SIRIUS included activities in a) computational method development, b) analysis of inertial particle microfluidics (IPMF) through computer simulations, and c) knowledge transfer with stakeholders.
a) In terms of computational method development, we investigated the “immersed-boundary-lattice-Boltzmann method” which forms the basis for the simulation of the interaction of particles and flow. We found a way to predict the stability and accuracy of this method before running any simulations, making it easier for scientists to plan simulations.
Simulations of IPMF in curved channels (such as spiralling channels) are very challenging since there are hardly any available computational methods with all required features. We started developing a novel method that has the potential to overcome these shortcomings. We were not able to finish this part of the project due to the complexity of the algorithm and plan to continue this work in a different project.
We developed a new algorithm to calculate the forces that the fluid exerts on the particles flowing in channels. This algorithm gives scientists the ability to understand how exactly particles are influenced by the flow inside channels.
b) The SIRIUS team conducted several simulation-based projects to understand the interaction of multiple particles in IPMF and the characterisation of the properties of individual particles in bespoke channel geometries.
In microfluidics, particles influence the behaviour of other particles nearby through “hydrodynamic interactions” (such as we feel a car driving by). In IPMF, these interactions can lead to the spontaneous formation of pairs or trains of particles where particles flow in groups. Understanding under which circumstances these groups form is of high importance as this behaviour determines how easily different blood cell types can be separated. Through our simulations we found that size and softness of the particles play crucial roles. We were able to explain why an existing microfluidic device, designed for the separation of circulating tumour cells from blood cells, does not perform as well as expected. Our work opens up the possibility to design more reliable IPMF devices.
Another microfluidic application is “cytometry” where the properties of biological cells are measured by exposing individual cells to specific flow fields that stretch the cells. We investigated how particles of different properties behave in a so-called “cross-slot junction”, a geometry often used to stretch cells. For example, the company Cytovale Inc. (California) uses this technology for early sepsis detection. Through our simulations, we learned how the particle properties influence the way the particles travel through the junction. Our findings give experimental researchers the tools to design better geometries to probe biological cells for more accurate disease detection.
We also investigated the flow of “dense suspensions” in IPMF. Undiluted blood is an example of a dense suspension where 45% of the volume of the fluid consists of blood cells. While IPMF is usually applied to diluted blood samples (with cell concentrations of 1% or less), it is a major challenge to scale this method to undiluted blood. Our simulations show that there is a non-trivial interaction of IPMF and the high concentration of blood cells. We found that different types of blood cells tend to segregate under certain conditions, potentially enabling the separation of different cell types even at higher cell concentrations.
c) As the SIRIUS project was of computational nature, it is crucial to validate simulation results and transfer knowledge with experimental researchers and end users.
One of the SIRIUS researchers spent six months in the experimental lab of Prof. Ian Papautsky (Chicago). We validated parts of our simulation results and exchanged ideas between modellers and experimentalists. Importantly, the SIRIUS team learned about the practical needs of experimentalists. Likewise, the experimentalists learned from us which IPMF mechanisms are important under which circumstances and how the design of IPMF devices can be improved to achieve better separation of biological cells.
We worked closely with Cytovale Inc. These interactions taught us how to improve our computational IPMF models, while our simulations provided unprecedented insight into the particle dynamics in cross-slot junctions.
Finally, we distilled most of our knowledge in modelling and simulating IPMF in a tutorial review paper that serves as a single point of entry for researchers who want to get started in this area.
Concluding, the SIRIUS project enabled the development of new and improved numerical algorithms. We performed several simulation investigations and uncovered fundamental mechanisms of IPMF. Interacting with experimental researchers, we contributed to knowledge transfer between computational modelling and experimental communities, thus enabling improved real-world applications.
