Tag Archives: nanoparticles

Happy New Year!

Decorative photograph of sculpture of a skeletal person leading a skeletal dinosaurThis year I have written about 20,000 words in 52 posts (including this one); and, since this is the last post of the year, I thought I would take a brief look back at what has preoccupied me in 2021.  Perhaps, not surprisingly the impact of the coronavirus on our lifestyle has featured regularly – almost every week for a month between mid-March and mid-April when we were in lockdown in the UK.  However, the other topics that I have written about frequently are my research on the dynamics of nanoparticles and, in the last six months, on dealing with uncertainty in digital engineering and decision making.  I have also returned several times to innovation processes and transitioning lab-based research into industry.  While following the COP26 in early November, I wrote a series of three posts focussed on energy consumption and the paradigm shifts required to slow down climate change.  There are some connections between these topics: viruses are nanoparticles whose transport and dynamics we do not fully understand; and, digital engineering tools are being used to explore zero-carbon approaches to, for example, energy generation and air transport.  The level of complexity, innovation and urgency associated with developing solutions to these challenges mean that there are always some unknowns and uncertainty when making associated decisions.

The links below are grouped by the topics mentioned above.  I expect there will be more on all of these topics in 2022; however, the topic of next week’s post is unknown because I have not written any posts in advance.  I hope that the uncertainty about the topic of the next post will keep you reading in 2022! 

Coronavirus pandemic: ‘Distancing ourselves from each other‘ on January 13th, 2021; ‘On the impact of writing on well-being‘ on March 3rd, 2021; ‘Collegiality as a defence against pandemic burnout‘ on March 24th, 2021; ‘It’s tiring looking at yourself‘ on March 31st, 2021; ‘Switching off and walking in circles‘ on April 7th, 2021; ‘An upside to lockdown‘ on April 14th, 2021; ‘A brief respite in a long campaign to overcome coronavirus‘ on June 23rd, 2021; and ‘It is hard to remain positive‘ November 3rd 2021.

Energy and climate change: ‘When you invent the ship, you invent the shipwreck‘ on August 25th, 2021; ‘It is hard to remain positive‘ November 3rd 2021; ‘Where we are and what we have‘ on November 24th, 2021; ‘Disruptive change required to avoid existential threats‘ on December 1st, 2021; and ‘Bringing an end to thermodynamic whoopee‘ on December 8th, 2021.

Innovation processes: ‘Slowly crossing the valley of death‘ on January 27th, 2021; ‘Out of the valley of death into a hype cycle?‘ on February 24th, 2021; ‘Innovative design too far ahead of the market?‘ on May 5th, 2021 and ‘Jigsaw puzzling without a picture‘ on October 27th, 2021.

Nanoparticles: ‘Going against the flow‘ on February 3rd, 2021; ‘Seeing things with nanoparticles‘ on March 10th, 2021; and ‘Nano biomechanical engineering of agent delivery to cells‘ on December 15th, 2021.

Uncertainty: ‘Certainty is unattainable and near-certainty is unaffordable‘ on May 12th, 2021; ‘Neat earth objects make tomorrow a little less than certain‘ on May 26th, 2021; ‘Negative capability and optimal ambiguity‘ on July 7th, 2021; ‘Deep uncertainty and meta ignorance‘ on July 21st, 2021; ‘Somethings will always be unknown‘ on August 18th, 2021; ‘Jigsaw puzzling without a picture‘ on October 27th, 2021; and, ‘Do you know RIO?‘ on November 17th, 2021.

Nano biomechanical engineering of agent delivery to cells

figure 1 from [1] with text explanationWhile many of us are being jabbed in the arm to deliver an agent that stimulates our immune system to recognize the coronavirus SARS-CoV-2 as a threat and destroy it, my research group has been working, in collaboration with colleagues at the European Commission Joint Research Centre, on the dynamics of nanoparticles [1] [see ‘Size matters‘ on October 23rd, 2019] which could be used as carriers for the targeted delivery of therapeutic, diagnostic and imaging agents in the human body [2].  The use of nanoparticles to mechanically stimulate stem cells to activate signalling pathways and modulate their differentiation also has some potential [3]. In studies of the efficacy of nanoparticles in these biomedical applications, the concentration of nanoparticles interacting with the cell is a primary factor influencing both the positive and negative effects.  Such studies often involve exposing a monolayer of cultured cells adhered to the bottom of container to a dose of nanoparticles and monitoring the response over a period of time.  Often, the nominal concentration of the nanoparticles in biological medium supporting the cells is reported and used as the basis for determining the dose-response relationships.  However, we have shown that this approach is inaccurate and leads to misleading results because the nanoparticles in solution are subject to sedimentation due to gravity, Brownian motion [see ‘Slow moving nanoparticles‘ on December 13th, 2017] and inter-particle forces [see ‘ Going against the flow‘ on February 3rd, 2021] which affect their transport within the medium [see graphic] and the resultant concentration adjacent to the monolayer of cells.  Our experimental results using the optical method of caustics [see ‘Holes in fluids‘ on October 22nd, 2014] have shown that nanoparticle size, colloidal stability and solution temperature influence the distribution of nanoparticles in solution.  For particles larger than 60 nm in diameter (about one thousandth of the diameter of a human hair) the nominal dose differs significantly from the dose experienced by the cells.  We have developed and tested a theoretical model that accurately describes the settling dynamics and concentration profile of nanoparticles in solution which can be used to design in vitro experiments and compute dose-response relationships.

References

[1] Giorgi F, Macko P, Curran JM, Whelan M, Worth A & Patterson EA. 2021 Settling dynamics of nanoparticles in simple and biological media. Royal Society Open Science, 8:210068.

[2] Daraee H, Eatemadi A, Abbasi E, Aval SF, Kouhi M, & Akbarzadeh A. 2016 Application of gold nanoparticles in biomedical and drug delivery. Artif. Cells Nanomed. Biotechnol. 44, 410–422. (doi:10.3109/21691401.2014.955107)

[3] Wei M, Li S, & Le W. 2017 Nanomaterials modulate stem cell differentiation: biological
interaction and underlying mechanisms. J. Nanobiotechnol. 15, 75. (doi:10.1186/s12951-
017-0310-5)

Seeing things with nanoparticles

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.

 

Going against the flow

Decorative photograph of a mountain riverLast week I wrote about research we have been carrying out over the last decade that is being applied to large scale structures in the aerospace industry (see ‘Slowly crossing the valley of death‘ on January 27th, 2021). I also work on very much smaller ‘structures’ that are only tens of nanometers in diameter, or about a billion times smaller than the test samples in last week’s post (see ‘Toxic nanoparticles?‘ on November 13th, 2013). The connection is the use of light to measure shape, deformation and motion; and then utilising the measurements to validate predictions from theoretical or computational models. About three years ago, we published research which demonstrated that the motion of very small particles (less than about 300 nanometres) at low concentrations (less than about a billion per millilitre) in a fluid was dominated by the molecules of the fluid rather than interactions between the particles (see Coglitore et al, 2017 and ‘Slow moving nanoparticles‘ on December 13th, 2017). This data confirmed results from earlier molecular dynamic simulations that contradicted predictions using the Stokes-Einstein equation, which was derived by Einstein in his PhD thesis for a ‘Stokes’ particle undergoing Brownian motion. The Stokes-Einstein equation works well for large particles but the physics of motion changes when the particles are very small and far apart so that Van der Waals forces and electrostatic forces play a dominant role, as we have shown in a more recent paper (see Giorgi et al, 2019).  This becomes relevant when evaluating nanoparticles as potential drug delivery systems or assessing the toxicological impact of nanoparticles.  We have shown recently that instruments based on dynamic scattering of light from nanoparticles are likely to be inaccurate because they are based on fitting measurement data to the Stokes-Einstein equation.  In a paper published last month, we found that asymmetric flow field flow fractionation (or AF4)  in combination with dynamic light scattering when used to detect the size of nanoparticles in suspension, tended to over-estimate the diameter of particles smaller than 60 nanometres at low concentrations by upto a factor of two (see Giorgi et al, 2021).  Someone commented recently that our work in this area was not highly cited but perhaps this is unsurprising when it undermines a current paradigm.  We have certainly learnt to handle rejection letters, to redouble our efforts to demonstrate the rigor in our research and to present conclusions in a manner that appears to build on existing knowledge rather than demolishing it.

Sources:

Coglitore, D., Edwardson, S.P., Macko, P., Patterson, E.A. and Whelan, M., 2017. Transition from fractional to classical Stokes–Einstein behaviour in simple fluids. Royal Society open science, 4(12), p.170507.

Giorgi, F., Coglitore, D., Curran, J.M., Gilliland, D., Macko, P., Whelan, M., Worth, A. and Patterson, E.A., 2019. The influence of inter-particle forces on diffusion at the nanoscale. Scientific reports, 9(1), pp.1-6.

Giorgi, F., Curran, J.M., Gilliland, D., La Spina, R., Whelan, M.P. & Patterson, E.A. 2021, Limitations of nanoparticles size characterization by asymmetric flow field-fractionation coupled with online dynamic light scattering, Chromatographia, doi.org/10/1007/s10337-020-03997-7.

Image is a photograph of a fast flowing mountain river taken in Yellowstone National Park during a roadtrip across the USA in 2006.