Point of care testing of biochemical markers for monitoring astronauts during long duration missions in deep space
-
Simona Ferraro
,
Sohini Sengupta
,
Anilkumar Dave
Abstract
Background
Investigations into human performance and health status during long-duration spaceflights are ongoing aboard the International Space Station (ISS) and are critical for planning missions beyond Low Earth Orbit (LEO). This review evaluates the current evidence on point-of-care-testing (POCT) in space, discussing requirements for POCT to support astronaut health during extended deep space missions and the potential for technology transfer to terrestrial healthcare.
Contents
Microgravity disrupts biochemical and hormonal regulation, leading to reversible homeostatic dysregulation across multiple organ systems in astronauts during spaceflight in LEO. Missions beyond LEO may significantly increase risks of morbidity and mortality in particular for cardiovascular disease. The ability to assess key organ functions by expanding the range of detectable biomarkers on POCTs is crucial for ongoing health monitoring, urgent clinical decisions, and future mission planning. The recent implementation of high-sensitivity cardiac troponin I on POCT will be essential for early identifying myocardial injury and facilitating telemedicine support. Furthermore, the development and use of reference change values (RCV) in space environment, derived from biomarkers measured longitudinally in real-time onboard, will be crucial to differentiate clinically relevant changes in biomarkers levels from alterations induced by microgravity. This approach may overcome the use of traditional cut-off values which are assessed and generally applied under stable terrestrial conditions.
Summary
Clinical laboratory capabilities on the ISS are currently minimal. As missions lengthen, and extend beyond LEO, enhanced POCT is needed. Limited data on POCT performance in space highlight the importance of laboratory professionals’ involvement to ensure high-quality testing and accurate interpretation.
Acknowledgments
C.E.M. thanks the WorldQuant and GI Research Foundation, NASA (NNX14AH50G, NNX17AB26G, NNH18ZTT001N-FG2,80NSSC22K0254, 80NSSC23K0832, 24-24NSCOR_2-0008, 24-24FLAG_2-0099 and 22-22SBR_2-0104), the National Institutes of Health (R01ES032638 and U54AG089334) and the LLS (MCL7001-18, LLS 9238-16, 7029-23).
-
Research ethics: Not applicable.
-
Informed consent: Not applicable.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. SF: Conceptualization; SF, AD, SS, JS, CED writing the draft, RC, MC, GVZ, revising the draft; SM writing the final draft.
-
Use of Large Language Models, AI and Machine Learning Tools: None declared.
-
Conflict of interest: C.E.M. is a co-Founder of MedAstra.
-
Research funding: None declared.
-
Data availability: Not applicable.
References
1. Rea, DJ, Miller, RS, Crucian, BE, Valentine, RW, Cristoforetti, S, Bearg, SB, et al.. Single drop cytometry onboard the International Space Station. Nat Commun 2024;15:2634. https://doi.org/10.1038/s41467-024-46483-6.Search in Google Scholar PubMed PubMed Central
2. Ferraro, S, Dave, A, Cereda, C, Verduci, E, Marcovina, S, Zuccotti, G. Space research to explore novel biochemical insights on Earth. Clin Chim Acta 2024;558:119673. https://doi.org/10.1016/j.cca.2024.119673.Search in Google Scholar PubMed
3. Afshinnekoo, E, Scott, RT, MacKay, MJ, Pariset, E, Cekanaviciute, E, Barker, R, et al.. Fundamental biological features of spaceflight: advancing the field to enable deep-space exploration. Cell 2020;183:1162–84. https://doi.org/10.1016/j.cell.2020.10.050.Search in Google Scholar PubMed PubMed Central
4. Delp, MD, Charvat, JM, Limoli, CL, Globus, RK, Ghosh, P. Apollo lunar astronauts show higher cardiovascular disease mortality: possible deep space radiation effects on the vascular endothelium. Sci Rep 2016;6:29901. https://doi.org/10.1038/srep29901.Search in Google Scholar PubMed PubMed Central
5. Khine, HW, Steding-Ehrenborg, K, Hastings, JL, Kowal, J, Daniels, JD, Page, RL, et al.. Effects of prolonged spaceflight on atrial size, atrial electrophysiology, and risk of atrial fibrillation. Circ Arrhythm Electrophysiol 2018;11:e005959. https://doi.org/10.1161/circep.117.005959.Search in Google Scholar PubMed
6. Aunon-Chancellor, SM, Pattarini, JM, Moll, S, Sargsyan, A. Venous thrombosis during spaceflight. N Engl J Med 2020;382:89–90. https://doi.org/10.1056/nejmc1905875.Search in Google Scholar PubMed
7. Goodenow-Messman, DA, Gokoglu, SA, Kassemi, M, Myers, JGJr. Numerical characterization of astronaut CaOx renal stone incidence rates to quantify in-flight and post-flight relative risk. NPJ Microgravity 2022;8:2. https://doi.org/10.1038/s41526-021-00187-z.Search in Google Scholar PubMed PubMed Central
8. Rowe, WJ. The Apollo 15 space syndrome. Circulation 1998;97:119–20. https://doi.org/10.1161/01.cir.97.1.119.Search in Google Scholar PubMed
9. Cowen, D, Zhang, R, Komorowski, M. Infections in long-duration space missions. Lancet Microbe 2024;5:100875. https://doi.org/10.1016/s2666-5247-24-00098-3.Search in Google Scholar
10. Portable diagnostics technology assessment for space missions. https://ntrs.nasa.gov/api/citations/20100011008/downloads/20100011008.pdf [Accessed 9 December 2024]Search in Google Scholar
11. Crucian, B, Valentine, R, Calaway, K, Miller, R, Rubins, K, Hopkins, M, et al.. 2021. Spaceflight validation of technology for point-of-care monitoring of peripheral blood WBC and differential in astronauts during space missions. Life Sci Space Res 2021 31:29–33. https://doi.org/10.1016/j.lssr.2021.07.003.Search in Google Scholar PubMed
12. Smith, SM, Davis-Street, JE, Fontenot, TB, Lane, HW. Assessment of a portable clinical blood analyzer during space flight. Clin Chem 1997;43:1056–65. https://doi.org/10.1093/clinchem/43.6.1056.Search in Google Scholar
13. https://issnationallab.org/press-releases/1drop-diagnostics-leverage-microgravity-improve-medical-diagnostics/ [Accessed 9 December 2024].Search in Google Scholar
14. Beshay, M, Hatch, M, Vu, K, Mudanyali, O, Karlovac, N; 2016. http://www.intopsys.com/wpcontent/uploads/2016/02/NASA-HRP-Conference-2016.pdf [Accessed 9 December 2024].Search in Google Scholar
15. Han, GR, Goncharov, A, Eryilmaz, M, Ye, S, Palanisamy, B, Ghosh, R, et al.. Machine learning in point-of-care testing: innovations, challenges, and opportunities. Nat Commun 2025;16:3165. https://doi.org/10.1038/s41467-025-58527-6.Search in Google Scholar PubMed PubMed Central
16. Land, KJ, Boeras, DI, Chen, X-S, Ramsay, AR, Peeling, RW. Reassured diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes. Nat Microbiol 2019;4:46–54. https://doi.org/10.1038/s41564-018-0295-3.Search in Google Scholar PubMed PubMed Central
17. CLSI document EP28-A3c – Defining. Establishing and verifying reference intervals in the clinical laboratory. https://clsi.org/shop/standards/ep28/ [Accessed 9 December 2024].Search in Google Scholar
18. Strangman, GE, Sawyer, A, Fabre, KM, Urquieta, E, Hury, J, Wu, J, et al.. Deep-space applications for point-of-care technologies. Curr Opin Biom Engin 2019;11:45–50. https://doi.org/10.1016/j.cobme.2019.08.014.Search in Google Scholar
19. Roda, A, Mirasoli, M, Guardigli, M, Zangheri, M, Caliceti, C, Calabria, D, et al.. Advanced biosensors for monitoring astronauts’ health during long-duration space missions. Biosens Bioelectron 2018;111:18–26. https://doi.org/10.1016/j.bios.2018.03.062.Search in Google Scholar PubMed
20. Lewandowski, BE, Schkurko, CM, Miller, RS, Valentine, RW, Calaway, KM, Yang, JD, et al.. Technology modification, development, and demonstrations for future spaceflight medical systems at NASA. Front. Space Technol 2024;5:1384457. https://www.frontiersin.org/journals/spacetechnologies/articles/10.3389/frspt.2024.1384457/full [Accessed 9 December 2024].10.3389/frspt.2024.1384457Search in Google Scholar
21. https://www.nasa.gov/missions/station/recycling-in-space-waste-handling-in-a-microgravity-environment-challenge/ [Accessed 4 July 2025].Search in Google Scholar
22. https://www.nasa.gov/artemis-accords/ [Accessed 4 July 2025].Search in Google Scholar
23. https://science.nasa.gov/learn/basics-of-space-flight/chapter11-4/#:∼:text=Passive%20thermal%20control%20is%20obtained,spacecraft%20from%20excess%20solar%20heating [Accessed 4 July 2025].Search in Google Scholar
24. Dobney, W, Mols, L, Mistry, D, Tabury, K, Baselet, B, Baatout, S. Evaluation of deep space exploration risks and mitigations against radiation and microgravity. Front Nucl Med 2023;3:1225034. https://doi.org/10.3389/fnume.2023.1225034.Search in Google Scholar PubMed PubMed Central
25. Fogtman, A, Baatout, S, Baselet, B, Berger, T, Hellweg, CE, Jiggens, P, et al.. Towards sustainable human space exploration – priorities for radiation research to quantify and mitigate radiation risks. Npj Microgravity 2023;9:8. https://doi.org/10.1038/s41526-023-00262-7.Search in Google Scholar PubMed PubMed Central
26. Patel, S. The effects of microgravity and space radiation on cardiovascular health: from low-Earth orbit and beyond. Int J Cardiol Heart Vasc 2020;30:100595. https://doi.org/10.1016/j.ijcha.2020.100595.Search in Google Scholar PubMed PubMed Central
27. Mircea, AA, Pistritu, DV, Fortner, A, Tanca, A, Liehn, EA, Bucur, O. Space travel: the radiation and microgravity effects on the cardiovascular system. Int J Mol Sci 2024;25:11812. https://doi.org/10.3390/ijms252111812.Search in Google Scholar PubMed PubMed Central
28. Khera, A, Budoff, MJ, O’Donnell, CJ, Ayers, CA, Locke, J, de Lemos, JA, et al.. Astronaut cardiovascular health and risk modification (Astro-CHARM) coronary calcium atherosclerotic cardiovascular disease risk calculator. Circulation 2018;138:1819–27. https://doi.org/10.1161/circulationaha.118.033505.Search in Google Scholar
29. Charvat, JM, Leonard, D, Barlow, CE, DeFina, LF, Willis, BL, Lee, SMC, et al.. Long-term cardiovascular risk in astronauts: comparing NASA mission astronauts with a healthy cohort from the cooper Center longitudinal Study. Mayo Clin Proc 2022;97:1237–46. https://doi.org/10.1016/j.mayocp.2022.04.003.Search in Google Scholar PubMed
30. Ade, CJ, Broxterman, RM, Charvat, JM, Barstow, TJ. Incidence rate of cardiovascular disease end points in the national Aeronautics and Space Administration Astronaut Corps. J Am Heart Assoc 2017;6:e005564. https://doi.org/10.1161/jaha.117.005564.Search in Google Scholar PubMed PubMed Central
31. Gallo, C, Ridolfi, L, Scarsoglio, S. Cardiovascular deconditioning during long-term spaceflight through multiscale modeling. NPJ Microgravity 2020;6:27. https://doi.org/10.1038/s41526-020-00117-5.Search in Google Scholar PubMed PubMed Central
32. Clément, G. Fundamentals of space medicine, 2nd ed. Springer; 2011. https://link.springer.com/book/10.1007/978-1-4419-9905-4 [Accessed 9 December 2024].Search in Google Scholar
33. McDermott, M, Kimenai, D, Anand, A, Huang, Z, Houston, A, McDermott, M, et al.. Adoption of high-sensitivity cardiac troponin for risk stratification of patients with suspected myocardial infarction: a multicentre cohort study. Lancet Reg Health Eur 2024;43:100960. https://doi.org/10.1016/j.lanepe.2024.100960.Search in Google Scholar PubMed PubMed Central
34. Horwich, TB, Patel, J, MacLellan, WR, Fonarow, GC. Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 2003;108:833–8. https://doi.org/10.1161/01.cir.0000084543.79097.34.Search in Google Scholar PubMed
35. Shibata, S, Wakeham, DJ, Thomas, JD, Abdullah, SM, Platts, S, Bungo, MW, et al.. Cardiac effects of long-duration space flight. J Am Coll Cardiol 2023;82:674–84. https://doi.org/10.1016/j.jacc.2023.05.058.Search in Google Scholar PubMed
36. Welsh, P, Preiss, D, Hayward, C, Shah, ASV, McAllister, D, Briggs, A, et al.. Cardiac troponin T and troponin I in the general population. Circulation 2019;139:2754–64. https://doi.org/10.1161/circulationaha.118.038529.Search in Google Scholar
37. Toprak, B, Solleder, H, Di Carluccio, E, Greenslade, JH, Parsonage, WA, Schulz, K, et al.. Artificial Intelligence in Suspected Myocardial Infarction Study (ARTEMIS) group. Diagnostic accuracy of a machine learning algorithm using point-of-care high-sensitivity cardiac troponin I for rapid rule-out of myocardial infarction: a retrospective study. Lancet Digit Health 2024;6:e729–38. https://doi.org/10.1016/s2589-7500-24-00191-2.Search in Google Scholar
38. Frings-Meuthen, P, Luchitskaya, E, Jordan, J, Tank, J, Lichtinghagen, R, Smith, SM, et al.. Natriuretic peptide resetting in astronauts. Circulation 2020;141:1593–5. https://doi.org/10.1161/circulationaha.119.044203.Search in Google Scholar
39. Olde Engberink, RHG, van Oosten, PJ, Weber, T, Tabury, K, Baatout, S, Siew, K, et al.. The kidney, volume homeostasis and osmoregulation in space: current perspective and knowledge gaps. NPJ Microgravity 2023;9:29. https://doi.org/10.1038/s41526-023-00268-1.Search in Google Scholar PubMed PubMed Central
40. Michel, L, Mincu, RI, Mahabadi, AA, Settelmeier, S, Al-Rashid, F, Rassaf, T, et al.. Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta-analysis. Eur J Heart Fail 2020;22:350–61. https://doi.org/10.1002/ejhf.1631.Search in Google Scholar PubMed
41. Li, J, Wagar, EA, Meng, QH. Comprehensive assessment of biotin interference in immunoassays. Clin Chim Acta 2018;487:293–8. https://doi.org/10.1016/j.cca.2018.10.013.Search in Google Scholar PubMed
42. Eggers, KM, Hammarsten, O, Lindahl, B. Differences between high-sensitivity cardiac troponin T and I in stable populations: underlying causes and clinical implications. Clin Chem Lab Med 2022;61:380–7. https://doi.org/10.1515/cclm-2022-0778.Search in Google Scholar PubMed
43. Garmany, A, Yamada, S, Park, S, Terzic, A. Plasma biomarkers of first all-civilian space flight to the international space station. Mayo Clin Proc 2024;99:1523–5. https://doi.org/10.1016/j.mayocp.2024.05.024.Search in Google Scholar PubMed PubMed Central
44. Stavnichuk, M, Mikolajewicz, N, Corlett, T, Morris, M, Komarova, SV. A systematic review and meta-analysis of bone loss in space travelers. NPJ Microgravity 2020;6:13. https://doi.org/10.1038/s41526-020-0103-2.Search in Google Scholar PubMed PubMed Central
45. Garrett-Bakelman, FE, Darshi, M, Green, SJ, Gur, RC, Lin, L, Macias, BR, et al.. The NASA Twins Study: a multidimensional analysis of a year-long human spaceflight. Science 2019;364:eaau8650. https://doi.org/10.1126/science.aau8650.Search in Google Scholar PubMed PubMed Central
46. Smith, SM, Heer, MA, Shackelford, LC, Sibonga, JD, Ploutz-Snyder, L, Zwart, SR. Benefits for bone from resistance exercise and nutrition in long-duration spaceflight: evidence from biochemistry and densitometry. J Bone Miner Res 2012;27:1896–906. https://doi.org/10.1002/jbmr.1647.Search in Google Scholar PubMed
47. Braga, F, Ferraro, S, Mozzi, R, Dolci, A, Panteghini, M. Biological variation of neuroendocrine tumor markers chromogranin A and neuron-specific enolase. Clin Biochem 2013;46:148–51. https://doi.org/10.1016/j.clinbiochem.2012.09.005.Search in Google Scholar PubMed
48. Matomäki, P, Kainulainen, H, Kyröläinen, H. Corrected whole blood biomarkers – the equation of Dill and Costill revisited. Phys Rep 2018;6:e13749. https://doi.org/10.14814/phy2.13749.Search in Google Scholar PubMed PubMed Central
49. White, NJ, Wenthe, A. Managing hemostasis in space. Arterioscler Thromb Vasc Biol 2023;43:2079–87. https://doi.org/10.1161/atvbaha.123.318783.Search in Google Scholar PubMed
50. Kunz, H, Quiriarte, H, Simpson, RJ, Ploutz-Snyder, R, McMonigal, K, Sams, C, et al.. Alterations in hematologic indices during long-duration spaceflight. BMC Hematol 2017;17:12. https://doi.org/10.1186/s12878-017-0083-y.Search in Google Scholar PubMed PubMed Central
51. Smith, SM. Red blood cell and iron metabolism during space flight. Nutrition 2002;18:864–6. https://doi.org/10.1016/s0899-9007-02-00912-7.Search in Google Scholar
52. Olivari, M. Space technology transfers and their commercialisation. Organisation for Economic Co-operation and Development (OECD) science, technology, and industry policy papers. https://www.oecd.org/en/publications/space-technology-transfers-and-their-commercialisation_0e78ff9f-en.html [Accessed 9 July 2025].Search in Google Scholar
53. Wilde, JH, Sun, YY, Simpson, SR, Hill, ER, Fu, Z, Bian, EJ, et al.. A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system. Nat Biomed Eng 2025;9:716–29. https://doi.org/10.1038/s41551-025-01362-3.Search in Google Scholar PubMed PubMed Central
54. Scarpa, J, Parazynski, S, Strangman, G. Space exploration as a catalyst for medical innovations. Front Med 2023;10:1226531. https://doi.org/10.3389/fmed.2023.1226531.Search in Google Scholar PubMed PubMed Central
55. Zimmerman, MS, Carswell Smith, AG, Sable, CA, Echko, MM, Wilner, LB, Olsen, HE; Congenital Heart Disease Collaborators (GBD), et al.. Global, regional, and national burden of congenital heart disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Child Adolesc Health. 2020;4:185–200, https://doi.org/10.1016/s2352-4642-19-30402-x.Search in Google Scholar
56. Ferraro, S, Biganzoli, E, Mannarino, S, Lanzoni, M, Zuccotti, G, Plebani, M, et al.. High-sensitivity cardiac troponin and the management of congenital heart disease in newborns and infants. Clin Chem 2024;70:486–96. https://doi.org/10.1093/clinchem/hvad215.Search in Google Scholar PubMed
57. Cheng, SPS, Heo, K, Joos, E, Vervoort, D, Joharifard, S. Barriers to accessing congenital heart surgery in Low- and middle-income countries: a systematic review. World J Pediatr Congenit Heart Surg 2024;15:94–103. https://doi.org/10.1177/21501351231204328.Search in Google Scholar PubMed
58. https://www.asc-csa.gc.ca/eng/iss/bio-analyzer.asp [Accessed 4 July 2025]Search in Google Scholar
59. McIntyre, ABR, Rizzardi, L, Yu, AM, Alexander, N, Rosen, GL, Botkin, DJ, et al.. Nanopore sequencing in microgravity. NPJ Microgravity 2016;2:16035. https://doi.org/10.1038/npjmgrav.2016.35.Search in Google Scholar PubMed PubMed Central
60. Castro-Wallace, SL, Chiu, CY, John, KK, Stahl, SE, Rubins, KH, McIntyre, ABR, et al.. Nanopore DNA sequencing and genome assembly on the international space station. Sci Rep 2017;7:18022. https://doi.org/10.1038/s41598-017-18364-0.Search in Google Scholar PubMed PubMed Central
61. Overbey, EG, Kim, J, Tierney, BT, Park, J, Houerbi, N, Lucaci, AG, et al.. The space omics and medical atlas (SOMA) and international astronaut biobank. Nature 2024;632:1145–54. https://doi.org/10.1038/s41586-024-07639-y.Search in Google Scholar PubMed PubMed Central
62. Mason, CE, Green, J, Adamopoulos, KI, Afshin, EE, Baechle, JJ, Basner, M, et al.. A second space age spanning omics, platforms, and medicine across orbits. Nature 2024;632:995–1008. https://doi.org/10.1038/s41586-024-07586-8.Search in Google Scholar PubMed PubMed Central
63. Jones, CW, Overbey, EG, Lacombe, J, Ecker, AJ, Meydan, C, Ryon, K, et al.. Molecular and physiological changes in the SpaceX Inspiration4 civilian crew. Nature 2024;632:1155–64. https://doi.org/10.1038/s41586-024-07648-x.Search in Google Scholar PubMed PubMed Central
64. Kim, J, Tierney, BT, Overbey, EG, Dantas, E, Fuentealba, M, Park, J, et al.. Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight. Nat Commun 2024;15:4954. https://doi.org/10.1038/s41467-024-49211-2.Search in Google Scholar PubMed PubMed Central
65. Tierney, BT, Kim, J, Overbey, EG, Ryon, KA, Foox, J, Sierra, MA, et al.. Longitudinal multi-omics analysis of host microbiome architecture and immune responses during short-term spaceflight. Nat Microbiol 2024;9:1661–75. https://doi.org/10.1038/s41564-024-01635-8.Search in Google Scholar PubMed PubMed Central
66. Park, J, Overbey, EG, Narayanan, SA, Kim, J, Tierney, BT, Damle, N, et al.. Spatial multi-omics of human skin reveals KRAS and inflammatory responses to spaceflight. Nat Commun 2024;15:4773. https://doi.org/10.1038/s41467-024-48625-2.Search in Google Scholar PubMed PubMed Central
67. Houerbi, N, Kim, J, Overbey, EG, Batra, R, Schweickart, A, Patras, L, et al.. Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight. Nat Commun 2024;15:4862. https://doi.org/10.1038/s41467-024-48841-w.Search in Google Scholar PubMed PubMed Central
68. Grigorev, K, Nelson, TM, Overbey, EG, Houerbi, N, Kim, J, Najjar, D, et al.. Direct RNA sequencing of astronaut blood reveals spaceflight-associated m6A increases and hematopoietic transcriptional responses. Nat Commun 2024;15:4950. https://doi.org/10.1038/s41467-024-48929-3.Search in Google Scholar PubMed PubMed Central
69. Garcia-Medina, JS, Sienkiewicz, K, Narayanan, SA, Overbey, EG, Grigorev, K, Ryon, KA, et al.. Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight. Precis Clin Med 2024;7:pbae007. https://doi.org/10.1093/pcmedi/pbae007.Search in Google Scholar PubMed PubMed Central
70. https://etd.gsfc.nasa.gov/our-work/lunar-gnss-receiver-experiment-lugre/ [Accessed 4 July 2025]Search in Google Scholar
71. https://www.axiomspace.com/missions/ax3 [Accessed4 July 2025].Search in Google Scholar
72. Asachi, P, Ghanem, G, Burton, J, Aintablian, H, Chiem, A. Utility of ultrasound in managing acute medical conditions in space: a scoping review. Ultrasound J 2023;15:47. https://doi.org/10.1186/s13089-023-00349-y.Search in Google Scholar PubMed PubMed Central
© 2025 Walter de Gruyter GmbH, Berlin/Boston
