Development of an electrochemical CCL17/TARC biosensor toward rapid triage and monitoring of classic Hodgkin lymphoma

Rinaldi, C., Corrigan, D. K., Dennany, L., Jarrett, R. F. , Lake, A. and Baker, M. J. (2021) Development of an electrochemical CCL17/TARC biosensor toward rapid triage and monitoring of classic Hodgkin lymphoma. ACS Sensors, 6(9), pp. 3262-3272. (doi: 10.1021/acssensors.1c00972) (PMID:34478275)

Abstract

A point-of-care blood test for the 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 nonspecific clinical presentation 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 undertreatment, impacting patient morbidity and mortality. Here, we present an amperometric CCL17/TARC immunosensor, based on the utilization 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 treatment intervention. The immunosensor also discriminated between paired blood samples of all seven cHL patients, respectively, collected 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 implications for patients, while streamlining current healthcare pathways.

• Item Type: Articles
• Additional Information: The authors thank the Engineering and Physical Sciences Research Council (grant EP/L015595/1) and CDT Medical Devices at the University of Strathclyde. The authors also thank patients who donated blood as part of the following clinical studies: Investigation of The Cause of Hodgkin lymphoma (ITCH) (Leukaemia Research Fund grant 05045 and Leukaemia Lymphoma Research grant 08031), Biomarkers And Classical Hodgkin lymphoma (BACH) (grant CSO ASM/14/02), and Study of Healthy Adult Response to EBV (SHARE) (Kay Kendall Leukaemia Fund 377).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jarrett, Professor Ruth and Lake, Ms Annette
• Authors: Rinaldi, C., Corrigan, D. K., Dennany, L., Jarrett, R. F., Lake, A., and Baker, M. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: ACS Sensors
• Publisher: American Chemical Society
• ISSN: 2379-3694
• ISSN (Online): 2379-3694
• Published Online: 03 September 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in ACS Sensors 6(9): 3262-3272
• Publisher Policy: Reproduced under a Creative Commons License