Tag Archives: research

Passive nanorheology measurements

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What do marshmallows, jelly (or Jell-O), cream cheese and Chinese soup dumplings have in common?  They are often made with gelatin.  Gelatin is derived from the skin and bones of cattle and pigs through the partial hydrolysis of collagen.  Gelatin is a physical hydrogel meaning that it consists of a three-dimensional network of polymer molecules in which a large amount of water is absorbed, as much as 90% in gelatin.  These polymer molecules are cross-linked by hydrogen bonds, hydrophobic interactions and chain entanglements.  External stimuli, such as temperature, can change the level of cross-linking causing the material to transition between its solid, liquid and gel states.  This is why jelly sets in the fridge and melts when it’s heated up – the cross-links holding the molecules together break down.  This type of responsive behaviour allows the properties of hydrogels to be controlled at the micro and sub-micron scale for a host of applications including tissue engineering, drug delivery, water treatment, wearable technologies, and supercapacitors.  However, the design and manufacture of soft hydrogels can be challenging due to the lack of technology for measuring the local properties.  Current quantitative techniques for measuring the properties of hydrogels usually focus on bulk properties and provide little data about local variations or real-time responses to external stimuli.  My colleagues and I have used gold nanoparticles as probes in hydrogels to map the properties at the microscale of thermosensitive hydrogels undergoing real-time transition from the solid to gel phases [see ‘Passive nanorheological tool to characterise hydrogels’].  This is an extension, or perhaps more accurately an application, of our earlier work on tracking nanoparticles through the vitreous humour of the eye [see ‘Nanoparticle motion-through heterogeneous hydrogels’ on November 6th, 2024].  The novel technique, which yields passive nanorheological measurements, allows us to evaluate local viscosity, identify time-varying heterogeniety and monitor dynamic phase transitions at the micro through to nano scale.  The significant challenges of other techniques, such as weak signals due to high water content and the dynamism of hydrogels, are overcome with a fast, inexpensive and user-friendly technology.  Although, even with these advantages, you are unlikely to use it when you are making jelly or roasting marshmallows over the campfire; however, it is really useful for understanding the transport of drugs through biological hydrogels or designing manufacturing processes for artificial tissue.

Reference

Moira Lorenzo Lopez, Victoria R. Kearns, Eann A. Patterson & Judith M. Curran, Passive nanorheological tool to characterise hydrogels, Nanoscale, 2025,17, 15338-15347.

Image: Figure 5 from the above reference showing a hydrogel transitioning to a gel phase as result of an increase in temperature with 100 nm diameter gold nanoparticles with some particles (yellow arrows) at the interface between phases.  The image was taken in an inverted optical microscope set up for tracking the nanoparticles.

Star sequence minimises distortion

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It is some months since I have written about engineering so this post is focussed on some mechanical engineering.  The advent of pneumatic and electric torque wrenches has made it impossible for the ordinary motorist to change a wheel because it is very difficult to loosen wheel nuts by hand when they have been tightened by a powered wrench which most of us do not have available.  This has probably made motoring safer but also means we are more likely to need assistance when we have a flat tire.  It also means that the correct tightening pattern for nuts and bolts is less widely known.  A star-shaped sequence is optimum, i.e., if you have six bolts numbered sequentially around a circle then you start with #1, move across the diameter to #4, then to #2 followed by #5 across the diameter, then to #3 and across the diameter to #6.  This sequence is optimum for flanges, bolted joints in the frames of buildings and joining machine parts as well as wheel nuts.  We have recently discovered that it works in reverse, in the sense that it is the optimum sequence for releasing parts made by additive manufacturing (AM) from the baseplate of the AM machine (see ‘If you don’t succeed try and try again’ on September 29th, 2021).  Additive manufacturing induces large residual stresses as a consequence of the cycles of heat input to the part during manufacturing and some of these stresses are released when it is removed from the baseplate of the AM machine, which causes distortion of the part.  Together with a number of collaborators, I have been researching the most effective method of building thin flat plates using additive manufacturing (see ‘On flatness and roughness’ on January 19th, 2022).  We have found that building the plate vertically layer-by-layer works well when the plate is supported by buttresses on its edges.  We have used two in-plane buttresses and four out-of-plane buttresses, as shown in the photograph, to achieve parts that have comparable flatness to those made using traditional methods.  It turns out that optimum order for the removal of the buttresses is the same star sequence used for tightening bolts and it substantially reduces distortion of the plate compared to some other sequences.  Perhaps in retrospect, we should not be surprised by this result; however, hindsight is a wonderful thing.

The current research is funded jointly by the National Science Foundation (NSF) in the USA and the Engineering and Physical Sciences Research Council (EPSRC) in the UK and the project was described in ‘Slow start to an exciting new project on thermoacoustic response of AM metals’ on September 9th 2020.

Image: Photograph of a geometrically-reinforced thin plate (230 x 130 x 1.2 mm) built vertically layer-by-layer using the laser powder bed fusion process on a baseplate (shown removed from the AM machine) with the supporting buttresses in place.

Sources:

Patterson EA, Lambros J, Magana-Carranza R, Sutcliffe CJ. Residual stress effects during additive manufacturing of reinforced thin nickel–chromium plates. IJ Advanced Manufacturing Technology;123(5):1845-57, 2022.

Khanbolouki P, Magana-Carranza R, Sutcliffe C, Patterson E, Lambros J. In situ measurements and simulation of residual stresses and deformations in additively manufactured thin plates. IJ Advanced Manufacturing Technology; 132(7):4055-68, 2024.

Reproducibility in science and technology

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Schematic diagram from cited paper in Open Research EuropeIt has been suggested that there is crisis in science concerning the reproducibility of data [1].  New research findings are usually published based on data collected only by the group reporting the new findings, which raises the probability of bias in the results as well as reducing their likely validity.  It also creates a temptation to tamper with or falsify data given the incentives to publish.  It is unlikely that any prestigious journal would publish work that simply demonstrates that previously published findings can be reproduced consistently.  Yet, when they have tried to reproduce published data from experiments, many researchers have been unable to do so [2], which perhaps perversely makes the attempt to reproduce results publishable.  However, if no one has attempted to reproduce a published dataset then it stands until demonstrated to not be reproducible, which implies that much of the data in the published literature could be irreproducible and hence of dubious value.  This is a bigger problem than it might seem, because most scientific and technological innovation is built on the findings of fundamental research.  Hence, we are building on shaky foundations if results are not reproducible. Similarly, the transition from prototypes to reliable products is dependent on achieving reproducibility in the real-world of results obtained with a prototype in the laboratory.  I have been discussing these issues with a close collaborator for a number of years and last week we published a letter, in Open Research Europe, summarizing our views.  In ‘Achieving reproducibility in the innovation process’ [3], we propose that a different approach to reproducibility is required for each phase of the innovation process, i.e., discovery, translation and application, because reproducibility has different implications in each phase.  The diagram, reproduced from the paper (CC-BY-4.0), shows our ideas schematically but follow the link to read and comment on them.

References

[1] Baker, M. (2016). Reproducibility crisis. Nature, 533(26), 353-66.

[2] Camerer, C. F., Dreber, A., Holzmeister, F., Ho, T. H., Huber, J., Johannesson, M., … & Wu, H. (2018). Evaluating the replicability of social science experiments in Nature and Science between 2010 and 2015. Nature Human Behaviour, 2(9), 637-644.

[3] Whelan M & Patterson EA, (2025). Achieving reproducibility in the innovation process, Open Research Europe, 5:25. https://doi.org/10.12688/openreseurope.19408.1

Corona-induced transition from molecular to particle motion in biological media

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Light signatures generated by particles in a nanoscopeIn last month’s post [see ‘Nanoparticle motion through heterogeneous hydrogels’ on November 6th, 2024], I described our recent work on tracking nanoparticles through a model of the vitreous humour and mentioned it was the first of two articles published in the Nature journal, Scientific Reports.  In the second article, we explored the use of caustics in an optical microscope [see ‘Seeing the invisible’ on October 29th, 2014] to track nanoparticles in biofluids.  Nanoparticles are below the resolution of an optical microscope because they are substantially smaller than the wavelength of visible light; hence, they are usually tracked using fluorescent markers or tags attached chemically to the nanoparticles.  These tags can influence both the motion of the particles and biological activity so caustics provide a label-free technique that allows particles to be tracked in real-time using a standard optical microscope.  In most of our previous research, we have tracked nanoparticles in transparent fluids such as water, glycerol-water mixtures, or the hydrogels described in last month’s post.  In our latest work, we have tracked small nanoparticles with diameters from 10 to 100 nm in common cell culture media with different concentrations of serum proteins.  These fluids are a ‘soup’ of complex protein molecules that interact with one another and the gold nanoparticles being tracked.  We found that the presence of proteins caused a reduction in the rate of diffusion for both positively- and negatively-charged particles and we concluded that the proteins form a corona around each nanoparticle effectively enlarging its diameter.  For larger nanoparticles, and those positively-charged, the enlargement appears to cause a transition from molecular motion, in which particle diameter is unimportant, to particle motion where larger particles diffuse more slowly.  We first explored this transition from fractional to classical Stokes-Einstein behaviour in simple fluids in 2017 [‘Slow moving nanoparticles‘ on December 13th 2017] and it seems likely to be complicated in these complex fluids.  Hence, understanding protein dynamics as well nanoparticle dynamics will be essential to the development of nanotechnologies applicable in biological environments.  So, we have lots more work to do!

Sources:

Schleyer G, Patterson EA, Curran JM. Label free tracking to quantify nanoparticle diffusion through biological media. Scientific Reports. 2024 Aug 13;14(1):18822.

Coglitore D, Edwardson SP, Macko P, Patterson EA, Whelan MP, Transition from fractional to classical Stokes-Einstein behaviour in simple fluids, Royal Society Open Science, 4:170507, 2017.