Transient Metabolite Detection for Single-Cell Metabolomics and Diagnostics

用于单细胞代谢组学和诊断的瞬时代谢物检测

• 批准号: 8358296
• 负责人: Daniel Alan Heller
• 金额: $ 274.35万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358296
• 关键词: Benchmarking; Binding; Cancer Biology; Cells; Clinical Engineering; Data; Detection; Development; Diagnostic; Event; Fingerprint; Fluorescence; Future; Genomics; Life; Ligands; Malignant Neoplasms; Measurement; Measures; Metabolic; Metabolism; Nanotubes; Neoplasm Metastasis; Pharmaceutical Preparations; Research Personnel; Staging; Techniques; Time; Toxicology; Work; abstracting; cancer cell; cancer diagnosis; clinically relevant; functional genomics; human tissue; improved; metabolomics; nanomaterials; public health relevance; sensor; single walled carbon nanotube; small molecule

DESCRIPTION (Provided by the applicant) Abstract: This work will develop the capability to spatially detect a wide range of metabolites quantitatively and in real- time within a single cell. Few techniques are available to measure metabolite concentrations, although they are a key indicator of a cell's genomic expression, and the capability of metabolite flux measurements, resolved spatially and transiently, is heretofore unrealized. This project will provide these abilities to benefit several fields, including metabolomics, functional genomics, toxicology, cancer biology, metabolic engineering, and clinical diagnostics. The sensors will consist of single-walled carbon nanotubes which emit photostable near-infrared fluorescence which is highly environmentally sensitive. The nanotubes will be functionalized with ligands which bind to important metabolites and the binding event will be transduced by spectral shifts in the nanotube's emission. The investigator's group will introduce these nanotube sensors into live cells in order to answer important questions relevant to cancer biology and cell metabolism. Concomitantly, the team will work towards the rapid and real-time detection of clinically-relevant metabolites for early cancer diagnosis and the benchmarking of metastasis. We will also re-construct multiplexed metabolite data in order to conduct single- cell metabolomic fingerprinting. Public Health Relevance: Metabolites are small molecules produced in the body which may be used in the future to detect cancer at earlier stages, better understand the biology of cancer, and improve the development of important drugs. This project develops sensors using nanomaterials to detect many classes of metabolites within single cells and in human tissues.

描述（由申请人提供） 摘要：这项工作将开发在单个细胞内定量、实时地空间检测多种代谢物的能力。尽管代谢物浓度是细胞基因组表达的关键指标，但很少有技术可用于测量代谢物浓度，并且迄今为止尚未实现空间和瞬时解析代谢物通量测量的能力。该项目将提供这些能力，使多个领域受益，包括代谢组学、功能基因组学、毒理学、癌症生物学、代谢工程和临床诊断。这些传感器将由单壁碳纳米管组成，可发射对环境高度敏感的光稳定近红外荧光。纳米管将用与重要代谢物结合的配体进行功能化，并且结合事件将通过纳米管发射的光谱变化进行转导。研究小组将把这些纳米管传感器引入活细胞中，以回答与癌症生物学和细胞代谢相关的重要问题。与此同时，该团队将致力于快速实时检测临床相关代谢物，以进行早期癌症诊断和转移的基准测试。我们还将重新构建多重代谢物数据，以进行单细胞代谢组指纹分析。 公共健康相关性：代谢物是体内产生的小分子，将来可用于早期检测癌症，更好地了解癌症的生物学，并改进重要药物的开发。该项目开发使用纳米材料的传感器来检测单细胞和人体组织内的多种代谢物。

项目成果

Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant.

通过光学纳米传感器植入物进行非侵入性卵巢癌生物标志物检测。

• 发表时间: 2018-04
• 影响因子: 13.6
• 作者: Williams, Ryan M;Lee, Christopher;Galassi, Thomas V;Harvey, Jackson D;Leicher, Rachel;Sirenko, Maria;Dorso, Madeline A;Shah, Janki;Olvera, Narciso;Dao, Fanny;Levine, Douglas A;Heller, Daniel A
• 通讯作者: Heller, Daniel A

Helical polycarbodiimide cloaking of carbon nanotubes enables inter-nanotube exciton energy transfer modulation.

碳纳米管的螺旋聚碳二亚胺隐形能够实现纳米管间激子能量转移调制。

• 发表时间: 2014-11-05
• 影响因子: 15
• 作者: Budhathoki;Jena, Prakrit V;Roxbury, Daniel;Heller, Daniel A
• 通讯作者: Heller, Daniel A

A Fluorescent Carbon Nanotube Sensor Detects the Metastatic Prostate Cancer Biomarker uPA.

荧光碳纳米管传感器检测转移性前列腺癌生物标志物 uPA。

• 发表时间: 2018
• 影响因子: 8.9
• 作者: Williams, Ryan M;Lee, Christopher;Heller, Daniel A
• 通讯作者: Heller, Daniel A

Hyperspectral Microscopy of Near-Infrared Fluorescence Enables 17-Chirality Carbon Nanotube Imaging.

近红外荧光高光谱显微镜可实现 17 手性碳纳米管成像。

• 发表时间: 2015-09-21
• 影响因子: 4.6
• 作者: Roxbury, Daniel;Jena, Prakrit V;Williams, Ryan M;Enyedi, Balázs;Niethammer, Philipp;Marcet, Stéphane;Verhaegen, Marc;Blais;Heller, Daniel A
• 通讯作者: Heller, Daniel A

Tumour-specific PI3K inhibition via nanoparticle-targeted delivery in head and neck squamous cell carcinoma.

通过纳米颗粒靶向递送对头颈鳞状细胞癌进行肿瘤特异性 PI3K 抑制。

• 发表时间: 2017-02-13
• 影响因子: 16.6
• 作者: Mizrachi, Aviram;Shamay, Yosi;Shah, Janki;Brook, Samuel;Soong, Joanne;Rajasekhar, Vinagolu K;Humm, John L;Healey, John H;Powell, Simon N;Baselga, José;Heller, Daniel A;Haimovitz;Scaltriti, Maurizio
• 通讯作者: Scaltriti, Maurizio