# Development and Commercialization of a Sample Preparation System for Time Resolved Cryo-Electron Microscopy

> **NIH NIH R42** · HUMMINGBIRD PRECISION MACHINE COMPANY · 2021 · $840,405

## Abstract

Cryo-electron microscopy (cryo-EM) is a powerful technique for imaging biological molecules in
which samples are preserved in a frozen, hydrated state before imaging using an electron beam.
The technique provides an alternative to X-ray crystallography for structural characterization of
biological samples that are not crystallizable or do not crystallize in their native state. While cryo-
EM sample preparation technique has become more efficient in recent years with the
development of automatic sample vitrification systems to perform grid preparation, the field of
cryo-EM is hindered by the inability to perform time-resolved experiments on a sufficiently fast
time scale to observe the progression of many biological reactions due to the inherent lag of
traditional blotting methods. The Frank group at Columbia University has developed a lab-
prototype of a system to enable this missing capability and enables millisecond time control over
the reaction time of sampling biological reactions in the grid preparation process.
The purpose of this Fast-Track STTR proposal is to develop the time-resolved system built by the
Frank group into a commercial production unit and launch it as a product. Initial Phase I
milestones in the proposed work will focus on building a prototype with added control of reaction
parameters to determine necessary control variables in the system and to optimize sample grid
preparation and time resolution. Further work in Phase II of this Fast-Track proposal will create a
streamlined, user-friendly production unit which will maintain the necessary controls as
determined in initial milestones, while optimizing manufacturing time and reducing overall
production costs. The resulting system will add another dimension to the field of cryo-EM,
providing users with the capability to capture transient intermediates in reaction progression
studies and further clarifying proposed reaction mechanisms with time resolution.

## Key facts

- **NIH application ID:** 10231377
- **Project number:** 4R42GM139495-02
- **Recipient organization:** HUMMINGBIRD PRECISION MACHINE COMPANY
- **Principal Investigator:** JOACHIM FRANK
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $840,405
- **Award type:** 4N
- **Project period:** 2020-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231377

## Citation

> US National Institutes of Health, RePORTER application 10231377, Development and Commercialization of a Sample Preparation System for Time Resolved Cryo-Electron Microscopy (4R42GM139495-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10231377. Licensed CC0.

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