Biosensor; Cell culture; Gold nanoparticle; Hydrogel; Microcarrier; Nanoparticles; Plasmonics; Self-assembly; Cell expansion; Gold Nanoparticles; Growth support; High-throughput; Microcarriers; Plate configuration; Surface area; Well plates; Electronic, Optical and Magnetic Materials; Computer Science (miscellaneous); Atomic and Molecular Physics, and Optics; Instrumentation; Electrical and Electronic Engineering
Abstract :
[en] Microcarriers (MCs, typically 50–200 µm) are promising growth supports for high-throughput cell expansion, with capability to overcome the limitations of surface area availability and nutrient access encountered by cell culture in 2D well plate configurations. Equipping MCs with in-built capability to sense molecular biomarkers is a key step forward to meet the emerging demands of personalized cell-based therapies. However, integrating sensing functionality into MCs is non-trivial due to fabrication limitations imposed by their large size, curved surfaces, and their suspension in fluid. If achieved, the sensor-integrated MCs should face further concerns of reduced stability and cytocompatibility during cell-culture. Here we demonstrate plasmonic microcarriers (PMCs) that integrate spectroscopic sensing and cell expansion functions through the deposition of gold nanoparticle (AuNP) assemblies on dextran-based MCs. Hydrogel characteristics of the dextran microcarriers was found to profoundly enhance the binding density and kinetics of AuNPs, as seen by attainment of saturated densities in few seconds, and at nanoparticle concentrations only twice that of the surface sites. The approaches to prepare PMCs are distinguished by simple, scalable routes, without need for sophisticated lab infrastructure. The capability of PMCs to act as spectroscopic transducers was demonstrated by surface-enhanced spectroscopic (SERS) detection of a model molecular probe. The growth, proliferation and migration of human mesenchymal stem cells on the PMCs was found to be comparable to that of the uncoated MCs. The results pave the way to smart, multifunctional cell growth supports to interrogate, control and report cell behavior during culture.
Disciplines :
Chemistry
Author, co-author :
Stoffels, Charlotte ; Université de Liège - ULiège ; Materials Research and Technology (MRT), Luxembourg Institute of Science and Technology (LIST), Belvaux, Luxembourg
Grysan, Patrick; Materials Research and Technology (MRT), Luxembourg Institute of Science and Technology (LIST), Belvaux, Luxembourg
Sion, Caroline; Université de Lorraine, CNRS, LRGP, Nancy, France
Rastogi, Rishabh ; Materials Research and Technology (MRT), Luxembourg Institute of Science and Technology (LIST), Belvaux, Luxembourg ; Laboratory Light, nanomaterials & nanotechnologies – L2n, the University of Technology of Troyes & CNRS ERL 7004, Troyes, France
Beggiato, Matteo ; Materials Research and Technology (MRT), Luxembourg Institute of Science and Technology (LIST), Belvaux, Luxembourg ; Doctoral School in Science and Engineering (DSSE), Faculty of Science, Technology and Medicine (FSTM), University of Luxembourg, Belval, Luxembourg
Olmos, Eric; Université de Lorraine, CNRS, LRGP, Nancy, France
Krishnamoorthy, Sivashankar ; Materials Research and Technology (MRT), Luxembourg Institute of Science and Technology (LIST), Belvaux, Luxembourg
Language :
English
Title :
Plasmonic microcarriers for sensing and cell expansion
Authors thank Esther Lentzen for NanoSIMS measurements and Asmaa El Moul for Ultramicrotomy. Funding from INTERREG Grand Region V via IMPROVE-STEM project, and Fonds National de la Recherche (FNR) Luxembourg via MASSENA and PLASENS ( C15/MS/10459961 ) projects is gratefully acknowledged.
Coskun, A.F., Cetin, A.E., Galarreta, B.C., Alvarez, D.A., Altug, H., Ozcan, A., Lensfree optofluidic plasmonic sensor for real-time and label-free monitoring of molecular binding events over a wide field-of-view. Sci. Rep. 4 (2014), 1–7, 10.1038/srep06789.
Guliy, O.I., Zaitsev, B.D., Mehta, S.K., Borodina, I.A., Analysis of microbial cell viability in a liquid using an acoustic sensor. Ultrasound Med. Biol. 46 (2020), 1026–1039, 10.1016/j.ultrasmedbio.2019.12.010.
Bilek, M.M., McKenzie, D.R., Plasma modified surfaces for covalent immobilization of functional biomolecules in the absence of chemical linkers: towards better biosensors and a new generation of medical implants. Biophys. Rev. 2 (2010), 55–65, 10.1007/s12551-010-0028-1.
Weltin, A., Slotwinski, K., Kieninger, J., Moser, I., Jobst, G., Wego, M., Ehret, R., Urban, G.A., Cell culture monitoring for drug screening and cancer research: a transparent, microfluidic, multi-sensor microsystem. Lab Chip 14 (2014), 138–146, 10.1039/c3lc50759a.
Sabaté del Río, J., Ro, J., Yoon, H., Park, T.-E., Cho, Y.-K., Integrated technologies for continuous monitoring of organs-on-chips: current challenges and potential solutions. Biosens. Bioelectron., 224, 2023, 115057, 10.1016/j.bios.2022.115057.
Fuchs, S., Johansson, S., Tjell, A.Ø., Werr, G., Mayr, T., Tenje, M., In-line analysis of organ-on-chip systems with sensors: integration, fabrication, challenges, and potential. ACS Biomater. Sci. Eng. 7 (2021), 2926–2948.
Couto, P.S., Rotondi, M.C., Bersenev, A., Hewitt, C.J., Nienow, A.W., Verter, F., Rafiq, Q.A., Expansion of human mesenchymal stem/stromal cells (hMSCs) in bioreactors using microcarriers: lessons learnt and what the future holds. Biotechnol. Adv., 2020, 107636.
Ornelas-González, A., González-González, M., Rito-Palomares, M., Microcarrier-based stem cell bioprocessing: GMP-grade culture challenges and future trends for regenerative medicine. Crit. Rev. Biotechnol., 2021, 1–15.
Koh, B., Sulaiman, N., Fauzi, M.B., Law, J.X., Ng, M.H., Idrus, R.B.H., Yazid, M.D., Three dimensional microcarrier system in mesenchymal stem cell culture: a systematic review. Cell Biosci 10 (2020), 1–16.
Li, X., Soler, M., Szydzik, C., Khoshmanesh, K., Schmidt, J., Coukos, G., Mitchell, A., Altug, H., Label-free optofluidic nanobiosensor enables real-time analysis of single-cell cytokine secretion. Small 14 (2018), 1–11, 10.1002/smll.201800698.
Han, Q., Bradshaw, E.M., Orn Nilsson, B., Hafler Cd, D.A., Love, J.C., Multidimensional analysis of the frequencies and rates of cytokine secretion from single cells by quantitative microengraving †. Lab. Chip. 10 (2010), 1337–1492, 10.1039/b926849a.
Torres, A.J., Hill, A.S., Love, J.C., Nanowell-based immunoassays for measuring single-cell secretion: characterization of transport and surface binding. Anal. Chem., 86, 2014, 34, 10.1021/ac4030297.
Young, A.T., Rivera, K.R., Erb, P.D., Daniele, M.A., Monitoring of microphysiological systems: integrating sensors and real-time data analysis toward autonomous decision-making. ACS Sens. 4 (2019), 1454–1464, 10.1021/acssensors.8b01549.
Ma, C., Fan, R., Ahmad, H., Shi, Q., Comin-Anduix, B., Chodon, T., Koya, R.C., Liu, C.C., Kwong, G.A., Radu, C.G., Ribas, A., Heath, J.R., A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells. Nat. Med. 17 (2011), 738–743, 10.1038/nm.2375.
Braeckmans, K., De Smedt, S.C., Leblans, M., Pauwels, R., Demeester, J., Encoding microcarriers: present and future technologies. Nat. Rev. Drug Discov. 1 (2002), 447–456.
Sabetsky, V.A., Martiouchine, S.V., Nesterova, Z.V., Development of novel optically encoded microspheres for microarrays. Proceeding of the SPIE - International Soc. Opt. Eng., Inst. of Highly Pure Biopreparations, 7 Pudozhskaya str, St. Petersburg, Russian Federation, 2002, 78–81 197110.
Vafajoo, A., Rostami, A., Parsa, S.F., Salarian, R., Rabiee, N., Rabiee, G., Rabiee, M., Tahriri, M., Vashaee, D., Tayebi, L., Multiplexed microarrays based on optically encoded microbeads. Biomed. Microdevices. 20 (2018), 1–14.
Rastogi, R., Arianfard, H., Moss, D., Juodkazis, S., Adam, P.-M., Krishnamoorthy, S., Analyte Co-localization at electromagnetic gap hot-spots for highly sensitive (bio)molecular detection by plasmon enhanced spectroscopies. ACS Appl. Mater. Interfaces. 13 (2021), 9113–9121, 10.1021/acsami.0c17929.
Rastogi, R., Dogbe Foli, E.A., Vincent, R., Poovathingal, S., Adam, P.-M., Krishnamoorthy, S., Hierarchically structured plasmonic nanoparticle assemblies with dual-length scale electromagnetic hot spots for enhanced sensitivity in the detection of (bio)molecular analytes. J. Phys. Chem. C. 125 (2021), 8647–8655, 10.1021/acs.jpcc.0c10467.
Fang, Y., Seong, N.H., Dlott, D.D., Measurement of the distribution of site enhancements in surface-enhanced raman scattering. Science 321:80 (2008), 388–392, 10.1126/science.1159499.
Ferreyra, N., Coche-Guérente, L., Fatisson, J., Lopez Teijelo, M., Labbé, P., Layer-by-layer self-assembled multilayers of redox polyelectrolytes and gold nanoparticles. Chem. Commun. 3 (2003), 2056–2057, 10.1039/b305347d.
Malekzad, H., Beggiato, M., Hegemann, D., Gaiser, S., Duday, D., Krishnamoorthy, S., Rational route to fabrication of uni-dimensional surface gradients presenting stochastic and periodic arrangement of nanoparticles. Appl. Surf. Sci., 581, 2022, 151763, 10.1016/j.apsusc.2021.151763.
Azzam, E.M.S., Bashir, A., Shekhah, O., Alawady, A.R.E., Birkner, A., Grunwald, C., Wöll, C., Fabrication of a surface plasmon resonance biosensor based on gold nanoparticles chemisorbed onto a 1,10-decanedithiol self-assembled monolayer. Thin Solid Films 518 (2009), 387–391, 10.1016/J.TSF.2009.07.120.
Ahmed, S.R., Kim, J., Tran, V.T., Suzuki, T., Neethirajan, S., Lee, J., Park, E.Y., In situ self-assembly of gold nanoparticles on hydrophilic and hydrophobic substrates for influenza virus-sensing platform. Sci. Rep., 7, 2017, 44495, 10.1038/srep44495.
Krishnamoorthy, S., Krishnan, S., Thoniyot, P., Low, H.Y., Inherently reproducible fabrication of plasmonic nanoparticle arrays for SERS by combining nanoimprint and copolymer lithography. ACS Appl. Mater. Interfaces., 3, 2011, 10.1021/am1011518.
Maenosono, S., Okubo, T., Yamaguchi, Y., Overview of nanoparticle array formation by wet coating. J. Nanoparticle Res. 5 (2003), 5–15.
Namsani, S., Singh, J.K., Dewetting dynamics of a gold film on graphene: implications for nanoparticle formation. Faraday Discuss 186 (2016), 153–170, 10.1039/C5FD00118H.
Hinrichsen, E.L., Feder, J., Jøssang, T., Geometry of random sequential adsorption. J. Stat. Phys. 44 (1986), 793–827, 10.1007/BF01011908.
Kim, K., Ryoo, H., Lee, Y.M., Shin, K.S., Adsorption characteristics of Au nanoparticles onto poly(4-vinylpyridine) surface revealed by QCM, AFM, UV/vis, and Raman scattering spectroscopy. J. Colloid Interface Sci. 342 (2010), 479–484, 10.1016/j.jcis.2009.10.019.
Reznickova, A., Kolska, Z., Siegel, J., Svorcik, V., Grafting of gold nanoparticles and nanorods on plasma-treated polymers by thiols. J. Mater. Sci. 47 (2012), 6297–6304, 10.1007/s10853-012-6550-8.
Zhao, W., Liu, X., Xu, Y., Wang, S., Sun, T., Liu, S., Wu, X., Xu, Z., Polymer nanopillar array with Au nanoparticle inlays as a flexible and transparent SERS substrate. RSC Adv 6 (2016), 35527–35531, 10.1039/C6RA06329B.
Cheng, J., Liu, Y., Mao, H., Zhao, W., Ye, Y., Zhao, Y., Zhang, L., Li, M., Huang, C., Wafer-level fabrication of 3D nanoparticles assembled nanopillars and click chemistry modification for sensitive SERS detection of trace carbonyl compounds. Nanotechnology, 31, 2020, 265301.
Yap, F.L., Thoniyot, P., Krishnan, S., Krishnamoorthy, S., Nanoparticle cluster arrays for high-performance sers through directed self-assembly on flat substrates and on optical fibers. ACS Nano 6 (2012), 2056–2070, 10.1021/nn203661n.
Paquet, C., de Haan, H.W., Leek, D.M., Lin, H.-Y., Xiang, B., Tian, G., Kell, A., Simard, B., Clusters of superparamagnetic iron oxide nanoparticles encapsulated in a hydrogel: a particle architecture generating a synergistic enhancement of the T2 relaxation. ACS Nano 5 (2011), 3104–3112, 10.1021/nn2002272.
Xu, D., Lv, H., Liu, B., Encapsulation of metal nanoparticle catalysts within mesoporous zeolites and their enhanced catalytic performances: a review. Front. Chem., 6, 2018, 550.
Chirea, M., García-Morales, V., Manzanares, J.A., Pereira, C., Gulaboski, R., Silva, F., Electrochemical characterization of polyelectrolyte/gold nanoparticle multilayers self-assembled on gold electrodes. J. Phys. Chem. B. 109 (2005), 21808–21817, 10.1021/jp0537815.
Mühlig, S., Cialla, D., Cunningham, A., März, A., Weber, K., Bürgi, T., Lederer, F., Rockstuhl, C., Stacked and tunable large-scale plasmonic nanoparticle arrays for surface-enhanced raman spectroscopy. J. Phys. Chem. C. 118 (2014), 10230–10237, 10.1021/jp409688p.
Turkevich, J., Colloidal gold. Part II. Gold Bull. 18 (1985), 125–131, 10.1007/bf03214694.
Turkevich, J., Stevenson, P.C., Hillier, J., A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss. Faraday Soc. 11 (1951), 55–75.
Turkevich, J., Colloidal gold. Part I - Historical and preparative aspects, morphology and structure. Gold Bull 18 (1985), 86–91, 10.1007/BF03214690.
Kolesnikova, T.A., Kohler, D., Skirtach, A.G., Möhwald, H., Laser-induced cell detachment, patterning, and regrowth on gold nanoparticle functionalized surfaces. ACS Nano 6 (2012), 9585–9595, 10.1021/nn302891u.
Beggiato, M., Rastogi, R., Dupont-Gillain, C., Krishnamoorthy, S., Confined adsorption within nanopatterns as generic means to drive high adsorption efficiencies on affinity sensors. Sens. Actuat. B Chem., 366, 2022, 131945, 10.1016/j.snb.2022.131945.
Beggiato, M., Payen, H., Dupont-Gillain, C., Krishnamoorthy, S., Impact of tether length and flexibility on the efficiency of analyte capture by tethered receptors. Sens. Actuat. Rep., 5, 2023, 100148, 10.1016/j.snr.2023.100148.
Moore, N.W., Kuhl, T.L., The role of flexible tethers in multiple ligand-receptor bond formation between curved surfaces. Biophys. J. 91 (2006), 1675–1687, 10.1529/biophysj.105.079871.
Maaloum, M., Courvoisier, A., Elasticity of single polymer chains. Macromolecules 32 (1999), 4989–4992, 10.1021/ma981023p.
Jeppesen, C., Impact of polymer tether length on multiple ligand-receptor bond formation. Science 293:80 (2001), 465–468, 10.1126/science.293.5529.465.
Moreira, A.G., Marques, C.M., The role of polymer spacers in specific adhesion. J. Chem. Phys. 120 (2004), 6229–6237, 10.1063/1.1651088.
Reeves, D., Cheveralls, K., Kondev, J., Regulation of biochemical reaction rates by flexible tethers. Phys. Rev. E., 84, 2011, 21914, 10.1103/PhysRevE.84.021914.
Mikac, L., Jurkin, T., Štefanić, G., Ivanda, M., Gotić, M., Synthesis of silver nanoparticles in the presence of diethylaminoethyl-dextran hydrochloride polymer and their SERS activity. J. Nanoparticle Res. 19 (2017), 1–12, 10.1007/s11051-017-3989-1.
Verschuuren, M.A., Megens, M., Ni, Y., van Sprang, H., Polman, A., Large area nanoimprint by substrate conformal imprint lithography (SCIL). Adv. Opt. Techn. 6 (2017), 243–264, 10.1515/aot-2017-0022.
Rastogi, R., Dogbe Foli, E.A., Vincent, R., Adam, P.-M., Krishnamoorthy, S., Engineering electromagnetic hot-spots in nanoparticle cluster arrays on reflective substrates for highly sensitive detection of (bio)molecular analytes. ACS Appl. Mater. Interfaces. 13 (2021), 32653–32661, 10.1021/acsami.1c01953.
Kleinman, S.L., Sharma, B., Blaber, M.G., Henry, A.-I., Valley, N., Freeman, R.G., Natan, M.J., Schatz, G.C., Van Duyne, R.P., Structure enhancement factor relationships in single gold nanoantennas by surface-enhanced Raman excitation spectroscopy. J. Am. Chem. Soc. 135 (2013), 301–308.
Blaber, M.G., Schatz, G.C., Extending SERS into the infrared with gold nanosphere dimers. Chem. Commun. 47 (2011), 3769–3771.
Schop, D., Janssen, F.W., van Rijn, L.D.S., Fernandes, H., Bloem, R.M., de Bruijn, J.D., van Dijkhuizen-Radersma, R., Growth, metabolism, and growth inhibitors of mesenchymal stem cells. Tissue Eng. Part A. 15 (2009), 1877–1886.
Rafiq, Q.A., Ruck, S., Hanga, M.P., Heathman, T.R.J., Coopman, K., Nienow, A.W., Williams, D.J., Hewitt, C.J., Qualitative and quantitative demonstration of bead-to-bead transfer with bone marrow-derived human mesenchymal stem cells on microcarriers: utilising the phenomenon to improve culture performance. Biochem. Eng. J. 135 (2018), 11–21.
