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3D Fourier Imaging System for High Throughput Analyses of Cancer Organoids

Award Number: R21CA267222
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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3D Fourier Imaging System for High Throughput Analyses of Cancer Organoids - Challenges. Tumor spheroids (and organoids) have become an instrumental tool in cancer research. These self-organized, three-dimensional (3D) systems can recapitulate phenotypic and functional traits of patient tumors in vivo, thereby serving as a powerful testing bed to study tumor heterogeneity, interactions with the environment (e.g., extracellular matrix), and responses to external stimuli (e.g., chemotherapy, radiation). Fully harnessing spheroids' utility, however, is stymied by lack of high-throughput analysis methods. Conventional bright-ﬁeld microscopy, although widely used to monitor spheroids in culture, fails to capture detailed cellular organizations; advanced ﬂuorescent microscopy can resolve individual cells, but its imaging throughput is restricted by the small ﬁeld-of-view (FOV) and the scanning mechanisms involved. Innovations. We aim to advance a new volumetric imaging microscope (VIM) for single cell analyses in tumor spheroids. Speciﬁcally, we will explore integrating Fourier ptychographic microscopy (FPM) with diffraction tomography. FPM is based on a spatially coded-illumination technique, collecting low resolution image sequences while changing the position of a point-light source. These images are then numerically combined in the Fourier space, which allows FPM to achieve both wide ﬁeld-of-view and high spatial resolution in 2D images. We reason that full 3D microscopic images can be recovered by accounting for optical diffraction during the numerical reconstruction. Approaches. Aim 1. System development. We will build a VIM system featuring: i) a new numerical algorithm to reconstruct 3D volumetric images; ii) a new light-illumination strategy to speed up the data acquisition; iii) microﬂuidic cartridges optimized for spheroid culture and drug treatment; and iv) multicolor imaging capacity for molecular detection. The complete VIM will resolve individual cells constituting a spheroid at high resolution (lateral, 0.4 µm; axial, 1 µm) in a large imaging volume. Aim 2. Treatment monitoring with tumor spheroids. We will test VIM's practical utility: VIM-enabled spheroid imaging will reveal earlier than bulk imaging whether a spheroid is responsive or resistance to drug treatment. To generate a tumor model, we will use primary GBM cells from patients. GBM spheroids will be grown and treated with drug (temozolomide) inside microﬂuidic cartridges. We will use the VIM to monitor how single cells change their phenotypes under treatment, and correlate these changes with treatment outcomes. Impact. The VIM will be a transformative tool for cancer research, empowering researchers with rich data sets and substantially advanced analytics. Immediate applications include better monitoring of anticancer drug responses in 3D cell culture, analyzing cellular heterogeneity, and prospectively detecting cellular fate under various physiological conditions. These outcomes will strengthen the clinical and scientiﬁc utility of tumor spheroids in cancer research.


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: 2026 ( Subtotal = $0 )
2026	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	3	3/30/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $223,840 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	3	2/21/2024	NON-COMPETING CONTINUATION	$212,058
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	3	4/17/2024	NON-COMPETING CONTINUATION	$11,782
														Subtotal = $223,840

Issue Date FY: 2023 ( Subtotal = $192,424 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	2	2/22/2023	NON-COMPETING CONTINUATION	$192,424
														Subtotal = $192,424

Issue Date FY: 2022 ( Subtotal = $196,350 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	1	2/22/2022	NEW	$196,350
														Subtotal = $196,350

Grand Total All Awards = $612,614

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3D Fourier Imaging System for High Throughput Analyses of Cancer Organoids

Award Number: R21CA267222

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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