Magneto-Nano Protein Chip and Multiplex Sorter for Monitoring Tumor Markers

用于监测肿瘤标志物的磁纳米蛋白质芯片和多重分选机

• 批准号: 7067893
• 负责人: SHAN X. WANG
• 金额: $ 43.54万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067893
• 关键词: biomarker; biomedical equipment development; clinical research; cooperative study; flow cytometry; immunomagnetic separation; magnetism; microarray technology; microprocessor /microchip; nanotechnology; neoplasm /cancer diagnosis; protein quantitation /detection

We are developing a magneto-nano sensor protein chip and a multiplex magnetic sorter based on magnetic nanoparticles that allow rapid conversion of discrete biomolecule binding events into electrical signals. These nanotechnologies can detect target molecules down to the single molecule level in less than an hour. Such sensitivity and detection speed are unavailable or impractical with current technologies. The two main components of this project, a magneto-nano sensor chip and a nanoparticle-based magnetic sorter, can operate independently or in conjunction. The maqneto-nano sensor chip will recognize and quantitate protein tumor markers and relevant protein profiles in mouse and human serum samples with unprecedented sensitivity and specificity. These magneto-nano sensors function by exhibiting significant resistance changes which are induced solely by external magnetic fields and are therefore insensitive to solution conditions such as buffers, pH or ionic strength. Biological sensing is accomplished by affinity labeling both the sensor surface and magnetic nanoparticles to simultaneously attach to distinct domains of specifically targeted biological molecules. The magneto-nano sensor then detects the attachment of the biomolecules through the magnetic field induced by the magnetic nanoparticles. For sufficiently small sensors and appropriate magnetic nanoparticle tags, affinity bonding due to a single, specific molecule can be detected as a simple change in the sensor electrical resistance so that expensive excitation sources or remote sensors are not required. The magnetic sorter will rapidly segregate biomolecules. based upon the tunable magnetic properties of the magnetic nanoparticles which bind them, by causing them to deflect at different speeds under a given magnetic field and gradient. In particular, we will be extending technologies to capture and characterize circulating tumor cells from mouse and human serum samples and subsequently analyze the cell lysate for monitoring cancer therapy. Relevance to public health: The magneto-nano sensor protein chips and multiplex magnetic sorter developed in this project can ultimately be used by cancer biologists as well as clinical oncologists to rapidly follow numerous proteins in clinical samples in an automated and high throughput fashion. By essentially applying patient serum or tissue samples to the magneto-nano sensor chip, one can readily ascertain the presence or absence of a large number of tumor markers. Additionally, the multiplex magnetic sorter can perform high throughput enrichment of circulating tumor targets or depletion of impurities, improving complex proteomic analysis that currently suffers from poor signal-to-noise ratio.

我们正在开发基于磁性的磁纳诺传感器蛋白芯片和一个基于磁性的多重磁磁划； 允许将离散生物分子结合事件快速转化为电信号的纳米颗粒。 这些纳米技术可以在不到一个小时的时间内检测到靶分子至单分子水平。 这种灵敏度和检测速度对当前技术不可用或不切实际。两个主 该项目的组件，一种磁光纳米传感器芯片和基于纳米颗粒的磁性混蛋，可以 独立或共同操作。 Maqneto-Nano传感器芯片将识别和定量蛋白质 肿瘤标记和相关的蛋白质谱在小鼠和人血清样品中具有前所未有的 灵敏度和特异性。这些磁通传感器通过表现出明显的电阻变化来起作用 仅由外部磁场诱导，因此对溶液条件不敏感 作为缓冲，pH或离子强度。生物传感是通过将两个传感器标记来实现的 表面和磁性纳米颗粒同时连接到特定靶向的不同域 生物分子。然后，Magneto-Nano传感器检测到生物分子的附着 磁场由磁性纳米颗粒诱导。对于足够小的传感器和合适的传感器 磁性纳米颗粒标签，由于单个特定分子而引起的亲和力键合可检测到一个简单的 传感器电阻的变化，以使昂贵的激发源或遥控传感器不是 必需的。磁性扰格器将迅速分离生物分子。基于可调磁 磁性纳米颗粒的特性通过使它们以不同的速度偏转来结合它们 在给定的磁场和梯度下。特别是，我们将扩展技术以捕获和 表征来自小鼠和人血清样品的循环肿瘤细胞，然后分析 细胞裂解物用于监测癌症治疗。 与公共卫生的相关性：磁纳诺传感器蛋白芯片和多重磁性分辨率 在该项目中开发的癌症生物学家以及临床肿瘤学家最终可以使用 以自动化和高通量方式在临床样品中遵循许多蛋白质。从本质上讲 将患者血清或组织样品应用于磁纳诺传感器芯片，可以轻松确定 存在或不存在大量肿瘤标记。此外，多路复用磁划者可以 对循环肿瘤靶标或杂质耗尽的高吞吐量富集，改善复合物 蛋白质组学分析目前遭受信噪比差。