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Heterogeneity of protein corona (PC) composition using highly sensitive magnetic levitation (MagLev) system

Award Number: R03EB034817
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Heterogeneity of protein corona (PC) composition using highly sensitive magnetic levitation (MagLev) system - ABSTRACT The evolution of PC (layer of proteins/biomolecules that adsorbs at the surface of NPs upon contact by biological fluids) in vivo still remains highly challenging due to the complexity of human physiology, the complex nature of the biomolecules adsorbs on the surface, which is one of the main barriers of clinical translation of nanomaterials. The ex vivo approaches for preparation of PC on the surface of the model NPs do not provide homogenous corona formation as commonly perceived in the literature and the composition of the PC varies even across identical NPs with the same sizes in the same batch and using the same biological fluid. The current available PC characterizations or isolation techniques are not able to detect small variations in the composition of the PC and heterogeneity of the PC structure. Therefore, non-specific extraction and pool analysis of the PC in ex vivo condition may cause error and/or misinterpretation of the PC outcomes which significantly influence the clinical translation of NPs. We show in the preliminary data that although the standard MagLev systems are able to separate PC coated and uncoated NPs however, it is not able to discriminate among PC coated NPs with various PC composition at the surface of the NPs due their very similar density and low resolution of the standard MagLev systems. In this exploratory research we aim to develop a higher sensitivity MagLev system to show the heterogeneity and variation of PC composition on the surface of the NPs, a critical ignored factor in clinical translation of nanomaterials and failures of nanomedicine. In such highly sensitive MagLev configuration, the resolution enhances 1 to 3 orders of magnitude (compared with sensitivity of standard MagLev system (i.e., 10-3 g/cm3)) which is high enough to separate PC coated NPs with different PC coverages/compositions (e.g., number and type of the proteins at the surface) and very slight differences in the density (ranging from 0.001 g/cm3 to 0.00001 g/cm3 which is not detectable using standard MagLev system). Our preliminary data using a prototype high sensitivity MagLev system as proof-of-concept, confirms that how identical objects (i.e., commercial identical nylon particles) with the same density and levitation heights in the standard MagLev system have significant different levitation heights in a high sensitivity (prototype) MagLev system indicating low resolution of the standard of the MagLev systems to detect such small variations/changes. The current state-of- the-art in this type of separation is that there are simple proofs-of-concept of many of its foundational concepts, but little use of fully developed methods by biologists and clinicians. This project will both solidify the fundamental biophysical science of MagLev as a simple analytical tool in biochemistry and provide demonstrations of uses for nanomedicine applications.


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: 2025 ( Subtotal = $67,501 )
2025	2025	THE REGENTS OF THE UNIVERSITY OF COLORADO	1420 AUSTIN BLUFFS PKWY	COLORADO SPRINGS	CO	80918	EL PASO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	004	3	3/20/2025	NON-COMPETING CONTINUATION	$73,000
2025	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	1420 AUSTIN BLUFFS PKWY	COLORADO SPRINGS	CO	80918	EL PASO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	10/23/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$73,000
2025	2024	HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES	426 AUDITORIUM RD	EAST LANSING	MI	48824	INGHAM	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	1	2/21/2025	NEW	-$1
2025	2024	HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES	426 AUDITORIUM RD	EAST LANSING	MI	48824	INGHAM	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	10/23/2024	NEW	-$78,499
2025	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	1420 AUSTIN BLUFFS PKWY	COLORADO SPRINGS	CO	80918	EL PASO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	2	2/21/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
														Subtotal = $67,501

Issue Date FY: 2024 ( Subtotal = $78,500 )
2024	2024	HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES	426 AUDITORIUM RD	EAST LANSING	MI	48824	INGHAM	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	4/26/2024	NEW	$78,500
														Subtotal = $78,500

Grand Total All Awards = $146,001

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Heterogeneity of protein corona (PC) composition using highly sensitive magnetic levitation (MagLev) system

Award Number: R03EB034817

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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