Identifying candidate biomarkers of ionizing radiation in human pulmonary microvascular lumens using microfluidics—A pilot study

Larry J. Millet; Richard J. Giannone; Michael S. Greenwood; Carmen M. Foster; Kathleen M. O’neil; Alexander D. Braatz; Sandra M. Davern

doi:10.3390/mi12080904

Identifying candidate biomarkers of ionizing radiation in human pulmonary microvascular lumens using microfluidics—A pilot study

Larry J. Millet, Richard J. Giannone, Michael S. Greenwood, Carmen M. Foster, Kathleen M. O’neil, Alexander D. Braatz, Sandra M. Davern

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

The microvasculature system is critical for the delivery and removal of key nutrients and waste products and is significantly damaged by ionizing radiation. Single-cell capillaries and microvasculature structures are the primary cause of circulatory dysfunction, one that results in morbidities leading to progressive tissue and organ failure and premature death. Identifying tissue-specific biomarkers that are predictive of the extent of tissue and organ damage will aid in developing medical countermeasures for treating individuals exposed to ionizing radiation. In this pilot study, we developed and tested a 17 µL human-derived microvascular microfluidic lumen for identifying candidate biomarkers of ionizing radiation exposure. Through mass-spectrometry-based proteomics, we detected 35 proteins that may be candidate early biomarkers of ionizing radiation exposure. This pilot study demonstrates the feasibility of using humanized microfluidic and organ-on-a-chip systems for biomarker discovery studies. A more elaborate study of sufficient statistical power is needed to identify candidate biomarkers and test medical countermeasures of ionizing radiation.

Original language	English
Article number	904
Journal	Micromachines
Volume	12
Issue number	8
DOIs	https://doi.org/10.3390/mi12080904
State	Published - Aug 2021

Funding

This manuscript has been authored by UT-Battelle, LLC, under contract DE-AC05-00OR22725 with the US Department of Energy (DOE). The US government retains and the publisher, by accepting the article for publication, acknowledges that the US government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for US government purposes. DOE will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan accessed on 14 May 2021). Notice: This work was funded by the Laboratory Directed Research and Development program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the US Department of Energy under contract DE-AC05-00OR22725. Microfluidic systems were fabricated and assembled through an approved user project of the Nanofabrication Research Laboratory at the Center for Nanophase Materials Sciences, which is a Department of Energy Office of Science User Facility. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Department of Energy. Acknowledgments: Notice: This work was funded by the Laboratory Directed Research and Development program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the US Department of Energy under contract DE-AC05-00OR22725. Microfluidic systems were fabricated and assembled through an approved user project of the Nanofabrication Research Laboratory at the Center for Nanophase Materials Sciences, which is a Department of Energy Office of Science User Facility. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Department of Energy. Funding: This manuscript has been authored by UT-Battelle, LLC, under contract DE-AC05-00OR22725 with the US Department of Energy (DOE). The US government retains and the publisher, by accepting the article for publication, acknowledges that the US government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for US government purposes. DOE will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan accessed on 14 May 2021).

Funders	Funder number
Center for Nanophase Materials Sciences
DOE Public Access Plan
U.S. Department of Energy	DE-AC05-00OR22725
Oak Ridge National Laboratory

Keywords

Mass spectrometry
Microfluidics
Microvascular cells
Proteomics
γ radiation

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10.3390/mi12080904

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@article{5571e8d67e2e40e08eec45e4ca3ae807,

title = "Identifying candidate biomarkers of ionizing radiation in human pulmonary microvascular lumens using microfluidics—A pilot study",

abstract = "The microvasculature system is critical for the delivery and removal of key nutrients and waste products and is significantly damaged by ionizing radiation. Single-cell capillaries and microvasculature structures are the primary cause of circulatory dysfunction, one that results in morbidities leading to progressive tissue and organ failure and premature death. Identifying tissue-specific biomarkers that are predictive of the extent of tissue and organ damage will aid in developing medical countermeasures for treating individuals exposed to ionizing radiation. In this pilot study, we developed and tested a 17 µL human-derived microvascular microfluidic lumen for identifying candidate biomarkers of ionizing radiation exposure. Through mass-spectrometry-based proteomics, we detected 35 proteins that may be candidate early biomarkers of ionizing radiation exposure. This pilot study demonstrates the feasibility of using humanized microfluidic and organ-on-a-chip systems for biomarker discovery studies. A more elaborate study of sufficient statistical power is needed to identify candidate biomarkers and test medical countermeasures of ionizing radiation.",

keywords = "Mass spectrometry, Microfluidics, Microvascular cells, Proteomics, γ radiation",

author = "Millet, {Larry J.} and Giannone, {Richard J.} and Greenwood, {Michael S.} and Foster, {Carmen M.} and O{\textquoteright}neil, {Kathleen M.} and Braatz, {Alexander D.} and Davern, {Sandra M.}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = aug,

doi = "10.3390/mi12080904",

language = "English",

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AU - Millet, Larry J.

AU - Giannone, Richard J.

AU - Greenwood, Michael S.

AU - Foster, Carmen M.

AU - O’neil, Kathleen M.

AU - Braatz, Alexander D.

AU - Davern, Sandra M.

PY - 2021/8

Y1 - 2021/8

N2 - The microvasculature system is critical for the delivery and removal of key nutrients and waste products and is significantly damaged by ionizing radiation. Single-cell capillaries and microvasculature structures are the primary cause of circulatory dysfunction, one that results in morbidities leading to progressive tissue and organ failure and premature death. Identifying tissue-specific biomarkers that are predictive of the extent of tissue and organ damage will aid in developing medical countermeasures for treating individuals exposed to ionizing radiation. In this pilot study, we developed and tested a 17 µL human-derived microvascular microfluidic lumen for identifying candidate biomarkers of ionizing radiation exposure. Through mass-spectrometry-based proteomics, we detected 35 proteins that may be candidate early biomarkers of ionizing radiation exposure. This pilot study demonstrates the feasibility of using humanized microfluidic and organ-on-a-chip systems for biomarker discovery studies. A more elaborate study of sufficient statistical power is needed to identify candidate biomarkers and test medical countermeasures of ionizing radiation.

AB - The microvasculature system is critical for the delivery and removal of key nutrients and waste products and is significantly damaged by ionizing radiation. Single-cell capillaries and microvasculature structures are the primary cause of circulatory dysfunction, one that results in morbidities leading to progressive tissue and organ failure and premature death. Identifying tissue-specific biomarkers that are predictive of the extent of tissue and organ damage will aid in developing medical countermeasures for treating individuals exposed to ionizing radiation. In this pilot study, we developed and tested a 17 µL human-derived microvascular microfluidic lumen for identifying candidate biomarkers of ionizing radiation exposure. Through mass-spectrometry-based proteomics, we detected 35 proteins that may be candidate early biomarkers of ionizing radiation exposure. This pilot study demonstrates the feasibility of using humanized microfluidic and organ-on-a-chip systems for biomarker discovery studies. A more elaborate study of sufficient statistical power is needed to identify candidate biomarkers and test medical countermeasures of ionizing radiation.

KW - Mass spectrometry

KW - Microfluidics

KW - Microvascular cells

KW - Proteomics

KW - γ radiation

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Identifying candidate biomarkers of ionizing radiation in human pulmonary microvascular lumens using microfluidics—A pilot study

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