# Development of Sub 100 nm Resolution X-ray Nanotomography of Centimeter-Sized Tissues

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $369,802

## Abstract

Project 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:** 10085683
- **Project number:** 5R01MH115265-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Chris Johnson Jacobsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $369,802
- **Award type:** 5
- **Project period:** 2018-01-05 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085683

## Citation

> US National Institutes of Health, RePORTER application 10085683, Development of Sub 100 nm Resolution X-ray Nanotomography of Centimeter-Sized Tissues (5R01MH115265-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10085683. Licensed CC0.

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