Abstract: 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.

Abstract: The present invention provides compositions and methods that allow lipid membranes to be imaged optically at nanoscale resolution via a lipid-optimized form of expansion microscopy, also referred to as membrane expansion microscopy (mExM). mExM, via a post-expansion antibody labeling protocol, enables protein-lipid relationships to be imaged in organelles such as mitochondria, the endoplasmic reticulum, the nuclear membrane, and the Golgi apparatus. mExM may be of use in a variety of biological contexts, including the study of cell-cell interactions, intracellular transport, and neural connectomics.

Abstract: The invention encompasses hydrogels, monomer precursors of the hydrogels, methods for the preparation thereof, and methods of use therefor. The linking of monomers can take place using non-radical, bioorthogonal reactions such as copper-free click-chemistry.

Abstract: The invention provides a method for preparing an expanded cell or tissue sample suitable for microscopic analysis. Expanding the sample can be achieved by binding, e.g., anchoring, key biomolecules to a DMAA-TF polymer network and swelling, or expanding, the polymer network, thereby moving the biomolecules apart as further described herein. As the biomolecules are anchored to the polymer network isotropic expansion of the polymer network retains the spatial orientation of the biomolecules resulting in an expanded, or enlarged, sample.

Abstract: 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.

Abstract: A method for diagnosing cancer in an expanded biological tissue sample of a patient comprising providing at least one sample image of the expanded biological tissue sample; providing a computer configured to analyze the sample; analyzing, with the computer, the sample detect and segment nuclei; calculating, with the computer, molecular characteristics of those nuclei; and determining, with the computer, a diagnosis of cancer of the sample by comparing the sample with a benign normal tissue reference.

Abstract: The invention encompasses hydrogels, monomer precursors of the hydrogels, methods for the preparation thereof, and methods of use therefor. The linking of monomers can take place using non-radical, bioorthogonal reactions such as copper-free click-chemistry.

Abstract: 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.

Abstract: The invention encompasses hydrogels, monomer precursors of the hydrogels, methods for the preparation thereof, and methods of use therefor. The linking of monomers can take place using non-radical, bioorthogonal reactions such as copper-free click-chemistry.

Abstract: The invention provides a method for preparing an expanded renal (kidney) tissue sample suitable for microscopic analysis. Expanding the kidney sample can be achieved by binding, e.g., anchoring, key biomolecules to a polymer network and swelling, or expanding, the polymer network, thereby moving the biomolecules apart as further described herein. As the biomolecules are anchored to the polymer network, isotropic expansion of the polymer network retains the spatial orientation of the biomolecules resulting in an expanded, or enlarged, kidney sample.

Abstract: The invention provides a method for preparing an expanded biological specimen suitable for microscopic analysis. Expanding the biological sample can be achieved by anchoring biomolecules to a polymer network and swelling, or expanding, the polymer network, thereby moving the biomolecules apart as further described below. As the biomolecules are anchored to the polymer network isotropic expansion of the polymer network retains the spatial orientation of the biomolecules resulting in an expanded, or enlarged, biological specimen.

Abstract: The invention, in some aspects, relates to the preparation and use of signaling reporter islands (SiRIs) in single cells. Compositions of the invention that produce SiRIs can be delivered to a cell resulting in the presence of one or more SiRIs in the cell. Methods of the invention include detecting signals generated by elements in the SiRIs in a cell and use of the detected signals to determine and analyze simultaneous physiological processes within the cell, or cells.

Abstract: 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.

Abstract: The present description provides methods, assays and reagents for linearly expanding a peptide. The methods and/or linear expanded peptide described herein have several uses such as, but not limited to, peptide (protein) sequencing, high-resolution interrogation of the proteome and enabling ultrasensitive diagnostics critical for early detection of diseases.

Abstract: 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.

Abstract: The present invention leverages the techniques for expansion microscopy (ExM) to provide improved high-throughput super-resolution whole-organ imaging methodology to image protein architectures over whole organs with nanoscale resolution by using high-throughput microscopes in combination with samples that have been iteratively expanded more than once, in a method referred to herein as “iterative expansion microscopy” (iExM). In the 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 samples that have been already expanded using ExM techniques one or more additional times to iteratively expand them such that, for example, a 5-fold expanded specimen can be expanded again 3- to 4-fold, resulting in as much as a 17- to 19-fold or more linear expansion.

Abstract: Synthetic minimal cells (SMC) are provided for delivering a therapeutic or diagnostic agent to a subject or to a site within a subject in need of treatment or diagnosis. SMCs may be targeted to the site or sense the site and initiate production and release of the therapeutic or diagnostic agent. SMCs comprise a sensor, at least one genetic circuit and outputting means to deliver the therapeutic agent.

Abstract: 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.

Abstract: The present invention provides methods for analyzing polynucleotides such as genomic DNA. In some embodiments, the disclosure provides a method for preparing and amplifying a genomic DNA library in situ in a fixed biological sample. The method comprises treating a fixed biological sample with an insertional enzyme complex to produce tagged fragments of genomic DNA. The method further comprises circularizing the tagged fragments of genomic DNA. The method further comprises amplifying the tagged fragments of genomic DNA.

Abstract: The invention provides a method for preparing an expanded cell or tissue sample suitable for microscopic analysis. Expanding the sample can be achieved by binding, e.g., anchoring, key biomolecules to a DMAA-TF polymer network and swelling, or expanding, the polymer network, thereby moving the biomolecules apart as further described herein. As the biomolecules are anchored to the polymer network isotropic expansion of the polymer network retains the spatial orientation of the biomolecules resulting in an expanded, or enlarged, sample.