Chimia最新文献

In our lab we have been developing techniques that attempt to capture or amplify signals in pooled compound mixtures for several years. DNA encoded libraries (DELs) are the most widely used pooled mixtures in early drug discovery. DELs are massive collections of small molecules, where each individual molecule is covalently linked to a unique DNA strand that can serve as an identification tag by sequencing. The industry standard for selecting DELs is affinity enrichment, which inherently can only search for direct binding. We outline here two of the ways that we are attempting to extend the potential of DEL screens into new areas.

This review explores the control of therapeutic activity through programmed assembly of supramolecular systems. We examine the use of nucleic acids as scaffolds to create tailored assemblies of ligands, including glycan and peptide-based systems, drug-like small molecules or reagents for proximity-induced reactions. We discuss the principles of cooperativity in multivalent interactions, emphasizing their potential to enhance binding affinity and therapeutic efficacy and the opportunity to control their activity through strand displacement. We highlight seminal studies and illustrative case examples and address the challenges faced in translating these designs into clinical applications. Furthermore, we explore recent advancements that demonstrate successful in vivo applications, particularly in the context of anticoagulation therapies. This review aims to provide insights into the future of responsive therapeutic systems that leverage the programmability of supramolecular assemblies to develop potent and adaptable therapeutics.

For centuries, diagnostic technologies have played a key role in medicine. Effective diagnostics can help clinicians identify the presence and extent of disease in their patients, as well as their general health. Precipitated by advances in biochemistry, chemistry, and engineering, the 20th and 21st centuries have witnessed rapid advancement in diagnostic technologies. However, these improvements have brought increased complexity and a corresponding move towards more centralized and specialized laboratories. This has led to significant healthcare disparities between high- and low/middle-income regions. However, with the introduction of paper-based diagnostics this paradigm has begun to shift, with new assay formats designed for point-of-care (PoC) or at-home use. By leveraging innovations from multiple fields, these paper-based tests can translate complex assay procedures into easy-to-use, single-step tests for the end user. In this review, we summarize the interdisciplinary beginnings of paper-based diagnostics, detailing their development through market introduction and commercial successes, and discuss the current state-of-the-art. Finally, we highlight areas for improvement and propose pathways that could enable increasingly complex chemistries to be performed on simple paper-based devices.

Fundamental science can sometimes take a long time until it is useful for practical applications, as was the case for Raman spectroscopy. For a long time, it lacked powerful excitation sources and sensitive detectors. However as technology evolved, the number of exciting applications has boomed. Modern Raman spectroscopy has significant advantages, especially in sample preparation. Handheld Raman devices can be very compact and therefore be easily taken to the sample instead of bringing the sample to the lab. Non-destructive measurements obviously are important in gemmology and mineralogy, even in space. In the field of archaeology, pigments in precious ancient paintings, scrolls or books can be identified. This application is also used to identify fraud and falsification and in studies from a medical school they have reported that Raman spectroscopy can be applied to distinguish cancerous tissue from healthy tissue. Due to the mobility and ruggedness of the handheld hardware, Raman spectroscopy can be used for police, firefighters, and military applications for identification of explosives and illicit drugs or warfare substances. With SERS (Surface Enhanced Raman Spectroscopy), Raman spectroscopy can even be used for trace analysis. The SERS effect enhances the sensitivity of the Raman signal by a factor of up to 107. This enables, for example, measuring pesticide residuals on fruit or vegetable surfaces for food safety. It can also be used to identify traces of drugs, e.g. in urine. However, one of the most common Raman-applications is the identity check or verification of incoming goods (RMID) in the pharma industries, directly in the warehouse. Users appreciate the ease of use and the ruggedness of the Raman hardware.

High-performance data acquisition and processing (DAQ) systems are characterized by their ability to capture, process, and transmit data with high speed, precision, and efficiency. Among commercial solutions for Fourier transform mass spectrometry (FTMS), the FTMS Boosters developed by Spectroswiss stand out. These systems enhance the capabilities of FTMS platforms, such as Orbitrap and ion cyclotron resonance (ICR) instruments, by improving mass resolution, sensitivity, and data handling. This review highlights the impact of FTMS Boosters across six key applications: mass spectrometry imaging, charge detection mass spectrometry (CDMS) and charge determination analysis (CHARDA), biopharmaceutical analysis, isotope ratio and trace analyses, super-resolution mass spectrometry, and complex mixture analysis. By advancing FTMS capabilities, FTMS Boosters not only elevate performance but also extend the operational lifespan of legacy FTMS systems, offering a sustainable and cost-effective path to improved MS functionality. As FTMS technologies advance with an increasing focus on acquiring and processing big data, FTMS Boosters, and other high-performance DAQ systems are set to become indispensable in addressing the growing demands of data-intensive scientific research and applications.

 It is an enormous challenge to bring chemical sensing concepts from a controlled laboratory setting into the field while maintaining accuracy. In an environment of uncontrolled, fluctuating temperatures and a lack of repeated calibration, sensor reliability can rapidly deteriorate the accuracy. Today, many sensing concepts are explored for home use or as wearable sensors, and it is paramount to understand and optimize the chemistry for reliable measurements to become possible. This review focuses on the well-established class of potentiometric sensors, mostly known for the measurement of pH, with a range of electrolytes, and how conceptual advances can be used to make them as robust and sensitive as possible. While drawing from recent work of the group at the University of Geneva, the importance of symmetry is stressed to minimize the influence of temperature. The development of self-powered sensing systems that no longer require a battery is explained. This is then connected to protocols in which the sensitivity of these sensors can be reliably improved beyond that dictated by the Nernst equation.

We present α-Al2O3 XAS, XES and RIXS measurements across the Al L2/L3 edges at about 79 eV excitation energy. In the emission spectra, we identify two fluorescence peaks, corresponding to electronic transitions into the 2p core hole from mixed states of Al 3s and Al 3d character, both mixed with O 2p orbitals. Even if the XAS spectrum shows more than one resonance, surprisingly only one clear RIXS signal with energy loss equal to 10.7 eV is present in the data. Nevertheless, this allows us to tentatively extract from the measured high-resolution data the linewidths for fluorescence and RIXS transitions, with the latter being almost a factor of two smaller than the former.

The browser has become an indispensable tool for a variety of everyday tasks, yet its potential in scientific data processing remains underexplored and is often perceived as slow. This paper presents four examples of advanced web applications that we have developed during the last 20 years and demonstrates the browser's ability to compete with traditionally installed software. These applications were made possible through the development of over 100 open-source libraries, extending the FAIR (Findable, Accessible, Interoperable, and Reusable) principles to include not only data but also software.

The detection and identification of the building blocks of life, from amino acids to more complex molecules such as certain lipids, is a crucial but highly challenging task for current and future space exploration missions in our Solar System. To date, Gas Chromatography Mass Spectrometry has been the main technology applied. Although it has shown excellent performance in laboratory research, it has not yet been able to provide a conclusive answer regarding the presence or absence of a signature of life, extinct or extant, in space exploration. In this contribution we present the current measurement capabilities of our space prototype laser-based mass spectrometer for organics detection. The developed mass spectrometer currently allows the detection and identification of small organic molecules, such as amino acids and nucleobases, at sample concentrations at the level of femtomole mm-2, using the same measurement protocol. The latter is highly relevant to space exploration, since with the instrumentation in use so far only one class of organics can be measured with one instrument configuration.

The management of scientific data plays a key role in all research areas and has increased in importance. Providing researchers with customizable data management tools is crucial for effectively managing data according to the FAIR principles. These principles have been defined by Wilkinson et al. in 2016, which describe how scientific data should be managed.[1] To support the specific needs of researchers at Empa, openBIS[2] was chosen as a FAIR compliant data management platform. OpenBIS is an Electronic Laboratory Notebook (ELN) and Laboratory Information Management System (LIMS) developed at ETH. The commissioning of this platform for the case of an analytical chemistry lab presented multiple challenges. In this paper, solutions to adapt openBIS as a digital platform to integrate the laboratory data workflow in chemical analysis and for spectroscopy instruments are presented. Two laboratory projects as case studies are described, consisting of a data pipeline and a complex dashboard for data collection, visualization and interaction. These examples show a successful integration of the data management platform in accordance with the FAIR data guidelines along with maximizing efficiency for laboratory personnel.