Recent applications of Chemical Imaging to pharmaceutical process monitoring and quality control

Chemical Imaging (CI) is an emerging platform technology that integrates conventional imaging and spectroscopy to attain both spatial and spectral information from an object. Vibrational spectroscopic methods, such as Near Infrared (NIR) and Raman spectroscopy, combined with imaging are particularly useful for analysis of biological/pharmaceutical forms. The rapid, non-destructive and non-invasive features of CI mark its potential suitability as a process analytical tool for the pharmaceutical industry, for both process monitoring and quality control in the many stages of drug production. This paper provides an overview of CI principles, instrumentation and analysis. Recent applications of Raman and NIR-CI to pharmaceutical quality and process control are presented; challenges facing Cl implementation and likely future developments in the technology are also discussed. (C) 2007 Elsevier B.V. All rights reserved.

Experimental Investigation of Stretch Blow Molding, Part 2: Analysis of Process Variables, Blowing Kinematics, and Bottle Properties

The work presented in this paper takes advantage of newly developed instrumentation suitable for in process monitoring of an industrial stretch blow molding machine. The instrumentation provides blowing pressure and stretch rod force histories along with the kinematics of polymer contact with the mould wall. A Design of Experiments pattern was used to qualitatively relate machine inputs with these process parameters and the thickness distribution of stretch blow molded PET (polyethylene terephtalate) bottles. Material slippage at the mold wall and thickness distribution is also discussed in relation to machine inputs. The key process indicators defined have great potential for use in a closed loop process control system and for validation of process simulations.

Experimental Investigation of Stretch Blow Molding, Part 1: Instrumentation in an Industrial Environment

In spite of intensive research, computational modeling of the injection stretch blow molding (ISBM) still cannot match the accuracy of other polymer processes such as injection molding. There is a lack of understanding of the interdependence among the machine parameters set up by the operators, process parameters, material behavior, and the resulting final thickness distribution and performance of the molded product. The work presented in this paper describes a set of instrumentation tools developed for investigation of the ISBM process in an industrial setting. Results are presented showing the pressure and air temperature evolution inside the mold, the stretch rod force and displacement history, and the moment of contact of the polymer with seven discrete locations on the mold.

Modelling and Instrumentation of Stretch Blow Moulding

The injection stretch blow moulding process is used to manufacture PET containers used in the soft drinks and carbonated soft drinks industry. The process consists of a test tube like specimen known as a preform which is heated, stretch and blown into a mould to form the container. This research is focused on developing a validated simulation of the process thus enabling manufacturers to design their products in a virtual environment without the need to waste time, material and energy. The simulation has been developed using the commercial FEA package Abaqus and has been validated using state of the art data acquisition system consisting of measurements for preform temperature (inner and outer wall) using a device known as THERMOscan (Figure 1), stretch rod force and velocity, internal pressure and air temperature inside the preform using an instrumented stretch rod and the?exact?timing of when the preform touches the mould wall using contact sensors.? In addition, validation studies have also been performed by blowing a perform without a mould and using high sped imaging technology in cooperation with an advanced digital image correlation system (VIC 3D) to provided new quantitative information on the behaviour of PET during blowing.? The approach has resulted in a realistic simulation in terms of accurate input parameters, preform shape evolution and prediction of final properties.

Implementation of hospital-wide computer information system :a case study of this change process

This case study examines the impact of a computer information system as it was being implemented in one Ontario hospital. The attitudes of a cross section of the hospital staff acted as a barometer to measure their perceptions of the implementation process. With The Mississauga Hospital in the early stages of an extensive computer implementation project, the opportunity existed to identify staff attitudes about the computer system, overall knowledge and compare the findings with the literature. The goal of the study was to develop a greater base about the affective domain in the relationship between people and the computer system. Eight exploratory questions shaped the focus of the investigation. Data were collected from three sources: a survey questionnaire, focused interviews, and internal hospital documents. Both quantitative and qualitative data were analyzed. Instrumentation in the study consisted of a survey distributed at two points in time to randomly selected hospital employees who represented all staff levels.Other sources of data included hospital documents, and twenty-five focused interviews with staff who replied to both surveys. Leavitt's socio-technical system, with its four subsystems: task, structure, technology, and people was used to classify staff responses to the research questions. The study findings revealed that the majority of respondents felt positive about using the computer as part of their jobs. No apparent correlations were found between sex, age, or staff group and feelings about using the computer. Differences in attitudes, and attitude changes were found in potential relationship to the element of time. Another difference was found in staff group and perception of being involved in the decision making process. These findings and other evidence about the role of change agents in this change process help to emphasize that planning change is one thing, managing the transition is another.

Mid-infrared filters for astronomical and remote sensing instrumentation

As improvements to the optical design of spectrometer and radiometer instruments evolve with advances in detector sensitivity, use of focal plane detector arrays and innovations in adaptive optics for large high altitude telescopes, interest in mid-infrared astronomy and remote sensing applications have been areas of progressive research in recent years. This research has promoted a number of developments in infrared coating performance, particularly by placing increased demands on the spectral imaging requirements of filters to precisely isolate radiation between discrete wavebands and improve photometric accuracy. The spectral design and construction of multilayer filters to accommodate these developments has subsequently been an area of challenging thin-film research, to achieve high spectral positioning accuracy, environmental durability and aging stability at cryogenic temperatures, whilst maximizing the far-infrared performance. In this paper we examine the design and fabrication of interference filters in instruments that utilize the mid-infrared N-band (6-15 µm) and Q-band (16-28 µm) atmospheric windows, together with a rationale for the selection of materials, deposition process, spectral measurements and assessment of environmental durability performance.

Application of logistic regression for fault analysis in an industrial printing process

A statistical technique for fault analysis in industrial printing is reported. The method specifically deals with binary data, for which the results of the production process fall into two categories, rejected or accepted. The method is referred to as logistic regression, and is capable of predicting future fault occurrences by the analysis of current measurements from machine parts sensors. Individual analysis of each type of fault can determine which parts of the plant have a significant influence on the occurrence of such faults; it is also possible to infer which measurable process parameters have no significant influence on the generation of these faults. Information derived from the analysis can be helpful in the operator's interpretation of the current state of the plant. Appropriate actions may then be taken to prevent potential faults from occurring. The algorithm is being implemented as part of an applied self-learning expert system.

Time reduction in a forced-convection thermal process using simplified transient analysis

This study investigates the utilisation of a simplified model in the transient analysis of a thermal cooling process. In such process the external thermal resistance between the surface and the surroundings is high compared to the system internal thermal resistance, so that the first controls the heat transfer process. In this case the Biot number is lower than 0.1. Aluminium reels were utilised, which, with proper internal instrumentation, furnished experimental results for the thermal cooling process. Based on experimental data, a simplified model for the determination of the process film coefficient was used. Subsequently, experimental and theoretical results were compared. The change of the airflow direction was also investigated for the cooling process, aiming at process time optimisation. (C) 2001 Elsevier B.V. Ltd.

Development of an instrumentation system embedded on FPGA for real time measurement of mechanical vibrations in rotating machinery

The real-time monitoring of events in an industrial plant is vital, to monitor the actual conditions of operation of the machinery responsible for the manufacturing process. A predictive maintenance program includes condition monitoring of the rotating machinery, to anticipate possible conditions of failure. To increase the operational reliability it is thus necessary an efficient tool to analyze and monitor the equipments, in real-time, and enabling the detection of e.g. incipient faults in bearings. To fulfill these requirements some innovations have become frequent, namely the inclusion of vibration sensors or stator current sensors. These innovations enable the development of new design methodologies that take into account the ease of future modifications, upgrades, and replacement of the monitored machine, as well as expansion of the monitoring system. This paper presents the development, implementation and testing of an instrument for vibration monitoring, as a possible solution to embed in industrial environment. The digital control system is based on an FPGA, and its configuration with an open hardware design tool is described. Special focus is given to the area of fault detection in rolling bearings. © 2012 IEEE.

The smear layer created by scaling and root planing is physiologically eliminated in a biphasic process

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Detection of glucose and triglycerides using information visualization methods to process impedance spectroscopy data

In this paper we discuss the detection of glucose and triglycerides using information visualization methods to process impedance spectroscopy data. The sensing units contained either lipase or glucose oxidase immobilized in layer-by-layer (LbL) films deposited onto interdigitated electrodes. The optimization consisted in identifying which part of the electrical response and combination of sensing units yielded the best distinguishing ability. It is shown that complete separation can be obtained for a range of concentrations of glucose and triglyceride when the interactive document map (IDMAP) technique is used to project the data into a two-dimensional plot. Most importantly, the optimization procedure can be extended to other types of biosensors, thus increasing the versatility of analysis provided by tailored molecular architectures exploited with various detection principles. (C) 2012 Elsevier B.V. All rights reserved.

Rapid microbiological detection method based on ultrasonic instrumentation

Los métodos de detección rápida de microorganismos se están convirtiendo en una herramienta esencial para el control de calidad en el área de la biotecnología, como es el caso de las industrias de alimentos y productos farmacéuticos y bioquímicos. En este escenario, el objetivo de esta tesis doctoral es desarrollar una técnica de inspección rápida de microoganismos basada en ultrasonidos. La hipótesis propuesta es que la combinación de un dispositivo ultrasónico de medida y un medio líquido diseñado específicamente para producir y atrapar burbujas, pueden constituir la base de un método sensible y rápido de detección de contaminaciones microbianas. La técnica presentada es efectiva para bacterias catalasa-positivas y se basa en la hidrólisis del peróxido de hidrógeno inducida por la catalasa. El resultado de esta reacción es un medio con una creciente concentración de burbujas. Tal medio ha sido estudiado y modelado desde el punto de vista de la propagación ultrasónica. Las propiedades deducidas a partir del análisis cinemático de la enzima se han utilizado para evaluar el método como técnica de inspección microbiana. En esta tesis, se han investigado aspectos teóricos y experimentales de la hidrólisis del peróxido de hidrógeno. Ello ha permitido describir cuantitativamente y comprender el fenómeno de la detección de microorganismos catalasa-positivos mediante la medida de parámetros ultrasónicos. Más concretamente, los experimentos realizados muestran cómo el oxígeno que aparece en forma de burbujas queda atrapado mediante el uso de un gel sobre base de agar. Este gel fue diseñado y preparado especialmente para esta aplicación. A lo largo del proceso de hidrólisis del peróxido de hidrógeno, se midió la atenuación de la onda y el “backscattering” producidos por las burbujas, utilizando una técnica de pulso-eco. Ha sido posible detectar una actividad de la catalasa de hasta 0.001 unidades/ml. Por otra parte, este estudio muestra que por medio del método propuesto, se puede lograr una detección microbiana para concentraciones de 105 células/ml en un periodo de tiempo corto, del orden de unos pocos minutos. Estos resultados suponen una mejora significativa de tres órdenes de magnitud en comparación con otros métodos de detección por ultrasonidos. Además, la sensibilidad es competitiva con modernos y rápidos métodos microbiológicos como la detección de ATP por bioluminiscencia. Pero sobre todo, este trabajo muestra una metodología para el desarrollo de nuevas técnicas de detección rápida de bacterias basadas en ultrasonidos. ABSTRACT In an industrial scenario where rapid microbiological methods are becoming essential tools for quality control in the biotechnological area such as food, pharmaceutical and biochemical; the objective of the work presented in this doctoral thesis is to develop a rapid microorganism inspection technique based on ultrasounds. It is proposed that the combination of an ultrasonic measuring device with a specially designed liquid medium, able to produce and trap bubbles could constitute the basis of a sensitive and rapid detection method for microbial contaminations. The proposed technique is effective on catalase positive microorganisms. Well-known catalase induced hydrogen peroxide hydrolysis is the fundamental of the developed method. The physical consequence of the catalase induced hydrogen peroxide hydrolysis is an increasingly bubbly liquid medium. Such medium has been studied and modeled from the point of view of ultrasonic propagation. Properties deduced from enzyme kinematics analysis have been extrapolated to investigate the method as a microbial inspection technique. In this thesis, theoretical and experimental aspects of the hydrogen peroxide hydrolysis were analyzed in order to quantitatively describe and understand the catalase positive microorganism detection by means of ultrasonic measurements. More concretely, experiments performed show how the produced oxygen in form of bubbles is trapped using the new gel medium based on agar, which was specially designed for this application. Ultrasonic attenuation and backscattering is measured in this medium using a pulse-echo technique along the hydrogen peroxide hydrolysis process. Catalase enzymatic activity was detected down to 0.001 units/ml. Moreover, this study shows that by means of the proposed method, microbial detection can be achieved down to 105 cells/ml in a short time period of the order of few minutes. These results suppose a significant improvement of three orders of magnitude compared to other ultrasonic detection methods for microorganisms. In addition, the sensitivity reached is competitive with modern rapid microbiological methods such as ATP detection by bioluminescence. But above all, this work points out a way to proceed for developing new rapid microbial detection techniques based on ultrasound.

Multivariate monitoring of a biological wastewater treatment process: a case study at Melbourne Water's Western Treatment Plant

Biological wastewater treatment is a complex, multivariate process, in which a number of physical and biological processes occur simultaneously. In this study, principal component analysis (PCA) and parallel factor analysis (PARAFAC) were used to profile and characterise Lagoon 115E, a multistage biological lagoon treatment system at Melbourne Water's Western Treatment Plant (WTP) in Melbourne, Australia. In this study, the objective was to increase our understanding of the multivariate processes taking place in the lagoon. The data used in the study span a 7-year period during which samples were collected as often as weekly from the ponds of Lagoon 115E and subjected to analysis. The resulting database, involving 19 chemical and physical variables, was studied using the multivariate data analysis methods PCA and PARAFAC. With these methods, alterations in the state of the wastewater due to intrinsic and extrinsic factors could be discerned. The methods were effective in illustrating and visually representing the complex purification stages and cyclic changes occurring along the lagoon system. The two methods proved complementary, with each having its own beneficial features. (C) 2003 Elsevier B.V. All rights reserved.

Process systems modelling and applications in granulation: A review

Granulation is one of the fundamental operations in particulate processing and has a very ancient history and widespread use. Much fundamental particle science has occurred in the last two decades to help understand the underlying phenomena. Yet, until recently the development of granulation systems was mostly based on popular practice. The use of process systems approaches to the integrated understanding of these operations is providing improved insight into the complex nature of the processes. Improved mathematical representations, new solution techniques and the application of the models to industrial processes are yielding better designs, improved optimisation and tighter control of these systems. The parallel development of advanced instrumentation and the use of inferential approaches provide real-time access to system parameters necessary for improvements in operation. The use of advanced models to help develop real-time plant diagnostic systems provides further evidence of the utility of process system approaches to granulation processes. This paper highlights some of those aspects of granulation. (c) 2005 Elsevier Ltd. All rights reserved.

Computer control of chemical process plants with special reference to distillation

A sieve plate distillation column has been constructed and interfaced to a minicomputer with the necessary instrumentation for dynamic, estimation and control studies with special bearing on low-cost and noise-free instrumentation. A dynamic simulation of the column with a binary liquid system has been compiled using deterministic models that include fluid dynamics via Brambilla's equation for tray liquid holdup calculations. The simulation predictions have been tested experimentally under steady-state and transient conditions. The simulator's predictions of the tray temperatures have shown reasonably close agreement with the measured values under steady-state conditions and in the face of a step change in the feed rate. A method of extending linear filtering theory to highly nonlinear systems with very nonlinear measurement functional relationships has been proposed and tested by simulation on binary distillation. The simulation results have proved that the proposed methodology can overcome the typical instability problems associated with the Kalman filters. Three extended Kalman filters have been formulated and tested by simulation. The filters have been used to refine a much simplified model sequentially and to estimate parameters such as the unmeasured feed composition using information from the column simulation. It is first assumed that corrupted tray composition measurements are made available to the filter and then corrupted tray temperature measurements are accessed instead. The simulation results have demonstrated the powerful capability of the Kalman filters to overcome the typical hardware problems associated with the operation of on-line analyzers in relation to distillation dynamics and control by, in effect, replacirig them. A method of implementing estimator-aided feedforward (EAFF) control schemes has been proposed and tested by simulation on binary distillation. The results have shown that the EAFF scheme provides much better control and energy conservation than the conventional feedback temperature control in the face of a sustained step change in the feed rate or multiple changes in the feed rate, composition and temperature. Further extensions of this work are recommended as regards simulation, estimation and EAFF control.