Development and validation of lens-free polarized microscopy to identify mono-sodium urate and calcium pyrophosphate crystals from synovial fluid

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ABSTRACT Crystal arthropathy is the most common type of inflammatory arthritis, caused by the deposition of either monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPP) crystals in or around joints, clinically recognized as either gout or pseudogout. Diagnosis of crystal arthropathy can be established by identifying MSU or CPPD crystals in the synovial fluid with a compensated polarized light microscope (CPLM). CPLM has been the gold- standard diagnostic instrument for crystal arthropathy since 1961. However, given the limited field of view (FOV) of CPLM, examination for crystals can be laborious. Furthermore, the sensitivity of CPLM can be affected by crystal concentration, size, and birefringent properties (particularly for CPP crystals), as well as technician experience. There exists the need to develop an inexpensive high-resolution, wide-FOV polarized microscopic device for synovial fluid screening, with improved sensitivity. Lens-free on-chip microscopy has developed in the past decade. The advantages of the lens-free microscope include high-resolution, wide FOV, low cost and compact instrumentation. However, lens-free technology has not been adapted to perform polarized imaging due to a fundamental difference in its imaging principle. We have developed a way to overcome this challenge and have preliminary data showing the ability of our system to accurately detect both MSU and CPP crystals. The proposed lens-free polarized on-chip microscope will enable the rapid screening and sensitive detection of birefringent crystals in synovial fluid samples of patients, greatly improving the sensitivity and efficiency of gout and pseudogout diagnosis.