Commercial Development of a Novel Microfluidic Platform for Real-Time Biopharmaceutical Analysis

Project SummaryBiopharmaceuticals are complex molecules manufactured in living cellsand as a resultfrequent quality testing is required for developmentregulatory approvaland manufacturingCapillary isoelectric focusingcIEFis a widely used analytical technique that provides rapid detection of most protein modificationsMass spectrometryMSmeasures intrinsic molecular weightand has the unique capability of identifying the specific nature of a given protein modificationCombining cIEF and MS is a powerful and highly effective approach to determining compositional differences between protein isoformsHowevercurrent methodologies require labor intensive preparative chromatography to isolate sufficient material for the combined cIEF and MS analysisand so are severely limited in capacity and throughputTo address this issueIntabio has developed the Blazesystema proprietary protein analytics platform that will be the first commercially available system to seamlessly integrate cIEF with MS analysisThe Blaze system utilizes a novel microfluidic chip design to integrateseparation of protein isoforms by isoelectric focusingimaging of protein isoforms bynm absorption for detection and quantitationandMS sample preparation and delivery by electrospray into an adjacent mass spectrometer to detect and identify each isoformThe Blaze systemandapos s integration of these steps drastically reduces the analysis time to only minutes per sampleThis SBIR project will advance the development of the Blaze instrumentsoftware and consumable kitand will establish a consumable manufacturing process to prepare for commercial launchPhasewill focus on advancing the core innovationthe chip and clamshellThe clamshell holds the microfluidic chip in the instrument and acts as the world to chip interfaceproviding inputs for reagentssamplespressure and electrodesIn Phasethe laser bonding process for the three layer chip will be optimized to improve yield and chip performance by exploring multiple combinations of bonding parametersAdditionallyprototype designs to integrate the chip and clamshell into a singlecartridgefor improved ease of use will be designed and testedPhasewill advance the prototype cartridge to a commercialdisposable version and set up the commercial manufacturing process for the chip cartridgeCommercial instrument and software development will also be completed in PhaseInstrument development will address strategies to reduce material cost and integrate an internal autosampler functionsoftware development will refine integration and display of cIEF and MS dataas well as complete cfrpartcomplianceThe innovation and research from this project will advance the fields of protein separation science and expand the microfluidic technology fieldThis project will also transform biopharmaceutical drug development and manufacturing by enabling more frequentcomprehensive testingThis will result in profound productivity gainstranslating into a greater number of higher quality drugs developed in less time and with less costProject Narrative The development of the BlazeTM instrument system for real time protein analytics will address a critical bottleneck in the development and manufacturing of biopharmaceuticalsenabling higher quality drugs to be developed in less time and preventing manufacturing issues that could delay the availability of these important drugs to patientsThe Blaze system will accomplish this by being the first commercially available system to integrate three key analytical functionscIEF separation for protein isoform detectionwhole column imaging for quantitationand ionized electrospray into a back end mass spectrometer for analysisThis innovation will greatly reduce the time and lab infrastructure required for protein analyticsenabling drug developers to have access to high quality information during the biopharmaceutical development and manufacturing process much sooner and on many more samples than is currently possible