Contributions of David Joy to Electron Microscopy at the NIH (ca. 1980-2020).

Contributions of David Joy to Electron Microscopy at the NIH (ca. 1980-2020).
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David Joy 对 NIH 电子显微镜的贡献(约 1980-2020 年)。

DOI:
10.1093/micmic/ozad067.214
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发表时间:
2023
期刊:
Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada
影响因子:
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通讯作者:
Leapman,RichardD
Leapman,RichardD
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文献类型:
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作者:
Leapman,RichardD

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喜悦在扫描电子显微镜和扫描透射电子显微镜领域做出了许多重要贡献,他的研究甚至在他直接感兴趣的领域之外也有很大的影响,包括在美国国立卫生研究院。大约在1979年,David一直在考虑在NIH建立一个职位,建立一个日立200kev H700H分析电子显微镜(AEM),配备一个电子能量损失光谱仪(可能是世界上第一个这样的商业鳗鱼系统),这是David和他的同事在贝尔实验室设计的[1]。美国国立卫生研究院突然对鳗鱼感兴趣,很大程度上是因为1978年发表在《科学》杂志上的一项关于亚细胞检测氟标记生物化合物的研究,大卫与人合著[2]。最后,大卫决定留在新泽西,而我发现自己在NIH,在那里我加入了查克·菲奥里和其他几个对将AEM应用于生物系统感兴趣的人。我们的团队包括以基思·戈伦为首的有才华的计算机科学家,他开发了第一批使用大卫光谱仪进行纳米分析的数字控制鳗鱼系统[3]之一,当时这种光谱仪依赖于使用光电倍增管对能量损失光谱进行连续检测。尽管串联鳗鱼的效率相对较低,但通过使用大卫的光谱仪,仍有可能证明检测生物元素的核心边缘的可行性,如图1[3]所示。后来,我们能够获得Gatan并行检测鳗鱼系统[4],并在1990年左右,专用的VG显微镜HB501场发射STEM,它极大地提高了灵敏度,只有几个原子的生物元素,如钙和铁[5]。最近,我们一直在使用STEM断层扫描技术对1-2微米厚的塑料切片进行结构细胞生物学研究[6],并使用包括连续块面扫描[7]和聚焦离子束扫描[8]在内的体积EM方法对整个真核细胞进行成像。令人惊讶的是,在这项工作中,我们开始依赖大卫开创的另一种技术-蒙特卡罗背散射电子模拟,其中包括低能1至2keV电子的非弹性和弹性散射[9,10]。在这里,大卫的贡献对于理解可达到的空间分辨率的极限,以及开发新的获取数据的方法以提高3D超微结构的质量[11]至关重要,如图2所示。因此,喜悦的开创性科学贡献对于在美国国立卫生研究院及其他地方发展成分和结构生物技术至关重要[12]。
David Joy has made many important contributions to the fields of scanning electron microscopy (SEM) and scanning transmission electron microscopy (STEM), and his research has had an enormous reach even outside his immediate areas of interest, including at the National Institutes of Health (NIH). In around 1979, David had been considering a position at the NIH to establish an Hitachi 200-keV H700H analytical electron microscope (AEM), equipped with an electron energy loss spectrometer (probably the first such commercial EELS system in the world), which David and his colleagues had designed at Bell Labs [1]. NIH’s sudden interest in EELS had been largely due to a study on subcellular detection of fluorine-labeled biological compounds, published in Science in 1978 and co-authored by David [2]. In the end, David decided to remain in New Jersey, and instead I found myself at NIH, where I joined Chuck Fiori and a few others who were interested in applying AEM to biological systems. Our group included talented computer scientists led by Keith Gorlen, who developed one of the first digitally controlled EELS systems for nanoanalysis [3] using David’s spectrometer, which at that time relied on serial detection of the energy loss spectrum using a photomultiplier tube. Despite the relatively low efficiency of serial EELS, by using David’s spectrometer, it was nevertheless possible to demonstrate the feasibility of detecting core-edges of biological elements, as illustrated in Fig. 1 [3]. Later on, we were able to obtain a Gatan parallel-detection EELS system [4] and in around 1990, a dedicated VG Microscopes HB501 field-emission STEM, which greatly improved sensitivity down to just a few atoms of biological elements like calcium and iron [5]. More recently, we have been using STEM tomography for structural cell biological studies on 1–2 micrometer-thick plastic sections [6], as well as using volume EM methods including serial block-face SEM [7] and focused ion-beam SEM [8] to image whole eukaryotic cells. Surprisingly, in this endeavor, we have come to rely on another technique that David had pioneered–Monte Carlo simulations for backscattered electrons incorporating inelastic as well as elastic scattering of low energy 1 to 2 keV electrons [9, 10]. Here again, David’s contributions have been essential for understanding the limits of achievable spatial resolution, and for developing new ways to acquire data that enhance the quality of 3D ultrastructure [11] as indicated in Fig. 2. Thus, David Joy’s pioneering scientific contributions have been crucial for developing both compositional and structural biological techniques at the NIH and beyond [12].