{"response":{"award":[{"abstractText":"The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is to advance the current state-of-the-art biological detection technologies. Both in vitro diagnostics and the pharmaceutical industry rely on biotechnology tools to discover and develop new molecular interactions. Since all biological pathways rely on protein-DNA and protein-protein interactions, not only is accurate characterization of these interactions crucial, but they are prime targets for disruption with small molecules in disease treatment. Emerging diseases call for new diagnostic tests and thus new molecular discoveries. This Technology Translation (PFI-TT) project will pave the way to commercialization of a new technology based on light interference. There will be a direct societal impact by enabling better diagnostics and therapeutics. In addition, we will train several women engineering PhD students in technology development and entrepreneurship. \r\n\r\nThe proposed project builds on innovations in Interferometric reflectance imaging sensor (IRIS) technology. The underlying measurement principle is based on the interference of light reflected from an optically transparent thin film—the same phenomenon that gives rainbow colors to a soap film when illuminated by white light. The proposed innovation uses a different approach than the conventional method of enhancing the signal through complex optical resonances; instead, we exploit the power of signal averaging to achieve very high sensitivity in a simple instrument platform. By design, the IRIS technique is resilient to the background signal due to variations in the solution (termed “bulk effect”). The proposed new technique will further improve the ability to distinguish molecular binding on the surface from the variations in the bulk solution. The proposed IRIS platform is unique among all label-free optical biosensors with multiplexed detection of molecular binding kinetics on Si microfludic chips as low-cost consumables. Hundreds of capture probes can be arrayed on the IRIS chip and tested against a target molecule in parallel. The expected low cost of the instrument will allow for integration of parallel sensors to achieve high throughput and multiplexing simultaneously.\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":"TRUSTEES OF BOSTON UNIVERSITY","awardeeAddress":"1 SILBER WAY","awardeeCity":"BOSTON","awardeeCountryCode":"US","awardeeDistrict":"07","awardeeDistrictCode":"MA07","awardeeName":"Trustees of Boston University","awardeePhone":"6173534365","awardeeStateCode":"MA","awardeeZipCode":"022151703","cfdaNumber":"47.084","date":"04/24/2020","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"249996","expDate":"10/31/2022","fundAgencyCode":"4900","fundProgramName":"PFI-Partnrships for Innovation","fundsObligated":["FY 2020 = $249,996.00"],"fundsObligatedAmt":"249996","histAwd":"false","id":"1941195","initAmendmentDate":"04/24/2020","jrnl":[{"artTitl":"Sensitive and real-time detection of IgG using interferometric reflecting imaging sensor system","auth":"Bakhshpour, Monireh and Chiodi, Elisa and Celebi, Iris and Saylan, Yeeren and Ünlü, Nese Lortlar and Ünlü, M. Selim and Denizli, Adil","dgtlObjId":"https://doi.org/10.1016/j.bios.2021.113961","jrnlTitl":"Biosensors and Bioelectronics","jrnlVol":"201","jrnlYr":"2022","parPblcId":"10401318"},{"artTitl":"Instrument-Free Protein Microarray Fabrication for Accurate Affinity Measurements","auth":"Celebi, Iris and Geib, Matthew T. and Chiodi, Elisa and Lortlar Ünlü, Nese and Ekiz Kanik, Fulya and Ünlü, Selim","dgtlObjId":"https://doi.org/10.3390/bios10110158","jrnlTitl":"Biosensors","jrnlVol":"10","jrnlYr":"2020","parPblcId":"10233924"},{"artTitl":"Multiplexed Affinity Measurements of Extracellular Vesicles Binding Kinetics","auth":"Chiodi, Elisa and Daaboul, George G. and Marn, Allison M. and Ünlü, M. Selim","dgtlObjId":"https://doi.org/10.3390/s21082634","jrnlTitl":"Sensors","jrnlVol":"21","jrnlYr":"2021","parPblcId":"10233926"},{"artTitl":"The Effects of Three-Dimensional Ligand Immobilization on Kinetic Measurements in Biosensors","auth":"Chiodi, Elisa and Marn, Allison M. and Bakhshpour, Monireh and Lortlar Ünlü, Nese and Ünlü, M. Selim","dgtlObjId":"https://doi.org/10.3390/polym14020241","jrnlTitl":"Polymers","jrnlVol":"14","jrnlYr":"2022","parPblcId":"10321134"},{"artTitl":"Highly Multiplexed Label-Free Imaging Sensor for Accurate Quantification of Small-Molecule Binding Kinetics","auth":"Chiodi, Elisa and Marn, Allison M. and Geib, Matthew T. and Ekiz Kanik, Fulya and Rejman, John and AnKrapp, David and Ünlü, M. Selim","dgtlObjId":"https://doi.org/10.1021/acsomega.0c03708","jrnlTitl":"ACS Omega","jrnlVol":"5","jrnlYr":"2020","parPblcId":"10233876"},{"artTitl":"The Role of Surface Chemistry in the Efficacy of Protein and DNA Microarrays for Label-Free Detection: An Overview","auth":"Chiodi, Elisa and Marn, Allison M. and Geib, Matthew T. and Ünlü, M. Selim","dgtlObjId":"https://doi.org/10.3390/polym13071026","jrnlTitl":"Polymers","jrnlVol":"13","jrnlYr":"2021","parPblcId":"10233927"},{"artTitl":"Simultaneous evaluation of multiple microarray surface chemistries through real-time interferometric imaging","auth":"Chiodi, Elisa and Sola, Laura and Brambilla, Dario and Cretich, Marina and Marn, Allison Marie and Ünlü, M. Selim and Chiari, Marcella","dgtlObjId":"https://doi.org/10.1007/s00216-019-02276-1","jrnlTitl":"Analytical and Bioanalytical Chemistry","jrnlVol":"412","jrnlYr":"2020","parPblcId":"10233922"},{"artTitl":"Bulk-Effect-Free Method for Binding Kinetic Measurements Enabling Small-Molecule Affinity Characterization","auth":"Marn, Allison M. and Chiodi, Elisa and Ünlü, M. Selim","dgtlObjId":"https://doi.org/10.1021/acsomega.0c05994","jrnlTitl":"ACS Omega","jrnlVol":"6","jrnlYr":"2021","parPblcId":"10233873"},{"artTitl":"Multiplexed, High-Sensitivity Measurements of Antibody Affinity Using Interferometric Reflectance Imaging Sensor","auth":"Marn, Allison M. and Needham, James and Chiodi, Elisa and Ünlü, M. Selim","dgtlObjId":"https://doi.org/10.3390/bios11120483","jrnlTitl":"Biosensors","jrnlVol":"11","jrnlYr":"2021","parPblcId":"10321135"}],"latestAmendmentDate":"04/24/2020","managingPec":"166200","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"Selim Unlu","perfAddress":"881 Commonwealth Avenue","perfCity":"BOSTON","perfCountryCode":"US","perfDistrict":"08","perfDistrictCode":"MA08","perfLocation":"Trustees of Boston University","perfStateCode":"MA","perfZipCode":"021303000","pi":["Selim Unlu selimunlu@gmail.com"],"piEmail":"selimunlu@gmail.com","piFirstName":"Selim","piId":"000217932","piLastName":"Unlu","poEmail":"","poName":"Samir Iqbal","poPhone":"","primaryProgram":["01002021DB NSF RESEARCH & RELATED ACTIVIT"],"progEleCode":"166200","program":"Light generation & detection","progRefCode":"091E","projectOutComesReport":"
\n

Both in vitro Diagnostics and Pharma rely on biotechnology tools to discover and develop new molecular interactions. Emerging diseases call for new blood/urine/saliva tests and thus new molecular discoveries. Demand for continuous monitoring of prognosis require new detection modalities. As liquid biopsies are poised to replace surgical biopsies, there is an increasing demand to measure the affinities of biomarkers both for new medicines and diagnostics. The need for better understanding of binding kinetics using native proteins and ligands is the driving motivation for molecular kinetics by Label Free Detection (LFD).  Since fluorescent or luminescent probes may alter the functions of probe molecules, the only reliable characterization methods are label-free for this need which remains unmet due to significant challenges of existing LFD technologies. The instruments are not only expensive but fall short of providing the desired sensitivity and accuracy. Existing platforms suffer from ?bulk effect? ? background signal due to refractive index variations in the analyte solution because of concentration and temperature changes.  To address these emerging market and technical challenges, there is a need for a robust, quantitative, and high-sensitivity label-free detector small capable of accurate analysis binding kinetics of biomolecules from proteins to small molecular weight analytes.

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Intellectual Merits: Our innovation ? Interferometric Reflectance Imaging Sensor (IRIS) technology utilizing interference of light from an optically transparent thin film?the same phenomenon that gives rainbow colors to a soap film when illuminated by white light. Our technology builds on strong lineage of basic and applied research sponsored by NSF and industry and defies the conventional wisdom that calls for enhancing the signal through complex optical resonances. Instead, we exploit the power of signal averaging in shot noise limited operation to achieve virtually unlimited sensitivity in a simple interferometric platform. Unlike other label-free IRIS technique is overcomes the bulk effect, and we devised a new proprietary technique based on creating an illumination spectrum for which the total reflectance intensity does not depend on the index variations of the analyte solution.

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In this PFI-TT project, we prototyped a robust, compact, and automated IRIS instrument capable of multiplexed measurement of binding kinetics. We developed a virtually bulk-effect-free method, without a reference channel or any computational correction, for measuring kinetic binding using IRIS. We reduced to practice and patented this technology under the PFI-TT project. Based on the market research conducted under an I-CORPS program, we have identified the bulk-effect free operation as a significant distinguishing feature for IRIS. Our project led to launching a Boston University start-up: iRiS Kinetics Inc. The intellectual outcomes of the NSF-TT project have been disseminated in 9 journal publications and the key findings are protected as BU patents and will potentially be licensed to iRiS Kinetics. PFI-TT project was also instrumental in creation of new IP with applications beyond the project scope on single-particle detection and a uniform light source concept with broad potential applications.  

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Broader Impacts: We consider the development of a diverse and highly skilled workforce with entrepreneurship training as the most significant impact of this program. Four PhD students have been trained under the PFI-TT program. Two PhD students, Elisa Chiodi and Allison Marn, have participated directly in the I-CORPS activities. In addition, Iris Celebi and Celalettin Yurdakul participated in the Lean Launch program conducted by Boston University Office of Technology Development. For all 4 PhD students, entrepreneurship and commercialization played an important role in their PhD dissertation work. All 4 PhD students completed their PhDs. Allison Marn (2021) has started a faculty position at Roger Williams University.  Yurdakul (2021), Chiodi (2022) and Celebi (2023) have moved into R&D jobs in industry.

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Another significant outcome of this project is the commercialization of IRIS technology for multiplexed binding kinetics measurements. Currently, iRiS Kinetics markets MX-100 as an alternative to Surface Plasmon Resonance (SPR) label-free binding kinetics readers. IRIS technology offers a more sensitive instruments at a lower cost. Potentially, there is a direct societal impact by enabling better diagnostics and therapeutics. With the robust analysis offered by IRIS, therapeutic antibodies can now be characterized more accurately. Small molecule binding can be studied on multiplexed sensors without detrimental effects of background solution variations and environmental factors.   Furthermore, this program led to the development of a new method for interferometric single particle detection with potential impact in ultrasensitive digital detection poised to impact emerging liquid biopsies.  

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\n\t\t\t\t \tLast Modified: 05/30/2023
\n\t\t\t\t\tModified by: M. Selim Unlu

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  • \n\"iRiS\n
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    Photograph of the commercial multiplexed affinity reader marketed by iRiS Kinetics Inc. Key technologies developed under the PFI-TT program enabled the technology translation to a commercial product.
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    Claude Dufresne
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    Public Domain
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    M. Selim Unlu
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    iRiS Kinetics MX-100
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  • \n\"IRIS\n
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    A schematic of how IRIS platform works.
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    M Selim Unlu
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    Public Domain
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    M. Selim Unlu
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    IRIS Platform
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  • \n\"SLAS\n
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    At SLAS 2022 Exhibit: (from left: Selim �nl�, Elisa Chiodi (EE PhD 2022) Iris Celebi (EE PhD 2023) Nese Lortlar �nl� (MD), Mete Aslan (current PhD student) - Right most Claude Dufresne (CEO axiVEND, industry mentor I-CORPS)
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    M Selim Unlu
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    Public Domain
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    M. Selim Unlu
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    SLAS 2022 Exhibit - iRiS Team
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  • \n\"First\n
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    At AACC 2019: From Left Selim ?nl?, Celalettin Yurdakul (EE PhD 2021), Allison Marn (EE PhD 2021), Iris Celebi (EE PhD 2023). 3 of the 4 students trained under PFI-TT program.
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    M Selim Unlu
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    Public Domain
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    M. Selim Unlu
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    First Exhibit for Team iRiS Kinetics
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","publicAccessMandate":"1","publicationResearch":["Biosensors and Bioelectronics~2022~201~Bakhshpour, Monireh and Chiodi, Elisa and Celebi, Iris and Saylan, Yeeren and Ünlü, Nese Lortlar and Ünlü, M. Selim and Denizli, Adil~https://doi.org/10.1016/j.bios.2021.113961~Sensitive and real-time detection of IgG using interferometric reflecting imaging sensor system~113961~10401318~10401318~OSTI~2023-05-15 01:31:11.946","Biosensors~2020~10~Celebi, Iris and Geib, Matthew T. and Chiodi, Elisa and Lortlar Ünlü, Nese and Ekiz Kanik, Fulya and Ünlü, Selim~https://doi.org/10.3390/bios10110158~Instrument-Free Protein Microarray Fabrication for Accurate Affinity Measurements~158~10233924~10233924~OSTI~2023-05-15 01:31:11.983","Sensors~2021~21~Chiodi, Elisa and Daaboul, George G. and Marn, Allison M. and Ünlü, M. Selim~https://doi.org/10.3390/s21082634~Multiplexed Affinity Measurements of Extracellular Vesicles Binding Kinetics~2634~10233926~10233926~OSTI~2023-05-15 01:31:11.996","Polymers~2022~14~Chiodi, Elisa and Marn, Allison M. and Bakhshpour, Monireh and Lortlar Ünlü, Nese and Ünlü, M. Selim~https://doi.org/10.3390/polym14020241~The Effects of Three-Dimensional Ligand Immobilization on Kinetic Measurements in Biosensors~10321134~10321134~OSTI~2023-05-15 01:31:11.936","ACS Omega~2020~5~Chiodi, Elisa and Marn, Allison M. and Geib, Matthew T. and Ekiz Kanik, Fulya and Rejman, John and AnKrapp, David and Ünlü, M. Selim~https://doi.org/10.1021/acsomega.0c03708~Highly Multiplexed Label-Free Imaging Sensor for Accurate Quantification of Small-Molecule Binding Kinetics~25358 to 25364~10233876~10233876~OSTI~2023-05-15 01:31:12.003","Polymers~2021~13~Chiodi, Elisa and Marn, Allison M. and Geib, Matthew T. and Ünlü, M. Selim~https://doi.org/10.3390/polym13071026~The Role of Surface Chemistry in the Efficacy of Protein and DNA Microarrays for Label-Free Detection: An Overview~1026~10233927~10233927~OSTI~2023-05-15 01:31:11.96","Analytical and Bioanalytical Chemistry~2020~412~Chiodi, Elisa and Sola, Laura and Brambilla, Dario and Cretich, Marina and Marn, Allison Marie and Ünlü, M. Selim and Chiari, Marcella~https://doi.org/10.1007/s00216-019-02276-1~Simultaneous evaluation of multiple microarray surface chemistries through real-time interferometric imaging~3477 to 3487~10233922~10233922~OSTI~2023-05-15 01:31:11.966","ACS Omega~2021~6~Marn, Allison M. and Chiodi, Elisa and Ünlü, M. Selim~https://doi.org/10.1021/acsomega.0c05994~Bulk-Effect-Free Method for Binding Kinetic Measurements Enabling Small-Molecule Affinity Characterization~6836 to 6841~10233873~10233873~OSTI~2023-05-15 01:31:12.01","Biosensors~2021~11~Marn, Allison M. and Needham, James and Chiodi, Elisa and Ünlü, M. Selim~https://doi.org/10.3390/bios11120483~Multiplexed, High-Sensitivity Measurements of Antibody Affinity Using Interferometric Reflectance Imaging Sensor~10321135~10321135~OSTI~2023-05-15 01:31:11.953"],"startDate":"05/01/2020","title":"PFI-TT: Interferometric Imaging for Multiplexed Molecular Kinetics","transType":"Standard Grant","ueiNumber":"THL6A6JLE1S7"}],"metadata":{"offset":0,"rpp":25,"totalCount":1}}}