Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis

Zhang, Yibo; Lee, Seung Yoon Celine; Zhang, Yun; Furst, Daniel; Fitzgerald, John; Ozcan, Aydogan

Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis

Type

Article

Authors

Zhang, Yibo
Lee, Seung Yoon Celine
Zhang, Yun
Furst, Daniel
Fitzgerald, John

Ozcan, Aydogan

Date

2016-06-30

Abstract

Gout is a form of crystal arthropathy where monosodium urate (MSU) crystals deposit and elicit inflammation in a joint. Diagnosis of gout relies on identification of MSU crystals under a compensated polarized light microscope (CPLM) in synovial fluid aspirated from the patient's joint. The detection of MSU crystals by optical microscopy is enhanced by their birefringent properties. However, CPLM partially suffers from the high-cost and bulkiness of conventional lens-based microscopy, and its relatively small field-of-view (FOV) limits the efficiency and accuracy of gout diagnosis. Here we present a lens-free polarized microscope which adopts a novel differential and angle-mismatched polarizing optical design achieving wide-field and high-resolution holographic imaging of birefringent objects with a color contrast similar to that of a standard CPLM. The performance of this computational polarization microscope is validated by imaging MSU crystals made from a gout patient's tophus and steroid crystals used as negative control. This lens-free polarized microscope, with its wide FOV (>20 mm2), cost-effectiveness and field-portability, can significantly improve the efficiency and accuracy of gout diagnosis, reduce costs, and can be deployed even at the point-of-care and in resource-limited clinical settings.

Citation

Zhang, Y., Lee, S. Y. C., Zhang, Y., Furst, D., Fitzgerald, J., & Ozcan, A. (2016). Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis. Scientific Reports, 6(1). doi:10.1038/srep28793

Acknowledgements

The Ozcan Research Group at UCLA gratefully acknowledges the support of the Presidential Early Career Award for Scientists and Engineers (PECASE), the Army Research Office (ARO; W911NF-13-1-0419 and W911NF-13-1-0197), the ARO Life Sciences Division, the National Science Foundation (NSF) CBET Division Biophotonics Program, the NSF Emerging Frontiers in Research and Innovation (EFRI) Award, the NSF EAGER Award, NSF INSPIRE Award, NSF Partnerships for Innovation: Building Innovation Capacity (PFI:BIC) Program, Office of Naval Research (ONR), the Howard Hughes Medical Institute (HHMI), Vodafone Americas Foundation, and KAUST. This work is based upon research performed in a laboratory renovated by the National Science Foundation under Grant No. 0963183, which is an award funded under the American Recovery and Reinvestment Act of 2009 (ARRA).