Tag Archives: research

Seeing things with nanoparticles

1 Reply

Photograph showing optical microscope and ancilliary equipment set up on an optical benchLast week brought excitement and disappointment in approximately equal measures for my research on tracking nanoparticles [see ‘Slow moving nanoparticles‘ on December 13th, 2017 and ‘Going against the flow‘ on February 3rd, 2021]. The disappointment was that our grant proposal on ‘Optical tracking of virus-cell interaction’ was not ranked highly enough to receive funding from Engineering and Physical Sciences Research Council. Rejection is an occupational hazard for academics seeking to win grants and you learn to accept it, learn from the constructive criticism and look for ways of reworking the ideas into a new proposal. If you don’t compete then you can’t win. The excitement was that we have moved our apparatus for tracking nanoparticles into a new laboratory, which has been set up for it, so that we can start work on a pilot study looking at the ‘Interaction of bacteria and viruses with cellular and hard surfaces’.  We are also advertising for a PhD student to start in September 2021 to work on ‘Developing pre-clinical models to optimise nanoparticle based drug delivery for the treatment of diabetic retinopathy‘.  This is an exciting development because it represents our first step from fundamental research on tracking nanoparticles in biological media towards clinical applications of the technology. Diabetic retinopathy is an age-related condition that threatens your sight and currently is managed by delivery of drugs to the inside of the eye which requires frequent visits to a clinic for injections into the vitreous fluid of the eye.  There is potential to use nanoparticles to deliver drugs more efficiently and to support these developments we plan that the PhD student will use our real-time, non-invasive, label-free tracking technology to quantify nanoparticle motion through the vitreous fluid and the interaction of nanoparticles with the cells of the retina.

 

Out of the valley of death into a hype cycle?

4 Replies

Fig 5 from Middleton et al with full captionThe capability to identify damage and track its propagation in structures is important in ensuring the safe operation of a wide variety of engineering infrastructure, including aircraft structures. A few years ago, I wrote about research my group was performing, in the INSTRUCTIVE project [see ‘INSTRUCTIVE final reckoning‘ on January 9th, 2019] with Airbus and Strain Solutions Limited, to deliver a new tool for monitoring the development of damage using thermoelastic stress analysis (TSA) [see ‘Counting photons to measure stress‘ on November 18th, 2015].  We collected images using a TSA system while a structural component was subject to cycles of load that caused damage to initiate and propagate during a fatigue test. The series of images were analysed using a technique based on optical flow to identify apparent movement between the images which was taken as indication of the development of damage [1]. We demonstrated that our technique could indicate the presence of a crack less than a millimetre in length and even identify cracks initiating under the heads of bolts using experiments performed in our laboratory [see ‘INSTRUCTIVE update‘ on October 4th, 2017].  However, this technique was susceptible to errors in the images when we tried to use low-cost sensors and to changes in the images caused by flight cycle loading with varying amplitude and frequency of loads.  Essentially, the optical flow approach could be fooled into identifying damage propagation when a sensor delivered a noisy image or the shape of the load cycle was changed.  We have now overcome this short-coming by replacing the optical flow approach with the orthogonal decomposition technique [see ‘Recognising strain‘ on October 28th, 2015] that we developed for comparing data fields from measurements and predictions in validation processes [see ‘Million to one‘ on November 21st, 2018] .  Each image is decomposed to a feature vector and differences between the feature vectors are indicative of damage development (see schematic in thumbnail from [2]).  The new technique, which we have named the differential feature vector method, is sufficiently robust that we have been able to use a sensor costing 1% of the price of a typical TSA system to identify and track cracks during cyclic loading.  The underpinning research was published in December 2020 by the Royal Society [2] and the technique is being implemented in full-scale ground-tests on aircraft structures as part of the DIMES project.  Once again, a piece of technology is emerging from the valley of death [see ‘Slowly crossing the valley of death‘ on January 27th, 2021] and, without wishing to initiate the hype cycle [see ‘Hype cycle‘ on September 23rd, 2015], I hope it will transform the use of thermal imaging for condition monitoring.

Logos of Clean Sky 2 and EUThe INSTRUCTIVE and DIMES projects have received funding from the Clean Sky 2 Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under grant agreements No. 685777 and No. 820951 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.

References

[1] Middleton CA, Gaio A, Greene RJ & Patterson EA, Towards automated tracking of initiation and propagation of cracks in Aluminium alloy coupons using thermoelastic stress analysis, J. Non-destructive Testing, 38:18, 2019.

[2] Middleton CA, Weihrauch M, Christian WJR, Greene RJ & Patterson EA, Detection and tracking of cracks based on thermoelastic stress analysis, R. Soc. Open Sci. 7:200823, 2020.

Reduction in usefulness of reductionism

1 Reply

decorative paintingA couple of months ago I wrote about a set of credibility factors for computational models [see ‘Credible predictions for regulatory decision-making‘ on December 9th, 2020] that we designed to inform interactions between researchers, model builders and decision-makers that will establish trust in the predictions from computational models [1].  This is important because computational modelling is becoming ubiquitous in the development of everything from automobiles and power stations to drugs and vaccines which inevitably leads to its use in supporting regulatory applications.  However, there is another motivation underpinning our work which is that the systems being modelled are becoming increasingly complex with the likelihood that they will exhibit emergent behaviour [see ‘Emergent properties‘ on September 16th, 2015] and this makes it increasingly unlikely that a reductionist approach to establishing model credibility will be successful [2].  The reductionist approach to science, which was pioneered by Descartes and Newton, has served science well for hundreds of years and is based on the concept that everything about a complex system can be understood by reducing it to the smallest constituent part.  It is the method of analysis that underpins almost everything you learn as an undergraduate engineer or physicist. However, reductionism loses its power when a system is more than the sum of its parts, i.e., when it exhibits emergent behaviour.  Our approach to establishing model credibility is more holistic than traditional methods.  This seems appropriate when modelling complex systems for which a complete knowledge of the relationships and patterns of behaviour may not be attainable, e.g., when unexpected or unexplainable emergent behaviour occurs [3].  The hegemony of reductionism in science made us nervous about writing about its short-comings four years ago when we first published our ideas about model credibility [2].  So, I was pleased to see a paper published last year [4] that identified five fundamental properties of biology that weaken the power of reductionism, namely (1) biological variation is widespread and persistent, (2) biological systems are relentlessly nonlinear, (3) biological systems contain redundancy, (4) biology consists of multiple systems interacting across different time and spatial scales, and (5) biological properties are emergent.  Many engineered systems possess all five of these fundamental properties – you just to need to look at them from the appropriate perspective, for example, through a microscope to see the variation in microstructure of a mass-produced part.  Hence, in the future, there will need to be an increasing emphasis on holistic approaches and systems thinking in both the education and practices of engineers as well as biologists.

For more on emergence in computational modelling see Manuel Delanda Philosophy and Simulation: The Emergence of Synthetic Reason, Continuum, London, 2011. And, for more systems thinking see Fritjof Capra and Luigi Luisi, The Systems View of Life: A Unifying Vision, Cambridge University Press, 2014.

References:

[1] Patterson EA, Whelan MP & Worth A, The role of validation in establishing the scientific credibility of predictive toxicology approaches intended for regulatory application, Computational Toxicology, 17: 100144, 2021.

[2] Patterson EA &Whelan MP, A framework to establish credibility of computational models in biology. Progress in biophysics and molecular biology, 129: 13-19, 2017.

[3] Patterson EA & Whelan MP, On the validation of variable fidelity multi-physics simulations, J. Sound & Vibration, 448:247-258, 2019.

[4] Pruett WA, Clemmer JS & Hester RL, Physiological Modeling and Simulation—Validation, Credibility, and Application. Annual Review of Biomedical Engineering, 22:185-206, 2020.

Psychological entropy increased by ineffectual leaders

3 Replies

Decorative image of a flowerYou might have wondered why I used ‘entropy’, and ‘psychological entropy’ in particular, as examples in my post on drowning in information a couple of weeks ago [‘We are drowning in information while starving for wisdom‘ on January 20th, 2021].  It was not random.  I spent some of the Christmas break catching up on my reading pile of interesting looking scientific papers and one on psychological entropy stimulated my thinking.  Psychological entropy is the concept that our brains are self-organising systems in a continual dialogue with the environment which leads to the emergence of a relatively small number of stable low-entropy states.  These states could be considered to be assemblies of neurons or patterns of thoughts, perhaps a mindset.  When we are presented with a new situation or problem to solve for which the current assembly or mindset is unsuitable then we start to generate new ideas by generating more and different assemblies of neurons in our brains.  Our responses become unpredictable as the level of entropy in our minds increases until we identify a new approach that deals effectively with the new situation and we add it to our list of available low-entropy stable states.  If the external environment is constantly changing then our brains are likely to be constantly churning through high entropy states which leads to anxiety and psychological stress.  Effective leaders can help us cope with changing environments by providing us with a narrative that our brains can use as a blueprint for developing the appropriate low-entropy state.  Raising psychological entropy by the right amount is conducive to creativity in the arts, science and leadership but too much leads to mental breakdown.

Sources:

Hirsh JB, Mar RA, Peterson JB. Psychological entropy: A framework for understanding uncertainty-related anxiety. Psychological review. 2012 Apr;119(2):304

Handscombe RD & Patterson EA, The Entropy Vector: connecting science and business, Singapore: World Scientific Press, 2004.