| NSF Org: |
TI Translational Impacts |
| Recipient: |
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| Initial Amendment Date: | September 10, 2019 |
| Latest Amendment Date: | October 6, 2021 |
| Award Number: | 1926636 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Alastair Monk
amonk@nsf.gov (703)292-4392 TI Translational Impacts TIP Directorate for Technology, Innovation, and Partnerships |
| Start Date: | September 15, 2019 |
| End Date: | February 28, 2022 (Estimated) |
| Total Intended Award Amount: | $748,638.00 |
| Total Awarded Amount to Date: | $898,365.00 |
| Funds Obligated to Date: |
FY 2020 = $149,727.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
8 HARRIS CT STE C5 MONTEREY CA US 93940-5715 (925)708-4171 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
8 Harris Ct. STE C5 Monterey CA US 93940-5713 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | SBIR Phase II |
| Primary Program Source: |
01002021DB NSF RESEARCH & RELATED ACTIVIT |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.084 |
ABSTRACT
The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be the development of an analytical instrument to detect protein changes across all stages of protein production. The production of highly-engineered therapeutic proteins has outpaced the development of analytical assays to guarantee effectiveness, purity, and shelf life of the drug. A key control parameter during manufacturing is protein conformation; currently, this is difficult to monitor with commercially available technology. The goal of this project is to provide manufacturers with a new generation of analytical technology that allows them to identify variations between batches. This technology also provides information about product stability so manufacturers can guarantee a longer shelf life for their products, regardless of storage conditions. It is anticipated that this instrument will increase efficacy at all stages, from discovery through scaled-up production and formulation to pre-release certification.
This SBIR Phase II project aims to improve biotherapeutic drug production through the commercialization of analytical technology that provides a new metric for the rapid QC/QA assessment of the conformation of proteins. The gold standard for determining protein conformation is x-ray crystallography - a time-consuming technique that requires high quality crystals and a high-energy physics facility to produce coherent x-rays. The proposed highly sensitive bench-top ion mobility spectrometer detects small variations in the cross-sectional area of a protein and detects small conformational changes. This provides a capability to determine protein stability during discovery when only microgram quantities of recombinantly expressed proteins are available. This process also indicates if a protein refolded after it was subjected to a pH change during purification, and thus it may be used to identify challenges to long-term shelf life. This instrument will be used to demonstrate that for the first time, ion mobility will produce highly-reproducible and biologically relevant measurements of the quality of biomanufactured proteins.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
Project Outcomes Report for NSF Award 1926636
Project title: Ion Mobility Spectrometer for Macromolecular Analysis
Type of Project: SBIR Phase II
Recipient Company: IonDX, Inc., 8 Harris Ct., C5, Monterey, CA 93940
Recipient Contact: W. Henry Benner, Ph.D. (PI)
Performance period: 09/15/2019 ? 02/28/2022
Funding for this project enabled IonDX to commercialize a new type of ion mobility spectrometer. The spectrometer is used by scientists to characterize macromolecules, such a biotherapeutic proteins, throughout all stages of drug development. The trademarked name of the spectrometer (IMgeniusTM ) is derived from I = Ion, M = Mobility and the genius part stems from its simple design. The performance specifications of IMgenius allow bioanalytical scientists to quantify certain properties of proteins in several new way that leads to a better understanding of the function and stability of the protein and ultimately to a well-developed drug product.
Three R&D phases were used to develop the spectrometer. In phase I, physical principles were evaluated as techniques for quantifying the conformation of proteins. The conformation of a protein determines its function and when a protein is denatured, its shape or conformation is altered which destroys is function. We determined that a combination of aerodynamic and electrostatic forces could be engineered into a device to measure the size of a molecule by determining how fast a molecular ion flies through a gas under the influence of an electric field. We then simulated the performance of a bench-top sized spectrometer based on these physical principles.
In Phase II of the project, we fabricated a prototype instrument and evaluated its performance by analyzing a series of pure proteins. We also established a plan to provide investigators with early access to the instrument so we could discover how to make it more user friendly, how to make the analyses more reproducible and how to process raw data into tables and charts as is needed report results in a clear and concise manner. We learned that several components needed to be replaced with higher quality components. We used this feedback from early users to design a precommercial instrument, which we fabricated and tested.
In Phase III of the project, we finalized the design and fabricated several commercial instruments. We established a customer relations program to provide the user with pre-installation site modification requirements, developed an installation protocol and provided the user with training and service. We established a marketing plan and developed application notes that describe the technology and how IMgenius can be used to study protein stability, survey proteins for glycosylation, analyze lipoproteins, quantify protein folding patterns and detect protein-nucleic acid binding patterns.
Last Modified: 04/01/2022
Modified by: W H Benner
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