{"response":{"award":[{"abstractText":"The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to provide analytical technology that will foster the commercial development of complicated biomanufactured products. The most pressing need is to reduce the time and cost to bring the latest generation of biotherapeutic drugs to market. Currently, upwards of eight years and $1B is spent to move a candidate drug from discovery through final approval. Along the way $300M is consumed by analytical testing procedures to certify the product. The American healthcare system will benefit from new and less expensive analytical technologies that reduce certification costs and lead to less expensive drugs. Manufacturing efficiency also can be improved using the proposed technology. Biomanufactured products are harvested from cultured cells, and there are times when the culturing process fails to produce a perfect product. Detecting impurities and spoilage during manufacturing will further reduce manufacturing costs and directly benefit the consumer through the delivery of better therapeutic products and treatment regimens.\r\n\r\nThis SBIR Phase I project proposes to quantify the validity of an ion mobility spectrometer as a high-throughput tool for screening conformational variation, purity, and aggregation of biotherapeutic drugs. Conformation imparts functionality to a protein and any variation in conformation implies there is a variation in biochemical activity, which is undesirable. Ion mobility is a technique that determines molecular cross-section, which in turn is a measure of a molecule's conformation. The gold standard for determining protein conformation is x-ray crystallography, a methodology limited by throughput. There is an unmet need to develop faster ways to measure protein conformation. The proposed technology determines a protein conformation rapidly across all phases of biotherapeutic drug development from discovery, expression system testing, scale up and manufacturing. Additionally, the patented design for this ion mobility spectrometer provides a way to measure changes in conformation that might result as a consequence of exposure to thermal, chemical, and photo-induced stress as needed for drug stability and developability testing. The proposed work will quantify resolution, reproducibility, accuracy, and throughput for this benchtop instrument. The evaluation will be performed using antigen-antibody pairs and several biotherapeutic drugs in collaboration with an academic group and industry partners.\r\n\r\nThis 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.","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"ION DX, INC.","awardeeAddress":"8 HARRIS CT STE C5","awardeeCity":"MONTEREY","awardeeCountryCode":"US","awardeeDistrict":"19","awardeeDistrictCode":"CA19","awardeeName":"Ion Dx, Inc.","awardeePhone":"9257084171","awardeeStateCode":"CA","awardeeZipCode":"939405715","cfdaNumber":"47.084","date":"06/14/2018","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"225000","expDate":"03/31/2019","fundAgencyCode":"4900","fundProgramName":"SBIR Phase I","fundsObligated":["FY 2018 = $225,000.00"],"fundsObligatedAmt":"225000","histAwd":"false","id":"1819381","initAmendmentDate":"06/14/2018","latestAmendmentDate":"06/14/2018","managingPec":"537100","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"JTUZH4SWHKQ3","pdPIName":"William H Benner","perfAddress":"8 Harris Ct., STE C-5","perfCity":"Monterey","perfCountryCode":"US","perfDistrict":"19","perfDistrictCode":"CA19","perfLocation":"Ion Dx, Inc.","perfStateCode":"CA","perfZipCode":"939405715","pi":["William H Benner hbenner@iondx.com"],"piEmail":"hbenner@iondx.com","piFirstName":"William","piId":"269940694","piLastName":"Benner","piMiddeInitial":"H","poEmail":"rshuman@nsf.gov","poName":"Ruth Shuman","poPhone":"7032922160","primaryProgram":["01001819DB NSF RESEARCH & RELATED ACTIVIT"],"progEleCode":"537100","program":"SMALL BUSINESS PHASE I, Biotechnology","progRefCode":"5371, 8038","projectOutComesReport":"
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Biotherapeutic drugs such as therapeutic antibodies are difficult to characterize because of their molecular complexity and the way they are manufactured. These drugs are long compact protein chains of approx. 1300 amino acids. They are excreted by cells cultured in large tanks and require many process and purification steps that sometimes can go wrong. Their complexity forces rigid control (an expense) over the cell culturing process and results in an extensive analytical effort to prove batch-to-batch conformity. The development of advanced analytical methods for characterizing complicated proteins has not kept up with the growth in biotherapeutic drug discovery and production.

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Ion Dx designed and fabricated a simple stand-alone bench top ion mobility spectrometer to solve this unmet need to characterize biotherapeutic drugs rapidly during all stages of product development. Ion mobility determines molecular size, aka, molecular shape. The advantages of our design for a bench top ion mobility spectrometer over commercially available ion mobility spectrometers are 1) minimal space is required, 2) operation is simple, 3) purchasing and operating costs are much less, 4) sample consumption is minimal and 5) multiple assays are offered. Our technology will help certify that the molecular shape remains constant during all the bioprocessing steps.

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We participated in NSF's Beat-the-Odds Boot Camp during which we conducted interviews with potential end users of our technology. We learned that biotherapeutic manufacturers desire to expand their analytical capabilities to include analytical techniques for quantifying the conformation of their products. Specifically, they are looking for rapid and accurate methods that will determine protein stability, variation in conformation and instruments that provide analysis of  multiple attributes and will easily fit into automated sample workflows.

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During the course of this project, the performance of a first prototype spectrometer was evaluated and several updated features were added to meet customers expectations. This led to fabrication of a second-generation prototype that was 1/3 the initial size, operates at atmospheric pressure, thus minimizing vacuum pumping requirements (a cost and complexity reduction), operates in static and scanning modes for improved molecular characterization and produces three analytical measurements. We generated data that quantified measurement reproducibility (+/- 0.8 %), sensitivity (0.4 ?g of sample required), provides flexibility to meet individual customers? analytical needs (3 modes of operation), and allowed us to solve a number of engineering design hurdles necessary for transitioning to a Phase II project.  

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\n\t\t\t\t \tLast Modified: 04/02/2019
\n\t\t\t\t\tModified by: W H Benner

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","publicAccessMandate":"1","startDate":"07/01/2018","title":"SBIR Phase I: Ion Mobility Spectrometer for Macromolecular Analysis","transType":"Standard Grant","ueiNumber":"JTUZH4SWHKQ3"}],"metadata":{"offset":0,"rpp":25,"totalCount":1}}}