In recent years, much attention has been directed towards the development of global methods for on-line process monitoring, especially since the Food and Drug Administration (FDA) launched the ...Process Analytical Technology (PAT) guidance, stimulating biopharmaceutical companies to update their monitoring tools to ensure a pre-defined final product quality. The ideal technologies for biopharmaceutical processes should operate in situ, be non-invasive and generate on-line information about multiple key bioprocess and/or metabolic variables. A wide range of spectroscopic techniques based on in situ probes have already been tested in mammalian cell cultures, such as near infrared (NIR), mid infrared (MIR), 2D fluorescence and dielectric capacitance spectroscopy; similarly, the electronic nose technique based on chemical array sensors has been tested for in situ off-gas analysis of mammalian cell cultures. All these methods provide series of spectra, from which meaningful information must be extracted. In this sense, data mining techniques such as principal components regression (PCR), partial least squares (PLS) or artificial neural networks (ANN) have been applied to handle the dense flow of data generated from the real-time process analyzers. Furthermore, the implementation of feedback control methods would help to improve process performance and ultimately ensure reproducibility. This review discusses the suitability of several spectroscopic techniques coupled with chemometric methods for improved monitoring and control of mammalian cell processes.
The use of engineered cells, tissues, and organs has the opportunity to change the way injuries and diseases are treated. Commercialization of these groundbreaking technologies has been limited in ...part by the complex and costly nature of their manufacture. Process-related variability and even small changes in the manufacturing process of a living product will impact its quality. Without real-time integrated detection, the magnitude and mechanism of that impact are largely unknown. Real-time and non-destructive sensor technologies are key for in-process insight and ensuring a consistent product throughout commercial scale-up and/or scale-out. The application of a measurement technology into a manufacturing process requires cell and tissue developers to understand the best way to apply a sensor to their process, and for sensor manufacturers to understand the design requirements and end-user needs. Furthermore, sensors to monitor component cells' health and phenotype need to be compatible with novel integrated and automated manufacturing equipment. This review summarizes commercially relevant sensor technologies that can detect meaningful quality attributes during the manufacturing of regenerative medicine products, the gaps within each technology, and sensor considerations for manufacturing.
The milling industry envisions solutions to become fully compatible with the industry 4.0 technology where sensors interconnect devices, machines and processes. In this contest, the work presents an ...integrated solution merging a deeper understanding and control of the process due to real-time data collection by MicroNIR sensors (VIAVI, Santa Rosa, CA)-directly from the manufacturing process-and data analysis by Chemometrics. To the aim the sensors were positioned at wheat cleaning and at the flour blends phase and near infrared spectra (951-1608 nm) were collected online. Regression models were developed merging the spectra information with the results obtained by reference analyses, i.e., chemical composition and rheological properties of dough by Farinograph
(Brabender GmbH and Co., Duisburg, Germany), Alveograph
(Chopin, NG Villeneuve-la-Garenne Cedex, France) and Extensograph
.(Brabender GmbH and Co., Duisburg, Germany) The model performance was tested by an external dataset obtaining, for most of the parameters, R
higher than 0.80 and Root Mean Squares Errors in prediction lower than two-fold the value of the reference method errors. The real-time implementation resulted in optimal (100% of samples) or really good (99.9%-80% of samples) prediction ability. The proposed work succeeded in the implementation of a process analytical approach with Industrial Internet of Things near infrared (IIoT NIR) devices for the prediction of relevant grain and flour characteristics of common wheat at the industrial level.
Process analytical technology (PAT) is used to monitor and control critical process parameters in raw materials and in-process products to maintain the critical quality attributes and build quality ...into the product. Process analytical technology can be successfully implemented in pharmaceutical and biopharmaceutical industries not only to impart quality into the products but also to prevent out-of-specifications and improve the productivity. PAT implementation eliminates the drawbacks of traditional methods which involves excessive sampling and facilitates rapid testing through direct sampling without any destruction of sample. However, to successfully adapt PAT tools into pharmaceutical and biopharmaceutical environment, thorough understanding of the process is needed along with mathematical and statistical tools to analyze large multidimensional spectral data generated by PAT tools. Chemometrics is a chemical discipline which incorporates both statistical and mathematical methods to obtain and analyze relevant information from PAT spectral tools. Applications of commonly used PAT tools in combination with appropriate chemometric method along with their advantages and working principle are discussed. Finally, systematic application of PAT tools in biopharmaceutical environment to control critical process parameters for achieving product quality is diagrammatically represented.
•A methodology is proposed to maximize the efficiency for PAT-SEIG system.•The selection of the SEIG system is crucial to operate PAT off-grid.•An electrical-hydraulic parameters analysis caused ...variations in the PAT efficiency.•Electrical parameters with high influence on the overall efficiency are identified.•Using the new method, the global peak efficiency increased about 50%.
The use of pump working as turbine (PAT) was identified by many researchers as a way to improve the energy efficiency in the water systems. However, the majority of the researches consider the hydraulic machine connected to the electrical grid, which may not fit best when these recovery systems are located in rural or remote areas. To improve the efficiency in these recovery systems for rural areas, this research contributes for a further study and optimization of the off-grid PAT systems with induction generators. The current manuscript proposes a methodology to obtain the best efficiency of the PAT-SEIG (Self-Excited Induction Generator) system when operating under different speeds and loads. For these systems, the selection of capacitors for the SEIG is critical to maximizing the energy efficiency. A methodology is proposed to estimate and select the correct SEIG model parameters and, thus, compute the best capacitor values to improve the PAT-SEIG energy efficiency. Special attention is given to the impact the SEIG parameters have in the efficiency of the recovery system. The accuracy of the analytical model improved, reducing the error between analytical and experimental results from 50.8% (for a model with constant parameters) to 13.2% (with parameters changing according to the operating point of the system). These results showed an increase of the overall PAT system efficiency from 26% to 40% for the analyzed case study.
Photoacoustic tomography (PAT) of the human brain is challenging due to the fact that the skull strongly absorbs and scatters light, and attenuates and distorts ultrasound as well. For the first ...time, we demonstrated the feasibility of PAT through a whole adult human skull. A photon recycler (PR) was built to increase light transmittance through the skull. Both a graphite target and a canine brain were imaged through the skull. Use of the PR was found to improve the photoacoustic signal-to-noise ratio by a factor of 2.4. In addition, subtraction of photoacoustic signals that arise from light absorption within the skull significantly improved the contrast of the target. Our results indicate that PAT can potentially be applied to in vivo human brain imaging.
Photoacoustic tomography (PAT) is an imaging modality that utilizes the photoacoustic effect. In PAT, a photoacoustic image is computed from measured data by modeling ultrasound propagation in the ...imaged domain and solving an inverse problem utilizing a discrete forward operator. However, in realistic measurement geometries with several ultrasound transducers and relatively large imaging volume, an explicit formation and use of the forward operator can be computationally prohibitively expensive. In this work, we propose a transformation-based approach for efficient modeling of photoacoustic signals and reconstruction of photoacoustic images. In the approach, the forward operator is constructed for a reference ultrasound transducer and expanded into a general measurement geometry using transformations that map the formulated forward operator in local coordinates to the global coordinates of the measurement geometry. The inverse problem is solved using a Bayesian framework. The approach is evaluated with numerical simulations and experimental data. The results show that the proposed approach produces accurate 3-D photoacoustic images with a significantly reduced computational cost both in memory requirements and time. In the studied cases, depending on the computational factors, such as discretization, over the 30-fold reduction in memory consumption was achieved without a reduction in image quality compared to a conventional approach.
Photoacoustic tomography (PAT) is a hybrid imaging technique that has broad preclinical and clinical applications. Based on the photoacoustic effect, PAT directly measures specific optical ...absorption, which is the product of the tissue-intrinsic optical absorption coefficient and the local optical fluence. Therefore, quantitative PAT, such as absolute oxygen saturation (sO₂) quantification, requires knowledge of the local optical fluence, which can only be estimated through invasive measurements or sophisticated modeling of light transportation. In this Letter, we circumvent this requirement by taking advantage of the dynamics in sO₂. The new method works when the sO₂ transition can be simultaneously monitored with multiple wavelengths. For each wavelength, the ratio of photoacoustic amplitudes measured at different sO₂ states is utilized. Using the ratio cancels the contribution from optical fluence and allows calibration-free quantification of absolute sO₂. The new method was validated through both phantom and in vivo experiments.
Z. Liu and co‐workers introduce on page 1886 a new generation of photothermal theranostic agents based on functionalized WS2 nanosheets, a two‐dimensional transition‐metal dichalcogenide. Bimodal in ...vivo CT/photoacoustic imaging reveals strong tumor contrast after either local or systemic injection of WS2‐PEG, which then enables highly effective photothermal ablation of tumors in a mouse model.
In water distribution networks (WDN) equipped with pump as turbines (PATs), in addition to water pressure problems, energy production by PATs is also necessary in abnormal conditions. Reliability ...indices are the most important parameters in determining the efficiency of systems when components fail. In this research, while proving the correlation weakness of a number of previous indices with the energy, a new energy reliability index is introduced, and it's integrated with previous reliability indices. Since checking the performance of networks from different aspects leads to increasing accuracy and reducing design and operation costs, in the following, the correlation of each of the integrated indices with the performance indices (PI) of adequacy, equity, energy, adequacy- equity, adequacy-energy, equity-energy, and total are calculated for two WDNs. Finally, the most critical network pipes for repair and maintenance (for each of the performance indices) are determined.
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