Development of a Hand-Held Cancer Biomarker Monitor

项目描述（由申请人提供）：该项目将开发一种基于免疫层析技术和纳米粒子电化学免疫分析的手持式癌症生物标志物监测仪，用于快速、灵敏、低成本地检测人类血液样本中的癌症生物标志物。包括癌胚抗原（CEA）、CA15-3和人乳蛋白在内的乳腺癌生物标志物将被用作模型生物标志物来证明原理。该装置的原理是基于纳米粒子驱动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，方便地实现了电化学免疫分析的多重功能和显著的信号放大。结合免疫层析分离技术，新型生物传感器微分析装置将为多种乳腺癌生物标志物的快速检测提供一种便携、灵敏、简单、低成本的工具。整个分析时间将少于10分钟，检出限比截止值低10倍。该装置将用于检测乳腺癌患者的样本，并将用传统的酶联免疫吸附试验（ELISA）验证结果。如果该项目成功，该装置将成为帮助癌症早期诊断、监测治疗反应和为癌症患者提供实时预后信息的有效创新工具。该装置还可用于其他癌症生物标志物的检测。

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.