Practical high resolution microscopy of un-cut, un-embedded lung biopsies

Project Summary and Relevance The aim of this Phase II SBIR proposal from Applikate TechnologiesLLCis to build on the successful completion of our Phase I milestones with the designconstructionand testing of prototype devices and software for implementing the ClearView tissue histology system in clinical settings by laboratory personnelClearView is a novel approach to performing complete and non destructive imaging of tissue specimens for lung and other cancersLung cancer biopsy diagnosis error rates may run as high asAlthough there are many potential sources of errorimportant aspects relate to limitations of current methods for tissue processing and analysisStandard methods limit the amount of tissue that can be visualized by the diagnostic pathologist and that is available for personalized medicine testingThey also are not amenable to consultation with off site experts and are dependent on manual processing by adequately trained histotechnologistsApplikate Technologies has developed ClearViewa completenon destructivefasttissue processing and imaging approach to histology that improves on limits of slide based histology by providing complete tissue visualizationreducing artifacts of preparationpermitting improved quantitative interpretationshowing additional growth pattern informationand eliminating extensive manual preparationThe ClearView system yields images that arein many casessuperior even to traditionally processed histology slides with pseudo coloring that is virtually indistinguishable from conventional stainingall in an entirely digital format ready for remote access and storageAnd ClearView is fast enough to provide diagnostic quality images in under two hours for same day diagnosisWe have also demonstratedduring our Phase I fundingthat the ClearView process yields orders of magnitude more DNA for molecular analyses and is compatible with immunohistochemical stainingFurthermorethe methodology is applicable not only to lung cancer diagnosisbut to evaluation of practically any solid tissue cancerThe specific aims of the proposal are toDevelop an application specifichigh speed multiphoton microscope and associated softwareDevelop the ClearView prototype tissue chamberandDevelop the ClearView prototype tissue processorThese three elementsalong with proprietary reagentsform the core of the ClearView systemFollowing in house testingtwo complete prototype systems will be placed in two hospitalsone a large tertiary care center and the second a mid sized hospitalfor on site testing and feedback by non expert users in a clinical settingSuccessful completion of these aims will set the stage for a Phase III transition to regulatory approval and provide a proven platform for early implementation through service work for academic research and clinical research groups