Abstract
In recent years, the integration of microphysiological systems (including organoids and organ-on-a-chip) with advanced in-orbit detection technologies is driving a fundamental transformation in the research paradigm of space life sciences. This paper systematically reviews the advantages of microphysiological systems in mimicking the three-dimensional structure and physiological functions of human organs, and summarizes their application practices on platforms such as the International Space Station, covering research progress and key findings in multiple tissue models, including brain, bone, and immune tissue. It also provides a detailed review of the latest developments in in-situ detection technologies such as high-content fluorescence imaging, light-sheet microscopy, Raman spectroscopy, and nanopore sequencing. Furthermore, it analyzes major current challenges in the field, including limited technology integration, a lack of long-term culture systems, and insufficient multi-modal data fusion. Finally, it looks ahead to the future development direction of intelligent and integrated space experimental platforms, emphasizing that the deep integration of multi-modal sensing, artificial intelligence, and automation methods will propel space life science research into a new stage of multi-scale, systematic, and precise analysis.
Introduction
In the grand journey of human exploration of space, extraterrestrial survival and health protection are the eternal cornerstones. Since the first human entered space, we have clearly recognized that the special environmental factors in space, especially microgravity and galactic cosmic radiation, have a profound impact on living organisms from the molecular, cellular to tissue and system levels [1]. These effects are not single, isolated symptoms, but constitute a complex "space adaptation syndrome", the core manifestations of which include continuous bone loss, muscle atrophy, immune dysfunction, cardiovascular disorders, visual impairment caused by fluid transfer, and changes in neurosensory perception [2]. The famous "twin study" by the National Aeronautics and Space Administration (NASA) compared and analyzed astronaut Scott Kelly (on orbit for 340 days) with his identical twin brother Mark (ground control group) , as shown in Figure1: The left side shows a pair of genetically identical twins, representing the ground control group (wearing green clothing) and the spaceflight group (wearing blue clothing) , respectively; the middle is a three-dimensional time axis structure, which shows that data were collected on biomedical indicators (including biochemistry, cognition, epigenome, gene expression, immunity, metabolomics, microbiome, proteomics, physiology, and telomeres) in the three stages of pre-flight, during-flight, and post-flight; the right side presents the integrated analysis results through concentric ring diagrams, which are used to guide the biomedical assessment of future space missions. This study revealed at the molecular level that spaceflight can cause significant changes in gene expression profiles, telomere dynamics, DNA methylation patterns, and cognitive functions . This fully illustrates the profound and extensive impact of the space environment [3].
Fig.1: NASA twin comparison experiment [1]
However, space life science research has long faced two major challenges: insufficient physiological relevance of model systems and limitations in real-time on-orbit detection capabilities. Traditional two-dimensional cell culture models, due to their lack of tissue-level three-dimensional structure, cell-cell/cell-matrix interactions, and heterogeneity of physiological microenvironment, are difficult to truly reflect the complex response of organisms in the space environment [4]. On the other hand, due to limitations in on-orbit analysis methods, most experimental samples need to be frozen and returned to Earth for analysis. This process inevitably introduces artificial artifacts caused by cryopreservation, temperature fluctuations, and drastic changes in the gravitational environment (from microgravity to 1 G) , resulting in the loss or distortion of some key (especially space environment-specific) instantaneous biological signals, and their limitations are self-evident.
In recent years, two major technological waves have been working together to propel space life science into a new era. One is the rise of microphysiological systems. Models such as organoids and organ-on-a-chip utilize stem cells or primary tissue cells to self-organize in vitro to form miniature three-dimensional structures with key structures and functions of organs in vivo, providing an unprecedented platform for simulating human physiology and pathology in the space environment [5]. The other is the breakthrough of advanced on-orbit detection technology. The development and application of technologies such as high-content fluorescence microscopy, light sheet imaging, Raman spectroscopy, and even nanopore sequencing have made it possible to perform in-situ, real-time, and dynamic analysis of life processes [6]. The combination of these two is transforming space life science from a "descriptive science" to a "predictive science" and a "mechanistic science".
This paper aims to systematically review the applicationsand breakthroughs of microphysiological systems in space life sciences, and to focus on the latest advancements in supporting on-orbit detection technologies. By analyzing the current paradigm shift and challenges, and looking ahead to the development trends of integrated platforms, this article seeks to provide researchers in related fields with a comprehensive reference and promote a deep leap from "observational description" to "mechanism analysis" in space life sciences.
1 Space microphysiological systems: from model building to scientific discovery
Microphysiological systems, particularly organoids and organ-on-a-chip, are reshaping the research landscape of space biology. They are elevating scientific research from the simple cellular level to the more complex tissue and organ level, enabling us to ask and answer more complex questions within a more physiologically relevant system.
1.1 Model advantages and spatial applicability
Organoids are three-dimensional cell clusters formed by pluripotent stem cells (including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) ) or adult stem cells/progenitor cells through a self-organization process under the induction of a specific combination of factors. They can simulate the cell type, spatial structure and some functions of the source organ [7]. For example, intestinal organoids can form polarized epithelium with crypt-villous structure [8]; brain organoids can differentiate into different brain regions and form functional neural connections [9]. Organ-on-a-chip is a masterpiece of bioengineering. It uses microfluidic technology combined with biosensor units to construct a micro-engineered system containing living cells, tissue barriers and fluid stimulation on a chip to simulate physiological functions at the organ level, such as respiratory mechanical stretching of the lungs, metabolism of the liver, filtration of the kidneys, etc.[10] As shown in Figure2, the research path from stem cell differentiation to chip integration is clearly conveyed by using colors to distinguish tissue types and arrows to indicate the direction of the process.
Compared with traditional two-dimensional models, microphysiological systems have unparalleled advantages in space research:
(1) Extremely high physiological relevance: Three-dimensional structures better preserve cell polarity, intercellular communication and nutrient/metabolite gradients, and can more realistically reflect the tissue's response to the spatial environment. For example, in bone organoids, the regulation of microgravity on the interaction between osteoblasts and osteoclasts in three-dimensional space can be studied. This is not possible in two-dimensional models [13].
(2) Great potential for mechanism research: It can study processes that cannot be observed in two-dimensional models, such as morphogenesis, cell migration, angiogenesis and multicellular synergy. This is crucial for understanding how the space environment affects tissue development, regeneration and repair [14].
(3) Platform for personalized medicine and precision research: Patient-specific iPSCs can be used to construct disease models (such as hereditary osteoporosis, familial Alzheimer's disease, etc.) to study the impact of individual genetic background on space environment sensitivity, paving the way for the realization of "precision aerospace medicine" [15].
1.2 Study of the microphysiological system on the International Space Station
The International Space Station has become the main platform for research on space microphysiological systems. The Tissue Chips in Space project, initiated by the National Center for Translational Science (NCATS) in cooperation with the International Space Station National Laboratory (ISS National Lab) , is the core force that systematically promotes the development of this field [16].
1.2.1 On-orbit practice of diversified organizational models
Since 2018, various microphysiological system models have been sent to the International Space Station. For example, the brain organ-on-a-chip developed by Emulate is used to study the effects of microgravity on blood-brain barrier function and neuroinflammation [17]. Immunochips have been used to study the activation and inhibition mechanisms of T cells under microgravity, revealing the possible damage to T cell receptor signaling pathways [18]. Blood-brain barrier chips are used to study whether the space environment increases the permeability of the blood-brain barrier and thus affects the health of the central nervous system by co-culturing human brain microvascular endothelial cells, pericytes and astrocytes [19]. Bone-cartilage chips directly simulate joint interfaces and study the potential causes of common joint discomfort and degeneration in astronauts [20]. In addition, the automated heart organ-on-a-chip platform uses engineered human heart tissues (EHTs) combined with magnetic sensing technology to monitor the contractility, rhythm and mitochondrial function of heart tissues in real time under microgravity. It found that spaceflight leads to an increase in the frequency of arrhythmias, a continuous decrease in contractility and mitochondrial damage, revealing the key role of oxidative stress and metabolic disorders in space-induced cardiac dysfunction [21].
1.2.2 Breakthroughs in brain organoid research
Using brain organoids derived from iPSCs, scientists studied the effects of microgravity on neural development on the International Space Station. Preliminary results suggest that microgravity may affect the proliferation and differentiation rhythm of neural stem cells and alter the expression profiles of genes related to synapse formation and function. This provides key clues for understanding the potential impact of long-term spaceflight on cognitive function [22].
1.2.3 Contributions of the Chinese space station
China's space station has planned and implemented a number of life science experimental projects, including space stem cell differentiation and organ-on-a-chip technology, aiming to study bionic chips of important and sensitive organs in the space complex environment and develop non-contact in-situ visualization continuous monitoring technology, demonstrating a comprehensive layout in this field [23].
1.2.4 Moving towards systems biology
The core is to realize multi-organ interaction in order to support more complex system research. For example, by using microfluidic technology to fluidly couple the intestinal chip and the liver chip, a "gut-liver" cascade model can be constructed, which can simulate the whole process of "intestinal absorption-liver first-pass metabolism" that occurs in the human body after oral administration of drugs. Studying such multi-organ cascade reactions in the space microgravity environment is of direct significance for evaluating the effectiveness and safety of drugs used by astronauts. Research based on such multi-organ integrated platforms will mark that space microphysiological system research is moving from isolated organ models to system-level physiological simulation, representing an important development direction in this field [24].
1.3 Current Challenges
In the study of space microphysiological systems, scientists have made many groundbreaking discoveries that surpass traditional cell culture models. However, to achieve long-term, stable and controllable space life experiments, a series of key technical bottlenecks still exist. For example, under microgravity conditions, the efficiency of nutrient delivery, metabolite removal and gas exchange is very different from that on the ground, which puts extremely high demands on the fluid dynamics design within the chip. In addition, how to achieve in-situ, continuous and non-invasive monitoring of cell culture status under unmanned conditions has become a core problem restricting the credibility and scientific value of experiments [25-26]. It is worth noting that in the planning of China's manned spaceflight engineering application mission, "high-throughput, non-contact, real-time imaging and multi-parameter sensing of space organ-on-a-chip" has been listed as a key direction that urgently needs to be broken through [27]. Therefore, promoting the transformation of space life experiments from "result retrospection" to "process observation" requires the deep integration of innovative sensing methods and high-precision in-situ measurement and control technologies.
2 On-orbit monitoring technology: from endpoint analysis to real-time analysis
The increasing sophistication of advanced on-orbit detection technologies is another major pillar for achieving "mechanism analysis" in space life sciences. These technologies enable researchers to acquire data directly in the space environment, avoiding the attenuation and loss of critical signals during sample return.
2.1 Molecular Imaging Technology
The development of molecular imaging technology has made it possible to observe the morphology, structure, and chemical composition of biological samples in orbit, non-destructively, and in real time. In the future, combined with artificial intelligence-assisted image analysis and multimodal integration strategies, this technology is expected to play a more crucial role in revealing the fundamental laws governing the influence of microgravity on life activities, providing theoretical basis and technical support for health assurance in long-term space missions.
2.1.1 Advances in fluorescence microscopy imaging techniques
Space biology imaging has evolved from basic bright-field and wide-field fluorescence imaging to laser scanning confocal microscopy (LSCM) and spinning-disk confocal microscopy (SDCM) . The latter, through a high-speed rotating pinhole disk, achieves optical slicing, eliminates defocus interference, and significantly reduces photobleaching and phototoxicity, making it particularly suitable for long-term in vivo imaging of organoid samples of similar thickness. Meanwhile, four-dimensional light-sheet fluorescence microscopy (three-dimensional space & time) excites samples from the side with a thin light sheet, combined with detection by a vertically positioned sCMOS camera, achieving high-speed, high-resolution, and low-damage volumetric imaging of samples. It has been used on the International Space Station to track the entire neural development process of brain organoids, recording the division, migration, and differentiation events of neural progenitor cells, providing unprecedented spatiotemporal resolution data. Fluorescence microscopy, with its high resolution, three-dimensional imaging capabilities, and good compatibility with live samples, has become the " gold standard " for observing cell morphology, structural dynamics, and molecular localization in on-orbit life science experiments. It plays a key role in biological research under microgravity conditions in space, as shown in Figure3.
Fig.3: Imaging of individually labeled lung organoids using confocal fluorescence microscopy [28]
High-content imaging systems, as key tools in space life science research, provide an integrated, multi-scale, multi-dimensional analysis platform for observing cells and tissues under microgravity conditions in orbit. Represented by the "Light Microscope Module" on the International Space Station and the commercial platform "CubeLab", these systems integrate automated microscopy, fluorescent labeling, and intelligent image analysis technologies, enabling long-term, dynamic, and non-invasive observation of the culture process of various biological samples, from two-dimensional cells to three-dimensional organoids. This technological integration not only standardizes and increases the throughput of in-orbit experimental procedures but also allows researchers to move beyond the observation of single phenomena, analyzing the network-based adaptive changes in cell structure and function under microgravity conditions from a systems biology perspective. Therefore, with the development of in-orbit artificial intelligence analysis algorithms and novel fluorescent probe technologies, high-content imaging is evolving towards greater intelligence and higher throughput, powerfully driving the transformation of space life science from phenomenon description to mechanism analysis.
In-orbit live cell dynamic monitoring technology, especially fluorescence microscopy combined with time-lapse photography, provides a key research tool for a deeper understanding of the dynamic laws of cell behavior under space microgravity. This technology system can record biological activities of live cells and organoids in the process of in-orbit culture for a long time in a non-invasive manner, thereby capturing real-time dynamic information that is difficult to obtain in traditional ground experiments. Based on this method, researchers can analyze the regulation patterns and spatiotemporal characteristics of microgravity on basic life processes such as multi-organ interactions, cell connections and communication, and tissue barrier function from a system level, providing direct visual evidence and quantitative basis for explaining the unique physiological and pathological phenomena in the space environment [29].
2.1.2 Raman spectroscopy and label-free detection
Raman spectroscopy does not require fluorescent labeling. It obtains the biochemical "fingerprint" information of a sample by detecting the vibrational spectrum of molecular bonds, and is particularly suitable for long-term live cell monitoring and metabolite analysis [30].
Raman spectroscopy microscopy is a non-invasive technique based on molecular inelastic scattering spectroscopy that can obtain the "fingerprint" of the sample's intrinsic chemical composition without any fluorescent labeling. It acquires biochemical characteristic information of the sample by capturing the vibrational modes of molecular chemical bonds, and has the unique advantages of being in situ, non-destructive, and suitable for long-term live cell observation. It has shown important value in space life science experiments, as shown in Figure4.
In the monitoring of cellular metabolic state, Raman spectroscopy has been applied to analyze the metabolic response of cells under microgravity conditions in real time. For example, this technology can track key biological processes such as lipid metabolism dynamics, changes in nucleic acid structure, and accumulation of metabolites related to oxidative stress [31].
In the field of drug effect evaluation, Raman spectroscopy can achieve rapid and in-situ evaluation of the efficacy of compounds by comparing the dynamic changes in cell spectra before and after drug treatment. This technology is particularly suitable for on-orbit screening of drug protective efficacy in space environment, and provides a potential high-throughput technology platform for drug development and intervention strategy optimization for special pathophysiological states in space [32].
Fig.4: Raman imaging and Raman spectroscopy of prostate cancer cells [33].
2.1.3 Photoacoustic microscope
Photoacoustic microscopy, as a multi-scale imaging technique, successfully combines the high contrast of optical imaging with the deep penetration of ultrasound imaging, providing a powerful tool for biomedical research. Its working principle is based on the photoacoustic effect: when a pulsed laser irradiates biological tissue, the internal light absorbers absorb light energy, generating thermoelastic expansion and exciting ultrasonic signals; by detecting these signals, the light absorption distribution map inside the tissue can be reconstructed. This characteristic allows for high-resolution functional imaging of the microvascular network structure and blood oxygen saturation within organoids without the need for exogenous contrast agents, providing crucial technical support for studies on angiogenesis and oxygen metabolism. Its non-invasive, high-resolution, and functional imaging characteristics make it a promising core tool for in-orbit life science research.
2.2 Space gene sequencing
Nanopore sequencing technology, with its real-time capability, long read length, and excellent portability, has become a revolutionary tool for conducting on-orbit genomics research in extreme environments such as space stations. This technology can operate directly in the microgravity environment of space, enabling in-situ, real-time analysis of the dynamic response mechanisms of genomes, transcriptomes, and epigenetics of living systems under multiple factors such as cosmic radiation, microgravity, and confined space stress. This provides crucial technical support for establishing a real-time monitoring system for life systems on space stations and ensuring the health and safety of astronauts on long-term stays. Its main applications include:
(1) Real-time monitoring of the environmental microbiome: By sequencing the microbial communities in the air, surfaces, and water systems inside the space station, the microbial composition can be identified in real time, and potential pathogens or drug-resistant bacteria can be quickly identified, providing immediate data support for the management of environmental hygiene and microbial safety inside the space station. Studies have confirmed that the on-orbit identification results are highly consistent with historical culture data, and species that are difficult to detect using traditional culture methods can be detected.
(2) Monitoring the health status of astronauts: By analyzing the dynamic changes in the transcriptome of peripheral blood mononuclear cells and other cells of astronauts, it is possible to monitor in real time the changes in gene expression related to key physiological processes such as immune dysfunction, DNA damage repair, and cellular stress response, providing molecular-level evidence for assessing the health status of astronauts.
(3) On-orbit intelligent experimental closed loop: Transcriptome analysis of cells, model organisms or organoid models cultured in orbit enables scientists to remotely adjust experimental parameters or plans based on the preliminary sequencing results obtained in real time, realizing "data-driven" intelligent experimental design, which greatly improves the efficiency of space experiments and scientific output.
With the continuous increase in sequencing throughput and the evolution of library preparation processes toward automation and integration, it has become possible to complete deep sequencing analysis of whole genomes, whole transcriptomes, and even epigenomes in the space station environment in the future. This will provide the most direct and comprehensive evidence for a deeper understanding of the genetic and epigenetic effects caused by the space environment, and promote space life science research into a new paradigm [34-36], as shown in Figure5.
Fig.5: Multi-omics differential exploration.
2.3 Multimodal technology integration and intelligent analysis
Single technologies often reveal only one aspect of complex biological problems. The core development trend for the future lies in integrating multiple technology platforms to build an integrated analytical capability encompassing "detection-imaging-spectroscopy-sequencing", and deeply integrating artificial intelligence (AI) for high-throughput data interpretation and knowledge discovery. Organoids and organ-on-a-chip models provide ideal platforms for studying biological processes in a highly simulated three-dimensional microenvironment within the body. However, their inherent complex spatial structure and cellular heterogeneity place higher demands on analytical techniques, urgently requiring the development of analytical strategies capable of in-situ, multimodal integration to simultaneously address the three core questions of "where" (spatial location) , "what" (cellular identity and morphology) , and "what happened" (molecular function and state) , as shown in Figure6.
Fig.6: Multimodal technology integration [37].
The integration of such multi-technology platforms inevitably generates massive amounts of heterogeneous, multimodal scientific data, including high-dimensional images, spectra, sequences, and various environmental sensor data. Achieving spatiotemporal synchronization and deep fusion of this data, and uncovering profound biological patterns from it, has become a significant challenge and opportunity. In this process, AI and machine learning (ML) algorithms are playing an indispensable role.
(1) Multimodal association analysis: Through AI-driven association analysis, data from different modalities can be accurately mapped and cross-validated in spatial coordinates. For example, the location of specific cell subpopulations observed by fluorescence imaging can be associated with metabolic state information obtained by Raman spectroscopy; or differentially expressed genes identified by nanopore sequencing can be verified with corresponding phenotypic changes observed under confocal microscopy, thereby constructing a complete causal chain from gene to phenotype. By integrating image phenotype and transcriptome data, a "genotype-phenotype" association model can be established to systematically discover key genes and signaling pathways that drive the formation of spatially specific phenotypes [38].
(2) Artificial intelligence and automation closed loop: Machine learning algorithms are used to automatically analyze, extract features and classify phenotypes of massive in-situ imaging and omics data. Key pathways and targets sensitive to microenvironmental disturbances can be quickly identified, thereby intelligently guiding subsequent experimental design and verification. Combined with an automated experimental platform, high-throughput, unattended intelligent space experiments become possible, greatly improving research efficiency [39].
Therefore, multimodal integration is not merely a simple aggregation of single technologies, but rather a seamless weaving of multidimensional information, including genomics, proteomics, metabolomics, chemical composition, functional phenotypes, and morphological characteristics, with spatial coordinates at its core. Ultimately, it directly maps the entire causal spectrum from molecular perturbations to functional phenotypic changes in organoids and other "micro-organs." In this context, establishing standardized, structured space biology multimodal databases will become a key infrastructure for advancing this field. Such databases will enable large-scale data sharing, cross-validation, and in-depth secondary data mining, thereby maximizing the scientific output of each experiment and accelerating the translation of new discoveries into clinical applications.
3 Challenges, outlook and future platform vision
Despite significant advancements in space microphysiological systems and on-orbit detection technologies, the current space life science research system still suffers from a fragmented, "independent" approach. Various culture devices, microscopic imaging equipment, sequencers, and other instruments are often relatively independent, with inconsistent data formats, making continuous, complementary, and multi-dimensional observation of the same biological sample difficult. Future development urgently needs to overcome these limitations and evolve towards greater integration, automation, and intelligence.
3.1 Current core challenges and bottlenecks
3.1.1 Insufficient technology integration
Integrating complex sample preparation, culture, detection and analysis steps into a stable, automated and compact flight hardware is technically very difficult. At the same time, there is a lack of effective connection between the culture module, imaging system, biochemical analysis and sequencing equipment. Samples need to be transferred between different platforms, which is not only cumbersome and easy to introduce contamination, but also makes it difficult to achieve continuous, multi-parameter dynamic tracking of the same live sample [40].
3.1.2 Limited multidimensional detection capabilities
Despite significant advancements in advanced imaging techniques, such as light-sheet microscopy, there are still considerable limitations in their three-dimensional, high-resolution, and dynamic imaging capabilities when dealing with complex, three-dimensional organoids or tissue samples from real biological systems. This is particularly true in space life science experiments, where samples often possess characteristics such as large size, complex structure, and non-ideal optical properties (e.g., opacity or strong scattering) , making in-situ, non-destructive observation of the fine internal structures extremely challenging. This limitation directly impacts scientists' ability to fully analyze biological processes in orbit and restricts multi-scale correlation analysis from morphology to function and from macroscopic to microscopic levels.
To overcome this bottleneck, future development requires further advancements in multidimensional imaging technologies that offer deeper penetration, higher resolution, and greater intelligence. Simultaneously, it's essential to integrate imaging techniques with artificial intelligence methods, employing computational imaging, image reconstruction, and enhancement analysis to extract deeper information from limited data. This will allow for the maximum extraction of reliable biological information, even under conditions where technology is not yet fully ideal.
3.1.3 Insufficient validation of long-term culture
Currently, most space microphysiological system experiments still have relatively short cycles (several weeks to several months) . In order to study the long-term chronic effects of the space environment (such as aging and tumorigenesis) , it is necessary to develop a space microphysiological detection experimental platform that can support stable culture for several months or even several years. At the same time, the construction of multi-organ microarrays that can better simulate the interaction of human systems is an inevitable direction for the future [41-42].
3.1.4 Automation, intelligence, and insufficient throughput
Currently, many experimental procedures cannot be fully automated, limiting the complexity and throughput of experiments. At the same time, the real-time nature and level of intelligence in data analysis are insufficient; in-depth data mining relies heavily on ground teams, failing to fully leverage the decision support role of on-orbit analysis.
3.1.5 The widespread lack of standardization and normalization
From system construction and cultivation to data collection, formatting, and metadata description, the entire field urgently needs to establish internationally recognized and unified standards and norms to ensure the reliability, comparability, and reproducibility of research results.
3.2 Conception of future space-based life science experiment platform
Future space-based life science experimental platforms will no longer be collections of single-function instruments, but will evolve into intelligent, automated, and integrated experimental systems capable of supporting multimodal, end-to-end sample culture. The microgravity environment eliminates the dominant influence of gravity, allowing previously obscured fundamental biological laws, such as weak intercellular interactions and the convection processes of biological fluids, to become clearly visible. Simultaneously, deep-space radiation, confined spaces, and other combined factors create an ideal environmental system for studying the stress, adaptation, and evolution of life in space.
Through systematic integration (connecting the original and extended modules) , comprehensive cross-disciplinary approaches (multi-species/multi-scale) , in-depth detection (from molecular to individual level, multimodal, multi-level) , and validity verification (data analysis, AI-driven iteration) , this approach utilizes cutting-edge space multi-omics integration strategies, combined with various advanced molecular imaging technologies and a multimodal detection system based on microphysiological pathology, to propel organoid research from two-dimensional static to four-dimensional dynamic (space & time &multi-omics) . This will construct a more systematic, comprehensive, in-depth, and effective space microphysiological system experimental and detection research system, as shown in Figure7.
Fig.7: Concept of the space microphysiological system experiment and detection platform.
The core design philosophy and features of this platform include:
(1) High integration and modularity: The platform integrates multiple culture units (supporting static culture, perfusion culture, and multi-organ interaction modes) and multiple detection modalities (such as high-content bright-field/fluorescence microscopy, light sheet microscopy, confocal Raman spectroscopy imaging, photoacoustic imaging, etc.) . Through a precise automated scheduling system (such as robotic arms and rotating stages) , it achieves iterative, multimodal observation of the same live sample at different time points, forming a dynamic multidimensional data chain that runs through the entire experimental cycle. This design maximizes the preservation of the original state of the sample, realizing true multimodal correlation detection.
(2) Closed-loop intelligent research capability: The system integrates in-situ multi-type sensor data (monitoring pH, dissolved oxygen, glucose, lactic acid, transmembrane resistance, etc.) , molecular imaging data, and on-orbit omics analysis streams in real time, and performs real-time data analysis and pattern recognition with the help of edge computing and built-in AI algorithms. Based on preset rules or real-time feedback, the system can automatically trigger or adjust experimental conditions to form a self-optimizing and self-guided closed-loop feedback research mechanism.
(3) Full-chain automation and high-throughput design: From sample loading, culture medium and reagent replacement, and waste liquid treatment to the in-situ fixation, lysis, or nucleic acid extraction and preparation of the final sample, the design supports the simultaneous execution of complex experimental tasks such as multi-condition organoid culture, large-scale drug screening, or gene screening, achieving a high degree of automation throughout the entire process. This design will significantly reduce the operational workload of astronauts and improve the reliability and throughput of experiments.
Therefore, the planned "Space Microphysiological System Experiment and Detection Platform" on the Chinese space station is based on highly integrated and standardized modules (SPUs) . It will collaboratively operate multimodal molecular imaging technologies such as high-content microscopy, light-sheet fluorescence3D microscopy, confocal Raman spectroscopy, and photoacoustic imaging, and organically link with on-orbit nanopore sequencing capabilities. This will enable multi-scale, systematic, and in-situ analysis of space microphysiological and pathological systems, from macroscopic morphology and 3D structure to microscopic chemical composition and molecular expression. This platform will not only obtain a series of new and remarkable scientific results through systematic space physiological and pathological research and drug intervention experiments, promoting a deeper understanding of the essence of life phenomena and providing scientific evidence for human health maintenance and space protection, but also provide core technological support and data foundation for the country's long-term strategic deployment in the fields of space life sciences and biomedicine by constructing a multi-dimensional, interconnected experimental and detection system. Through innovative utilization of the unique space environment, this platform is expected to promote systematic research in space life sciences from molecular mechanisms to functional realization, and from basic exploration to application transformation, marking the formal entry of space life science research into the "era of precise analysis of space life sciences" driven by multimodal big data.
3.3 Scientific prospects and far-reaching impact
With the increasing sophistication and widespread application of these advanced technology platforms, the field of space life sciences is expected to achieve breakthroughs in the following areas:
(1) Deepening of basic mechanism research: At the molecular and cellular level, we systematically reveal the precise molecular pathways and regulatory networks of classic biological effects such as bone loss, immunosuppression, cardiovascular dysfunction and neurodegenerative changes caused by space environmental factors such as microgravity and radiation, and explore new drug targets with intervention potential.
(2) Precision practice of aerospace medicine: Based on the microphysiological system and rapid on-orbit diagnostic technology derived from astronaut induced pluripotent stem cells (iPSC) , it is possible to realize personalized and prospective assessment of individual health status and disease risk of astronauts in the future, and formulate highly customized nutrition, exercise and drug protection strategies accordingly [43].
(3) Supporting manned deep space exploration missions: The experience, verified technologies and generated data accumulated in near-Earth orbit missions will provide key support for future long-term extraterrestrial missions such as lunar research stations and Mars exploration, including the optimization of life support systems, the construction of long-term health monitoring and maintenance systems, and the establishment of on-orbit medical decision support systems [44].
(4) Promote the development of terrestrial medicine and biotechnology: With the help of the “space-ground co-disease”research system, the space environment can accelerate certain pathological processes (such as bone loss, muscle atrophy, immune aging, etc.) , which can significantly promote the understanding of the mechanisms of major human diseases such as osteoporosis, sarcopenia, neurodegenerative diseases, and autoimmune diseases, and accelerate the research and development of innovative drugs and treatment strategies. In addition, the new mechanisms such as bioprinting, drug crystal growth, and protein assembly explored in the microgravity environment of space will also provide new principles and new paths for the application of terrestrial biotechnology [45].
4 Conclusion
The deep integration of space microphysiological systems and advanced on-orbit detection technologies is driving a fundamental transformation in the paradigm of space life science research. This integration has achieved a leap from observing macroscopic phenomena to elucidating microscopic mechanisms, from endpoint analysis to real-time dynamic monitoring, and from studying isolated organ functions to multi-scale system integration. Although challenges remain in areas such as technology integration, long-term stable culture, and multimodal data analysis, its rapid development and broad application prospects have made it a new engine for space life science research.
Looking to the future, space life sciences will not only provide crucial health support for manned deep space exploration missions, but also significantly contribute to terrestrial life science and medical research by revealing the laws governing life activities in extreme environments, truly realizing the grand vision of "integration of space and earth, serving human health". This path, moving from "phenomenon description" to "mechanism-driven" and from "platform construction" to "precise analysis", is both challenging and full of significant opportunities, and will undoubtedly lead us into a new era of deeper understanding of life.