Detecting Cell-secreted Growth Factors in Microfluidic Devices Using Bead-based Biosensors

Overview

Journal Microsyst Nanoeng

Date 2018 Jul 3

PMID 29963323

Citations 17

Authors

Kyung Jin Son

Pantea Gheibi

Gulnaz Stybayeva

Ali Rahimian

Alexander Revzin

Affiliations

Soon will be listed here.

Abstract

Microfluidic systems provide an interesting alternative to standard macroscale cell cultures due to the decrease in the number of cells and reagents as well as the improved physiology of cells confined to small volumes. However, the tools available for cell-secreted molecules inside microfluidic devices remain limited. In this paper, we describe an integrated microsystem composed of a microfluidic device and a fluorescent microbead-based assay for the detection of the hepatocyte growth factor (HGF) and the transforming growth factor (TGF)-β1 secreted by primary hepatocytes. This microfluidic system is designed to separate a cell culture chamber from sensing chambers using a permeable hydrogel barrier. Cell-secreted HGF and TGF-β1 diffuse through the hydrogel barrier into adjacent sensing channels and are detected using fluorescent microbead-based sensors. The specificity of sensing microbeads is defined by the choice of antibodies; therefore, our microfluidic culture system and sensing microbeads may be applied to a variety of cells and cell-secreted factors.

Citing Articles

Molecularly Imprinted Polymer Sensor Empowered by Bound States in the Continuum for Selective Trace-Detection of TGF-beta.

Zito G, Siciliano G, Seifalinezhad A, Miranda B, Lanzio V, Schwartzberg A Adv Sci (Weinh). 2024; 11(41):e2401843.

PMID: 39236340 PMC: 11538715. DOI: 10.1002/advs.202401843.

Integration of secreted signaling molecule sensing on cell monitoring platforms: a critical review.

Azuaje-Hualde E, Alonso-Cabrera J, de Pancorbo M, Benito-Lopez F, Basabe-Desmonts L Anal Bioanal Chem. 2024; 416(30):7249-7266.

PMID: 39048740 PMC: 11584473. DOI: 10.1007/s00216-024-05435-1.

Microphysiological systems for human aging research.

Park S, Laskow T, Chen J, Guha P, Dawn B, Kim D Aging Cell. 2024; 23(3):e14070.

PMID: 38180277 PMC: 10928588. DOI: 10.1111/acel.14070.

Biosensor integrated tissue chips and their applications on Earth and in space.

Yau A, Wang Z, Ponthempilly N, Zhang Y, Wang X, Chen Y Biosens Bioelectron. 2022; 222:114820.

PMID: 36527831 PMC: 10143284. DOI: 10.1016/j.bios.2022.114820.

Biosensors to Monitor Cell Activity in 3D Hydrogel-Based Tissue Models.

Fedi A, Vitale C, Giannoni P, Caluori G, Marrella A Sensors (Basel). 2022; 22(4).

PMID: 35214418 PMC: 8879987. DOI: 10.3390/s22041517.

References

Przybyla L, Voldman J . Attenuation of extrinsic signaling reveals the importance of matrix remodeling on maintenance of embryonic stem cell self-renewal. Proc Natl Acad Sci U S A. 2012; 109(3):835-40. PMC: 3271888. DOI: 10.1073/pnas.1103100109. View

Dunn J, Yarmush M, Koebe H, Tompkins R . Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration. FASEB J. 1989; 3(2):174-7. DOI: 10.1096/fasebj.3.2.2914628. View

Son K, Rahimian A, Shin D, Siltanen C, Patel T, Revzin A . Microfluidic compartments with sensing microbeads for dynamic monitoring of cytokine and exosome release from single cells. Analyst. 2015; 141(2):679-88. DOI: 10.1039/c5an01648g. View

Mellott M, Searcy K, Pishko M . Release of protein from highly cross-linked hydrogels of poly(ethylene glycol) diacrylate fabricated by UV polymerization. Biomaterials. 2001; 22(9):929-41. DOI: 10.1016/s0142-9612(00)00258-1. View

Mazutis L, Gilbert J, Ung W, Weitz D, Griffiths A, Heyman J . Single-cell analysis and sorting using droplet-based microfluidics. Nat Protoc. 2013; 8(5):870-91. PMC: 4128248. DOI: 10.1038/nprot.2013.046. View

Sackmann E, Fulton A, Beebe D . The present and future role of microfluidics in biomedical research. Nature. 2014; 507(7491):181-9. DOI: 10.1038/nature13118. View

Chattopadhyay P, Gierahn T, Roederer M, Love J . Single-cell technologies for monitoring immune systems. Nat Immunol. 2014; 15(2):128-35. PMC: 4040085. DOI: 10.1038/ni.2796. View

Rounds R, Ibey B, Beier H, Pishko M, Cote G . Microporated PEG spheres for fluorescent analyte detection. J Fluoresc. 2006; 17(1):57-63. DOI: 10.1007/s10895-006-0143-3. View

Annabi N, Nichol J, Zhong X, Ji C, Koshy S, Khademhosseini A . Controlling the porosity and microarchitecture of hydrogels for tissue engineering. Tissue Eng Part B Rev. 2010; 16(4):371-83. PMC: 2946907. DOI: 10.1089/ten.TEB.2009.0639. View

10.

Zhu H, Stybayeva G, Macal M, Ramanculov E, George M, Dandekar S . A microdevice for multiplexed detection of T-cell-secreted cytokines. Lab Chip. 2008; 8(12):2197-205. DOI: 10.1039/b810244a. View

11.

Love J, Ronan J, Grotenbreg G, van der Veen A, Ploegh H . A microengraving method for rapid selection of single cells producing antigen-specific antibodies. Nat Biotechnol. 2006; 24(6):703-7. DOI: 10.1038/nbt1210. View

12.

Haque A, Gheibi P, Gao Y, Foster E, Son K, You J . Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels. Sci Rep. 2016; 6:33980. PMC: 5041105. DOI: 10.1038/srep33980. View

13.

Liu Y, Yan J, Howland M, Kwa T, Revzin A . Micropatterned aptasensors for continuous monitoring of cytokine release from human leukocytes. Anal Chem. 2011; 83(21):8286-92. PMC: 3235337. DOI: 10.1021/ac202117g. View

14.

Bradshaw E, Kent S, Tripuraneni V, Orban T, Ploegh H, Hafler D . Concurrent detection of secreted products from human lymphocytes by microengraving: cytokines and antigen-reactive antibodies. Clin Immunol. 2008; 129(1):10-8. PMC: 2577144. DOI: 10.1016/j.clim.2008.06.009. View

15.

Lee A, Arena C, Beebe D, Palecek S . Development of macroporous poly(ethylene glycol) hydrogel arrays within microfluidic channels. Biomacromolecules. 2010; 11(12):3316-24. PMC: 3006031. DOI: 10.1021/bm100792y. View

16.

Choi N, Kim J, Chapin S, Duong T, Donohue E, Pandey P . Multiplexed detection of mRNA using porosity-tuned hydrogel microparticles. Anal Chem. 2012; 84(21):9370-8. DOI: 10.1021/ac302128u. View

17.

Cruise G, Scharp D, Hubbell J . Characterization of permeability and network structure of interfacially photopolymerized poly(ethylene glycol) diacrylate hydrogels. Biomaterials. 1998; 19(14):1287-94. DOI: 10.1016/s0142-9612(98)00025-8. View

18.

Pradhan S, Hassani I, Seeto W, Lipke E . PEG-fibrinogen hydrogels for three-dimensional breast cancer cell culture. J Biomed Mater Res A. 2016; 105(1):236-252. DOI: 10.1002/jbm.a.35899. View

19.

Zhou Q, Son K, Liu Y, Revzin A . Biosensors for Cell Analysis. Annu Rev Biomed Eng. 2015; 17:165-90. DOI: 10.1146/annurev-bioeng-071114-040525. View

20.

Wong A, Perez-Castillejos R, Love J, Whitesides G . Partitioning microfluidic channels with hydrogel to construct tunable 3-D cellular microenvironments. Biomaterials. 2008; 29(12):1853-61. PMC: 2288785. DOI: 10.1016/j.biomaterials.2007.12.044. View