# Technology for sample preparation and storage for cryo-electron microscopy

> **NIH NIH R43** · MITEGEN, LLC · 2020 · $225,000

## Abstract

Project Summary
 As a result of technical advances in the last decade, single-particle cryo-electron microscopy (cryo-EM) has
emerged as a powerful approach to obtaining near atomic resolution structures of large biomolecular complexes,
membrane proteins, and other biologically and biomedically important targets that in many cases have been
intractable to X-ray crystallography. Cryo-EM requires only small amounts of biomolecule dispersed in solution
and has become a first choice for initial attempts at structure determination. Enormous investments have been
and continue to be made in new microscopes and cryo-EM facilities at universities and biomedical research
institutes in the US and around the world. However, current sample preparation and handling protocols – largely
based on work from the 1980s, are complex, time consuming, error-prone, and often yield suboptimal outcomes.
They are a major factor limiting efficient use of these expensive new facilities.
 This Phase I SBIR project builds on insights into fundamental processes of cryocooling, vitrification, and the
thermomechanical response of multicomponent systems, and on MiTeGen's extensive expertise in development
of tools and instruments for microsample manipulation and cryocooling. New sample holding supports will be
developed that increase maximum sample cooling rates and sample quality, reduce mechanical stresses during
cooling that are the primary source of resolution-degrading sample motion in the electron beam, facilitate
characterization and optimization of sample preparation and cryocooling processes, and enable sample
identification and tracking. A new automated sample cooling instrument will be developed that uses liquid
nitrogen rather than liquid ethane as the primary sample coolant while delivering outstanding sample vitrification
performance. The longer-term goal of this project is to deliver an integrated cryo-EM solution comprised of
improved sample supports and tools for their safe handling, storage, and tracking, improved tools for sample
thinning/removal, and an automated sample cryocooling and cryostorage system with integrated sample tracking
that eliminates manual manipulations, provides a stable, contaminant-free cold chain from sample plunging to
the microscope, and that substantially improves the efficiency of cryo-EM structure determination pipelines.

## Key facts

- **NIH application ID:** 10010925
- **Project number:** 1R43GM137720-01
- **Recipient organization:** MITEGEN, LLC
- **Principal Investigator:** Benjamin Arthur Apker
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $225,000
- **Award type:** 1
- **Project period:** 2020-06-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10010925

## Citation

> US National Institutes of Health, RePORTER application 10010925, Technology for sample preparation and storage for cryo-electron microscopy (1R43GM137720-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10010925. Licensed CC0.

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