Magnetoresistive Sensor Platform for Parallel Cancer Marker Detection

描述(申请人提供)：早期诊断对癌症和许多其他疾病的治疗至关重要。然而，今天的诊断方法往往依赖于对个别疾病标志物的检测，在少数情况下，这些疾病标志物在早期诊断中的价值有限。重要的是，越来越多的证据表明，通过检测血清样本中大量相关生物标志物的存在，可以提高诊断、预后和分层的准确性。为此，建立一个能够高吞吐量和高检测灵敏度的平台是至关重要的第一步。这样的平台还必须处理数量极其有限的样品，并满足越来越短的周转时间的需求。这些相同的属性是发现和筛选新的疾病标志物方面取得进展的核心。犹他大学的这一多学科项目旨在创建一种基于纳米技术的新平台--多路磁阻免疫分析系统--用于癌症的早期检测。它将胰腺癌作为平台开发和性能验证的第一步。胰腺癌是美国癌症相关死亡的第四大常见原因。5年生存率约为4%，是所有癌症中最低的，这突显了该项目的重要性。项目目标包括：(1)显著提高磁阻传感器性能的战略(例如，噪声和信号属性、内部响应校准、捕获基板阵列上地址的设计和布局、传感器(即读取器)和扫描阵列之间的分离以及信号转导的分析描述符)；(2)合成新型磁性纳米颗粒作为具有强烈磁性特征的标签；(3)整合流体力学方面的进展，以增加进入固相阵列的样品和标签的流量，作为减少TAT和同时降低背景信号的手段；以及(4)设计和建造仪器，在不到一分钟的时间内定量读取数千个免疫分析地址。相关性(见说明)：该项目的重点是开发一个基于纳米技术的癌症早期诊断平台。我们的目标是构建和测试这项技术，它基于读取当今大多数笔记本电脑和便携式音乐媒体播放器中硬盘驱动器的磁学概念，将以前所未有的灵敏度同时快速检测大量疾病标记。

DESCRIPTION (provided by applicant): Early diagnosis is critical to the treatment of cancer and many other diseases. Today's diagnostic methods, however, often rely on the detection of individual and, in a few instances, small numbers of disease markers that have limited value in early diagnosis. Importantly, there is a growing body of evidence demonstrating that the diagnostic, prognostic, and stratification accuracy can be improved by detecting the presence of a large number of relevant biomarkers in serum samples. To this end, the creation of a platform capable of high throughput and high detection sensitivity stands as a vital first step. Such a platform must also handle samples of preciously limited volume and meet the demand for ever shorter turn-around-times. These same attributes are at the heart of advances in the discovery and screening of new disease markers. This multidisciplinary project at the University of Utah seeks to create a new nanotechnology-based platform - the multiplexed magnetoresistive immunoassay (mMRIA) system - for the early detection of cancer. It targets pancreatic cancer as the first step in platform development and performance validation. Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States. The 5-year survival rate of ~4%, the lowest of any cancer, underscores the importance of the project. Project goals include: (1) strategies to markedly enhance magnetoresistive sensor performance (e.g., noise and signal attributes, internal response calibration, design and layout of the addresses on the capture substrate array, separation between sensor (i.e., reader) and scanned array, and analytical descriptors of signal transduction); (2) synthesis of novel magnetic nanoparticles to serve as labels with a strong magnetic signature; (3) integration of advances in hydrodynamics to increase sample and label flux to the solid phase array as a means to reduce TAT and simultaneously lower the background signal; and (4) design and construction of instrumentation to quantitatively read thousands of immunoassay addresses in less than one minute. RELEVANCE (See instructions): This project is focused on the development of a nanotechnology-based platform for the early diagnosis of cancer. The goal is to construct and test this technology, which is based on the magnetics concepts that read the hard disk drive in most of today's laptop computers and portable music media players, that will simultaneously and rapidly detect large numbers of disease markers at unprecedented levels of sensitivity.