Abstract: A sample injector for use in a fluid separation system for separating compounds of a fluidic sample in a mobile phase, the sample injector comprising a switchable valve, a sample loop in fluid communication with the valve and configured for receiving the fluidic sample, a metering device in fluid communication with the sample loop and configured for introducing a metered amount of the fluidic sample on the sample loop, and a control unit configured for controlling switching of the valve to transfer the sample loop between a low pressure state and a high pressure state via an intermediate state and for controlling the metering device during the intermediate state to at least partially equilibrate a pressure difference in the sample loop between the low pressure state and the high pressure state.

Abstract: The present disclosure is directed to a single-end sequencing method for improved detection of genomic rearrangements such as deletions, insertions, inversions, and translocations that are present in a polynucleotide. A first priming event allows for sequencing of a target sequence, and a second priming event on an adapter allows for identification of the sequences amplified and tagged by selective amplification. The combination of priming events in the same direction facilitates read alignment and the identification of any genomic rearrangements.

Abstract: Novel tools and techniques are provided for implementing digital microscopy imaging using deep learning-based segmentation and/or implementing instance segmentation based on partial annotations. In various embodiments, a computing system might receive first and second images, the first image comprising a field of view of a biological sample, while the second image comprises labeling of objects of interest in the biological sample. The computing system might encode, using an encoder, the second image to generate third and fourth encoded images (different from each other) that comprise proximity scores or maps. The computing system might train an AI system to predict objects of interest based at least in part on the third and fourth encoded images. The computing system might generate (using regression) and decode (using a decoder) two or more images based on a new image of a biological sample to predict labeling of objects in the new image.

Abstract: A gas-liquid separator includes a fluid inlet, a shell including an inside surface enclosing an interior space, an outlet structure with fingers converging toward a longitudinal axis, and a dripper including a dripper tip. The fingers terminate at fingertips located proximate to an outside surface of the dripper. Gas exit ports are defined between adjacent fingers, and by the dripper. The gas-liquid separator defines a liquid flow path from the fluid inlet, along the inside surface, along one or more of the fingers, converging along the dripper outside surface, and to the dripper tip. The gas-liquid separator also defines a gas flow path from the fluid inlet, through the interior space, and through the gas exit ports. The gas-liquid separator may be utilized in fluid separation systems such as liquid chromatography or supercritical fluid chromatography/extraction systems.

Abstract: Chromogenic conjugates for color-based detection of targets are described. The conjugates comprise a chromogenic moiety such as a rhodamine, rhodol or fluorescein. The chromogenic moiety is linked to a peroxidase substrate. The chromogenic conjugates can be used in immunohistochemical analysis and in situ hybridization. The conjugates can be used to detect 1, 2, 3 or more targets in a sample by color.

Abstract: The invention is an improved multiplex capillary electrophoresis instrument or module with at least four and preferably six user-accessible vertically stacked drawers. An x-z stage moves samples from the user accessible drawers to the capillary array for analysis. An additional mechanical stage moves the array from side-to-side. The x-z stage, coupled with the additional array stage allows the system to sample all wells of a 384 well plate with a 96-capillary array. A computer program allows users to add capillary electrophoresis jobs to a queue corresponding to the analysis of rows or plates of samples without stopping or interrupting runs in progress.

Abstract: An inductively coupled plasma-mass spectrometry (ICP-MS) system includes an ion trap, in which ions are trapped and subsequent ejected by mass-selective ejection (MSE). The system may have a linear quadrupole configuration, in which the ion trap is a linear ion trap (LIT) that is preceded by a pre-LIT linear quadrupole device and/or a post-LIT quadrupole device. The pre-LIT and/or post-LIT quadrupole device may be configured or operated as an RF-only ion guide or as a mass filter or mass analyzer, with or without mass scanning. The system may be utilized in particular for multi-element analysis of fast transient signals produced from ion pulses, where the sample under analysis is a single particle, single biological cell, or a cloud or aerosol produced for example by single-shot laser ablation.

Abstract: A method of enriching for a fragment of a genome, as well as corresponding compositions and kits, are provided. In certain embodiments, the method comprises: (a) contacting a sample comprising fragmented DNA with a Cas9-gRNA complex comprising mutant Cas9 protein that has inactivated nuclease activity and a Cas9-associated guide RNA that is complementary to a site in the DNA, to produce a Cas9-fragment complex that comprises a fragment of the fragmented DNA; and (b) isolating the complex. In addition, other methods and compositions for Cas9/CRISPR-mediated nucleic acid manipulation are also provided.

Abstract: Novel tools and techniques are provided for implementing digital microscopy imaging using deep learning-based segmentation and/or implementing instance segmentation based on partial annotations. In various embodiments, a computing system might receive first and second images, the first image comprising a field of view of a biological sample, while the second image comprises labeling of objects of interest in the biological sample. The computing system might encode, using an encoder, the second image to generate third and fourth encoded images (different from each other) that comprise proximity scores or maps. The computing system might train an AI system to predict objects of interest based at least in part on the third and fourth encoded images. The computing system might generate (using regression) and decode (using a decoder) two or more images based on a new image of a biological sample to predict labeling of objects in the new image.

Abstract: The present invention provides methods and kits to improve the signal from sialic acids labeled with the dye 1, 2-diamino-4, 5-methylenedioxybenzene (“DMB”). The methods include labeling the sialic acids with DMB in an aqueous solution comprising the amino acid glycine, with pH adjusted to 1.5-3.2 by an acid, such as phosphoric acid or hydrochloric acid, and a reductant.

Abstract: Provided herein is a method for making a pool of probes by primer extension. In certain embodiments, the method comprises hybridizing a first population of oligonucleotides comprising a top strand sequence having the following formula V1-B-3? with a second population of oligonucleotides comprising a bottom strand sequence having the following formula V2?-B?-3? to provide a population of duplexes. After hybridizing, the 3? ends of the oligonucleotides in the duplexes are extended to produce a population of double stranded products comprising a top strand sequence having the following formula V1-B-V2, where V2 is complementary to V2?.

Abstract: The present invention provides methods to improve the sensitivity of detecting glycosylamines released from glycoconjugates, such as glycoproteins or glycopeptides, by enzymatic digestion when labeling them with amine-reactive dyes.

Abstract: The present invention provides methods, devices, and kits to improve procedures for reducing carbohydrates, such as glycans released from glycoconjugates, or for labeling carbohydrates by reductive amination.

Abstract: A sample management device which comprises a source flow path in which a fluidic sample can flow, a volume flow adjustment unit configured for adjusting a volume flow of the fluidic sample to be branched off from the source flow path at a fluidic coupling point, and a fluidic valve fluidically coupled with the source flow path and with the volume flow adjustment unit, wherein the fluidic valve is switchable into a branch off state in which the fluidic coupling point is established within the source flow path to branch off an adjustable volume of the fluidic sample from the source flow path via the fluidic coupling point while a flow of the fluidic sample in the source flow path continues.

Abstract: Provided herein are methods for inducing CRISPR/Cas-based gene regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using modified single guide RNAs (sgRNAs) that enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a modified sgRNA to correct a mutation in a target gene associated with the genetic disease.

Abstract: Provided herein are methods for inducing CRISPR/Cas-based gene regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using modified single guide RNAs (sgRNAs) that enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a modified sgRNA to correct a mutation in a target gene associated with the genetic disease.

Abstract: In some examples, a filter assembly may include a filter including a first gasket having a first channel adjacent to a first side of the filter and a second gasket having a second channel adjacent to a second side of the filter. The first gasket and the second gasket may include a beveled surface adjacent to the filter. The first channel and the second channel may include a diameter of from about 0.01 mm to about 0.5 mm. A finger tightening system may securely hold the filter without any leaks.

Abstract: Provided herein are methods for inducing CRISPR/Cas-based gene regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using modified single guide RNAs (sgRNAs) that enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a modified sgRNA to correct a mutation in a target gene associated with the genetic disease.

Abstract: A system for monitoring cell-substrate impedance of excitable cells at millisecond time resolution and methods of assessing cell beating by monitoring cell-substrate impedance of beating cells at millisecond time resolution.

Abstract: Provided herein, among other things, are a variety of methods for transposase-mediated tagging and amplification of short DNA fragments, e.g., between about 150 bp and 1.5 Kb in length. In some aspects, the method includes tagging the DNA fragments with a first primer sequence using barcoded transposases followed by a primer extension reaction to introduce a second primer sequence, e.g., using random or gene-specific primers. Kits for performing this method are also provided.