Long-duration space missions expose astronauts to microgravity and ionizing radiation, increasing the risk of hematological disorders such as acute myeloid leukemia (AML). Real-time health monitoring requires compact, autonomous, and reliable diagnostic tools capable of operating under extreme conditions. This study presents the adaptation of a commercial spiral microfluidic chip (Fluidic 382) for label-free, size-based separation of blood cells, with potential integration into metrological systems for space applications. The device exploits Dean-flow hydrodynamic forces to isolate red blood cells, white blood cells, and pathological blasts from AML patient samples without fluorescent markers or complex preparation. Experimental results demonstrate separation efficiencies exceeding 90% for white blood cells and 83% for leukemic blasts, with strong reproducibility across multiple donors. Numerical simulations using COMSOL Multiphysics confirm experimental findings with a relative error below 1%, supporting the device's predictive capability and metrological reliability. The chip's compact design, low power consumption, and compatibility with automated fluidic systems make it suitable for integration into portable diagnostic platforms for space missions. The quantitative agreement between experimental and simulated data establishes a foundation for developing metrological protocols to validate cell separation performance under microgravity conditions. This work advances precision diagnostics for extreme environments, contributing to space metrology and personalized health monitoring in aerospace medicine.

Astronauts have been reported to have an unusually high rate of kidney stone formation during spaceflight, which represents a risk for the health and for the space mission success. Our studies in humans adapted to simulated microgravity (bedrest) demonstrate that exposure to microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion thus increasing the risk of renal stone formation. Vasopressin, the main hormone involved in water balance regulation, promotes urine concentration and reduces bone mass. Interestingly, measurements of vasopressin in astronauts (from 24 h to 8 days after launch), revealed concentrations considerably elevated compared to ground, suggesting a critical role for this hormone in renal stone risk in microgravity. In line, in a previous 10-days bedrest study, we provided evidence that bedrest is associated with an early increased risk of stone formation that was monitored by novel identified biomarkers. The impact of simulated microgravity in risk of stone formation is currently under investigation in a more recent 21-day bedrest campaign as part of Science for Bed Rest program of Italian Space Agency (ASI). This study involves, for the first time, men and women, thus allowing a more general understanding of sex difference in hormonal response to simulated microgravity. Preliminary results indicate a tendency toward increased vasopressin levels, evaluated as copeptin, a validated and reliable surrogate marker of vasopressin, over 21-day bedrest both in men (n=6) and women (n=6) with a peak at day 15. These preliminary data suggest that both men and women may respond to changes in blood volume or osmolality during bedrest and release higher amount of vasopressin to restore decreased plasma and extracellular volume known to occur consequently to adaptation to microgravity. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Human exploration beyond low Earth orbit poses unique health and operational challenges, with space radiation recognized as one of the most significant hazards. This comprehensive review examines the complex nature of the space radiation environment, its biological effects on humans and life support systems, and current strategies for risk assessment and mitigation. It details the composition and properties of galactic cosmic rays (GCRs) and solar particle events (SPEs), their interactions with spacecraft shielding, and the resulting biological impacts ranging from DNA damage to systemic effects including cancer, cardiovascular disease, and central nervous system impairments. Special emphasis is given to the combined effects of radiation and microgravity, which together alter cellular function and influence health outcomes. The paper also explores the effects of radiation on plants and microorganisms as biological components of bioregenerative life support systems (BLSS). The issue of radiation-induced degradation of food and pharmaceuticals is also considered. Existing and emerging countermeasures, encompassing passive and active shielding, pharmacological agents, nutrition, physiological adaptations like synthetic hibernation, and personalized risk assessment through targeted crew selection are critically reviewed. Additionally, the work highlights the importance of high-fidelity analog studies, space-based experiments, and advanced risk models integrating physical, biological, and operational data to inform future mission planning. Finally, the paper reviews existing infrastructures, experimental platforms, and European research programs, emphasizing the critical role of ground-based accelerators, space analog environments, and in-flight studies in advancing our understanding of radiation risks. By identifying key knowledge gaps and proposing a structured mitigation framework, this study presents a strategic roadmap for protecting human health and sustaining life during long-duration missions to the Moon, Mars, and beyond. (The review work described in the paper stems from the discussions within the working group on Radiation sponsored by the Italian Space Agency.)

Background: Establishing whether sex-specific differences exist in physiological responses to environmental insults, such as microgravity, is a major priority in modern physiology. With females now comprising 40% of current NASA astronauts, we still have a limited understanding of sex differences in adaptations to microgravity despite their increasing exposure to spaceflight. In this study, we compared electrophysiological changes in motor unit (MU) properties between males and females subjected to head-down tilt bed rest, a well-established experimental microgravity analog. Methods: Nine healthy young males (YM; 18–36 years) and nine healthy young females (YF; 18–31 years) underwent 21 days of −6° head-down tilt bed rest. Before and after bed rest, knee extensor maximal voluntary contraction (MVC) was assessed by isometric dynamometry, while vastus lateralis (VL) cross-sectional area (CSA) at 50% of femur length was evaluated by panoramic ultrasound. Intramuscular electromyography (iEMG) recordings were obtained from the VL to evaluate MU properties and neuromuscular junction (NMJ) transmission during voluntary contractions at 25% MVC. Statistical analysis was performed using linear mixed models (fixed effects: time and sex; cluster variable: subject). Results: Knee extensor MVC declined similarly in YM (−21.4%, p < 0.001) and YF (−22.3%, p < 0.001) following bed rest. VL CSA showed a parallel reduction (YM: −11.9%, p < 0.001; YF: −13.19%, p < 0.001). However, iEMG analysis revealed a significant sex × time interaction (p = 0.004) for motoneuron firing rate, with YF showing a greater decrease (−9.8%, p < 0.001) compared to YM (−5.1%, p < 0.001). Conversely, only YM showed a reduction in motor unit potential (MUP) area (−7.2%, p = 0.001), suggesting decreased MU size with disuse. Finally, impaired NMJ transmission, reflected by increased near fiber jiggle (+11.1%, p=0.036), was observed exclusively in YM. Conclusion: Despite a comparable loss of muscle strength and size, young males and females exhibit distinct neuromuscular adaptations to simulated microgravity. Females demonstrated greater central vulnerability, as indicated by the larger decline in motoneuron firing rate, whereas exclusively males showed signs of a more peripheral neuromuscular remodeling, as suggested by a reduced MU size and impaired NMJ transmission. These findings may be of considerable relevance for human health during spaceflight and may help guide the development of sex-specific countermeasures. Funding: This study was carried out within the framework of the collaboration agreement n. 2025-4-HB.0 between ASI and the University of Padua for the “Neuromyo” project. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

This work analyzes the implications of PP implementation in biologically active human space modules, using the BEATRICE (Bioregenerative Experimentation for Analog Testing and Resource optimization exploiting ISRU, autonomous Cultivation and MFC-based Energy harvesting) BLSS architecture as a conceptual case study. The study examines the transition from a lunar Category II framework to potential Martian Category IV compliance, characterized by stringent forward-contamination constraints. In this scenario, quantitative microbiological monitoring, containment verification strategies, filtration performance validation, and probabilistic contamination modelling approaches must also be considered. By translating COSPAR PP principles into measurable engineering requirements, this work highlights the central role of metrology in enabling sustainable human exploration while preserving the scientific integrity of extraterrestrial environments.

We demonstrate a novel biomedical application of a commercial spiral microfluidic chip (Fluidic 382), originally developed for particle sorting, by repurposing it for label-free, size-based isolation of pathological blood cells, including leukemic blasts from acute myeloid leukemia (AML) samples. For the first time, we establish and validate a streamlined protocol for cell separation using Dean-driven hydrodynamic forces in a chip not originally designed for blood analysis. Using a 9-turn, 6-outlet spiral channel configuration, we achieved high-efficiency sorting of red and white blood cells from healthy donors and selectively enriched pathological blasts from AML patient blood. The device’s performance was validated through flow cytometry and numerical simulations, demonstrating strong agreement between experimental and computational results with less than 1% relative error. With its compact footprint, reagent-free operation, and automation potential, this method represents a significant advance toward point-of-care blood diagnostics in extreme environments, particularly space missions. The chip’s ability to separate pathological cells in microgravity-compatible conditions offers a promising route for real-time astronaut health monitoring, supporting early detection and mitigation of radiation-induced haematological disorders such as AML.

Human space missions beyond Low Earth Orbit (LEO), such as to the Moon and Mars, will require increased crew autonomy in health management, due to communication delays and limited resupply. These missions pose unique biomedical challenges, including radiation exposure, altered gravity, and prolonged isolation, which can affect physiology and compromise available treatments. This review examines current efforts in pharmaceutical and biomedical strategies to support health preservation during long-duration missions. We discuss technologies needed to assure drug stability and storage, also considering potential modifications of pharmacokinetics in space, and the potential of nanotechnologies, physical therapies, and in-situ manufacturing. Non-pharmacological tools for diagnostics, trauma care, and tissue regeneration are highlighted for their promise in enhancing medical self-sufficiency. These advances are not only critical for ensuring mission success and crew safety beyond LEO, yet may also translate to healthcare solutions in remote or underserved Earth settings. Ciofani et al., discuss the unique medical and pharmaceutical challenges in maintaining and supplying medical care for crews involved for human space missions beyond Low Earth Orbit, such as to the Moon and Mars. They highlight opportunities for repurposing existing innovative technologies and biomedical advances to support crew health during long-duration missions.

In the era of outer space exploration, wearable and smart devices have become more important than ever before. This creates the need for quantitative fabrication of functionalized materials. From liquid film to coating, with the rapid development of manufacturing technology, the demand for real-time characterization of soft materials keeps increasing. Digital holography (DH) has been proven to be a good tool for soft matter measurements; it has been successfully applied in thin film characterization in different scenarios. Here, we demonstrate how a closed-loop manufacturing process based on DH monitoring can help to achieve the fabrication of uniform and ultrathin functionalized polymeric membranes. Thanks to the amazing full-field characterization capability of digital holography at the micrometer scale, detailed information of liquid film evolution is revealed with unprecedented precision. From the motion of liquid flows to nanoparticle clusters on membrane surfaces, holographic imaging demonstrates its inherent ability to perform non-contact, label-free measurements; this allows for continuous iteration of film functionalization process. We believe that holography-based membrane and thin liquid film forming processes will open new possibilities for advanced biomaterials.

Spaceflight missions represent a new exposome, unpredicted by evolution. Life-threatening agents activate non-specific stress responses involving the psycho-immune-neuroendocrine network. The main molecular pathways regulating this network and those affected by spaceflight exposome/microgravity are reported in various experimental setups. They include gut microbiota-derived metabolites, potentially valuable for countermeasure development. Meaningfully, the application of neuromodulation techniques, like the non-invasive transcutaneous vagal stimulation, for the prevention of pathophysiological alterations related to stress responses, is discussed.

To support safe human space exploration, it is important to understand how different effectors, including gravitational forces, influence living organisms. Indeed, altered levels of gravity affect the physiological function of multiple cells, tissues, and organs in living organisms. Previous studies suggested that microgravity modifies plasma membrane permeability and cellular metabolism in erythrocyte, modifying cholesterol and phospholipid levels. However, to support human safe space exploration, it is also relevant to understand the effects of hypergravity. Therefore, the aim of this study was to investigate in vivo the impact of hypergravity on lipid phenotype and oxidative stress in mouse erythrocytes. Animals were housed in the Italian Space Agency's Mice Drawer System (MDS-ASI), a facility designed to house rodents on the International Space Station (ISS) and adapted by Thales Alenia Space to the Large Diameter Centrifuge (LDC-ESA), to expose mice to a 3xg environment for 14 days. After exposure, a tissue-sharing protocol allowed us to purify and analyze erythrocytes. Our results show that the exposure of mice to altered gravity induced the reduction of unsaturation degree in erythrocyte membranes correlated to a lower stearoyl-CoA desaturase (SCD-1) activity. Moreover, the hyper-gravity induced both a decline in antioxidant defences, indicated by the significant decrease in total glutathione, and a grow of the inflammatory status, supported by an increase in the AA/EPA ratio.

Holographic flow cytometry has been widely used on both single cell and high throughput cells analysis. To perform real-time digital holographic recording, off-axis interferometer is one of the optimal solutions. Conventional offaxis interferometer setups, such as the Mach-Zehnder geometry, have difficulty producing stable holographic interference fringes under strong environmental disturbances. For this reason, Sagnac geometry could be a good candidate for future holographic microscopy, especially for biological experiments which will be performed during space travel. Here we will present a series of flow cytometry measurements based on Sagnac interferometer. We demonstrate that both single-cell tomography and spatiotemporal digital holography (STDH) can be implemented based on the holograms acquired by Sagnac system. By optimizing the reconstruction process and improving the hologram assembly method, the Sagnac structure can achieve the same imaging field of view (FoV) and resolution as conventional off-axis interferometry geometry. We believe that the digital holographic microscope based on the Sagnac optical geometry will be one of the possible strategies for implementing rapid cell detection in space missions.

Changes in endocrine and kidney functions have been associated with spaceflight. Here, we discuss the most relevant evidence about the impact of spaceflight on the cardiometabolic system, the cardiorenal function and the reproductive/gonadal axis. Notably, these changes appear to be interrelated with other organ/system functions, suggesting the need of a systemic approach leading to a more comprehensive understanding of physiological and health-related impacts of the space environment. Therefore, this review will also focus on the need to move space endocrinological research to multi-omics approaches and the implementation of “machine learning” and “data mining” strategies.

Here we demonstrate for the first time that an antibody-gold nanoparticles (AuNPs)-polymer conjugate thin-film biosensor can easily be fabricated to selectively capture Tau protein. Gold nanoparticles (AuNPs) are employed as sensing elements, thus capitalizing on their propensity to undergo assembly or disassembly in response to the adsorption or conjugation of various biomolecules on their surface, thereby forming robust interactions with the target analyte. We show that the Tau protein in its different aggregation phases can be detected, by restricting the reaction area on the solid thin polymer film and thus reducing the diffusion effects usually encountered in immunosensors. A limit of detection (LOD) of 460 pg/mL was reached, demonstrating a great potential for detecting Tau in aggregation states. This sensor based on thin polymer film could open new routes for sensing and monitoring Tau protein in biological assays and biomedical diagnosis.

Traditional methods for cell separation, such as density gradient centrifugation and flow cytometry, are limited by factors like large sample volumes, high costs, and the potential for cellular damage. In contrast, microfluidic-based sorting provides a compact, cost-effective, and high-throughput platform with minimal mechanical stress. This study evaluates the performance of a commercial spiral microfluidic chip and a custom-made 3D-printed chip for size-based separation of MCF-7 breast cancer cells and white blood cells from a spiked sample. The custom-made 3D-printed chip was fabricated using Digital Light Processing 3D printing, offering rapid prototyping and high precision. Experimental results demonstrate the efficient separation of MCF-7 cells, with a high recovery rate, and suggest that the 3D-printed chip performs comparably to commercial alternatives. The study highlights the potential of 3D-printed microfluidics for label-free cell separation, with promising applications in circulating tumor cell isolation, single-cell analysis, and personalized medicine. Further refinement of chip geometry and optimization of flow conditions could enhance sorting precision and scalability, making this approach a valuable tool for both diagnostic and research applications. Additionally, structural health monitoring (SHM) and nondestructive testing (NDT) techniques play a crucial role in aerospace applications, ensuring the integrity and reliability of components subjected to extreme conditions. These methodologies could be further explored to assess and enhance the fabrication quality of 3D-printed microfluidic chips, bridging the gap between biomedical and aerospace applications.

The detailed molecular insight is particularly important because even minor structural modifications in proteins, such as Tau, amyloid or synuclein family, are closely linked to the initiation and progression of neurodegenerative disorders, thereby making them critical targets for early diagnostic efforts. In the context of extended space missions, where long-term monitoring is crucial, our innovative approach could prove invaluable for tracking astronauts’ health, with the introduction of the pyro-electrohydrodynamic jetting (p-jet) technique. This method exploits a combination of thermal and electrical forces to accurately deposit and concentrate biomolecules onto chemically treated surfaces. Here we demonstrate that p-jet technology can effectively concentrate highly diluted biomolecules into distinct fluorescent micro-spots on a reactive substrate, confirming its potential as a powerful tool in biosensing. One of the key challenges addressed here is to enhance the binding efficiency of low-abundance proteins to improve the detection sensitivity. To this end, we used bovine serum albumin (BSA) as a model protein to evaluate its immobilization within the p-jet spots. Our results revealed that, especially when covalent bonding is employed, the p-jet method produces a reliable, concentration-dependent signal, achieving an impressive limit of detection (LOD) of 4.5fM—far surpassing the sensitivity of standard ELISA techniques. Taking a step further towards clinical applications, we applied the p-jet technique to detect pre-aggregated Tau protein in artificial urine, which mimics human biological fluids. This approach allowed us to detect Tau at femtomolar concentrations (LOD of 130 fM) while preserving its structural integrity. With its minimal sample requirements and cost-effective nature, this p-jet technique marks an advancement in the early monitoring of neurodegenerative syndromes, with significant potential for diverse point-of-care (POC) scenarios. It could also play a key role in contexts such as long-term human space exploration missions, where early diagnosis of neurodegeneration is crucial.

Imaging flow cytometry is a cutting-edge technology for analyzing cell features. Here we show the advantage of using this system to study cell nucleus of tumor cells, using ovarian cancer A2780 cell line as model. Amnis Image stream it has been used as a standard comparison tool respect to quantitative phase imaging to study cell features.

IntroductionThe future of human space missions relies on the ability to provide adequate food resources for astronauts and also to reduce stress due to the environment (microgravity and cosmic radiation). In this context, microgreens have been proposed for the astronaut diet because of their fast-growing time and their high levels of bioactive compounds and nutrients (vitamins, antioxidants, minerals, etc.), which are even higher than mature plants, and are usually consumed as ready-to-eat vegetables.MethodsOur study aimed to identify the best light recipe for the soilless cultivation of two cultivars of radish microgreens (Raphanus sativus, green daikon, and rioja improved) harvested eight days after sowing that could be used for space farming. The effects on plant metabolism of three different light emitting diodes (LED) light recipes (L1—20% red, 20% green, 60% blue; L2—40% red, 20% green, 40% blue; L3—60% red, 20% green, 20% blue) were tested on radish microgreens hydroponically grown. A fluorimetric-based technique was used for a real-time non-destructive screening to characterize plant methabolism. The adopted sensors allowed us to quantitatively estimate the fluorescence of flavonols, anthocyanins, and chlorophyll via specific indices verified by standardized spectrophotometric methods. To assess plant growth, morphometric parameters (fresh and dry weight, cotyledon area and weight, hypocotyl length) were analyzed.ResultsWe observed a statistically significant positive effect on biomass accumulation and productivity for both cultivars grown under the same light recipe (40% blue, 20% green, 40% red). We further investigated how the addition of UV and/or far-red LED lights could have a positive effect on plant metabolite accumulation (anthocyanins and flavonols).DiscussionThese results can help design plant-based bioregenerative life-support systems for long-duration human space exploration, by integrating fluorescence-based non-destructive techniques to monitor the accumulation of metabolites with nutraceutical properties in soilless cultivated microgreens.