Abstract: A circuit and method for providing high-voltage radio-frequency (RF) energy to an instrument at multiple frequencies includes a plurality of inputs each configured to receive an RF voltage signal oscillating at a corresponding frequency, and a step-up circuit for generating magnified RF voltage signals based on the received RF voltage signals. The step-up circuit includes an LC network operable to isolate the RF voltage signals at the plurality inputs from one another while preserving a voltage magnification from each input to a common output at each of the corresponding frequencies.

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 disclosure is generally directed to detecting nucleic acids. In particular, disclosed herein are methods and compositions for determining the sequence (or identity) and location of RNA and other molecules in situ. The present invention is generally related to a method for detecting nucleic acids, the method including providing a tissue sample; providing an array comprising a plurality of oligonucleotide probes attached to a surface of the array, in which each oligonucleotide probe, of the plurality of oligonucleotide probes, includes a location barcode sequence, a primer binding sequence, and a priming sequence; releasing the plurality of oligonucleotide probes from the array surface; contacting the tissue sample with the released oligonucleotide probes; and allowing the released oligonucleotide probes to diffuse into the tissue sample.

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: 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: An ion pump with a housing enclosing an interior, a gas inlet having a through-hole extending into the interior of the ion pump, at least one cathode, at least one anode positioned in proximity to the at least one cathode, a magnet disposed on an opposite side of the at least one cathode from the anode, and a blocking shield disposed between the gas inlet and the at least one cathode. The blocking shield is electrically connected to the at least one anode. An associated method installs the blocking shield by inserting components of the blocking shield assembly through the gas inlet, and assembling (inside the interior of the ion pump) the inserted components to form the blocking shield.

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: Devices, systems and methods for monitoring excitable cells, such as cardiomyocytes, on microelectrode arrays that couple the electro-stimulation of excitable cells to induce or regulate cardiomyocyte beating and the simultaneous measurement of impedance and extracellular recording to assess changes in cardiomyocyte beating, viability, morphology or electrophysical properties in response to a plurality of treatments.

Abstract: In one embodiment, a power source for providing high-voltage radio-frequency (RF) energy to an instrument such as a mass spectrometer includes an RF power amplifier having an output, an oscillating RF signal generator configured to provide first and second RF signals respectively oscillating at first and second frequencies to the RF power amplifier, and a step-up circuit for magnifying the RF power amplifier output. The step-up circuit includes an LC resonator network tuned to the first and second frequencies, and an output for providing the magnified voltage to a rod assembly of the mass spectrometer.

Abstract: A capillary electrophoresis system includes a capillary reservoir. The capillary reservoir includes a capillary tip flow chamber configured to receive respective capillary tips and to conduct fluid past the capillary tips, and an electrode flow chamber in which an electrode is disposed and configured to conduct fluid past the electrode, the electrode flow chamber being separate from and in fluid communication with the capillary tip flow chamber. An ultraviolet (UV) light absorbance-based multiplexed capillary electrophoresis system includes a first enclosure and a second enclosure. The first enclosure covers a UV light source, and includes a slit. The second enclosure covers the first enclosure, a collimating lens, and a capillary window.