Automated Platform for Fixed Tissue Microdissection

ABSTRACT Large banks of archived human tumor tissues including cancer biopsies harbor enormous amounts of disease relevant information that may facilitate development of novel therapeutic approaches and assist in our basic understanding of fundamental biological processes However the resource is clearly underused due to a number of technical challenges associated with the retrieval of molecular information hidden in the RNA DNA and proteins locked inside the samples Current microdissection platforms especially those with single cell resolution are typically sample specific complex expensive and overly dependent on manual user intervention at key steps Despite the need these limitations make integration within standard lab clinical sample processing workflows difficult Rapid cell and region specific nucleic acid extraction from formalin fixed tumor biopsies and archived tissue samples is perhaps one of the most desirable and technically challenging applications To facilitate the use of the archived and clinical tissue specimens we propose to develop an automated platform AutopicK MTM for high throughput fixed tissue microdissection Automatic molecular retrieval from archived and clinical FFPE tissue samples will be based on our recently developed cell and tissue acquisition CTAS technology using GEandapos s proprietary approach for rapid extraction of histological regions of interest ROIs from FFPE tissues Importantly the collected FFPE ROIs are optimized for direct molecular interrogation and compatible with most enzymatic reactions including protocols used for Next Generation Sequencing NGS The proposed instrument will feature auto calibration ROI auto recognition collection and dispensing into multiwell plate formats Our preliminary studies convincingly demonstrate that sample collection may be performed with cellular resolution with a tissue dissociation step that ensures compatibility of isolated DNA with a range of downstream protocols including amplification labeling and sequencing As both NeuroInDx and GEGR technologies can be implemented at low cost AutopicK MTM will have a serious price advantage over existing competitors Moreover the new instrument will remain compatible with fresh frozen live cell and fixed single cell samples making the AutopicK MTM the most versatile single cell acquisition and tissue microdissection platform on the market This Fast Track application will test all critical parameters of the proposed approach including tissue processing and initial instrument architecture in Phase I Commercial prototype of the proposed instrument and a complete workflow will be developed and validated in Phase II NARRATIVE The goal of this FastTrack SBIR is to develop and validate a cost effective microdissection system capable of fully automating microdissection and molecular analysis of single cells and ROIs from an array of tissue and culture samples Importantly the instrument will be optimized for microdissection of FFPE tissues such as tumor specimen which are routinely processed for diagnostic purposes The proposed fully automated concept AutopicK MTM will take advantage of the cell and tissue acquisition CTAS technology developed and commercialized by NeuroInDx and GE Global Research GEGR proprietary technologies permitting efficient region specific nucleic acid extraction from FFPE tissues and their direct use for downstream molecular analysis including Next Generation Sequencing NGS The proposed instrument will close existing gaps in clinical and pharmaceutical service workflows facilitating tumor specific analysis for diagnostic and drug development purposes Moreover because both NeuroInDx and GEGR technologies can be implemented at low cost AutopicK MTM will have a serious price advantage over existing competitors This taken together with unprecedented applicability of AutopicK MTM to nearly the whole range of research and clinical applications involving the acquisition and analysis of single cells ensure successful commercialization of the proposed instrument