Diamond Light Source - eBIC for Industry

eBIC for Industry is a recently inaugurated center offering professional cryo-EM services to the global pharmaceutical and biotech industry. Situated at eBIC, a UK National Centre for cryo-...

 
Diamond Light Source

eBIC for Industry is a recently inaugurated center offering professional cryo-EM services to the global pharmaceutical and biotech industry. Situated at eBIC, a UK National Centre for cryo-electron microscopy, the partnership...

eBIC for Industry is a recently inaugurated center offering professional cryo-EM services to the global pharmaceutical and biotech industry. Situated at eBIC, a UK National Centre for cryo-electron microscopy, the partnership between Thermo Fisher Scientific and Diamond Light Source provides access to state-of-the-art microscopes and world-class experience. The density of high-end microscopes, access to complementary synchrotron-based techniques, and the on-site manufacturer experience in our team make eBIC for Industry a unique offer to the life science sector. 

"We were lucky to be the first UK site to have a K3 camera installed and in January, with support from Gatan, were able to get Latitude up and running at full speed. We’re now routinely getting 180 images an hour for our clients, which is an almost 3-fold increase in acquisition rates over the old K2 when the bigger chip size is also taken into consideration. This has translated in larger data sets for our users and shorter acquisition times, hence cost savings for their research budgets. We were are now able to collect enough data to get 2.3 Å apoferritin in 40 minutes!"
- Jason Van Rooyen, Senior Industrial Liaison Scientist, Cryo-Electron Microscopy at eBIC for Industry

Why choose eBIC for your research?

eBIC for Industry at Diamond Light Source provides industrial scientists with scalable on-demand access to state-of-the-art experimental equipment and expertise in the field of cryo-electron microscopy, for single particle analysis and cryo-tomography.

Their dedicated latest generation cryo-EM microscopes and detectors allow industrial users to routinely visualize macro-molecular complexes at near-atomic resolution, leveraging this powerful technique to solve difficult-to-crystallize and dynamic proteins of therapeutic interest.

eBIC for Industry provides an effective way in which to apply cryo-electron microscopy to your research, without the need for a large upfront investment in in-house equipment and expertise. Their experts are on hand to support you throughout the process; they are experienced in the challenges and workings of the pharma industry and have a breadth of knowledge from across an extensive customer base.

Confidentiality and data security are key for all of their industrial customers, and they apply stringent measures to ensure your data are stored and managed securely. Along with state-of-the-art facilities, the team will provide on-the-job training to ensure you get the most out of your time at Diamond.

Download further information about eBIC for Industry

Benefits for structural biology

Structural biology enables you to obtain absolute actionable insight into the mechanisms and interactions of partner molecules in fundamental biological or disease processes.

Using cryo-electron microscopy for your research enables you to:

  • Achieve structural information without the need to crystallize your target protein 
  • Image protein complexes and protein-ligand interactions
  • Study macromolecules in as close to a native state as possible
  • Identify and characterize dynamic biological states by observing multiple conformations.

Applications

Antibodies and vaccine research
Cryo-EM is an effective technique to map the interactions between antibodies and antigens in biological drug and vaccine design studies. Near-atomic resolution structures of entire viruses and virus-like particles are routinely achievable with this technique.
 
Characterization of nanotechnology/drug delivery systems
By providing structural information in as near to native conditions as possible, cryo-EM can support development and manufacturing programs for the design of new drug delivery systems such as liposomes and dendrimers. Elucidating structure-function relationships during the design of macromolecular-based nanotech devices is also commonly achieved using this technique. 
 
Drug discovery/rational design
Near-atomic resolutions can now be readily achieved using cryo-EM. These reveal not only the presence of but also the mechanism by which, compounds bind with their protein targets. Cryo-EM has, therefore, become indispensable to pharmaceutical R&D groups wanting to investigate the structures of difficult to crystallize proteins. In addition, many membrane proteins of considerable therapeutic interest, such as channels and receptors, are readily amenable to solution by cryo-EM. 

Want to know more?

Make an inquiry
Join the Industrial Liaison Group's mailing list
Meeting the team

The flow of a single ML step

Material science is at the core of a large majority of research topics at the Centre for Nanoscience and Nanotechnology (C2N). Innovating in this field is of crucial...

Material science is at the core of a large majority of research topics at the Centre for Nanoscience and Nanotechnology (C2N). Innovating in this field is of crucial importance. The Materials Department has two general objectives:

  • To conduct its own research activities in material science, from the physics of growth to the control of various material properties
  • To interact with the 3 other departments (Photonics, Nanoelectronics, Microsystems and Nanobiofluidics), collaborate with external groups and provide samples and devices

Understanding growth mechanisms and correlating the material properties with their growth conditions is one of the main challenges of the Department. To this aim, we use advanced equipment for growth and analysis. We also develop adapted theoretical and numerical tools. Our activities in material science focus mainly on nanostructures made of III-V semiconductors, Si/Ge, novel 2D materials (2D Materials team) and functional oxides (OXIDE team). Hybridization of these various materials is another challenge, opening the way to novel functionalities. These activities are pursued in strong interaction with photonics, nanoelectronics, devices, and systems.

Lab Highlight

In-situ growth in a transmission electron microscope of semiconductor nanostructures: Atomic Step Flow on a Nanofacet

The project Nanomax associates specialists (from the Ecole Polytechnique and C2N) in the epitaxial growth of nano-objects from the experimental and theoretical points of view. 

The goal is to investigate fundamental issues of solid phase nucleation and growth (from a supersaturated vapor phase) that cannot be solved by ex situ observation (due to the evolution of nanostructures during post-growth cooling). The pilot project in NANOMAX is MBE of III-V semiconductor nanowires. Other investigations include chemical vapor deposition of various nano-objects ranging from semiconductor quantum dots to carbon nanotubes. NANOMAX is the first ever attempt to implement MBE in a TEM column. Moreover, its goal is real atomic resolution during growth, which has never been achieved so far. NANOMAX thus implies significant technical developments, regarding both hardware and software, such as the implementation of effusion cells in the vicinity of a modified objective lens and stage (http://www.tempos.fr).

A remarkable specificity of nanocrystals is the strong influence of their surfaces and edges on their properties. The important role of crystal boundaries also manifests itself at the growth stage. Indeed, surfaces influence the morphology and crystalline arrangement of nanostructures, not only as regards thermodynamics but also via their growth dynamics. This is notably illustrated in the vapor-liquid-solid (VLS) growth of semiconductor nanowires (NWs). In this method, vapor containing the NW constituents is supplied to a liquid catalyst nanoparticle. Upon supersaturation of the catalyst droplet, crystallization occurs: A nanocrystal forms, one of its facets in contact with the droplet. This nanofacet is where crystal growth further proceeds. A detailed and real-time observation of the liquid-solid interface is thus expected to clarify the role of the boundaries in the crystallization process. We observe the VLS growth of GaAs NWs in real time. We use a modified FEI environmental TEM equipped with an image aberration corrector. Two ports were designed to implement Ga and As4 molecular beam sources in the TEM. NW formation is catalyzed by Au particles dispersed on a heating carrier membrane, and in situ growth is performed by molecular beam epitaxy at 400 °C. At this temperature, the Au particles alloy with Ga to form liquid droplets. Upon As supersaturation of the droplets, GaAs NWs of hexagonal shape crystallize under the droplets. The boundaries of this system consist of the NW-catalyst interface, the NW sidewalls, and the surface of the liquid catalyst particle. We examine the formation of the WZ phase. The sidewalls of the NWs are {11-20} facets, and the hexagon sides are ⟨10-10⟩ directions. We first present an atomically resolved growth observation in a ⟨11-20⟩ zone axis. The electron beam is then parallel to the LS interface, and the atomic columns parallel to the beam produce a strong contrast.

Nevertheless, the observation conditions adopted in these studies, with the electron beam parallel to the LS interface, provide an incomplete picture of ML formation and progression. Here, we present in addition bird’s eye views of growing NWs which reveal essential complementary information. A two-dimensional projection of the growing ML is visualized, from the early stage of formation to ML completion. We confirm that WZ layers start from the periphery of the NW top facet, and we image, analyze, and model the progression of the step within this hexagonal perimeter. Relevant edge energies are extracted. This leads to a better understanding of the formation of the nanocrystal and ultimately to a better control of its structure.

Reference :

Atomic step flow on a nanofacet
J.-C. Harmand, G. Patriarche, F. Glas, F. Panciera, I. Florea, J.-L. Maurice, L. Travers et Y. Ollivier; Physical Review Letters, 121, 166101 (2018)
DOI : 10.1103/PhysRevLett.121.166101

Electron Beam Induced Artifacts During In-Situ TEM

At the Lab at ASU, their research is primarily focused on the synthesis and characterization of nanostructured materials for structural and functional applications. They...

At the Lab at ASU, their research is primarily focused on the synthesis and characterization of nanostructured materials for structural and functional applications. They develop new synthesis techniques for thin films and investigate their synthesis-structure-property relationships. The overarching goal is to engineer the microstructure of thin films to enhance their mechanical properties and functionality. The lab also has an active interest in creating soft, polymer-based micro platforms that can be used as scaffolds for biohybrid devices or for studying cellular mechanics.

Publication Highlights

Izadi, E.; Darbal, A.; Sarkar, R.; Rajagopalan, J. Grain rotations in ultrafine-grained aluminum films studied using in situ TEM straining with automated crystal orientation mapping. Mater. Des.113 (Jan. 2017), pp. 186-194; doi: 10.1016/j.matdes (2016)

" In-situ TEM straining allows probing deformation mechanisms of ultrafine-grained and nanocrystalline metals. While obtaining statistically meaningful information about microstructural changes using conventional bright-field/dark-field imaging or diffraction is time-consuming, automated crystal orientation mapping in TEM (ACOM-TEM) enables tracking orientation changes of hundreds of grains simultaneously. We use this technique to uncover extensive grain rotations during in-situ tensile deformation of a freestanding, ultrafine-grained aluminum film (thickness 200 nm, mean grain size 180 nm). During loading, both the fraction of grains that undergo rotations and the magnitude of their rotations increase with strain. The rotations are partially or fully reversible in a significant fraction of grains during unloading, leading to notable inelastic strain recovery. More surprisingly, the direction of rotation remains unchanged for a small fraction of grains during unloading, despite a sharp reduction in the applied stress. The ACOM-TEM measurements also provide evidence of reversible and irreversible grain/twin boundary migrations in the film. These microstructural observations point to a highly inhomogeneous and constantly evolving stress distribution in the film during both loading and unloading."

Lab Focus

Sarkar, R. et al. Electron beam induced artifacts during in situ TEM deformation of nanostructured metals. Sci. Rep. 5, 16345; doi: 10.1038/srep16345 (2015).

"A critical assumption underlying in-situ transmission electron microscopy studies is that the electron beam (e-beam) exposure does not fundamentally alter the intrinsic deformation behavior of the materials being probed. Here, we show that e-beam exposure causes increased dislocation activation and marked stress relaxation in aluminum and gold films spanning a range of thicknesses (80 – 400 nm) and grain sizes (50 – 220 nm). Furthermore, the e-beam induces anomalous sample necking, which unusually depends more on the e-beam diameter than intensity. Notably, the stress relaxation in both aluminum and gold occurs at beam energies well below their damage thresholds. More remarkably, the stress relaxation and/or sample necking is significantly more pronounced at lower accelerating voltages (120 kV versus 200 kV) in both the metals. These observations in aluminum and gold, two metals with highly dissimilar atomic weights and properties, indicate that e-beam exposure can cause anomalous behavior in a broad spectrum of nanostructured materials, and simultaneously suggest a strategy to minimize such artifacts."

Additional Publications

21. E. Izadi, A. Darbal, R. Sarkar, J. Rajagopalan, “Grain rotations in ultrafine-grained aluminum films studied using in situ TEM straining with automated crystal orientation mapping,” Materials and Design 113, 186–194, 2017 (pdf).

20. R. Sarkar, C. Ebner, I. Izadi, C. Rentenberger, and J. Rajagopalan, “Revealing anelasticity and structural rearrangements in nanoscale metallic glass films using in situ TEM diffraction,” Materials Research Letters, 2016 DOI:10.1080/21663831.2016.1228709 (pdf).

19. T. W. Sowers, R. Sarkar, S. E. Prameela, E. Izadi and J. Rajagopalan, “Capillary driven flow of polydimethylsiloxane in open rectangular micro channels,” Soft Matter 12, 5818-5823, 2016 (pdf).

18. C. Ebner, R. Sarkar, J. Rajagopalan, and C. Rentenberger, “Local, atomic-­level elastic strain measurements of metallic glass thin films by electron diffraction,” Ultramicroscopy 165, 51–58, 2016 (pdf).

17. E. Izadi and J. Rajagopalan, “Texture dependent strain rate sensitivity of ultrafine-grained aluminum films,” Scripta Materialia 114, 65-69, 2016 (pdf).

16. R. Sarkar, C. Rentenberger and J. Rajagopalan, “Electron beam induced artifacts during in situ TEM deformation of nanostructured metals,” Scientific Reports 5, 16345, 2015 (pdf).

15. S. Singh, R. Sarkar, H.-X. Xie, C. Mayer, J. Rajagopalan, and N. Chawla, “Tensile behavior of single-crystal tin whiskers,” Journal of Electronic Materials 43, 978-982, 2014 (pdf)

14. B. J. Williams, S. A. Anand, J. Rajagopalan and M. T. A. Saif, “A self-propelled biohybrid swimmer at low Reynolds number,” Nature Communications 5, 3081, 2014 (pdf)

13. J. Rajagopalan and M. T. A. Saif, “Fabrication of freestanding 1-D PDMS microstructures using capillary micromolding,” Journal of Microelectromechanical Systems 22, 992-994, 2013 (pdf)

12. J. Rajagopalan and M. T. A. Saif, “Effect of microstructural heterogeneity on the mechanical behavior of nanocrystalline metal films,” Journal of Materials Research 26, 2826-2832, 2011 (pdf)

11. J. Rajagopalan and M. T. A. Saif, “MEMS sensors and microsystems for cell mechano-biology,” Journal of Micromechanics and Microengineering 21, 054002, 2011 (pdf)

10. J. Rajagopalan, A. Tofangchi and M. T. A. Saif, “Linear, high-resolution bioMEMS force sensors with large measurement range,” Journal of Microelectromechanical Systems 19, 1380-1389, 2010 (pdf)

9. W. Kang, J. Rajagopalan and M. T. A. Saif, “In situ uniaxial mechanical testing of small scale materials – a review,” Nanoscience and Nanotechnology Letters 2, 282-287, 2010 (pdf)

8. J. Rajagopalan, A. Tofangchi and M. T. A. Saif, “Drosophila neurons actively regulate axonal tension in vivo,” Biophysical Journal 99, 3208-3215, 2010 (pdf)

7. J. Rajagopalan, C. Rentenberger, P. H. Karnthaler, G. Dehm and M. T. A. Saif, “In situ TEM study of microplasticity and Bauschinger effect in nanocrystalline metals,” Acta Materialia 58, 4772-4782, 2010 (pdf)

6. J. Rajagopalan, J. H. Han and M. T. A. Saif, “On plastic strain recovery in freestanding nanocrystalline metal thin films,” Scripta Materialia 59, 921-926, 2008 (pdf)

5. J. Rajagopalan, J. H. Han and M. T. A. Saif, “Bauschinger effect in unpassivated freestanding nanoscale metal films,” Scripta Materialia 59, 734-737, 2008 (pdf)

4. J. Rajagopalan, J. H. Han, and M. T. A. Saif, “Plastic deformation recovery in freestanding nanocrystalline aluminum and gold thin films,” Science 315, 1831-1834, 2007 (pdf)

3. J. Rajagopalan and M. T. A. Saif, “A single degree of freedom model for thermoelastic damping,” Journal of Applied Mechanics 74, 461-468, 2007 (pdf)

2. J. Rajagopalan, K. Balasubramaniam and C. V. Krishnamurthy, “A phase reconstruction algorithm for Lamb wave based structural health monitoring of anisotropic multilayered composite plates,” Journal of the Acoustical Society of America 119, 872-878, 2006 (pdf)

1. J. Rajagopalan, K. Balasubramaniam and C. V. Krishnamurthy, “A single transmitter multi receiver (STMR) PZT array for guided ultrasonic wave based structural health monitoring of large isotropic plate structures,” Smart Materials and Structures 15, 1190-1196, 2006 (pdf)

Lab focus

...

Lab focus

"To offer a state-of-the-art facility and processing capabilities open to all scientists and researchers in Australia and overseas to help realise outstanding research in materials and/or devices requiring sub-micrometre feature size for applications in, though not restricted to, photonics/opto-electronics."

 

The ANFF ACT is located at the Australian National University. Their facilities are based on photonic/electronic materials growth, processing and fabrication of devices including micro electro mechanical systems (MEMS). These facilities provide a range of capabilities and services for the micro/nanofabrication of photonic and related devices as well as the fabrication of waveguides and photonic crystals.

Inside RF/DC sputter coater, ANUOptoelectronic devices such as semiconductor lasers, photodetectors and modulators are widely used for communications, data storage, and medical applications. Further, photonic crystals, with their ability to confine light and guide and control its propagation, promise an entire suite of ultra-compact optical devices analogous to those of semiconductor electronics. Hence the node is internationally recognized for supporting both state-of-the-art research and proof-of-concept development for the industry.

ANFF-ACT also enjoys access to two well-known ANU research groups at the Laser Physics Centre and the Department of Electronic Materials Engineering. These groups bring expertise in the capabilities of high energy ion implantation, Si-etching, optical characterisation, and two metal organic chemical vapor deposition (MOCVD) reactors for the growth of III-V compound semiconductor multi- layers based on GaAs, AIGaAs, InGaAs, InP, InGaAsP, InAlGaAs, GaSb, InSb, and InGaAsN. These reactors enable the fabrication nanowires, quantum dots, quantum wells, strained layers, and devices.

Specialist fields:

  • micro/nano fabrication of photonic and related devices
  • fabrication of waveguides and photonic crystals
  • Micro-electro-mechanical-systems MEMS

Flagship facilities:

  • Raith 150 electron beam lithography system for nanostructure fabrication
  • RF /DC sputtering system for metal and dielectric multi-layer deposition
  • Cluster tool for dry etching and deposition
  • Dual beam focused ion beam
  • Nano imprint lithography

Please visit the lab's website for more information.

Publications

Lab focus

The Ringe Group was established in 2014 in the department of Materials Science and NanoEngineering (MSNE) at Rice University, Houston, TX, USA. Emilie Ringe and her...

Lab focus

The Ringe Group was established in 2014 in the department of Materials Science and NanoEngineering (MSNE) at Rice University, Houston, TX, USA. Emilie Ringe and her group focus on understanding and controlling light-matter interactions in small metallic nanoparticles for applications in biological sensing, enhanced spectroscopy, and light-driven heterogeneous catalysis.

By using correlated optical spectroscopy and electron microscopy tools, the group studies a phenomenon called localized surface plasmon resonance (LSPR), a type of light-matter interaction. LSPRs are a collective oscillation of the conduction electrons in a metal particle that leads to bright colors as well as strong electric fields at the surface of the particle. The resonance frequency changes with the surrounding environment, such that LSPR have exciting applications as nanosensors. Moreover, the strong fields can boost the catalytic activity of the metal surfaces.

Both electrons and photons can interact with plasmon resonances, yielding either photons or electrons. Using electron energy loss spectroscopy (EELS) and cathodoluminescence (CL), techniques using an electron-based excitation and yielding an electron and a photon signal, respectively, the Ringe group studies the symmetry and localization of plasmon modes. Recently, work on Au/Pd nanoparticles has demonstrated that these alloy nanoparticles containing a poor plasmonic metal (Pd in this case) can nevertheless sustain a strong plasmonic response, enabling applications such as plasmon-enhanced photocatalysis and in-situ reaction monitoring and switching. Multiple size-dependent LSPRs and strong spatially localized fields at the Pd-rich tip of stellated particles were observed, where the composition is in fact least favorable for plasmon resonances. A strong substrate coupling was demonstrated via EELS tilt series and shows that Pd is fully participating in the resonances observed. Results are shown below.

 

 

 

 

 

 

 

 

Please visit the lab's website for more information.

Publications

E. Ringe, C.J. DeSantis, S.M. Collins, M. Duchamp, R.E. Dunin-Borkowski, S.E. Skrabalak, P.A. Midgley. "Resonances of nanoparticles with poor plasmonic metal tips" Scientific Reports 5. 2015, 17431, doi:10.1038/srep17431.