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

Award Number: R44GM137675
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	SIGRAY, INC.	5750 IMHOFF DR	CONCORD	CA	94520	CONTRA COSTA	USA	Biomedical Research and Research Training	000	3	9/28/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $786,248 )
2021	2021	SIGRAY, INC.	5750 IMHOFF DR STE I	CONCORD	CA	94520	CONTRA COSTA	USA	Biomedical Research and Research Training	000	3	6/14/2021	NON-COMPETING CONTINUATION	$786,248
														Subtotal = $786,248

Issue Date FY: 2020 ( Subtotal = $857,728 )
2020	2020	SIGRAY, INC.	5750 IMHOFF DR STE I	CONCORD	CA	94520	CONTRA COSTA	USA	Biomedical Research and Research Training	000	2	4/13/2020	COMPETING CONTINUATION	$857,728
														Subtotal = $857,728

Grand Total All Awards = $1,643,976

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

Award Number: R44GM137675

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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