A New Superconducting Detector Technology for Mass Spectrometry of Large Biomolecules

项目摘要/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。这样的信息 在包括分子生物学、病理学、蛋白质组学和药学在内的许多生命科学学科中寻找 工业。这是我们在理解生命过程方面取得根本性进展所需的关键信息。 然而，这一愿景将需要开发一种有效检测分子的技术，但目前还没有 是存在的。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，使我们能够制造探测器并将其商业化 使这一宏伟愿景成为可能的技术。这项技术是基于一种使用超导的新专利方法。 可以100%记录撞击分子的材料，即使是最重的蛋白质和蛋白质复合体。 现在有方法可以从组织和水溶液中将任何质量的生物分子作为离子发射到质量中 光谱仪效率高，无碎裂或变性。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)打开了新的 分子分析和测绘的机会。我们设计的质谱计可以传递这些离子 安装在具有极高质量分辨率(&gt；200,000)的探测器上。然而，探测器目前是 这一令人兴奋的发展。有了新的探测器技术，一种全新的成像质谱仪可以 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Skdle)提供100% 在检测的同时，捕捉到蛋白质等未碎裂的大质量分子的高质量分辨率。它很快 (&gt；108分子/秒)，并且可扩展到大范围(&gt；4 cm2)。过去完成了一个概念验证项目 年。作为我们宏伟愿景的一部分，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 用光谱测绘细胞中的所有分子。我们已经建立了一支由学术和商业专家组成的生物团队 质谱学(MS)、超导探测器和电子学。我们将开发一种高度平行的镶嵌 探测器晶片上带有集成超导电子器件的探测器。商业化的第一步，这 第一阶段计划是与SeeQC，Inc.(以前)合作，对探测器及其电子设备进行全面模拟 Hypres，Inc.)。完成后，我们将对其预期表现有很高的信心。在我们的第二阶段，我们 我将制作一个带有SeeQC的工作检测器，并在真实生物分子上的测试MS系统中评估其性能 标本。将用于高性能飞行时间质谱仪的SCDL探测器商业化是第一阶段 我们对探测器技术的计划。在我们开发的第二阶段，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，探测器将被用来记录百万像素的光斑 这将使我们能够将成像质谱仪的空间分辨率提高到100纳米以下。这个 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展。

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.