A MALDI LTQ Orbitrap XL Mass Spectrometer for BioImaging

用于生物成像的 MALDI LTQ Orbitrap XL 质谱仪

• 批准号: 8826301
• 负责人: Veronique Dartois
• 金额: $ 41.79万
• 依托单位: RBHS-NEW JERSEY MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8826301
• 关键词: Biological Markers; Biopsy; Collaborations; Communicable Diseases; Detection; Funding; HIV-1; Histocompatibility Testing; Housing; Image; Imagery; In Situ; Infectious Agent; Infectious Diseases Research; Institutes; Label; Laboratories; Lipids; Mass Spectrum Analysis; Neuraxis; New Jersey; Outcome; Pathology; Pharmaceutical Preparations; Request for Proposals; Research; Research Institute; Research Personnel; Resolution; Sampling; Slice; Spatial Distribution; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Technology; Tissues; United States National Institutes of Health; Universities; Virulence; animal tissue; base; bioimaging; biosafety level 3 facility; combat; drug candidate; drug discovery; experience; human tissue; indexing; instrumentation; mass spectrometer; medical schools; microbial; novel; pathogen; public health research; tool; two-dimensional

 DESCRIPTION (provided by applicant): With this proposal, we are requesting funds to acquire a MALDI LTQ Orbitrap XL mass spectrometer from Thermo Scientific for bioimaging at the Public Health Research Institute (PHRI), which will be used under biosafety level 3 (BSL3) biocontainment within the Rutgers Regional Biocontainment Laboratory (RBL). PHRI is a Center within New Jersey Medical School/ Rutgers, the State University of New Jersey. The RBL is one of thirteen national facilities designated by the National Institutes of Health (NIH) for research n biosafety level 3 (BSL3) infectious agents, http://njms.Rutgers.edu/research/rbl/index.cfm. The mass spectrometer will be used to support infectious disease research in the BSL3 facility within the Analytical Imaging Shared Facility. MALDI Mass Spectrometry Imaging (MSI) involves visualization of the 2-dimensional spatial distribution of drugs, drug candidates and discovery compounds and their metabolites, lipids and biomarkers within label-free thin slices of sample, such as animal or human tissue/biopsies, with a spatial resolution of around 10-100mm. The imaging resolution enables the detection of differential distribution and concentration gradients across tissue types within a single tissue slice. For example, adjacent infected and uninfected regions can be compared. The unmatched capabilities of MALDI MS imaging as an in-situ analysis tool offers parallel imaging of potentially thousands of analytes at up to cellular resolution. MSI is a fast evolving technology that can take research on infectious disease pathology and drug discovery to a new level. Our experience housing an imaging mass spectrometer in BSL3 facilities (we are currently the only lab to do so) has demonstrated that demand for this type of instrumentation is very high and increasing. Indeed, we currently cannot accommodate the users need within our institute and have had to turn down multiple requests for collaboration from external investigators. In addition to expanding our user base, the MALDI LTQ Orbitrap XL would bring novel capabilities to PHRI, such as imaging of lipids at the host-pathogen interface, imaging of new drug molecules to eradicate HIV-1 from central nervous system reservoirs, and imaging of markers of microbial virulence. A new MALDI Orbitrap XL in our well-supported facility would expand and promote opportunities for novel BSL3 pathogen research. The outcome will be new and better ways to combat infectious diseases.

 描述（由申请人提供）：通过本提案，我们申请资金从Thermo Scientific购买MALDI LTQ Orbitrap XL质谱仪，用于公共卫生研究所（PHRI）的生物成像，该质谱仪将在罗格斯地区生物防护实验室（RBL）内的生物安全3级（BSL 3）生物防护下使用。PHRI是新泽西医学院/罗格斯大学和新泽西州立大学的一个中心。RBL是美国国立卫生研究院（NIH）指定的13个国家机构之一，用于研究生物安全3级（BSL 3）传染性病原体，www.example.com。质谱仪将用于支持分析成像共享设施内BSL 3设施的传染病研究。MALDI质谱成像（MSI）涉及药物、候选药物和发现化合物及其代谢物、脂质和生物标志物在样品（例如动物或人体组织/活检）的无标记薄片内的二维空间分布的可视化，空间分辨率约为10 - 100 mm。成像分辨率使得能够检测单个组织切片内跨组织类型的差异分布和浓度梯度。例如，可以比较相邻的感染区域和未感染区域。MALDI MS成像作为原位分析工具的无与伦比的功能提供了高达细胞分辨率的潜在数千种分析物的并行成像。MSI是一种快速发展的技术，可以将传染病病理学和药物发现的研究提升到一个新的水平。我们在BSL 3设施中安装成像质谱仪的经验（我们是目前唯一一家这样做的实验室）表明，对这种仪器的需求非常高，而且还在不断增长。事实上，我们目前无法满足我们研究所内的用户需求，不得不拒绝外部调查人员的多项合作请求。除了扩大我们的用户群外，MALDI LTQ Orbitrap XL还将为PHRI带来新的功能，例如在宿主-病原体界面处的脂质成像，从中枢神经系统储库中根除HIV-1的新药分子成像，以及微生物毒力标记物的成像。在我们得到良好支持的设施中，新的MALDI Orbitrap XL将扩大和促进新型BSL 3病原体研究的机会。其结果将是新的和更好的方法来防治传染病。

项目成果

Bedaquiline and Pyrazinamide Treatment Responses Are Affected by Pulmonary Lesion Heterogeneity in Mycobacterium tuberculosis Infected C3HeB/FeJ Mice.

Bedaquiline和吡嗪酰胺治疗反应受肺病变异质性的影响，感染了C3HEB/FEJ小鼠。

• DOI: 10.1021/acsinfecdis.5b00127
• 发表时间: 2016-04-08
• 期刊: ACS infectious diseases
• 影响因子: 5.3
• 作者: Irwin SM;Prideaux B;Lyon ER;Zimmerman MD;Brooks EJ;Schrupp CA;Chen C;Reichlen MJ;Asay BC;Voskuil MI;Nuermberger EL;Andries K;Lyons MA;Dartois V;Lenaerts AJ
• 通讯作者: Lenaerts AJ

Lesion Penetration and Activity Limit the Utility of Second-Line Injectable Agents in Pulmonary Tuberculosis.

• DOI: 10.1128/aac.00506-21
• 发表时间: 2021-09-17
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Ernest JP;Sarathy J;Wang N;Kaya F;Zimmerman MD;Strydom N;Wang H;Xie M;Gengenbacher M;Via LE;Barry CE 3rd;Carter CL;Savic RM;Dartois V
• 通讯作者: Dartois V

Impact of immunopathology on the antituberculous activity of pyrazinamide.

• DOI: 10.1084/jem.20180518
• 发表时间: 2018-08-06
• 期刊: The Journal of experimental medicine
• 作者: Blanc L;Sarathy JP;Alvarez Cabrera N;O'Brien P;Dias-Freedman I;Mina M;Sacchettini J;Savic RM;Gengenbacher M;Podell BK;Prideaux B;Ioerger T;Dick T;Dartois V
• 通讯作者: Dartois V

Heterogeneous drug penetrance of veliparib and carboplatin measured in triple negative breast tumors.

• DOI: 10.1186/s13058-017-0896-4
• 发表时间: 2017-09-11
• 期刊: Breast cancer research : BCR
• 作者: Bartelink IH;Prideaux B;Krings G;Wilmes L;Lee PRE;Bo P;Hann B;Coppé JP;Heditsian D;Swigart-Brown L;Jones EF;Magnitsky S;Keizer RJ;de Vries N;Rosing H;Pawlowska N;Thomas S;Dhawan M;Aggarwal R;Munster PN;Esserman LJ;Ruan W;Wu AHB;Yee D;Dartois V;Savic RM;Wolf DM;van 't Veer L
• 通讯作者: van 't Veer L

An In Vitro Caseum Binding Assay that Predicts Drug Penetration in Tuberculosis Lesions.

预测结核病灶中药物渗透的体外酪蛋白结合测定。

• DOI: 10.3791/55559
• 发表时间: 2017
• 期刊: Journal of visualized experiments : JoVE
• 作者: Sarathy,JansyP;Liang,Hsin-PinHo;Weiner,Danielle;Gonzales,Jacqueline;Via,LauraE;Dartois,Véronique
• 通讯作者: Dartois,Véronique