Development of a Hand-Held Cancer Biomarker Monitor

描述(申请人提供)：该项目将开发一种基于免疫层析技术和基于纳米颗粒的电化学免疫分析的手持式癌症生物标记物监测器，用于快速、灵敏和低成本地检测人体血液样本中的癌症生物标记物。乳腺癌生物标记物包括癌胚抗原(CEA)、CA15-3和人乳巨球蛋白将作为模型生物标记物来论证原理的证明。所提出的装置的原理是基于纳米粒子动力的多重生物电化学免疫检测和免疫层析分离技术。利用多个金属磷酸盐纳米颗粒标记，可以方便地实现电化学免疫分析的多重能力和显著的信号放大。与免疫层析分离技术相结合，新的生物传感器微量分析设备将为快速检测多个乳腺癌生物标志物提供一种便携式、灵敏、简单和低成本的工具。完整的分析时间将不到10分钟，检测下限将低于截止值的10倍。该设备将用于检测乳腺癌患者的样本，结果将通过传统的酶联免疫吸附试验(ELISA)进行验证。如果该项目成功，建议的设备将成为帮助癌症早期诊断、监测治疗反应和提供癌症患者实时预后信息的有效和创新的工具。该装置还可用于其他癌症生物标志物的检测。 公共卫生相关性：癌症是全球范围内一个重大且日益严重的公共卫生问题。在美国，它是仅次于心脏病的第二大死因。据估计，约有565,650名美国人预计将死于癌症，每天超过1,500人(癌症事实和数字，2008年)。降低死亡率的关键是尽早发现癌症。然而，大多数患者在晚期被诊断为癌症。例如，在美国，72%的肺癌患者、57%的结直肠癌患者和34%的乳腺癌患者被诊断为晚期。传统上，癌症的诊断、筛查和分期以及对治疗反应的评估主要基于乳房X光检查、磁共振成像(MRI)和活检。这些方法虽然有很高的检测率，但昂贵、耗时、侵入性和不适，在预测给定肿瘤的进展潜力和治疗反应方面有很大的局限性。因此，需要一种廉价、非侵入性、快速、简单、灵敏度和特异度高的工具来检测癌症生物标志物，以辅助癌症早期诊断、监测治疗反应和提供癌症患者的实时预后信息。为了快速、灵敏、低成本和多重检测人体血液中的癌症生物标志物，迫切需要研制一种手持式癌症生物标志物监测仪。乳腺癌生物标记物包括癌胚抗原(CEA)、CA15-3和人乳巨球蛋白(HMAM)将作为模型来演示原理的证明。如果该项目成功，开发的设备还可以应用于血液等生物液中其他肿瘤生物标志物的非侵入性监测。

DESCRIPTION (provided by applicant): The project will develop a Hand-Held cancer biomarker monitor based on imunochromatographic technology and nanoparticle based electrochemical immunoassay for rapid, sensitive, and low- cost detection of cancer biomarkers in human blood samples. Breast cancer biomarkers including carcinoenbryonic antigen (CEA), CA15-3 and human mammaglobin will be used as model biomarkers to demonstrate the proof of principle. The principle of the proposed device is based on nanoparticle-powered multiplex bioelectrochemical immunodetection and immunochromatographic separation technique. The multiplex capabilities and significant signal amplification of electrochemical immunoassay are realized conveniently by the use of multiple metallic phosphate nanoparticle labels. Integrating with immunochromatographic separation technology, the new biosensor microanalysis device will provide a portable, sensitive, simple, and low-cost tool for the rapid detection of multiple breast cancer biomarkers. The complete assay time will be less than 10 minutes and the detection limits are 10 times lower than the cutoff values. The device will be used to detect the samples from breast cancer patients and the results will be validated with traditional enzyme-linked immunosorbent assay (ELISA). If the project is successful, the proposed device will be an effective and innovative tool in aiding early cancer diagnosis, monitoring response to therapy and providing real-time prognostic information in patients with cancers. The developed device can also be applied for the detection of other cancer biomarkers. PUBLIC HEALTH RELEVANCE: Cancer is a major and increasing public health problem worldwide. In US, it is the second leading cause of death, just behind heart disease. It is estimated around about 565,650 Americans are expected to die of cancer, more than 1,500 people a day (Cancer Facts and Figures, 2008). The key to decrease the death rate is to detect the cancers as early as possible. However, the majority of patients are diagnosed as having cancer at a late stage. For example, 72% of lung cancer patients, 57% of colorectal cancer patients, and 34% of breast cancer patients in the US are diagnosed at late stage. Traditionally, the diagnosis, screening and staging of cancer, as well as the evaluation of response to therapy have been primarily based on mammography, magnetic resonance imaging (MRI) and biopsy. These methods, although having a high detection rate, are expensive, time-consuming, invasive and uncomfortable, and have significant limitations for predicting a given tumor's potential for progression and response to treatment. There is, therefore, a need for an inexpensive, noninvasive, quick and simple tool with a high sensitivity and specificity for the detection of cancer biomarkers in aiding early cancer diagnosis, monitoring response to therapy and providing real-time prognostic information in patients with cancers. The proposed research for developing a hand-held cancer biomarker monitor is greatly needed for rapid, sensitive, low- cost, and multiplex detection of cancer biomarkers in human blood. Breast cancer biomarkers including carcinoenbryonic antigen (CEA), CA15-3 and human mammaglobin (HMAM) will be used as models to demonstrate the proof of principle. If the project is successful, the developed device can also be applied for the noninvasive monitoring of other tumor biomarkers in biological fluids such as blood.