WestCHEM, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow G1 1RD, U.K.
Department of Biomedical Engineering, University of Strathclyde, 40 George Street, Glasgow G1 1QE, U.K.
ACS Sens. 2021 Sep 24;6(9):3262-3272. doi: 10.1021/acssensors.1c00972. Epub 2021 Sep 3.
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 ( = 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.
一种即时检测血液测试,用于检测新兴生物标志物 CCL17/TARC,可能会彻底改变经典霍奇金淋巴瘤 (cHL) 的临床管理。由于临床表现不具特异性且缺乏诊断测试,初级保健诊断具有挑战性,导致诊断延迟。治疗监测会出现假阳性和假阴性结果,导致不必要的化疗毒性或治疗不足,从而影响患者的发病率和死亡率。在这里,我们提出了一种基于利用硫醇化杂双功能交联剂和三明治抗体检测的 CCL17/TARC 电化学免疫传感器,以促进 cHL 的新型初级保健分诊和化疗监测策略。该免疫传感器在临床测试中表现出优异的分析性能;线性度(=0.986)、检测限(194pg/mL)和定量下限(387-50000pg/mL)。该生物传感器基于治疗前干预采集的血清 CCL17/TARC 浓度,能够区分所有 42 名新诊断的 cHL 患者和健康志愿者。该免疫传感器还能够区分所有 7 名 cHL 患者的配对血液样本,分别在治疗前和化疗期间采集,这归因于化疗反应后血清 CCL17/TARC 浓度下降。总的来说,我们首次展示了电化学 CCL17/TARC 生物传感器在 cHL 初级保健分诊和化疗监测方面的潜力,这将对患者产生积极的临床和社会心理影响,同时简化当前的医疗保健途径。