A microscope for ultra-high multiplex spatial imaging of transcripts and proteins in tissues

Massachusetts General Hospital, Boston MA

Investigators

Abstract

In this proposal, 13 NIH-funded faculty from the Massachusetts General Hospital request to purchase a Vizgen MERSCOPE. The MERSCOPE is a new technology for multiplex measurement of up to 550 genes in tissue from any organism, including human. The technology offers exceptional accuracy, reproducibility, and dynamic range, and permits measurement at true single cell resolution, with an established preparation protocol. It is thus complementary to standard RNA FISH and enables measurement of hundreds instead of 4- 12 transcripts in tissue sections. In particular, the faculty will use the Vizgen MERSCOPE to carry out unprecedented and foundational studies to decipher cell type and state localization and cell-cell interactions in a diverse set of diseases. Preliminary data using an instrument at Vizgen demonstrated that this technology generates quantitative, highly reproducible data that map well back to our single cell RNA- sequencing dataset from colorectal cancer, and reveals cell-cell interactions at single-cell resolution. The MERSCOPE will be operated and maintained in the MGH Cancer Center / Molecular Pathology Confocal Core Facility, where it will be accessible to all the Major and Minor Users, as well as to a wider community of researchers from MGH and neighboring Boston institutions. The staff member who will be primarily responsible for the MERSCOPE is the manager of the microscopes and imaging instruments at the MGH Cancer Center and has extraordinary expertise in imaging technologies and computation. She is available to operate and maintain the system and to instruct new users. This new equipment will enable cutting-edge research efforts supported by major NIH grants, including the NIH DP2 Innovator awards and U54, P01 and R01 projects. It will provide transformative capabilities for single cell spatial transcriptomics to a community of trainees and researchers at the MGH and beyond. Finally, it will help establish general methodologies for the use of spatial genomics technologies applicable in all organisms and across human health and disease. 1