Periodic Reporting for period 1 - ViBRheo (Desing of a Virtual Blood Rheometer for Thrombotic Process Characterization)
Okres sprawozdawczy: 2022-01-01 do 2023-12-31
The COVID-19 pandemic marked an unprecedented health crisis of this century. Critically ill patients, ranging from 20 to 30 percent, faced coagulopathies leading to thrombotic complications. Understanding the clotting mechanism remains elusive, emphasizing the need for effective treatment strategies to prevent complications. Traditional clinical treatments proved inefficient or had adverse effects, hindering widespread adoption.
A robust and continuous diagnosis is crucial for implementing proper prophylactic strategies. Viscoelastic characterization of whole blood, utilizing rheological tests, emerges as an integral indicator. Although viscoelastic testing was explored for diagnosing coagulopathies, routine use was delayed due to the need for specific adaptations to the new disease protocols. Thrombus formation, a natural multiscale mechanism in blood, involves wide spatiotemporal ranges, making computational modeling complex. ViBRheo introduced a Lagrangian heterogeneous multiscale method to address diagnostic challenges. This method streamlines viscometric technique calibration, explores novel flow configurations for rheological characterization, and identifies biomarkers systematically.
The project's overall objective was to construct a computational rheometer to characterize blood's viscoelastic alterations related to coagulopathies. Four focus areas included building a computational package for full-Lagrangian heterogeneous multiscale approaches, creating a multiscale virtual rheometer for hemostasis testing, correlating viscoelastic properties with coagulation alterations for biomarker identification, and evaluating flow configurations for meaningful rheological correlations.
In conclusion, ViBRheo successfully developed a particle-based computational multiscale method for rheological characterization, modeling microscale blood clotting features over large spatiotemporal scales. The project coincided with constructing a computational tool for multiscale coupling and developing mesoscale models to reproduce complex blood clotting features. ViBRheo's findings provide characteristic fingerprints for passive rheology, facilitating differentiation or identification of complex biological and synthetic systems like viruses, cells, proteins, or polymers.
A robust and continuous diagnosis is crucial for implementing proper prophylactic strategies. Viscoelastic characterization of whole blood, utilizing rheological tests, emerges as an integral indicator. Although viscoelastic testing was explored for diagnosing coagulopathies, routine use was delayed due to the need for specific adaptations to the new disease protocols. Thrombus formation, a natural multiscale mechanism in blood, involves wide spatiotemporal ranges, making computational modeling complex. ViBRheo introduced a Lagrangian heterogeneous multiscale method to address diagnostic challenges. This method streamlines viscometric technique calibration, explores novel flow configurations for rheological characterization, and identifies biomarkers systematically.
The project's overall objective was to construct a computational rheometer to characterize blood's viscoelastic alterations related to coagulopathies. Four focus areas included building a computational package for full-Lagrangian heterogeneous multiscale approaches, creating a multiscale virtual rheometer for hemostasis testing, correlating viscoelastic properties with coagulation alterations for biomarker identification, and evaluating flow configurations for meaningful rheological correlations.
In conclusion, ViBRheo successfully developed a particle-based computational multiscale method for rheological characterization, modeling microscale blood clotting features over large spatiotemporal scales. The project coincided with constructing a computational tool for multiscale coupling and developing mesoscale models to reproduce complex blood clotting features. ViBRheo's findings provide characteristic fingerprints for passive rheology, facilitating differentiation or identification of complex biological and synthetic systems like viruses, cells, proteins, or polymers.
ViBRheo embarked on constructing a computational framework, initially exploring various alternatives using open-source codes. LAMMPS was chosen to implement the software for each scale. The framework's creation involved three stages: micro scale definition, macro scales definition, and concurrent coupling of the scales. Different coupling schemes were formulated and tested for code stability. Initial calibration occurred at BCAM's computation cluster, with further evaluation at DIPC. ViBRheo secured supercomputing resources via the Spanish Supercomputing Network, using Marenostrum @ BSC (Barcelona, Spain), granted 4M CPU hours.
The framework's formulation and description were published in the Journal of Fluid Mechanics [1], and the codes were made available on GitHub. The proposed scheme derived microscopic information on-the-fly, eliminating the need for constitutive relations for stress. Smoothed dissipative particle dynamics (SDPD) discretized the fluctuating Navier-Stokes equations for both microscopic and macroscopic scales. Validation demonstrated effective stress transfer across scales, enhancing fluid response at the continuum level. The Lagrangian heterogeneous multiscale method (LHMM) offered a promising approach for modeling complex biological fluids, concurrently exploring different spatial and temporal scales. This methodology holds potential for advancing our understanding of biological systems, aiding diagnostic and therapeutic strategies.
ViBRheo focused on constructing a multiscale rheometer for blood modeling, identifying key microscopic features: micro-scale species aggregations, small proteins transport, coagulation kinetics, and virus-scale transport. Models for features a) to c) used SDPD, while feature d) employed the Rigid Multiblob Methodology. Published results and preprints detailed modifications for diffusional transport of species, validation of blood kinetics, and cellular-level aggregation during a secondment at Forschungszentrum Julich (FZJ).
ViBRheo developed virtual twins of rheological devices to assess viscoelastic alterations from identified microscopic features. A generalized mesoscale model incorporated hydrodynamic interactions, bonding, and surface tension using SDPD to reproduce biological aggregations. Evaluation revealed correlations between cluster properties and model parameters, published in [2]. The model identified the insufficiency of a single biomarker, proposing the combined use of fractal dimension and MSD for a comprehensive assessment. ViBRheo also investigated dynamic aggregation/disaggregation of red blood cells using explicit mesh-like membrane representation, exploring three aggregation schemes.
For the flow of aggregates with complex morphologies, ViBRheo focused on understanding confinement's overall effect and designing passive tracers for rheological information retrieval. Results, published in [3, 4], demonstrated that SARS-CoV-2's diffusional mechanisms are influenced by spike characteristics, providing insights for designing microrheological devices for virus screening and characterization.
The results of this project were published in four journal articles and three preprints were submitted
[1] Nicolas Moreno* and Marco Ellero. Journal of Fluid Mechanics. 969, A2. (2023)
[2] Elnaz Zohravi, Nicolas Moreno*, and Marco Ellero. Soft Matter, 19, 7399-7411 (2023)
[3] Daniela Moreno-Chaparro, Nicolas Moreno*, Florencio Balboa-Usabiaga, and Marco Ellero. 158 (10): 104108 (2023)
[4] Nicolas Moreno*, Daniela Moreno-Chaparro, Florencio Balboa Usabiaga, and Marco Ellero. Scientific Reports, 12, 11080 (2022).
Throughout the project, the fellow attended 8 international conferences, 2 as invited speakers, sharing project outcomes with biophysics, rheology, fluid dynamics, and math experts. They engaged in 4 public dissemination events: Pi Day (NAUKAS Mar '22), BBK Zientzia (BBK Foundation Jul '22), Pint of Science (PoS Bilbao May '23), and Biophysical Seminars (FZJ, Germany, Nov '23). An invited session at PARTICLES 2023 was organized. The project's official webpage (https://vibrheo.bcamath.org/) was established, and results were shared through social media, BCAM, and GitHub (https://github.com/nmorenoch).
The framework's formulation and description were published in the Journal of Fluid Mechanics [1], and the codes were made available on GitHub. The proposed scheme derived microscopic information on-the-fly, eliminating the need for constitutive relations for stress. Smoothed dissipative particle dynamics (SDPD) discretized the fluctuating Navier-Stokes equations for both microscopic and macroscopic scales. Validation demonstrated effective stress transfer across scales, enhancing fluid response at the continuum level. The Lagrangian heterogeneous multiscale method (LHMM) offered a promising approach for modeling complex biological fluids, concurrently exploring different spatial and temporal scales. This methodology holds potential for advancing our understanding of biological systems, aiding diagnostic and therapeutic strategies.
ViBRheo focused on constructing a multiscale rheometer for blood modeling, identifying key microscopic features: micro-scale species aggregations, small proteins transport, coagulation kinetics, and virus-scale transport. Models for features a) to c) used SDPD, while feature d) employed the Rigid Multiblob Methodology. Published results and preprints detailed modifications for diffusional transport of species, validation of blood kinetics, and cellular-level aggregation during a secondment at Forschungszentrum Julich (FZJ).
ViBRheo developed virtual twins of rheological devices to assess viscoelastic alterations from identified microscopic features. A generalized mesoscale model incorporated hydrodynamic interactions, bonding, and surface tension using SDPD to reproduce biological aggregations. Evaluation revealed correlations between cluster properties and model parameters, published in [2]. The model identified the insufficiency of a single biomarker, proposing the combined use of fractal dimension and MSD for a comprehensive assessment. ViBRheo also investigated dynamic aggregation/disaggregation of red blood cells using explicit mesh-like membrane representation, exploring three aggregation schemes.
For the flow of aggregates with complex morphologies, ViBRheo focused on understanding confinement's overall effect and designing passive tracers for rheological information retrieval. Results, published in [3, 4], demonstrated that SARS-CoV-2's diffusional mechanisms are influenced by spike characteristics, providing insights for designing microrheological devices for virus screening and characterization.
The results of this project were published in four journal articles and three preprints were submitted
[1] Nicolas Moreno* and Marco Ellero. Journal of Fluid Mechanics. 969, A2. (2023)
[2] Elnaz Zohravi, Nicolas Moreno*, and Marco Ellero. Soft Matter, 19, 7399-7411 (2023)
[3] Daniela Moreno-Chaparro, Nicolas Moreno*, Florencio Balboa-Usabiaga, and Marco Ellero. 158 (10): 104108 (2023)
[4] Nicolas Moreno*, Daniela Moreno-Chaparro, Florencio Balboa Usabiaga, and Marco Ellero. Scientific Reports, 12, 11080 (2022).
Throughout the project, the fellow attended 8 international conferences, 2 as invited speakers, sharing project outcomes with biophysics, rheology, fluid dynamics, and math experts. They engaged in 4 public dissemination events: Pi Day (NAUKAS Mar '22), BBK Zientzia (BBK Foundation Jul '22), Pint of Science (PoS Bilbao May '23), and Biophysical Seminars (FZJ, Germany, Nov '23). An invited session at PARTICLES 2023 was organized. The project's official webpage (https://vibrheo.bcamath.org/) was established, and results were shared through social media, BCAM, and GitHub (https://github.com/nmorenoch).
Key impacts include the construction of a virtual tool for understanding COVID-19-related coagulopathies, a thermodynamically consistent multiscale framework considering thermal memory effects, and a groundbreaking line in mesoscale virus modeling. The framework's applicability extends beyond blood rheology, encompassing complex fluid flows, multiphase systems, polymer melts, colloidal suspensions, and other biomedical advection-diffusion-reaction-related problems.
The investigation into microscopic transport at virus scales led to novel mesoscale models enabling the estimation of enveloped virus diffusion, applicable to various viruses. ViBRheo's interdisciplinary interactions between numerical modelers, clinicians, rheologists, virologists, and experimental groups pave the way for future in-silico design of high-impact R&I products, including patient-specific devices for coagulopathies analysis.
The investigation into microscopic transport at virus scales led to novel mesoscale models enabling the estimation of enveloped virus diffusion, applicable to various viruses. ViBRheo's interdisciplinary interactions between numerical modelers, clinicians, rheologists, virologists, and experimental groups pave the way for future in-silico design of high-impact R&I products, including patient-specific devices for coagulopathies analysis.