Presentation by C. B. Adiels at AI for Scientific Data Analysis, Gothenburg, 31 May 2023

Phase-contrast image before virtual staining. (Image reproduced from https://doi.org/10.1101/2022.07.18.500422.)
Dynamic live/apoptotic cell assay using phase-contrast imaging and deep learning
Caroline B. Adiels

Chemical live/dead assay has a long history of providing information about the viability of cells cultured in vitro. The standard methods rely on imaging chemically-stained cells using fluorescence microscopy and further analysis of the obtained images to retrieve the proportion of living cells in the sample. However, such a technique is not only time-consuming but also invasive. Due to the toxicity of chemical dyes, once a sample is stained, it is discarded, meaning that longitudinal studies are impossible using this approach. Further, information about when cells start programmed cell death (apoptosis) is more relevant for dynamic studies. Here, we present an alternative method where cell images from phase-contrast time-lapse microscopy are virtually-stained using deep learning. In this study, human endothelial cells are stained live or apoptotic and subsequently counted using the self-supervised single-shot deep-learning technique (LodeSTAR). Our approach is less labour-intensive than traditional chemical staining procedures and provides dynamic live/apoptotic cell ratios from a continuous cell population with minimal impact. Further, it can be used to extract data from dense cell samples, where manual counting is unfeasible.

Date: 31 May 2023
Time: 10:30
Place: MC2 Kollektorn
Event: AI for Scientific Data Analysis: Miniconference

“Coffee Rings” presented at Gothenburg Science Festival 2023

Coffee Ring exposition at science festival Gothenburg. (Photo by C. Beck Adiels.)
Our recent work on “coffee rings” was presented at the Gothenburg Science Festival, which, with about 100 000 visitors each year, is one of the largest popular science events in Europe.

On Wednesday 19th April 2023, Marcel Rey, Laura Natali, Daniela Pérez Guerrero and Caroline Adiels set up a stand in Nordstan.

In this guided exhibition, visitors were able to observe the flow inside a drying droplet using optical microscopes. They learned how the suspended solid coffee particles flow from the inside towards the edge of the coffee droplet, where they accumulate and cause the characteristic coffee ring pattern after drying.

Nowadays, the coffee ring effect presents still a major challenge in ink-jet printing or coating technologies, where a uniform drying is required. We thus shared our recently developed strategies to overcome the coffee ring effect and obtain a uniform deposit of drying droplets.

And finally, visitors were also offered a freshly-brewed espresso to not only drink but also to experience the “coffee ring effect” hands on.

Dynamic live/apoptotic cell assay using phase-contrast imaging and deep learning on bioRxiv

Phase-contrast image before virtual staining. (Image by the Authors.)
Dynamic live/apoptotic cell assay using phase-contrast imaging and deep learning
Zofia Korczak, Jesús Pineda, Saga Helgadottir, Benjamin Midtvedt, Mattias Goksör, Giovanni Volpe, Caroline B. Adiels
bioRxiv: https://doi.org/10.1101/2022.07.18.500422

Chemical live/dead assay has a long history of providing information about the viability of cells cultured in vitro. The standard methods rely on imaging chemically-stained cells using fluorescence microscopy and further analysis of the obtained images to retrieve the proportion of living cells in the sample. However, such a technique is not only time-consuming but also invasive. Due to the toxicity of chemical dyes, once a sample is stained, it is discarded, meaning that longitudinal studies are impossible using this approach. Further, information about when cells start programmed cell death (apoptosis) is more relevant for dynamic studies. Here, we present an alternative method where cell images from phase-contrast time-lapse microscopy are virtually-stained using deep learning. In this study, human endothelial cells are stained live or apoptotic and subsequently counted using the self-supervised single-shot deep-learning technique (LodeSTAR). Our approach is less labour-intensive than traditional chemical staining procedures and provides dynamic live/apoptotic cell ratios from a continuous cell population with minimal impact. Further, it can be used to extract data from dense cell samples, where manual counting is unfeasible.

Press release on Extracting quantitative biological information from bright-field cell images using deep learning

Virtually-stained generated image for lipid-droplet.

The article Extracting quantitative biological information from bright-field cell images using deep learning has been featured in a press release of the University of Gothenburg.

The study, recently published in Biophysics Reviews, shows how artificial intelligence can be used to develop faster, cheaper and more reliable information about cells, while also eliminating the disadvantages from using chemicals in the process.

Here the links to the press releases on Cision:
Swedish: Effektivare studier av celler med ny AI-metod
English: More effective cell studies using new AI method

Here the links to the press releases in the News of the University of Gothenburg:
Swedish: Effektivare studier av celler med ny AI-metod
English: More effective cell studies using new AI method

Extracting quantitative biological information from brightfield cell images using deep learning featured in AIP SciLight

The article Extracting quantitative biological information from brightfield cell images using deep learning
has been featured in: “Staining Cells Virtually Offers Alterative Approach to Chemical Dyes”, AIP SciLight (July 23, 2021).

Scilight showcases the most interesting research across the physical sciences published in AIP Publishing Journals.

Scilight is published weekly (52 issues per year) by AIP Publishing.

Extracting quantitative biological information from bright-field cell images using deep learning published in Biophysics Reviews

Virtually-stained generated image for lipid-droplet.
Extracting quantitative biological information from bright-field cell images using deep learning
Saga Helgadottir, Benjamin Midtvedt, Jesús Pineda, Alan Sabirsh, Caroline B. Adiels, Stefano Romeo, Daniel Midtvedt, Giovanni Volpe
Biophysics Rev. 2, 031401 (2021)
arXiv: 2012.12986
doi: 10.1063/5.0044782

Quantitative analysis of cell structures is essential for biomedical and pharmaceutical research. The standard imaging approach relies on fluorescence microscopy, where cell structures of interest are labeled by chemical staining techniques. However, these techniques are often invasive and sometimes even toxic to the cells, in addition to being time-consuming, labor-intensive, and expensive. Here, we introduce an alternative deep-learning-powered approach based on the analysis of bright-field images by a conditional generative adversarial neural network (cGAN). We show that this approach can extract information from the bright-field images to generate virtually-stained images, which can be used in subsequent downstream quantitative analyses of cell structures. Specifically, we train a cGAN to virtually stain lipid droplets, cytoplasm, and nuclei using bright-field images of human stem-cell-derived fat cells (adipocytes), which are of particular interest for nanomedicine and vaccine development. Subsequently, we use these virtually-stained images to extract quantitative measures about these cell structures. Generating virtually-stained fluorescence images is less invasive, less expensive, and more reproducible than standard chemical staining; furthermore, it frees up the fluorescence microscopy channels for other analytical probes, thus increasing the amount of information that can be extracted from each cell.

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.

Press release on joint research on intercellular communication mechanism by Biological Physics Lab and Soft Matter Lab

The article Intercellular Communication Induces Glycolytic Synchronisation Waves published in PNAS has been featured in the News of the Faculty of Science of Gothenburg University.

Here the links to the press releases:
Swedish: Forskare har knäckt koden för cellkommunikation
English: Researchers have broken the code for cell communication

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.