Crystal-induced arthropathy is a disease process where the nucleation and growth of crystals in the synovial fluid of joints elicit painful arthritis-like symptoms. Monosodium urate (MSU, leading to gout) and calcium pyrophosphate dihydrate (CPPD, leading to pseudogout) are the most frequently observed crystals in joint space. Correct diagnosis of the crystal identity is critical for the appropriate course of treatment.

Nowadays, Raman spectroscopy is evolving as a potential diagnostic tool in identifying such crystals. In this work, a cost-efficient automated Raman device (CARD) in combination with a practical and efficient sample preparation method was used for chemically selective diagnosis of MSU and CPPD crystals in an automated fashion. The samples were prepared by brief enzymatic digestion treatment of synovial fluid followed by a customized filtration process which was able to congregate crystals over a submillimeter sized spot. The data acquisition and collection were automated to collect multiple spectra distributed over the filtration spot. CARD could detect MSU crystals at sub-clinical concentrations of 0.1 mg/mL and 1 mg/mL for CPPD crystals.

In addition, CARD was compared with the clinical standard compensated polarized light microscopic (CPLM) analysis of synovial fluid aspirates (N = 174) collected from symptomatic patients. Kappa coefficients were used to measure the agreement between CARD and CPLM. CARD and CPLM analyses agreed in 89.7% of samples (156 out of 174). In diagnosing gout (MSU), the Kappa coefficient for CARD and CPLM was 0.84 (95% CI 0.75-0.94). In diagnosing pseudogout (CPPD), the Kappa coefficient for CARD and CPLM was 0.61 (95% CI 0.42-0.81). Kappa coefficients indicated that CARD and CPLM had excellent agreement in diagnosing gout, and good agreement in diagnosing pseudogout.

This cost-efficient automated Raman device (CARD) holds the potential to be a novel tool for clinical diagnosis of arthritic crystals in synovial fluid at the point of care.