Single drop cytometry onboard the International Space Station.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 Mar 2024
25 Mar 2024
Historique:
received:
20
10
2023
accepted:
29
02
2024
medline:
26
3
2024
pubmed:
26
3
2024
entrez:
26
3
2024
Statut:
epublish
Résumé
Real-time lab analysis is needed to support clinical decision making and research on human missions to the Moon and Mars. Powerful laboratory instruments, such as flow cytometers, are generally too cumbersome for spaceflight. Here, we show that scant test samples can be measured in microgravity, by a trained astronaut, using a miniature cytometry-based analyzer, the rHEALTH ONE, modified specifically for spaceflight. The base device addresses critical spaceflight requirements including minimal resource utilization and alignment-free optics for surviving rocket launch. To fully enable reduced gravity operation onboard the space station, we incorporated bubble-free fluidics, electromagnetic shielding, and gravity-independent sample introduction. We show microvolume flow cytometry from 10 μL sample drops, with data from five simultaneous channels using 10 μs bin intervals during each sample run, yielding an average of 72 million raw data points in approximately 2 min. We demonstrate the device measures each test sample repeatably, including correct identification of a sample that degraded in transit to the International Space Station. This approach can be utilized to further our understanding of spaceflight biology and provide immediate, actionable diagnostic information for management of astronaut health without the need for Earth-dependent analysis.
Identifiants
pubmed: 38528030
doi: 10.1038/s41467-024-46483-6
pii: 10.1038/s41467-024-46483-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2634Subventions
Organisme : National Aeronautics and Space Administration (NASA)
ID : 80NSSC18C0162
Informations de copyright
© 2024. The Author(s).
Références
National Aeronautics and Space Administration. Humans to Mars. https://www.nasa.gov/humans-in-space/humans-to-mars/ (2023).
Rucker, M. et al. NASA’s strategic analysis cycle 2021 (SAC21) human Mars architecture. In Proc. 2022 IEEE Aerospace Conference (AERO) 1–10 (IEEE, 2022).
National Aeronautics and Space Administration. Apollo 11 Mission Overview. https://www.nasa.gov/mission_pages/apollo/missions/apollo11.html (2015).
Cucinotta, F. A. Review of NASA approach to space radiation risk assessments for Mars exploration. Health Phys. 108, 131–142 (2015).
doi: 10.1097/HP.0000000000000255
pubmed: 25551493
Stavnichuk, M., Mikolajewicz, N., Corlett, T., Morris, M. & Komarova, S. V. A systematic review and meta-analysis of bone loss in space travelers. NPJ Microgravity 6, 13 (2020).
doi: 10.1038/s41526-020-0103-2
pubmed: 32411816
pmcid: 7200725
Xue, X. et al. Biological effects of space hypomagnetic environment on circadian rhythm. Front Physiol. 12, 643943 (2021).
doi: 10.3389/fphys.2021.643943
pubmed: 33767637
pmcid: 7985258
Dion, K. L. Interpersonal and group processes in long-term spaceflight crews: perspectives from social and organizational psychology. Aviat. Space Environ. Med. 75, C36–C43 (2004).
pubmed: 15267074
Goldstein, M. A., Cheng, J. & Schroeter, J. P. The effects of increased gravity and microgravity on cardiac morphology. Aviat. Space Environ. Med 69, A12–A16 (1998).
pubmed: 10776447
Lee, A. G. et al. Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update. NPJ Microgravity 6, 7 (2020).
doi: 10.1038/s41526-020-0097-9
pubmed: 32047839
pmcid: 7005826
Crucian, B. E., Cubbage, M. L. & Sams, C. F. Altered cytokine production by specific human peripheral blood cell subsets immediately following space flight. J. Interferon Cytokine Res. 20, 547–556 (2000).
doi: 10.1089/10799900050044741
pubmed: 10888111
Fujii, M. D. & Patten, B. M. Neurology of microgravity and space travel. Neurol. Clin. 10, 999–1013 (1992).
doi: 10.1016/S0733-8619(18)30192-0
pubmed: 1435667
Aunon-Chancellor, S. M., Pattarini, J. M., Moll, S. & Sargsyan, A. Venous thrombosis during spaceflight. N. Engl. J. Med. 382, 89–90 (2020).
doi: 10.1056/NEJMc1905875
pubmed: 31893522
National Aeronautics and Space Administration. Human System Risk Board. https://www.nasa.gov/hhp/hsrb (2023).
Garrett-Bakelman, F. E. et al. The NASA twins study: a multidimensional analysis of a year-long human spaceflight. Science 364, eaau8650 (2019).
Jett, J. H., Martin, J. C. & Saunders, G. C. In Lunar Bases and Space Activities of the 21st Century (ed. Mendell, W.W.) 687–696 (Lunar and Planetary Institute, Houston, 1985).
Roussel, M., Benard, C., Ly-Sunnaram, B. & Fest, T. Refining the white blood cell differential: the first flow cytometry routine application. Cytometry A 77, 552–563 (2010).
doi: 10.1002/cyto.a.20893
pubmed: 20506466
Zhu, X., Ni, Y., Cheng, M., Chen, Q. & Zhang, A. Evaluation of a fluorescence flow cytometry reagent for anti-Mullerian hormone detection. Acta Biochim Biophys. Sin. (Shanghai) 52, 1427–1429 (2020).
doi: 10.1093/abbs/gmaa122
pubmed: 33249447
Du, X., Wang, R., Zhai, J. & Xie, X. Surface PEGylation of ionophore-based microspheres enables determination of serum sodium and potassium ion concentration under flow cytometry. Anal. Bioanal. Chem., 415, 4233–4243 (2022).
Irving, D. Reagents for measuring intracellular enzyme activity with flow cytometry. Am. Clin. Lab 16, 16–17 (1997).
pubmed: 10175957
Dunbar, S. A. Applications of Luminex xMAP technology for rapid, high-throughput multiplexed nucleic acid detection. Clin. Chim. Acta 363, 71–82 (2006).
doi: 10.1016/j.cccn.2005.06.023
pubmed: 16102740
Zhao, Y. et al. Single cell RNA expression analysis using flow cytometry based on specific probe ligation and rolling circle amplification. ACS Sens. 5, 3031–3036 (2020).
doi: 10.1021/acssensors.0c01569
pubmed: 32935538
Tang, H., Panemangalore, R., Yarde, M., Zhang, L. & Cvijic, M. E. 384-Well multiplexed Luminex cytokine assays for lead optimization. J. Biomol. Screen. 21, 548–555 (2016).
doi: 10.1177/1087057116644164
pubmed: 27095819
Cook, D. B. et al. Multiplexing protein and gene level measurements on a single Luminex platform. Methods 158, 27–32 (2019).
doi: 10.1016/j.ymeth.2019.01.018
pubmed: 30742996
Pregibon, D. C., Toner, M. & Doyle, P. S. Multifunctional encoded particles for high-throughput biomolecule analysis. Science 315, 1393–1396 (2007).
doi: 10.1126/science.1134929
pubmed: 17347435
Chan, E.Y. & Bae, M. Z. PEG-based microparticles. US patent 9,617,383 (2017).
Chan, M. Z. & Chan, E.Y. Multicoded analytical nanostrips. US patent 9,568,425 (2017).
Shapiro, H. Practical Flow Cytometry 4th edn (Wiley, 2003).
Balestrieri, E., Daponte, P. & Rapuano, S. In-flight space flow cytometer specification requirements. In 17th Symposium IMEKO TC 4, 3rd Symposium IMEKO TC 19 and 15th IWADC Workshop (IMEKO, 2010).
Dubeau-Laramée, G., Rivière, C., Jean, I., Mermut, O. & Cohen, L. Y. Microflow1, a sheathless fiber-optic flow cytometry biomedical platform: demonstration onboard the international space station. Cytom. Part A 85, 322–331 (2014).
doi: 10.1002/cyto.a.22427
Phipps, W.S. et al. Reduced-gravity environment hardware demonstrations of a prototype miniaturized flow cytometer and companion microfluidic mixing technology. J Vis. Exp., e51743, (2014).
Chan, E. & Sharpe, J.Z. Capillary manipulation of samples. US patent 10,449,537 (2019).
Chan, E.Y. Sample consumable. US patent D785,781 (2017).
Chan, E.Y. Sample consumable and loader US patent 10,180,442 (2017).
Chan, E. Y. & Chan, M. Z. Microfluidic Passive Mixing Chip. US patent 9,194,780 (2015).
Crucian, B. & Sams, C. Reduced gravity evaluation of potential spaceflight-compatible flow cytometer technology. Cytometry B Clin. Cytom. 66, 1–9 (2005).
doi: 10.1002/cyto.b.20057
pubmed: 15924305
Shi, W., Zheng, S., Kasdan, H. L., Fridge, A. & Tai, Y. C. Leukocyte count and two-part differential in whole blood based on a portable microflow cytometer. In TRANSDUCERS 2009—2009 International Solid-State Sensors, Actuators and Microsystems Conference in Transducers 616–619 (IEEE, 2009).
Xun, W., Yang, D., Huang, Z., Sha, H. & Chang, H. Cellular immunity monitoring in long-duration spaceflights based on an automatic miniature flow cytometer. Sens. Actuators B: Chem. 267, 419–429 (2018).
doi: 10.1016/j.snb.2018.04.031
Dickerson, W. M. et al. Point-of-care microvolume cytometer measures platelet counts with high accuracy from capillary blood. PLoS One 16, e0256423 (2021).
doi: 10.1371/journal.pone.0256423
pubmed: 34437590
pmcid: 8389400
ESA/NASA. Samantha Cristoforetti Minerva Mission B-Rolls: May 2022. rHEALTH ONE NASA human research. https://www.esa.int/esatv/Videos/2022/05/Samantha_Cristoforetti_Minerva_Mission_B-Rolls/May_2022_-_rHEALTH_ONE_NASA_Human_Research (2022).
Cristoforetti, S. Trip Down Memory Lane. https://www.tiktok.com/@astrosamantha/video/7147723810697940230 (2022).
Crucian, B. et al. Spaceflight validation of technology for point-of-care monitoring of peripheral blood WBC and differential in astronauts during space missions. Life Sci. Space Res. (Amst.) 31, 29–33 (2021).
doi: 10.1016/j.lssr.2021.07.003
pubmed: 34689947
Chan, E.Y. Fluidics module. US patent 10,279,347 B2 (2019).
Chan, E. Y. & Sharpe, J. Z. Optical block. US patent 9,835,542 (2017).
Sams, C. F., Crucian, B. E., Clift, V. L. & Meinelt, E. M. Development of a whole blood staining device for use during space shuttle flights. Cytometry 37, 74–80 (1999).
doi: 10.1002/(SICI)1097-0320(19990901)37:1<74::AID-CYTO9>3.0.CO;2-H
pubmed: 10451509
Schkurko, C. et al. An in-situ laboratory analysis capability for exploration spaceflight. In 93rd Annual Scientific Meeting 1–11 (Aerospace Medical Association, 2023).
National Aeronautics and Space Administration. Human research roadmap. https://humanresearchroadmap.nasa.gov/Gaps (2023).
Ohnishi, K. & Ohnishi, T. The biological effects of space radiation during long stays in space. Biol. Sci. Space 18, 201–205 (2004).
doi: 10.2187/bss.18.201
pubmed: 15858386
Thorne, M. C. Background radiation: natural and man-made. J. Radio. Prot. 23, 29–42 (2003).
doi: 10.1088/0952-4746/23/1/302
Spidlen, J., Breuer, K. & Brinkman, R. Preparing a minimum information about a flow cytometry experiment (MIFlowCyt) compliant manuscript using the International Society for Advancement of Cytometry (ISAC) FCS file repository (FlowRepository.org). Curr. Protoc. Cytom. Chapter 10, Unit 10.18 (2012).