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Article

20 April 2022 | English

Flexibility between lab and fab

Compound semiconductor functionality is all about the layer structure. But unlike a cake, it’s rare that you wish to slice up your wafer to see what is going on inside. Fortunately, though, in this instance you can turn to metrology technologies, such as X-ray diffractometry (XRD), to generate accurate and precise structural metrology in a non-destructive manner. Here, advanced capabilities beyond the rocking curves are becoming ever more important for the production of epitaxial wafers. Production of compound semiconductor wafers continues to rise, as our society seeks to unlock the potential of these materials that offer significant sustainability benefits. If you are a regular reader of this magazine, you will know all too well about the energy savings that come from the widespread deployment of compound semiconductors in LEDs or power converters. Increasing manufacturing excellence of compound semiconductors lowers cost so that these chips can feature in even more electronic products shipped and sold around the globe. The epitaxial growth these devices is monitored by XRD techniques – but what does the maturation of the compound semiconductor industry mean for analytical XRD instruments and those who use them?

Products:
X'Pert3 MRD (XL), X'Pert3 MRD
Technology:
X-ray Diffraction (XRD)
Industry:
Semiconductors, Electronics/Optics
Flexibility between lab and fab
Article

30 March 2022 | English

Heavy Mineral Sands Mining and Downstream Processing Value of Mineralogical Monitoring Using XRD

Heavy mineral sands are the source of various commodities such as white titanium dioxide pigment and titanium metal. The three case studies in this paper show the value of X-ray diffraction (XRD) and statistical methods such as data clustering for process optimization and quality control during heavy mineral processing. The potential of XRD as an automatable, reliable tool, useful in the characterization of heavy mineral concentrates, product streams and titania slag is demonstrated. The recent development of ultra-high-speed X-ray detectors and automated quantification allows for ‘on the fly’ quantitative X-ray diffraction analysis and truly interactive process control, especially in the sector of heavy mineral concentration and processing. Apart from the information about the composition of a raw ore, heavy mineral concentrate and the various product streams or titania slag, this paper provides useful information by the quantitative determination of the crystalline phases and the amorphous content. The analysis of the phases can help to optimize the concentration of ores and reduction of ilmenite concentrate. Traditionally, quality control of heavy mineral concentrates and titania slag relies mainly on elemental, chemical, gravimetrical, and magnetic analysis. Since the efficiency of concentration of minerals in the different product streams and reduction depends on the content of the different minerals, and for the latter on the titanium and iron phases such as ilmenite FeTiO3, rutile TiO2, anatase TiO2, or the various titanium oxides with different oxidation stages, fast and direct analysis of the phases is required.

Products:
Empyrean range, X'Pert3 range, Aeris range
Technology:
X-ray Diffraction (XRD)
Industry:
Mining
Heavy Mineral Sands Mining and Downstream Processing Value of Mineralogical Monitoring Using XRD
Article

13 December 2021 | English

How Malvern Panalytical helps enable additive manufacturing breakthroughs

Additive manufacturing (or AM) is fast taking off as a way to produce a wide range of components more efficiently, sustainably, and cost-effectively. John Duffy, Sector Marketing Manager for Advanced Materials, shares his views on what the additive manufacturing world looks like today, what it might look like in future, and how Malvern Panalytical helps make that future a reality. Please login or register for free to read more.

Products:
Empyrean range, Mastersizer 3000, Zetium
Industry:
Advanced Manufacturing
How Malvern Panalytical helps enable additive manufacturing breakthroughs
Article

13 December 2021 | English

How Malvern Panalytical enables battery manufacturing innovation

Battery power is increasingly being recognized as a viable option for sustainable energy storage and electric transportation. Umesh Tiwari, Global Manager for Advanced Materials and an expert in batteries and renewable energies, discusses the current battery landscape, the future of battery technologies, and the solutions Malvern Panalytical can provide. Please login or register for free to read the full article.

Products:
Mastersizer 3000
Technology:
X-ray Diffraction (XRD), X-ray Fluorescence (XRF)
Industry:
Energy/Battery, Fuel cells
How Malvern Panalytical enables battery manufacturing innovation
Article

03 December 2021 | English

A controlled blend

This article introduces an energy dispersive X-ray fluorescence (EDXRF) spectrometer for on-line elemental analysis in liquid process flows: Malvern Panalytical’s Epsilon Xflow. This technology enables the user to analyze, control and steer liquid-based production processes in real time, thereby optimizing production processes and blending operations. The analytical performance of the on-line spectrometer is demonstrated using two applications: on-line monitoring of the sulfur concentration in diesel to meet sulfur concentration levels prescribed by Euro VI, China VI, Bharat Stage VI, Tier 3 regulations, and the analysis of catalysts poisons in hydrotreating and fluid catalytic cracking (FCC) processes.

Products:
Epsilon Xflow
Technology:
X-ray Fluorescence (XRF), Energy Dispersive X-ray Fluorescence (EDXRF)
Industry:
Oils, Fuels and Chemicals
A controlled blend
Article

17 June 2021 | English

Characterization of Recombinant Adeno-Associated Viruses (rAAVs) for Gene Therapy Using Orthogonal Techniques

Viruses are increasingly used as vectors for delivery of genetic material for gene therapy and vaccine applications. Recombinant adeno-associated viruses (rAAVs) are a class of viral vector that is being investigated intensively in the development of gene therapies. To develop efficient rAAV therapies produced through controlled and economical manufacturing processes, multiple challenges need to be addressed starting from viral capsid design through identification of optimal process and formulation conditions to comprehensive quality control. Addressing these challenges requires fit-for-purpose analytics for extensive characterization of rAAV samples including measurements of capsid or particle titer, percentage of full rAAV particles, particle size, aggregate formation, thermal stability, genome release, and capsid charge, all of which may impact critical quality attributes of the final product. Importantly, there is a need for rapid analytical solutions not relying on the use of dedicated reagents and costly reference standards. In this study, we evaluate the capabilities of dynamic light scattering, multiangle dynamic light scattering, and SEC–MALS for analyses of rAAV5 samples in a broad range of viral concentrations (titers) at different levels of genome loading, sample heterogeneity, and sample conditions. The study shows that DLS and MADLS® can be used to determine the size of full and empty rAAV5 (27 ± 0.3 and 33 ± 0.4 nm, respectively). A linear range for rAAV5 size and titer determination with MADLS was established to be 4.4 x 1011 – 8.7 x 1013 cp/mL for the nominally full rAAV5 samples and 3.4 x 1011 – 7 x 1013 cp/mL for the nominally empty rAAV5 samples with 3–8% and 10–37% CV for the full and empty rAAV5 samples, respectively. The structural stability and viral load release were also inferred from a combination of DLS, SEC–MALS, and DSC. The structural characteristics of the rAAV5 start to change from 40 oC onward, with increasing aggregation observed. With this study, we explored and demonstrated the applicability and value of orthogonal and complementary label-free technologies for enhanced serotype-independent characterization of key properties and stability profiles of rAAV5 samples.

Products:
Contract Research - Chemistry
Technology:
Dynamic Light Scattering, Differential Scanning Calorimetry (DSC), Size Exclusion Chromatography (SEC), Multi-Angle Dynamic Light Scattering (MADLS)
Industry:
Pharmaceutical, Biologics
Characterization of Recombinant Adeno-Associated Viruses (rAAVs) for Gene Therapy Using Orthogonal Techniques
Article

17 February 2021 | English

Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor

Biophysical screening of compound libraries for the identification of ligands that interact with a protein is efficient, but does typically not reveal if (or how) ligands may interfere with its functional properties. For this a biochemical/functional assay is required. But for proteins whose function is dependent on a conformational change, such assays are typically complex or have low throughput. Here we have explored a high-throughput second-harmonic generation (SHG) biosensor to detect fragments that induce conformational changes upon binding to a protein in real time and identify dynamic regions. Multiwell plate format SHG assays were developed for wild-type and six engineered single-cysteine mutants of acetyl choline binding protein (AChBP), a homologue to ligand gated ion channels (LGICs). They were conjugated with second harmonic-active labels via amine or maleimide coupling.

Products:
Creoptix WAVE
Technology:
Grating-coupled interferometry (GCI)
Measurement type:
Binding affinity
Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor
Article

05 February 2021 | English

Structures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation

Narcolepsy type 1 (NT1) is a chronic neurological disorder that impairs the brain’s ability to control sleep-wake cycles. Current therapies are limited to the management of symptoms with modest effectiveness and substantial adverse effects. Agonists of the orexin receptor 2 (OX2R) have shown promise as novel therapeutics that directly target the pathophysiology of the disease. However, identification of drug-like OX2R agonists has proven difficult. Here we report cryo-electron microscopy structures of active-state OX2R bound to an endogenous peptide agonist and a small-molecule agonist. The extended carboxy-terminal segment of the peptide reaches into the core of OX2R to stabilize an active conformation, while the small-molecule agonist binds deep inside the orthosteric pocket, making similar key interactions. Comparison with antagonist-bound OX2R suggests a molecular mechanism that rationalizes both receptor activation and inhibition. Our results enable structure-based discovery of therapeutic orexin agonists for the treatment of NT1 and other hypersomnia disorders.

Products:
Creoptix WAVE
Industry:
Pharmaceutical
Measurement type:
Binding affinity
Structures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation
Article

17 December 2020 | English

Grating-coupled interferometry reveals binding kinetics and affinities of Ni ions to genetically engineered protein layers

Reliable measurement of the binding kinetics of low molecular weight analytes to their targets is still a challenging task. Often, the introduction of labels is simply impossible in such measurements, and the application of label-free methods is the only reliable choice. By measuring the binding kinetics of Ni(II) ions to genetically modified flagellin layers, we demonstrate that: (1) Grating-Coupled Interferometry (GCI) is well suited to resolve the binding of ions, even at very low protein immobilization levels; (2) it supplies high quality kinetic data from which the number and strength of available binding sites can be determined, and (3) the rate constants of the binding events can also be obtained with high accuracy. Experiments were performed using a flagellin variant incorporating the C-terminal domain of the nickel-responsive transcription factor NikR. GCI results were compared to affinity data from titration calorimetry. We found that besides the low-affinity binding sites characterized by a micromolar dissociation constant (Kd), tetrameric FliC-NikRC molecules possess high-affinity binding sites with Kd values in the nanomolar range. GCI enabled us to obtain real-time kinetic data for the specific binding of an analyte with molar mass as low as 59 Da, even at signals lower than 1 pg/mm2.

Products:
Creoptix WAVE
Technology:
Grating-coupled interferometry (GCI)
Measurement type:
Label-free analysis, Molecular weight, Binding kinetics
Grating-coupled interferometry reveals binding kinetics and affinities of Ni ions to genetically engineered protein layers
Article

07 December 2020 | English

BAM1/2 receptor kinase signaling drives CLE peptide-mediated formative cell divisions in Arabidopsis roots

Cell division is often regulated by extracellular signaling networks to ensure correct patterning during development. In Arabidopsis, the SHORT-ROOT (SHR)/SCARECROW (SCR) transcription factor dimer activates CYCLIND6;1 (CYCD6;1) to drive formative divisions during root ground tissue development. Here, we show plasma-membrane-localized BARELY ANY MERISTEM1/2 (BAM1/2) family receptor kinases are required for SHR-dependent formative divisions and CYCD6;1 expression, but not SHR-dependent ground tissue specification. Root-enriched CLE ligands bind the BAM1 extracellular domain and are necessary and sufficient to activate SHR-mediated divisions and CYCD6;1 expression. Correspondingly, BAM-CLE signaling contributes to the restriction of formative divisions to the distal root region. Additionally, genetic analysis reveals that BAM-CLE and SHR converge to regulate additional cell divisions outside of the ground tissues. Our work identifies an extracellular signaling pathway regulating formative root divisions and provides a framework to explore this pathway in patterning and evolution.

Products:
Creoptix WAVE
Industry:
Environment
Measurement type:
Binding kinetics
BAM1/2 receptor kinase signaling drives CLE peptide-mediated formative cell divisions in Arabidopsis roots