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

Rinaldi, Christopher and Corrigan, Damion K. and Dennany, Lynn and Jarrett, Ruth F. and Lake, Annette and Baker, Matthew J. (2021) Development of an electrochemical CCL17/TARC biosensor towards rapid triage and monitoring of classic Hodgkin Lymphoma. ACS Sensors, 6 (9). pp. 3262-3272. ISSN 2379-3694 (https://doi.org/10.1021/acssensors.1c00972)

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Abstract

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.

ORCID iDs

Rinaldi, Christopher, Corrigan, Damion K. ORCID logoORCID: https://orcid.org/0000-0002-4647-7483, Dennany, Lynn ORCID logoORCID: https://orcid.org/0000-0002-5481-1066, Jarrett, Ruth F., Lake, Annette and Baker, Matthew J. ORCID logoORCID: https://orcid.org/0000-0003-2362-8581;
CORE (COnnecting REpositories)