Analytical techniques for multiplex analysis of protein biomarkers

Introduction: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. Areas covered: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. Expert commentary: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine

Evaluation of Cerebrospinal Fluid α‐Synuclein Seed Amplification Assay in Progressive Supranuclear Palsy and Corticobasal Syndrome

Publication status: PublishedFunder: National Institutes of Health Center for Alzheimer's and Related DementiasFunder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265Funder: PSP Association; doi: http://dx.doi.org/10.13039/100011707Funder: CBD SolutionsBackground: Seed amplification assay (SAA) testing has been developed as a biomarker for the diagnosis of α‐synuclein‐related neurodegenerative disorders. Objective: The objective of this study was to assess the rate of α‐synuclein SAA positivity in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) and to analyze clinical and pathological features of SAA‐positive and ‐negative cases. Methods: A total of 96 cerebrospinal fluid samples from clinically diagnosed PSP (n = 59) and CBS (n = 37) cases were analyzed using α‐synuclein SAA. Results: Six of 59 (10.2%) PSP cases were α‐synuclein SAA positive, including one case who was MSA‐type positive. An exploratory analysis showed that PSP cases who were Parkinson's disease–type positive were older and had a shorter disease duration compared with SAA‐negative cases. In contrast, 11 of 37 (29.7%) CBS cases were α‐synuclein SAA positive, including two cases who were MSA‐type positive. Conclusions: Our results suggest that α‐synuclein seeds can be detected in PSP and CBS using a cerebrospinal fluid α‐synuclein SAA, and in PSP this may impact on clinical course. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Ion cyclotron resonance heating for tungsten control in various JET H-mode scenarios

Ion cyclotron resonance heating (ICRH) in the hydrogen minority scheme provides central ion heating and acts favorably on the core tungsten transport. Full wave modeling shows that, at medium power level (4 MW), after collisional redistribution, the ratio of power transferred to the ions and the electrons vary little with the minority (hydrogen) concentration n H/n e but the high-Z impurity screening provided by the fast ions temperature increases with the concentration. The power radiated by tungsten in the core of the JET discharges has been analyzed on a large database covering the 2013-2014 campaign. In the baseline scenario with moderate plasma current (I p = 2.5 MA) ICRH modifies efficiently tungsten transport to avoid its accumulation in the plasma centre and, when the ICRH power is increased, the tungsten radiation peaking evolves as predicted by the neo-classical theory. At higher current (3-4 MA), tungsten accumulation can be only avoided with 5 MW of ICRH power with high gas injection rate. For discharges in the hybrid scenario, the strong initial peaking of the density leads to strong tungsten accumulation. When this initial density peaking is slightly reduced, with an ICRH power in excess of 4 MW,very low tungsten concentration in the core (∼10-5) is maintained for 3 s. MHD activity plays a key role in tungsten transport and modulation of the tungsten radiation during a sawtooth cycle is correlated to the fishbone activity triggered by the fast ion pressure gradient

Calculations to support JET neutron yield calibration: Modelling of neutron emission from a compact DT neutron generator

At the Joint European Torus (JET) the ex-vessel fission chambers and in-vessel activation detectors are used as the neutron production rate and neutron yield monitors respectively. In order to ensure that these detectors produce accurate measurements they need to be experimentally calibrated. A new calibration of neutron detectors to 14 MeV neutrons, resulting from deuterium–tritium (DT) plasmas, is planned at JET using a compact accelerator based neutron generator (NG) in which a D/T beam impinges on a solid target containing T/D, producing neutrons by DT fusion reactions. This paper presents the analysis that was performed to model the neutron source characteristics in terms of energy spectrum, angle–energy distribution and the effect of the neutron generator geometry. Different codes capable of simulating the accelerator based DT neutron sources are compared and sensitivities to uncertainties in the generator's internal structure analysed. The analysis was performed to support preparation to the experimental measurements performed to characterize the NG as a calibration source. Further extensive neutronics analyses, performed with this model of the NG, will be needed to support the neutron calibration experiments and take into account various differences between the calibration experiment and experiments using the plasma as a source of neutrons