and Relevance The aim of this Phase II SBIR proposal from Applikate Technologies, LLC, is to build on the successful completion of our Phase I milestones with the design, construction, and testing of prototype devices and software for implementing the ClearView tissue histology system in clinical settings by laboratory personnel. ClearView is a novel approach to performing complete and non-destructive imaging of tissue specimens for lung and other cancers. Lung cancer biopsy diagnosis error rates may run as high as 15%. Although there are many potential sources of error, important aspects relate to limitations of current methods for tissue processing and analysis. Standard methods limit the amount of tissue that can be visualized by the diagnostic pathologist and that is available for personalized-medicine testing. They also are not amenable to consultation with off-site experts and are dependent on manual processing by adequately trained histotechnologists. Applikate Technologies has developed ClearView, a complete, non-destructive, fast, tissue processing and imaging approach to histology that improves on limits of slide-based histology by providing complete tissue visualization, reducing artifacts of preparation, permitting improved quantitative interpretation, showing additional growth pattern information, and eliminating extensive manual preparation. The ClearView system yields images that are, in many cases, superior even to traditionally processed histology slides with pseudo-coloring that is virtually indistinguishable from conventional staining, all in an entirely digital format ready for remote access and storage. And ClearView is fast enough to provide diagnostic quality images in under two hours for same day diagnosis. We have also demonstrated, during our Phase I funding, that the ClearView process yields orders of magnitude more DNA for molecular analyses and is compatible with immunohistochemical staining. Furthermore, the methodology is applicable not only to lung cancer diagnosis, but to evaluation of practically any solid tissue cancer.
The specific aims of the proposal are to: 1) Develop an application-specific, high-speed multiphoton microscope and associated software; 2) Develop the ClearView prototype tissue chamber, and 3) Develop the ClearView prototype tissue processor. These three elements, along with proprietary reagents, form the core of the ClearView system. Following in-house testing, two complete prototype systems will be placed in two hospitals, one a large tertiary care center and the second a mid-sized hospital, for on-site testing and feedback by non-expert users in a clinical setting. Successful 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.
Establishing the diagnosis of lung cancer and determining the best course of treatment is critically dependent on the histologic evaluation of tissue biopsies. Yet, traditional methods have considerable problems relating to slow processing, limited available tissue, and difficulty in obtaining expert consultations. As a result, efficiency of care and diagnostic accuracy suffer, increasing the potential need for additional procedures with associated non-trivial patient risk and costs. This proposal seeks to develop and test prototype instrumentation and software for ClearView, a novel approach for tissue processing that maximizes the accuracy and efficiency of lung biopsies, including personalized medicine testing, and extensible to cancers from other organs.