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

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.

Pathological crystal imaging with single‐shot computational polarized light microscopy

“…Efforts have been made to create new approaches for quantitative polarized light microscopy . To reconstruct the full Stokes parameters of polarized light, these approaches capture several images while mechanically or electronically rotating the polarizers, which unavoidably adds complexity and cost to the imaging system, and limits the imaging frame rate.…”

Systematic review and quality analysis of emerging diagnostic measures for calcium pyrophosphate crystal deposition disease

“…One potential approach to the cost issue may be via lens-free polarised microscopy, with wide-field holographic imaging of birefringent objects, as recently tested, with success, for identification of urate crystals from a tophus. 36 This approach employs sensing and imaging methodology that can potentially be broadly adapted to use in conventional mobile electronic devices. 36 However, it has not yet clear whether it will be reliable for synovial fluid samples or for identification of CPPD crystals, which can include both nonbirefringent and highly polymorphic particulates.…”

“…36 This approach employs sensing and imaging methodology that can potentially be broadly adapted to use in conventional mobile electronic devices. 36 However, it has not yet clear whether it will be reliable for synovial fluid samples or for identification of CPPD crystals, which can include both nonbirefringent and highly polymorphic particulates.…”

Magnetically responsive layer-by-layer microcapsules can be retained in cells and under flow conditions to promote local drug release without triggering ROS production

“…In comparison to crystalline steroid preparations currently used clinically to treat inflammation in arthritic joints, such as Depo-Medrol ® , our crystals were more homogenous in size and shape, have a smoother surface and are of similar size. 49 To confirm stable polymer layers, LbL encapsulated dexamethasone crystals were imaged using fluorescence microscopy and scanning electron microscopy, before and after dissolution with acetonitrile (ESI Fig. S1 †).…”