Tag: Giovanni Volpe

Delayed Active Swimmer in a Velocity Landscape published in Physical Review of Research

Experimental setup. (Top) Thermophoretic microswimmer undergoes active Brownian motion in a spatially-varying laser intensity profile that controls the self-thermophoretic propulsion of the swimmer using a feedback loop. (Bottom) Sample trajectory of the microswimmer over 15 minutes in a chamber. Colors indicate instantaneous velocity. (Image from the manuscript.)
Delayed Active Swimmer in a Velocity Landscape
Viktor Holubec, Alexander Fischer, Giovanni Volpe, Frank Cichos
Physical Review Research 8, L022017 (2026)
arXiv: 2505.11042
doi: 10.1103/xn9x-ppjx

Active systems in nature and synthetic environments commonly exhibit spatially heterogeneous activity patterns and time-delayed responses from internal feedback mechanisms, exemplified by bacterial chemotaxis. We study an idealized active gas where particles modulate their self-propulsion based on local environmental conditions with such delays. Through integrated theoretical, computational, and experimental approaches, we demonstrate that steady-state density distributions and collective polarization exhibit characteristic peaks and valleys as functions of response delay time. We find that delays can amplify polarization by nearly an order of magnitude and trigger complete polarization reversal when particle displacement during the delay period surpasses the persistence length. Multiparticle simulations incorporating interparticle interactions validate that these phenomena remain robust in sufficiently dilute collective systems. Since density and polarization determine the current in active matter, our findings show that temporally programming the delay time allows control over both static and dynamic states in active systems, with implications for biological microswimmers and engineered microrobots.

Three-dimensional quantitative tissue clearing reveals differences in osteovascular niche of aged and young human mesenchymal stromal cells published in Nature Biomedical Engineering

Visualization of the vasculature within human bone from a 75-year-old patient by immunostaining with antibodies against CD31. (Image from the manuscript.)
Three-dimensional quantitative tissue clearing reveals differences in osteovascular niche of aged and young human mesenchymal stromal cells
Nelson Tsz Long Chu, Ostap Dregval, Yu-Wei Chang, Emil Kriukov, Xin Tian, Xin Liu, Dana Trompet, Misty Shuo Zhang, Lei Li, Zhong Li, Emiliano Gomez Ruiz, Joana B. Pereira, Mats Brittberg, Björn Barenius, Lars Sävendahl, Ralf H. Adams, Inger Gjertsson, Claes Ohlsson, Giovanni Volpe & Andrei S. Chagin
Nature Biomedical Engineering (2026)
bioRxiv: 10.1101/2025.10.07.680053
doi: 10.1038/s41551-026-01645-3

Human bone marrow mesenchymal stromal/stem cells (BM-MSCs) are widely used in clinical trials and tissue engineering, yet their native microenvironment remains poorly understood. Here we introduce a tissue-clearing protocol, DeepBone, for human bones and integrate it with simultaneous mRNA and protein detection. Using this protocol, we spatially map BM-MSCs relative to key bone microenvironment components, including human blood capillaries, adipocytes, sinusoids and bony trabeculae. Quantitative analysis reveals that the native microenvironment of human BM-MSCs in young bone is enriched in vasculature, sinusoids, bone matrix and adipocytes. In contrast, in aged bone, BM-MSCs show no preferential association with bone or adipocytes. Proliferative BM-MSCs are predominantly found along blood vessels. Moreover, we identify a specialized microenvironment for BM-MSCs in young bone, characterized by sinusoids coiled around trabeculae and enriched by R-type vessels. These findings provide insights into the native niches of BM-MSCs, offering a foundation for the development of tissue engineering strategies that mimic their physiological context.

Latent space-driven quantification of biofilm formation using time-resolved droplet microfluidics published in Microchemical Journal

Automated segnmentation of bacterial structures within a droplet. The image shows a bright-field microscopy view where a large biofilm region (green, outlined in blue) has been segmented from surrounding features. Small aggregates (yellow contours) are also highlighted. This segmentation enables structural differentiation of biofilm components for downstream quantitative analysis. (Image by D. Pérez Guerrero.)
Latent space-driven quantification of biofilm formation using time-resolved droplet microfluidics
Daniela Pérez Guerrero, Jesús Manuel Antúnez Domínguez, Aurélie Vigne, Daniel Midtvedt, Wylie Ahmed, Lisa D. Muiznieks, Giovanni Volpe, Caroline Beck Adiels
Microchemical Journal 225, 117685 (2026)
arXiv: 2507.07632
DOI: 10.1016/j.microc.2026.117685

Bacterial biofilms play crucial roles across diverse contexts, from public health risks to beneficial applications in bioremediation, biodegradation, and wastewater treatment. However, tools that enable high-resolution, dynamic analysis of their responses to environmental cues and collective cellular behaviors remain limited. Here, we present a droplet-based microfluidic platform that combines continuous in situ microscopy with subsequent unsupervised deep learning for quantitative analysis of biofilm development. In our setup, Bacillus subtilis cells are encapsulated in monodisperse aqueous microdroplets containing Lysogeny Broth, suspended in an oil phase and immobilized within microfabricated traps, providing continuous optical access throughout biofilm formation at the water–oil interface. The platform supports both fluorescence and bright-field imaging, enabling high-throughput, time-resolved monitoring of thousands of droplets under controlled conditions. To extract quantitative information from these large datasets, we developed an automated analysis pipeline based on a Variational Autoencoder (VAE) trained directly on microscopy images from our experiments. This unsupervised model enables segmentation and latent-space representation of bacterial structures without manual annotation or synthetic training data. Post-segmentation size thresholding enables classification of bacterial aggregates and larger biofilm-like clusters, including quantification of biofilm porosity, thereby supporting detailed morphological and temporal analyses across droplets and conditions. By integrating droplet microfluidics with unsupervised deep learning, our platform provides a scalable, robust, and rapid approach for high-throughput quantitative studies of biofilm behavior. It resolves complex structural biofilm patterns, bypasses the need for manual annotation, and opens new opportunities to probe environmental determinants of biofilm formation. Departing from earlier methods, our framework fuses biological training data with unsupervised models to quantify microbial community dynamics across scales, offering a generalizable platform for future high-resolution microbiology.

Mapping individual molecular connectomes in Alzheimer’s disease published in Alzheimer’s & Dementia

Diagnostic classification. (Image from the article.)
Mapping individual molecular connectomes in Alzheimer’s disease
Zhilei Xu, Mite Mijalkov, Jiawei Sun, Yu-Wei Chang, Arianna Sala, Giovanni Volpe, Mario Severino, Mattia Veronese, Sara Garcia-Ptacek, Joana B. Pereira, for the Alzheimer’s Disease Neuroimaging Initiative
Alzheimer’s & Dementia 22, e71310 (2026)
DOI: 10.1002/alz.71310

INTRODUCTION
Mapping individual differences is crucial to improve personalized medicine approaches in Alzheimer’s disease (AD), which is characterized by strong inter-individual variability in the accumulation patterns of tau and amyloid beta pathology.

METHODS
We assess the progression of AD across the disease continuum by building individual molecular connectomes using longitudinal positron emission tomography (PET) data.

RESULTS
We demonstrate that these connectomes constitute a unique fingerprint, capable of identifying a single individual from a large group of subjects. Alterations in the connectomes discriminate different diagnostic groups and predict cognitive decline to a higher extent than conventional PET measures. We introduce a novel gene-specific transcription network analysis that linked individual tau and amyloid connectomes to a common transcriptomic profile of apoptosis, with the tau connectome being specifically related to pyrimidine metabolism, and the amyloid connectome to histone acetylation.

DISCUSSION
Individual molecular connectome mapping provides a novel and sensitive framework to monitor AD progression.

Highlights

  • Individual molecular connectomes constitute a unique fingerprint, capable of identifying a single individual from a large group of subjects.
  • Alterations in individual molecular connectomes significantly increase both across the Alzheimer’s disease (AD) continuum and over time.
  • Alterations in individual molecular connectomes discriminate different diagnostic groups and predict cognitive decline to a higher extent than conventional positron emission tomography measures.
  • Susceptibilities of individual tau and amyloid connectomes to AD are linked to a common transcriptomic profile of apoptosis, with the tau connectome being specifically related to pyrimidine metabolism, and the amyloid connectome to histone acetylation.

Tracking early cognitive decline in preclinical AD with brain MRI similarity published in Alzheimer’s & Dementia

Parcellation of the brain cortex. (Image from the article.)
Tracking early cognitive decline in preclinical AD with brain MRI similarity
Jiawei Sun, Blanca Zufiria-Gerbolés, Massimiliano Passaretti, Giovanni Volpe, Mite Mijalkov, Joana B. Pereira, for the Alzheimer’s Disease Neuroimaging Initiative
Alzheimer’s & Dementia 22, e71170 (2026)
DOI: 10.1002/alz.71170

INTRODUCTION
Early detection of neuroanatomical changes in preclinical Alzheimer’s disease (AD) is critical for timely intervention. However, conventional magnetic resonance imaging (MRI) and fluid biomarkers often lack sensitivity to subtle structural alterations in early disease stages.

METHODS
To identify early brain alterations, we applied a perturbation-based brain similarity approach to cognitively normal participants from Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Open Access Series of Imaging Studies (OASIS), stratified by amyloid status. We evaluated its predictive performance for cognition and diagnostic conversion against cortical thickness, volumetric MRI, and fluid biomarkers.

RESULTS
In both cohorts, brain similarity consistently outperformed other biomarkers across cognitive domains and amyloid groups. It also achieved superior accuracy in predicting clinical conversion and exhibited associations with cytoarchitectural organization.

DISCUSSION
These findings highlight brain similarity as a sensitive marker of early neuroanatomical disruption in AD. Its ability to detect subtle structural changes before overt atrophy underscores its potential for early disease monitoring and treatment assessment in preclinical AD trials.

Highlights

  • Brain similarity captures early brain changes in preclinical Alzheimer’s disease (AD).
  • Brain similarity outperforms conventional biomarkers such as cortical thickness, volume measures, and fluid biomarkers in predicting cognitive decline.
  • Brain similarity predicts conversion to mild cognitive impairment and AD more accurately than traditional imaging markers, and its predictive performance is further improved when combined with fluid biomarkers.
  • Brain similarity captures structural disruptions associated with cortical layer II of the cytoarchitectonic lamina of human neocortex.

Label-free mass and size characterization of few-kDa biomolecules by hierarchical vision transformer augmented nanofluidic scattering microscopy published in Nature Communications

The principle of differential imaging in NSM, in which we subtract the light scattered (yellow arrows indicate the scattered-light direction) by an empty nanochannel from the light scattered by the same channel with a molecule inside. A sequence of differential images of a nanochannel containing a diffusing single molecule obtained in this way is combined into a kymograph, which then contains the full molecular trajectory. (Image from the article.)
Label-free mass and size characterization of few-kDa biomolecules by hierarchical vision transformer augmented nanofluidic scattering microscopy
Henrik K. Moberg, Bohdan Yeroshenko, Joachim Fritzsche, David Albinsson, Barbora Spackova, Daniel Midtvedt, Giovanni Volpe, Christoph Langhammer
Nature Communications 17, 2533 (2026)
DOI: 10.1038/s41467-026-70514-z

Nanofluidic scattering microscopy characterizes single molecules in subwavelength nanofluidic channels label-free, using the interference of visible light scattered by the molecule and nanochannel. It determines a molecule’s hydrodynamic radius by tracking its diffusion trajectory and its molecular weight by analyzing its scattering intensity along that trajectory. However, using standard analysis algorithms, it is limited to characterization of proteins larger than ≈ 60 kDa. Here, we push this limit by one order of magnitude to below ≈ 6 kDa molecular weight and ≈ 1.5 nm hydrodynamic radius — as we exemplify on the peptide hormone insulin — by using ultrasmall nanofluidic channels and by analyzing the data with a hierarchical vision transformer. When we benchmark this approach against the theoretical limit set by the Cramér–Rao Lower Bound, we find that it can be approached with sufficiently long molecular trajectories. This enables quantitative label-free single-molecule microscopy for biologically relevant families of sub-10-kDa molecules, such as cytokines, chemokines and peptide hormones.

International conference “Protein Folding in Real Time: From Molecules to Disease”, Aula Medica, KI, Stockholm, 11-13 March 2026

Giovanni Volpe opens the Protein Folding in Real Time conference. (Photo by A. Ciarlo)
The international conference Protein Folding in Real Time: From Molecules to Disease opened today, 11 March 2026, at Aula Medica, KI, Stockholm.

The conference brings together researchers from multiple disciplines, including biophysics, molecular biology, computational science, and medicine, to discuss recent advances in the study of protein folding. Proteins must fold into precise three-dimensional structures to perform their biological functions, and failures in this process are associated with several diseases, including neurodegenerative disorders and cancer.

During the three-day meeting, participants attend a series of lectures and discussions covering topics such as single-molecule biophysics, high-resolution experimental techniques for observing folding dynamics, advanced molecular simulations, and artificial intelligence approaches for predicting folding pathways. Particular attention is given to the challenge of observing protein folding in real time, capturing transient intermediate states that determine whether proteins reach their functional structure or misfold.

The event also highlights the interdisciplinary and international nature of the initiative. Representatives from the Embassies of Italy, Japan, and Spain, together with UNESCO, take part in the meeting, emphasizing the global interest in advancing research on protein folding and its biomedical implications. The initiative aims to integrate experimental measurements, computational modeling, and data-driven approaches to build a predictive framework for protein folding dynamics. By combining advanced imaging, force spectroscopy, and machine learning methods, the initiative seeks to better understand how folding processes occur inside living systems and how their disruption can lead to disease.

Overall, the conference provides an opportunity for scientists from different institutions to exchange ideas, establish collaborations, and shape future research directions in the field of protein folding and misfolding. The launch of this initiative represents an important step toward bridging molecular-level observations with biomedical applications, ultimately contributing to improved strategies for diagnosing and treating diseases related to protein misfolding.

Technological Excellence Requires Human and Social Context on ArXiv

Why breakthrough research needs humanities and social sciences. (From an artwork by Jacopo Sacquegno.)
Technological Excellence Requires Human and Social Context
Karl Palmås, Mats Benner, Monica Billger, Ben Clarke, Raimund Feifel, Julia Fernandez-Rodriguez, Anna Foka, Juliette Griffié, Claes Gustafsson, Kerstin Hamilton, Johan Holmén, Kristina Lindström, Tobias Olofsson, Joana B. Pereira, Marisa Ponti, Julia Ravanis, Sviatlana Shashkova, Emma Sparr, Pontus Strimling, Fredrik Höök, Giovanni Volpe
arXiv: 2603.10653

Breakthrough technologies increasingly shape social institutions, economic systems, and political futures. Yet models of research excellence associated with such technologies often prioritize technical performance, scalability, and short-term innovation metrics while treating ethical, social, and cultural dimensions as secondary considerations. This perspective article argues that such separation is no longer tenable. We propose a broader understanding of excellence that combines technical rigor with ethical robustness, social intelligibility, and long-term relevance. The rapid emergence of generative and agentic artificial intelligence further underscores this argument. As technological systems increasingly operate through language, interpretation, and normative alignment, expertise traditionally cultivated in the humanities and social sciences becomes integral to the design, governance, and responsible deployment of such systems. Drawing on historical examples and contemporary research practices, this article examines five interconnected domains where the humanities and social sciences, treated as integrated dimensions of research practice, can strengthen technological development: (1) ethical, legal, and social integration in agenda-setting and research design; (2) plural and reflexive foresight practices that shape technological futures; (3) graduate education as a leverage point for cross-disciplinary literacy; (4) visualization and communication as epistemic and civic practices; and (5) institutional frameworks that move beyond rigid distinctions between basic and applied research. Across these dimensions, we propose practical strategies for embedding interdisciplinary collaboration structurally rather than symbolically.

Roadmap on Deep Learning for Microscopy published in Journal of Physics: Photonics

Spatio-temporal spectrum diagram of microscopy techniques and their applications. (Image by the Authors of the manuscript.)
Roadmap on Deep Learning for Microscopy
Giovanni Volpe, Carolina Wählby, Lei Tian, Michael Hecht, Artur Yakimovich, Kristina Monakhova, Laura Waller, Ivo F. Sbalzarini, Christopher A. Metzler, Mingyang Xie, Kevin Zhang, Isaac C.D. Lenton, Halina Rubinsztein-Dunlop, Daniel Brunner, Bijie Bai, Aydogan Ozcan, Daniel Midtvedt, Hao Wang, Nataša Sladoje, Joakim Lindblad, Jason T. Smith, Marien Ochoa, Margarida Barroso, Xavier Intes, Tong Qiu, Li-Yu Yu, Sixian You, Yongtao Liu, Maxim A. Ziatdinov, Sergei V. Kalinin, Arlo Sheridan, Uri Manor, Elias Nehme, Ofri Goldenberg, Yoav Shechtman, Henrik K. Moberg, Christoph Langhammer, Barbora Špačková, Saga Helgadottir, Benjamin Midtvedt, Aykut Argun, Tobias Thalheim, Frank Cichos, Stefano Bo, Lars Hubatsch, Jesus Pineda, Carlo Manzo, Harshith Bachimanchi, Erik Selander, Antoni Homs-Corbera, Martin Fränzl, Kevin de Haan, Yair Rivenson, Zofia Korczak, Caroline Beck Adiels, Mite Mijalkov, Dániel Veréb, Yu-Wei Chang, Joana B. Pereira, Damian Matuszewski, Gustaf Kylberg, Ida-Maria Sintorn, Juan C. Caicedo, Beth A Cimini, Muyinatu A. Lediju Bell, Bruno M. Saraiva, Guillaume Jacquemet, Ricardo Henriques, Wei Ouyang, Trang Le, Estibaliz Gómez-de-Mariscal, Daniel Sage, Arrate Muñoz-Barrutia, Ebba Josefson Lindqvist, Johanna Bergman
Journal of Physics: Photonics 8, 012501 (2026)
arXiv: 2303.03793
doi: 10.1088/2515-7647/ae0fd1

Through digital imaging, microscopy has evolved from primarily being a means for visual observation of life at the micro- and nano-scale, to a quantitative tool with ever-increasing resolution and throughput. Artificial intelligence, deep neural networks, and machine learning (ML) are all niche terms describing computational methods that have gained a pivotal role in microscopy-based research over the past decade. This Roadmap encompasses key aspects of how ML is applied to microscopy image data, with the aim of gaining scientific knowledge by improved image quality, automated detection, segmentation, classification and tracking of objects, and efficient merging of information from multiple imaging modalities. We aim to give the reader an overview of the key developments and an understanding of possibilities and limitations of ML for microscopy. It will be of interest to a wide cross-disciplinary audience in the physical sciences and life sciences.