A photonic biosensor-integrated tissue chip platform for real-time sensing of lung epithelial inflammatory markers.

John S Cognetti, Maya T Moen, Matthew G Brewer, Michael R Bryan, Joshua D Tice, James L McGrath, Benjamin L Miller
Author Information
  1. John S Cognetti: Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA. Benjamin_miller@urmc.rochester.edu.
  2. Maya T Moen: Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA. Benjamin_miller@urmc.rochester.edu.
  3. Matthew G Brewer: Department of Dermatology, University of Rochester, Rochester, NY 14642, USA.
  4. Michael R Bryan: Department of Dermatology, University of Rochester, Rochester, NY 14642, USA.
  5. Joshua D Tice: QuidelOrtho, Inc., Rochester, NY, 14626, USA.
  6. James L McGrath: Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA. Benjamin_miller@urmc.rochester.edu. ORCID
  7. Benjamin L Miller: Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA. Benjamin_miller@urmc.rochester.edu. ORCID

Abstract

Tissue chip (TC) devices, also known as microphysiological systems (MPS) or organ chips (OCs or OoCs), seek to mimic human physiology on a small scale. They are intended to improve upon animal models in terms of reproducibility and human relevance, at a lower monetary and ethical cost. Virtually all TC systems are analyzed at an endpoint, leading to widespread recognition that new methods are needed to enable sensing of specific biomolecules in real time, as they are being produced by the cells. To address this need, we incorporated photonic biosensors for inflammatory cytokines into a model TC. Human bronchial epithelial cells seeded in a microfluidic device were stimulated with lipopolysaccharide, and the cytokines secreted in response sensed in real time. Sensing analyte transport through the TC in response to disruption of tissue barrier was also demonstrated. This work demonstrates the first application of photonic sensors to a human TC device, and will enable new applications in drug development and disease modeling.

References

ACS Sens. 2018 Dec 28;3(12):2716-2725 [PMID: 30507116]
Biomicrofluidics. 2016 Aug 26;10(4):044111 [PMID: 27648113]
Molecules. 2020 Apr 24;25(8): [PMID: 32344649]
Lab Chip. 2018 Jul 10;18(14):2023-2035 [PMID: 29892739]
Neurobiol Aging. 2001 Nov-Dec;22(6):837-42 [PMID: 11754990]
Cell Mol Bioeng. 2020 Jan 31;13(2):125-139 [PMID: 32175026]
Small. 2019 Feb;15(6):e1804111 [PMID: 30632319]
Lab Chip. 2022 Mar 29;22(7):1286-1296 [PMID: 35266462]
Neuroscience. 2015 Aug 27;302:103-11 [PMID: 25286385]
Cell Biol Toxicol. 2018 Feb;34(1):39-49 [PMID: 28638955]
Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):E2231-40 [PMID: 27044092]
Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):E2293-E2302 [PMID: 28265064]
Cell Stem Cell. 2020 Mar 5;26(3):309-329 [PMID: 32142662]
Int J Mol Sci. 2019 Aug 21;20(17): [PMID: 31438472]
Int J Mol Sci. 2020 Dec 23;22(1): [PMID: 33374733]
Front Physiol. 2018 Jul 03;9:815 [PMID: 30018569]
Micromachines (Basel). 2021 Jul 12;12(7): [PMID: 34357226]
Brain Behav Immun. 2006 Sep;20(5):449-55 [PMID: 16309883]
J Invest Dermatol. 2020 Feb;140(2):361-369.e3 [PMID: 31381894]
J Neurotrauma. 2009 Sep;26(9):1497-1507 [PMID: 19257803]
J Cell Biol. 1993 May;121(3):485-9 [PMID: 8486730]
Chin Med J (Engl). 2018 May 20;131(10):1191-1198 [PMID: 29722338]
Anal Bioanal Chem. 2011 Jan;399(1):205-11 [PMID: 20938769]
Mol Med Rep. 2019 Mar;19(3):1817-1823 [PMID: 30628691]
Cells. 2022 Apr 14;11(8): [PMID: 35456017]
Per Med. 2011 Mar;8(2):161-173 [PMID: 21695041]
Nat Rev Neurol. 2018 Mar;14(3):133-150 [PMID: 29377008]
Biol Psychiatry. 2010 Nov 15;68(10):930-41 [PMID: 20692646]
Lab Chip. 2021 Aug 7;21(15):2913-2921 [PMID: 34160511]
Am J Physiol Lung Cell Mol Physiol. 2001 Mar;280(3):L493-502 [PMID: 11159033]
World J Gastroenterol. 2019 Aug 14;25(30):4125-4147 [PMID: 31435168]
Molecules. 2019 Jan 31;24(3): [PMID: 30709027]
Sci Rep. 2014 Apr 22;4:4736 [PMID: 24751898]
Nat Rev Neurol. 2010 Jul;6(7):393-403 [PMID: 20551947]
Lab Chip. 2020 Aug 26;20(17):3132-3143 [PMID: 32756644]
Langmuir. 2015 Jun 16;31(23):6267-76 [PMID: 25402969]
Curr Probl Dermatol. 2011;41:80-92 [PMID: 21576949]
Ann Periodontol. 2001 Dec;6(1):78-86 [PMID: 11887474]
Anal Chem. 1999 Jul 1;71(13):2475-81 [PMID: 10405611]
Microsyst Nanoeng. 2016 Jun 06;2:16022 [PMID: 31057823]
Anal Chem. 2013 Mar 5;85(5):2787-94 [PMID: 23360389]
Anal Chem. 2013 Nov 19;85(22):10653-7 [PMID: 24171505]
Am J Physiol. 1993 Nov;265(5 Pt 1):L472-8 [PMID: 8238534]
Sensors (Basel). 2021 Aug 31;21(17): [PMID: 34502753]
Lab Chip. 2014 Jul 21;14(14):2456-68 [PMID: 24850320]
Nature. 2011 Sep 28;477(7366):526-8 [PMID: 21956311]
Anal Chem. 2010 Mar 1;82(5):1975-81 [PMID: 20143780]
IEEE Trans Biomed Eng. 2018 Feb;65(2):431-439 [PMID: 29346110]
Cell. 2021 Sep 2;184(18):4597-4611 [PMID: 34478657]
Lab Chip. 2017 Sep 12;17(18):3026-3036 [PMID: 28795174]
Lab Chip. 2017 Jan 31;17(3):448-459 [PMID: 28001148]
Neurosci Lett. 1995 Dec 29;202(1-2):17-20 [PMID: 8787820]
Lab Chip. 2019 Aug 7;19(15):2568-2580 [PMID: 31243422]
Br J Cancer. 2004 Jun 14;90(12):2312-6 [PMID: 15150588]
J Exp Med. 1966 Feb 1;123(2):365-78 [PMID: 4379352]
Lab Chip. 2021 Dec 21;22(1):71-79 [PMID: 34878455]
J Cereb Blood Flow Metab. 2019 Mar;39(3):395-410 [PMID: 30565961]
Small. 2018 Jun;14(26):e1800698 [PMID: 29806234]
Fluids Barriers CNS. 2018 Aug 31;15(1):23 [PMID: 30165870]
Nature. 2007 Feb 15;445(7129):749-53 [PMID: 17301789]
Methods. 2006 Apr;38(4):331-41 [PMID: 16487724]
Microsc Res Tech. 1997 Sep 1;38(5):488-99 [PMID: 9376652]
Micromachines (Basel). 2021 Jan 28;12(2): [PMID: 33525451]

Grants

  1. UG3 TR003281/NCATS NIH HHS
  2. UH3 TR003281/NCATS NIH HHS

MeSH Term

Humans
Reproducibility of Results
Lab-On-A-Chip Devices
Epithelial Cells
Biosensing Techniques
Lung