The History of Electron Microscopy
History of the Electron Microscope in Cell Biology
The First American Electron Microscopes听
An electrostatic emission electron microscope, using a standard cathode ray tube, was demonstrated in 1934 at the University of Toronto by Walter Kohl, a visiting lecturer from Germany.听 It was likely the first example of electron microscopy of any kind in North America.
The first transmission EM constructed outside Germany was completed in 1935 or 1936 by Paul Anderson and Kenneth Fitzsimmons of Washington State University (Fig. 1A).听 Gordon H. Scott at the Medical School of Washington University in St. Louis started an EM program in the same year with an emission EM in 1935 and a transmission EM in 1939, constructed by Sterling Newberry (Fig. 1B).听 Neither of these programs continued.听 The resolution did not exceed that of the light microscope.
Also, in 1935, E.F. Burton established an EM program at the University of Toronto, starting with the first instrument constructed by Cecil Hall, followed by the construction by James Hillier and Albert E. Prebus 1938 of the first high-resolution EM in North America (Fig. 1C).
Hillier and Prebus were succeeded by William Ladd and John H.L. Watson, who refined the EM to yield a resolution of better than 10 nm in 1939, matching the performance of the German EMs at the time.
Hillier was hired by Alexander Zworykin (a pioneer in television development) and designed highly successful electron microscopes for RCA, eventually becoming RCA's overall head of research.
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The Development of the Electron Microscope in Canada
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History of the Electron Microscopy (EM) Laboratory in the Department of Anatomy & Cell Biology (formerly Department of Anatomy)
Gary C. Bennett and S Kelly Sears
The history of electron microscopy in 大发彩票平台's Department of Anatomy is closely tied to the pioneering efforts of Prof. Charles P. Leblond and Prof. Yves Clermont, both trailblazers in the field of biological electron microscopy.
The journey began in the 1940s with the acquisition of the RCA EMU-2B transmission electron microscope (TEM) (Fig. 1a and b). Initially, this instrument was housed in the Department of Physics, within the Eaton Electronics Building, rather than in the Department of Anatomy.
In 1958, the department installed its first electron microscope, the Siemens Elmiscope 1 TEM, in the EM Laboratory located in the Strathcona Anatomy & Dentistry Building (formerly known as the Strathcona Medical Building; refer also to the history of the SADB, Fig. 2). The Elmiscope 1 saw extensive use until 1972, after which it was sold to the Montreal General Hospital.
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Figures 1a and b.听听RCA EMU-2B TEM (currently on display at the Strathcona Anatomy & Dentistry Building). 听
Figure 2. Siemens Elmiskop 1 TEM.听
A Siemens Elmiscope 1A 100 kV TEM, was purchased in 1964 from Universit茅 Laval.听 Despite its bad reputation, the 1A was used for 21 years and was one of the longest-serving microscopes in the department (Fig. 2).
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Figures 2a and b.听听(a) Siemens Elmiskop 1A 100 kV TEM. See also <>.听 (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, presented to 大发彩票平台 circa 1961.听 "In Canada, home of the first practical electron microscope, the Elmiskop 1 found a particularly receptive market.听 By 1963, several universities and labs had purchased the microscope, including 大发彩票平台 (which had three,听two in the Department of Anatomy), the University of Alberta, the National Research Council of Canada, and Atomic Energy Canada Limited."
Soon after obtaining the Elmiscope 1a, the RCA EMU-2B TEM was moved from the Eaton Electronics Research Laboratory to the departmental EM Laboratory and was operational until 1967.听 The RCA EMU-2B TEM is currently displayed in the basement of the Strathcona Anatomy & Dentistry Building.听 In the mid-1960s, the department obtained two Hitachi HS-7S 80 kV TEMs (Fig. 3).听 These served for almost 15 years before selling one to the Royal Victoria Hospital and the second to an art restorer.听 In 1972, Siemens Company offered the department a demonstrator model of the Elmiskop 101 TEM purchased for $25,000 (Fig. 4).听 This microscope was in service for many years and trained all new researchers in the laboratory.
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听听听 Figure 3. Hitachi HS-7S 80 kV TEM 听听听听听听 Figure 4. Siemens Elmiskop 101
A new generation of instruments came online in the late 1970s and early 1980s.听 The moving parts in electron microscopes were replaced with integrated circuits in the new age of computers.听 With help from the Faculty of Medicine, the department acquired two new TEMs, the Philips EM400 and Philips EM400T (Figs. 5 and 6).听 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.听 The EM400T had a double condenser aperture system optimized听for high-resolution materials research but did not provide sufficient contrast for imaging biological samples.听 Fortunately, the department was given a previously owned Philips EM301 TEM, which supplanted the EM400T until both were decommissioned in early 2000 (Fig. 7).
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Figure 5.听听Philips EM400 120 kV TEM听Figure 6.听听Philips EM400T 120 kV TEM听听听听听听听听听
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Figure 7.听听Philips EM301 100 kV TEM
In 1986, the department received a $600,000 MRC Major Equipment Grant to purchase the JEOL JEM-2000FX S/TEM equipped with听Kevex X-ray energy dispersive spectrometer (XEDS).听 This instrument also was equipped for scanning-transmission electron microscopy (S/TEM; Fig. 8). Unlike a regular SEM that can detect听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.听 The XEDS system in this microscope enabled the identification and localization of virtually any element in biological tissues.听 Prof. Hershey Warshawsky used it听to detect calcium and iron atoms in the enamel sections of teeth.听 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 大发彩票平台 Reporter (Feb 13, 1986).
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Figure 8. JEOL JEM-2000FX 200 kV S/TEM
Scientific and technical staff: The EM Laboratory was administered initially by Dieter Curlis, the chief technician.听 He was succeeded by Ed Sanborn and his technician, Pat Coen.听 After leaving 大发彩票平台 for Universit茅 de Montr茅al, Sanborn was succeeded by Bertie Van Heyningen. Van Heyningen was followed by Prof. Hershey Warshawsky, the first long-term director of the EM Laboratory (1965 to 1973).听 Warshawsky played a听crucial role in obtaining many of the departmental electron microscopes.听 Prof. Michael Lalli succeeded Warshawsky as director of the EM Laboratory and served until 1998, except for one year when Prof. Louis Hermo was director.听 Other technical staff who worked in the lab over the years included Julius Batky (founder of Marivac/Canemco, a Canadian supplier of EM equipment and consumables), Ingrid Simons, Henry Szczawinzki, Kathy Hewitt, Ruth Partridge, Cathy Tang, Sonia Bujold, Aliki Michaelidou, Patricia Hales, Matilda Cheung, Caroline Tanguay, Jeannie Mui, Lee Ann Monaghan, and many others.
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History of the Facility for Electron Microscopy Research (FEMR)
Critical Investments and Commitments
By the late 1990s, it became evident that acquiring, operating, and maintaining advanced electron microscopes and ancillary equipment, while users were scattered across faculties and departments at 大发彩票平台's downtown campus, presented significant organizational challenges. Instruments were primarily confined to single departments, which were individually responsible for securing funding for operation and maintenance. This approach led to duplication of instruments, services, technical and scientific personnel, and, most critically, increased costs.
To address chronic underfunding, the creation of a core facility for electron microscopy at 大发彩票平台 was proposed. This facility would feature shared instrumentation, offering substantial benefits to multi-faculty and multi-departmental users of expensive scientific instruments.
Formation and Objectives of the FEMR
Under the leadership of Prof. Hojatollah Vali as Director and Dr. S. Kelly Sears as Research Manager, the Facility for Electron Microscopy Research (FEMR) was formally launched in 2001, initially relying on functional but outdated research infrastructure. The integration of various electron microscopy (EM) laboratories into a single, cross-departmental, cross-faculty, and cross-institutional core facility was envisioned to:
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Consolidate imaging strengths and address weaknesses.
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Enhance cross-disciplinary and interdisciplinary research in medicine, science, and engineering.
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Improve the quality and scope of research and research training, fostering integration within research-intensive learning environments.
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Ensure financial stability for research, service delivery, and technological advancement.
As advanced research instruments transitioned from niche tools for specialists to essential tools for broader scientific applications, FEMR recognized the necessity for specialized knowledge, expert training, and a commitment to shared infrastructure. This approach supported affordable user fees while sustaining investigator-driven technology-based research and equipment development through research and maintenance grants.
Evolution and Achievements
Since its inception, FEMR has collaborated with researchers across Montreal and Quebec, acquiring expertise and cutting-edge infrastructure to enable world-class research. The facility remains investigator-driven, supported by grants for instruments, operations, and maintenance, ensuring ongoing technology-based research and development.
FEMR has benefited from generous government and institutional support, including:
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Three CFI infrastructure awards (CFI-LEF 744, CFI-LEF 11505, and CFI-LEF 30797).
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Numerous NSERC and CIHR grants for operations, maintenance, and equipment.
FEMR has evolved into a world-class, multi-user, multidisciplinary, multi-faculty, and multi-institutional shared equipment facility, featuring state-of-the-art light and electron microscopy research infrastructure. Operating on a cost-recovery basis, FEMR has led initiatives such as the Montreal Network for Materials, Molecular and Structural Imaging (MNMSMI) through the 2000 CFI-LEF 744 grant ($8.9 million, PI: H. Vali). MNMSMI, a regional center for scientific excellence, fosters research, technological development, and expertise in electron microscopy. The consortium includes FEMR, Universit茅 de Montr茅al's Laboratoire de Recherche sur les Tissus Calcifi茅s et Biomat茅riaux, and 脡cole Polytechnique's Centre de Caract茅risation Microscopique des Mat茅riaux (CM)虏 (refer to Table 1 for equipment details).
Table 1.听 Major Instruments & Equipment obtained from CFI-LEF 744.
| Instrument/Equipment | Location |
|---|---|
| Hitachi S-4700 FE-SEM | 大发彩票平台 |
| Hitachi S-3000N VP-SEM | 大发彩票平台 |
| JEOL JSM-6340F FE-SEM | Universit茅 de Montr茅al |
| JEOL JEM-2100F 200 kV FE-TEM | 脡cole Polytechnique |
| Hitachi FB-2000A FIB | 脡cole Polytechnique |
| Gatan Multiscan CCD Camera Model 791 (x2) | 大发彩票平台/Universit茅 de Montr茅al |
| Leica Microsystems EM UCT Ultramicrotome | Universit茅 de Montr茅al |
| Leica Microsystems EM BAF060 Freeze-Fracture System | 大发彩票平台 |
In 2008, a CFI-LEF grant (11505; PI - J.J.M. Bergeron) was awarded to the FEMR as the lead institute and to Universit茅 Laval to create the regional Facility for Electron Cryomicroscopy and Cryo-Electron Microscopy (FECCET).听 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 the 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.听 Major Instruments & Equipment obtained from CFI-LEF 11505.
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| Instrument/Equipment | Location |
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| FEI Titan Krios 300 kV Cryo-STEM w/Gatan Imaging Filter | 大发彩票平台, Universit茅 Laval |
| FEI Tecnai G2 F20 200 kV Cryo-STEM | 大发彩票平台, Universit茅 Laval |
| FEI Tecnai G2 Spirit 120 kV Cryo-TEM | 大发彩票平台, Universit茅 Laval |
| FEI Vitrobot Mark IV (x2) | 大发彩票平台, Universit茅 Laval |
| Leica Microsystems EM PACT2 High-Pressure Freezer (x2) | 大发彩票平台 /听Universit茅 Laval |
| Leica Microsystems EM AFS2 Automatic Freeze Substitution | 大发彩票平台 |
| Leica Microsystems EM CPD030 Critical-Point Dryer | 大发彩票平台 |
| Leica Microsystems EM UC7/FC7 Cryo-ultramicrotome | Universit茅 Laval |
| High-Performance Computing | 大发彩票平台 /Universit茅 Laval |
In 2012, the FEMR received a $4.54 million CFI-LEF grant (30979; PI鈥擬. McKee) to advance the multimodal workflow capability for cryogenic correlative light-electron microscopy (cryo-CLEM; Table 3).
Table 3.听 Instruments & equipment obtained from CFI-LEF 30797.
| Instrument/Equipment | Location |
|---|---|
| FEI Helios Nanolab 660 DualBeam Leica Microsystems EM VCT100 Cryogenic Transfer System | 大发彩票平台 |
| FEI CorrSight Digital Fluorescent Microscope | 大发彩票平台 |
| Leica Microsystems EM UC7/FC7 Cryo-ultramicrotome | 大发彩票平台 |
| Leica Microsystems EM ACE600 High-Resolution Sputter Coater | 大发彩票平台 |
| High-Performance Computing | 大发彩票平台/CalCul Quebec/Compute Canada |
Due to the CFI investments over this period, the FEMR has been highly successful in obtaining almost $10M worth of peer-reviewed, tri-council operation and maintenance grants and other equipment and support grants (Table 4).听 In addition, as cutting-edge research increasingly relies on the services and specialized equipment that is too costly for departmental or individual procurement, many researchers across disciplines and faculties have acquired funding for their research projects based on the availability of state-of-the-art infrastructure and expertise at the FEMR.
Table 4.听 Equipment, Operation & Maintenance Grants 1999-2024.
| Funding Agency/ Program | PI. | Purpose | Amount | Year(s) Awarded |
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| CIHR MME (MT- 14210) |
Bergeron, J. | JEOL JEM-2011 TEM, service contracts, & salary support | $703,878 | 1999-2002 |
| 大发彩票平台 | Vali, H. | Cash contribution to FEMR | $1.16 Million | 2001-2014 |
| 大发彩票平台 | Bergeron, J. | Service contracts; salary support | $670,530 | 2002-2007 |
| FQRNT-CBB | Tabrizian, M. | Salary support | $550,000 | 2002-2011 |
| 大发彩票平台 | Vali, H. | Renovations to Rooms B/4 to B/9, B/21 to B/27 | $275,000 | 2003 |
| CIHR-MME (MME- 67417) |
Bergeron, J. | FEI Tecnai 12 120 kV TEM & Leica Microsystems UCT Cryo-ultramicrotome | $295,884 | 2003 |
| 大发彩票平台 | 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 |
| CIHR-RRG (MT- 165625) |
Bergeron, J. | Service contracts; salary support | $689,280 | 2007-2012 |
| 大发彩票平台 | 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听 2009 |
| 大发彩票平台 | Vali, H. | Renovations Rooms B/21 to B/27; B/31, B/32, B/32A, B/32B | $4.5 Million | 2009-2010 |
| NSERC-RTI (EQPEQ 406251-11) |
Rouiller, I. | AMT XR-80C CCD camera for FEI Tecnai G2 Spirit Cryo-TEM | $83,122 | 2011 |
| NanoQu茅bec - MCRF | Tabrizian, M. | Salary support | $320,000 | 2011-2014 |
| 大发彩票平台 | 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 |
| 大发彩票平台 | Gauvin, R. | Hitachi SU8230 FE-STEM | $550,000 | 2013 |
| FEI Company | Vali, H. | Operational and maintenance support | $650,000 | 2013-2018 |
| 大发彩票平台 | 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 |
| 大发彩票平台 | Vali, H. | EDAX Octane Silicon Drift Detector (SDD) Microanalytical System for FEI Tecnai G2 F20 Cryo-STEM | $80,000 | 2014 |
| CFI-JELF | Moores, A. | Thermo Scientific听Talos 200FX G2 TEM | $2,000,000 | 2017 |
| CFI-JELF | Ortega, J., Vargas, J., Tocheva, E. | Gatan GIF BioQuantum LS and K3 DED | $1,900,000 | 2018 |
| NSERC-RTI | Vargas, J & Strauss, M | TVIPS XF416 16MP CMOS Camera | $140,000 | 2019 |
| CFI-JELF | McKee, M. | 听Leica EM VCT500 Cryotransfer System, EM ACE600 Sputter Coater, and EM CPD300 CPD | $281,000 | 2019 |
| 大发彩票平台 - Office of the Provost | Ortega, J. | Operational Support | $300,000 p.a. | 2020 -2023 |
| CFI- Innovation Fund | Mountanabbir, O, McKee, M, Gauvin, R... | Leica EM ICE HPF | $350,000 | 2020 |
| CFI-Innovation Fund | Ortega, J. et al. | Multiscale 3D Cryo Imaging: From Organs to Molecules | $20,702,128 | 2023 |
| NSERC-RTI | Ortega, J. et al. | AMT Nanosprint15 MKII 15 MP CMOS Camera | $150,000 | 2023 |
| 大发彩票平台 - Office of the Provost | Ortega, J. | Operational Support | $240,000 | 2024 |
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Financial Contributions
Since 1999, the Office of the Vice-Principal Research & International Relations (OVPRIR), along with the Faculties of Dentistry, Engineering, Medicine, and Science, has provided an annual cash contribution of $135,000 to FEMR for the salaries of scientific and technical staff. In 2019, the Office of the Provost committed an additional $300,000 per year to support FEMR's operations.
Space Allocation
Research space, recognized as an institutional resource, has been allocated to FEMR by the Faculties of Dentistry, Engineering, Medicine, and Science based on 大发彩票平台's programmatic needs and strategic research priorities. The most significant portion of FEMR's space is situated in the basement of the Strathcona Anatomy & Dentistry Building, including:
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A Wet Lab and Sample Preparation Lab.
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Five rooms housing Transmission Electron Microscopes (TEMs) and Scanning Electron Microscopes (SEMs).
Additional space is allocated to FEMR in the W.H. Wong Engineering Building, which also hosts TEMs and SEMs.
Renovation and Construction Investments
大发彩票平台 has made substantial investments to support FEMR's facilities:
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In 2003, $275,000 was allocated to renovate the Wet Lab and Cryo-Lab in the Strathcona Anatomy & Dentistry Building.
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In 2009, 大发彩票平台 invested $4.5 million to renovate and update research spaces, enabling the installation of advanced instruments, including:
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Titan Krios 300 kV cryo-STEM
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Tecnai G2 F20 cryo-STEM
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Tecnai G2 Spirit 120 kV cryo-TEM
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