# A high precision piezo driven replacement goniometer for cryoelectron microscopy

> **NIH NIH R43** · HUMMINGBIRD PRECISION MACHINE COMPANY · 2021 · $241,587

## Abstract

Project Summary
Project Title: A high precision piezo driven replacement goniometer for cryoelectron
microscopy
Company Name: Hummingbird Precision Machine Co., dba Hummingbird Scientific
Principal Investigator: Joseph Stevick
Summary:
Biomolecular structures resolved by cryoelectron microscopy (Cryo-EM) have
significantly advanced our understanding of life processes, specifically in the areas of
drug design, vaccines, and other microbiological health solutions. The technique has
been so successful and transformative that it was awarded the Nobel Prize for Chemistry
in 2017, and more recently was used to solve the structure of the RNA-dependent RNA
polymerase from the COVID-19 virus. The biochemical models produced by Cryo-EM
studies like this one are vital to researching anti-viral drugs and other microbiological
solutions in addition to helping shape our basic understanding of molecular machinery.
However, there is a significant technology gap in Cryo-EM hardware that has been
overlooked. Transmission electron microscope (TEM) side-entry goniometers (sample
positioning systems) were designed before the Cryo-EM technique was developed, and
cryogenic side-entry holders are unstable and inconvenient. As a result, closed-loop
automated of Cryo-EM workflows becomes inefficient and limited to what the positioning
system can achieve rather than what is scientifically important. Time consuming image
tracking and error correction methods are currently used to compensate for the poor
mechanical positioning capabilities of goniometers and side-entry holders.
Our solution is to design a modern sample motion control stage and a corresponding
sample holder as a purpose-built combination that is optimized for repeatability, accuracy,
and stability at cryogen temperatures. The proposed design will improve state-of-the-
art Cryo-EM automation by more than an order of magnitude in precision and
increase Dewar life by a factor of 5. This improvement is made possible by a unique
ground-up design that optimizes the stage, holder, and cryo-system simultaneously. In
Aim 1, we will optimize the stage and holder, utilizing an unconventional design that limits
coupled motion, and employs modern mechatronic technologies and sensing methods
that will dramatically improve the closed-loop precision of our stage in comparison with
current goniometers. In Aim 2, we will optimize the cryo-system design for stable -170°C
sample temperatures and ease of use in concert with the stage and holder. As a
commercial product, this device would act as a simple retrofit replacement to goniometers
on thousands of TEMs that are already dedicated to biological research. Our long-term
objective is to empower more scientists with the instruments they need to achieve the
best possible Cryo-EM results without having to struggle with basic hardware issues.

## Key facts

- **NIH application ID:** 10254580
- **Project number:** 1R43GM142332-01
- **Recipient organization:** HUMMINGBIRD PRECISION MACHINE COMPANY
- **Principal Investigator:** Norman James Salmon
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $241,587
- **Award type:** 1
- **Project period:** 2021-09-20 → 2024-06-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254580

## Citation

> US National Institutes of Health, RePORTER application 10254580, A high precision piezo driven replacement goniometer for cryoelectron microscopy (1R43GM142332-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10254580. Licensed CC0.

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