Massachusetts Institute of Technology

Glyphic Biotechnologies, Inc.

Harvard College

Asmamaw T Wassie

Edward Stuart Boyden

David Dodd

Joshua Young Cynming Yang

Andrew John Price

Elaine Jean Su

Daniel Masao Estandian

Gerardo Fabian Delgado

Boyang Hua

Fei Chen

Shahar Alon

Alexi Georges Choueiri

Yael Gregory Maguire

Shuguang Zhang

Evan R Daugharthy

Andreas Mershin

Patrick J Moran

David Kong

Karolina Corin

Andrew C Payne

George M Church

Adam H Marblestone

Jonathan Scheiman

Chih-Chieh Yu

Or A Shemesh

Deblina Sarkar

Jinyoung Kang

Anubhav Sinha

Daniel Goodwin

The present invention provides biological samples of interest that have been iteratively expanded in a method referred to herein as iterative direct expansion microscopy (id-ExM). In the id-ExM method, biological samples of interest are permeated with a swellable material that results in the sample becoming embedded in the swellable material, and then the sample can be expanded isotropically in three dimensions. The process of iteratively expanding the samples can be applied to expand samples one or more additional times such that, for example, a 5-fold expanded sample can be expanded again to achieve high expansion factors, for example, 20× to 100× or more linear expansion.

Iterative direct expansion microscopy

Provided herein are methods and systems for sequencing proteins. One or more methods disclosed herein may use linkers having an amino acid-reactive group and an additional reactive moiety that may be used to couple a polymerizable molecule. The linker may couple to a polymerizable molecule and an amino acid of a peptide and a capture moiety via the polymerizable molecule, followed by cleavage of the amino acid from the peptide. Further processing and analysis may be conducted using, for example, nanopores or nanogaps.

Protein sequencing via coupling of polymerizable molecules

The present description provides methods, assays and reagents useful for sequencing proteins. Sequencing proteins in a broad sense involves observing the plausible identity and order of amino acids, which is useful for sequencing single polypeptide molecules or multiple molecules of a single polypeptide. In one aspect, the methods are useful for sequencing multiple polypeptides. The methods and reagents described herein can be useful for high resolution interrogation of the proteome and enabling ultrasensitive diagnostics critical for early detection of diseases.

Single-molecule protein and peptide sequencing

'The present disclosure provides methods and systems for sequencing proteins. One or more methods disclosed herein may use linkers having an amino acid-reactive group and an additional reactive moiety that may be used to couple a polymerizable molecule. The linker may couple to a polymerizable molecule and an amino acid of a peptide and a capture moiety via the polymerizable molecule, followed by cleavage of the amino acid from the peptide. Further processing and analysis may be conducted using, for example, nanopores or nanogaps. '

The present disclosure provides methods and systems for sequencing proteins. One or more methods disclosed herein may use linkers having an amino acid-reactive group and an additional reactive moiety that may be used to couple a polymerizable molecule. The linker may couple to a polymerizable molecule and an amino acid of a peptide and a capture moiety via the polymerizable molecule, followed by cleavage of the amino acid from the peptide. Further processing and analysis may be conducted using, for example, nanopores or nanogaps.

The present invention relates to a method for amplifying at least one target RNA in a fixed and, optionally, expanded biological sample. In an embodiment of the invention, the method comprises incubating the fixed biological sample with a pair of polynucleotides complementary to non-overlapping and proximal sequences of a target RNA, wherein the polynucleotide pair hybridizes to the target RNA; ligating the polynucleotide pair using a ligase; and amplifying the ligation product. The invention further provides methods for detecting and optionally quantifying and/or sequencing the amplification product. As the method comprises hybridizing polynucleotide pairs to a target RNA in a fixed biological sample, the target RNA can be hybridized in situ.

Multiplexed signal amplified FISH via splinted ligation amplification and sequencing

The invention, in some aspects relates to compositions and methods for imaging biological systems and physiological activity and conditions in cells.

Stochastic arrangement of reagents in clusters&#x2014;STARC

The invention provides in situ nucleic acid sequencing to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ sequencing of nucleic acids in a process referred to herein as 'expansion sequencing' (ExSEQ).

Augmenting in situ nucleic acid sequencing of expanded biological samples with in vitro sequence information

The invention enables in situ genomic and transcriptomic assessment of nucleic acids to be conducted in biological specimens that have been physically expanded. The invention leverages the techniques for expansion microscopy (ExM) to provide new methods for in situ genomic and transcriptomic assessment of nucleic in a new process referred to herein as 'expansion fluorescent in situ hybridization' (ExFISH).

Nanoscale imaging of proteins and nucleic acids via expansion microscopy

In exemplary implementations of this invention, an electronic olfactor determines whether a scent being tested matches the scent of a positive control. The electronic olfactor can perform this scent matching even in a changing olfactory environment, and even if the positive control scent is a combination of hundreds or thousands of different odorants. No prior training is needed, and no attempt is made to identify a single odorant that is unambiguously responsible for a scent. Instead, a computer compares the total scent pattern of a positive control sample with the total scent pattern of a test sample, across a sweep of many permutations of electrical inputs to scent sensors, to try to find any condition under which the total scent patterns do not match. If such a condition cannot be found, then the computer declares a match between the test and target scents.

Methods and apparatus for artificial olfaction

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Boston, MA, United States of America

Asmamaw T Wassie