# Development of a Laboratory Transmission X-ray Microscope for Rapid 3D Cellular Tomography using Zernike Phase Contrast with 2.7 keV

> **NIH NIH R44** · SIGRAY, INC. · 2021 · $786,248

## Abstract

Project Summary/Abstract
X-ray microscopy has newly developed into an important new cellular imaging technique for
visualizing and measuring intact cells in three dimensions. The development of these systems,
enabled by advances in x-ray optic and detector technology, has been primarily driven at
synchrotron light source facilities. The first laboratory x-ray microscopes for cellular imaging
were introduced by the proposal’s co-PI in 2009 and utilized the absorption contrast of “water
window” (285-540eV) x-rays for imaging. The system enabled unstained cellular tomography
for the first time in the laboratory. However, the system operational energy is too low for most
mammalian cells, which are larger in diameter than eukaryotic (yeast, bacteria, etc.) cells that
the water window enables.
We propose to develop a new 2.7 keV x-ray laboratory cellular microscope to provide fast (~30
minute) and high contrast complete 3D imaging of unstained cells of up to 80um in diameter
and their organelles at 30nm resolution. The system operates using Zernike phase contrast at
2.7 keV energy x-rays, which provides higher contrast than even absorption contrast of 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 proposed Phase II 24-month project is to develop a complete prototype 2.7 keV Zernike
phase contrast system for cellular imaging and to experimentally verify its performance.

## Key facts

- **NIH application ID:** 10144488
- **Project number:** 5R44GM137675-03
- **Recipient organization:** SIGRAY, INC.
- **Principal Investigator:** David Vine
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $786,248
- **Award type:** 5
- **Project period:** 2020-04-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144488

## Citation

> US National Institutes of Health, RePORTER application 10144488, Development of a Laboratory Transmission X-ray Microscope for Rapid 3D Cellular Tomography using Zernike Phase Contrast with 2.7 keV (5R44GM137675-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10144488. Licensed CC0.

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