Biomarker Quantitation by NP-MS Tissue Imaging.

描述(申请人提供)：MALDI组织成像，当通过纳米颗粒(NP)基质植入实现时，在我们的实验室和NIDA-IRP正在成熟成为用于生物标记物和药物发现的有用的临床前工具。来自连续冠状切片的可定量再现的图像表明，现在在啮齿动物的疾病和损伤模型中相对定量是可能的。纳米颗粒(NP)基质植入可以对啮齿动物疾病和损伤模型中生物标记物水平的差异进行数值量化。没有一种商业仪器能够对组织进行质量分子成像，其软件能够分析和显示这些高质量的数据集。1)在我们之前的第二阶段下开发的用于分析我们MALDI-Ion Mobility-MS成像系统的多维数据的软件和硬件将得到扩展，以满足这一需求，并将通过先进的材料分析技术，如亚纳米分辨率的蔡司猎户座氦离子显微镜，在将分子图像质量与NP基质的纳米尺度表征相关联方面具有双重用途。2)独特的核壳NP基质的持续生长将继续得益于先进的材料分析，对植入组织后NP的结构和颗粒分布的测量。3)将标准纳入组织表面的方案将尝试证明MALDI-MS成像中的相对和绝对定量的能力。

DESCRIPTION (provided by applicant): MALDI tissue imaging, when enabled by Nanoparticulate (NP) Matrix implantation, is maturing into a useful preclinical tool for biomarker and drug discovery in our laboratory and at NIDA-IRP. Quantitatively reproducible images from serial coronal sections suggest that relative quantitation is now possible in rodent models of disease and injury. Nanoparticulate (NP) matrix implantation allows numerical quantitation of differences in biomarker levels in rodent disease and injury models. No commercial instrument which performs mass spectral molecular imaging of tissues has software capable of analyzing and displaying these quality data sets. 1) Software and hardware developed under our antecedent phase II for analyzing the multidimensional data from our MALDI-Ion Mobility-MS imaging system will be expanded to serve this need and will also have dual use in correlating molecular image quality with the nano-scale characterization of the NP matrices by advance materials analysis techniques such as the subnanometer resolution Zeiss Orion Helium Ion Microscope. 2) The continued growth of unique core shell NP matrices will continue to be aided by advanced materials analysis measurement of the NP structures and particle size distributions after implantation into the tissue. 3) Protocols for standards incorporation into and onto the tissue surface will attempt to prove the capability of relative and absolute quantitation in MALDI-MS imaging.