Development of an electrochemical CCL17/TARC biosensor towards rapid triage and monitoring of classic Hodgkin Lymphoma

A point-of-care blood test for detection of an emerging biomarker, CCL17/TARC, could prove transformative for the clinical management of classic Hodgkin Lymphoma (cHL). Primary care diagnosis is challenging due to non-specific clinical presenta-tion and lack of a diagnostic test, leading to significant diagnostic delays. Treatment monitoring encounters false-positive and -negative results, leading to avoidable chemotherapy toxicity, or under-treatment, impacting patient morbidity and mortality. Here, we present an amperometric CCL17/TARC immunosensor, based on the utilisation of a thiolated heterobifunctional cross-linker and sandwich antibody assay, to facilitate novel primary care triage and chemotherapy monitoring strategies for cHL. The immunosensor shows excellent analytical performance for clinical testing; linearity (R2 = 0.986), detection limit (194 pg/ml) and lower and upper limits of quantitation (387-50,000 pg/ml). The biosensor differentiated all 42 newly diagnosed cHL patients from healthy volunteers, based on serum CCL17/TARC concentration, using blood samples collected prior to treat-ment intervention. The immunosensor also discriminated between paired blood samples of all 7 cHL patients respectively, col-lected prior to treatment and during chemotherapy, attributed to the decrease in serum CCL17/TARC concentration following chemotherapy response. Overall, we have shown, for the first time, the potential of an electrochemical CCL17/TARC biosensor for primary care triage and chemotherapy monitoring for cHL, which would have positive clinical and psychosocial implica-tions for patients, whilst streamlining current healthcare pathways.