Monitoring of the primary drying of a lyophilization process in vials

An innovative and modular system (LyoMonitor) for monitoring the primary drying of a lyophilization process in vials is illustrated: it integrates some commercial devices (pressure gauges, moisture sensor and mass spectrometer), an innovative balance and a manometric temperature measurement system based on an improved algorithm (DPE) to estimate sublimating interface temperature and position, product temperature profile, heat and mass transfer coefficients. A soft-sensor using a multipoint wireless thermometer can also estimate the previous parameters in a large number of vials. The performances of the previous devices for the determination of the end of the primary drying are compared. Finally, all these sensors can be used for control purposes and for the optimization of the process recipe; the use of DPE in a control loop will be shown as an exampl

Emerging PAT for freeze-drying processes for advanced process control

Lyophilization is a widely used drying operation, but long processing times are a major drawback. Most lyophilization processes are conducted by a recipe that is not changed or optimized after implementation. With the regulatory demanded quality by design (QbD) approach, the process can be controlled inside an optimal range, ensuring safe process conditions. Process analytical technology (PAT) is crucial because it allows real-time monitoring and is part of a control strategy. In this work, emerging PAT (manometric temperature measurement (MTM), comparative pressure measurement, heat flux sensors, and ice ruler) are used for measurements during the freeze-drying process, and their potential for implementation inside a control strategy is outlined

Frost Growth Detection Using Capacitive Sensor

Frost buildup on surfaces could be an undesired situation in many applications. In refrigeration and heat pump system, typically, frost grows on the fin surface of the heat exchanger due to different environmental/operational conditions. On one hand, it can block the air flow and increase air-side pressure drop; on the other hand, can increase the thermal resistance and deteriorate heat transfer performance. As a result, frost buildup can significantly reduce the system’s COP. Therefore, most systems encountered frost buildup run the defrost cycle. The frost growth process is affected by many factors, such as environmental conditions (air humidity, temperature, flow rate), operational conditions (working fluids, saturated temperature), heat exchangers (structures, fin type and fin surface wettability) et. al.. All those factors are coupled together, which makes frost growth a very complex dynamic process with variable spatial distribution of its characteristic parameters. It is very important to dynamically detect frost growth for both effective defrost control and precise frost modelling. In this work, a capacitive sensor for frost detection has been developed, which consists of three parts as shown in Figure 1(a): 1) commercial capacitive to digital converter (FDC2214 from Texas Instruments and the resolution of the reading is 0.0001pF), 2) PCB connector and 3) fabricated electrodes. The fabricated copper electrode is attached to the PCB connector, which is mounted to the capacitive to digital converter and connected to the computer by a USB interface. Capacitance variation can be measured when the target properties changes. The interdigital electrodes has a high sensitivity and were fabricated by lithophotography, using copper laminates/ deposited copper thin layer as shown in Figure 1(b) The sensitivity can be affected by metallization ratios, width and thickness of the insulation layer, which are also explored in this work. The frost grows on a cold plate which is placed in the wind tunnel with a controlled air temperature, humidity and flow rate. The electrode of the capacitive sensor is located beside the side wall of the cold plate, as shown in Figure 1(c). The frost growth process can be detected and reflected by the capacitance variation of the sensor, as shown in Figure 2, the capacitance variation can reflect different stage of the frost growth period, starting from condensation to mature growth. Images are also captured by a CCD camera to calibrate the signal. This work demonstrates the dynamic frost growth detection at the first time and could play a significant role to understanding frost growth mechanism and defrost control strategy

Single Vial Monitoring of Pharmaceutical Freeze Drying Processes using Through Vial Impedance Spectroscopy

Currently, there is no single process analytical technology (PAT) in the market that can provide non-invasively, product and process related information which is representative of the entire batch at key stages of the freeze drying process: (i) the ice nucleation onset and the ice solidification endpoint, and the resulting ice crystal structure at the end of the freezing stage; and (ii) the true batch endpoint of ice sublimation to ensure all the ice is removed before switching to the secondary drying stage. Through Vial Impedance Spectroscopy (TVIS) employs a pair of electrodes that measure the electrical impedance of the glass vial and its contents. TVIS has been used as a PAT tool for the non-invasive monitoring of the critical events during the freeze drying process. While it has already been established previously that the TVIS parameters, (sensitive to product temperature) and ′(0.2) (largely sensitive to phase change) can be employed together to determine the ice nucleation onset and the ice solidification endpoint respectively, and ″ can be used for drying rate determination (largely sensitive to ice cylinder height), the present work involves the use of and ′(0.2) to demonstrate a direct dependency of ice nucleation temperature (or the freezing method) on the ice growth time, and subsequently the stability of the ice crystal microstructure determined using ″. Further, the present study establishes a high sensitivity of another TVIS parameter, ′(100 ), towards the changes in the shape of the ice sublimation interface and subsequently the removal of the last vestiges of ice from a single vial during primary drying. This feature has been exploited for the prediction of the primary drying endpoint at any vial location by employing a mathematical methodology, which has been extended to a simple sugar solution, wherein visual imaging cannot be used to detect ice disappearance. Finally, TVIS was multiplexed with batch measurement sensors (comparative pressure measurement and pressure rise test) for a comparison between the batch endpoint and the TVIS endpoints predicted at the shelf edge and the core. It has been demonstrated none of the PAT tools can determine the true endpoint of the batch (though the TVIS method is a significant improvement over one that relies on the thermocouple response). In conclusion, the study highlights a significant potential of TVIS for delivering additional product and process related information when it is multiplexed with batch measurement tools non-invasively, such as the thermal history of the sample before primary drying and the primary drying endpoints at various locations on the shelf

Icing Effects on Power Lines and Anti-icing and De-icing Methods

Icing on power lines may lead to compromise safety and reliability of electric supply network. Prolong icing can lead to power breakdown and collapse of towers. Since power transmission lines are mostly overhead and could face the direct impact of icing, and it is one of the main challenges faced by power distribution companies in cold regions. When the ice accretion crosses the safety limit then deicing action can be carried out. We can find number of deicing methods that are used in different parts of the world. However, all of these deicing techniques have their own advantages and disadvantages on implementation. It is one of the most difficult as well as dangerous process to perform deicing on power lines. If a fault is detected and that has been occurred due to icing or during routine maintenance, extra care must be taken in order to ensure safety of the personals when performing de-icing of lines. However, as technology evolved, new ways and techniques are adopted with the help of sensors that give quick feedback to control room in the national grid via wireless communication network for real time action. In the thesis we have discussed atmospheric icing impacts on power lines in the cold regions across the world. A literature review has been done for anti-icing and deicing methods that are currently adopted in the power distribution network. Methods that are used against ice buildups have also been analyzed. This work also shows the impacts of icing and deicing techniques presently adopted, and also throws light on their pros and cons during maintenance operations. It provides an overview of the evolving technology trends that are practiced to ensure the availability of existing power transmission system in cold climate regions

Index to NASA Tech Briefs, 1975

This index contains abstracts and four indexes--subject, personal author, originating Center, and Tech Brief number--for 1975 Tech Briefs

Monitoring rock freezing and thawing by novel geoelectrical and acoustic techniques

Automated monitoring of freeze-thaw cycles and fracture propagation in mountain rockwalls is 23 needed to provide early warning about rockfall hazards. Conventional geoelectrical methods 24 such as electrical resistivity tomography (ERT) are limited by large and variable ohmic contact 25 resistances, requiring galvanic coupling with metal electrodes inserted into holes drilled into 26 rock, and which can be loosened by rock weathering. We report a novel experimental 27 methodology that combined capacitive resistivity imaging (CRI), ERT and microseismic event 28 recording to monitor freeze-thaw of six blocks of hard and soft limestones under conditions 29 simulating an active layer above permafrost and seasonally frozen rock in a non-permafrost 30 environment. Our results demonstrate that the CRI method is highly sensitive to freeze-thaw 31 processes; it yields property information equivalent to that obtained with conventional ERT and 32 offers a viable route for non-galvanic long-term geoelectrical monitoring, extending the benefits 33 of the methodology to soft/hard rock environments. Contact impedances achieved with CRI are 34 less affected by seasonal temperature changes, the aggregate state of the pore water (liquid or 35 frozen), and the presence of low-porosity rock with high matrix resistivities than those achieved 36 with ERT. Microseismic monitoring has the advantage over acoustic emissions that events were 37 recorded in relevant field distances of meters to decameters from cracking events. For the first 38 time we recorded about 1000 microcracking events and clustered them in four groups according 39 to frequency and waveform. Compared to previous studies, mainly on ice-cracking in glaciers, 40 the groups are attributed to single- or multiple-stage cracking events such as crack coalescence

Process Analytical Technology for monitoring pharmaceuticals freeze drying - A Comprehensive Review

The goal of this paper is to review the available process analytical technology tools for monitoring the batch freeze-drying process for pharmaceuticals. These systems aim evaluating in-line product temperature, sublimation flow rate, and values of some model parameters in such a way that it can be used for in-line or off-line process optimization. A detailed survey of the systems proposed in the literature is presented, grouping them on the basis of monitored variable, namely, product temperature, heat flux to the product, sublimation flux, and, finally, other variables. The advantages and drawbacks of the techniques are critically assessed, taking into account the possibility of using them not only at lab-scale but also at production scale, beside, obviously, the possibility of getting reliable measurements of the desired variables

Marine icing sensor array for measuring ice thickness

Marine Icing is the process of ice accumulation on ships and other offshore structures in cold regions that can create serious working conditions besides the adverse effects to the offshore operations efficiency. Monitoring of icing conditions together with a number of de-icing strategies is therefore important in decreasing the safety hazards and increase the working effectiveness. Detection of the ice accretion rate on the offshore structures is a challenge due to the harsh environment and the multiphase property of the ice. This thesis is focused on developing a low cost array sensor for the ice accretion detection applicable to the harsh marine environments. We utilized a stray-capacitance technique that encodes a layered multiphase icing accretion uniquely. Capacitive sensors are popular in diverse industrial settings due to their relative simplicity, robustness and low cost. The sensor transducers are compatible with the printed circuit board technology which made this research time effective. The thesis is based on three distinct publications, two journal papers (IEEE, MDPI) and one peer-reviewed conference paper (IEEE), each in a separate chapter. All publications include a theoretical background, simulations, and experimental validation. The underlying novel approach that is more or less shared in all applications is the use of linearly independent sensor array for unique multiphase ice detection. The first two papers utilize a different inter-electrode spacing array but a different signal conditioning algorithm. The third paper then uses an array of constant spacing but different dielectric layer height. As stated above, the main objective of this work is to measure the multiphase icing accretion which consists of water above ice, the real situation which has not been addressed to date. A number of different techniques have been developed over the last two decades mainly as a response to the rapidly expanding offshore oil&gas in northern regions, offshore wind power generation, or shipping across or fishing in arctic waters. This thesis outlines three methods that can be directly applied to these industries

Standard Meteorological Measurements

Instruments that measure weather variables have been invented and tested since the time of Leonardo de Vinci. The earliest instruments were crude by today’s standards and required manual observation and notation of the weather variable of interest. In recent years, the miniaturization of circuits–sensors and the use of electronic processors have made it possible to collect ever-increasing numbers of observations on scales not previously considered. In many agricultural applications, the primary portion of the atmosphere that is of interest is the lower planetary boundary layer, or that layer affected by the earth’s surface. Accurate measurement of weather variables in the lower planetary boundary layer requires an understanding of the interactions among the atmosphere, plant communities, and soils. Temperature and pressure are often measured because of their role in air movement and energy exchange between the earth’s surface and the atmosphere. Temperature is perhaps of greater interest in agricultural applications because it is a driving variable that determines the rate of growth and development of an organism, and thus determines what species can grow in a region. Wind speed and direction are measured because of their role in convective energy exchange and the movement of spores, pollen, odors, and chemicals as they drift in the atmosphere. Precipitation amount, intensity, frequency, and form are important in determining the availability of water for crops and play an important role in soil erosion by water and in water quality issues. Solar radiation and relative humidity are additional weather variables, important to agriculture, that are often measured by appropriate sensors at automated weather stations. These variables will be discussed by Klassen and Bugbee (2005, this volume) and Campbell and Diak (2005, this volume)