A New Superconducting Detector Technology for Mass Spectrometry of Large Biomolecules

用于大生物分子质谱分析的新型超导探测器技术

• 批准号: 9907501
• 负责人: Thomas Fred Kelly
• 金额: $ 22.13万
• 依托单位: STEAM INSTRUMENTS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-15 至 2021-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907501
• 关键词: Acceleration; Address; Affect; Area; Automobile Driving; Biological; Biological Sciences; Cells; Charge; Collaborations; Complex; Detection; Development; Disadvantaged; Discipline; Drug Industry; Electronics; Electrons; Engineering; Enzymes; Evaluation; Foundations; Fourier Transform; Goals; Government; Health Sciences; Heavy Ions; Image; Impulsivity; Industry; Ions; Isotopes; Kinetics; Knowledge; Lasers; Lead; Legal patent; Life; Link; Maps; Mass Spectrum Analysis; Methods; Molecular; Molecular Analysis; Molecular Biology; Pathology; Pattern; Performance; Persons; Pharmacotherapy; Phase; Process; Program Development; Proteins; Proteomics; Research; Resolution; Specimen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Speed; Statistical Distributions; Steam; System; Technology; Testing; Time; Tissue Sample; Tissues; Variant; Vision; Work; base; commercialization; data acquisition; design; detector; disease diagnosis; instrument; ion source; ionization; ionization technique; mass analyzer; mass spectrometer; mass spectrometric imaging; models and simulation; programs; protein complex; simulation; single molecule; tandem mass spectrometry; time of flight mass spectrometry; vibration; voltage; water solution

Project Summary/Abstract The long-term goal of our efforts is to enable identification and mapping of every molecule in a cell. Such information is sought in many life-science disciplines including molecular biology, pathology, proteomics and for the pharmaceutical industry. It is critical information needed to underpin fundamental advances in our understanding of life processes. However, this vision will require development of a technology for efficient detection of molecules, that does not yet exist. Detectors for biomolecules are the foundation of analytical instruments such as mass spectrometers. We have developed and experimentally proven new concepts that will allow us to build and commercialize a detector technology enabling this grand vision. The technology is based on a new patented approach to using superconducting materials which can record 100% of the impinging molecules, even the heaviest proteins and protein complexes. Methods are now available to launch biomolecules of any mass from tissue and water solutions as ions into mass spectrometers with high efficiency and no fragmentation or denaturing. Such soft laser-ionization methods as MALDI (matrix-assisted laser desorption/ionization) and DIVE (desorption by impulsive vibrational excitation) open new opportunities for molecular analysis and mapping. We have designs for mass spectrometers that can deliver these ions onto a detector with very high mass resolving power (>200,000). However, the detector is currently the missing link in this exciting development. With the new detector technology, a whole new class of imaging mass spectrometers can be developed and brought to market. Our superconducting detector technology (a superconducting delay line or SCDL, pronounced skiddle) delivers 100% detection while capturing the high mass resolving power on unfragmented large-mass molecules like proteins. It is fast (>108 molecules/second) and expandable to large areas (>4 cm2). A proof-of-concept project was completed in the past year. We are commercializing this technology for biomolecule time-of-flight detection as part of our grand vision to spectroscopically map all molecules in a cell. We have built a team of academic and commercial experts in biological mass spectrometry (MS) and superconducting detectors and electronics. We will develop a highly parallel tessellated detector with integrated superconducting electronics on the detector wafer. The first step in commercialization, this Phase I program, is thorough simulation of the detector and its electronics in collaboration with SeeQC, Inc. (formerly Hypres, Inc.). When complete, we will have a high level of confidence in its expected performance. In our Phase II, we will fabricate a working detector with SeeQC and evaluate its performance in a test MS system on real biomolecular specimens. Commercializing the SCDL detector for high performance time-of-flight mass spectrometry is the first stage of our plans for this detector technology. In our second stage of development, we will design and build the technology for recording time-of-flight encoded images. In other words, the detector will be used to record megapixel stigmatic images that will allow us to push the spatial resolution of the imaging mass spectrometer to better than 100 nm. The proposed new detector technology will enable major advancements in life sciences and related industries.

项目概要/摘要 我们努力的长期目标是能够识别和绘制细胞中的每个分子。此类信息 被许多生命科学学科所追求，包括分子生物学、病理学、蛋白质组学和制药 行业。这是支持我们对生命过程的理解取得根本进展所需的关键信息。 然而，这一愿景需要开发一种有效检测分子的技术，而该技术目前还没有实现。 存在。生物分子检测器是质谱仪等分析仪器的基础。我们有 开发并经过实验验证的新概念将使我们能够构建探测器并将其商业化 技术实现这一宏伟愿景。该技术基于一种使用超导的新专利方法 可以记录 100% 撞击分子的材料，甚至是最重的蛋白质和蛋白质复合物。 现在有方法可以将组织和水溶液中任何质量的生物分子以离子形式发射到质量中 光谱仪效率高，无碎片或变性。 MALDI 等软激光电离方法 （基质辅助激光解吸/电离）和 DIVE（脉冲振动激发解吸）开辟了新的领域 分子分析和绘图的机会。我们设计了可以传递这些离子的质谱仪 到具有极高质量分辨能力 (>200,000) 的探测器上。然而，探测器目前是缺失的环节 这一令人兴奋的发展。借助新的检测器技术，全新类型的成像质谱仪可以 被开发并推向市场。 我们的超导探测器技术（超导延迟线或 SCDL，发音为 skiddle）可实现 100% 检测，同时捕获未碎片的大质量分子（如蛋白质）的高质量分辨率。速度很快 （>108 分子/秒）并可扩展到大面积（>4 cm2）。概念验证项目已于过去完成 年。我们正在将这项用于生物分子飞行时间检测的技术商业化，作为我们宏伟愿景的一部分 绘制细胞内所有分子的光谱图。我们建立了一支由生物领域学术和商业专家组成的团队 质谱 (MS) 和超导探测器和电子设备。我们将开发一个高度并行的棋盘格 探测器晶片上集成了超导电子器件。这是商业化的第一步 第一阶段计划是与 SeeQC, Inc.（以前称为 海普尔斯公司）。完成后，我们将对其预期性能充满信心。在我们的第二阶段，我们 将使用 SeeQC 制造工作探测器，并在真实生物分子的测试 MS 系统中评估其性能 标本。用于高性能飞行时间质谱分析的 SCDL 探测器商业化是第一阶段 我们对此探测器技术的计划。在我们的第二个发展阶段，我们将设计和构建技术 用于记录飞行时间编码图像。换句话说，探测器将用于记录百万像素的象散 这些图像将使我们能够将成像质谱仪的空间分辨率提高到 100 nm 以上。这 拟议的新探测器技术将使生命科学和相关行业取得重大进步。