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.

我们正在研制磁纳米传感器蛋白质芯片和基于磁纳米传感器的多功能磁分选仪。 这些纳米颗粒允许离散的生物分子结合事件快速转化为电信号。 这些纳米技术可以在不到一小时的时间内检测到单个分子水平的目标分子。 这样的灵敏度和检测速度对于当前技术是不可用的或不切实际的。两个主要 该项目的组成部分，磁纳米传感器芯片和基于纳米颗粒的磁性分选机，可以 独立地或联合地操作。这种巨纳米传感器芯片将识别和定量蛋白质 小鼠和人血清样品中的肿瘤标志物和相关蛋白质谱， 敏感性和特异性。这些磁纳米传感器的功能表现出显着的电阻变化 其仅由外部磁场感应，因此对溶液条件不敏感， 缓冲液、pH值或离子强度。生物传感是通过亲和标记传感器 表面和磁性纳米颗粒同时附着到特定靶向的不同区域 生物分子然后，磁纳米传感器检测生物分子的附着， 由磁性纳米颗粒诱导的磁场。对于足够小的传感器和适当的 磁性纳米颗粒标签，由于单个的亲和键合，特定的分子可以被检测为简单的 传感器电阻发生变化，因此不会出现昂贵的激励源或远程传感器 必需的.磁性分选器将快速分离生物分子。基于可调磁性 通过使它们以不同的速度偏转， 在给定的磁场和梯度下。特别是，我们将扩展技术， 表征来自小鼠和人血清样品的循环肿瘤细胞，并随后分析 用于监测癌症治疗的细胞裂解物。 与公共卫生的相关性：磁纳米传感器蛋白质芯片和多路磁分选仪 在这个项目中开发的最终可以被癌症生物学家和临床肿瘤学家用来快速 以自动化和高通量的方式跟踪临床样品中的许多蛋白质。通过基本 将患者血清或组织样品施加到磁纳米传感器芯片上，可以容易地确定 存在或不存在大量肿瘤标志物。此外，多路磁分选机可以 进行循环肿瘤靶标的高通量富集或杂质的消耗，改善复杂性， 蛋白质组学分析，目前遭受不良的信号噪声比。