Ultrasensitive Nanoscale Magnetic Sensors for Label-free Analysis of Cancer

用于癌症无标记分析的超灵敏纳米磁传感器

• 批准号: 7692257
• 负责人: Song Jin
• 金额: $ 15.95万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-24 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7692257
• 关键词: Binding; Blood specimen; Charge; Chemistry; Computers; DNA; Detection; Development; Device Designs; Devices; Elements; Family; Label; Magnetism; Malignant Neoplasms; Measurement; Modeling; Modification; Molecular Analysis; Monitor; Nucleotides; Oligonucleotide Probes; Oligonucleotides; Operative Surgical Procedures; Performance; Preparation; Property; Sampling; Semiconductors; Squid; Staging; Surface; TP53 gene; Technology; Temperature; Time; Training; Transition Elements; Urine; Validation; cancer diagnosis; cost; density; design; detector; electrical measurement; genetic analysis; improved; innovative technologies; magnetic field; mutant; nanocrystal; nanomaterials; nanoscale; new technology; novel; point of care; response; sensor; success; tumor progression

DESCRIPTION (provided by applicant): In this resubmitted application responding to Innovative Technologies for Molecular Analysis of Cancer (FOA CA-07-033), we seek to develop a novel type of sensor technology that exploits the emerging nanoscale dilute magnetic semiconductor (DMS) materials to enable ultrasensitive label-free electrical detection of DNA molecules for genetic analysis of cancer. The sensing mechanism is the following: the semiconducting properties of the properly biofunctionalized DMS nanomaterials are modulated by surface charges upon specific binding of target molecules to surface probe molecules, which leads to significant magnetic property changes that can be detected using highly sensitive giant magnetoresistance (GMR) magnetic field sensors found in computer hard disks. Outperforming any current technologies, the proposed sensors promise to be simple, specific, high throughput, robust, potentially compatible with high density arrays and multiplexing, and potentially boast low cost and good manufacturability on a large scale. In this application, we will demonstrate the proof-of-principle operation and validate the extremely high sensitivity of the proposed sensors using two families of DMS nanomaterials and model DNA samples from the p53 gene. The specific steps are: 1) synthesize and characterize nanomaterials of transition metal doped ZnO and Cr-doped ZnTe, and demonstrate robust ferromagnetism near room temperature; 2) develop and optimize strategies to attach suitable oligonucleotides onto the surface of these nanomaterials for use as the sensing elements of proposed sensors; 3) demonstrate and understand the magnetic property changes upon applying complementary target oligonucleotides from p53 genes to surface modified nanomaterials using a SQUID magnetometer; 4) construct integrated sensor devices using commercial GMR devices, and demonstrate proof-of-principle real-time electrical sensing measurements with model analytes of target oligonucleotides; and 5) evaluate and quantify the sensor response versus DNA concentrations and demonstrate the detection of complementary target p53 oligonucleotide down to concentration of 0.1 femtomolar (fM), and the differentiation of wild type and single nucleotide mismatched mutant p53 at the concentration of 10 fM through the optimization of sensors. The success of this project will enable inexpensive table-top or even handheld turn-key electrical devices that will allow heathcare professionals to perform robust high throughput but yet highly sensitive analysis of urine, serum, and blood samples for the detection and diagnosis of cancer, the monitoring of cancer progression, and the determination of response to therapy with little training and sample preparation in point-of-care settings.

DESCRIPTION (provided by applicant): In this resubmitted application responding to Innovative Technologies for Molecular Analysis of Cancer (FOA CA-07-033), we seek to develop a novel type of sensor technology that exploits the emerging nanoscale dilute magnetic semiconductor (DMS) materials to enable ultrasensitive label-free electrical detection of DNA molecules for genetic analysis of cancer.传感机制是：适当生物功能化的DMS纳米材料的半导体特性受到表面电荷的调节，该靶分子对表面探针分子的特异性结合，这会导致可使用高度敏感的巨型磁场（GMR）磁场的高度敏感的磁性磁场（GMR）在计算机上发现的高度敏感的巨型磁层（GMR）。拟议的传感器胜过任何当前技术的表现都将是简单，特定，高吞吐量，健壮的，有可能与高密度阵列和多重阵列兼容的，并且有可能大规模拥有低成本和良好的生产性。在此应用中，我们将使用两个DMS纳米材料家族和p53基因的DNA样品模型来证明原则运行的原则运算，并验证所提出的传感器的极高灵敏度。具体步骤是：1）合成和表征过渡金属掺杂ZnO和CR掺杂的Znte的纳米材料，并在室温附近演示强大的铁磁性； 2）制定并优化策略，将合适的寡核苷酸连接到这些纳米材料的表面上，以用作提议的传感器的传感元素； 3）在使用鱿鱼磁力计应用于从p53基因到表面修饰的纳米材料的互补靶寡核苷酸时，证明并了解磁性变化； 4）使用商业GMR设备构建集成的传感器设备，并通过靶寡核苷酸模型分析物展示了原则的实时实时电气传感测量；和5）评估和量化传感器响应与DNA浓度，并证明了互补靶标的p53寡核苷酸的检测到浓度为0.1 promtolar（FM），以及通过传感器的优化在10 fm的浓度下，野生型和单核苷酸不匹配的突变体p53的分化。该项目的成功将使廉价的桌面甚至是手持式交钥匙电气设备，这将使Heathcare Professionals对尿液，血清和血液样本进行良好的高吞吐量但高度敏感的分析，以检测和诊断癌症的检测和诊断，对癌症进展的监测以及对几乎没有训练和样本制备的治疗的响应，并在点对上进行了点击式准备。

项目成果

Mesoporous zirconium oxide nanomaterials effectively enrich phosphopeptides for mass spectrometry-based phosphoproteomics.

• DOI: 10.1039/b908788e
• 发表时间: 2009-11-21
• 期刊: Chemical communications (Cambridge, England)
• 作者: Nelson CA;Szczech JR;Xu Q;Lawrence MJ;Jin S;Ge Y
• 通讯作者: Ge Y

Synthesis and magnetic properties of Gd doped EuS nanocrystals with enhanced Curie temperatures.

• DOI: 10.1021/ja104314c
• 发表时间: 2010-11-17
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Selinsky, Rachel S.;Han, Jae Hyo;Perez, Elvin A. Morales;Guzei, Ilia A.;Jin, Song
• 通讯作者: Jin, Song

Element-specific magnetometry of EuS nanocrystals.

EuS 纳米晶体的元素特异性磁力测定。

• DOI: 10.1063/1.3251777
• 发表时间: 2009
• 期刊: Applied physics letters
• 影响因子: 4
• 作者: Selinsky,RachelS;Keavney,DavidJ;Bierman,MatthewJ;Jin,Song
• 通讯作者: Jin,Song

Effective enrichment and mass spectrometry analysis of phosphopeptides using mesoporous metal oxide nanomaterials.

• DOI: 10.1021/ac100877a
• 发表时间: 2010-09-01
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Nelson, Cory A.;Szczech, Jeannine R.;Dooley, Chad J.;Xu, Qingge;Lawrence, Matthew J.;Zhu, Haoyue;Jin, Song;Ge, Ying
• 通讯作者: Ge, Ying