The ActiveMatter project leads to a startup creation: Inside Therapeutics

Audrey Nsamela, co-founder of InsideTx, applied her research to nanomedicine formulation with microfluidics. (Image from InsideTx.)
Leveraging the work of Audrey Nsamela during the Active Matter project, a new company named Inside Therapeutics (Inside Tx) has been created.

Inside Therapeutics aims to provide innovative nanoparticle manufacturing platforms to help with the novel generation of RNA-LNP therapeutics development. Based on innovative microfluidic technology developed during the Active Matter project, this novel platform will help unlock the main sticking points of the current RNA-LNP drug development process including:

  • The synthesis of very low volumes during for the drug discovery (or screening) phase.
  • Ensuring a seamless scalability of the RNA-LNP manufacturing.
  • Allowing for continuous production of high quality nanoparticles.

It opens up new perspectives for research and industrial applications were lipid or polymeric-based nanoparticles are required.

Feel free to reach out to Audrey at audrey.nsamela@insidetx.com should you have any questions!

Logo of Inside Therapeutics. (Image from InsideTx.)

A platform for stop flow gradient generation to investigate chemotaxis published in Angewandte Chemie

A controlled gradient of hydrogen peroxide is generated in a microfluidic chip where a precise pressure retroactive loop prevents any external flow to interfere with the chemotaxis response of catalytic microswimmers. (Image by A. Nsamela.)
A platform for stop flow gradient generation to investigate chemotaxis
Z. Xiao, A. Nsamela, B. Garlan, and J. Simmchen
Angew. Chemie Int. Ed., Feb. 2022
chemRxiv: 10.26434/chemrxiv-2021-sxqm1
DOI: 10.1002/anie.202117768

The ability of artificial microswimmers to respond to external stimuli and the mechanistical details of their origins belong to the most disputed challenges in interdisciplinary science. Therein, the creation of chemical gradients is technically challenging, because they quickly level out due to diffusion. Inspired by pivotal stopped ow experiments in chemical kinetics, we show that microfluidics gradient generation combined with a pressure feedback loop for precisely controlling the stop of the flows, can enable us to study mechanistical details of chemotaxis of artificial Janus micromotors, based on a catalytic reaction. We find that these copper Janus particles display a chemotactic motion along the concentration gradient in both, positive and negative direction and we demonstrate the mechanical reaction of the particles to unbalanced drag forces, explaining this behaviour.

Audrey Nsamela presented a poster at MicroTAS 2021 hybrid conference in Palm Springs

The Miniaturized Systems for Chemistry and Life Sciences (or MicroTAS) conference took place this year on October 10-14th in a hybrid configuration, both online and in-person in Palm Springs (USA). This conference unite top researchs groups from all over the world and present the most recent advances in MEMS. Audrey attended the conference online from Paris and presented her poster on the development of a sperm sorting platform including chemotaxis guidance.

Audrey Nsamela and Jesús Domínguez both present a poster at MNF conference in Toulouse

The Micro-Nano-Fluidics meeting took place in Toulouse (France) in September 2021. This conference was organized by a french research group and covered mainly 6 topics: Nanofluidics, Chemical Engineering, Flow-waves interactions, Flow chemistry, Diagnostics and clinics, Organ-on-Chip. Audrey and Jesús attended the 2 days conference and presented their poster. Audrey’s poster was focused on the development of a microfluidic platform for sperm sorting, while Jesús’s poster described his work on microfluidic droplet generation for bacteria encapsulation and biofilm studies. This national conference was a great opportunity for both ESRs to meet other researchers in microfluidics and discuss about applications in Active Matter.

Group picture.

Round Table Discussion on Fluids and Active Matter

A screenshot taken during the round table discussion of 13 September 2021.

In our third round table we had the pleasure of Gareth Alexander, Ignacio Pagonabarraga and Julia Yeomans as our guest panellists. This time the overall theme was “Fluids and Active Matter” and hosted by Chun-Jen Chen, Davide Breoni, Danne van Roon, Audrey Nsamela, Dana Hassan and Sandrine Heijnen. 

It started out with an interesting discussion regarding the motivation to get in and what amazes them the most in the field of active matter. Here it became clear that active systems can have their passive counterparts, and works for easy transitions from active to passive systems, but at the same time, such active systems still have the potential to answer many fundamental questions. From this topic, one of the key takeaways was that the project that you are currently working on should be the subject that amazes you the most. 

The next topic that stood as the centre of the discussion was turbulence. Turbulence is an interesting phenomenon where a lot of things are still unknown. The intriguing concept here was that real, or fluid-dynamical, turbulence is different from active turbulence. As a clarification, Julia Yeomans introduced the following comparison. Real turbulence is observed in a waterfall where the energy follows the Kolmogorov cascade. In active turbulence, the energy originates from the individual particles moving and does not follow the same energy trend  as real turbulence. 

As one of the final topics, we were wondering what are the main takeaways regarding active nematics, especially if it’s not your field. We got it set for you in four points. One, it is fundamentally unstable and therefore creates flows. Point number two, motile topological effects. Number three, the potential connection it has to biological systems and the ability to explain similar processes. Finally, number four, the fact that we are looking at non-equilibrium systems.

Round Table Discussion on Introduction to Theoretical Active Matter

A screenshot taken during the round table discussion of 7 September 20201.

The first round table in the theoretical training gave a chance to start an interesting discussion which will continue in the following meetings.

The organizing ESRs were Ayten Gülce Bayram, Laura Natali, Liam Ruske, Jérémie Bertrand, Davide Breoni and Audrey Nsamela. They welcomed and introduced the three guests of the session: Nuno Araújo from the University of Lisbon, Jan Wehr from the University of Arizona and Denis Bartolo from École normale supérieure de Lyon.

The round table started with a personal question to the speakers about their interests and motivations for working in theoretical active matter. Having different backgrounds, the answers were very different, Nuno was attracted by non-intuitive behaviors observed in active matter experiments, while Jan started from a purely mathematical point of view and then moved towards physics of active systems. Denis provided another motivation, being head of a lab that deals with both theory and experiments.

The following discussion focused on the interaction and hierarchy between theory, simulations, and experiments. They all agree that establishing a constructive collaboration with experimental groups is not easy, but at the same time, it can have many benefits for both sides. However, none of the three elements is necessary for the others: a good paper can be presenting a theory not connected with experiments, even if its possible applications are not foreseeable yet. Denis firmly pointed out the difference between the observations and the tools (theoretical, numerical, and experimental) employed to explain it.

We also had a few more specific questions for the speakers, such as the distinctions in thinking between mathematicians and theoretical physicists, the possible applications to financial markets, and the differences in modeling artificial flocks and human crowds, which are often controlled by non-hydrodynamic variables.

We concluded the meeting by asking every one of our guests their tips for communicating the theory of active matter to a larger public. Here the answers were more relaxed and can be summed up as: trying to avoid technical and mathematical details while explaining the importance of the research problems, also using more familiar examples such as simulations employed in animation movies.

The Active Matter network has a new logo !

New ActiveMatter logos: color and BW version. (Image by ActiveMatter ESRs)
With a joint effort of the ESR students, a new logo for the ActiveMatter website was designed. The idea started as a handdrawing on a piece of paper and was quickly adapted to a better version with drawing softwares. More than 15 logos were suggested and submitted to a vote. The competition was fierce but we all came to agree on one of them and we are happy to present you the new official logo of the ITN ActiveMatter !

Microfluidics for Microswimmers, a tutorial review published in Small

Illustration of the synergies between microfluidics and microswimmers described in this review: from the fabrication, to the design of environments and envisioned applications. (Image by A. Nsamela.)
Microfluidics for Microswimmers: Engineering Novel Swimmers and Constructing Swimming Lanes on the Microscale, a Tutorial Review

Priyanka Sharan, Audrey Nsamela, Sasha Cai Lesher-Pérez and Juliane Simmchen Small, 2007403 (2021) doi: 10.1002/smll.202007403

Abstract: This paper provides an updated review of recent advances in microfluidics applied to artificial and biohybrid microswimmers. Sharing the common regime of low Reynolds number, the two fields have been brought together to take advantage of the fluid characteristics at the microscale, benefitting microswimmer research multifold. First, microfluidics offer simple and relatively low‐cost devices for high‐fidelity production of microswimmers made of organic and inorganic materials in a variety of shapes and sizes. Microscale confinement and the corresponding fluid properties have demonstrated differential microswimmer behaviors in microchannels or in the presence of various types of physical or chemical stimuli. Custom environments to study these behaviors have been designed in large part with the help of microfluidics. Evaluating microswimmers in increasingly complex lab environments such as microfluidic systems can ensure more effective implementation for in‐field applications. The benefits of microfluidics for the fabrication and evaluation of microswimmers are balanced by the potential use of microswimmers for sample manipulation and processing in microfluidic systems, a large obstacle in diagnostic and other testing platforms. In this review various ways in which these two complementary technology fields will enhance microswimmer development and implementation in various fields are introduced.

Effect of viscosity on microswimmers: a comparative study published in ChemNanoMat

Illustration of the four types of microswimmers used in the viscosity study. (Image by A. Nsamela.)
Effect of viscosity on microswimmers: a comparative study

Audrey Nsamela, Priyanka Sharan, Aidee Garcia-Zintzun, Sandra Heckel, Purnesh Chattopadhyay, Linlin Wang, Martin Wittmann, Thomas Gemming, James Saenz and Juliane Simmchen ChemNanoMat (2021) doi: 10.1002/cnma.202100119

Abstract: Although many biological fluids like blood and mucus exhibit high viscosities, there are still many open questions concerning the swimming behavior of microswimmers in highly viscous media, limiting research to idealized laboratory conditions instead of application‐oriented scenarios. Here, we analyze the effect of viscosity on the swimming speed and motion pattern of four kinds of microswimmers of different sizes which move by contrasting propulsion mechanisms: two biological swimmers (bovine sperm cells and Bacillus subtilis bacteria) which move by different bending patterns of their flagellaand two artificial swimmers with catalytic propulsion mechanisms (alginate microtubes and Janus Pt@SiO 2 spherical microparticles). Experiments consider two different media (glycerol and methylcellulose) with increasing viscosity, but also the impact of surface tension, catalyst activity and diffusion coefficients are discussed and evaluated.

Rond Table Discussion on: Advanced Control of Active Matter

The last round table of this workshop regarded the topic advanced control of active matter. As organizers of round table, Audrey Nsamela, Chun-Jen Chen, Sandrine Heijnen, Harshith Bachimanchi and Alireza Khoshzaban, we welcomed and introduced our esteemed guests, namely Jérémie Palacci from University of San Diego, Clemens Bechinger from Konstanz University, Frank Cichos from Leipzig University, and Lucio Isa from ETH Zurich.

The round table started out with a clarification on advanced control of active matter. Active matter can be controlled by numerous external stimuli but implementing control on individual particles or artificial entities is what qualifies as advanced control. Currently, the control of active matter is still far from the behavior and control micro-organisms have on that scale; hence a big challenge lies there for us. Jérémie Palacci introduced an interesting research topic where they found a way to regulate the swimming process of E. Coli by light illumination. Here genetic modification was used to control the proton pump involved in the energy transportation process.

Advanced control of active matter can be applied to model systems where the control is lacking, for example biological systems. In a biological system the control over an organism is limited to the external stimuli that are applied and won’t always result in the same reaction. Therefore, using active particles showing predictable and reproducible behaviors when exposed to a stimulus works perfectly to model and to probe different parameters and thus provide a deeper understanding of the system. The fact advanced control of active matter doesn’t have an application outside of modelling systems is something we shouldn’t be ashamed of.

We concluded the meeting by asking every one of our guests what the promising research directions in the advanced control of active matter are. All of them had a different perspective. Starting with  Clemens Bechinger, who was most invested in the further exploration of the applications for model systems. Lucio Isa is mainly looking forward to explore the different materials that we can use to create active material that can subsequently be controlled. Frank Cichos mentioned the importance of looking into new ways to create active particles. So far nature was able to achieve production of active entities with limited waste whereas human production is rather inefficient. Jérémie Palacci pointed out that the current man-made active matter systems are reacting to a strong signal in a well-controlled environment, where nature faces many more factors and still works. It would be interesting to design a system that is resistant to noise.