Detection of Intracellular Monosodium Urate Crystals in Gout Synovial Fluid Using Optical Diffraction Tomography

Overview

Journal Sci Rep

Specialty Science

Date 2021 May 12

PMID 33976275

Citations 7

Authors

Sangwoo Park

Lucy Eunju Lee

Hanna Kim

Ji Eun Kim

Seung Jun Lee

Sunggyu Yoon

Seungwoo Shin

Heemin Kang

YongKeun Park

Jason Jungsik Song

Seongsoo Lee

Affiliations

Soon will be listed here.

Abstract

Optical diffraction tomography (ODT) enables imaging of unlabeled intracellular components by measuring the three-dimensional (3D) refractive index (RI). We aimed to detect intracellular monosodium urate (MSU) crystals in synovial leukocytes derived from gout patients using ODT. The 3D RI values of the synthetic MSU crystals, measured by ODT, ranged between 1.383 and 1.440. After adding synthetic MSU crystals to a macrophage, RI tomograms were reconstructed using ODT, and the reconstructed RI tomograms discerned intracellular and extracellular MSU crystals. We observed unlabeled synthetic MSU crystal entry into the cytoplasm of a macrophage through time-lapse imaging. Furthermore, using gout patient-derived synovial leukocytes, we successfully obtained RI tomogram images of intracellular MSU crystals. The 3D RI identification of MSU crystals was verified with birefringence through polarization-sensitive ODT measurements. Together, our results provide evidence that this novel ODT can identify birefringent MSU crystals in synovial leukocytes of patients with gout.

Citing Articles

On-Chip Polarization Light Microscopy.

Pedrosa T, de Araujo R, Wachsmann-Hogiu S Biosensors (Basel). 2025; 15(2).

PMID: 39996981 PMC: 11853662. DOI: 10.3390/bios15020079.

Lens-free on-chip 3D microscopy based on wavelength-scanning Fourier ptychographic diffraction tomography.

Wu X, Zhou N, Chen Y, Sun J, Lu L, Chen Q Light Sci Appl. 2024; 13(1):237.

PMID: 39237522 PMC: 11377727. DOI: 10.1038/s41377-024-01568-1.

Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research.

Medina-Ramirez I, Macias-Diaz J, Masuoka-Ito D, Zapien J Discov Nano. 2024; 19(1):64.

PMID: 38594446 PMC: 11003950. DOI: 10.1186/s11671-024-04003-x.

Ptychographic lens-less birefringence microscopy using a mask-modulated polarization image sensor.

Kim J, Song S, Kim H, Kim B, Park M, Oh S Sci Rep. 2023; 13(1):19263.

PMID: 37935759 PMC: 10630341. DOI: 10.1038/s41598-023-46496-z.

Improved polarized light microscopic detection of gouty crystals via dissolution with formalin and ethylenediamine tetraacetic acid.

Hemstapat R, Duangiad P, Tangketsarawan B, Phuagpan T, Chienwiwattanawong S, Tangsrianugul N Sci Rep. 2023; 13(1):7505.

PMID: 37160946 PMC: 10170089. DOI: 10.1038/s41598-023-34570-5.

References

Yoon J, Jo Y, Kim M, Kim K, Lee S, Kang S . Identification of non-activated lymphocytes using three-dimensional refractive index tomography and machine learning. Sci Rep. 2017; 7(1):6654. PMC: 5532204. DOI: 10.1038/s41598-017-06311-y. View

Roshanzadeh A, Park S, Ganjbakhsh S, Park J, Lee D, Lee S . Surface Charge-Dependent Cytotoxicity of Plastic Nanoparticles in Alveolar Cells under Cyclic Stretches. Nano Lett. 2020; 20(10):7168-7176. DOI: 10.1021/acs.nanolett.0c02463. View

Wang J, Huang W, Wang C, Liu R . Dynamic process of phagocytosis and forms of macrophage cell death induced by ingestion of apoptotic neutrophils. Sci China Life Sci. 2014; 57(10):1018-23. DOI: 10.1007/s11427-014-4726-y. View

Paul D, Achouri S, Yoon Y, Herre J, Bryant C, Cicuta P . Phagocytosis dynamics depends on target shape. Biophys J. 2013; 105(5):1143-50. PMC: 3762343. DOI: 10.1016/j.bpj.2013.07.036. View

Shin S, Kim K, Yoon J, Park Y . Active illumination using a digital micromirror device for quantitative phase imaging. Opt Lett. 2015; 40(22):5407-10. DOI: 10.1364/OL.40.005407. View

Yoon J, Kim K, Park H, Choi C, Jang S, Park Y . Label-free characterization of white blood cells by measuring 3D refractive index maps. Biomed Opt Express. 2015; 6(10):3865-75. PMC: 4605046. DOI: 10.1364/BOE.6.003865. View

Kuo C, Grainge M, Zhang W, Doherty M . Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol. 2015; 11(11):649-62. DOI: 10.1038/nrrheum.2015.91. View

Swan A, Amer H, Dieppe P . The value of synovial fluid assays in the diagnosis of joint disease: a literature survey. Ann Rheum Dis. 2002; 61(6):493-8. PMC: 1754135. DOI: 10.1136/ard.61.6.493. View

Murray C, Dellavalle R, Danaei G, Fahimi A, Flaxman D, Gabriel S . The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA. 2013; 310(6):591-608. PMC: 5436627. DOI: 10.1001/jama.2013.13805. View

10.

Brunsting A, Mullaney P . Differential light scattering from spherical mammalian cells. Biophys J. 1974; 14(6):439-53. PMC: 1334522. DOI: 10.1016/S0006-3495(74)85925-4. View

11.

Kim E, Park S, Kim Y, Moon M, Park J, Lee K . Self-luminescent photodynamic therapy using breast cancer targeted proteins. Sci Adv. 2020; 6(37). PMC: 7486108. DOI: 10.1126/sciadv.aba3009. View

12.

Starr T, Bauler T, Malik-Kale P, Steele-Mortimer O . The phorbol 12-myristate-13-acetate differentiation protocol is critical to the interaction of THP-1 macrophages with Salmonella Typhimurium. PLoS One. 2018; 13(3):e0193601. PMC: 5851575. DOI: 10.1371/journal.pone.0193601. View

13.

Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J . Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440(7081):237-41. DOI: 10.1038/nature04516. View

14.

Park S, Ahn J, Jo Y, Kang H, Kim H, Cheon Y . Label-Free Tomographic Imaging of Lipid Droplets in Foam Cells for Machine-Learning-Assisted Therapeutic Evaluation of Targeted Nanodrugs. ACS Nano. 2020; 14(2):1856-1865. DOI: 10.1021/acsnano.9b07993. View

15.

Debnath S, Park Y . Real-time quantitative phase imaging with a spatial phase-shifting algorithm. Opt Lett. 2011; 36(23):4677-9. DOI: 10.1364/OL.36.004677. View

16.

Daigneault M, Preston J, Marriott H, Whyte M, Dockrell D . The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. PLoS One. 2010; 5(1):e8668. PMC: 2800192. DOI: 10.1371/journal.pone.0008668. View

17.

Pascual E, Batlle-Gualda E, Martinez A, Rosas J, Vela P . Synovial fluid analysis for diagnosis of intercritical gout. Ann Intern Med. 1999; 131(10):756-9. DOI: 10.7326/0003-4819-131-10-199911160-00007. View

18.

van Rooij J, Kalkman J . Polarization contrast optical diffraction tomography. Biomed Opt Express. 2020; 11(4):2109-2121. PMC: 7173917. DOI: 10.1364/BOE.381992. View