AM) or 3D printing has been hailed as the third industrial revolution as it has caused a paradigm shift in the way objects have been manufactured. Conventionally, converting a raw material to a fully finished and assembled, usable product comprises several steps which can be eliminated by using this process as functional products can be created directly from the raw material at a fraction of the time originally consumed. Thus, AM has found applications in several sectors including automotive, aerospace, printed electronics, and healthcare. AM is increasingly being used in the healthcare sector, given its potential to fabricate patient-specific customized implants with required accuracy and precision. Implantable heart valves, rib cages, and bones are some of the examples where AM technologies are used. A vast variety of materials including ceramics, metals, polymers, and composites have been processed to fabricate intricate implants using 3D printing. The applications of AM in dentistry include maxillofacial implants, dentures, and other prosthetic aids. It may also be used in surgical training and planning, as anatomical models can be created at ease using AM. This article gives an overview of the AM process and reviews in detail the applications of 3D printing in dentistry. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.
A 32 x 32 capacitive micromachined ultrasonic transducer array manufactured in standard CMOS.
Lemmerhirt, David F; Cheng, Xiaoyang; White, Robert; Rich, Collin A; Zhang, Man; Fowlkes, J Brian; Kripfgans, Oliver D
2012-07-01
As ultrasound imagers become increasingly portable and lower cost, breakthroughs in transducer technology will be needed to provide high-resolution, real-time 3-D imaging while maintaining the affordability needed for portable systems. This paper presents a 32 x 32 ultrasound array prototype, manufactured using a CMUT-in-CMOS approach whereby ultrasonic transducer elements and readout circuits are integrated on a single chip using a standard integrated circuit manufacturing process in a commercial CMOS foundry. Only blanket wet-etch and sealing steps are added to complete the MEMS devices after the CMOS process. This process typically yields better than 99% working elements per array, with less than ±1.5 dB variation in receive sensitivity among the 1024 individually addressable elements. The CMUT pulseecho frequency response is typically centered at 2.1 MHz with a -6 dB fractional bandwidth of 60%, and elements are arranged on a 250 μm hexagonal grid (less than half-wavelength pitch). Multiplexers and CMOS buffers within the array are used to make on-chip routing manageable, reduce the number of physical output leads, and drive the transducer cable. The array has been interfaced to a commercial imager as well as a set of custom transmit and receive electronics, and volumetric images of nylon fishing line targets have been produced.
Optical design and tolerancing of an ophthalmological system
NASA Astrophysics Data System (ADS)
Sieber, Ingo; Martin, Thomas; Yi, Allen; Li, Likai; Rübenach, Olaf
2014-09-01
Tolerance analysis by means of simulation is an essential step in system integration. Tolerance analysis allows for predicting the performance of a system setup of real manufactured parts and for an estimation of the yield with respect to evaluation figures, such as performance requirements, systems specification or cost demands. Currently, optical freeform optics is gaining importance in optical systems design. The performance of freeform optics often strongly depends on the manufacturing accuracy of the surfaces. For this reason, a tolerance analysis with respect to the fabrication accuracy is of crucial importance. The characterization of form tolerances caused by the manufacturing process is based on the definition of straightness, flatness, roundness, and cylindricity. In case of freeform components, however, it is often impossible to define a form deviation by means of this standard classification. Hence, prediction of the impact of manufacturing tolerances on the optical performance is not possible by means of a conventional tolerance analysis. To carry out a tolerance analysis of the optical subsystem, including freeform optics, metrology data of the fabricated surfaces have to be integrated into the optical model. The focus of this article is on design for manufacturability of freeform optics with integrated alignment structures and on tolerance analysis of the optical subsystem based on the measured surface data of manufactured optical freeform components with respect to assembly and manufacturing tolerances. This approach will be reported here using an ophthalmological system as an example.
Infrared thermography of welding zones produced by polymer extrusion additive manufacturing.
Seppala, Jonathan E; Migler, Kalman D
2016-10-01
In common thermoplastic additive manufacturing (AM) processes, a solid polymer filament is melted, extruded though a rastering nozzle, welded onto neighboring layers and solidified. The temperature of the polymer at each of these stages is the key parameter governing these non-equilibrium processes, but due to its strong spatial and temporal variations, it is difficult to measure accurately. Here we utilize infrared (IR) imaging - in conjunction with necessary reflection corrections and calibration procedures - to measure these temperature profiles of a model polymer during 3D printing. From the temperature profiles of the printed layer (road) and sublayers, the temporal profile of the crucially important weld temperatures can be obtained. Under typical printing conditions, the weld temperature decreases at a rate of approximately 100 °C/s and remains above the glass transition temperature for approximately 1 s. These measurement methods are a first step in the development of strategies to control and model the printing processes and in the ability to develop models that correlate critical part strength with material and processing parameters.
U.S. Wind Energy Manufacturing and Supply Chain: A Competitiveness Analysis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fullenkamp, Patrick H; Holody, Diane S
The goal of the project was to develop a greater understanding of the key factors determining wind energy component manufacturing costs and pricing on a global basis in order to enhance the competitiveness of U.S. manufacturers, and to reduce installed systems cost. Multiple stakeholders including DOE, turbine OEMs, and large component manufactures will all benefit by better understanding the factors determining domestic competitiveness in the emerging offshore and next generation land-based wind industries. Major objectives of this project were to: 1. Carry out global cost and process comparisons for 5MW jacket foundations, blades, towers, and permanent magnet generators; 2. Assessmore » U.S. manufacturers’ competitiveness and potential for cost reduction; 3. Facilitate informed decision-making on investments in U.S. manufacturing; 4. Develop an industry scorecard representing the readiness of the U.S. manufacturers’ to produce components for the next generations of wind turbines, nominally 3MW land-based and 5MW offshore; 5. Disseminate results through the GLWN Wind Supply Chain GIS Map, a free website that is the most comprehensive public database of U.S. wind energy suppliers; 6. Identify areas and develop recommendations to DOE on potential R&D areas to target for increasing domestic manufacturing competitiveness, per DOE’s Clean Energy Manufacturing Initiative (CEMI). Lists of Deliverables 1. Cost Breakdown Competitive Analyses of four product categories: tower, jacket foundation, blade, and permanent magnet (PM) generator. The cost breakdown for each component includes a complete Bill of Materials with net weights; general process steps for labor; and burden adjusted by each manufacturer for their process categories of SGA (sales general and administrative), engineering, logistics cost to a common U.S. port, and profit. 2. Value Stream Map Competitiveness Analysis: A tool that illustrates both information and material flow from the point of getting a customer order at the manufacturing plant; to the orders being forwarded by the manufacturing plant to the material suppliers; to the material being received at the manufacturing plant and processed through the system; to the final product being shipped to the Customer. 3. Competitiveness Scorecard: GLWN developed a Wind Industry Supply Chain Scorecard that reflects U.S. component manufacturers’ readiness to supply the next generation wind turbines, 3MW and 5MW, for land-based and offshore applications. 4. Wind Supply Chain Database & Map: Expand the current GLWN GIS Wind Supply Chain Map to include offshore elements. This is an on-line, free access, wind supply chain map that provides a platform for identifying active and emerging suppliers for the land-based and offshore wind industry, including turbine component manufacturers and wind farm construction service suppliers.« less
Powder Bed Layer Characteristics: The Overseen First-Order Process Input
NASA Astrophysics Data System (ADS)
Mindt, H. W.; Megahed, M.; Lavery, N. P.; Holmes, M. A.; Brown, S. G. R.
2016-08-01
Powder Bed Additive Manufacturing offers unique advantages in terms of manufacturing cost, lot size, and product complexity compared to traditional processes such as casting, where a minimum lot size is mandatory to achieve economic competitiveness. Many studies—both experimental and numerical—are dedicated to the analysis of how process parameters such as heat source power, scan speed, and scan strategy affect the final material properties. Apart from the general urge to increase the build rate using thicker powder layers, the coating process and how the powder is distributed on the processing table has received very little attention to date. This paper focuses on the first step of every powder bed build process: Coating the process table. A numerical study is performed to investigate how powder is transferred from the source to the processing table. A solid coating blade is modeled to spread commercial Ti-6Al-4V powder. The resulting powder layer is analyzed statistically to determine the packing density and its variation across the processing table. The results are compared with literature reports using the so-called "rain" models. A parameter study is performed to identify the influence of process table displacement and wiper velocity on the powder distribution. The achieved packing density and how that affects subsequent heat source interaction with the powder bed is also investigated numerically.
Slater, C Stewart; Savelski, Mariano J; Hitchcock, David; Cavanagh, Eduardo J
2016-01-01
An environmental analysis has been conducted to determine the cradle to gate life cycle emissions to manufacture the green solvent, 2-methyl tetrahydrofuran. The solvent is considered a greener chemical since it can be manufactured from renewable resources with a lower life cycle footprint. Analyses have been performed using different methods to show greenness in both its production and industrial use. This solvent can potentially be substituted for other ether and chlorinated solvents commonly used in organometallic and biphasic reactions steps in pharmaceutical and fine chemical syntheses. The 2-methyl tetrahydrofuran made from renewable agricultural by-products is marketed by Penn A Kem under the name ecoMeTHF™. The starting material, 2-furfuraldehyde (furfural), is produced from corn cob waste by converting the available pentosans by acid hydrolysis. An evaluation of each step in the process was necessary to determine the overall life cycle and specific CO2 emissions for each raw material/intermediate produced. Allocation of credits for CO2 from the incineration of solvents made from renewable feedstocks significantly reduced the overall carbon footprint. Using this approach, the overall life cycle emissions for production of 1 kg of ecoMeTHF™ were determined to be 0.191 kg, including 0.150 kg of CO2. Life cycle emissions generated from raw material manufacture represents the majority of the overall environmental impact. Our evaluation shows that using 2-methyl tetrahydrofuran in an industrial scenario results in a 97% reduction in emissions, when compared to typically used solvents such as tetrahydrofuran, made through a conventional chemical route.
Diversification and cumulative evolution in New Caledonian crow tool manufacture.
Hunt, Gavin R; Gray, Russell D
2003-01-01
Many animals use tools but only humans are generally considered to have the cognitive sophistication required for cumulative technological evolution. Three important characteristics of cumulative technological evolution are: (i) the diversification of tool design; (ii) cumulative change; and (iii) high-fidelity social transmission. We present evidence that crows have diversified and cumulatively changed the design of their pandanus tools. In 2000 we carried out an intensive survey in New Caledonia to establish the geographical variation in the manufacture of these tools. We documented the shapes of 5550 tools from 21 sites throughout the range of pandanus tool manufacture. We found three distinct pandanus tool designs: wide tools, narrow tools and stepped tools. The lack of ecological correlates of the three tool designs and their different, continuous and overlapping geographical distributions make it unlikely that they evolved independently. The similarities in the manufacture method of each design further suggest that pandanus tools have gone through a process of cumulative change from a common historical origin. We propose a plausible scenario for this rudimentary cumulative evolution. PMID:12737666
Pozzolanic filtration/solidification of radionuclides in nuclear reactor cooling water
DOE Office of Scientific and Technical Information (OSTI.GOV)
Englehardt, J.D.; Peng, C.
1995-12-31
Laboratory studies to investigate the feasibility of one- and two-step processes for precipitation/coprecipitating radionuclides from nuclear reactor cooling water, filtering with pozzolanic filter aid, and solidifying, are reported in this paper. In the one-step process, ferrocyanide salt and excess lime are added ahead of the filter, and the resulting filter cake solidifies by a pozzolanic reaction. The two-step process involves addition of solidifying agents subsequent to filtration. It was found that high surface area diatomaceous synthetic calcium silicate powders, sold commercially as functional fillers and carriers, adsorb nickel isotopes from solution at neutral and slightly basic pH. Addition of themore » silicates to cooling water allowed removal of the tested metal isotopes (nickel, iron, manganese, cobalt, and cesium) simultaneously at neutral to slightly basic pH. Lime to diatomite ratio was the most influential characteristic of composition on final strength tested, with higher lime ratios giving higher strength. Diatomaceous earth filter aids manufactured without sodium fluxes exhibited higher pozzolanic activity. Pozzolanic filter cake solidified with sodium silicate and a ratio of 0.45 parts lime to 1 part diatomite had compressive strength ranging from 470 to 595 psi at a 90% confidence level. Leachability indices of all tested metals in the solidified waste were acceptable. In light of the typical requirement of removing iron and desirability of control over process pH, a two-step process involving addition of Portland cement to the filter cake may be most generally applicable.« less
Lee, B S; Choi, S; Yoon, J H; Park, J Y; Won, M S
2012-02-01
A magnet system for a 28 GHz electron cyclotron resonance ion source is being developed by the Korea Basic Science Institute. The configuration of the magnet system consists of 3 solenoid coils for a mirror magnetic field and 6 racetrack coils for a hexapole magnetic field. They can generate axial magnetic fields of 3.6 T at the beam injection part and 2.2 T at the extraction part. A radial magnetic field of 2.1 T is achievable at the plasma chamber wall. A step type winding process was employed in fabricating the hexapole coil. The winding technique was confirmed through repeated cooling tests. Superconducting magnets and a cryostat system are currently being manufactured.
Laminated composite of magnetic alloy powder and ceramic powder and process for making same
Moorhead, Arthur J.; Kim, Hyoun-Ee
1999-01-01
A laminated composite structure of alternating metal powder layers, and layers formed of an inorganic bonding media powder, and a method for manufacturing same are discosed. The method includes the steps of assembling in a cavity alternating layers of a metal powder and an inorganic bonding media of a ceramic, glass, and glass-ceramic. Heat, with or without pressure, is applied to the alternating layers until the particles of the metal powder are sintered together and bonded into the laminated composite structure by the layers of sintered inorganic bonding media to form a strong composite structure. The method finds particular application in the manufacture of high performance magnets wherein the metal powder is a magnetic alloy powder.
Laminated composite of magnetic alloy powder and ceramic powder and process for making same
Moorhead, A.J.; Kim, H.
1999-08-10
A laminated composite structure of alternating metal powder layers, and layers formed of an inorganic bonding media powder, and a method for manufacturing same are disclosed. The method includes the steps of assembling in a cavity alternating layers of a metal powder and an inorganic bonding media of a ceramic, glass, and glass-ceramic. Heat, with or without pressure, is applied to the alternating layers until the particles of the metal powder are sintered together and bonded into the laminated composite structure by the layers of sintered inorganic bonding media to form a strong composite structure. The method finds particular application in the manufacture of high performance magnets wherein the metal powder is a magnetic alloy powder. 9 figs.
NASA Astrophysics Data System (ADS)
Angelastro, A.; Campanelli, S. L.; Casalino, G.
2017-09-01
This paper presents a study on process parameters and building strategy for the deposition of Colmonoy 227-F powder by CO2 laser with a focal spot diameter of 0.3 mm. Colmonoy 227-F is a nickel alloy especially designed for mold manufacturing. The substrate material is a 10 mm thick plate of AISI 304 steel. A commercial CO2 laser welding machine was equipped with a low-cost powder feeding system. In this work, following another one in which laser power, scanning speed and powder flow rate had been studied, the effects of two important process parameters, i.e. hatch spacing and step height, on the properties of the built parts were analysed. The explored ranges of hatch spacing and step height were respectively 150-300 μm and 100-200 μm, whose dimensions were comparable with that of the laser spot. The roughness, adhesion, microstructure, microhardness and density of the manufactured specimens were studied for multi-layer samples, which were made of 30 layers. The statistical significance of the studied process parameters was assessed by the analysis of the variance. The process parameters used allowed to obtain both first layer-to-substrate and layer-to-layer good adhesions. The microstructure was fine and almost defect-free. The microhardness of the deposited material was about 100 HV higher than that of the starting powder. The density as high as 98% of that of the same bulk alloy was more than satisfactory. Finally, simultaneous optimization of density and roughness was performed using the contour plots.
High throughput wafer defect monitor for integrated metrology applications in photolithography
NASA Astrophysics Data System (ADS)
Rao, Nagaraja; Kinney, Patrick; Gupta, Anand
2008-03-01
The traditional approach to semiconductor wafer inspection is based on the use of stand-alone metrology tools, which while highly sensitive, are large, expensive and slow, requiring inspection to be performed off-line and on a lot sampling basis. Due to the long cycle times and sparse sampling, the current wafer inspection approach is not suited to rapid detection of process excursions that affect yield. The semiconductor industry is gradually moving towards deploying integrated metrology tools for real-time "monitoring" of product wafers during the manufacturing process. Integrated metrology aims to provide end-users with rapid feedback of problems during the manufacturing process, and the benefit of increased yield, and reduced rework and scrap. The approach of monitoring 100% of the wafers being processed requires some trade-off in sensitivity compared to traditional standalone metrology tools, but not by much. This paper describes a compact, low-cost wafer defect monitor suitable for integrated metrology applications and capable of detecting submicron defects on semiconductor wafers at an inspection rate of about 10 seconds per wafer (or 360 wafers per hour). The wafer monitor uses a whole wafer imaging approach to detect defects on both un-patterned and patterned wafers. Laboratory tests with a prototype system have demonstrated sensitivity down to 0.3 µm on un-patterned wafers and down to 1 µm on patterned wafers, at inspection rates of 10 seconds per wafer. An ideal application for this technology is preventing photolithography defects such as "hot spots" by implementing a wafer backside monitoring step prior to exposing wafers in the lithography step.
Process performance and product quality in an integrated continuous antibody production process.
Karst, Daniel J; Steinebach, Fabian; Soos, Miroslav; Morbidelli, Massimo
2017-02-01
Continuous manufacturing is currently being seriously considered in the biopharmaceutical industry as the possible new paradigm for producing therapeutic proteins, due to production cost and product quality related benefits. In this study, a monoclonal antibody producing CHO cell line was cultured in perfusion mode and connected to a continuous affinity capture step. The reliable and stable integration of the two systems was enabled by suitable control loops, regulating the continuous volumetric flow and adapting the operating conditions of the capture process. For the latter, an at-line HPLC measurement of the harvest concentration subsequent to the bioreactor was combined with a mechanistic model of the capture chromatographic unit. Thereby, optimal buffer consumption and productivity throughout the process was realized while always maintaining a yield above the target value of 99%. Stable operation was achieved at three consecutive viable cell density set points (20, 60, and 40 × 10 6 cells/mL), together with consistent product quality in terms of aggregates, fragments, charge isoforms, and N-linked glycosylation. In addition, different values for these product quality attributes such as N-linked glycosylation, charge variants, and aggregate content were measured at the different steady states. As expected, the amount of released DNA and HCP was significantly reduced by the capture step for all considered upstream operating conditions. This study is exemplary for the potential of enhancing product quality control and modulation by integrated continuous manufacturing. Biotechnol. Bioeng. 2017;114: 298-307. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Sustainable Energy Solutions Task 3.0:Life-Cycle Database for Wind Energy Systems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Twomey, Janet M.
2010-03-01
The benefits of wind energy had previously been captured in the literature at an overview level with relatively low transparency or ability to understand the basis for that information. This has limited improvement and decision-making to larger questions such as wind versus other electrical sources (such as coal-fired plants). This research project has established a substantially different approach which is to add modular, high granularity life cycle inventory (lci) information that can be used by a wide range of decision-makers, seeking environmental improvement. Results from this project have expanded the understanding and evaluation of the underlying factors that can improvemore » both manufacturing processes and specifically wind generators. The use of life cycle inventory techniques has provided a uniform framework to understand and compare the full range of environmental improvement in manufacturing, hence the concept of green manufacturing. In this project, the focus is on 1. the manufacturing steps that transform materials and chemicals into functioning products 2. the supply chain and end-of-life influences of materials and chemicals used in industry Results have been applied to wind generators, but also impact the larger U.S. product manufacturing base. For chemicals and materials, this project has provided a standard format for each lci that contains an overview and description, a process flow diagram, detailed mass balances, detailed energy of unit processes, and an executive summary. This is suitable for integration into other life cycle databases (such as that at NREL), so that broad use can be achieved. The use of representative processes allows unrestricted use of project results. With the framework refined in this project, information gathering was initiated for chemicals and materials in wind generation. Since manufacturing is one of the most significant parts of the environmental domain for wind generation improvement, this project research has developed a fundamental approach. The emphasis was place on individual unit processes as an organizing framework to understand the life cycle of manufactured products. The rearrangement of unit processes provides an efficient and versatile means of understanding improved manufactured products such as wind generators. The taxonomy and structure of unit process lci were developed in this project. A series of ten unit process lci were developed to sample the major segments of the manufacturing unit process taxonomy. Technical and economic effectiveness has been a focus of the project research in Task three. The use of repeatable modules for the organization of information on environmental improvement has a long term impact. The information developed can be used and reused in a variety of manufacturing plants and for a range of wind generator sizes and designs. Such a modular approach will lower the cost of life cycle analysis, that is often asked questions of carbon footprint, environmental impact, and sustainability. The use of a website for dissemination, linked to NREL, adds to the economic benefit as more users have access to the lci information. Benefit to the public has been achieved by a well-attended WSU conference, as well as presentations for the Kansas Wind Energy Commission. Attendees represented public interests, land owners, wind farm developers, those interested in green jobs, and industry. Another benefit to the public is the start of information flow from manufacturers that can inform individuals about products.« less
NASA Astrophysics Data System (ADS)
Chen, Y. G.; Yang, H.; Zhang, B. Q.; Liu, Y. L.; Yin, J. C.; Wei, W.; Zhong, Y.
2017-02-01
A novel restraint spraying-Conform (RS-C) process, which directly combines spraying with Conform to process metals in one step, has been proposed. Al-20Si alloy selected as experimental material was successfully fabricated by the RS-C process. The microstructures were dominated with fine and uniform primary silicon phases. The tensile strength and elongation to failure of the Al-20Si alloy were 204 MPa and 7.2% respectively after the RS-C process. The wear resistance of the processed Al-20Si alloy was increased significantly, about 1.7 times over the as-cast ingot. The experimental results indicate that RS-C is a promising near net shape forming technology.
Entz, Michael; King, D Ryan; Poelzing, Steven
2017-12-01
With the sudden increase in affordable manufacturing technologies, the relationship between experimentalists and the designing process for laboratory equipment is rapidly changing. While experimentalists are still dependent on engineers and manufacturers for precision electrical, mechanical, and optical equipment, it has become a realistic option for in house manufacturing of other laboratory equipment with less precise design requirements. This is possible due to decreasing costs and increasing functionality of desktop three-dimensional (3-D) printers and 3-D design software. With traditional manufacturing methods, iterative design processes are expensive and time consuming, and making more than one copy of a custom piece of equipment is prohibitive. Here, we provide an overview to design a tissue bath and stabilizer for a customizable, suspended, whole heart optical mapping apparatus that can be produced significantly faster and less expensive than conventional manufacturing techniques. This was accomplished through a series of design steps to prevent fluid leakage in the areas where the optical imaging glass was attached to the 3-D printed bath. A combination of an acetone dip along with adhesive was found to create a water tight bath. Optical mapping was used to quantify cardiac conduction velocity and action potential duration to compare 3-D printed baths to a bath that was designed and manufactured in a machine shop. Importantly, the manufacturing method did not significantly affect conduction, action potential duration, or contraction, suggesting that 3-D printed baths are equally effective for optical mapping experiments. NEW & NOTEWORTHY This article details three-dimensional printable equipment for use in suspended whole heart optical mapping experiments. This equipment is less expensive than conventional manufactured equipment as well as easily customizable to the experimentalist. The baths can be waterproofed using only a three-dimensional printer, acetone, a glass microscope slide, c-clamps, and adhesive. Copyright © 2017 the American Physiological Society.
Automated Array Assembly, Phase 2
NASA Technical Reports Server (NTRS)
Daiello, R. V.
1978-01-01
The purpose of the overall program is to establish technological readiness and provide verification for the elements of a manufacturing sequence which would ultimately be suitable for the large-scale production of silicon solar-array modules at a selling price of less than $500/kW. A program and process plan for accomplishing this objective was developed and put into operation. Three junction-formation processes are shown; since cost analysis shows that they do not differ greatly in cost, each should be considered for technical merits and possible future cost reduction. The progress made in the various process steps of the plan is described, and conclusions are presented.
Metal Matrix Composite Material by Direct Metal Deposition
NASA Astrophysics Data System (ADS)
Novichenko, D.; Marants, A.; Thivillon, L.; Bertrand, P. H.; Smurov, I.
Direct Metal Deposition (DMD) is a laser cladding process for producing a protective coating on the surface of a metallic part or manufacturing layer-by-layer parts in a single-step process. The objective of this work is to demonstrate the possibility to create carbide-reinforced metal matrix composite objects. Powders of steel 16NCD13 with different volume contents of titanium carbide are tested. On the base of statistical analysis, a laser cladding processing map is constructed. Relationships between the different content of titanium carbide in a powder mixture and the material microstructure are found. Mechanism of formation of various precipitated titanium carbides is investigated.
Passivation of Plasmonic Colors on Bulk Silver by Atomic Layer Deposition of Aluminum Oxide.
Guay, Jean-Michel; Killaire, Graham; Gordon, Peter G; Barry, Sean T; Berini, Pierre; Weck, Arnaud
2018-05-01
We report the passivation of angle-independent plasmonic colors on bulk silver by atomic layer deposition (ALD) of thin films of aluminum oxide. The colors are rendered by silver nanoparticles produced by laser ablation and redeposition on silver. We then apply a two-step approach to aluminum oxide conformal film formation via ALD. In the first step, a low-density film is deposited at low temperature to preserve and pin the silver nanoparticles. In the second step, a second denser film is deposited at a higher temperature to provide tarnish protection. This approach successfully protects the silver and plasmonic colors against tarnishing, humidity, and temperature, as demonstrated by aggressive exposure trials. The processing time associated with deposition of the conformal passivation layers meets industry requirements, and the approach is compatible with mass manufacturing.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bahder, G.; Bopp, L.A.; Eager, G.S.
This report covers the continuation of the work to develop technology to manufacture chemically crosslinked polyethylene insulated power cables in the ac voltage range of 138 kV to 345 kV having insulation thicknesses approximately equal to that of oil impregnated paper insulated cables. It also incorporates the development of field molded splices and terminations for new high voltage stress 138 kV cables. After reviewing the main equipment elements, incorporated in the pilot extrusion line, the special features of this system are noted and a step-by-step description of the cable extrusion process is given. Optimization of the process and introduction ofmore » modifications in the equipment culminated with the production of 138 kV cables. Results of laboratory tests to demonstrate the high quality of the cables are given. The development of molded splices and molded stress control cones was initiated with the work on model cables and followed by the making of splices and terminations on 138 kV cables. The molded components are made with the same purified insulating compound as used in the manufacture of the cables. Both the molded splices and the molded stress control cones have been fully tested in the laboratory. Following the completion of the development of the 138 kV cable a high stress 230 kV crosslinked polyethylene cable was developed and optimized. A full evaluation program similar to the one utilized on the 138 kV cable was carried out. Subsequently, work to develop a 345 kV high voltage stress cable, having insulation thickness of 1.02'' was undertaken. 345 kV cables were successfully manufactured and tested. However, additional work is required to further optimize the quality of this cable.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barbee, T. W.; Schena, D.
This was a collaborative effort between Lawrence Livermore National Security, LLC as manager and operator of Lawrence Livermore National Laboratory (LLNL) and TroyCap LLC, to develop manufacturing steps for commercial production of nano-structure capacitors. The technical objective of this project was to demonstrate high deposition rates of selected dielectric materials which are 2 to 5 times larger than typical using current technology.
Direct Bio-printing with Heterogeneous Topology Design.
Ahsan, Amm Nazmul; Xie, Ruinan; Khoda, Bashir
2017-01-01
Bio-additive manufacturing is a promising tool to fabricate porous scaffold structures for expediting the tissue regeneration processes. Unlike the most traditional bulk material objects, the microstructures of tissue and organs are mostly highly anisotropic, heterogeneous, and porous in nature. However, modelling the internal heterogeneity of tissues/organs structures in the traditional CAD environment is difficult and oftentimes inaccurate. Besides, the de facto STL conversion of bio-models introduces loss of information and piles up more errors in each subsequent step (build orientation, slicing, tool-path planning) of the bio-printing process plan. We are proposing a topology based scaffold design methodology to accurately represent the heterogeneous internal architecture of tissues/organs. An image analysis technique is used that digitizes the topology information contained in medical images of tissues/organs. A weighted topology reconstruction algorithm is implemented to represent the heterogeneity with parametric functions. The parametric functions are then used to map the spatial material distribution. The generated information is directly transferred to the 3D bio-printer and heterogeneous porous tissue scaffold structure is manufactured without STL file. The proposed methodology is implemented to verify the effectiveness of the approach and the designed example structure is bio-fabricated with a deposition based bio-additive manufacturing system.
Shape memory alloy wires turn composites into smart structures: II. Manufacturing and properties
NASA Astrophysics Data System (ADS)
Michaud, Veronique J.; Schrooten, Jan; Parlinska, Magdelena; Gotthardt, Rolf; Bidaux, Jacques-Eric
2002-07-01
The manufacturing route and resulting properties of adaptive composites are presented in the second part of this European project report. Manufacturing was performed using a specially designed frame to pre-strain the SMA wires, embed them into Kevlar-epoxy prepregs, and maintain them during the curing process in an autoclave. Composite compounds were then tested for strain response, recovery stress response in a clamped-clamped configuration, as well as vibrational response. Through the understanding of the transformational behavior of constrained SMA wires, interesting and unique functional properties of SMA composites could be measured, explained and modeled. Large recovery stresses and as a consequence, a change in vibrational response in a clamped- clamped condition, or a reversible shape change in a free standing condition, could be generated by the SMA composites in a controllable way. These properties were dependent on composite design aspects and exhibited a reproducible and stable behavior, provided that the properties of the matrix, of the wires and the processing route were carefully optimized. In conclusion, the achievements of this effort in areas such as thermomechanics, transformational and vibrational behavior and durability of SMA based composites provide a first step towards a reliable materials design, and potentially an industrial application.
Computer-aided dental prostheses construction using reverse engineering.
Solaberrieta, E; Minguez, R; Barrenetxea, L; Sierra, E; Etxaniz, O
2014-01-01
The implementation of computer-aided design/computer-aided manufacturing (CAD/CAM) systems with virtual articulators, which take into account the kinematics, constitutes a breakthrough in the construction of customised dental prostheses. This paper presents a multidisciplinary protocol involving CAM techniques to produce dental prostheses. This protocol includes a step-by-step procedure using innovative reverse engineering technologies to transform completely virtual design processes into customised prostheses. A special emphasis is placed on a novel method that permits a virtual location of the models. The complete workflow includes the optical scanning of the patient, the use of reverse engineering software and, if necessary, the use of rapid prototyping to produce CAD temporary prostheses.
Process for producing advanced ceramics
Kwong, Kyei-Sing
1996-01-01
A process for the synthesis of homogeneous advanced ceramics such as SiC+AlN, SiAlON, SiC+Al.sub.2 O.sub.3, and Si.sub.3 N.sub.4 +AlN from natural clays such as kaolin, halloysite and montmorillonite by an intercalation and heat treatment method. Included are the steps of refining clays, intercalating organic compounds into the layered structure of clays, drying the intercalated mixture, firing the treated atmospheres and grinding the loosely agglomerated structure. Advanced ceramics produced by this procedure have the advantages of homogeneity, cost effectiveness, simplicity of manufacture, ease of grind and a short process time. Advanced ceramics produced by this process can be used for refractory, wear part and structure ceramics.
Barriobero-Vila, Pere; Gussone, Joachim; Haubrich, Jan; Sandlöbes, Stefanie; Da Silva, Julio Cesar; Cloetens, Peter; Schell, Norbert; Requena, Guillermo
2017-01-01
Selective laser melting is a promising powder-bed-based additive manufacturing technique for titanium alloys: near net-shaped metallic components can be produced with high resource-efficiency and cost savings. For the most commercialized titanium alloy, namely Ti-6Al-4V, the complicated thermal profile of selective laser melting manufacturing (sharp cycles of steep heating and cooling rates) usually hinders manufacturing of components in a one-step process owing to the formation of brittle martensitic microstructures unsuitable for structural applications. In this work, an intensified intrinsic heat treatment is applied during selective laser melting of Ti-6Al-4V powder using a scanning strategy that combines porosity-optimized processing with a very tight hatch distance. Extensive martensite decomposition providing a uniform, fine lamellar α + β microstructure is obtained along the building direction. Moreover, structural evidence of the formation of the intermetallic α2-Ti3Al phase is provided. Variations in the lattice parameter of β serve as an indicator of the microstructural degree of stabilization. Interconnected 3D networks of β are generated in regions highly affected by the intensified intrinsic heat treatment applied. The results obtained reflect a contribution towards simultaneous selective laser melting-manufacturing and heat treatment for fabrication of Ti-6Al-4V parts. PMID:28772630
Vaccine provision: Delivering sustained & widespread use.
Preiss, Scott; Garçon, Nathalie; Cunningham, Anthony L; Strugnell, Richard; Friedland, Leonard R
2016-12-20
The administration of a vaccine to a recipient is the final step in a development and production process that may have begun several decades earlier. Here we describe the scale and complexity of the processes that brings a candidate vaccine through clinical development to the recipient. These challenges include ensuring vaccine quality (between 100 and 500 different Quality Control tests are performed during production to continually assess safety, potency and purity); making decisions about optimal vaccine presentation (pre-filled syringes versus multi-dose vials) that affect capacity and supply; and the importance of maintaining the vaccine cold chain (most vaccines have stringent storage temperature requirements necessary to maintain activity and potency). The ultimate aim is to make sure that an immunogenic product matching the required specifications reaches the recipient. The process from concept to licensure takes 10-30years. Vaccine licensure is based on a file submitted to regulatory agencies which contains the comprehensive compilation of chemistry, manufacturing information, assay procedures, preclinical and clinical trial results, and proposals for post-licensure effectiveness and safety data collection. Expedited development and licensure pathways may be sought in emergency settings: e.g., the 2009 H1N1 influenza pandemic, the 2014 West African Ebola outbreak and meningococcal serogroup B meningitis outbreaks in the United States and New Zealand. Vaccines vary in the complexity of their manufacturing process. Influenza vaccines are particularly challenging to produce and delays in manufacturing may occur, leading to vaccine shortages during the influenza season. Shortages can be difficult to resolve due to long manufacturing lead times and stringent, but variable, local regulations. New technologies are driving the development of new vaccines with simplified manufacturing requirements and with quality specifications that can be confirmed with fewer tests. These technologies could have far-reaching effects on supply, cost of goods, and on response timing to a medical need until product availability. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
ASRM process development in aqueous cleaning
NASA Technical Reports Server (NTRS)
Swisher, Bill
1992-01-01
Viewgraphs are included on process development in aqueous cleaning which is taking place at the Aerojet Advanced Solid Rocket Motor (ASRM) Division under a NASA Marshall Space and Flight Center contract for design, development, test, and evaluation of the ASRM including new production facilities. The ASRM will utilize aqueous cleaning in several manufacturing process steps to clean case segments, nozzle metal components, and igniter closures. ASRM manufacturing process development is underway, including agent selection, agent characterization, subscale process optimization, bonding verification, and scale-up validation. Process parameters are currently being tested for optimization utilizing a Taguci Matrix, including agent concentration, cleaning solution temperature, agitation and immersion time, rinse water amount and temperature, and use/non-use of drying air. Based on results of process development testing to date, several observations are offered: aqueous cleaning appears effective for steels and SermeTel-coated metals in ASRM processing; aqueous cleaning agents may stain and/or attack bare aluminum metals to various extents; aqueous cleaning appears unsuitable for thermal sprayed aluminum-coated steel; aqueous cleaning appears to adequately remove a wide range of contaminants from flat metal surfaces, but supplementary assistance may be needed to remove clumps of tenacious contaminants embedded in holes, etc.; and hot rinse water appears to be beneficial to aid in drying of bare steel and retarding oxidation rate.
Fully-Enclosed Ceramic Micro-burners Using Fugitive Phase and Powder-based Processing
NASA Astrophysics Data System (ADS)
Do, Truong; Shin, Changseop; Kwon, Patrick; Yeom, Junghoon
2016-08-01
Ceramic-based microchemical systems (μCSs) are more suitable for operation under harsh environments such as high temperature and corrosive reactants compared to the more conventional μCS materials such as silicon and polymers. With the recent renewed interests in chemical manufacturing and process intensification, simple, inexpensive, and reliable ceramic manufacturing technologies are needed. The main objective of this paper is to introduce a new powder-based fabrication framework, which is a one-pot, cost-effective, and versatile process for ceramic μCS components. The proposed approach employs the compaction of metal-oxide sub-micron powders with a graphite fugitive phase that is burned out to create internal cavities and microchannels before full sintering. Pure alumina powder has been used without any binder phase, enabling more precise dimensional control and less structure shrinkage upon sintering. The key process steps such as powder compaction, graphite burnout during partial sintering, machining in a conventional machine tool, and final densification have been studied to characterize the process. This near-full density ceramic structure with the combustion chamber and various internal channels was fabricated to be used as a micro-burner for gas sensing applications.
Fully-Enclosed Ceramic Micro-burners Using Fugitive Phase and Powder-based Processing
Do, Truong; Shin, Changseop; Kwon, Patrick; Yeom, Junghoon
2016-01-01
Ceramic-based microchemical systems (μCSs) are more suitable for operation under harsh environments such as high temperature and corrosive reactants compared to the more conventional μCS materials such as silicon and polymers. With the recent renewed interests in chemical manufacturing and process intensification, simple, inexpensive, and reliable ceramic manufacturing technologies are needed. The main objective of this paper is to introduce a new powder-based fabrication framework, which is a one-pot, cost-effective, and versatile process for ceramic μCS components. The proposed approach employs the compaction of metal-oxide sub-micron powders with a graphite fugitive phase that is burned out to create internal cavities and microchannels before full sintering. Pure alumina powder has been used without any binder phase, enabling more precise dimensional control and less structure shrinkage upon sintering. The key process steps such as powder compaction, graphite burnout during partial sintering, machining in a conventional machine tool, and final densification have been studied to characterize the process. This near-full density ceramic structure with the combustion chamber and various internal channels was fabricated to be used as a micro-burner for gas sensing applications. PMID:27546059
Baronsky-Probst, J; Möltgen, C-V; Kessler, W; Kessler, R W
2016-05-25
Hot melt extrusion (HME) is a well-known process within the plastic and food industries that has been utilized for the past several decades and is increasingly accepted by the pharmaceutical industry for continuous manufacturing. For tamper-resistant formulations of e.g. opioids, HME is the most efficient production technique. The focus of this study is thus to evaluate the manufacturability of the HME process for tamper-resistant formulations. Parameters such as the specific mechanical energy (SME), as well as the melt pressure and its standard deviation, are important and will be discussed in this study. In the first step, the existing process data are analyzed by means of multivariate data analysis. Key critical process parameters such as feed rate, screw speed, and the concentration of the API in the polymers are identified, and critical quality parameters of the tablet are defined. In the second step, a relationship between the critical material, product and process quality attributes are established by means of Design of Experiments (DoEs). The resulting SME and the temperature at the die are essential data points needed to indirectly qualify the degradation of the API, which should be minimal. NIR-spectroscopy is used to monitor the material during the extrusion process. In contrast to most applications in which the probe is directly integrated into the die, the optical sensor is integrated into the cooling line of the strands. This saves costs in the probe design and maintenance and increases the robustness of the chemometric models. Finally, a process measurement system is installed to monitor and control all of the critical attributes in real-time by means of first principles, DoE models, soft sensor models, and spectroscopic information. Overall, the process is very robust as long as the screw speed is kept low. Copyright © 2015 Elsevier B.V. All rights reserved.
Efficient 'Optical Furnace': A Cheaper Way to Make Solar Cells is Reaching the Marketplace
DOE Office of Scientific and Technical Information (OSTI.GOV)
von Kuegelgen, T.
In Bhushan Sopori's laboratory, you'll find a series of optical furnaces he has developed for fabricating solar cells. When not in use, they sit there discreetly among the lab equipment. But when a solar silicon wafer is placed inside one for processing, Sopori walks over to a computer and types in a temperature profile. Almost immediately this fires up the furnace, which glows inside and selectively heats up the silicon wafer to 800 degrees centigrade by the intense light it produces. Sopori, a principal engineer at the National Renewable Energy Laboratory, has been researching and developing optical furnace technology formore » around 20 years. He says it's a challenging technology to develop because there are many issues to consider when you process a solar cell, especially in optics. Despite the challenges, Sopori and his research team have advanced the technology to the point where it will benefit all solar cell manufacturers. They are now developing a commercial version of the furnace in partnership with a manufacturer. 'This advanced optical furnace is highly energy efficient, and it can be used to manufacture any type of solar cell,' he says. Each type of solar cell or manufacturing process typically requires a different furnace configuration and temperature profile. With NREL's new optical furnace system, a solar cell manufacturer can ask the computer for any temperature profile needed for processing a solar cell, and the same type of furnace is suitable for several solar cell fabrication process steps. 'In the future, solar cell manufacturers will only need this one optical furnace because it can be used for any process, including diffusion, metallization and oxidation,' Sopori says. 'This helps reduce manufacturing costs.' One startup company, Applied Optical Systems, has recognized the furnace's potential for manufacturing thin-film silicon cells. 'We'd like to develop thin-film silicon cells with higher efficiencies, up to 15 to 18 percent, and we believe this furnace will enable us to do so,' says A. Rangappan, founder and CEO of Applied Optical Systems. Rangappan also says it will take only a few minutes for the optical furnace to process a thin-film solar cell, which reduces manufacturing costs. Overall, he estimates the company's solar cell will cost around 80 cents per watt. For manufacturing these thin-film silicon cells, Applied Optical Systems and NREL have developed a partnership through a cooperative research and development agreement (CRADA) to construct an optical furnace system prototype. DOE is providing $500,000 from its Technology Commercialization Development Fund to help offset the prototype's development costs because of the technology's significant market potential. The program has provided the NREL technology transfer office with a total of $4 million to expand such collaborative efforts between NREL researchers and companies. Applied Optical will construct a small version of the optical furnace based on the prototype design in NREL's process development and integration laboratory through a separate CRADA. This small furnace will only develop one solar cell wafer at a time. Then, the company will construct a large, commercial-scale optical furnace at its own facilities, which will turn out around 1,000 solar cell wafers per hour. 'We hope to start using the optical furnace for manufacturing within four to five years,' Rangappan says. Meanwhile, another partnership using the optical furnace has evolved between NREL and SiXtron Advanced Materials, another startup. Together they'll use the optical furnace to optimize the metallization process for novel antireflective solar cell coatings. The process is not only expected to yield higher efficiencies for silicon-based solar cells, but also lowers processing costs and eliminates safety concerns for manufacturers. Most solar cell manufacturers currently use a plasma-enhanced chemical vapor deposition (PECVD) system with compressed and extremely pyrophoric silane gas (SiH4) for applying passivation antireflective coatings (ARC). If silane is exposed to air, the SiH4 will explode - a serious safety issue for high-volume manufacturers. SiXtron's process uses a solid, silicon-based polymer that's converted into noncompressed, nonexplosive gas, which then flows to a standard PECVD system. 'The solid source is so safe to handle that it can be shipped by FedEx,' says Zbigniew Barwicz, president and CEO of SiXtron. Barwicz says manufacturers can use the same PECVD processing equipment for the SiXtron process that they already use for SiH4, a plug-and-play solution. For this novel passivation ARC process, NREL is helping to optimize the metallization parameters. NREL has developed a new technology called optical processing. One of the applications of this process is fire-through contact formation of silicon solar cells.« less
Automated packaging platform for low-cost high-performance optical components manufacturing
NASA Astrophysics Data System (ADS)
Ku, Robert T.
2004-05-01
Delivering high performance integrated optical components at low cost is critical to the continuing recovery and growth of the optical communications industry. In today's market, network equipment vendors need to provide their customers with new solutions that reduce operating expenses and enable new revenue generating IP services. They must depend on the availability of highly integrated optical modules exhibiting high performance, small package size, low power consumption, and most importantly, low cost. The cost of typical optical system hardware is dominated by linecards that are in turn cost-dominated by transmitters and receivers or transceivers and transponders. Cost effective packaging of optical components in these small size modules is becoming the biggest challenge to be addressed. For many traditional component suppliers in our industry, the combination of small size, high performance, and low cost appears to be in conflict and not feasible with conventional product design concepts and labor intensive manual assembly and test. With the advent of photonic integration, there are a variety of materials, optics, substrates, active/passive devices, and mechanical/RF piece parts to manage in manufacturing to achieve high performance at low cost. The use of automation has been demonstrated to surpass manual operation in cost (even with very low labor cost) as well as product uniformity and quality. In this paper, we will discuss the value of using an automated packaging platform.for the assembly and test of high performance active components, such as 2.5Gb/s and 10 Gb/s sources and receivers. Low cost, high performance manufacturing can best be achieved by leveraging a flexible packaging platform to address a multitude of laser and detector devices, integration of electronics and handle various package bodies and fiber configurations. This paper describes the operation and results of working robotic assemblers in the manufacture of a Laser Optical Subassembly (LOS), its subsequent automated testing and burn/in process; and the placement of the LOS into a package body and hermetically sealing the package. The LOS and Package automated assembler robots have achieved a metrics of less than 1 um accuracy and 0.1 um resolution. The paper also discusses a method for the critical alignment of a single-mode fiber as the last step of the manufacturing process. This approach is in contrast to the conventional manual assembly where sub-micron fiber alignment and fixation steps are performed much earlier during the assembly process. Finally the paper discusses the value of this automated platform manufacturing approach as a key enabler for low cost small form factor optical components for the new XFP MSA class of transceiver modules.
NASA Astrophysics Data System (ADS)
Weber, C.; Pohl, S.; Poertner, R.; Pino-Grace, Pablo; Freimark, D.; Wallrapp, C.; Geigle, P.; Czermak, P.
Cell based therapy promises the treatment of many diseases like diabetes mellitus, Parkinson disease or stroke. Microencapsulation of the cells protects them against host-vs-graft reactions and thus enables the usage of allogenic cell lines for the manufacturing of cell therapeutic implants. The production process of such implants consists mainly of the three steps expansion of the cells, encapsulation of the cells, and cultivation of the encapsulated cells in order to increase their vitality and thus quality. This chapter deals with the development of fixed-bed bioreactor-based cultivation procedures used in the first and third step of production. The bioreactor system for the expansion of the stem cell line (hMSC-TERT) is based on non-porous glass spheres, which support cell growth and harvesting with high yield and vitality. The cultivation process for the spherical cell based implants leads to an increase of vitality and additionally enables the application of a medium-based differentiation protocol.
NASA Technical Reports Server (NTRS)
Wolf, M.
1979-01-01
To facilitate the task of objectively comparing competing process options, a methodology was needed for the quantitative evaluation of their relative cost effectiveness. Such a methodology was developed and is described, together with three examples for its application. The criterion for the evaluation is the cost of the energy produced by the system. The method permits the evaluation of competing design options for subsystems, based on the differences in cost and efficiency of the subsystems, assuming comparable reliability and service life, or of competing manufacturing process options for such subsystems, which include solar cells or modules. This process option analysis is based on differences in cost, yield, and conversion efficiency contribution of the process steps considered.
Folgueiras-Amador, Ana A; Philipps, Kai; Guilbaud, Sébastien; Poelakker, Jarno; Wirth, Thomas
2017-11-27
Flow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to produce isoindolinones. The combination with inline mass spectrometry facilitates a much easier combination of chemical steps in a single flow process. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
An evolutionary sensor approach for self-organizing production chains
NASA Astrophysics Data System (ADS)
Mocan, M.; Gillich, E. V.; Mituletu, I. C.; Korka, Z. I.
2018-01-01
Industry 4.0 is the actual great step in industrial progress. Convergence of industrial equipment with the power of advanced computing and analysis, low-cost sensing, and new connecting technologies are presumed to bring unexpected advancements in automation, flexibility, and efficiency. In this context, sensors ensure information regarding three essential areas: the number of processed elements, the quality of production and the condition of tools and equipment. To obtain this valuable information, the data resulted from a sensor has to be firstly processed and afterward used by the different stakeholders. If machines are linked together, this information can be employed to organize the production chain with few or without human intervention. We describe here the implementation of a sensor in a milling machine that is part of a simple production chain, capable of providing information regarding the number of manufactured pieces. It is used by the other machines in the production chain, in order to define the type and number of pieces to be manufactured by them and/or to set optimal parameters for their working regime. Secondly, the information achieved by monitoring the machine and manufactured piece dynamic behavior is used to evaluate the product quality. This information is used to warn about the need of maintenance, being transmitted to the specialized department. It is also transmitted to the central unit, in order to reorganize the production by involving other machines or by reconsidering the manufacturing regime of the existing machines. A special attention is drawn on analyzing and classifying the signals acquired via optical sensor from simulated processes.
Construction of an automated fiber pigtailing machine
DOE Office of Scientific and Technical Information (OSTI.GOV)
Strand, O.T.
1996-01-01
At present, the high cost of optoelectronic (OE) devices is caused in part by the labor-intensive processes involved with packaging. Automating the packaging processes should result in a significant cost reduction. One of the most labor-intensive steps is aligning and attaching the fiber to the OE device, the so-called pigtailing process. Therefore, the goal of this 2-year ARPA-funded project is to design and build 3 low-cost machines to perform sub-micron alignments and attachments of single-mode fibers to different OE devices. These Automated Fiber Pigtailing Machines (AFPMS) are intended to be compatible with a manufacturing environment and have a modular designmore » for standardization of parts and machine vision for maximum flexibility. This work is a collaboration among Uniphase Telecommunications Products (formerly United Technologies Photonics, UTP), Ortel, Newport/Klinger, the Massachusetts Institute of Technology Manufacturing Institute (MIT), and Lawrence Livermore National Laboratory (LLNL). UTP and Ortel are the industrial partners for whom two of the AFPMs are being built. MIT and LLNL make up the design and assembly team of the project, while Newport/Klinger is a potential manufacturer of the AFPM and provides guidance to ensure that the design of the AFPM is marketable and compatible with a manufacturing environment. The AFPM for UTP will pigtail LiNbO{sub 3} waveguide devices and the AFPM for Ortel will pigtail photodiodes. Both of these machines will contain proprietary information, so the third AFPM, to reside at LLNL, will pigtail a non-proprietary waveguide device for demonstrations to US industry.« less
Pre-Finishing of SiC for Optical Applications
NASA Technical Reports Server (NTRS)
Rozzi, Jay; Clavier, Odile; Gagne, John
2011-01-01
13 Manufacturing & Prototyping A method is based on two unique processing steps that are both based on deterministic machining processes using a single-point diamond turning (SPDT) machine. In the first step, a high-MRR (material removal rate) process is used to machine the part within several microns of the final geometry. In the second step, a low-MRR process is used to machine the part to near optical quality using a novel ductile regime machining (DRM) process. DRM is a deterministic machining process associated with conditions under high hydrostatic pressures and very small depths of cut. Under such conditions, using high negative-rake angle cutting tools, the high-pressure region near the tool corresponds to a plastic zone, where even a brittle material will behave in a ductile manner. In the high-MRR processing step, the objective is to remove material with a sufficiently high rate such that the process is economical, without inducing large-scale subsurface damage. A laser-assisted machining approach was evaluated whereby a CO2 laser was focused in advance of the cutting tool. While CVD (chemical vapor deposition) SiC was successfully machined with this approach, the cutting forces were substantially higher than cuts at room temperature under the same machining conditions. During the experiments, the expansion of the part and the tool due to the heating was carefully accounted for. The higher cutting forces are most likely due to a small reduction in the shear strength of the material compared with a larger increase in friction forces due to the thermal softening effect. The key advantage is that the hybrid machine approach has the potential to achieve optical quality without the need for a separate optical finishing step. Also, this method is scalable, so one can easily progress from machining 50-mm-diameter samples to the 250-mm-diameter mirror that NASA desires.
Assessment of molecular contamination in mask pod
NASA Astrophysics Data System (ADS)
Foray, Jean Marie; Dejaune, Patrice; Sergent, Pierre; Gough, Stuart; Cheung, D.; Davenet, Magali; Favre, Arnaud; Rude, C.; Trautmann, T.; Tissier, Michel; Fontaine, H.; Veillerot, M.; Avary, K.; Hollein, I.; Lerit, R.
2008-04-01
Context/ study Motivation: Contamination and especially Airbone Molecular Contamination (AMC) is a critical issue for mask material flow with a severe and fairly unpredictable risk of induced contamination and damages especially for 193 nm lithography. It is therefore essential to measure, to understand and then try to reduce AMC in mask environment. Mask material flow was studied in a global approach by a pool of European partners, especially within the frame of European MEDEA+ project, so called "MUSCLE". This paper deals with results and assessment of mask pod environment in term of molecular contamination in a first step, then in a second step preliminary studies to reduce mask pod influence and contamination due to material out gassing. Approach and techniques: A specific assessment of environmental / molecular contamination along the supply chain was performed by all partners. After previous work presented at EMLC 07, further studies were performed on real time contamination measurement pod at different sites locations (including Mask manufacturing site, blank manufacturing sites, IC fab). Studies were linked to the main critical issues: cleaning, storage, handling, materials and processes. Contamination measurement campaigns were carried out along the mask supply chain using specific Adixen analyzer in order to monitor in real time organic contaminants (ppb level) in mask pods. Key results would be presented: VOC, AMC and humidity level on different kinds of mask carriers, impact of basic cleaning on pod outgassing measurement (VOC, NH3), and process influence on pod contamination... In a second step, preliminary specific pod conditioning studies for better pod environment were performed based on Adixen vacuum process. Process influence had been experimentally measured in term of molecular outgassing from mask pods. Different AMC experimental characterization methods had been carried out leading to results on a wide range of organic and inorganic contaminants: by inline techniques based on Adixen humidity, also VOC and organic sensors, together by off-line techniques already used in the extensive previous mask pods benchmark (TD-GCMS & Ionic Chromatography). Humidity and VOC levels from mask carriers had shown significant reduction after Adixen pod conditioning process. Focus had been made on optimized vacuum step (for AMC) after particles carrier cleaning cycle. Based upon these key results new procedures, as well as guidelines for mask carrier cleaning optimization are proposed to improve pod contamination control. Summary results/next steps: This paper reports molecular contamination measurement campaigns performed by a pool of European partners along the mask supply chain. It allows us to investigate, identify and quantify critical molecular contamination in mask pod, as well as VOC and humidity, issues depending on locations, uses, and carrier's type. Preliminary studies highlight initial process solutions for pods conditioning that are being used for short term industrialization and further industrialized.
Materials Processing and Manufacturing Technologies for Diamond Substrates Multichip Modules
1994-10-14
document are those of the authors and should not be intepreted as representing the official policies, either express or implied, of the Defense Advanced...release of the diamond at the end of the deposition step, "* deposition of non-uniform films for stress/flatness control. 75kW Reactor & Modelling Studies...too strong (the film releases partially or not at all) to too weak (the film delaminates during the run from growth stresses), and are continuing to
Advanced manufacturing rules check (MRC) for fully automated assessment of complex reticle designs
NASA Astrophysics Data System (ADS)
Gladhill, R.; Aguilar, D.; Buck, P. D.; Dawkins, D.; Nolke, S.; Riddick, J.; Straub, J. A.
2005-11-01
Advanced electronic design automation (EDA) tools, with their simulation, modeling, design rule checking, and optical proximity correction capabilities, have facilitated the improvement of first pass wafer yields. While the data produced by these tools may have been processed for optimal wafer manufacturing, it is possible for the same data to be far from ideal for photomask manufacturing, particularly at lithography and inspection stages, resulting in production delays and increased costs. The same EDA tools used to produce the data can be used to detect potential problems for photomask manufacturing in the data. A production implementation of automated photomask manufacturing rule checking (MRC) is presented and discussed for various photomask lithography and inspection lines. This paper will focus on identifying data which may cause production delays at the mask inspection stage. It will be shown how photomask MRC can be used to discover data related problems prior to inspection, separating jobs which are likely to have problems at inspection from those which are not. Photomask MRC can also be used to identify geometries requiring adjustment of inspection parameters for optimal inspection, and to assist with any special handling or change of routing requirements. With this foreknowledge, steps can be taken to avoid production delays that increase manufacturing costs. Finally, the data flow implemented for MRC can be used as a platform for other photomask data preparation tasks.
NASA Astrophysics Data System (ADS)
Tabassum, Shafia; Murtaza, Ahmar; Ali, Hasan; Uddin, Zia Mohy; Zehra, Syedah Sadaf
2017-10-01
For rapid osseointegration of dental implant fixtures, various surface treatments including plasma spraying, hydroxyapatite coating, acid-etching, and surface grooving are used. However undesirable effects such as chemical modifications, loss of mechanical properties, prolonged processing times and post production treatment steps are often associated with these techniques. The osseointegration rate of the dental implants can be promoted by increasing the surface area of the dental implant, thus increasing the bone cells - implant material contact and allow bone tissues to grow rapidly. Additive Manufacturing (AM) techniques can be used to fabricate dental implant fixtures with desirable surface area in a single step manufacturing process. AM allows the use of Computer Aided Designing (CAD) for customised rapid prototyping of components with precise control over geometry. In this study, the dental implant fixture that replaces the tooth root was designed on commercially available software COMSOL. Nickel - titanium alloy was selected as build materials for dental implant. The geometry of the dental fixture was varied by changing the interspacing distance (thread pitch) and number of threads to increase the total surface area. Three different microstructures were introduced on the surface of dental implant. The designed models were used to examine the effect of changing geometries on the total surface area. Finite Element Analysis (FEA) was performed to investigate the effect of changing geometries on the mechanical properties of the dental implant fixtures using stress analysis.
Manufacturing Solid Dosage Forms from Bulk Liquids Using the Fluid-bed Drying Technology.
Qi, Jianping; Lu, Y I; Wu, Wei
2015-01-01
Solid dosage forms are better than liquid dosage forms in many ways, such as improved physical and chemical stability, ease of storage and transportation, improved handling properties, and patient compliance. Therefore, it is required to transform dosage forms of liquid origins into solid dosage forms. The functional approaches are to absorb the liquids by solid excipients or through drying. The conventional drying technologies for this purpose include drying by heating, vacuum-, freeze- and spray-drying, etc. Among these drying technologies, fluidbed drying emerges as a new technology that possesses unique advantages. Fluid-bed drying or coating is highly efficient in solvent removal, can be performed at relatively low temperatures, and is a one-step process to manufacture formulations in pellet forms. In this article, the status of the art of manufacturing solid dosage forms from bulk liquids by fluid-bed drying technology was reviewed emphasizing on its application in solid dispersion, inclusion complexes, self-microemulsifying systems, and various nanoscale drug delivery systems.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gesta, E.; Intelligent Insect Control, 118 Chemin des Alouettes, Castelnau-le-Lez, 34170; Skovmand, O., E-mail: osk@insectcontrol.net
The purpose of this study is to understand the influence of the yarn processing on the migration of additives molecules, especially insecticide, within polyethylene (PE) yarns. Yarns were manufactured in the laboratory focusing on three key-steps (spinning, post-stretching and heat-setting). Influence of each step on yarn properties was investigated using tensile tests, differential scanning calorimetry and wide-angle X-ray diffraction. The post-stretching step was proved to be critical in defining yarn mechanical and structural properties. Although a first orientation of polyethylene crystals was induced during spinning, the optimal orientation was only reached by post-stretching. The results also showed that the heat-settingmore » did not significantly change these properties. The presence of additives crystals at the yarn surface was evidenced by scanning-electron microscopy. These studies performed at each yarn production step allowed a detailed analysis of the additives’ ability to migrate. It is concluded that while post-stretching decreased the migration rate, heat-setting seems to boost this migration.« less
Sheraba, Norhan S; Diab, Mohamed R; Yassin, Aymen S; Amin, Magdy A; Zedan, Hamdallah H
2015-01-01
Snake bites represent a serious public health problem, particularly in rural areas worldwide. Antitoxic sera preparations are antibodies from immunized animals and are considered to be the only treatment option. The purification of antivenom antibodies should aim at obtaining products of consistent quality, safety, efficacy, and adherence to good manufacturing practice principles. Endotoxins are an integral component of the outer cell surface of Gram-negative bacteria. They are common contaminates of the raw materials and processing equipment used in the manufacturing of antivenoms. In this work, and as a part of quality control testing, we establish and examine an environmental monitoring program for identification of potential sources of endotoxin-producing Gram-negative bacteria throughout the whole steps of antivenom preparation. In addition, we follow all the steps of preparation starting from crude plasma till finished product using a validated sterility and endotoxin testing.Samples from air, surface, and personnel were collected and examined through various stages of manufacturing for the potential presence of Gram-negative bacteria. A validated sterility and endotoxin test was carried out in parallel at the different production steps. The results showed that air contributed to the majority of bacterial isolates detected (48.43%), followed by surfaces (37.5%) and then personnel (14%). The most common bacterial isolates detected were Achromobacter xylosoxidans, Ochrobactrum anthropi, and Pseudomonas aeruginosa, which together with Burkholderia cepacia were both also detected in cleaning water and certain equipment parts. A heavy bacterial growth with no fungal contamination was observed in all stages of antivenom manufacturing excluding the formulation stage. All samples were positive for endotoxin including the finished product.Implementation and continued evaluation of quality assurance and quality improvement programs in aseptic preparation is essential in ensuring the safety and quality of these products. Antitoxic sera preparations are the only treatment option for snake bites worldwide. They are prepared by immunizing animals, usually horses, with snake venom and collecting horse plasma, which is then subjected to several purification steps in order to finally prepare the purified immunoglobulins. Components of the bacterial cell wall known as endotoxins can constitute a potential hazardous contamination known as pyrogen in antisera, which can lead to fever and many other adverse reactions to the person subjected to it.In this work, we monitored the environment associated with the different steps of production and purification of snake antivenom prepared from immunized horses. We examined the air quality, surface, and personnel for possible sources of contamination, particularly the presence of Gram-negative bacteria, which is the major source of endotoxin presence. We also monitored all stages of preparation by sterility and endotoxin testing. Our results showed that air contributed to the majority of bacterial isolates. Sterility testing revealed the presence of bacterial contamination in all the intermediate steps, as only the final preparation after filtration was sterile. Endotoxin was present in all tested samples and the final product. Good manufacturing practice procedures are essential in any facility involved in antisera production. © PDA, Inc. 2015.
A quality by design study applied to an industrial pharmaceutical fluid bed granulation.
Lourenço, Vera; Lochmann, Dirk; Reich, Gabriele; Menezes, José C; Herdling, Thorsten; Schewitz, Jens
2012-06-01
The pharmaceutical industry is encouraged within Quality by Design (QbD) to apply science-based manufacturing principles to assure quality not only of new but also of existing processes. This paper presents how QbD principles can be applied to an existing industrial pharmaceutical fluid bed granulation (FBG) process. A three-step approach is presented as follows: (1) implementation of Process Analytical Technology (PAT) monitoring tools at the industrial scale process, combined with multivariate data analysis (MVDA) of process and PAT data to increase the process knowledge; (2) execution of scaled-down designed experiments at a pilot scale, with adequate PAT monitoring tools, to investigate the process response to intended changes in Critical Process Parameters (CPPs); and finally (3) the definition of a process Design Space (DS) linking CPPs to Critical to Quality Attributes (CQAs), within which product quality is ensured by design, and after scale-up enabling its use at the industrial process scale. The proposed approach was developed for an existing industrial process. Through enhanced process knowledge established a significant reduction in product CQAs, variability already within quality specifications ranges was achieved by a better choice of CPPs values. The results of such step-wise development and implementation are described. Copyright © 2012 Elsevier B.V. All rights reserved.
Method of manufacturing large dish reflectors for a solar concentrator apparatus
Angel, Roger P [Tucson, AZ; Olbert, Blain H [Tucson, AZ
2011-12-27
A method of manufacturing monolithic glass reflectors for concentrating sunlight in a solar energy system is disclosed. The method of manufacturing allows large monolithic glass reflectors to be made from float glass in order to realize significant cost savings on the total system cost for a solar energy system. The method of manufacture includes steps of heating a sheet of float glass positioned over a concave mold until the sheet of glass sags and stretches to conform to the shape of the mold. The edges of the dish-shaped glass are rolled for structural stiffening around the periphery. The dish-shaped glass is then silvered to create a dish-shaped mirror that reflects solar radiation to a focus. The surface of the mold that contacts the float glass preferably has a grooved surface profile comprising a plurality of cusps and concave valleys. This grooved profile minimizes the contact area and marring of the specular glass surface, reduces parasitic heat transfer into the mold and increases mold lifetime. The disclosed method of manufacture is capable of high production rates sufficiently fast to accommodate the output of a conventional float glass production line so that monolithic glass reflectors can be produced as quickly as a float glass production can make sheets of float glass to be used in the process.
Development and test of combustion chamber for Stirling engine heated by natural gas
NASA Astrophysics Data System (ADS)
Li, Tie; Song, Xiange; Gui, Xiaohong; Tang, Dawei; Li, Zhigang; Cao, Wenyu
2014-04-01
The combustion chamber is an important component for the Stirling engine heated by natural gas. In the paper, we develop a combustion chamber for the Stirling engine which aims to generate 3˜5 kWe electric power. The combustion chamber includes three main components: combustion module, heat exchange cavity and thermal head. Its feature is that the structure can divide "combustion" process and "heat transfer" process into two apparent individual steps and make them happen one by one. Since natural gas can mix with air fully before burning, the combustion process can be easily completed without the second wind. The flame can avoid contacting the thermal head of Stirling engine, and the temperature fields can be easily controlled. The designed combustion chamber is manufactured and its performance is tested by an experiment which includes two steps. The experimental result of the first step proves that the mixture of air and natural gas can be easily ignited and the flame burns stably. In the second step of experiment, the combustion heat flux can reach 20 kW, and the energy utilization efficiency of thermal head has exceeded 0.5. These test results show that the thermal performance of combustion chamber has reached the design goal. The designed combustion chamber can be applied to a real Stirling engine heated by natural gas which is to generate 3˜5 kWe electric power.
Challenges and opportunities in the manufacture and expansion of cells for therapy.
Maartens, Joachim H; De-Juan-Pardo, Elena; Wunner, Felix M; Simula, Antonio; Voelcker, Nicolas H; Barry, Simon C; Hutmacher, Dietmar W
2017-10-01
Laboratory-based ex vivo cell culture methods are largely manual in their manufacturing processes. This makes it extremely difficult to meet regulatory requirements for process validation, quality control and reproducibility. Cell culture concepts with a translational focus need to embrace a more automated approach where cell yields are able to meet the quantitative production demands, the correct cell lineage and phenotype is readily confirmed and reagent usage has been optimized. Areas covered: This article discusses the obstacles inherent in classical laboratory-based methods, their concomitant impact on cost-of-goods and that a technology step change is required to facilitate translation from bed-to-bedside. Expert opinion: While traditional bioreactors have demonstrated limited success where adherent cells are used in combination with microcarriers, further process optimization will be required to find solutions for commercial-scale therapies. New cell culture technologies based on 3D-printed cell culture lattices with favourable surface to volume ratios have the potential to change the paradigm in industry. An integrated Quality-by-Design /System engineering approach will be essential to facilitate the scaled-up translation from proof-of-principle to clinical validation.
Stent manufacturing using cobalt chromium molybdenum (CoCrMo) by selective laser melting technology
NASA Astrophysics Data System (ADS)
Omar, Mohd Asnawi; Baharudin, BT-HT; Sulaiman, S.
2017-12-01
This paper reviews the capabilities of additive manufacturing (AM) technology and the use of Cobalt super alloy stent fabrication by looking at the dimensional accuracy and mechanical properties of the stent. Current conventional process exhibit many processes which affect the supply chain, costing, and post processing. By alternatively switching to AM, the step of production can be minimized and thus customization of stent can be carried out according to patients need. The proposed methodology is a perfect choice as surgeons need to have an accurate size during stent implantation. It also is able to reduce time-to-market delivery in a matter of hours and from days. The suggested stent model was taken from the third party vendor and flow optimization was carried out using Materialise Magics TM software. By using SLM125TM printer, the printing parameters such as Energy Density (DE), Laser Power (PL), Scanning Speed (SS) and Hatching Distance (DH) was used to print the stent. The properties of the finished product, such as strength, surface finish and orientation was investigated.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Giraldi, M. R.; Francois, J. L.; Castro-Uriegas, D.
The purpose of this paper is to quantify the greenhouse gas (GHG) emissions associated to the hydrogen produced by the sulfur-iodine thermochemical process, coupled to a high temperature nuclear reactor, and to compare the results with other life cycle analysis (LCA) studies on hydrogen production technologies, both conventional and emerging. The LCA tool was used to quantify the impacts associated with climate change. The product system was defined by the following steps: (i) extraction and manufacturing of raw materials (upstream flows), (U) external energy supplied to the system, (iii) nuclear power plant, and (iv) hydrogen production plant. Particular attention wasmore » focused to those processes where there was limited information from literature about inventory data, as the TRISO fuel manufacture, and the production of iodine. The results show that the electric power, supplied to the hydrogen plant, is a sensitive parameter for GHG emissions. When the nuclear power plant supplied the electrical power, low GHG emissions were obtained. These results improve those reported by conventional hydrogen production methods, such as steam reforming. (authors)« less
Surface modification of acetaminophen particles by atomic layer deposition.
Kääriäinen, Tommi O; Kemell, Marianna; Vehkamäki, Marko; Kääriäinen, Marja-Leena; Correia, Alexandra; Santos, Hélder A; Bimbo, Luis M; Hirvonen, Jouni; Hoppu, Pekka; George, Steven M; Cameron, David C; Ritala, Mikko; Leskelä, Markku
2017-06-15
Active pharmaceutical ingredients (APIs) are predominantly organic solid powders. Due to their bulk properties many APIs require processing to improve pharmaceutical formulation and manufacturing in the preparation for various drug dosage forms. Improved powder flow and protection of the APIs are often anticipated characteristics in pharmaceutical manufacturing. In this work, we have modified acetaminophen particles with atomic layer deposition (ALD) by conformal nanometer scale coatings in a one-step coating process. According to the results, ALD, utilizing common chemistries for Al 2 O 3 , TiO 2 and ZnO, is shown to be a promising coating method for solid pharmaceutical powders. Acetaminophen does not undergo degradation during the ALD coating process and maintains its stable polymorphic structure. Acetaminophen with nanometer scale ALD coatings shows slowed drug release. ALD TiO 2 coated acetaminophen particles show cytocompatibility whereas those coated with thicker ZnO coatings exhibit the most cytotoxicity among the ALD materials under study when assessed in vitro by their effect on intestinal Caco-2 cells. Copyright © 2017 Elsevier B.V. All rights reserved.
Technology assessment of automation trends in the modular home industry
Phil Mitchell; Robert Russell Hurst
2009-01-01
This report provides an assessment of technology used in manufacturing modular homes in the United States, and that used in the German prefabricated wooden home industry. It is the first step toward identifying the research needs in automation and manufacturing methods that will facilitate mass customization in the home manufacturing industry. Within the United States...
Synchrotron x-ray microtomography of the interior microstructure of chocolate
NASA Astrophysics Data System (ADS)
Lügger, Svenja K.; Wilde, Fabian; Dülger, Nihan; Reinke, Lennart M.; Kozhar, Sergii; Beckmann, Felix; Greving, Imke; Vieira, Josélio; Heinrich, Stefan; Palzer, Stefan
2016-10-01
The structure of chocolate, a multicomponent food product, was analyzed using microtomography. Chocolate consists of a semi-solid cocoa butter matrix and a dense network of suspended particles. A detailed analysis of the microstructure is needed to understand mass transport phenomena. Transport of lipids from e.g. a filling or liquid cocoa butter is responsible for major problems in the confectionery industry such as formation of chocolate bloom, which is the formation of visible white spots or a grayish haze on the chocolate surface and leads to consumer rejections and thus large sales losses for the confectionery industry. In this study it was possible to visualize the inner structure of chocolate and clearly distinguish the particles from the continuous phase by taking advantage of the high density contrast of synchrotron radiation. Consequently, particle arrangement and cracks within the sample were made visible. The cracks are several micrometers thick and propagate throughout the entire sample. Images of pure cocoa butter, chocolate without any particles, did not show any cracks and thus confirmed that cracks are a result of embedded particles. They arise during the manufacturing process. Thus, the solidification process, a critical manufacturing step, was simulated with finite element methods in order to understand crack formation during this step. The simulation showed that cracks arise because of significant contraction of cocoa butter, the matrix phase, without any major change of volume of the suspended particles. Tempering of the chocolate mass prior to solidification is another critical step for a good product quality. We found that samples which solidified in an uncontrolled manner are less homogeneous than tempered samples. In summary, our study visualized for the first time the inner microstructure of tempered and untempered cocoa butter as well as chocolate without sample destruction and revealed cracks, which might act as transport pathways.
Badve, Mandar P; Gogate, Parag R; Pandit, Aniruddha B; Csoka, Levente
2014-01-01
The present work deals with application of hydrodynamic cavitation for intensification of delignification of wheat straw as an essential step in the paper manufacturing process. Wheat straw was first treated with potassium hydroxide (KOH) for 48 h and subsequently alkali treated wheat straw was subjected to hydrodynamic cavitation. Hydrodynamic cavitation reactor used in the work is basically a stator and rotor assembly, where the rotor is provided with indentations and cavitational events are expected to occur on the surface of rotor as well as within the indentations. It has been observed that treatment of alkali treated wheat straw in hydrodynamic cavitation reactor for 10-15 min increases the tensile index of the synthesized paper sheets to about 50-55%, which is sufficient for paper board manufacture. The final mechanical properties of the paper can be effectively managed by controlling the processing parameters as well as the cavitational parameters. It has also been established that hydrodynamic cavitation proves to be an effective method over other standard digestion techniques of delignification in terms of electrical energy requirements as well as the required time for processing. Overall, the work is first of its kind application of hydrodynamic cavitation for enhancing the effectiveness of delignification and presents novel results of significant interest to the paper and pulp industry opening an entirely new area of application of cavitational reactors. Copyright © 2013 Elsevier B.V. All rights reserved.
Guess, Adam J; Daneault, Beth; Wang, Rongzhang; Bradbury, Hillary; La Perle, Krista M D; Fitch, James; Hedrick, Sheri L; Hamelberg, Elizabeth; Astbury, Caroline; White, Peter; Overolt, Kathleen; Rangarajan, Hemalatha; Abu-Arja, Rolla; Devine, Steven M; Otsuru, Satoru; Dominici, Massimo; O'Donnell, Lynn; Horwitz, Edwin M
2017-10-01
Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body of data provides compelling evidence of the clinical safety of MSC therapy. However, generally accepted proof of therapeutic efficacy has not yet been reported. In an effort to generate a more effective therapeutic cell product, investigators are focused on modifying MSC processing protocols to enhance the intrinsic biologic activity. Here, we report a Good Manufacturing Practice-compliant two-step MSC manufacturing protocol to generate MSCs or interferon γ (IFNγ) primed MSCs which allows freshly expanded cells to be infused in patients on a predetermined schedule. This protocol eliminates the need to infuse cryopreserved, just thawed cells which may reduce the immune modulatory activity. Moreover, using (IFNγ) as a prototypic cytokine, we demonstrate the feasibility of priming the cells with any biologic agent. We then characterized MSCs and IFNγ primed MSCs prepared with our protocol, by karyotype, in vitro potential for malignant transformation, biodistribution, effect on engraftment of transplanted hematopoietic cells, and in vivo toxicity in immune deficient mice including a complete post-mortem examination. We found no evidence of toxicity attributable to the MSC or IFNγ primed MSCs. Our data suggest that the clinical risk of infusing MSCs or IFNγ primed MSCs produced by our two-step protocol is not greater than MSCs currently in practice. While actual proof of safety requires phase I clinical trials, our data support the use of either cell product in new clinical studies. Stem Cells Translational Medicine 2017;6:1868-1879. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
NASA Technical Reports Server (NTRS)
Cooper, Kenneth (Inventor); Chou, Yuag-Shan (Inventor)
2017-01-01
Systems and methods are provided for designing and fabricating contact-free support structures for overhang geometries of parts fabricated using electron beam additive manufacturing. One or more layers of un-melted metallic powder are disposed in an elongate gap between an upper horizontal surface of the support structure and a lower surface of the overhang geometry. The powder conducts heat from the overhang geometry to the support structure. The support structure acts as a heat sink to enhance heat transfer and reduce the temperature and severe thermal gradients due to poor thermal conductivity of metallic powders underneath the overhang. Because the support structure is not connected to the part, the support structure can be removed freely without any post-processing step.
Developing Induced Pluripotent Stem Cell-Based Therapy for the Masses.
Rao, Mahendra S; Atala, Anthony
2016-02-01
The discovery of induced pluripotent stem cells and the ability to manufacture them using clinically compliant protocols has the potential to revolutionize the field of regenerative medicine. However, realizing this potential requires the development of processes that are reliable, reproducible, and cost-effective and that at the same time do not compromise the safety of the individuals receiving this therapy. In the present report, we discuss how cost reductions can be obtained using our experience with obtaining approval of biologic agents, autologous therapy, and the recent approval of cord blood banks. Significance: For therapy to be widely available, the cost of manufacturing stem cells must be reduced. The steps proposed in the present report, when implemented, have the potential to reduce these costs significantly. ©AlphaMed Press.
Carbon fiber manufacturing via plasma technology
Paulauskas, Felix L.; Yarborough, Kenneth D.; Meek, Thomas T.
2002-01-01
The disclosed invention introduces a novel method of manufacturing carbon and/or graphite fibers that avoids the high costs associated with conventional carbonization processes. The method of the present invention avoids these costs by utilizing plasma technology in connection with electromagnetic radiation to produce carbon and/or graphite fibers from fully or partially stabilized carbon fiber precursors. In general, the stabilized or partially stabilized carbon fiber precursors are placed under slight tension, in an oxygen-free atmosphere, and carbonized using a plasma and electromagnetic radiation having a power input which is increased as the fibers become more carbonized and progress towards a final carbon or graphite product. In an additional step, the final carbon or graphite product may be surface treated with an oxygen-plasma treatment to enhance adhesion to matrix materials.
Converting baker's waste into alcohol. Revised final progress report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Halsey, R.; Wilson, P.B.
All types of baker's waste (including waste from candy manufacturers) can be converted into alcohol to be used as a fuel. All types of waste at any stage in process can be converted, such as: basic ingredients (including floor sweepings); dry mixes (including floor sweepings); dough at any stage; partially or fully cooked products; and day old returned products. The basic steps are the same, only the initial preparation will vary slightly. The variation will be: amount of water to be added and amount and type of nutrients (if any) to be added. The basic steps are: slurrying, liquefying tomore » put starch into liquid state, saccharifying to convert starch into fermentable sugars, fermentation to convert sugars into alcohol, and distillation to separate the alcohol from the mash. Each step is discussed in detail along with problems that may arise. Directions are given and materials (enzymes, yeast, etc.) and equipment are descibed briefly.« less
Low cost hydrogen/novel membrane technology for hydrogen separation from synthesis gas
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1986-02-01
To make the coal-to-hydrogen route economically attractive, improvements are being sought in each step of the process: coal gasification, water-carbon monoxide shift reaction, and hydrogen separation. This report addresses the use of membranes in the hydrogen separation step. The separation of hydrogen from synthesis gas is a major cost element in the manufacture of hydrogen from coal. Separation by membranes is an attractive, new, and still largely unexplored approach to the problem. Membrane processes are inherently simple and efficient and often have lower capital and operating costs than conventional processes. In this report current ad future trends in hydrogen productionmore » and use are first summarized. Methods of producing hydrogen from coal are then discussed, with particular emphasis on the Texaco entrained flow gasifier and on current methods of separating hydrogen from this gas stream. The potential for membrane separations in the process is then examined. In particular, the use of membranes for H{sub 2}/CO{sub 2}, H{sub 2}/CO, and H{sub 2}/N{sub 2} separations is discussed. 43 refs., 14 figs., 6 tabs.« less
NASA Astrophysics Data System (ADS)
Tong, J. B.; Lu, X.; Liu, C. C.; Wang, L. N.; Qu, X. H.
2015-03-01
High-Nb-containing TiAl alloys are a new generation of materials for high-temperature structural applications because of their superior high-temperature mechanical properties. The alloy powders can be widely used for additive manufacturing, thermal spraying, and powder metallurgy. Because of the difficulty of making microfine spherical alloy powders in quantity by conventional techniques, a compact method was proposed, which consisted of two-step ball milling of elemental powders and subsequent radio frequency (RF) argon plasma spheroidization. In comparison with conventional mechanical alloying techniques, the two-step milling process can be used to prepare alloy powders with uniform scale in a short milling time with no addition of process control agent. This makes the process effective and less contaminating. After RF argon plasma spheroidization, the powders produced exhibit good sphericity, and the number-average diameter is about 8.2 μm with a symmetric unimodal particle size distribution. The powders perform high composition homogeneity and contain predominately supersaturated α 2-Ti3Al phase. The oxygen and carbon contents of the spheroidized powder are 0.47% and 0.050%, respectively.
NASA Astrophysics Data System (ADS)
Vivek, Tiwary; Arunkumar, P.; Deshpande, A. S.; Vinayak, Malik; Kulkarni, R. M.; Asif, Angadi
2018-04-01
Conventional investment casting is one of the oldest and most economical manufacturing techniques to produce intricate and complex part geometries. However, investment casting is considered economical only if the volume of production is large. Design iterations and design optimisations in this technique proves to be very costly due to time and tooling cost for making dies for producing wax patterns. However, with the advent of Additive manufacturing technology, plastic patterns promise a very good potential to replace the wax patterns. This approach can be very useful for low volume production & lab requirements, since the cost and time required to incorporate the changes in the design is very low. This research paper discusses the steps involved for developing polymer nanocomposite filaments and checking its suitability for investment castings. The process parameters of the 3D printer machine are also optimized using the DOE technique to obtain mechanically stronger plastic patterns. The study is done to develop a framework for rapid investment casting for lab as well as industrial requirements.
Mass-manufacturable polymer microfluidic device for dual fiber optical trapping.
De Coster, Diane; Ottevaere, Heidi; Vervaeke, Michael; Van Erps, Jürgen; Callewaert, Manly; Wuytens, Pieter; Simpson, Stephen H; Hanna, Simon; De Malsche, Wim; Thienpont, Hugo
2015-11-30
We present a microfluidic chip in Polymethyl methacrylate (PMMA) for optical trapping of particles in an 80µm wide microchannel using two counterpropagating single-mode beams. The trapping fibers are separated from the sample fluid by 70µm thick polymer walls. We calculate the optical forces that act on particles flowing in the microchannel using wave optics in combination with non-sequential ray-tracing and further mathematical processing. Our results are compared with a theoretical model and the Mie theory. We use a novel fabrication process that consists of a premilling step and ultraprecision diamond tooling for the manufacturing of the molds and double-sided hot embossing for replication, resulting in a robust microfluidic chip for optical trapping. In a proof-of-concept demonstration, we show the trapping capabilities of the hot embossed chip by trapping spherical beads with a diameter of 6µm, 8µm and 10µm and use the power spectrum analysis of the trapped particle displacements to characterize the trap strength.
NASA Astrophysics Data System (ADS)
Zakaria, M.; Aminanda, Y.; Rashidi, S. A.; Mat Sah, M. A.
2018-04-01
The springback phenomena of CFRP after curing process through autoclave manufacturing method results on the out of tolerance for its utilisation in aerospace industry. This paper relates to the measurements of springback for Uni-directional flat laminate as a first steps to the springback study for the real aircraft composite laminate structures. A flat laminate with dimension of 300 mm x 300 mm, 400 mm x 400 mm and 500mm x 500 mm with different number of ply; 20, 24 and 28 are manufactured. The choice of dimension and number of lay-up corresponds to the dimension and lay-up of rib structure. After process, the springbacks are measured using 3D scanner (optical-based three-dimensional) with an accuracy of 42 micrometers to obtain an accurate measurement. The analysis of the effect of dimension and number of ply to the magnitude of springback are presented within the range of specimen studied in this work.
On-Demand Production of Flow-Reactor Cartridges by 3D Printing of Thermostable Enzymes.
Maier, Manfred; Radtke, Carsten P; Hubbuch, Jürgen; Niemeyer, Christof M; Rabe, Kersten S
2018-05-04
The compartmentalization of chemical reactions is an essential principle of life that provides a major source of innovation for the development of novel approaches in biocatalysis. To implement spatially controlled biotransformations, rapid manufacturing methods are needed for the production of biocatalysts that can be applied in flow systems. Whereas three-dimensional (3D) printing techniques offer high-throughput manufacturing capability, they are usually not compatible with the delicate nature of enzymes, which call for physiological processing parameters. We herein demonstrate the utility of thermostable enzymes in the generation of biocatalytic agarose-based inks for a simple temperature-controlled 3D printing process. As examples we utilized an esterase and an alcohol dehydrogenase from thermophilic organisms as well as a decarboxylase that was thermostabilized by directed protein evolution. We used the resulting 3D-printed parts for a continuous, two-step sequential biotransformation in a fluidic setup. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Failure Analysis Study and Long-Term Reliability of Optical Assemblies with End-Face Damage
NASA Technical Reports Server (NTRS)
Kichak, Robert A.; Ott, Melanie N.; Leidecker, Henning W.; Chuska, Richard F.; Greenwell, Christopher J.
2008-01-01
In June 2005, the NESC received a multi-faceted request to determine the long term reliability of fiber optic termini on the ISS that exhibited flaws not manufactured to best workmanship practices. There was a lack of data related to fiber optic workmanship as it affects the long term reliability of optical fiber assemblies in a harsh environment. A fiber optic defect analysis was requested which would find and/or create various types of chips, spalls, scratches, etc., that were identified by the ISS personnel. Once the defects and causes were identified the next step would be to perform long term reliability testing of similar assemblies with similar defects. The goal of the defect analysis would be for the defects to be observed and documented for deterioration of fiber optic performance. Though this report mostly discusses what has been determined as evidence of poor manufacturing processes, it also concludes the majority of the damage could have been avoided with a rigorous process in place.
Advanced Infusion Techniques with 3-D Printed Tooling
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nuttall, David; Elliott, Amy; Post, Brian K.
The manufacturing of tooling for large, contoured surfaces for fiber-layup applications requires significant effort to understand the geometry and then to subtractively manufacture the tool. Traditional methods for the auto industry use clay that is hand sculpted. In the marine pleasure craft industry, the exterior of the model is formed from a foam lay-up that is either hand cut or machined to create smooth lines. Engineers and researchers at Oak Ridge National Laboratory s Manufacturing Demonstration Facility (ORNL MDF) collaborated with Magnum Venus Products (MVP) in the development of a process for reproducing legacy whitewater adventure craft via digital scanningmore » and large scale 3-D printed layup molds. The process entailed 3D scanning a legacy canoe form, converting that form to a CAD model, additively manufacturing (3-D Print) the mold tool, and subtractively finishing the mold s transfer surfaces. Future work will include applying a gelcoat to the mold transfer surface and infusing using vacuum assisted resin transfer molding, or VARTM principles, to create a watertight vessel. The outlined steps were performed on a specific canoe geometry found by MVP s principal participant. The intent of utilizing this geometry is to develop an energy efficient and marketable process for replicating complex shapes, specifically focusing on this particular watercraft, and provide a finished product for demonstration to the composites industry. The culminating part produced through this agreement has been slated for public presentation and potential demonstration at the 2016 CAMX (Composites and Advanced Materials eXpo) exposition in Anaheim, CA. Phase I of this collaborative research and development agreement (MDF-15-68) was conducted under CRADA NFE-15-05575 and was initiated on May 7, 2015, with an introduction to the MVP product line, and concluded in March of 2016 with the printing of and processing of a canoe mold. The project partner Magnum Venous Products (MVP) is a small business. Phase II as discussed herein is under consideration by MVP as of this writing. Overall, it is anticipated that developing this process for manufacturing tooling for complex contoured surfaces has applicability to naval and other watercraft as well as bathrooms and large trucks.« less
Influence of heating and acidification on the flavor of whey protein isolate.
White, S S; Fox, K M; Jervis, S M; Drake, M A
2013-03-01
Previous studies have established that whey protein manufacture unit operations influence the flavor of dried whey proteins. Additionally, manufacturers generally instantize whey protein isolate (WPI; ≥ 90% protein) by agglomeration with lecithin to increase solubility and wettability. Whey protein isolate is often subjected to additional postprocessing steps in beverage manufacturing, including acidification and heat treatment. These postprocessing treatments may further influence formation or release of flavors. The objective of the first study was to characterize the effect of 2 processing steps inherent to manufacturing of acidic protein beverages (acidification and heat treatment) on the flavor of non-instant WPI. The second study sought to determine the effect of lecithin agglomeration, a common form of instantized (INST) WPI used in beverage manufacturing, on the flavor of WPI after acidification and heat treatment. In the first experiment, commercial non-instantized (NI) WPI were rehydrated and evaluated as is (control); acidified to pH 3.2; heated to 85°C for 5 min in a benchtop high temperature, short time (HTST) pasteurizer; or acidified to 3.2 and heated to 85°C for 30s (AH-HTST). In the second experiment, INST and NI commercial WPI were subsequently evaluated as control, acidified, heated, or AH-HTST. All samples were evaluated by descriptive sensory analysis, solid-phase microextraction (SPME), and gas chromatography-mass spectrometry. Acidification of NI WPI produced higher concentrations of dimethyl disulfide (DMDS) and sensory detection of potato/brothy flavors, whereas heating increased cooked/sulfur flavors. Acidification and heating increased cardboard, potato/brothy, and malty flavors and produced higher concentrations of aldehydes, ketones, and sulfur compounds. Differences between INST and NI WPI existed before treatment; INST WPI displayed cucumber flavors not present in NI WPI. After acidification, INST WPI were distinguished by higher intensity of cucumber flavor and higher concentrations of E-2-nonenal. No perceivable differences were observed between INST and NI WPI after heating; sulfur and eggy flavors increased in both types of WPI. After treatment, AH-INST-HTST samples were differentiated from AH-NI-HTST by grassy/hay and grainy flavor and increased lipid oxidation products. Further processing of WPI in food applications has negative effects on the flavor contributions of WPI. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Steiner, Denise; Finke, Jan Henrik; Kwade, Arno
2016-09-25
Orodispersible films possess a great potential as a versatile platform for nanoparticle-loaded oral dosage forms. In this case, poorly water-soluble organic materials were ground in a stirred media mill and embedded into a polymer matrix. The aim of this study was the shortening of this manufacturing process by the integration of several process steps into a stirred media mill without facing disadvantages regarding the film quality. Furthermore, this process integration is time conserving due to the high stress intensities provided in the mill and applicable for high solids contents and high suspension viscosities. Two organic materials, the model compound Anthraquinone and the active pharmaceutical ingredient Naproxen were investigated in this study. Besides the impact of the film processing on the crystallinity of the particles in the orodispersible film, a particle load of up to 50% was investigated with the new developed processing route. Additionally, a disintegration test was developed, combining an appropriate amount of saliva substitute and a clear endpoint determination. In summary, high nanoparticle loads in orodispersible films with good particle size preservation after film redispersion in water as well as a manufacturing of the film casting mass within a few minutes in a stirred media mill was achieved. Copyright © 2016 Elsevier B.V. All rights reserved.
EUV mask pilot line at Intel Corporation
NASA Astrophysics Data System (ADS)
Stivers, Alan R.; Yan, Pei-Yang; Zhang, Guojing; Liang, Ted; Shu, Emily Y.; Tejnil, Edita; Lieberman, Barry; Nagpal, Rajesh; Hsia, Kangmin; Penn, Michael; Lo, Fu-Chang
2004-12-01
The introduction of extreme ultraviolet (EUV) lithography into high volume manufacturing requires the development of a new mask technology. In support of this, Intel Corporation has established a pilot line devoted to encountering and eliminating barriers to manufacturability of EUV masks. It concentrates on EUV-specific process modules and makes use of the captive standard photomask fabrication capability of Intel Corporation. The goal of the pilot line is to accelerate EUV mask development to intersect the 32nm technology node. This requires EUV mask technology to be comparable to standard photomask technology by the beginning of the silicon wafer process development phase for that technology node. The pilot line embodies Intel's strategy to lead EUV mask development in the areas of the mask patterning process, mask fabrication tools, the starting material (blanks) and the understanding of process interdependencies. The patterning process includes all steps from blank defect inspection through final pattern inspection and repair. We have specified and ordered the EUV-specific tools and most will be installed in 2004. We have worked with International Sematech and others to provide for the next generation of EUV-specific mask tools. Our process of record is run repeatedly to ensure its robustness. This primes the supply chain and collects information needed for blank improvement.
NANEX: Process design and optimization.
Baumgartner, Ramona; Matić, Josip; Schrank, Simone; Laske, Stephan; Khinast, Johannes; Roblegg, Eva
2016-06-15
Previously, we introduced a one-step nano-extrusion (NANEX) process for transferring aqueous nano-suspensions into solid formulations directly in the liquid phase. Nano-suspensions were fed into molten polymers via a side-feeding device and excess water was eliminated via devolatilization. However, the drug content in nano-suspensions is restricted to 30 % (w/w), and obtaining sufficiently high drug loadings in the final formulation requires the processing of high water amounts and thus a fundamental process understanding. To this end, we investigated four polymers with different physicochemical characteristics (Kollidon(®) VA64, Eudragit(®) E PO, HPMCAS and PEG 20000) in terms of their maximum water uptake/removal capacity. Process parameters as throughput and screw speed were adapted and their effect on the mean residence time and filling degree was studied. Additionally, one-dimensional discretization modeling was performed to examine the complex interactions between the screw geometry and the process parameters during water addition/removal. It was established that polymers with a certain water miscibility/solubility can be manufactured via NANEX. Long residence times of the molten polymer in the extruder and low filling degrees in the degassing zone favored the addition/removal of significant amounts of water. The residual moisture content in the final extrudates was comparable to that of extrudates manufactured without water. Copyright © 2016 Elsevier B.V. All rights reserved.
Schaefer, Cédric; Clicq, David; Lecomte, Clémence; Merschaert, Alain; Norrant, Edith; Fotiadu, Frédéric
2014-03-01
Pharmaceutical companies are progressively adopting and introducing Process Analytical Technology (PAT) and Quality-by-Design (QbD) concepts promoted by the regulatory agencies, aiming the building of the quality directly into the product by combining thorough scientific understanding and quality risk management. An analytical method based on near infrared (NIR) spectroscopy was developed as a PAT tool to control on-line an API (active pharmaceutical ingredient) manufacturing crystallization step during which the API and residual solvent contents need to be precisely determined to reach the predefined seeding point. An original methodology based on the QbD principles was designed to conduct the development and validation of the NIR method and to ensure that it is fitted for its intended use. On this basis, Partial least squares (PLS) models were developed and optimized using chemometrics methods. The method was fully validated according to the ICH Q2(R1) guideline and using the accuracy profile approach. The dosing ranges were evaluated to 9.0-12.0% w/w for the API and 0.18-1.50% w/w for the residual methanol. As by nature the variability of the sampling method and the reference method are included in the variability obtained for the NIR method during the validation phase, a real-time process monitoring exercise was performed to prove its fit for purpose. The implementation of this in-process control (IPC) method on the industrial plant from the launch of the new API synthesis process will enable automatic control of the final crystallization step in order to ensure a predefined quality level of the API. In addition, several valuable benefits are expected including reduction of the process time, suppression of a rather difficult sampling and tedious off-line analyses. © 2013 Published by Elsevier B.V.
Carded Tow Real-Time Color Assessment: A Spectral Camera-Based System.
Furferi, Rocco; Governi, Lapo; Volpe, Yary; Carfagni, Monica
2016-08-31
One of the most important parameters to be controlled during the production of textile yarns obtained by mixing pre-colored fibers, is the color correspondence between the manufactured yarn and a given reference, usually provided by a designer or a customer. Obtaining yarns from raw pre-colored fibers is a complex manufacturing process entailing a number of steps such as laboratory sampling, color recipe corrections, blowing, carding and spinning. Carding process is the one devoted to transform a "fuzzy mass" of tufted fibers into a regular mass of untwisted fibers, named "tow". During this process, unfortunately, the correspondence between the color of the tow and the target one cannot be assured, thus leading to yarns whose color differs from the one used for reference. To solve this issue, the main aim of this work is to provide a system able to perform a spectral camera-based real-time measurement of a carded tow, to assess its color correspondence with a reference carded fabric and, at the same time, to monitor the overall quality of the tow during the carding process. Tested against a number of differently colored carded fabrics, the proposed system proved its effectiveness in reliably assessing color correspondence in real-time.
NASA Astrophysics Data System (ADS)
Chen, W. L.; Chao, F. L.
2018-04-01
Sustainable products become increasingly important for company in addressing eco-performance to satisfy global environmental regulations. Case study of flame guiding module reviewed design process and concerns related to the torch design. For enhancing flame height, the torch was embedded with an airflow guidance structure. The design process and design methodologies were investigated as an eco-design case study. Combine qualitative and CAE simulation were proposed to fulfil its main and auxiliary functions including reduction of impact during use. The design guidelines help prevent mistake arrangements, CAE helps understand combustion phenomenon. The flow field simulation enables fine tune of geometric design. Functional test and measurement are carried out to confirm the product features. On Eco-performance, we choose 5 items for evaluation the status of previous and redesign module, namely function need, low impact material, few manufacturing steps, low energy consumption, and safety. The radar diagram indicates that eco-performance of redesign module is better. Life cycle assessment calculated the carbon footprint of the manufacturing and processing stage with Eco-it. By using recycled steel in the flame module, it reduces raw material stage carbon footprint significantly.
Chocolate: A Marvelous Natural Product of Chemistry
NASA Astrophysics Data System (ADS)
Tannenbaum, Ginger
2004-08-01
Chocolate is a natural product as ubiquitous as television. Of course, it is eaten, but it is also found in air fresheners, marking pens, flavoring in a multitude of products including soda pop, and as an aroma in "chocolate-dyed" T-shirts. However, most of us are completely unaware of the complex chemical reactions that take place to produce chocolate and the necessary technology that has evolved to produce chocolate and all its byproducts. Processing results in a mixture of many components, an interesting contrast to most of the simple, one-step reactions introduced at the high school level. This article is a survey of chocolate from tree to table. After a brief introduction to the history of chocolate and how and where it is grown, the manufacturing process is examined, and the chemistry is explored. A bit of the jargon used in the industry is mentioned. Cocoa butter is a significant ingredient in chocolate, and an investigation of it introduces triglycerides, fatty acids, polymorphic behavior, and molecular packing of the fats in chocolate and how they affect the tempering process. There is a brief discussion of chocolate's non-Newtonian behavior and the resulting challenges presented in the manufacturing process. See Featured Molecules Featured on the Cover
FINAL REPORT: Transformational electrode drying process
DOE Office of Scientific and Technical Information (OSTI.GOV)
Claus Daniel, C.; Wixom, M.
2013-12-19
This report includes major findings and outlook from the transformational electrode drying project performance period from January 6, 2012 to August 1, 2012. Electrode drying before cell assembly is an operational bottleneck in battery manufacturing due to long drying times and batch processing. Water taken up during shipment and other manufacturing steps needs to be removed before final battery assembly. Conventional vacuum ovens are limited in drying speed due to a temperature threshold needed to avoid damaging polymer components in the composite electrode. Roll to roll operation and alternative treatments can increase the water desorption and removal rate without overheatingmore » and damaging other components in the composite electrode, thus considerably reducing drying time and energy use. The objective of this project was the development of an electrode drying procedure, and the demonstration of processes with no decrease in battery performance. The benchmark for all drying data was an 80°C vacuum furnace treatment with a residence time of 18 – 22 hours. This report demonstrates an alternative roll to roll drying process with a 500-fold improvement in drying time down to 2 minutes and consumption of only 30% of the energy compared to vacuum furnace treatment.« less
NASA Astrophysics Data System (ADS)
Langan, John
1996-10-01
The predominance of multi-level metalization schemes in advanced integrated circuit manufacturing has greatly increased the importance of plasma enhanced chemical vapor deposition (PECVD) and in turn in-situ plasma chamber cleaning. In order to maintain the highest throughput for these processes the clean step must be as short as possible. In addition, there is an increasing desire to minimize the fluorinated gas usage during the clean, while maximizing its efficiency, not only to achieve lower costs, but also because many of the gases used in this process are global warming compounds. We have studied the fundamental properties of discharges of NF_3, CF_4, and C_2F6 under conditions relevant to chamber cleaning in the GEC rf reference cell. Using electrical impedance analysis and optical emission spectroscopy we have determined that the electronegative nature of these discharges defines the optimal processing conditions by controlling the power coupling efficiency and mechanisms of power dissipation in the discharge. Examples will be presented where strategies identified by these studies have been used to optimize actual manufacturing chamber clean processes. (This work was performed in collaboration with Mark Sobolewski, National Institute of Standards and Technology, and Brian Felker, Air Products and Chemicals, Inc.)
Improving Metal Casting Process
NASA Technical Reports Server (NTRS)
1998-01-01
Don Sirois, an Auburn University research associate, and Bruce Strom, a mechanical engineering Co-Op Student, are evaluating the dimensional characteristics of an aluminum automobile engine casting. More accurate metal casting processes may reduce the weight of some cast metal products used in automobiles, such as engines. Research in low gravity has taken an important first step toward making metal products used in homes, automobiles, and aircraft less expensive, safer, and more durable. Auburn University and industry are partnering with NASA to develop one of the first accurate computer model predictions of molten metals and molding materials used in a manufacturing process called casting. Ford Motor Company's casting plant in Cleveland, Ohio is using NASA-sponsored computer modeling information to improve the casting process of automobile and light-truck engine blocks.
The people side of MRP (materiel requirements planning).
Lunn, T
1994-05-01
A montage of ideas and concepts have been successfully used to train and motivate people to use MRP II systems more effectively. This is important today because many companies are striving to achieve World Class Manufacturing status. Closed loop Materiel Requirements Planning (MRP) systems are an integral part of the process of continuous improvement. Successfully using a formal management planning system, such as MRP II, is a fundamental stepping stone on the path toward World Class Excellence. Included in this article are techniques that companies use to reduce lead time, simplify bills of materiel, and improve schedule adherence. These and other steps all depend on the people who use the system. The focus will be on how companies use the MRP tool more effectively.
Schuler, Friedrich; Schwemmer, Frank; Trotter, Martin; Wadle, Simon; Zengerle, Roland; von Stetten, Felix; Paust, Nils
2015-07-07
Aqueous microdroplets provide miniaturized reaction compartments for numerous chemical, biochemical or pharmaceutical applications. We introduce centrifugal step emulsification for the fast and easy production of monodisperse droplets. Homogenous droplets with pre-selectable diameters in a range from 120 μm to 170 μm were generated with coefficients of variation of 2-4% and zero run-in time or dead volume. The droplet diameter depends on the nozzle geometry (depth, width, and step size) and interfacial tensions only. Droplet size is demonstrated to be independent of the dispersed phase flow rate between 0.01 and 1 μl s(-1), proving the robustness of the centrifugal approach. Centrifugal step emulsification can easily be combined with existing centrifugal microfluidic unit operations, is compatible to scalable manufacturing technologies such as thermoforming or injection moulding and enables fast emulsification (>500 droplets per second and nozzle) with minimal handling effort (2-3 pipetting steps). The centrifugal microfluidic droplet generation was used to perform the first digital droplet recombinase polymerase amplification (ddRPA). It was used for absolute quantification of Listeria monocytogenes DNA concentration standards with a total analysis time below 30 min. Compared to digital droplet polymerase chain reaction (ddPCR), with processing times of about 2 hours, the overall processing time of digital analysis was reduced by more than a factor of 4.
NASA Astrophysics Data System (ADS)
Mahamood, Rasheedat M.
2018-03-01
Laser metal deposition (LMD) process belongs to the directed energy deposition class of additive manufacturing processes. It is an important manufacturing technology with lots of potentials especially for the automobile and aerospace industries. The laser metal deposition process is fairly new, and the process is very sensitive to the processing parameters. There is a high level of interactions among these process parameters. The surface finish of part produced using the laser metal deposition process is dependent on the processing parameters. Also, the economy of the LMD process depends largely on steps taken to eliminate or reduce the need for secondary finishing operations. In this study, the influence of laser power and gas flow rate on the microstructure, microhardness and surface finish produced during the laser metal deposition of Ti6Al4V was investigated. The laser power was varied between 1.8 kW and 3.0 kW, while the gas flow rate was varied between 2 l/min and 4 l/min. The microstructure was studied under an optical microscope, the microhardness was studied using a Metkon microhardness indenter, while the surface roughness was studied using a Jenoptik stylus surface analyzer. The results showed that better surface finish was produced at a laser power of 3.0 kW and a gas flow rate of 4 l/min.
Densitometric evaluation of three intra-oral radiographic films.
Seeliger, J E; Prinsloo, J J
1989-05-01
The radiographic, or diagnostic, quality of the processed radiograph depends upon a number of factors, one of the most important being the characteristics of the film. The purpose of this study was to determine which of three intra-oral radiographic films, obtainable in this country, would give the best results in terms of density range, speed, contrast and base plus fog values. Agfa Dentus, Flow X-Ray and Kodak (all speed group D films) were exposed, using a calibrated G.E. 1000 x-ray generator at 65 kVp, 10 mA and 50 impulses (1 second) exposure time. The target-film-distance was 40 cm, the total filtration 2.0 mm Aluminium and the half-value layer 2.7 mm Aluminium equivalent. An aluminium step-wedge with 8 steps, in steps of 1.5 mm, and a natural premolar tooth, with a carious lesion, embedded in acrylic, were used as phantoms. An 8 mm-thick layer of base-plate wax and a 3 mm-thick lead plate were used to simulate tissue-scatter and prevent back-scatter, respectively. To determine the base plug fog value, an unexposed film from the same batch was processed simultaneously with each of the three films evaluated. All processing was done in a Dürr AC 245 L processor with automatic replenishment and a 6-minute cycle. The processing chemicals, viz., Kolchem High Stability X-ray developer and fixer, were mixed and used in strict accordance with the manufacturer's recommendations. The radiographic densities of each step of the step-wedge, and of carious and normal dentine of the phantom tooth, were determined by means of an RMI Digital Densitometer.(ABSTRACT TRUNCATED AT 250 WORDS)
Double-Vacuum-Bag Process for Making Resin-Matrix Composites
NASA Technical Reports Server (NTRS)
Bradford, Larry J.
2007-01-01
A double-vacuum-bag process has been devised as a superior alternative to a single-vacuum-bag process used heretofore in making laminated fiber-reinforced resin-matrix composite-material structural components. This process is applicable to broad classes of high-performance matrix resins including polyimides and phenolics that emit volatile compounds (solvents and volatile by-products of resin-curing chemical reactions) during processing. The superiority of the double-vacuum-bag process lies in enhanced management of the volatile compounds. Proper management of volatiles is necessary for making composite-material components of high quality: if not removed and otherwise properly managed, volatiles can accumulate in interior pockets as resins cure, thereby forming undesired voids in the finished products. The curing cycle for manufacturing a composite laminate containing a reactive resin matrix usually consists of a two-step ramp-and-hold temperature profile and an associated single-step pressure profile as shown in Figure 1. The lower-temperature ramp-and-hold step is known in the art as the B stage. During the B stage, prepregs are heated and volatiles are generated. Because pressure is not applied at this stage, volatiles are free to escape. Pressure is applied during the higher-temperature ramp-and-hold step to consolidate the laminate and impart desired physical properties to the resin matrix. The residual volatile content and fluidity of the resin at the beginning of application of consolidation pressure are determined by the temperature and time parameters of the B stage. Once the consolidation pressure is applied, residual volatiles are locked in. In order to produce a void-free, high-quality laminate, it is necessary to design the curing cycle to obtain the required residual fluidity and the required temperature at the time of application of the consolidation pressure.
Chatterjee, Arindam; Gupta, Madan Mohan; Srivastava, Birendra
2017-01-01
Tablets have been choice of manufacturers over the years due to their comparatively low cost of manufacturing, packaging, shipping, and ease of administration; also have better stability and can be considered virtually tamper proof. A major challenge in formulation development of the tablets extends from lower solubility of the active agent to the elaborated manufacturing procedures for obtaining a compressible granular material. Moreover, the validation and documentation increases, as the numbers of steps increases for an industrially acceptable granulation process. Spherical crystallization (SC) is a promising technique, which encompass the crystallization, agglomeration, and spheronization phenomenon in a single step. Initially, two methods, spherical agglomeration, and emulsion solvent diffusion, were suggested to get a desired result. Later on, the introduction of modified methods such as crystallo-co-agglomeration, ammonia diffusion system, and neutralization techniques overcame the limitations of the older techniques. Under controlled conditions such as solvent composition, mixing rate and temperature, spherical dense agglomerates cluster from particles. Application of the SC technique includes production of compacted spherical particles of drug having improved uniformity in shape and size of particles, good bulk density, better flow properties as well as better solubility so SC when used on commercial scale will bring down the production costs of pharmaceutical tablet and will increase revenue for the pharmaceutical industries in the competitive market. This review summarizes the technologies available for SC and also suggests the parameters for evaluation of a viable product.
2017-09-01
Ulrich, Karl T., and Steven D. Eppinger. 2012. Product Design and Development, 5th ed. New York: McGraw-Hill Irwin. Warner, Jamie H., Franziska Schaffel...of tasks that an organization or business generally follows to transform a thought or idea of a product to a manufactured good. In the early stages...established product design and development processes. Karl Ulrich and Steven Eppinger (2012) state that one of the initial steps in the opportunity
Study of the Use of Oxygen-Absorbing Packaging Material to Prolong Shelf-Life of Rations
2010-05-28
technology can be used for retortable items (MRE 28 “Italian” entrée, chicken pesto with noodles ) since it maintained the 4 product shelf-life and...packages that have head spacing issues (e.g., retort item or those containing olive oil). Products included chicken pest with noodles (retorted entrée...of the MRE applesauce, they did not prevent the darkening problem. It is suspected that the retort processing step for applesauce manufacture may
Measure Guideline: High Efficiency Natural Gas Furnaces
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brand, L.; Rose, W.
2012-10-01
This Measure Guideline covers installation of high-efficiency gas furnaces. Topics covered include when to install a high-efficiency gas furnace as a retrofit measure, how to identify and address risks, and the steps to be used in the selection and installation process. The guideline is written for Building America practitioners and HVAC contractors and installers. It includes a compilation of information provided by manufacturers, researchers, and the Department of Energy as well as recent research results from the Partnership for Advanced Residential Retrofit (PARR) Building America team.
Measure Guideline. High Efficiency Natural Gas Furnaces
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brand, L.; Rose, W.
2012-10-01
This measure guideline covers installation of high-efficiency gas furnaces, including: when to install a high-efficiency gas furnace as a retrofit measure; how to identify and address risks; and the steps to be used in the selection and installation process. The guideline is written for Building America practitioners and HVAC contractors and installers. It includes a compilation of information provided by manufacturers, researchers, and the Department of Energy as well as recent research results from the Partnership for Advanced Residential Retrofit (PARR) Building America team.
NASA Technical Reports Server (NTRS)
Ryan, Robert
1993-01-01
The concept of rubustness includes design simplicity, component and path redundancy, desensitization to the parameter and environment variations, control of parameter variations, and punctual operations. These characteristics must be traded with functional concepts, materials, and fabrication approach against the criteria of performance, cost, and reliability. The paper describes the robustness design process, which includes the following seven major coherent steps: translation of vision into requirements, definition of the robustness characteristics desired, criteria formulation of required robustness, concept selection, detail design, manufacturing and verification, operations.
Method of making a hydrogen transport membrane, and article
Schwartz, Joseph M.; Corpus, Joseph M.; Lim, Hankwon
2015-07-21
The present invention relates to a method of manufacturing a hydrogen transport membrane and the composite article itself. More specifically, the invention relates to producing a membrane substrate, wherein the ceramic substrate is coated with a metal oxide slurry, thereby eliminating the need for an activation step prior to plating the ceramic membrane through an electroless plating process. The invention also relates to modifying the pore size and porosity of the substrate by oxidation or reduction of the particles deposited by the metal oxide slurry.
Persson, Oliver; Andersson, Niklas; Nilsson, Bernt
2018-01-05
Preparative liquid chromatography is a separation technique widely used in the manufacturing of fine chemicals and pharmaceuticals. A major drawback of traditional single-column batch chromatography step is the trade-off between product purity and process performance. Recirculation of impure product can be utilized to make the trade-off more favorable. The aim of the present study was to investigate the usage of a two-column batch-to-batch recirculation process step to increase the performance compared to single-column batch chromatography at a high purity requirement. The separation of a ternary protein mixture on ion-exchange chromatography columns was used to evaluate the proposed process. The investigation used modelling and simulation of the process step, experimental validation and optimization of the simulated process. In the presented case the yield increases from 45.4% to 93.6% and the productivity increases 3.4 times compared to the performance of a batch run for a nominal case. A rapid concentration build-up product can be seen during the first cycles, before the process reaches a cyclic steady-state with reoccurring concentration profiles. The optimization of the simulation model predicts that the recirculated salt can be used as a flying start of the elution, which would enhance the process performance. The proposed process is more complex than a batch process, but may improve the separation performance, especially while operating at cyclic steady-state. The recirculation of impure fractions reduces the product losses and ensures separation of product to a high degree of purity. Copyright © 2017 Elsevier B.V. All rights reserved.
Korasa, Klemen; Hudovornik, Grega; Vrečer, Franc
2016-10-10
Although process analytical technology (PAT) guidance has been introduced to the pharmaceutical industry just a decade ago, this innovative approach has already become an important part of efficient pharmaceutical development, manufacturing, and quality assurance. PAT tools are especially important in technologically complex operations which require strict control of critical process parameters and have significant effect on final product quality. Manufacturing of prolonged release film coated pellets is definitely one of such processes. The aim of the present work was to study the applicability of the at-line near-infrared spectroscopy (NIR) approach in the monitoring of pellet film coating and curing steps. Film coated pellets were manufactured by coating the active ingredient containing pellets with film coating based on polymethacrylate polymers (Eudragit® RS/RL). The NIR proved as a useful tool for the monitoring of the curing process since it was able to determine the extent of the curing and hence predict drug release rate by using partial least square (PLS) model. However, such approach also showed a number of limitations, such as low reliability and high susceptibility to pellet moisture content, and was thus not able to predict drug release from pellets with high moisture content. On the other hand, the at-line NIR was capable to predict the thickness of Eudragit® RS/RL film coating in a wide range (up to 40μm) with good accuracy even in the pellets with high moisture content. To sum up, high applicability of the at-line NIR in the monitoring of the prolonged release pellets production was demonstrated in the present study. The present findings may contribute to more efficient and reliable PAT solutions in the manufacturing of prolonged release dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.
Enhanced piezoresponse of highly aligned electrospun poly(vinylidene fluoride) nanofibers
NASA Astrophysics Data System (ADS)
Kang, Sung Bum; Won, Sang Hyuk; Im, Min Ji; Kim, Chan Ul; Park, Won Il; Baik, Jeong Min; Choi, Kyoung Jin
2017-09-01
Well-ordered nanostructure arrays with controlled densities can potentially improve material properties; however, their fabrication typically involves the use of complicated processing techniques. In this work, we demonstrate a uniaxial alignment procedure for fabricating poly(vinylidene fluoride) (PVDF) electrospun nanofibers (NFs) by introducing collectors with additional steps. The mechanism of the observed NF alignment, which occurs due to the concentration of lateral electric field lines around collector steps, has been elucidated via finite-difference time-domain simulations. The membranes composed of well-aligned PVDF NFs are characterized by a higher content of the PVDF β-phase, as compared to those manufactured from randomly orientated fibers. The piezoelectric energy harvester, which was fabricated by transferring well-aligned PVDF NFs onto flexible substrates with Ag electrodes attached to both sides, exhibited a 2-fold increase in the output voltage and a 3-fold increase in the output current as compared to the corresponding values obtained for the device manufactured from randomly oriented NFs. The enhanced piezoresponse observed for the aligned PVDF NFs is due to their higher β-phase content, denser structure, smaller effective radius of curvature during bending, greater applied strain, and higher fraction of contributing NFs.
A manufacturable process integration approach for graphene devices
NASA Astrophysics Data System (ADS)
Vaziri, Sam; Lupina, Grzegorz; Paussa, Alan; Smith, Anderson D.; Henkel, Christoph; Lippert, Gunther; Dabrowski, Jarek; Mehr, Wolfgang; Östling, Mikael; Lemme, Max C.
2013-06-01
In this work, we propose an integration approach for double gate graphene field effect transistors. The approach includes a number of process steps that are key for future integration of graphene in microelectronics: bottom gates with ultra-thin (2 nm) high-quality thermally grown SiO2 dielectrics, shallow trench isolation between devices and atomic layer deposited Al2O3 top gate dielectrics. The complete process flow is demonstrated with fully functional GFET transistors and can be extended to wafer scale processing. We assess, through simulation, the effects of the quantum capacitance and band bending in the silicon substrate on the effective electric fields in the top and bottom gate oxide. The proposed process technology is suitable for other graphene-based devices such as graphene-based hot electron transistors and photodetectors.
Autonomous Agents for Dynamic Process Planning in the Flexible Manufacturing System
NASA Astrophysics Data System (ADS)
Nik Nejad, Hossein Tehrani; Sugimura, Nobuhiro; Iwamura, Koji; Tanimizu, Yoshitaka
Rapid changes of market demands and pressures of competition require manufacturers to maintain highly flexible manufacturing systems to cope with a complex manufacturing environment. This paper deals with development of an agent-based architecture of dynamic systems for incremental process planning in the manufacturing systems. In consideration of alternative manufacturing processes and machine tools, the process plans and the schedules of the manufacturing resources are generated incrementally and dynamically. A negotiation protocol is discussed, in this paper, to generate suitable process plans for the target products real-timely and dynamically, based on the alternative manufacturing processes. The alternative manufacturing processes are presented by the process plan networks discussed in the previous paper, and the suitable process plans are searched and generated to cope with both the dynamic changes of the product specifications and the disturbances of the manufacturing resources. We initiatively combine the heuristic search algorithms of the process plan networks with the negotiation protocols, in order to generate suitable process plans in the dynamic manufacturing environment.
Additively Manufactured Low Cost Upper Stage Combustion Chamber
NASA Technical Reports Server (NTRS)
Protz, Christopher; Cooper, Ken; Ellis, David; Fikes, John; Jones, Zachary; Kim, Tony; Medina, Cory; Taminger, Karen; Willingham, Derek
2016-01-01
Over the past two years NASA's Low Cost Upper Stage Propulsion (LCUSP) project has developed Additive Manufacturing (AM) technologies and design tools aimed at reducing the costs and manufacturing time of regeneratively cooled rocket engine components. High pressure/high temperature combustion chambers and nozzles must be regeneratively cooled to survive their operating environment, causing their design fabrication to be costly and time consuming due to the number of individual steps and different processes required. Under LCUSP, AM technologies in Sintered Laser Melting (SLM) GRCop-84 and Electron Beam Freeform Fabrication (EBF3) Inconel 625 have been significantly advanced, allowing the team to successfully fabricate a 25k-class regenerative chamber. Estimates of the costs and schedule of future builds indicate cost reductions and significant schedule reductions will be enabled by this technology. Characterization of the microstructural and mechanical properties of the SLM-produced GRCop-84, EBF3 Inconel 625 and the interface layer between the two has been performed and indicates the properties will meet the design requirements. The LCUSP chamber is to be tested with a previously demonstrated SLM injector in order to advance the Technology Readiness Level (TRL) and demonstrate the capability of the application of these processes. NASA is advancing these technologies to reduce cost and schedule for future engine applications and commercial needs.
Technology for High Pure Aluminum Oxide Production from Aluminum Scrap
NASA Astrophysics Data System (ADS)
Ambaryan, G. N.; Vlaskin, M. S.; Shkolnikov, E. I.; Zhuk, A. Z.
2017-10-01
In this study a simple ecologically benign technology of high purity alumina production is presented. The synthesis process consists of three steps) oxidation of aluminum in water at temperature of 90 °C) calcinations of Al hydroxide in atmosphere at 1100 °C) high temperature vacuum processing of aluminum alpha oxide at 1750 °C. Oxidation of aluminum scrap was carried out under intensive mixing in water with small addition of KOH as a catalyst. It was shown that under implemented experimental conditions alkali was continuously regenerated during oxidation reaction and synergistic effect of low content alkali aqueous solution and intensive mixing worked. The product of oxidation of aluminum scrap is the powder of Al(OH)3. Then it can be preliminary granulated or directly subjected to thermal treatment deleting the impurities from the product (aluminum oxide). It was shown the possibility to produce the high-purity aluminum oxide of 5N grade (99.999 %). Aluminum oxide, synthesized by means of the proposed method, meets the requirements of industrial manufacturers of synthetic sapphire (aluminum oxide monocrystals). Obtained high pure aluminum oxide can be also used for the manufacture of implants, artificial joints, microscalpels, high-purity ceramics and other refractory shapes for manufacture of ultra-pure products.
Puri, Vibha; Brancazio, Dave; Desai, Parind M; Jensen, Keith D; Chun, Jung-Hoon; Myerson, Allan S; Trout, Bernhardt L
2017-11-01
The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited research on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore, studies that have applied the HME-IM process to molded tablets have used a noncontinuous 2-step approach. The present study develops maltodextrin (MDX)-based extrusion-molded immediate-release tablets for a crystalline drug (griseofulvin) using an integrated twin-screw HME-IM continuous process. At 10% w/w drug loading, MDX was selected as the tablet matrix former based on a preliminary screen. Furthermore, liquid and solid polyols were evaluated for melt processing of MDX and for impact on tablet performance. Smooth-surfaced tablets, comprising crystalline griseofulvin solid suspension in the amorphous MDX-xylitol matrix, were produced by a continuous process on a twin-screw extruder coupled to a horizontally opening IM machine. Real-time HME process profiles were used to develop automated HME-IM cycles. Formulation adjustments overcame process challenges and improved tablet strength. The developed MDX tablets exhibited adequate strength and a fast-dissolving matrix (85% drug release in 20 min), and maintained performance on accelerated stability conditions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Marković, Snežana; Kerč, Janez; Horvat, Matej
2017-03-01
We are presenting a new approach of identifying sources of variability within a manufacturing process by NIR measurements of samples of intermediate material after each consecutive unit operation (interprocess NIR sampling technique). In addition, we summarize the development of a multivariate statistical process control (MSPC) model for the production of enteric-coated pellet product of the proton-pump inhibitor class. By developing provisional NIR calibration models, the identification of critical process points yields comparable results to the established MSPC modeling procedure. Both approaches are shown to lead to the same conclusion, identifying parameters of extrusion/spheronization and characteristics of lactose that have the greatest influence on the end-product's enteric coating performance. The proposed approach enables quicker and easier identification of variability sources during manufacturing process, especially in cases when historical process data is not straightforwardly available. In the presented case the changes of lactose characteristics are influencing the performance of the extrusion/spheronization process step. The pellet cores produced by using one (considered as less suitable) lactose source were on average larger and more fragile, leading to consequent breakage of the cores during subsequent fluid bed operations. These results were confirmed by additional experimental analyses illuminating the underlying mechanism of fracture of oblong pellets during the pellet coating process leading to compromised film coating.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Owens, T.; Ungers, L.; Briggs, T.
1980-08-01
The purpose of this study is to estimate both quantitatively and qualitatively, the worker and societal risks attributable to four photovoltaic cell (solar cell) production processes. Quantitative risk values were determined by use of statistics from the California semiconductor industry. The qualitative risk assessment was performed using a variety of both governmental and private sources of data. The occupational health statistics derived from the semiconductor industry were used to predict injury and fatality levels associated with photovoltaic cell manufacturing. The use of these statistics to characterize the two silicon processes described herein is defensible from the standpoint that many ofmore » the same process steps and materials are used in both the semiconductor and photovoltaic industries. These health statistics are less applicable to the gallium arsenide and cadmium sulfide manufacturing processes, primarily because of differences in the materials utilized. Although such differences tend to discourage any absolute comparisons among the four photovoltaic cell production processes, certain relative comparisons are warranted. To facilitate a risk comparison of the four processes, the number and severity of process-related chemical hazards were assessed. This qualitative hazard assessment addresses both the relative toxicity and the exposure potential of substances in the workplace. In addition to the worker-related hazards, estimates of process-related emissions and wastes are also provided.« less
Pollock, James; Coffman, Jon; Ho, Sa V; Farid, Suzanne S
2017-07-01
This paper presents a systems approach to evaluating the potential of integrated continuous bioprocessing for monoclonal antibody (mAb) manufacture across a product's lifecycle from preclinical to commercial manufacture. The economic, operational, and environmental feasibility of alternative continuous manufacturing strategies were evaluated holistically using a prototype UCL decisional tool that integrated process economics, discrete-event simulation, environmental impact analysis, operational risk analysis, and multiattribute decision-making. The case study focused on comparing whole bioprocesses that used either batch, continuous or a hybrid combination of batch and continuous technologies for cell culture, capture chromatography, and polishing chromatography steps. The cost of goods per gram (COG/g), E-factor, and operational risk scores of each strategy were established across a matrix of scenarios with differing combinations of clinical development phase and company portfolio size. The tool outputs predict that the optimal strategy for early phase production and small/medium-sized companies is the integrated continuous strategy (alternating tangential flow filtration (ATF) perfusion, continuous capture, continuous polishing). However, the top ranking strategy changes for commercial production and companies with large portfolios to the hybrid strategy with fed-batch culture, continuous capture and batch polishing from a COG/g perspective. The multiattribute decision-making analysis highlighted that if the operational feasibility was considered more important than the economic benefits, the hybrid strategy would be preferred for all company scales. Further considerations outside the scope of this work include the process development costs required to adopt continuous processing. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:854-866, 2017. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers.
Pollock, James; Coffman, Jon; Ho, Sa V.
2017-01-01
This paper presents a systems approach to evaluating the potential of integrated continuous bioprocessing for monoclonal antibody (mAb) manufacture across a product's lifecycle from preclinical to commercial manufacture. The economic, operational, and environmental feasibility of alternative continuous manufacturing strategies were evaluated holistically using a prototype UCL decisional tool that integrated process economics, discrete‐event simulation, environmental impact analysis, operational risk analysis, and multiattribute decision‐making. The case study focused on comparing whole bioprocesses that used either batch, continuous or a hybrid combination of batch and continuous technologies for cell culture, capture chromatography, and polishing chromatography steps. The cost of goods per gram (COG/g), E‐factor, and operational risk scores of each strategy were established across a matrix of scenarios with differing combinations of clinical development phase and company portfolio size. The tool outputs predict that the optimal strategy for early phase production and small/medium‐sized companies is the integrated continuous strategy (alternating tangential flow filtration (ATF) perfusion, continuous capture, continuous polishing). However, the top ranking strategy changes for commercial production and companies with large portfolios to the hybrid strategy with fed‐batch culture, continuous capture and batch polishing from a COG/g perspective. The multiattribute decision‐making analysis highlighted that if the operational feasibility was considered more important than the economic benefits, the hybrid strategy would be preferred for all company scales. Further considerations outside the scope of this work include the process development costs required to adopt continuous processing. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:854–866, 2017 PMID:28480535
Development of a Self Aligned CMOS Process for Flash Lamp Annealed Polycrystalline Silicon TFTs
NASA Astrophysics Data System (ADS)
Bischoff, Paul
The emerging active matrix liquid crystal (AMLCD) display market requires a high performing semiconductor material to meet rising standards of operation. Currently amorphous silicon (a-Si) dominates the market but it does not have the required mobility for it to be used in AMLCD manufacturing. Other materials have been developed including crystallizing a-Si into poly-silicon. A new approach to crystallization through the use of flash lamp annealing (FLA) decreases manufacturing time and greatly improves carrier mobility. Previous work on FLA silicon for the use in CMOS transistors revealed significant lateral dopant diffusion into the channel greatly increasing the minimum channel length required for a working device. This was further confounded by the gate overlap due to misalignment during lithography patterning steps. Through the use of furnace dopant activation instead of FLA dopant activation and a self aligned gate the minimum size transistor can be greatly reduced. A new lithography mask and process flow were developed for the furnace annealing and self aligned gate. Fabrication of the self aligned devices resulted in oxidation of the Molybdenum self aligned gate. Further development is needed to successfully manufacture these devices. Non-self aligned transistors were made simultaneously with self aligned devices and used the furnace activation. These devices showed an increase in sheet resistance from 250 O to 800 O and lower mobility from 380 to 40.2 V/cm2s. The lower mobility can be contributed to an increase in implanted trap density indicating furnace annealing is an inferior activation method over FLA. The minimum transistor size however was reduced from 20 to 5 mum. With improvements in the self aligned process high performing small devices can be manufactured.
Kim, Sun Ae; Choi, Eun Sook; Kim, Nam Hee; Kim, Hye Won; Lee, Na Young; Cho, Tae Jin; Jo, Jun Il; Kim, Soon Han; Lee, Soon Ho; Ha, Sang Do; Rhee, Min Suk
2017-04-01
The present study examined the changes in microbiological composition during the production process of crab marinated in soy sauce, potential microbial hazards, potential contamination routes and effective critical control points. Crab and soy sauce samples were obtained from six different manufacturing plants at different stages, and their microbiological content was comprehensively assessed by quantitative and qualitative analyses. The results revealed the following: (1) the final products contained 4.0 log colony-forming units (CFU) g -1 aerobic plate counts (APCs) and 1.1 log CFU g -1 coliforms, which may have been introduced from the raw materials (the level of APCs in raw crab and soy sauce mixed with other ingredients was 3.8 log CFU g -1 and 4.0 log CFU mL -1 respectively); (2) marination of crab in soy sauce may allow cross-contamination by coliforms; (3) only Bacillus cereus and Staphylococcus aureus were qualitatively detected in samples at different stages of manufacture (detection rate of 28 and 5.6% respectively), and these bacteria may impact the microbiological quality and safety of crab marinated in soy sauce; and (4) bacterial counts were either maintained or increased during the manufacturing process (suggesting that no particular step can be targeted to reduce bacterial counts). Proper management of raw materials and the marination process are effective critical control points, and alternative interventions may be needed to control bacterial quantity. The results provide important basic information about the production of crab marinated in soy sauce and may facilitate effective implementation of sanitary management practices in related industries and research fields. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.
Prospects for reducing the processing cost of lithium ion batteries
Wood III, David L.; Li, Jianlin; Daniel, Claus
2014-11-06
A detailed processing cost breakdown is given for lithium-ion battery (LIB) electrodes, which focuses on: elimination of toxic, costly N-methylpyrrolidone (NMP) dispersion chemistry; doubling the thicknesses of the anode and cathode to raise energy density; and, reduction of the anode electrolyte wetting and SEI-layer formation time. These processing cost reduction technologies generically adaptable to any anode or cathode cell chemistry and are being implemented at ORNL. This paper shows step by step how these cost savings can be realized in existing or new LIB manufacturing plants using a baseline case of thin (power) electrodes produced with NMP processing and amore » standard 10-14-day wetting and formation process. In particular, it is shown that aqueous electrode processing can cut the electrode processing cost and energy consumption by an order of magnitude. Doubling the thickness of the electrodes allows for using half of the inactive current collectors and separators, contributing even further to the processing cost savings. Finally wetting and SEI-layer formation cost savings are discussed in the context of a protocol with significantly reduced time. These three benefits collectively offer the possibility of reducing LIB pack cost from $502.8 kWh-1-usable to $370.3 kWh-1-usable, a savings of $132.5/kWh (or 26.4%).« less
NASA Technical Reports Server (NTRS)
Williams, B. F.
1976-01-01
Manufacturing techniques are evaluated using expenses based on experience and studying basic cost factors for each step to evaluate expenses from a first-principles point of view. A formal cost accounting procedure is developed which is used throughout the study for cost comparisons. The first test of this procedure is a comparison of its predicted costs for array module manufacturing with costs from a study which is based on experience factors. A manufacturing cost estimate for array modules of $10/W is based on present-day manufacturing techniques, expenses, and materials costs.
Automatic localization of cochlear implant electrodes in CTs with a limited intensity range
NASA Astrophysics Data System (ADS)
Zhao, Yiyuan; Dawant, Benoit M.; Noble, Jack H.
2017-02-01
Cochlear implants (CIs) are neural prosthetics for treating severe-to-profound hearing loss. Our group has developed an image-guided cochlear implant programming (IGCIP) system that uses image analysis techniques to recommend patientspecific CI processor settings to improve hearing outcomes. One crucial step in IGCIP is the localization of CI electrodes in post-implantation CTs. Manual localization of electrodes requires time and expertise. To automate this process, our group has proposed automatic techniques that have been validated on CTs acquired with scanners that produce images with an extended range of intensity values. However, there are many clinical CTs acquired with a limited intensity range. This limitation complicates the electrode localization process. In this work, we present a pre-processing step for CTs with a limited intensity range and extend the methods we proposed for full intensity range CTs to localize CI electrodes in CTs with limited intensity range. We evaluate our method on CTs of 20 subjects implanted with CI arrays produced by different manufacturers. Our method achieves a mean localization error of 0.21mm. This indicates our method is robust for automatic localization of CI electrodes in different types of CTs, which represents a crucial step for translating IGCIP from research laboratory to clinical use.
Melt-processed polymeric cellular dosage forms for immediate drug release.
Blaesi, Aron H; Saka, Nannaji
2015-12-28
The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.
Li, Wen-Long; Qu, Hai-Bin
2016-10-01
In this paper, the principle of NIRS (near infrared spectroscopy)-based process trajectory technology was introduced.The main steps of the technique include:① in-line collection of the processes spectra of different technics; ② unfolding of the 3-D process spectra;③ determination of the process trajectories and their normal limits;④ monitoring of the new batches with the established MSPC (multivariate statistical process control) models.Applications of the technology in the chemical and biological medicines were reviewed briefly. By a comprehensive introduction of our feasibility research on the monitoring of traditional Chinese medicine technical process using NIRS-based multivariate process trajectories, several important problems of the practical applications which need urgent solutions are proposed, and also the application prospect of the NIRS-based process trajectory technology is fully discussed and put forward in the end. Copyright© by the Chinese Pharmaceutical Association.
A Survey of Terrestrial Approaches to the Challenge of Lunar Dust Containment
NASA Technical Reports Server (NTRS)
Aguilera, Tatiana; Perry, Jay L.
2009-01-01
Numerous technical challenges exist to successfully extend lunar surface exploration beyond the tantalizing first steps of Apollo. Among these is the challenge of lunar dust intrusion into the cabin environment. Addressing this challenge includes the design of barriers to intrusion as well as techniques for removing the dust from the cabin atmosphere. Opportunities exist for adapting approaches employed in dusty industrial operations and pristine manufacturing environments to cabin environmental quality maintenance applications. A survey of process technologies employed by the semiconductor, pharmaceutical, food processing, and mining industries offers insight into basic approaches that may be suitable for adaptation to lunar surface exploration applications.
Process for obtaining multiple sheet resistances for thin film hybrid microcircuit resistors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Norwood, D P
1989-01-31
A standard thin film circuit containing Ta/sub 2/N (100 ohms/square) resistors is fabricated by depositing on a dielectric substrate successive layers of Ta/sub 2/N, Ti and Pd, with a gold layer to provide conductors. The addition of a few simple photoprocessing steps to the standard TFN (thin film network) manufacturing process enables the formation of Ta/sub 2/N + Ti (10 ohms/square) and Ta/sub 2/N + Ti + Pd (1 ohm/square) resistors in the same otherwise standard thin film circuit structure. All three types of resistors are temperature-stable and laser-trimmable for precise definition of resistance values.
A biotechnological project with a gamma radiation source of 100,000 Ci
NASA Astrophysics Data System (ADS)
Lombardo, J. H.; Smolko, E. E.
A project for the production of radiovaccines and other bio-medical products is presented which includes a radiation facility provided with a gamma ray source equivalent to 100,000 Ci of Co-60. The whole process incorporates novel basic features in virus production and inactivation steps. The former is carried out in animals previously subjected to immunodepression through electromagnetic radiation. The later is obtained at low temperatures by using either electromagnetic or particle radiations. A vaccine manufacture process is shown to illustrate the utilization of ionizing radiations to obtain a foot and mouth disease virus (FMDV) vaccine with good antigenic quality and low cost.
Cesewski, Ellen; Haring, Alexander P; Tong, Yuxin; Singh, Manjot; Thakur, Rajan; Laheri, Sahil; Read, Kaitlin A; Powell, Michael D; Oestreich, Kenneth J; Johnson, Blake N
2018-06-13
Three-dimensional (3D) printing now enables the fabrication of 3D structural electronics and microfluidics. Further, conventional subtractive manufacturing processes for microelectromechanical systems (MEMS) relatively limit device structure to two dimensions and require post-processing steps for interface with microfluidics. Thus, the objective of this work is to create an additive manufacturing approach for fabrication of 3D microfluidic-based MEMS devices that enables 3D configurations of electromechanical systems and simultaneous integration of microfluidics. Here, we demonstrate the ability to fabricate microfluidic-based acoustofluidic devices that contain orthogonal out-of-plane piezoelectric sensors and actuators using additive manufacturing. The devices were fabricated using a microextrusion 3D printing system that contained integrated pick-and-place functionality. Additively assembled materials and components included 3D printed epoxy, polydimethylsiloxane (PDMS), silver nanoparticles, and eutectic gallium-indium as well as robotically embedded piezoelectric chips (lead zirconate titanate (PZT)). Electrical impedance spectroscopy and finite element modeling studies showed the embedded PZT chips exhibited multiple resonant modes of varying mode shape over the 0-20 MHz frequency range. Flow visualization studies using neutrally buoyant particles (diameter = 0.8-70 μm) confirmed the 3D printed devices generated bulk acoustic waves (BAWs) capable of size-selective manipulation, trapping, and separation of suspended particles in droplets and microchannels. Flow visualization studies in a continuous flow format showed suspended particles could be moved toward or away from the walls of microfluidic channels based on selective actuation of in-plane or out-of-plane PZT chips. This work suggests additive manufacturing potentially provides new opportunities for the design and fabrication of acoustofluidic and microfluidic devices.
Media Fill Test for validation of autologous leukocytes separation and labelling by (99m)Tc-HmPAO.
Urbano, Nicoletta; Modoni, Sergio; Schillaci, Orazio
2013-01-01
Manufacturing of sterile products must be carried out in order to minimize risks of microbiological contamination. White blood cells (WBC) labelled with (99m)Tc-exametazime ((99m)Tc-hexamethylpropyleneamine oxime; (99m)Tc-HMPAO) are being successfully applied in the field of infection/inflammation scintigraphy for many years. In our radiopharmacy lab, separation and labelling of autologous leukocytes with (99m)Tc-HMPAO were performed in a laminar flow cabinet not classified and placed in a controlled area, whereas (99m)Tc-HMPAO radiolabelling procedure was carried out in a hot cell with manipulator gloves. This study was conducted to validate this process using a Media Fill simulation test. The study was performed using sterile Tryptic Soy Broth (TSB) in place of active product, reproducing as closely as possible the routine aseptic production process with all the critical steps, as described in the our internal standard operative procedures (SOP). The final vials containing the media of each processed step were then incubated for 14 days and examined for the evidence of microbial growth. No evidence of turbidity was observed in all the steps assayed by the Media Fill. In the separation and labelling of autologous leukocytes with (99m)Tc-HmPAO, Media-Fill test represents a reliable tool to validate the aseptic process. Copyright © 2013 Elsevier Inc. All rights reserved.
Manufacturing interior furniture parts: a new look at an old problem
Edwin L. Lucas; Philip A. Araman
1975-01-01
The yields of interior furniture parts from four manufacturing sequences were compared. In three of the sequences, gang-ripping was the first step; in the fourth, the lumber was crosscut first. Though the grade of lumber used affects the percentage yield of parts, the manufacturing sequence used does not - but it will affect the cost per part. The selection of the best...
3D Printing in Zero-G ISS Technology Demonstration
NASA Technical Reports Server (NTRS)
Johnston, Mallory M.; Werkheiser, Mary J.; Cooper, Kenneth G.; Snyder, Michael P.; Edmunson, Jennifer E.
2014-01-01
The National Aeronautics and Space Administration (NASA) has a long term strategy to fabricate components and equipment on-demand for manned missions to the Moon, Mars, and beyond. To support this strategy, NASA and Made in Space, Inc. are developing the 3D Printing In Zero-G payload as a Technology Demonstration for the International Space Station. The 3D Printing In Zero-G experiment will be the first machine to perform 3D printing in space. The greater the distance from Earth and the longer the mission duration, the more difficult resupply becomes; this requires a change from the current spares, maintenance, repair, and hardware design model that has been used on the International Space Station up until now. Given the extension of the ISS Program, which will inevitably result in replacement parts being required, the ISS is an ideal platform to begin changing the current model for resupply and repair to one that is more suitable for all exploration missions. 3D Printing, more formally known as Additive Manufacturing, is the method of building parts/ objects/tools layer-by-layer. The 3D Print experiment will use extrusion-based additive manufacturing, which involves building an object out of plastic deposited by a wire-feed via an extruder head. Parts can be printed from data files loaded on the device at launch, as well as additional files uplinked to the device while on-orbit. The plastic extrusion additive manufacturing process is a low-energy, low-mass solution to many common needs on board the ISS. The 3D Print payload will serve as the ideal first step to proving that process in space. It is unreasonable to expect NASA to launch large blocks of material from which parts or tools can be traditionally machined, and even more unreasonable to fly up specialized manufacturing hardware to perform the entire range of function traditionally machining requires. The technology to produce parts on demand, in space, offers unique design options that are not possible through traditional manufacturing methods while offering cost-effective, high-precision, low-unit on-demand manufacturing. Thus, Additive Manufacturing capabilities are the foundation of an advanced manufacturing in space roadmap.
Beuer, Florian; Schweiger, Josef; Huber, Martin; Engels, Jörg; Stimmelmayr, Michael
2014-06-01
Various treatment concepts have been presented for the edentulous mandible. Manufacturing tension-free and precisely fitting bars on dental implants was previously a great challenge in prosthetic dentistry and required great effort. Modern computer aided design/computer aided manufacturing technology in combination with some clinical modifications of the established workflow enables the clinician to achieve precise results in a very efficient way. The innovative five-step concept is presented in a clinical case. © 2014 by the American College of Prosthodontists.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Williams, Joshua M.
Manufacturing tasks that are deemed too hazardous for workers require the use of automation, robotics, and/or other remote handling tools. The associated hazards may be radiological or nonradiological, and based on the characteristics of the environment and processing, a design may necessitate robotic labor, human labor, or both. There are also other factors such as cost, ergonomics, maintenance, and efficiency that also effect task allocation and other design choices. Handling the tradeoffs of these factors can be complex, and lack of experience can be an issue when trying to determine if and what feasible automation/robotics options exist. To address thismore » problem, we utilize common engineering design approaches adapted more for manufacturing system design in hazardous environments. We limit our scope to the conceptual and embodiment design stages, specifically a computational algorithm for concept generation and early design evaluation. In regard to concept generation, we first develop the functional model or function structure for the process, using the common 'verb-noun' format for describing function. A common language or functional basis for manufacturing was developed and utilized to formalize function descriptions and guide rules for function decomposition. Potential components for embodiment are also grouped in terms of this functional language and are stored in a database. The properties of each component are given as quantitative and qualitative criteria. Operators are also rated for task-relevant criteria which are used to address task compatibility. Through the gathering of process requirements/constraints, construction of the component database, and development of the manufacturing basis and rule set, design knowledge is stored and available for computer use. Thus, once the higher level process functions are defined, the computer can automate the synthesis of new design concepts through alternating steps of embodiment and function structure updates/decomposition. In the process, criteria guide function allocation of components/operators and help ensure compatibility and feasibility. Through multiple function assignment options and varied function structures, multiple design concepts are created. All of the generated designs are then evaluated based on a number of relevant evaluation criteria: cost, dose, ergonomics, hazards, efficiency, etc. These criteria are computed using physical properties/parameters of each system based on the qualities an engineer would use to make evaluations. Nuclear processes such as oxide conversion and electrorefining are utilized to aid algorithm development and provide test cases for the completed program. Through our approach, we capture design knowledge related to manufacturing and other operations in hazardous environments to enable a computational program to automatically generate and evaluate system design concepts.« less
21 CFR 680.1 - Allergenic Products.
Code of Federal Regulations, 2011 CFR
2011-04-01
...) Mold manufacturers shall maintain written standard operating procedures, developed by a qualified... representative species of mold subject to the standard operating procedures. The tests shall be performed at each manufacturing step during and subsequent to harvest, as specified in the standard operating procedures. Before...
21 CFR 680.1 - Allergenic Products.
Code of Federal Regulations, 2014 CFR
2014-04-01
...) Mold manufacturers shall maintain written standard operating procedures, developed by a qualified... representative species of mold subject to the standard operating procedures. The tests shall be performed at each manufacturing step during and subsequent to harvest, as specified in the standard operating procedures. Before...
21 CFR 680.1 - Allergenic Products.
Code of Federal Regulations, 2012 CFR
2012-04-01
...) Mold manufacturers shall maintain written standard operating procedures, developed by a qualified... representative species of mold subject to the standard operating procedures. The tests shall be performed at each manufacturing step during and subsequent to harvest, as specified in the standard operating procedures. Before...
21 CFR 680.1 - Allergenic Products.
Code of Federal Regulations, 2013 CFR
2013-04-01
...) Mold manufacturers shall maintain written standard operating procedures, developed by a qualified... representative species of mold subject to the standard operating procedures. The tests shall be performed at each manufacturing step during and subsequent to harvest, as specified in the standard operating procedures. Before...
Manufacturing cost/design trade-studies for flywheel
NASA Astrophysics Data System (ADS)
Noton, B. R.
1982-12-01
A procedure is described for enabling comparison of different flywheel designs based on both performance ratings, and manufacturing and inspection cost. Development of the methodology requires identification of all the steps in the manufacture and inspection of each design, the cost drivers, and the ground rules. A man-hour summary must also be provided. The approach to determine the recurring and nonrecurring manufacturing man-hours is presented. Cost drivers in composite manufacture are discussed as well as the approach to address cost driver data from industry. Some indications for cost driver data from industry. Some indications for cost reduction are included.
Supercritical Fluid Technologies to Fabricate Proliposomes.
Falconer, James R; Svirskis, Darren; Adil, Ali A; Wu, Zimei
2015-01-01
Proliposomes are stable drug carrier systems designed to form liposomes upon addition of an aqueous phase. In this review, current trends in the use of supercritical fluid (SCF) technologies to prepare proliposomes are discussed. SCF methods are used in pharmaceutical research and industry to address limitations associated with conventional methods of pro/liposome fabrication. The SCF solvent methods of proliposome preparation are eco-friendly (known as green technology) and, along with the SCF anti-solvent methods, could be advantageous over conventional methods; enabling better design of particle morphology (size and shape). The major hurdles of SCF methods include poor scalability to industrial manufacturing which may result in variable particle characteristics. In the case of SCF anti-solvent methods, another hurdle is the reliance on organic solvents. However, the amount of solvent required is typically less than that used by the conventional methods. Another hurdle is that most of the SCF methods used have complicated manufacturing processes, although once the setup has been completed, SCF technologies offer a single-step process in the preparation of proliposomes compared to the multiple steps required by many other methods. Furthermore, there is limited research into how proliposomes will be converted into liposomes for the end-user, and how such a product can be prepared reproducibly in terms of vesicle size and drug loading. These hurdles must be overcome and with more research, SCF methods, especially where the SCF acts as a solvent, have the potential to offer a strong alternative to the conventional methods to prepare proliposomes.
FEA Simulation of Free-Bending - a Preforming Step in the Hydroforming Process Chain
NASA Astrophysics Data System (ADS)
Beulich, N.; Craighero, P.; Volk, W.
2017-09-01
High-strength steel and aluminum alloys are essential for developing innovative, lightly-weighted space frame concepts. The intended design is built from car body parts with high geometrical complexity and reduced material-thickness. Over the past few years, many complex car body parts have been produced using hydroforming. To increase the accuracy of hydroforming in relation to prospective car concepts, the virtual manufacturing of forming becomes more important. As a part of process digitalization, it is necessary to develop a simulation model for the hydroforming process chain. The preforming of longitudinal welded tubes is therefore implemented by the use of three-dimensional free-bending. This technique is able to reproduce complex deflection curves in combination with innovative low-thickness material design for hydroforming processes. As a first step to the complete process simulation, the content of this paper deals with the development of a finite element simulation model for the free-bending process with 6 degrees of freedom. A mandrel built from spherical segments connected by a steel rope is located inside of the tube to prevent geometrical instability. Critical parameters for the result of the bending process are therefore evaluated and optimized. The simulation model is verified by surface measurements of a two-dimensional bending test.
ERIC Educational Resources Information Center
Baker, Nick, Ed.
1995-01-01
This issue of the quarterly newsletter "Rural Exchange" provides information and resources on accessible rural housing for the disabled. "Accessible Manufactured Housing Could Increase Rural Home Supply" (Nick Baker) suggests that incorporation of access features such as lever door handles and no-step entries into manufactured housing could help…
Feasibility and Scaling of Composite Based Additive Manufacturing
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nuttall, David; Chen, Xun; Kunc, Vlastimil
2016-04-27
Engineers and Researchers at Oak Ridge National Lab s Manufacturing Demonstration Facility (ORNL MDF) collaborated with Impossible Objects (IO) in the characterization of PEEK infused carbon fiber mat manufactured by means of CBAM composite-based additive manufacturing, a first generation assembly methodology developed by Robert Swartz, Chairman, Founder, and CTO of Impossible Objects.[1] The first phase of this project focused on demonstration of CBAM for composite tooling. The outlined steps focused on selecting an appropriate shape that fit the current machine s build envelope, characterized the resulting form, and presented next steps for transitioning to a Phase II CRADA agreement. Phasemore » I of collaborative research and development agreement NFE-15-05698 was initiated in April of 2015 with an introduction to Impossible Objects, and concluded in March of 2016 with a visitation to Impossible Objects headquarters in Chicago, IL. Phase II as discussed herein is under consideration by Impossible Objects as of this writing.« less
Friction-Stir-Welded and Spin-Formed End Domes for Cryogenic Tanks
NASA Technical Reports Server (NTRS)
Hales, S. J.; Tayon, W. A.; Domack, M. S.
2012-01-01
Manufacturing of single-piece end domes for cryogenic tanks employing spin forming of tailored, friction-stir-welded blanks of Al-Li alloy 2195 plate offers cost and reliability benefits. The introduction of plastic deformation into a friction stir weld is a unique feature of the proposed manufacturing route. This investigation addressed abnormal grain growth [AGG] within the friction stir weldments during postfabrication processing of a prototype dome. The phenomenon of AGG was observed during the solution heat treatment [SHT] phase of T8 tempering and is a major concern for meeting specifications. Such abrupt microstructural transitions can be detrimental to notch-sensitive mechanical properties, such as ductility and/or fracture toughness. If the issue of AGG cannot be resolved, then the acceptance of this approach as a viable manufacturing route may be in jeopardy. The innovative approach adopted in this investigation was the insertion of a stand-alone, Intermediate Annealing Treatment [IAT] between the spin forming and T8 processing operations. A simple, recovery annealing step was deemed to be the most readily-scalable solution when fabricating thin-walled, ellipsoidal domes. The research effort culminated in the development of an effective IAT, which resulted in a significant decrease in AGG following SHT. The processing philosophy adopted in designing the IAT is outlined and the microstructural reasons for success are discussed. The analytical results presented are consistent with promoting continuous grain growth during the IAT, thereby suppressing AGG during the SHT.
2011-01-01
Background A precise placement of dental implants is a crucial step to optimize both prosthetic aspects and functional constraints. In this context, the use of virtual guiding systems has been recognized as a fundamental tool to control the ideal implant position. In particular, complex periodontal surgeries can be performed using preoperative planning based on CT data. The critical point of the procedure relies on the lack of accuracy in transferring CT planning information to surgical field through custom-made stereo-lithographic surgical guides. Methods In this work, a novel methodology is proposed for monitoring loss of accuracy in transferring CT dental information into periodontal surgical field. The methodology is based on integrating 3D data of anatomical (impression and cast) and preoperative (radiographic template) models, obtained by both CT and optical scanning processes. Results A clinical case, relative to a fully edentulous jaw patient, has been used as test case to assess the accuracy of the various steps concurring in manufacturing surgical guides. In particular, a surgical guide has been designed to place implants in the bone structure of the patient. The analysis of the results has allowed the clinician to monitor all the errors, which have been occurring step by step manufacturing the physical templates. Conclusions The use of an optical scanner, which has a higher resolution and accuracy than CT scanning, has demonstrated to be a valid support to control the precision of the various physical models adopted and to point out possible error sources. A case study regarding a fully edentulous patient has confirmed the feasibility of the proposed methodology. PMID:21338504
Miszczycha, Stéphane D.; Perrin, Frédérique; Ganet, Sarah; Jamet, Emmanuel; Tenenhaus-Aziza, Fanny; Montel, Marie-Christine
2013-01-01
Shiga toxin-producing Escherichia coli (STEC) is an important cause of food-borne illness. The public health implication of the presence of STEC in dairy products remains unclear. Knowledge of STEC behavior in cheeses would help to evaluate the human health risk. The aim of our study was to observe the growth and survival of experimentally inoculated STEC strains in raw-milk cheeses manufactured and ripened according to five technological schemes: blue-type cheese, uncooked pressed cheese with long ripening and with short ripening steps, cooked cheese, and lactic cheese. Cheeses were contaminated with different STEC serotypes (O157:H7, O26:H11, O103:H2, and O145:H28) at the milk preparation stage. STEC growth and survival were monitored on selective media during the entire manufacturing process. STEC grew (2 to 3 log10 CFU · g−1) in blue-type cheese and the two uncooked pressed cheeses during the first 24 h of cheese making. Then, STEC levels progressively decreased in cheeses that were ripened for more than 6 months. In cooked cheese and in lactic cheese with a long acidic coagulation step (pH < 4.5), STEC did not grow. Their levels decreased after the cooking step in the cooked cheese and after the coagulation step in the lactic cheese, but STEC was still detectable at the end of ripening and storage. A serotype effect was found: in all cheeses studied, serotype O157:H7 grew less strongly and was less persistent than the others serotypes. This study improves knowledge of the behavior of different STEC serotypes in various raw-milk cheeses. PMID:23087038
Organic solvents in the pharmaceutical industry.
Grodowska, Katarzyna; Parczewski, Andrzej
2010-01-01
Organic solvents are commonly used in the pharmaceutical industry as reaction media, in separation and purification of synthesis products and also for cleaning of equipment. This paper presents some aspects of organic solvents utilization in an active pharmaceutical ingredient and a drug product manufacturing process. As residual solvents are not desirable substances in a final product, different methods for their removal may be used, provided they fulfill safety criteria. After the drying process, analyses need to be performed to check if amounts of solvents used at any step of the production do not exceed acceptable limits (taken from ICH Guideline or from pharmacopoeias). Also new solvents like supercritical fluids or ionic liquids are developed to replace "traditional" organic solvents in the pharmaceutical production processes.
1998-01-01
Don Sirois, an Auburn University research associate, and Bruce Strom, a mechanical engineering Co-Op Student, are evaluating the dimensional characteristics of an aluminum automobile engine casting. More accurate metal casting processes may reduce the weight of some cast metal products used in automobiles, such as engines. Research in low gravity has taken an important first step toward making metal products used in homes, automobiles, and aircraft less expensive, safer, and more durable. Auburn University and industry are partnering with NASA to develop one of the first accurate computer model predictions of molten metals and molding materials used in a manufacturing process called casting. Ford Motor Company's casting plant in Cleveland, Ohio is using NASA-sponsored computer modeling information to improve the casting process of automobile and light-truck engine blocks.
Nano-Electrochemistry and Nano-Electrografting with an Original Combined AFM-SECM
Ghorbal, Achraf; Grisotto, Federico; Charlier, Julienne; Palacin, Serge; Goyer, Cédric; Demaille, Christophe; Ben Brahim, Ammar
2013-01-01
This study demonstrates the advantages of the combination between atomic force microscopy and scanning electrochemical microscopy. The combined technique can perform nano-electrochemical measurements onto agarose surface and nano-electrografting of non-conducting polymers onto conducting surfaces. This work was achieved by manufacturing an original Atomic Force Microscopy-Scanning ElectroChemical Microscopy (AFM-SECM) electrode. The capabilities of the AFM-SECM-electrode were tested with the nano-electrografting of vinylic monomers initiated by aryl diazonium salts. Nano-electrochemical and technical processes were thoroughly described, so as to allow experiments reproducing. A plausible explanation of chemical and electrochemical mechanisms, leading to the nano-grafting process, was reported. This combined technique represents the first step towards improved nano-processes for the nano-electrografting. PMID:28348337
Bragg gratings inscription in step-index PMMA optical fiber by femtosecond laser pulses at 400 nm
NASA Astrophysics Data System (ADS)
Hu, X.; Kinet, D.; Chah, K.; Mégret, P.; Caucheteur, C.
2016-05-01
In this paper, we report photo-inscription of uniform Bragg gratings in trans-4-stilbenemethanol-doped photosensitive step-index polymer optical fiber. Gratings were produced at ~1575 nm by the phase mask technique with a femtosecond laser emitting at 400 nm with different average optical powers (8 mW, 13 mW and 20 mW). The grating growth dynamics in transmission were monitored during the manufacturing process, showing that the grating grows faster with higher power. Using 20 mW laser beam power, the reflectivity reaches 94 % (8 dB transmission loss) in 70 seconds. Finally, the gratings were characterized in temperature in the range 20 - 45 °C. The thermal sensitivity has been computed equal to - 86.6 pm/°C.
Yang, Heejung; Lee, Dong Young; Kang, Kyo Bin; Kim, Jeom Yong; Kim, Sun Ok; Yoo, Young Hyo; Sung, Sang Hyun
2015-05-10
A dry purified extract of Panax ginseng (PEG) was prepared using a manufacturing process that includes column chromatography, acid hydrolysis, and an enzyme reaction. During the manufacturing process, the more polar ginsenosides were altered into less polar forms via cleavage of their sugar chains and structural modifications of the aglycones, such as hydroxylation and dehydroxylation. The structural changes of ginsenosides during the intermediate steps from dried ginseng extract (DGE) to PEG were monitored by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectroscopy (UPLC-QTOF/MS). 22 ginsenosides isolated from PEG were used as the reference standards for determining of unknown ginsenosides and further suggesting of the metabolic markers. The elution order of 22 ginsenosides based on the type of aglycones, and the location and number of sugar chains can be used for the structural elucidation of unknown ginsenosides. This information could be used in a dereplication process for quick and efficient identification of ginsenoside derivatives in ginseng preparations. A dereplication approach helped the identification of the metabolic markers in the UPLC-QTOF/MS chromatograms during the conversion process with multivariate analyses, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) plots. These metabolic markers were identified by comparing with the dereplication information of the reference standards of 22 ginsenosides, or they were assigned using the pattern of the MS/MS fragmented ions. Consequently, the developed metabolic profiling approach using UPLC-QTOF/MS and multivariate analysis represents a new method for providing quality control as well as useful criteria for a similarity evaluation of the manufacturing process of ginseng preparations. Copyright © 2015 Elsevier B.V. All rights reserved.