Point-of-care testing: a disposable label-free electrochemical CA125 and HE4 immunosensors for early detection of ovarian cancer

IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Biomedical Microdevices Pub Date : 2023-05-04 DOI:10.1007/s10544-023-00659-x
Melike Bilgi Kamaç, Muhammed Altun, Merve Yılmaz, Ayla Yılmaz Aktan, Soner Aktan, Mustafa Kemal Sezgintürk
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引用次数: 2

Abstract

Cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are critical biomarkers for ovarian cancer diagnosis and progression monitoring; therefore, sensitive determination of their levels in body fluids is crucial. In recent study, label-free CA125 and HE4 immunosensors were prepared using disposable screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles for the sensitive, fast, and practical determination of CA125 and HE4. Differential pulse voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy methods were used for the electrochemical determination of antigens in four different linear ranges (1-100 pg mL− 1, 0.01-10 ng mL− 1, 10–50 ng mL− 1, and 50–500 ng mL− 1). High sensitivity, low limit of detection, and limit of quantification were obtained for each linear range with a correlation coefficient above 0.99. The application stability of CA125 and HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. Immunosensors showed high selectivity in nine different antigen mixtures. The reusability of the immunosensors has been tested up to 9 cycles. The Risk of Ovarian Malignancy Algorithm score% values were calculated using the concentration of CA125 and HE4 in the blood serum and evaluated in terms of ovarian cancer risk. For the point-of-care testing, CA125 and HE4 levels at pg mL− 1 concentration were measured in blood serum samples using the developed immunosensors and a hand-held electrochemical reader in approximately 20–30 s, and high recoveries were obtained. These disposable label-free immunosensors are user-friendly and can be used in point-of-care tests for rapid and practical detection of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

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即时检测:用于卵巢癌早期检测的一次性无标签电化学CA125和HE4免疫传感器
癌抗原125 (CA125)和人附睾分泌蛋白4 (HE4)是卵巢癌诊断和进展监测的重要生物标志物;因此,灵敏地测定它们在体液中的含量是至关重要的。在最近的研究中,我们利用利用还原氧化石墨烯、聚硫氨酸和金纳米颗粒修饰的一次性丝网印刷碳电极制备了无标记的CA125和HE4免疫传感器,以实现CA125和HE4的灵敏、快速和实用测定。采用差分脉冲伏安法、方波伏安法和电化学阻抗谱法在1 ~ 100 pg mL−1、0.01 ~ 10 ng mL−1、10 ~ 50 ng mL−1和50 ~ 500 ng mL−1四个线性范围内测定抗原。各线性范围灵敏度高、检出限低、定量限低,相关系数均在0.99以上。测定CA125和HE4免疫传感器的应用稳定性为60天,测定贮藏稳定性为16周。免疫传感器在9种不同抗原混合物中显示出高选择性。免疫传感器的可重复使用性已经测试了9个周期。采用血清CA125和HE4浓度计算卵巢恶性肿瘤风险算法评分%值,并根据卵巢癌风险进行评价。在护理点检测中,使用开发的免疫传感器和手持式电化学读取器在大约20-30秒内测量血清样品中pg mL−1浓度下的CA125和HE4水平,获得了高回收率。这些一次性无标签免疫传感器是用户友好的,可用于即时检测CA125和HE4,具有高选择性、灵敏度和可重复性。
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来源期刊
Biomedical Microdevices
Biomedical Microdevices 工程技术-工程:生物医学
CiteScore
6.90
自引率
3.60%
发文量
32
审稿时长
6 months
期刊介绍: Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology. General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules. Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.
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