Quantitative Digital Microscopy with Deep Learning published in Applied Physics Reviews

Particle tracking and characterization in terms of radius and refractive index.

Quantitative Digital Microscopy with Deep Learning
Benjamin Midtvedt, Saga Helgadottir, Aykut Argun, Jesús Pineda, Daniel Midtvedt, Giovanni Volpe
Applied Physics Reviews 8, 011310 (2021)
doi: 10.1063/5.0034891
arXiv: 2010.08260

Video microscopy has a long history of providing insights and breakthroughs for a broad range of disciplines, from physics to biology. Image analysis to extract quantitative information from video microscopy data has traditionally relied on algorithmic approaches, which are often difficult to implement, time consuming, and computationally expensive. Recently, alternative data-driven approaches using deep learning have greatly improved quantitative digital microscopy, potentially offering automatized, accurate, and fast image analysis. However, the combination of deep learning and video microscopy remains underutilized primarily due to the steep learning curve involved in developing custom deep-learning solutions. To overcome this issue, we introduce a software, DeepTrack 2.0, to design, train and validate deep-learning solutions for digital microscopy. We use it to exemplify how deep learning can be employed for a broad range of applications, from particle localization, tracking and characterization to cell counting and classification. Thanks to its user-friendly graphical interface, DeepTrack 2.0 can be easily customized for user-specific applications, and, thanks to its open-source object-oriented programming, it can be easily expanded to add features and functionalities, potentially introducing deep-learning-enhanced video microscopy to a far wider audience.

Optical trapping and critical Casimir forces published in EPJP

Measuring the dynamics of colloids interacting with critical Casimir interaction via blinking optical tweezers: graphical representation of the optical traps.

Optical trapping and critical Casimir forces
Agnese Callegari, Alessandro Magazzù, Andrea Gambassi & Giovanni Volpe
The European Physical Journal Plus (EPJP), 136, 213 (2021)
doi: 10.1140/epjp/s13360-020-01020-4
arXiv: 2008.01537

Critical Casimir forces emerge between objects, such as colloidal particles, whenever their surfaces spatially confine the fluctuations of the order parameter of a critical liquid used as a solvent. These forces act at short but microscopically large distances between these objects, reaching often hundreds of nanometers. Keeping colloids at such distances is a major experimental challenge, which can be addressed by the means of optical tweezers. Here, we review how optical tweezers have been successfully used to quantitatively study critical Casimir forces acting on particles in suspensions. As we will see, the use of optical tweezers to experimentally study critical Casimir forces can play a crucial role in developing nano-technologies, representing an innovative way to realize self-assembled devices at the nano- and microscale.

Intercellular Communication Induces Glycolytic Synchronisation Waves published in PNAS

Intercellular communication induces glycolytic synchronization waves between individually oscillating cells

Intercellular communication induces glycolytic synchronization waves between individually oscillating cells
Martin Mojica-Benavides, David D. van Niekerk, Mite Mijalkov, Jacky L. Snoep, Bernhard Mehlig, Giovanni Volpe, Caroline B. Adiels & Mattias Goksör
PNAS 118(6), e2010075118 (2021)
doi: 10.1073/pnas.2010075118
arXiv: 1909.05187

Metabolic oscillations in single cells underlie the mechanisms behind cell synchronization and cell-cell communication. For example, glycolytic oscillations mediated by biochemical communication between cells may synchronize the pulsatile insulin secretion by pancreatic tissue, and a link between glycolytic synchronization anomalies and type-2 diabetes has been hypotesized. Cultures of yeast cells have provided an ideal model system to study synchronization and propagation waves of glycolytic oscillations in large populations. However, the mechanism by which synchronization occurs at individual cell-cell level and overcome local chemical concentrations and heterogenic biological clocks, is still an open question because of experimental limitations in sensitive and specific handling of single cells. Here, we show how the coupling of intercellular diffusion with the phase regulation of individual oscillating cells induce glycolytic synchronization waves. We directly measure the single-cell metabolic responses from yeast cells in a microfluidic environment and characterize a discretized cell-cell communication using graph theory. We corroborate our findings with simulations based on a kinetic detailed model for individual yeast cells. These findings can provide insight into the roles cellular synchronization play in biomedical applications, such as insulin secretion regulation at the cellular level.

Fast and Accurate Nanoparticle Characterization Using Deep-Learning-Enhanced Off-Axis Holography published in ACS Nano

Phase and amplitude signals from representative particles for testing the performance of the Deep-learning approach

Fast and Accurate Nanoparticle Characterization Using Deep-Learning-Enhanced Off-Axis Holography
Benjamin Midtvedt, Erik Olsén, Fredrik Eklund, Fredrik Höök, Caroline Beck Adiels, Giovanni Volpe, Daniel Midtvedt
ACS Nano 15(2), 2240–2250 (2021)
doi: 10.1021/acsnano.0c06902
arXiv: 2006.11154

The characterisation of the physical properties of nanoparticles in their native environment plays a central role in a wide range of fields, from nanoparticle-enhanced drug delivery to environmental nanopollution assessment. Standard optical approaches require long trajectories of nanoparticles dispersed in a medium with known viscosity to characterise their diffusion constant and, thus, their size. However, often only short trajectories are available, while the medium viscosity is unknown, e.g., in most biomedical applications. In this work, we demonstrate a label-free method to quantify size and refractive index of individual subwavelength particles using two orders of magnitude shorter trajectories than required by standard methods, and without assumptions about the physicochemical properties of the medium. We achieve this by developing a weighted average convolutional neural network to analyse the holographic images of the particles. As a proof of principle, we distinguish and quantify size and refractive index of silica and polystyrene particles without prior knowledge of solute viscosity or refractive index. As an example of an application beyond the state of the art, we demonstrate how this technique can monitor the aggregation of polystyrene nanoparticles, revealing the time-resolved dynamics of the monomer number and fractal dimension of individual subwavelength aggregates. This technique opens new possibilities for nanoparticle characterisation with a broad range of applications from biomedicine to environmental monitoring.

Enhanced force-field calibration via machine learning published in Applied Physics Reviews

Representation of a particle in a force field
Enhanced force-field calibration via machine learning
Aykut Argun, Tobias Thalheim, Stefano Bo, Frank Cichos, Giovanni Volpe
Applied Physics Reviews 7, 041404 (2020)
doi: 10.1063/5.0019105
arXiv: 2006.08963

The influence of microscopic force fields on the motion of Brownian particles plays a fundamental role in a broad range of fields, including soft matter, biophysics, and active matter. Often, the experimental calibration of these force fields relies on the analysis of the trajectories of these Brownian particles. However, such an analysis is not always straightforward, especially if the underlying force fields are non-conservative or time-varying, driving the system out of thermodynamic equilibrium. Here, we introduce a toolbox to calibrate microscopic force fields by analyzing the trajectories of a Brownian particle using machine learning, namely recurrent neural networks. We demonstrate that this machine-learning approach outperforms standard methods when characterizing the force fields generated by harmonic potentials if the available data are limited. More importantly, it provides a tool to calibrate force fields in situations for which there are no standard methods, such as non-conservative and time-varying force fields. In order to make this method readily available for other users, we provide a Python software package named DeepCalib, which can be easily personalized and optimized for specific applications.

Funding:

ERC-founder H2020 European Research Council (ERC) Starting Grant ComplexSwimmers (677511).

Diagnosis of a genetic disease improves with machine learning, a summary in Swedish published in Fysikaktuellt

Neural networks consist of a series of connected layers of neurons, whose connection weights are adjusted to learn how to determine the diagnosis from the input data.

A summary in Swedish of our previously published article “Virtual genetic diagnosis for familial hypercholesterolemia powered by machine learning” has been published in Fysikaktuellt, the journal of the Swedish Physical Society (Svenska fysikersamfundet).

Article: “Diagnostisering av sjukdomar förbättras med maskininlärning”, Saga Helgadottir, Giovanni Volpe and Stefano Romeo (in Swedish)

Original article: Virtual genetic diagnosis for familial hypercholesterolemia powered by machine learning

Press release: 
Algoritm lär sig diagnostisera genetisk sjukdom (in Swedish)
An algorithm that learns to diagnose genetic disease (in English)

Feedback-controlled active brownian colloids with space-dependent rotational dynamics published in Nature Communications

Active Colloids with Position-Dependent Rotational Diffusivity

Active Colloids with Position-Dependent Rotational Diffusivity
Miguel Angel Fernandez-Rodriguez, Fabio Grillo, Laura Alvarez, Marco Rathlef, Ivo Buttinoni, Giovanni Volpe & Lucio Isa
Nature Communications 11, 4223 (2020)
doi: 10.1038/s41467-020-17864-4
arXiv: 1911.02291

The non-thermal nature of self-propelling colloids offers new insights into non-equilibrium physics. The central mathematical model to describe their trajectories is active Brownian motion, where a particle moves with a constant speed, while randomly changing direction due to rotational diffusion. While several feedback strategies exist to achieve position-dependent velocity, the possibility of spatial and temporal control over rotational diffusion, which is inherently dictated by thermal fluctuations, remains untapped. Here, we decouple rotational diffusion from thermal fluctuations. Using external magnetic fields and discrete-time feedback loops, we tune the rotational diffusivity of active colloids above and below its thermal value at will and explore a rich range of phenomena including anomalous diffusion, directed transport, and localization. These findings add a new dimension to the control of active matter, with implications for a broad range of disciplines, from optimal transport to smart materials.

Machine learning reveals complex behaviours in optically trapped particles published in Machine Learning: Science and Technology

Illustration of a fully connected neural network with three inputs, three outputs, and three hidden layers.

Machine learning reveals complex behaviours in optically trapped particles
Isaac C. D. Lenton, Giovanni Volpe, Alexander B. Stilgoe, Timo A. Nieminen & Halina Rubinsztein-Dunlop
Machine Learning: Science and Technology, 1 045009 (2020)
doi: 10.1088/2632-2153/abae76
arXiv: 2004.08264

Since their invention in the 1980s, optical tweezers have found a wide range of applications, from biophotonics and mechanobiology to microscopy and optomechanics. Simulations of the motion of microscopic particles held by optical tweezers are often required to explore complex phenomena and to interpret experimental data. For the sake of computational efficiency, these simulations usually model the optical tweezers as an harmonic potential. However, more physically-accurate optical-scattering models are required to accurately model more onerous systems; this is especially true for optical traps generated with complex fields. Although accurate, these models tend to be prohibitively slow for problems with more than one or two degrees of freedom (DoF), which has limited their broad adoption. Here, we demonstrate that machine learning permits one to combine the speed of the harmonic model with the accuracy of optical-scattering models. Specifically, we show that a neural network can be trained to rapidly and accurately predict the optical forces acting on a microscopic particle. We demonstrate the utility of this approach on two phenomena that are prohibitively slow to accurately simulate otherwise: the escape dynamics of swelling microparticles in an optical trap, and the rotation rates of particles in a superposition of beams with opposite orbital angular momenta. Thanks to its high speed and accuracy, this method can greatly enhance the range of phenomena that can be efficiently simulated and studied.

Anisotropic dynamics of a self-assembled colloidal chain in an active bath published on Soft Matter

Bright-field microscopy image of a magnetic chain trapped at the liquid-air interface in a bacterial bath

Anisotropic dynamics of a self-assembled colloidal chain in an active bath
Mehdi Shafiei Aporvari, Mustafa Utkur, Emine Ulku Saritas, Giovanni Volpe & Joakim Stenhammar
Soft Matter, 2020, 16, 5609-5614
doi: https://doi.org/10.1039/D0SM00318B
arXiv: 2002.09961

Anisotropic macromolecules exposed to non-equilibrium (active) noise are very common in biological systems, and an accurate understanding of their anisotropic dynamics is therefore crucial. Here, we experimentally investigate the dynamics of isolated chains assembled from magnetic microparticles at a liquid–air interface and moving in an active bath consisting of motile E. coli bacteria. We investigate both the internal chain dynamics and the anisotropic center-of-mass dynamics through particle tracking. We find that both the internal and center-of-mass dynamics are greatly enhanced compared to the passive case, i.e., a system without bacteria, and that the center-of-mass diffusion coefficient D features a non-monotonic dependence as a function of the chain length. Furthermore, our results show that the relationship between the components of D parallel and perpendicular with respect to the direction of the applied magnetic field is preserved in the active bath compared to the passive case, with a higher diffusion in the parallel direction, in contrast to previous findings in the literature. We argue that this qualitative difference is due to subtle differences in the experimental geometry and conditions and the relative roles played by long-range hydrodynamic interactions and short-range collisions.

Characterisation of Physical Processes from Anomalous Diffusion Data, special issue on Journal of Physics A

Logo of the AnDi challenge.

Characterisation of Physical Processes from Anomalous Diffusion Data
Guest Editors
Miguel A Garcia-March, Maciej Lewenstein, Carlo Manzo, Ralf Metzler, Gorka Muñoz-Gil, Giovanni Volpe
Journal of Physics A: Mathematical and Theoretical
URL: Special Issue on Characterisation of Physical Processes from Anomalous Diffusion Data

In many systems, stochastic transport deviates from the standard laws of Brownian motion. Determining the exponent α characterising anomalous diffusion and identifying the physical origin of this behaviour are crucial steps to understanding the nature of the systems under observation. However, the determination of these properties from the analysis of the measured trajectories is often difficult, especially when these trajectories are short, irregularly sampled, or switching between different behaviours.

Over the last years, several methods have been proposed to quantify anomalous diffusion and the underlying physical process, going beyond the classical calculation of the mean squared displacement. More recently, the advent of machine learning has produced a boost in the methods to quantify anomalous diffusion.

The AnDi challenge aims at bringing together a vibrating and multidisciplinary community of scientists working on this problem. The use of the same reference datasets will allow an unbiased assessment of the performance of methods for characterising anomalous diffusion from single trajectories. This Special Issue will report on these approaches and their performance.

The deadline for submissions will be 30th June 2021 and you can submit manuscripts through ScholarOne Manuscripts. All papers will be refereed according to the usual high standards of the journal.