Biology subjects

Voros, J.

Publications and source records attributed to Voros, J..

11 recordsLinked to original sources

bioRxiv2026

A three-compartment microfluidic platform for investigating signal transmission in the human sensory pathway

Neuropathic pain remains a significant challenge due to limited understanding of sensory signal transmission mechanisms along the sensory pathway. The sensory pathway involves peripheral nociceptors in the dorsal root ganglia (DRG) that transmit signals from skin to the central nervous system via dorsal horn neurons. Current in vitro models lack the compartmentalization and resolution needed to investigate signal modulation at distinct anatomical sites along this pathway. Here, we developed a three-compartment microfluidic platform combining human induced pluripotent stem cell (iPSC)-derived sensory neurons (hiSNs) with human primary epidermal keratinocytes (HPEKs) and iPSC-derived dorsal horn neurons (hiDHNs) in a spatially organized arrangement. The platform integrates polydimethylsiloxane (PDMS) axon-guiding microstructures with high-density microelectrode arrays (HD-MEAs), enabling single-axon electrophysiological recordings and sub-cellular level stimulation. We established viable co-cultures maintained for up to six weeks and characterized spontaneous activity across all conditions. Keratinocytes increased the number of active sensory neuron axons and their firing rates, demonstrating peripheral modulation of neuronal activity. Systematic frequency-dependent electrical stimulation revealed low-pass filtering properties at sensory neuron somata, with filtering characteristics modulated by co-culture with keratinocytes. This platform enables compartment-specific investigation of signal processing in the human sensory pathway and provides a tool for studying neuropathic pain mechanisms and testing potential therapeutics.

bioengineering↗

bioRxiv2025

HydroMEA: A 3D Hydrogel Based Microfluidic Device to Study Electrophysiology for Myelinated Nerve-on-Chip

Engineered in vitro platforms are powerful systems to study information flow in the nervous system. While existing polydimethylsiloxane (PDMS)-based microfluidic platforms offer precise architectures, the cultured neurons grow on two-dimensional (2D) planar multielectrode arrays (MEA). To mimic the native microenvironment, where neurons grow in three-dimensional (3D) extracellular matrices (ECM), 3D hydrogels can be designed to encapsulate cells and enable physiologically-mimicked behaviors. Here, we describe hydroMEA, a 3D platform fabricated by placing PDMS microstructures on a high-density MEA and filled with a desired hydrogel, to offer controlled topologies, physiologically-relevant microenvironments, and real-time electrophysiological measurements. First, we developed a gelatin methacryloyl (GelMA) hydrogel with incorporated ECM components and tuned the mechanical properties to match those of nerve tissue. The hydrogel was able to support: 1) the growth of iPSC-derived sensory neurons (hSNs) for >100 days; 2) co-cultures of hSN with human embryonic stem cell-derived Schwann cells (hSCs), to enable reliable 3D myelination. Next, hydroMEA were prepared for topologically- defined 3D growth and myelination in designated compartments. Finally, electrophysiological evaluation of hSN-hSCs co-cultures revealed increased conduction speeds indicating functional myelin. This platform is a promising tool to study cell-cell interactions and to functionally evaluate the effect of pharmacological compounds in a more translational manner.

bioengineering↗

bioRxiv2025

Assessment of environmental variables for species distribution modelling: insights from the mosaic distribution of red- and yellow-bellied toads

Species distribution modelling can possibly be improved through the preferential use of explanatory variables that reflect the natural history features of the species being modelled. Red- and yellow-bellied toads (genus Bombina) engage in an intricate mosaic distribution across Europe. Analysing new atlas data on these species mutual distribution in Hungary with principal coordinate analysis we identified their differential ecological preferences as forested, hilly and mountainous for B. variegata and open lowland for B. bombina. These locally operating parameters we consider to be good proxies for the essential species difference which resides in breeding in ephemeral puddles (B. variegata) versus larger permanent ponds (B. bombina). With two-species distribution modelling - in which the presence of one species is contrasted with the presence of the counterpart species - we obtained excellent model fit (AUC) for climate and elevation / land cover datasets alike (AUC=0.98 versus 0.95). For both models fit values dropped upon transference to surrounding countries, yet the latter model kept significantly higher predictive power (AUC=0.91) than the climate model (AUC=0.79). Swapping elevation for hilliness as suggested in the literature had a significant negative effect on model performance. We conclude that an informed parameter selection enhances model transferability, therewith improving our understanding of species-habitat associations. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/650429v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@5caa3forg.highwire.dtl.DTLVardef@1ad3857org.highwire.dtl.DTLVardef@14df970org.highwire.dtl.DTLVardef@3352ca_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIRed- and yellow-bellied toads engage in a yin-yang-like mosaic distribution across Europe. C_LIO_LISpecies differential habitat characteristics were studied with principal coordinates. C_LIO_LISpecies distribution modelling was with climate data and with landscape variables. C_LIO_LIModels produced with atlas data for Hungary were assessed over neighbouring countries. C_LIO_LITransferred models with elevation and forestation performed better than climate-based ones. C_LI

ecology↗

bioRxiv2025

An in vitro platform for characterizing axonal electrophysiology of individual human iPSC-derived nociceptors

Current treatments against severe forms of neuropathic pain demonstrate insufficient efficacy or lead to unwanted side effects as they fail to specifically target the affected nociceptors - a specialized subclass of sensory neurons conveying potentially damaging stimuli information to the central nervous system. Neuropathic pain may involve different nociceptor subtypes in different patients. Tools that can distinguish nociceptive axons would enable a more targeted compound screening. Therefore, we developed an in vitro platform combining a CMOS-based high-density microelectrode array with a polydimethylsiloxane (PDMS) guiding microstructure that captures the electrophysiological responses of nociceptors. Human induced pluripotent stem cell-derived (iPSC) nociceptors were cultured at low density with axons distributed through parallel 4 x 10 {micro}m microchannels exiting the seeding well before converging to a bigger axon-collecting channel. This configuration allowed the measurement of stimulation-induced responses of individual axons. Nociceptors were found to exhibit a great diversity of electrophysiological response profiles that can be classified into different functional archetypes. Moreover, we show that some responses are affected by applying the TRPV1 agonist capsaicin. Overall, results using our platform demonstrate that we were able to distinguish nociceptive axons from different subtypes. The platform provides a promising tool for screening potential candidates for nociceptor-specific drugs.

bioengineering↗

bioRxiv2024

Inkube: An all-in-one solution for neuron culturing, electrophysiology, and fluidic exchange

Culturing neuronal networks in vitro is a tedious and time-consuming endeavor. In addition, how the composition of the culture medium and environmental variables such as temperature, osmolarity, and pH affect the spiking behavior of neuronal cultures is difficult to study using electrophysiology. In this work, we present "inkube", an incubation system that has been combined with an electrophysiology setup and a fully automatic perfusion system. This setup allows for the precise measurement and control of the temperature of up to 4 microelectrode arrays (MEAs) in parallel. In addition, neuronal activity can be electrically induced and recorded from the MEAs. inkube can continuously monitor the medium level to automatically readjust osmolarity. Using inkubes unique capability to precisely control the environmental variables of a neural culture, we found that medium evaporation influences the spiking response. Moreover, decreasing medium temperature by only 1.5{degrees}C significantly affected spike latency, a measure commonly used to show plasticity in in vitro experiments. We finally provide a proof-of-concept experiment for drug screening applications, where inkube automatically and precisely varies the concentration of magnesium ions in the medium. Given its high level of autonomy, the system can record, stimulate, and control the medium continuously without user intervention. Both the hardware and the software of inkube are completely open-source. HighlightsO_LILow-cost, open-hardware/open-software electrophysiology setup C_LIO_LIFull incubation solution: Temperature, CO2, and humidity control C_LIO_LIPerfusion system for automatic fluidic exchange and drug testing with volume feedback C_LI

bioengineering↗

bioRxiv2024

Mitigation of chytrid infection on tadpoles with the antimicrobial metabolites of Xenorhabdus szentirmaii

Survival of amphibian assemblages is threatened by many factors. Among them, chytridiomycosis, the disease caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd) has great importance, also threatening the populations of the yellow-bellied toad (Bombina variegata), which has a scattered, isolated distribution in Hungary. Treatment with secondary metabolites of the entomopathogenic bacterium, Xenorhabdus szentirmaii is a promising method in the mitigation of chytridiomycosis, as recently demonstrated. To assess whether it may also be effective for lowering infection intensities in B. variegata tadpoles, we extracted cell-free culture media (CFCM) from liquid cultures of X. szentirmaii and tested their antifungal efficacy at a dilution of 0.1 % (v/v), while also measuring possible short-term malign effects on tadpoles experimentally infected with Bd or sham infection. According to our results, CFCM treatment alone did not compromise tadpoles survival probability, nor reduced the body mass and developmental speed of the individuals. At the same time, the treatment reduced the intensity and prevalence of Bd infection, but this effect was affected by the population of origin. The antimicrobial metabolites produced by X. szentirmaii may therefore be suitable for the safe mitigation of chytridiomycosis in B. variegata tadpoles, but further studies are needed, aiming to monitor and increase the efficacy of this method.

ecology↗

bioRxiv2024

Impact of microchannel width on axons for brain-on-chip applications

Technologies for axon guidance for in vitro disease models and bottom up investigations are increasingly being used in neuroscience research. One of the most prevalent patterning methods is using polydimethylsiloxane (PDMS) microstructures due to compatibility with microscopy and electrophysiology which enables systematic tracking of axon development with precision and efficiency. Previous investigations of these guidance platforms have noted axons tend to follow edges and avoid sharp turns; however, the specific impact of spatial constraints remains only partially explored. We investigated the influence of microchannel width beyond a constriction point, as well as the number of available microchannels, on axon growth dynamics. Further, by manipulating the size of micron/submicron-sized PDMS tunnels we investigated the space restriction that prevents growth cone penetration showing that restrictions smaller than 350nm were sufficient to exclude axons. This research offers insights into the interplay of spatial constraints, axon development, and neural behavior. The findings are important for designing in vitro platforms and in vivo neural interfaces for both fundamental neuroscience and translational applications in rapidly evolving neural implant technologies.

neuroscience↗

bioRxiv2024

A modular and flexible open source cell incubator system for mobile and stationary use

Culturing living cells in vitro requires the maintenance of physiological conditions for extended periods of time. Here, we introduce a versatile and affordable incubation system, addressing the limitations of traditional incubation systems. Conventionally, stationary cell incubators maintain constant temperature and gas levels for in vitro cell culturing. Combining such incubators with additional lab equipment proves challenging. The presented platform offers modularity and adaptability, enabling customization to diverse experimental needs. The system includes a main unit with a user-friendly interface as well as an interchangeable incubation chamber. We present two incubation chambers targeting two completely different use cases. The first chamber, named "inkugo" facilitates the transportation of cells for up to two hours without external power and for more than a day without an external CO2 source. The second chamber termed "inkubox" was designed to enable continuous electrophysiological recordings. Recordings from up to four neural cultures growing on high-density microelectrode arrays can be performed in parallel. The systems unique feature lies in its separability of control and incubation components, allowing one control unit to manage various custom chambers. The designs simplicity and the use of widely accessible components make the here proposed incubation system replicable for any laboratory. This platform fosters collaboration and experimentation in both decentralized and traditional laboratory settings, making it an invaluable addition to any cell culturing pipeline. Specifications table O_TBL View this table: org.highwire.dtl.DTLVardef@2c755borg.highwire.dtl.DTLVardef@ccd382org.highwire.dtl.DTLVardef@1522f81org.highwire.dtl.DTLVardef@ace0aeorg.highwire.dtl.DTLVardef@1d2e4c8_HPS_FORMAT_FIGEXP M_TBL C_TBL

cell biology↗

bioRxiv2021

Engineered biological neural networks on high density CMOS micro electrode arrays

In bottom-up neuroscience, questions on neural information processing are addressed by engineering small but reproducible biological neural networks of defined network topology in vitro. The network topology can be controlled by culturing neurons within polydimethylsiloxane (PDMS) microstructures that are combined with microelectrode arrays (MEAs) for electric access to the network. However, currently used glass MEAs are limited to 256 electrodes and pose a limitation to the spatial resolution as well as the design of more complex microstructures. The use of high density complementary metal-oxide-semiconductor (CMOS) MEAs greatly increases the spatiotemporal resolution, enabling sub-cellular readout and stimulation of neurons in defined neural networks. Unfortunately, the non-planar surface of CMOS MEAs complicates the attachment of PDMS microstructures. To overcome the problem of axons escaping the microstructures through the ridges of the CMOS MEA, we stamp-transferred a thin film of hexane-diluted PDMS onto the array such that the PDMS filled the ridges at the contact surface of the microstructures without clogging the axon guidance channels. Moreover, we provide an impedance-based method to visualize the exact location of the microstructures on the MEA and show that our method can confine axonal growth within the PDMS microstructures. Finally, the high spatiotemporal resolution of the CMOS MEA enabled us to show that we can guide action potentials using the unidirectional topology of our circular multi-node microstructure.

neuroscience↗

bioRxiv2020

Opto-E-Dura: a Soft, Stretchable ECoG Array for Multimodal, Multi-scale Neuroscience

Soft, stretchable materials hold great promise for the fabrication of biomedical devices due to their capacity to integrate gracefully with and conform to biological tissues. Conformal devices are of particular interest in the development of brain interfaces where rigid structures can lead to tissue damage and loss of signal quality over the lifetime of the implant. Interfaces to study brain function and dysfunction increasingly require multimodal access in order to facilitate measurement of diverse physiological signals that span the disparate temporal and spatial scales of brain dynamics. Here we present the Opto-e-Dura, a soft, stretchable, 16-channel electrocorticography array that is optically transparent. We demonstrate its compatibility with diverse optical and electrical readouts enabling multimodal studies that bridge spatial and temporal scales. The device is chronically stable for weeks, compatible with wide-field and 2-photon calcium imaging and permits the repeated insertion of penetrating multi-electrode arrays. As the variety of sensors and effectors realizable on soft, stretchable substrates expands, similar devices that provide large-scale, multimodal access to the brain will continue to improve fundamental understanding of brain function.

neuroscience↗

bioRxiv2019

UDCT: Unsupervised data to content transformation with histogram-matching cycle-consistent generative adversarial networks

The segmentation of images is a common task in a broad range of research fields. To tackle increasingly complex images, artificial intelligence (AI) based approaches have emerged to overcome the shortcomings of traditional feature detection methods. Owing to the fact that most AI research is made publicly accessible and programming the required algorithms is now possible in many popular languages, the use of such approaches is becoming widespread. However, these methods often require data labeled by the researcher to provide a training target for the algorithms to converge to the desired result. This labeling is a limiting factor in many cases and can become prohibitively time consuming. Inspired by Cycle-consistent Generative Adversarial Networks (cycleGAN) ability to perform style transfer, we outline a method whereby a computer generated set of images is used to segment the true images. We benchmark our unsupervised approach against a state-of-the-art supervised cell-counting network on the VGG Cells dataset and show that it is not only competitive but can also precisely locate individual cells. We demonstrate the power of this method by segmenting bright-field images of cell cultures, a live-dead assay of C.Elegans and X-ray-computed tomography of metallic nanowire meshes.

bioengineering↗