IDBR: TYPE A Ultrahigh Spatial Resolution Sub-organelle Molecular Mass Spectrometry Imaging Using Liquid Metal Ion Beam Desorption and Radiofrequency Ionization

IDBR：使用液态金属离子束解吸和射频电离的 A 型超高空间分辨率亚细胞器分子质谱成像

• 批准号: 1455668
• 负责人: Touradj Solouki
• 金额: $ 68.48万
• 依托单位: Baylor University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1455668&HistoricalAwards=false
• 关键词: IDBR; TYPE; Ultrahigh; Spatial; Resolution

An award is made to Baylor University to develop an ultrahigh spatial resolution mass spectrometry imaging (MSI) instrument. The potential impact of this research is far-reaching because no current technology is available to address the existing shortcomings in high spatial resolution MSI. The direct beneficiaries of this state-of-the-art technology will include students, researchers, and the society as a whole. This work is expected to open the door for a variety of technology transfer opportunities and potential industry collaborations with the university for mass production that will yield significant economic and societal benefits. Two qualified undergraduate students from underrepresented groups from Baylor outreach programs will be recruited to gain quality research experience. Moreover, two graduate students and a scientist will be trained in research activities and develop expertise in MSI to broaden their scientific knowledge. Research findings and presentations of all mentees in the project will be highlighted in annual Advanced Instrumentation Workshops that target undergraduate students and faculty mentors from Historically Black Colleges and Universities and Hispanic-serving institutions in Texas and nearby states. Virtual scientific networks will be used to disseminate research findings and promote new collaborations. These NSF supported activities will be used to broaden underrepresented student group participation in future biological MSI research. This research will allow construction of a cutting-edge molecular imaging instrument that will be accessed by Baylor faculty and students and utilized for teaching advanced instrumentation classes and to promote inter-institution collaborations. Outcomes from this research will be disseminated through publications and conference presentations to boost broader use of the new ultrahigh spatial resolution MSI.Mass spectrometry imaging (MSI) provides information on surface morphology but also generates highly desired details about specific molecular identities of different sample components. In conventional MSI, a primary laser or desorption beam is rastered across a sample surface to desorb and subsequently analyze different components of biological tissues to construct three-dimensional images. Hence, the spatial resolution in MSI is limited by desorption beam's dimensions (or laser footprint) and energy threshold required to desorb a sufficient number of substrate molecules from the surface for subsequent ionization and mass analysis. Moreover, low ionization efficiencies can severely limit both sensitivity and spatial resolution (typically to several microns) for characterization of cellular components. The purpose of this research is to provide novel analytical capabilities for highly specific and sensitive characterization of cell organelles at the molecular level. This project will create a new frontier in MSI by combining focused ion beam (FIB) neutral desorption with a newly discovered and highly efficient radio frequency ionization (RFI). Persistent challenges in subcellular MSI include achievement of adequate detection sensitivity, overcoming ionization bias, minimizing potential migration of substrate constituents during the analysis, and improving spatial resolution. Current MSI strategies typically address one of these challenges at the expense of another. To ameliorate current trade-offs in MSI, geometry of an RFI source will be optimized to ionize substantially larger portion of the desorbed neutral plume than currently possible. The unparalleled sensitivity of RFI is expected to reduce the primary beam power requirements for a liquid metal ion source (LMIS) to such an extent that imaging resolution in the x-y (surface) and z (depth) dimensions will support molecular level characterization. It will be possible to record 3D images and characterize cell structures and compositions to an unprecedented level of detail, with spatial resolutions an order of magnitude better than current MSI approaches.

贝勒大学获得了一个奖项，以开发一种高空间分辨率的质谱成像（MSI）仪器。这项研究的潜在影响是深远的，因为目前还没有技术可以解决高空间分辨率MSI的现有缺点。这项先进技术的直接受益者将包括学生、研究人员和整个社会。这项工作预计将为各种技术转让机会以及与大学进行大规模生产的潜在行业合作打开大门，这将产生显着的经济和社会效益。两名合格的本科生从贝勒外展计划代表性不足的群体将被招募，以获得高质量的研究经验。此外，两名研究生和一名科学家将接受研究活动方面的培训，并发展毛里求斯战略方面的专门知识，以扩大他们的科学知识。该项目中所有学员的研究结果和演示文稿将在年度先进仪器研讨会中突出显示，这些研讨会的目标是来自德克萨斯州和附近各州历史上黑人学院和大学以及西班牙裔服务机构的本科生和教师导师。将利用虚拟科学网络传播研究成果和促进新的合作。这些NSF支持的活动将用于扩大未来生物MSI研究中代表性不足的学生群体的参与。这项研究将允许建设一个尖端的分子成像仪器，将由贝勒教师和学生访问，并用于教学先进的仪器类，并促进机构间的合作。这项研究的成果将通过出版物和会议演讲传播，以促进更广泛地使用新的空间分辨率MSI. MS质谱成像（MSI）提供的表面形态信息，但也产生高度期望的细节有关特定的分子身份不同的样品成分。在常规MSI中，初级激光或解吸光束在样品表面上光栅化以解吸并随后分析生物组织的不同组分以构建三维图像。因此，MSI中的空间分辨率受到解吸束的尺寸（或激光足迹）和从表面解吸足够数量的衬底分子以用于随后的电离和质量分析所需的能量阈值的限制。此外，低电离效率可严重限制用于表征细胞组分的灵敏度和空间分辨率（通常为几微米）。本研究的目的是提供新的分析能力，在分子水平上的细胞器的高度特异性和灵敏度的表征。该项目将通过将聚焦离子束（FIB）中性解吸与新发现的高效射频电离（RFI）相结合，在MSI中开辟新的前沿。亚细胞MSI的持续挑战包括实现足够的检测灵敏度，克服电离偏差，最大限度地减少分析过程中底物成分的潜在迁移，以及提高空间分辨率。目前的MSI战略通常以牺牲另一个为代价来解决其中一个挑战。为了改善当前MSI中的权衡，RFI源的几何形状将被优化，以使解吸的中性羽流的部分比当前可能的部分大得多。RFI无与伦比的灵敏度预计将降低液态金属离子源（LMIS）的初级束功率要求，达到x-y（表面）和z（深度）维度的成像分辨率将支持分子水平表征的程度。它将有可能记录3D图像，并以前所未有的细节水平表征细胞结构和组成，空间分辨率比目前的MSI方法好一个数量级。