Synthesis and experimental study of liquid dispersions of magnetic  fluorescent polystyrene microspheres

Pavel V. Shalaev; Ekaterina V. Bondina; Natalya N.  Sankova; Ekaterina V. Parkhomchuk; Sergey A. Dolgushin

doi:10.17308/kcmf.2021.23/3312

Pavel V. Shalaev N. F. Gamaleya Federal Research Center for Epidemiology & Microbiology, 18 Gamaleya st., Moscow 123098, Russian Federation; National Research University of Electronic Technology, Bld. 1, Shokin Square, Zelenograd, Moscow 124498, Russian Federation; Aivok LLC, proezd 4922, bld. 4, Zelenograd, Moscow 124498, Russian Federation https://orcid.org/0000-0003-0552-9715
Ekaterina V. Bondina National Research University of Electronic Technology, Bld. 1, Shokin Square, Zelenograd, Moscow 124498, Russian Federation; Aivok LLC, proezd 4922, bld. 4, Zelenograd, Moscow 124498, Russian Federation https://orcid.org/0000-0002-1986-7961
Natalya N. Sankova Novosibirsk State University, 1 Pirogova str., Novosibirsk 630090, Russian Federation; Boreskov Institute of Catalysis Siberian Branch of the Russian Academy of Sciences, 5 Lavrentiev Ave. (Prospekt Akademika Lavrentieva 5), Novosibirsk 630090, Russian Federation https://orcid.org/0000-0002-1913-5293
Ekaterina V. Parkhomchuk Novosibirsk State University, 1 Pirogova str., Novosibirsk 630090, Russian Federation; Boreskov Institute of Catalysis Siberian Branch of the Russian Academy of Sciences, 5 Lavrentiev Ave. (Prospekt Akademika Lavrentieva 5), Novosibirsk 630090, Russian Federation https://orcid.org/0000-0003-2200-884X
Sergey A. Dolgushin N. F. Gamaleya Federal Research Center for Epidemiology & Microbiology, 18 Gamaleya st., Moscow 123098, Russian Federation; Aivok LLC, proezd 4922, bld. 4, Zelenograd, Moscow 124498, Russian Federation https://orcid.org/0000-0002-6965-6409

DOI: https://doi.org/10.17308/kcmf.2021.23/3312

Keywords: Immunofluorescence assay, Planar immunoassay, Microspheres, Fluorescence, Dispersion polymerization, Two-stage swelling

Abstract

Multiplex microsphere-based immunofluorescence assay is a reliable, accurate, and highly sensitive method for the detection of various biomolecules. However, for the moment, the wide application of the method in clinical practice is prevented by the high cost of reagents for analysis - magnetic spectrally encoded microspheres. Therefore, an urgent task is the development of new methods for the synthesis of microspheres with the required properties. The aim of this study was the creation of new magnetic fluorescent microspheres suitable for use in multiplex immunoassay.Samples of magnetic fluorescent polystyrene microspheres were synthesized by dispersion polymerization and two-stage
swelling methods. Experimental studies of geometric parameters, fluorescence, magnetic properties of the synthesized microspheres have been carried out.The results of the studies have shown that microspheres synthesized by dispersion polymerization are promising for the use in immunofluorescence analysis. The obtained results can be used for the development of new diagnostic multiplex test systems based on spectrally encoded microspheres.

Downloads

Download data is not yet available.

Author Biographies

Pavel V. Shalaev, N. F. Gamaleya Federal Research Center for Epidemiology & Microbiology, 18 Gamaleya st., Moscow 123098, Russian Federation; National Research University of Electronic Technology, Bld. 1, Shokin Square, Zelenograd, Moscow 124498, Russian Federation; Aivok LLC, proezd 4922, bld. 4, Zelenograd, Moscow 124498, Russian Federation

Engineer, National Research
Center for Epidemiology and Microbiology named after
Honorary Academician N.F. Gamaleya of the Ministry
of Health of the Russian Federation, Moscow;
Postgraduate Student, National Research University
of Electronic Technology - MIET, Zelenograd, Moscow;
Leading Development Engineer, Aivok LLC, Zelenograd,
Moscow, Russian Federation; e-mail: shalaev.pv@gmail.com

Ekaterina V. Bondina, National Research University of Electronic Technology, Bld. 1, Shokin Square, Zelenograd, Moscow 124498, Russian Federation; Aivok LLC, proezd 4922, bld. 4, Zelenograd, Moscow 124498, Russian Federation

Master Student, National
Research University of Electronic Technology - MIET,
Zelenograd, Moscow, Russian Federation; engineer,
Aivok LLC, Zelenograd, Moscow, Russian Federation;
e-mail: e_bondina97@mail.ru

Natalya N. Sankova, Novosibirsk State University, 1 Pirogova str., Novosibirsk 630090, Russian Federation; Boreskov Institute of Catalysis Siberian Branch of the Russian Academy of Sciences, 5 Lavrentiev Ave. (Prospekt Akademika Lavrentieva 5), Novosibirsk 630090, Russian Federation

Postgraduate Student,
Novosibirsk State University, Novosibirsk; Researcher
Associate, Boreskov Institute of Catalysis of the
Siberian Branch of the Russian Academy of Sciences,
Novosibirsk, Russian Federation; e-mail: natali_9999@bk.ru.

Ekaterina V. Parkhomchuk, Novosibirsk State University, 1 Pirogova str., Novosibirsk 630090, Russian Federation; Boreskov Institute of Catalysis Siberian Branch of the Russian Academy of Sciences, 5 Lavrentiev Ave. (Prospekt Akademika Lavrentieva 5), Novosibirsk 630090, Russian Federation

PhD in Chemistry,
Senior Researcher, Novosibirsk State University,
Novosibirsk; Senior Researcher, Boreskov Institute of
Catalysis of the Siberian Branch of the Russian
Academy of Sciences, Novosibirsk, Russian Federation;
e-mail: ekaterina@catalysis.ru

Sergey A. Dolgushin, N. F. Gamaleya Federal Research Center for Epidemiology & Microbiology, 18 Gamaleya st., Moscow 123098, Russian Federation; Aivok LLC, proezd 4922, bld. 4, Zelenograd, Moscow 124498, Russian Federation

PhD in Physics and Mathematics, Senior Researcher, National Research Center
for Epidemiology and Microbiology named after
Honorary Academician N.F. Gamaleya of the Ministry
of Health of the Russian Federation, Moscow; Director,
Aivok LLC, Zelenograd, Moscow, Russian Federation;
e-mail: dolgushin.sergey@gmail.com

References

Gu Z., Zhao, S., Xu G., Chen C., Wang Y., Gu H., Xu H. Solid-phase PCR based on thermostable, encoded magnetic microspheres for simple, highly sensitive and multiplexed nucleic acid detection. Sensors and Actuators B: Chemical. 2019;298: 126953. https://doi.org/10.1016/j.snb.2019.126953

Su R., Tang X., Feng L., Yao G. L., Chen J. Development of quantitative magnetic beads-based flow cytometry fluorescence immunoassay for aflatoxin B1. Microchemical Journal: 2020;155: 104715. https://doi.org/10.1016/j.microc.2020.104715

Klisara N., Peters J., Haasnoot W., Nielen M. W., Palaniappan A., Liedberg B. Functional fluorescence assay of botulinum neurotoxin A in complex matrices using magnetic beads. Sensors and Actuators B: Chemical: 2019;281: 912–919. https://doi.org/10.1016/j.snb.2018.10.100

Jin M., Luo J., Dou X., Yang M., Fan Z. A sensitive cytometric bead array for chlorpyrifos using magnetic microspheres. Microchemical Journal. 2020;156: 104847. https://doi.org/10.1016/j.microc.2020.104847

Ding L., Chen X., He L., Yu F., Yu S., Wang J., Qu L. Fluorometric immunoassay for the simultaneous determination of the tumor markers carcinoembryonic antigen and cytokeratin 19 fragment using two kinds of CdSe/ZnS quantum dot nanobeads and magnetic beads. Microchimica Acta. 2020;187(3): 1–8. https://link.springer.com/article/10.1007/s00604-019-3914-7

Wei X., Bian F., Cai X., Wang Y., Cai L., Yang J., Zhao Y. Multiplexed detection strategy for bladder cancer microRNAs based on photonic crystal barcodes. Analytical Chemistry. 2020;92(8): 6121–6127. Available at: https://pubs.acs.org/doi/10.1021/acs.analchem.0c00630

Priest J. W., Moss D. M. Measuring cryptosporidium serologic responses by multiplex bead assay. In: Mead J., Arrowood M. (eds). Cryptosporidium. Methods in Molecular Biology, vol. 2052. New York, NY: Humana; 2020. 61–85 p. https://doi.org/10.1007/978-1-4939-9748-0_5

Chen J. H.-K., Yip C. C.-Y., Chan J. F.-W., Poon R. W. S., To K. K.-W., Chan K. H., Yuen K. Y. Clinical performance of the luminex NxTAG CoV extended panel for SARS-CoV-2 detection in nasopharyngeal specimens of COVID-19 patients in Hong Kong. Journal of Clinical Microbiology. 2020;58(8): e00936-20. https://doi.org/10.1128/jcm.00936-20

Wilson R., Spiller D. G., Prior I. A., Veltkamp K. J., Hutchinson A. A simple method for preparing spectrally encoded magnetic beads for multiplexed detection. ACS Nano. 2007;1(5): 487–493. https://pubs.acs.org/doi/abs/10.1021/nn700289m

Graham H., Chandler D. J., Dunbar S. A. The genesis and evolution of bead-based multiplexing.Methods. 2019;158: 2–11. https://doi.org/10.1016/j.ymeth.2019.01.007

Ligler F. S., Kim J. S. The Microflow Cytometer.Boca Raton: Pan Stanford Publ.; 2010. 394 p. https://doi.org/10.1201/9780429109157

Dunbar S. A. Bead-based suspension arrays for the detection and identification of respiratory viruses. In: Tang Y. W., Stratton C. (eds) Advanced techniques in diagnostic microbiology. Boston, MA; Springer: 2013. 813–833 pp. https://doi.org/10.1007/978-1-4614-3970-7_42

Mountjoy K. G. ELISA versus LUMINEX assay for measuring mouse metabolic hormons and cytokines: sharing the lessons I have learned. Journal of Immunoassay and Immunochemistry. 2020: 1–20. https://doi.org/10.1080/15321819.2020.1838924

Ligler F. S., Erickson J. S., Golden J. P., Kim J. S, Nasir M., Howell P. J., Thangawng A. L., Hilliard L., Anderson G. P. Microflow cytometer. In: Proc. SPIE 7167, Frontiers in Pathogen Detection: From Nanosensors to Systems, 71670N, 19 February 2009. https://doi.org/10.1117/12.807671

Germeraad E. A., Achterberg R.P., Venema S., Post J., de Leeuw O., Koch G., van der Wal F.J., Beerens N. The development of a multiplex serological assay for avian influenza based on Luminex technology. Methods. 2019;158: 54–60. https://doi.org/10.1016/j.ymeth.2019.01.012

Choi J., Kwak, S. Y., Kang S., Lee S. S., Park M., Lim S., Hong S. I. Synthesis of highly crosslinked monodisperse polymer particles: effect of reaction parameters on the size and size distribution. Journal of Polymer Science Part A: Polymer Chemistry. 2002;40(23): 4368–4377. https://doi.org/10.1002/pola.10514

Barrett K. E. Dispersion polymerization in organic media. New York: John Wiley & Sons, Inc.; 1975. 338 p.

Lok K. P., Ober C. K. Particle size control in dispersion polymerization of polystyrene. Canadian Journal of Chemistry. 1985;63(1): 209–216. https://doi.org/10.1139/v85-033

Ugelstad J., Mork P. C., Kaggerud K. H., Ellingsen T., Berge A. Swelling of oligomer-polymer particles. New methods of preparation. Advances in Colloid and Interface Science. 1980;13(1-2): 101–140. https://doi.org/10.1016/0001-8686(80)87003-5

Ugelstad J., Mfutakamba H. R., Mørk P. C., Ellingsen T., Berge A., Schmid R., Nustad K. Preparation and application of monodisperse polymer particles. Journal of Polymer Science: Polymer Symposia. 1985;72(1): 225–240. https://doi.org/10.1002/polc.5070720125

Lee J. H., Gomez I. J., Sitterle V. B., Meredith J. C. Dye-labeled polystyrene latex microspheres prepared via a combined swelling-diffusion technique. Journal of Colloid and Interface Science. 2011;363(1): 137–144. https://doi.org/10.1016/j.jcis.2011.07.047

Ugelstad J.; Kaggerud K. H.; Hansen F. K.; Berge A. Absorption of low molecular weight compounds in aqueous dispersions of polymer-oligomer particles. A two step swelling process of polymer particles giving an enormous increase in absorption capacity. Die Makromolekulare Chemie. 1979;180(3): 737–744. https://doi.org/10.1002/macp.1979.021800317

Okubo M., Shiozaki M., Tsujihiro M., Tsukuda Y. Preparation of micron-size monodisperse polymer particles by seeded polymerization utilizing the dynamic monomer swelling method. Colloid and Polymer Science. 991;269(3): 222–226. https://doi.org/10.1007/bf00665495

Bedre J., Chandler D., Mize B. Method and system for manufacture and use of macroporous beads in a multiplex assay. Patent US9745438B2. 2009. Режим доступа: https://patents.google.com/patent/US9745438B2

Song J.S., Winnik M.A. Cross-linked, monodisperse, micron-sized polystyrene particles by twostage dispersion polymerization. Macromolecules. 2005;38(20): 8300–8307. DOI: https://doi.org/10.1021/ma050992z

Gao H., Matyjaszewski K. Synthesis of functional polymers with controlled architecture by CRP of monomers in the presence of cross-linkers: From stars to gels. Progress in Polymer Science. 2009;34(4): 317–350. https://doi.org/10.1016/j.progpolymsci.2009.01.001

Yang C., Guan Y., Xing J., Liu J.; Shan G., An Z., Liu H. Preparation of magnetic polystyrene microspheres with a narrow size distribution. AIChE Journal. 2005;51(7): 2011–2015. https://doi.org/10.1002/aic.10467

Šálek P., Horák D. Hypercrosslinked polystyrene microspheres by suspension and dispersion polymerization. e-Polymers. 2011;11(1). https://doi.org/10.1515/epoly.2011.11.1.688

Kawaguchi H. Functional polymer microspheres. Progress in Polymer Science.2000;25(8): 1171-1210. https://doi.org/10.1016/S0079-6700(00)00024-1

Hong J., Lee J., Rhym Y. M., Kim D. H., Shim S. E. Polyelectrolyte-assisted synthesis of polystyrene icrospheres

by dispersion polymerization and the subsequent formation of silica shell. Journal of Colloid and Interface Science. 2010;344(2): 410–416. https://doi.org/10.1016/j.jcis.2010.01.001

Liu N., Li Y., Liang W., Liu Y. Fluorescence-encoded polystyrene microspheres for the application of suspension array technology. Materials for Biomedical Engineering. 2019: 221–267.

https://doi.org/10.1016/b978-0-12-818433-2.00007-8

Tobias C., Climent E., Gawlitza K., Rurack K. Polystyrene microparticles with convergently grown mesoporous silica shells as a promising tool for multiplexed bioanalytical assays. ACS Applied Materials & Interfaces. 2020;13(1): 207–218. https://doi.org/10.1021/acsami.0c17940

Serkhacheva N. S., Gainanova A. A., Kuz’michevaG. M., Podbelskiy V. V., Sadovskaya N. V., Zybinskiy A. M., Domoroshchina E. N., Dorokhov A. V., Chernyshev V. V., Prokopov N. I., Gerval’d A. Yu. Composites based on polystyrene microspheres with nano-scaled titanium dioxide. International Journal of Polymer Analysis and Characterization. 2015;20(8): 743–753. https://doi.org/10.1080/1023666x.2015.1081190

Liu G., Guan Y., Ge Y., Xie L. Preparation of monodisperse magnetic polystyrene microspheres and its surface chemical modification. Journal of Applied Polymer Science. 2011;120(6): 3278–3283. https://doi.org/10.1002/app.33495

Pushparaj P. N. Multiple analyte profiling (xMAP) technology coupled with functional bioinformatics strategies: potential applications in protein diomarker profiling in autoimmune inflammatory diseases. In: Shaik N., Hakeem K., Banaganapalli B., Elango R. (eds). Essentials of Bioinformatics, Volume II. Springer, Cham.; 2019. 151–165 pp. https://doi.org/10.1007/978-3-030-18375-2_9

Fulwyler M. J., Perrings J. D., Cram L. S. Production of uniform microspheres. Review of Scientific Instruments. 1973;44(2): 204–206. https://doi.org/10.1063/1.1686082