The subject matter disclosed herein is generally directed to methods and systems for screening phenotypes associated with genetic elements and identifying genetic elements at the single-cell level using optical barcodes. A major advantage offered by this approach is the ability to screen for any cellular phenotype that can be identified by high-resolution microscopy—including live-cell phenotypes, protein localization, or highly multiplexed expression profile and mRNA localization in conjunction with a large array of genetic elements applied as a pool in a single test volume.

The disclosure provides methods, systems and related software, for automated or semi-automated sorting and/or isolating cells with visually distinguishable phenotypes. In some embodiments, the methods comprise providing a plurality cells with a photo-activatable detectable marker in their respective nuclei. The plurality of cells are imaged and, based on the image, the status for one or more visually identifiable phenotypes are determined. Cells determined to have the desired phenotype status are specifically exposed to a light wavelength for a time sufficient to uniquely activate the photo-activatable detectable marker in the individual cells with the desired phenotype status. The cells are then sorted on the basis of the activated detectable marker. The disclosure also provides methods for preparation and isolation of nuclei from fixed, adherent cells for analysis.

The present invention relates to a polypeptide comprising an epitope having a sequence homology of at least 75% to a sequence section of both Clostridium difficile toxin A and B. Moreover, the present invention refers to a vaccine comprising such polypeptide. The invention further relates to an antibody binding to Clostridium difficile toxins A and B and to a method for isolating and/or detecting such antibody and to uses of the polypeptides and antibodies.

This invention relates to methods of identifying, synthesizing, optimizing and profiling compounds that are inhibitors or activators of proteins, both naturally occurring endogenous proteins as well as certain variant forms of endogenous proteins, and novel methods of identifying such variants. The method accelerates the identification and development of compounds as potential therapeutically effective drugs by simplifying the pharmaceutical discovery and creation process through improvements in hit identification, lead optimization, biological profiling, and rapid elimination of toxic compounds. Implementation results in overall cost reductions in the drug discovery process resulting from the corresponding increases in efficiency.

The present invention provides methods for diagnosing lung cancer in a subject comprising (a) generating circulating tumor cell (CTC) data from a blood sample obtained from the subject based on a direct analysis comprising immunofluorescent staining and morphological characteristics of nucleated cells in the sample, wherein CTCs are identified in context of surrounding nucleated cells based on a combination of the immunofluorescent staining and morphological characteristics; (b) obtaining clinical data for the subject; (c) combining the CTC data with the clinical data to diagnose lung cancer in the subject.

Human pluripotent stem cells are differentiated in vitro into oligodendro-spheroids comprising oligodendrocytes for use in analysis, screening programs, and the like.

Embodiments herein described provide methods for determining phenotypic parameters of cell populations and expressing them in terms of tensors that can be compared with one another. Embodiments provide methods for determining phenotypic parameters of cell populations in response to an agent. Embodiments provide methods for comparing effects of an agent on phenotypic parameters to effects of reference standards whose in vivo effects are known. Embodiments provide methods for predicting the effect of an agent by the comparison with the known effects of reference standards. Embodiments provide methods for classifying agents by their effects on phenotypic parameters. Embodiments provide software and computer systems for calculating multiparametric tensors, compressing their complexity and comparing them after compression.

A system for assaying forces applied by cells includes an optically transparent substrate comprising a soft material having a Young's modulus within the range of about 3 kPa to about 100 kPa. An array of molecular patterns is disposed on a surface of the optically transparent substrate, the molecular patterns include fluorophore-conjugated patterns adherent to cells. The system includes at least one light source configured to excite the fluorophore-conjugated patterns and an imaging device configured to capture fluorescent light emitted from the fluorophore-conjugated patterns. Dimensional changes in the size of the patterns are used to determine contractile forces imparted by cells located on the patterns.

Techniques and systems are disclosed for a bioassay that is an in vitro mimic of peripheral nerve generation using the sensory neurons that innervate the peripheral nervous system. In some embodiments, the techniques may assist in detecting the bioactivity or potency of nerve grafts (e.g., processed, acellular human allografts) for fostering or supporting peripheral nerve regeneration. In various embodiments, techniques comprise affixing a harvested sensory neuron (e.g., a DRG) to a nerve graft segment to form a test construct; culturing the test construct in a medium; analyzing the test construct to indicate the amount of outgrowing peripheral nerve structure; and determining the potency of the nerve graft from a metric derived from the analysis. In some embodiments, techniques and materials may be used to test the effect of a varied test condition on peripheral nerve growth.

Disclosed is a marker for observing an effect of a compound or a drug on cells in real time. The marker is: 1) an amino acid sequence shown in SEQ No. 1 and/or SEQ No. 2; or 2) an amino acid sequence having a function for observing an effect of a compound or a drug on cells in real time and having at least more than 80%, preferably more than 85%, more preferably 90%, further preferably 95%, and most preferably 99% homology with the amino acid sequence shown in SEQ No. 1 and/or SEQ No. 2. Also disclosed is a method and a kit for observing an effect of a compound or a drug on cells in real time and use thereof.