Massachusetts Institute of Technology

Harvard College

The General Hospital Corporation

The Brigham and Women's Hospital, Inc.

The Broad Institute, Inc.

Whitehead Institute for Biomedical Research

J Christopher Love

Hidde L Ploegh

Todd Michael Gierahn

Jehnna Ronan

Viktor A Adalsteinsson

Denis Loginov

Alan Stockdale

Robert Samuel Langer

Klavs F Jensen

Alexander K Shalek

Armon R Sharei

Travis K Hughes

Nahyun Cho

Marc H Wadsworth, Ii

Paul Blainey

Bradley Bernstein

Bruce D Walker

Robert S Langer, Jr

Richard Dean Braatz

Navin Varadarajan

Robert S Langer

Navpreet Ranu

Nathalie Y R Agar

Peter Van Galen

Volker Hovestadt

Neil Chandra Dalvie

Shaina Carroll

Amos Enshen Lu

Yuan Gong

Craig A Mascarenhas

Boris Julg

Qing Han

Vinay Tripuraneni

Ang A Tu

Marc Havens Wadsworth

Sergio Andre Rodriguez Aponte

Kerry Love

Described herein are systems, methods, and apparatus for automatically identifying and recovering individual cells of interest from a sample of biological matter, e.g., a biological fluid. Also described are methods of enriching a cell type of interest. These systems, methods, and apparatus allow for coordinated performance of two or more of the following, e.g., all with the same device, thereby enabling high throughput: cell enrichment, cell identification, and individual cell recovery for further analysis (e.g., sequencing) of individual recovered cells.

Systems, methods, and apparatus for in vitro single-cell identification and recovery

The present application provides a method of assembling a container for one or multiple parallel steps of biochemical analysis on one or more cells comprising performing molecular bonding of a porous membrane on an apical or basal surface of an array having a plurality of wells, wherein the molecular bonding substantially isolates each well from adjacent wells.

Semi-permeable arrays for analyzing biological systems and methods of using same

The present disclosure relates to, inter alia, variants of the receptor binding domain of a coronavirus (e.g., SARS-CoV-2) having increased immunogenicity and reduced aggregation, and the use of the RBD variants in methods for preventing infection of the coronavirus.

SARS-CoV-2 antigens and uses thereof

Isolating or identifying a cell based on a physical property of said cell can include providing a cell suspension; passing said suspension through a microfluidic channel that includes a constriction; passing the cell suspension through the constriction; and, contacting said cell suspension solution with a compound. The constriction can be sized to preferentially deform a relatively larger cell compared to a relatively smaller cell.

Selective delivery of material to cells

Modifications to both hardware and enzymatic reactions used in single cell analyses such as but not limited to Seq-well that enable significant increases in the yield of transcripts per cell, portability and ease of use, increased scalability of the assay, and linkage of transcript information to other measurements made in the picowell arrays are disclosed.

Single cell analyses

The present invention relates to methods of detecting region(s) of interest in a gene comprising a polyA tail. The region(s) of interest can include gene(s), region(s), mutation(s), deletion(s), insertion(s), indel(s), and/or translocation(s). The region(s) can be greater than or less than 1 kilobases from the polyA tail. Methods can include forming a library of single cell transcripts comprising the region(s) in close proximity to a cell barcode and a unique molecular identifier (UMI). Methods for distinguishing cells by genotype can include amplifying the transcripts using PCR methods and detecting the cell barcode and UMI using single cell sequencing methods. Transcripts can be enriched using tagged region-specific PCR primers. Cell barcodes can be brought into close proximity to the region(s) by circularizing the transcripts. Sequencing of the transcripts can include using primer binding sites added during PCR amplification and library indexes for multiplexed sequencing.

Single cell sequencing libraries of genomic transcript regions of interest in proximity to barcodes, and genotyping of said libraries

The present invention relates to the analysis of complex single cell sequencing libraries. Disclosed are methods for enrichment of library members based on the presence of cell-of origin barcodes to identify and concentrate DNA that is relevant to interesting cells or components that would be expensive or difficult to study otherwise. Also, disclosed are methods of capturing cDNA library molecules by use of CRISPR systems, hybridization or PCR. The present invention allows for identifying the properties of rare cells in single cell RNA-seq data and accurately profile them through clustering approaches. Further information on transcript abundances from subpopulations of single cells can be analyzed at a lower sequencing effort. The methods also allow for linking TCR alpha and beta chains at the single cell level.

Single cell cellular component enrichment from barcoded sequencing libraries

Screening assays and methods of performing such assays are provided. In certain examples, the assays and methods may be designed to determine whether or not two or more species can associate with each other. In some examples, the assays and methods may be used to determine if a known antigen binds to an unknown monoclonal antibody.

Screening assays and methods

Aspects of the present disclosure relate to filtration systems and methods for production of biologically-produced products, which may include pharmaceutical and/or protein products. Certain biomanufacturing systems described herein comprise a bioreactor (e.g., a perfusion bioreactor, a chemostat) and a filter probe comprising a filter bundle comprising a plurality of hollow fibers (e.g., longitudinally aligned hollow fibers). According to some embodiments, a center-to-center distance between any two hollow fibers within the fiber bundle at one or more points along a length of the fiber bundle is relatively large (e.g., greater than or equal to an average outer diameter of the hollow fibers of the fiber bundle, greater than or equal to 1.1 times a minimum diameter of the two hollow fibers). In some embodiments, the hollow fibers within the fiber bundle are arranged in an array (e.g., a hexagonal, linear, annular, or square array).

Filtration systems and methods for manufacturing biologically-produced products

Systems and methods for single cell culture and analysis by microscopy and matrix assisted laser desorption ionization mass spectrometry are disclosed. The systems and methods isolate a plurality of cells in a plurality of wells such that a predetermined number of the plurality of wells contain one and only one cell. The plurality of wells allow for optical interrogation of the cells and subsequent matrix assisted laser desorption ionizing of molecules within the cells.

Systems and methods for single cell culture and analysis by microscopy and MALDI mass spectrometry

Growing community of inventors

Somerville, MA, United States of America

J Christopher Love