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

摘要 结晶性关节病是最常见的炎性关节炎类型， 临床上，关节内或关节周围存在尿酸盐（MSU）或焦磷酸钙二水合物（CPP）晶体 被认为是痛风或假性痛风。结晶性关节病的诊断可以通过鉴别 用补偿偏振光显微镜（CPLM）观察滑液中的MSU或CPPD晶体。葡语共同体已 自1961年以来一直是水晶关节病的黄金标准诊断仪器。然而，由于有限的 在CPLM的视场（FOV）中，晶体的检查可能是费力的。此外，CPLM的灵敏度 晶体浓度、尺寸和双折射特性（特别是CPP晶体）也会影响晶体的折射率 作为技术人员的经验。存在开发廉价的高分辨率、宽视场的需要 用于滑液筛查的偏振显微镜装置，具有改进的灵敏度。 无透镜片上显微镜在过去十年中得到了发展。无透镜显微镜的优点 包括高分辨率、宽FOV、低成本和紧凑仪器。然而，无镜头技术 由于其成像原理的根本差异，不适于执行偏振成像。我们 我已经开发出一种方法来克服这一挑战，并有初步的数据显示我们的系统的能力 精确检测MSU和CPP晶体。 所提出的无透镜偏振片上显微镜将能够快速筛选和灵敏检测 双折射晶体在患者的滑液样本中，大大提高了痛风的敏感性和效率 和假痛风诊断。

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.