Advances in biochemical engineering/biotechnology最新文献

Microfluidics has emerged as a powerful tool, enabling biotechnological processes to be performed on a microscale where certain physical processes (such as laminar flow, surface-to-volume ratio, and surface interactions) become dominant factors. At the same time, volumes and assay times are also reduced in microscale - which can substantially lower experimental costs. A decade ago, most microfluidic systems were only used for proof-of-concept studies; today, a wide array of microfluidic systems have been deployed to tackle various biotechnological research questions - especially regarding the analysis, screening, and understanding of cellular systems. Examples cover all biotechnological areas, from diagnostic applications in the field of medical biotechnology to the screening of potentially useful cells in the field of industrial biotechnology. As part of this review, we provide a brief introduction to microfluidics technology (including the vision of Lab-on-a-chip (LOC) systems) and survey some of the most notable applications of microfluidic technology in biotechnology to date.

Cellular therapies are creating a paradigm shift in the biomanufacturing industry. Particularly for autologous therapies, small-scale processing methods are better suited than the large-scale approaches that are traditionally employed in the industry. Current small-scale methods for manufacturing personalized cell therapies, however, are labour-intensive and involve a number of 'open events'. To overcome these challenges, new cell manufacturing platforms following a GMP-in-a-box concept have recently come on the market (GMP: Good Manufacturing Practice). These are closed automated systems with built-in pumps for fluid handling and sensors for in-process monitoring. At a much smaller scale, microfluidic devices exhibit many of the same features as current GMP-in-a-box systems. They are closed systems, fluids can be processed and manipulated, and sensors integrated for real-time detection of process variables. Fabricated from polymers, they can be made disposable, i.e. single-use. Furthermore, microfluidics offers exquisite spatiotemporal control over the cellular microenvironment, promising both reproducibility and control of outcomes. In this chapter, we consider the challenges in cell manufacturing, highlight recent advances of microfluidic devices for each of the main process steps, and summarize our findings on the current state of the art. As microfluidic cell culture devices have been reported for both adherent and suspension cell cultures, we report on devices for the key process steps, or unit operations, of both stem cell therapies and cell-based immunotherapies.

Droplet microfluidics has recently evolved as a prominent platform for high-throughput experimentation for various research fields including microbiology. Key features of droplet microfluidics, like compartmentalization, miniaturization, and parallelization, have enabled many possibilities for microbiology including cultivation of microorganisms at a single-cell level, study of microbial interactions in a community, detection and analysis of microbial products, and screening of extensive microbial libraries with ultrahigh-throughput and minimal reagent consumptions. In this book chapter, we present several aspects and applications of droplet microfluidics for its implementation in various fields of microbial biotechnology. Recent advances in the cultivation of microorganisms in droplets including methods for isolation and domestication of rare microbes are reviewed. Similarly, a comparison of different detection and analysis techniques for microbial activities is summarized. Finally, several microbial applications are discussed with a focus on exploring new antimicrobials and high-throughput enzyme activity screening. We aim to highlight the advantages, limitations, and current developments in droplet microfluidics for microbial biotechnology while envisioning its enormous potential applications in the future.

As an important building block in the chemical industry, methanol has become an attractive substrate in biorefinery owing to its abundance and low cost. With the development of synthetic biology, metabolic engineering of non-methylotrophy to construct synthetic methylotrophy has drawn increased attention. As for the metabolic construction of methanol assimilation pathway in some industrial hosts, several artificial methanol assimilation pathways have recently been designed and constructed based on the computer-aided design. Particularly, these artificial methanol assimilation pathways possess advantages of shorter reaction steps, stronger driving forces, and independence on oxygen. Accordingly, this chapter reviewed strategies of constructing synthetic methylotrophs, including introducing methanol metabolic modules derived from natural methylotrophs and designing artificial methanol assimilation pathways. Future challenges and prospects were also discussed.

In order to ensure a high level of product quality and safety, regular quality controls are mandatory, especially in the pharmaceutical industry. These quality controls are strictly regulated and require a high level of documentation. With the goal of complete traceability, these regulations are constantly being tightened, while a majority of laboratories are working still completely paper-based. This leads to an ever-increasing workload that keeps laboratory staff away from value-adding analytical work. In order to realize complete traceability, a reduction in documentation errors and at the same time a reduction of the individual workload, the digitization of complete workflows seems to be a promising solution.Due to the ongoing shortage of IT specialists and the resulting high implementation costs, many laboratories are understandably hesitant. In this chapter an alternative is presented on how to approach the digitization of complete workflows without the need for IT specialists. The example of quality control analysis of cytotoxic drug solutions was chosen to demonstrate the challenges of such a digitization project. In this way, we contribute to a comprehensive understanding of the tools already available, which can also help other laboratories in their digitization efforts. At the end compliance with GMP and EN ISO/IEC 17025 (2017) regulations was reached.

Microfluidic and lab-on-a-chip systems have become increasingly important tools across many research fields in recent years. As a result of their small size and precise flow control, as well as their ability to enable in situ process visualization, microfluidic systems are increasingly finding applications in environmental science and engineering. Broadly speaking, their main present applications within these fields include use as sensors for water contaminant analysis (e.g., heavy metals and organic pollutants), as tools for microorganism detection (e.g., virus and bacteria), and as platforms for the investigation of environment-related problems (e.g., bacteria electron transfer and biofilm formation). This chapter aims to review the applications of microfluidics in environmental science and engineering - with a particular focus on the foregoing topics. The advantages and limitations of microfluidics when compared to traditional methods are also surveyed, and several perspectives on the future of research and development into microfluidics for environmental applications are offered.

Methanol is a reduced one-carbon (C1) compound. It supports growth of aerobic methylotrophs that gain ATP from reduced redox equivalents by respiratory phosphorylation in their electron transport chains. Notably, linear oxidation of methanol to carbon dioxide may yield three reduced redox equivalents if methanol oxidation is NAD-dependent as, e.g., in Bacillus methanolicus. Methanol has a higher degree of reduction per carbon than glucose (6 vs. 4), and thus, lends itself as an ideal carbon source for microbial production of reduced target compounds. However, C-C bond formation in the RuMP or serine cycle, a prerequisite for production of larger molecules, requires ATP and/or reduced redox equivalents. Moreover, heat dissipation and a high demand for oxygen during catabolic oxidation of methanol may pose challenges for fermentation processes. In this chapter, we summarize metabolic pathways for aerobic methanol utilization, aerobic methylotrophs as industrial production hosts, strain engineering, and methanol bioreactor processes. In addition, we provide technological and market outlooks.