Chimia最新文献

Whether for classic biologics or advanced therapy medicinal products (ATMPs), laboratory applications, small-scale or large-scale productions, single-use technology (SUT), and its associated consumables are used everywhere. The advantages of deploying SUTs are well known. Wherever a single-use solution is available, it is tested and ultimately used. Based on milestones in the development of single-use systems and single-use platform technologies, this article provides an up-to-date overview of products available on the market and their manufacturers/suppliers. It also discusses process examples with SUTs, design options and configurations of single-use facilities and Switzerland's pioneering role in the development and implementation of SUTs. In addition, the authors show that SUT has already been established beyond the biopharmaceutical sector.

In 2024, the Swiss Industrial Biocatalysis Consortium (SIBC), celebrated its 20 years of bringing together experts from the pharma, flavor and fragrance, fine chemicals, and agrochemicals industries to discuss enzyme technology developments. In this perspective, we share recent examples of how our member organizations utilize biocatalysis in their respective industries. While the motivations for employing enzymatic synthesis and the end goals of various production processes may vary, we aim to emphasize the shared aspects that we are coming across. Over the past 20 years, those synergies have provided us with a fruitful basis for pre-competitive knowledge sharing around biocatalysis as a technology. We look forward to many more years of the SIBC and the surprises that await us through the potential of our enzymes.

The perfusion mode has become increasingly important in biopharmaceutical production in recent years. A bioreactor system used in many laboratories for the development of monoclonal antibodies (mAbs) production processes is the Sartorius' Ambr. 250 system. Vessels designed for perfusion mode are only available for its high throughput version, while the modular version of the Ambr 250 is not designed for perfusion mode. In this study, perfusion processes for the production of a mAb with Chinese Hamster Ovary (CHO) cells were realized in the Ambr 250 Modular in combination with Repligen's ATF 1 single-use device for the first time, to the authors' knowledge. After testing a semi-perfusion setup in well plates and the Ambr 250, an N-1 perfusion process was developed to produce ultra-high cell densities of more than 150 Å~ 106 cells mL-1 for the inoculation of subsequent mAb production processes. In a second step, continuous mAb production was successfully realized over 23 days in a proof-of-concept experiment, achieving a volumetric productivity of 0.65 g L-1 d-1. The results of the N-1 and continuous perfusion processes were comparable to a 3 L HyPerformaTM Glass bioreactor (Thermo Scientific) with an ATF 2 (Repligen).

In this article we present our perspective on how biotransformations can contribute to key sustainability challenges faced by the agrochemical industry. We focus on two key areas where biotransformations have enabled research breakthroughs, the preparative synthesis of metabolite standards and natural products. Increasingly stringent regulatory requirements have rendered early metabolite identification and production an expanding activity to progress an active ingredient to the market. We present a collaborative project on unspecific peroxygenases for selective oxidation of pyrethroid-related compounds, illustrating future directions in research for the production of metabolites. Natural products provide an opportunity to explore a vast chemical space and to have an improved sustainability profile. Nevertheless, their fermentation at large scale and low cost is still challenging, and we present strategies aiming at increasing the fermentation titre and batch purity.

Currently, all feed and food come from plant- or animal-based production systems. The potential of the natural biodiversity of microorganisms for the highly efficient production of nutrients has yet to be leveraged. We present an overarching concept that ranges from the development of a national collection of regional microalgae to the decentralised production of nutrient-rich biomass for animal feed production. The focus is on the substitution of classic plant-based feed to reduce competition for arable land, to increase the nutritive value of animal-based food, and to reduce methane emissions from ruminants. The photoautotrophic and mixotrophic cultivation of microalgae are well aligned with the goals of CO2 fixation and the later contribution to the valorisation of side streams from the food industry. We also present the initial results on strain adaptation to diverse cultivation conditions.

Radionuclides are used and produced for a variety of applications, such as in the framework of energy production and nuclear medicine. This requires appropriate monitoring which in turn translates into the analysis of a variety of radionuclides in demanding sample matrices. Radionuclide analysis is a challenging task and often requires complex chemical processing of the samples prior to radiometric measurements. This requirement arises due to interfering radionuclides as well as matrix elements, which typically prevent a direct measurement by α- and γ-spectrometry, liquid scintillation counting or mass spectrometry. Despite offering promising possibilities, electrochemical approaches have been rarely used so far for the separation and analysis of radionuclides. Here, we present the development of fast flow-through electrolytic separation approaches for the analysis of carrier-added/-free radionuclides in fundamental and applied research.

Metal-catalyzed hydrogen atom transfer (MHAT) has become a valuable approach for the functionalization of alkenes and toward complex molecular structures. This review discusses recent advancements in the field, particularly the integration of metal catalysis with photoredox catalysis which obviates the need for sacrificial reagents. Key transformations, including heterocycle formation, olefin hydrofunctionalization, and semi-pinacol rearrangements are examined in detail, highlighting the potential of photo-MHAT for efficient and sustainable synthetic strategies.

Multiscale simulations are essential techniques in computational chemistry, providing insights into complex phenomena across extended temporal and spatial scales. With a particular interest in the dynamics of such processes, we developed MiMiC, a framework for efficient multiscale molecular dynamics simulations suited for high-performance computing. One of its key characteristics is a flexible design where external specialized programs handle individual subsystems. This article reviews the core features and some recent advancements in MiMiC, particularly the integration of OpenMM and CP2K.

This perspective discusses the relevance of studying the intracellular pH of pathogenic bacteria. Acidic environments trigger phenotype switches, increasing stress tolerance and antibiotic persistence - key challenges in treating bacterial infections. Understanding these phenotypic adaptations under clinically relevant stress conditions is important for elucidating bacterial survival mechanisms. Here, we discuss fluorescent tools to monitor pH homeostasis in bacterial cells and how advances in this field could shed light on pathogen resilience to antibiotics and human immune responses.