Tag Archives: science

Nanoparticle motion through heterogeneous hydrogels

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Over the last couple of years, we have been transitioning a technique, which we developed for tracking the motion of nanoparticles using caustics [see ‘Slow moving nanoparticles‘ on December 13th 2017], from its initial use in exploring mechanics at the nanoscale to applications in nanobiology [See ‘Label-free real-time tracking of individual bacterium‘ on January 25th, 2023] where it has the advantages of functioning in real-time and being label-free (chemical labels can impact motion, protein interactions and cell behaviour).  In the summer, we had couple of articles published in consecutive issues of the Nature journal, Scientific Reports which describe our recent work.  In the first, we have explored the diffusion of nanoparticles through a synthetic analogue of the vitreous humour in order to support the design of novel therapeutics for retinal diseases.  Retinal diseases, such as macular degeneration and diabetic retinopathy, affects millions of people globally and treatment often involves frequent intravitreal injections of anti-vascular endothelium growth factor agents and corticoids.  Delivery of the appropriate dose to the retinal cell layer is challenging due to the complex nature of the vitreous and functionalised nanoparticles offer a potential solution.  In vivo animal testing is inappropriate because of the ethical concerns and poor representation of human eyes and ex vivo testing of cadaveric eyes is unreliable due to the instability of biomechanical and biochemical properties of the vitreous humour.  Hence, we used agar-hyaluronic acid hydrogels as an in vitro model of the vitreous and employed the caustic technique to track the motion of nanoparticles through the hydrogels.  The hydrogels had been validated as a representative model of the vitreous humour by other research groups.  Our tracking technique revealed that the electric charge on the nanoparticles did not affect their diffusion through the hydrogel; however, both the diameter of the particles and the heterogeneous nature of the gel influenced the diffusion.  Nanoparticles with diameters of 200, 100 and 50 nm moved progressively more quickly and over a larger area.  The diffusion rates in hydrogels with a high viscosity (about 450  Pa.s) were consistent throughout the gel implying that the gel was homogeneous, while gels with medium (about 40 Pa.s) to low (about 3 Pa.s) viscosity generated diffusion rates that were distributed bi-modally suggesting a heterogeneous gel with zones of low and high density in which the particles moved more or less freely.  The heterogeneity of a gel renders a global value for viscosity somewhat meaningless and makes comparisons difficult with the vitreous humour because it is also heterogeneous; however, global values of viscosity for porcine vitreous humour are typically 1 Pa.s.  We are continuing this research; however, our published work has demonstrated that the use of caustics in an optical microscope is a reproducible and inexpensive technique for exploring the design of novel nanoscale drug delivery systems for the eye.

Source: Lorenzo Lopez M, Kearns VR, Curran JM, Patterson EA. Diffusion of nanoparticles in heterogeneous hydrogels as vitreous humour in vitro substitutes. Scientific reports. 2024 Jul 29;14(1):1744.

Image: Random track of a nanoparticle superimposed on its image generated in the microscope using a pin-hole and narrowband filter.

Predicting release rates of hydrogen from stainless steel

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Decorative photograph showing electrolysis cellThe influence of hydrogen on the structural integrity of nuclear power plant, where water molecules in the coolant circuit can be split by electrolysis or radiolysis to produce hydrogen, has been a concern to engineers for decades.  However, plans for a hydrogen economy and commercial fusion reactors, in which plasma-facing structural components will likely be exposed to hydrogen, has accelerated interest in understanding the complex interactions of hydrogen with metals, especially in the presence of irradiation.  A key step in advancing our understanding of these interactions is the measurement and prediction of the uptake and release of hydrogen by key structural materials.  We have recently published a study in Scientific Reports in which we developed a method for predicting the amount hydrogen in a steel under test conditions.  We used a sample of stainless steel as an electrode (cathode) in an electrolysis cell that split water molecules producing hydrogen atoms that were attracted to the steel. After loading the steel with hydrogen in the cell, we measured the rate of release of the hydrogen from the steel over two minutes by monitoring the drop in current in the cell, using a technique called potentiostatic discharge.  We used our measurements to calibrate a model of hydrogen release rate, based on Fick’s second law of diffusion, which relates the rate of hydrogen motion (diffusion) to the surface area perpendicular to the motion and the concentration gradient in the direction of motion.  Finally, we used our calibrated model to predict the release rate of hydrogen over 24 hours and checked our predictions using a second measurement based on the hydrogen released when the steel was melted.  So, now we have a method of predicting the amount of hydrogen in a steel remaining in a sample many hours after exposure during electrolysis without destroying the test sample.  This will allow us to perform better defined tests on the influence of hydrogen on the performance of stainless steel in the extreme environments of fission and fusion reactors.

Source:

Weihrauch M, Patel M, Patterson EA. Measurements and predictions of diffusible hydrogen escape and absorption in cathodically charged 316LN austenitic stainless steel. Scientific Reports. 13(1):10545, 2023.

Image:

Figure 2a from Weihrauch et al , 2023 showing electrolysis cell setup for potentiostatic discharge experiments.

How many engineers do you need when the lights go out?

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An exemplar adverse outcome pathway for microplastics in aquatic species

From Galloway & Lewis, 2016

One to change the lightbulb and five to perform a Fault Tree Analysis (FTA).  A fault tree is a diagram that illustrates the relationship between failures at component and system levels.  Engineers use them to understand the mechanisms or logic that lead from component malfunctions to system breakdowns and to identify components that are critical to system reliability.  They are useful in optimizing designs, demonstrating compliance with safety requirements and as diagnostic tools when things go wrong.  There are some simple examples of fault trees for ‘no light in room’ and ‘missing the bus’ amongst others available from Visual Paradigm Online.  All of these examples illustrate qualitative relationships but we can also establish quantitative relationships using the rate of occurrence of each initiating event to arrive at a probability of failure (PoF) for the system.  There is an example for an indicator light in an automobile in a 2016 paper by Nabarun Das and William Taylor (see figure 2 in the paper).  An equivalent in biology are Adverse Outcome Pathways (AOPs) that identify the relationship between a molecular initiating event and a toxic effect through a series of key events.  For instance, microplastics causing altered gene expression and oxidative damage leading to altered fatty acid metabolism, stress response and altered cellular division resulting ultimately in population decline in aquatic species as shown in the graphic from a paper by Tamara Galloway and Ceri Lewis also published in 2016. Most AOPs are qualitative; however, quantitative Adverse Outcome Pathways (qAOPs) are starting to be developed as tools for quantitative risk assessment of chemicals.  Biologists and engineers are not using the same words, actually they are using entirely different vocabularies; nevertheless they are talking about the same methodologies.  An AOP network and an FTA are essentially the same concept and a probabilistic fault tree analysis is a quantitative adverse outcome pathway.  However, it seems unlikely that either biologists or engineers will adopt the language used by the other so they will be reliant on a few foolhardy interlocutors prepared to cross the discipline boundaries and highlight the opportunities for cross-fertilization of ideas and solutions.

Sources

Das N, Taylor W. Quantified fault tree techniques for calculating hardware fault metrics according to ISO 26262. In2016 IEEE Symposium on Product Compliance Engineering (ISPCE), pp. 1-8. IEEE, 2016. Also available at https://incompliancemag.com/article/quantified-fault-tree-techniques-for-calculating-hardware-fault-metrics-according-to-iso-26262/

Galloway TS, Lewis CN. Marine microplastics spell big problems for future generations. Proceedings of the national academy of sciences. 113(9):2331-3, 2016.

Taking an aircraft’s temperature as a health check

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The title of this post is the title of a talk that I will deliver during the Pint of Science Festival in Liverpool later this month.  At last year’s festival I spoke about the very small: Revealing the invisible: real-time motion of virus particles [see ‘Fancy a pint of science‘ on April 27th, 2022].  This year I am moving up the size scale and from biomedical engineering to aerospace engineering to talk about condition monitoring in aircraft structures based on our recent research in the INSTRUCTIVE [see ‘INSTRUCTIVE final reckoning‘ on January 9th 2019] and DIMES [see ‘Our last DIMES‘ on September 22, 2021] projects.  I am going describe how we have reduced the size and cost of infrared instrumentation for monitoring damage propagation in aircraft structures while at the same time increasing the resolution so that we can detect 1 mm increments in crack growth in metals and 6 mm diameter indications of damage in composite materials.  If you want to learn more how we did it and fancy a pint of science, then join us in Liverpool later this month for part of the world’s largest festival of public science.  This year we have a programme of engineering talks on Hope Street in Frederiks on May 22nd and in the Philharmonic Dining Rooms on May 23rd where I be the second speaker.

The University of Liverpool was the coordinator of the DIMES project and the other partners were Empa, Dantec Dynamics GmbH and Strain Solutions Ltd.  Strain Solutions Limited was the coordinator of the INSTRUCTIVE project in which the other participant was the University of Liverpool.  Airbus was the project manager for both projects.

The DIMES and INSTRUCTIVE projects  received funding from the Clean Sky 2 Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 820951 and 6968777 respectively.

The opinions expressed in this blog post reflect only the author’s view and the Clean Sky 2 Joint Undertaking is not responsible for any use that may be made of the information it contains.