# Cryo ptychography combined with x-ray fluorescence analysis of metals in cells

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $254,667

## Abstract

Summary
X-ray fluorescence microscopes (XFM) offer the highest sensitivity for studies of the role of trace metals in
cells, and they provide essential information for understanding the ultrastructural targeting of nanoparticles
used for potential cancer therapies. With NIH support, we have developed approaches to rapidly freeze cells
for the best preservation of trace metal content as well as cellular ultrastructure, and have shown that cryo x-
ray fluorescence microscopy can be used to effectively mitigate radiation damage limitations in the
Bionanoprobe, an instrument operated at the Advanced Photon Source (APS) at Argonne and open to
researchers based on peer-reviewed, no-cost beamtime proposals. In order to complement XFM's ability to
quantitatively image trace element distributions, we have developed high throughput x-ray ptychography (a
scanned coherent beam imaging method) to go beyond lens limits and simultaneously obtain 18 nm resolution
images of frozen hydrated eukaryotic cells, complementing XFM by providing a high resolution view of cellular
ultrastructure. We propose here to develop and validate cryo confocal light microscopy of Bionanoprobe-
mounted samples to complement XFM with the capability to image selectively labeled proteins, and to move
ptychography from 2D to 3D imaging. To validate these approaches and work from the beginning on a crucial
biomedical research project, we will do this in the context of ongoing research in the use of DNA-conjugated
nanoparticles containing titanium and/or gadolinium that are meant to target mitochondria for the treatment and
imaging of prostrate, breast, and other cancers. In this way, we will develop the methods needed to fully realize
the investment NIH has already made in the Bionanoprobe, and build upon Argonne's investment in increasing
its available access time at a new experimental station at the APS.

## Key facts

- **NIH application ID:** 9899251
- **Project number:** 5R01GM104530-08
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Chris Johnson Jacobsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,667
- **Award type:** 5
- **Project period:** 2013-02-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899251

## Citation

> US National Institutes of Health, RePORTER application 9899251, Cryo ptychography combined with x-ray fluorescence analysis of metals in cells (5R01GM104530-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9899251. Licensed CC0.

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