Development of a Hand-Held Cancer Biomarker Monitor

描述（由申请人提供）：该项目将开发一种基于免疫色谱技术和基于纳米颗粒的电化学免疫测定的手持式癌症生物标志物监测仪，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志物。乳腺癌生物标志物，包括癌胚抗原（CEA）、CA 15 -3和人乳腺珠蛋白将用作模型生物标志物，以证明原理证明。所提出的装置的原理是基于纳米粒子供电的多重生物电化学免疫检测和免疫色谱分离技术。通过使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。结合免疫层析分离技术，新的生物传感器微量分析装置将提供一个便携，灵敏，简单，低成本的工具，快速检测多种乳腺癌生物标志物。完整的检测时间将少于10分钟，检测限比截止值低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）对结果进行验证。如果该项目成功，该设备将成为帮助早期癌症诊断，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工具。所开发的设备也可用于检测其他癌症生物标志物。 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，它是第二大死亡原因，仅次于心脏病。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）。降低死亡率的关键是尽早发现癌症。然而，大多数患者被诊断为晚期癌症。例如，在美国，72%的肺癌患者、57%的结直肠癌患者和34%的乳腺癌患者在晚期被诊断出来。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线摄影、磁共振成像（MRI）和活检。这些方法虽然具有高检测率，但昂贵、耗时、侵入性和不舒适，并且对于预测给定肿瘤的进展潜力和对治疗的反应具有显著的限制。因此，需要一种廉价、非侵入性、快速和简单的工具，其具有高灵敏度和特异性，用于检测癌症生物标志物，以帮助早期癌症诊断、监测对治疗的反应并提供癌症患者的实时预后信息。非常需要用于开发手持式癌症生物标志物监测器的所提出的研究，以快速、灵敏、低成本和多重检测人血液中的癌症生物标志物。乳腺癌生物标志物，包括癌胚抗原（CEA），CA 15 -3和人乳房珠蛋白（HMAM）将被用作模型，以证明原理的证据。如果该项目成功，所开发的设备还可以应用于血液等生物液体中其他肿瘤生物标志物的无创监测。

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.