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Gaining interests and expediency of precision medicine for various diseases has led to the search for non invasive techniques like liquid biopsies involving study of circulating cell free DNA (cfDNA) for diagnostic as well as prognostic applications. Present study reports that cfDNA in plasma of patients with Rheumatoid Arthritis are fragmented, modified and hence remain undetected using qPCR, the commonly used analytical assay. They are immunogenic to peripheral blood cells and stimulate them to secrete TNF‐α, a pro‐inflammatory cytokine making it imperative to detect cfDNA in patients for an effective therapeutic intervention. Hereby a non‐invasive colorimetric assay for naked eye discernment of cfDNA using gold nanoparticles is proposed which is potent in detecting long and short cfDNA fragments from small amount of blood, is inexpensive, label free, easy to perform and allows visual detection. This can be further explored to assess its diagnostic and prognostics implications in various human disorders. Unmodified gold nanoparticles (AuNPs) have affinity towards cfDNA and show distinct color change upon interaction, but fail to do same with fragmented cfDNA. This mechanism has been further exploited to identify fragmentation status of cfDNA of RA patients which are found to be more fragmented and immunogenic in nature when compared with control samples. [ABSTRACT FROM AUTHOR]