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Cryo-EM CoRE

Cryogenic electron microscopy (Cryo-EM) is transforming our understanding of disease mechanisms and accelerating drug development in both academia and industry. The Dean’s Cryo-EM Core Facility at Mount Sinai offers state-of-the-art instrumentation capable of producing near atomic resolution data and is accessible to both internal and external users.

The Core provides two primary services:

  • Vitrobot vitrification system for sample preparation
  • Glacios 2 Cryo-TEM, from Thermo Fisher Scientific, for image acquisition

The Glacios 2 Cryo-TEM is a 200kV microscope that enables high-throughput, near-atomic data collection across a wide range biological target. Compared with the previous generation, it offers improved throughput, enhanced accessibility and integrated features such as Falcon 4i Direct Electron Detector and Thermo Scientific EPU Software, for superior image quality, automate data acquisition, and streamlined workflows. The system supports Single Particle Analysis (SPA), Tomography and Micro-ED applications. 

The Cryo-EM CoRE specializes in preparing proteins, nucleic acids, and other biological materials on glow-discharged grids for vitrification, followed by high-quality micrograph imaging. The Falcon 4i direct electron detection camera allows imaging of even the most challenging biological samples, making complex structural investigations possible.

In collaboration with the New York Structural Biology Center, we also provide comprehensive training and support for researchers in sample preparation and data acquisition. The Cryo-EM CoRE operates on weekdays, providing project consultation, sample preparation, data acquisition (screening sessions and overnight data collection), preliminary data processing, and data interpretation.

Explore the Cryo-Em CoRE

As the CoRE operates on a fee-for-service basis, all users must first register for an iLab account and have PI authorization before using services. Billing is initiated upon service request and invoiced after the session or on monthly basis.

New User Onboarding Steps:

  1. Create an iLab account
    • Ensure that you have access to the correct lab and funding sources to charge
    • Departmental administrators and PIs can approve requests to join a lab and grant you access to funding sources
  2. Complete the consultation request via iLab (Initial consultation is applicable for new users)
  3. Upon receiving the request, we will reach out to either set up an on-site or remote visit
  4. Once the samples are ready, sample preparation and imaging scheduling can be done via iLab.

The main equipment needed for the Cryo-EM CoRE are the Glacios 2 CryoTEM and the Vitrobot Mark IV.

  • Glacios 2 CryoTEM - Equipped with Ceta-M and Falcon 4i cameras, an X-FEG electron source, and a 12-slot autoloader. Maintained and validated periodically by CoRE staff.
  • Vitrobot Mark IV: Temperature and humidity-controlled vitrification system for sample preparation.

We offer Vitrobot training and certification for new users. The certification covers handling and preparing samples. Currently, Glacios 2 Cryo-TEM microscope operation and maintenance are performed only by CoRE Scientists.

The CoRE has a dedicated computational system installed with advanced image processing software and provides on-the-fly data processing using CryoSPARC. The four CoRE GPU workstations will help in analyzing and interpreting the initial data generated from the microscope.

  • We use iLab for instrument scheduling, ordering consumables, and billing.
  • Standard operation hours are Monday - Friday (10:00 AM - 5:30 PM). No access is provided outside working hours
  • Certified trained users will book the sample preparation equipment at a reduced cost (new policy on how the user is trained and certified will be implemented soon).
  • Before booking equipment, CoRE recommends that all new Cryo-EM users schedule a project consultation via email or the iLab booking system.
  • Cryo-EM users must reserve the Vitrobot Mark IV at least 24 hours in advance via the iLabs booking system.
  • We can provide preliminary on-the-fly 2D data processing using CryoSPARC for academic users during their Glacios 2 Cryo-TEM reservation.
  • We utilize Minerva to transfer screening images, raw data, project files to users anywhere over the internet (internal users within Mount Sinai).
  • In the event of an instrument/software malfunction, users will not be charged for the time during which the microscope/software was not functional. Affected users will also be given the opportunity to reserve a new microscope session for the next available time slot.
  • External academic Cryo-EM users are welcome to use our instrumentation.
  • We offer policies similar to internal users, and we encourage all external users to visit the facility and be present, if possible, during screening session.
  • We encourage users to bring their external HDDs or use the GLOBUS system to transfer screening images, raw data, project files to users anywhere over the internet
  • Industry users are welcome to use our EM facility (BSL 1 samples only)
  • Industry users are welcome to observe all steps of the Cryo-EM process (grid freezing, screening, and data collection) in-person or remotely.
  • We would be happy to work with your legal department(s) on necessary contracts and agreements.
  • Pricing is project-based and will be discussed during the contract development.

All users of our CryoEM CoRE facility are advised to acknowledge the support of the S10 awards in publications with acknowledgement as follows:

“This work utilized the Glacios 2 Cryo-TEM located at the Cryo-EM CoRE facility of the Icahn School of Medicine at Mount Sinai, which was acquired with funding from the National Institutes of Health (NIH) under grant number 1S10OD036213-01.

 

Meet the Cryo-EM CoRE Team

Aneel K Aggarwal, PhD
Aneel K Aggarwal, PhD

Facility Director

Daniel Wacker, PhD
Daniel Wacker, PhD

Facility Director

RAMPRADEEP SAMIAPPAN
RAMPRADEEP SAMIAPPAN

Core Scientist

Frequently Asked Questions

No. At this instance, the CoRE trains users on sample preparation and operation. Maintenance of Glacios 2 Cryo-TEM is performed by our CoRE Scientists.

The CoRE provides data acquisition and on-the-fly image processing using CryoSPARC. We will provide initial 2D classification obtained from the on-the fly data. No manual in-depth image processing will be performed with the user’s data.

Once the data acquisition is performed, the data is transferred to the user’s Minerva accounts and can be accessed via the following path:

(Sc/arion/projects/cryoemusers/username).

For external users, the data is transferred to CoRE’s Minerva account and is shared via GLOBUS system

(Sc/arion/projects/cryoemusers/samiar01/).

Please note that the data retention time is 90 days on Minerva and 30 days on the Glacios 2 Cryo-TEM storage server.

Yes, a summary report shall be provided to the users with all necessary information required for image processing equipment (Vitrobot Mark IV) for the new and external users.