The History of Electron Microscopy
The Development of Electron Microscopy in Canada.
The Electron Microscopy (EM) Laboratory of the Department of Anatomy & Cell Biology (formerly Department of Anatomy)
Gary Bennett and S Kelly Sears
The history of electron microscopy in the Department of Anatomy begins in the 1940’s with the purchase of an RCA EMU-2B transmission electron microscope (TEM; Fig. 1a and b). For the first few years, this instrument was housed, not in the department, but rather in the Department of Physics in the Eaton Electronics Building. The Siemens Elmiscope 1 TEM was purchased in 1958 and was the first electron microscope installed in the EM Laboratory of the Department of Anatomy in the Strathcona Anatomy and Dentistry Building (formerly Strathcona Medical Building; Fig. 2). It was heavily used until 1972 when it was sold to the Montreal General Hospital.
(a) (b )
Figure 1a and b. RCA EMU-2B TEM Figure 2. Siemens Elmiskop 1 TEM.
A Siemens Elmiscope 1A 100 kV TEM was purchased in 1964 from Université Laval. In spite of its bad reputation, this instrument was used for 21 years and one of the longest serving microscopes in the Department (Fig. 2).
Figures 2a and b. (a) Siemens Elmiskop 1A 100 kV TEM. See also <http://physicsmuseum.uq.edu.au/elmiskop-electron-microscope>. (b) Dr R. I. Birks shows a new Siemens Elmiskop 1A transmission electron microscope to Sir Henry Dale, National Institute of Medical Research, London, and Professor 'Hank' Frank Campbell MacIntosh, Department of Physiology, that was presented to McGill University circa 1961. "In Canada, home of the first practical electron microscope, the Elmiskop 1 found a particularly receptive market. By 1963, a number of universities and labs had purchased the microscope, including McGill University (which had three, two in the Department of Anatomy), the University of Alberta, the National Research Council of Canada, and Atomic Energy Canada Limited" (see also www.siemens.com/history/pool/newsarchiv/downloads/20120829_festschrift_siemens_kanada_engl.pdf).
Soon after obtaining the Elmiscope 1a, the RCA EMU-2B TEM was moved from the Eaton Electronics Research Laboratory to the departmental EM Laboratory where it functioned until 1967. This microscope is currently on display in the basement of the Strathcona Anatomy & Dentistry Building. In the mid-1960s, the department obtained two Hitachi HS-7S 80 kV TEMs (Fig. 3). These served for almost 15 years before one was sold to the Royal Victoria Hospital and the second to an art restorer. In 1972, Siemens Company offered the department a demonstrator model of the Elmiskop 101 TEM that was purchased for $25,000 (Fig. 4). This microscope was in service for many years and was used to train all new researchers in the laboratory.
Figure 3. Hitachi HS-7S 80 kV TEM Figure 4. Siemens Elmiskop 101
A new generation of instruments came online in the late 1970s and early 1980s when electron microscopes with moving parts were gradually replaced by those with integrated circuits in the new age of computers. With help from the Faculty of Medicine, the department acquired two new TEMs, the Philips EM400 and Philips EM400T (Figs. 5 and 6). The EM400 was the workhorse for the department until 2000 when it was replaced by the Philips EM410 TEM donated by the Department of Biology. The EM400T had a double condenser aperture system that was optimal for high resolution materials research, but did not provide sufficient contrast for imaging biological samples. Fortunately, the department was given a previously owned Philips EM301 TEM, which supplanted the EM400T until both were decommissioned in early 2000 (Fig. 7).
Figure 5. Philips EM400 120 kV TEM Figure 6. Philips EM400T 120 kV TEM
Figure 7. Philips 100 kV EM301 TEM
In 1986, the Department was awarded a $600,000 MRC Major Equipment Grant to purchase the JEOL JEM-2000FX S/TEM equipped with a Kevex X-ray energy dispersive spectrometer (XEDS). This instrument also was equipped for scanning-transmission electron microscopy (thus the term “S/TEM”; Fig. 8). Unlike a regular scanning electron microscope that can detect secondary electrons generated from the surface of a specimen, in S/TEM mode the rastered excitation electron beam passes through the thin biological section, generating secondary electrons that are detected and analyzed. The XEDS system in this microscope enabled the identification and localization of virtually any element present in biological tissues, and was used by Prof. Hershey Warshawsky to detect calcium and iron atoms in enamel sections. On the occasion of the inauguration of this “state-of-the-art” instrument, Warshawsky published a brief history of the departmental EM Laboratory in the McGill Reporter (Feb 13, 1986).
Figure 8. JEOL JEM-2000FX 200 kV S/TEM
The EM Laboratory was originally administered by Deiter Curlis, chief technician. He was succeeded by Ed Sandborn and his technician, Pat Coen. After leaving McGill for the Université de Montréal, Sandborn was succeeded by Berty Van Heyningen. She was in turn succeeded by Hershey Warshawsky, the first long-term director of the EM Laboratory (1965 to 1973). Warshawsky played a key role in obtaining many of the departmental electron microscopes. Technical staff in the lab at the time included Julius Batky and Ingrid Simons. Prof. Michael Lalli succeeded Warshawsky as director of the EM Laboratory and served in this position until 1998, except for one year when Prof. Louis Hermo was Director. Other dedicated EM technical staff over the years included Kathy Hewitt, Ruth Partridge, Cathy Tang, Sonia Bujold, Jeannie Mui, Aliki Michaelidou, Patricia Hales, Matilda Cheung, as well as many others.
History of the Facility for Electron Microscopy Research (FEMR)
Key Investments and commitments: It was generally acknowledged at McGill University in the late 1990’s that operating and maintaining expensive electron microscopes and ancillary equipment with users widely distributed across faculties and departments was a serious organizational challenge. Previously, the instruments and equipment were used primarily within a department and who were individually responsible for identifying appropriate sources of funding for operation and maintenance. This generally resulted in duplication of instruments, services, and technical and scientific personnel, and more importantly, attendant increased costs. As a long-term solution to chronic underfunding, it was proposed to create a core facility for electron microscopy at McGill with shared instrumentation that would greatly benefit multi-faculty and multi-departmental users of expensive scientific instruments
Under leadership of Professor Hojatollah Vali as Director and the support of Dr S Kelly Sears as Research Manager, FEMR was formally launched in 2001 with functional, but outdated and obsolete, infrastructure that was (often) duplicated and scattered in various departments throughout the downtown campus at McGill. The grouping of many of the electron microscopy (EM) laboratories into a single cross-departmental, cross-faculty and cross-institutional core facility was seen as a mechanism for (i) consolidating the strengths and rectifying weaknesses in imaging, (ii) enriching and expanding cross-disciplinary and interdisciplinary interaction and research in medicine, science and engineering, (iii) improving the quality and expanding the scope of research and research-training by providing shared instrumentation that fosters integration of research and education in research-intensive learning environments, and (iv) assuring the financial stability of research and service delivery and technological enhancement. This was viewed as especially relevant as advanced research instruments that were once of interest only to specialists are increasingly required by a wide array of scientists to solve critical research problems. As researchers become dependent on advanced instruments, they required highly specialized knowledge and expert training in their proper operation and use. Moreover, the committed sharing of advanced infrastructure to the research community offered the potential for the maintenance of user fees at affordable levels. At the same time, technology‐based research activities and technology development, including major equipment purchases, continues to be investigator‐driven through research, equipment and maintenance grants.
Since its inception, FEMR has worked with researchers from all academic institutions in the region of Montreal and elsewhere in Quebec to acquire the expertise and cutting-edge infrastructure to ensure researchers have the tools to conduct world-class research. For technology-based research activities and technology development, including major equipment purchases, FEMR continues to be investigator-driven from through research and equipment grants. FEMR has thus evolved, through generous government and institutional support, including three CFI infrastructure awards (CFI-LEF 744, CFI-LEF 11505, and CFI-LEF 30797) and numerous NSERC and CIHR operations and maintenance, and equipment grants, and the cooperation of researchers from institutions throughout the region of Montreal, into a world-class multi-user, multi-disciplinary, multi-faculty, multi-institutional shared equipment facility. With its state-of-the-art infrastructure for light and electron microscopy, FEMR has been able to operate on a cost recovery basis. In 2000, CFI-LEF 744 (PI - H. Vali, $8.9 million) was awarded to create the Montreal Network for Materials, Molecular and Structural Imaging (MNMSMI), a regional centre providing facilities and a multidisciplinary environment to pursue world-class science, to develop world-class technologies, and to maintain outstanding capabilities in electron microscopy research. In the CFI-744 application, the MNMSMI was designed as a consortium led by FEMR, in partnership with the Laboratoire de Recherche sur les Tissus Calcifiés et Biomatériaux (Université de Montréal), and the Centre de Caractérisation Microscopique des Matériaux (CM)2 (École Polytechnique) (See Table 1 for a list of instruments and equipment).
Table 1. Major Instruments & Equipment obtained from CFI-LEF 744.
|Hitachi S-4700 FE-SEM||McGill University|
|Hitachi S-3000N VP-SEM||McGill University|
|JEOL JSM-6340F FE-SEM||Université de Montréal|
|JEOL JEM-2100F 200 kV FE-TEM||École Polytechnique|
|Hitachi FB-2000A FIB||École Polytechnique|
|Gatan Multiscan CCD Camera Model 791 (x2)||McGill University/Université de Montréal|
|Leica Microsystems EM UCT Ultramicrotome||Université de Montréal|
|Leica Microsystems EM BAF060 Freeze-Fracture System||McGill University|
In 2008, a CFI-LEF grant (11505; PI - J. Bergeron) was awarded to FEMR as lead institute, and to Université Laval, to create the regional Facility for Electron Cryomicroscopy and Cryo-Electron Microscopy (FECCET). A total of $8.03M, combined with $736K from a CFI-LOF Grant (12824) awarded to Dr. I. Rouiller, a recruit in structural biology and cryo-EM at FEMR and appointed in the Department of Anatomy & Cell Biology, enabled the acquisition of state-of-the-art transmission electron microscopes and ancillary equipment for advanced sample preparation (Table 2).
Table 2. Major Instruments & Equipment obtained from CFI-LEF 11505.
|FEI Titan Krios 300 kV Cryo-STEM w/Gatan Imaging Filter||McGill University, Université Laval|
|FEI Tecnai G2 F20 200 kV Cryo-STEM||McGill University, Université Laval|
|FEI Tecnai G2 Spirit 120 kV Cryo-TEM||McGill University, Université Laval|
|FEI Vitrobot Mark IV (x2)||McGill University, Université Laval|
|Leica Microsystems EM PACT2 High Pressure Freezer (x2)||McGill University / Université Laval|
|Leica Microsystems EM AFS2 Automatic Freeze Substitution||McGill University|
|Leica Microsystems EM CPD030 Critical-Point Dryer||McGill University|
|Leica Microsystems EM UC7/FC7 Cryo-ultramicrotome||Université Laval|
|High-Performance Computing||McGill University /Université Laval|
In 2012, a CFI-LEF grant (30979; PI - M. McKee) of $4.54 million was awarded to FEMR to advance the multi-modal workflow capability for cryogenic correlative light-electron microscopy (cryo-CLEM; Table 3).
Table 3. Instruments & Equipment obtained from CFI-LEF 30797.
|FEI Helios Nanolab 660 DualBeam Leica Microsystems EM VCT100 Cryogenic Transfer System||McGill University|
|FEI CorrSight Digital Fluorescent Microscope||McGill University|
|Leica Microsystems EM UC7/FC7 Cryo-ultramicrotome||McGill University|
|Leica Microsystems EM ACE600 High Resolution Sputter Coater||McGill University|
|High Performance Computing||McGill University/CalCul Quebec/Compute Canada|
Partly as a result of the CFI investments over this period, FEMR has been highly successful in obtaining almost $10M worth of peer-reviewed, tri-council operation and maintenance grants, as well as other equipment and support grants (Table 4). In addition, as cutting-edge research is increasingly reliant on the services and specialized equipment that is too costly for departmental or individual procurement, many researchers across disciplines and faculties have been able to acquire funding for their own research projects on the basis of the availability of state-of-the-art infrastructure and expertise at FEMR.
Table 4. Equipment, Operation & Maintenance Grants 1999-2014.
|Funding Agency/ Program||P.I.||Purpose||Amount||Year(s)
|CIHR MME (MT-
|Bergeron, J.||JEOL JEM-2011 TEM, service contracts, & salary support||$703,878||1999-2002|
|McGill University||Vali, H.||Cash contribution to FEMR||$1.16 Million||2001-2014|
|McGill University||Bergeron, J.||Service contracts; salary support||$670,530||2002-2007|
|FQRNT-CBB||Tabrizian, M.||Ssalary support||$550,000||2002-2011|
|McGill University||Vali, H.||Renovations to Rooms B/4 to B/9, B/21 to B/27||$275,000||2003|
|Bergeron, J.||FEI Tecnai 12 120 kV TEM & Leica Microsystems UCT Cryo-ultramicrotome||$295,884||2003|
|McGill University||Vali, H.||Quartz X1 EDS on JEOL JEM-2000FX TEM||$36,000||2004|
|NSERC-RTI||Gauvin, R.||STEM detector on Hitachi S-4700 FE-SEM and EBSD on Hitachi S-3000N VP-SEM||$146,000||2007|
|Bergeron, J.||Service contracts; salary support||$689,280||2007-2012|
|McGill University||Vali, H.||AMT XR-60B CCD Camera and EDAX Genesis EDS on Philips CM200 TEM||$80,000||2008|
|CFI-IOF (11505)||Bergeron, J.||Operational Support||$963,6635||2008-2014|
|CFI-LOF (12824)||Rouiller, I.||Upgrade of FEI Tecnai G2 F20 Cryo-TEM||$736,153||2008-2014|
|FRSQ-GRASP||Gehring, K.||Salary support||$80,000||2009-2012|
|CFI-LOF||Gauvin, R.||SU8000 FE-SEM with an EDAX SDD EDS and EBSD system||$904,000||2009|
|CFI-LEF||McKee, M.||Gatan Precision Ion Polisher (PIPS)||$70,000||$70,000 2009|
|McGill University||Vali, H.||Renovations Rooms B/21 to B/27; B/31, B/32, B/32A, B/32B||$2.5 Million||2009-2010|
|Rouiller, I.||AMT XR-80C CCD camera for FEI Tecnai G2 Spirit Cryo-TEM||$83,122||2011|
|NanoQuébec - MCRF||Tabrizian, M.||Salary support||$320,000||2011-2014|
|McGill University||Vali, H.||Leica Microsystems Critical Point Dryer EM CPD030||$20,000||2012|
|CFI-LOF||Siwick, B.||Gatan Ultrascan 1000 CCD Camera for Philips CM200 TEM||$100,000||2012|
|FRQ-S-GRASP||Gehring, K.||Salary support||$100,000||2013-2018|
|CFI-IOF (30797)||McKee, M.||Operational support||$400,000||2013-2018|
|McGill University||Gauvin, R.||Hitachi SU8230 FE-STEM||$550,000||2013|
|FEI Company||Vali, H.||Operational and maintenance support||$650,000||2013-2018|
|McGill University||Vali, H.||FEI Quanta 450 FE-ESEM & FEI Inspect F-50 FE-SEM||$750,000||2013|
|NSERC-RTI||Kollman, J.||Gatan Model 626 Single Tilt Liquid Nitrogen Cryo Transfer Holder||$70,000||2013|
|CFI-LOF||Tamimi, F.||iXRF X-Beam micro-X-ray fluorescence (XRF) system for FEI Inspect F-50 FE-SEM||$100,000||2013|
|CFI-LOF (32601)||Schmeing, M., Rouiller, I., Kollman, J.||FEI Falcon 2 Direct Detection Device (DDD) & Tomography 4 SW on Titan Krios 300 kV Cryo-STEM||$743,200||2014-2019|
|CFI-IOF (32601)||Schmeing, M., Rouiller, I., Kollman, J.||Operational support||$90,000||2014-2019|
|FEI Company||Vali, H.||Phase plate on Titan Krios 300 kV Cryo-STEM||$1 million||2014|
|McGill University||Vali, H.||EDAX Octane Silicon Drift Detector (SDD) Microanalytical System for FEI Tecnai G2 F20 Cryo-STEM||$80,000||2014|
Since 1999, the Office of the Vice-Principal Research & International Relations (OVPRIR) and the Faculties of Dentistry, Engineering, Medicine, and Science have provided a cash contribution of $135K yr-1 to FEMR for salaries of scientific and technical staff.
As research space is an institutional resource, the Faculties of Dentistry, Engineering, Medicine, and Science have allocated space for FEMR based upon the programmatic needs and strategic research priorities of McGill. While the largest part of the assigned space for FEMR is located in the basement of the Strathcona Anatomy & Dentistry (SAD Building, including its Wet Lab, Cryo-Lab and five rooms for TEMs and SEM, FEMR also has space in the Rutherford Physics Building (TEM Room) and in the basement of the W.H. Wong Engineering Building (SEM and preparation rooms). In terms of costs for renovation and construction, McGill invested $275K in 2003 to renovate the Wet Lab and Cryo-Lab in the SAD Building. In 2009, McGill invested $2.5M to renovate and update the research space for the installation of the Titan Krios 300 kV cryo-STEM, Tecnai G2 F20 cryo-STEM, and the Tecnai G2 Spirit 120 kV cryo-TEM.