# Cryogenic High-throughput Cellular Imaging System

> **NIH NIH R44** · SIGRAY, INC. · 2022 · $998,003

## Abstract

Project Summary/Abstract
X-ray microscopy has evolved into an important ultrastructure imaging approach for visualizing
and measuring intact cells in three dimensions. Beamlines dedicated to cellular imaging have
been constructed at synchrotron facilities around the world, and the co-PI of this proposal
developed the first commercial laboratory x-ray microscope for cellular imaging. The
approaches thus far have centered around the use of “water window” x-rays, having energies
between 285 to 540eV and for which water is transparent but organic content is absorbing.
However, there are several major drawbacks to using these low energy x-rays: they severely limit
the size of cells that can be imaged (e.g., <10 µm when many mammalian cells are 10-100 µm).
This SBIR proposal aims to develop a 3D nano x-ray microscope capable of high throughput
(~30 minute) 3D imaging of cryogenically preserved cells of up to 80 µm in diameter at down to
30nm resolution. The system utilizes the phenomenon of Zernike phase contrast at higher (2.7
keV) energy x-rays, which can achieve even higher contrast for biological samples than water
window x-rays. Additionally, the system will enable several major advantages over water
window x-ray microscopy, including much larger cell imaging (80µm vs. 10µm), larger depth-of-
field for higher 3D resolution, and practical benefits (more stable x-ray source and larger
working distance to incorporate correlative techniques). The microscope uses the company’s
patented high brightness x-ray source and proprietary x-ray optic technology.
The project will develop the proposing company’s existing 2.7 keV ambient system to enable
cryogenic operation and optimize its performance for cellular imaging. The proposed Phase II
24-month project is to develop a complete cryogenic 2.7 keV system for cellular imaging and to
experimentally demonstrate its performance on mammalian cells.

## Key facts

- **NIH application ID:** 10545696
- **Project number:** 1R44GM148148-01
- **Recipient organization:** SIGRAY, INC.
- **Principal Investigator:** Wenbing Yun
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $998,003
- **Award type:** 1
- **Project period:** 2022-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10545696

## Citation

> US National Institutes of Health, RePORTER application 10545696, Cryogenic High-throughput Cellular Imaging System (1R44GM148148-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10545696. Licensed CC0.

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