Abstract: The invention provides methods and compositions for separately denaturing a probe and target in hybridization applications. The invention may, for example, eliminate the use of, or reduce the dependence on formamide in hybridization applications. Compositions for use in the invention include an aqueous composition comprising at least one polar aprotic solvent in an amount effective to denature double-stranded nucleotide sequences.

Abstract: A valve arrangement includes a valve module and a base module. The valve module includes a stator and a rotor, which is rotatable relative to the stator such that at least one fluid connection is formable between the stator and the rotor. The base module includes at least a part of a force control mechanism for selectively implementing a force-releasing or force-coupling of the rotor and the stator, whereby the valve module and the base module are selectively coupleable to or decoupleable from each other.

Abstract: An electrostatic lens for transporting charged particles in an axial direction includes a first group of first electrodes configured to receive a first DC potential from a DC voltage source, and a second group of second electrodes configured to receive a second DC potential from the DC voltage source different from the first DC potential. The first electrodes are interdigitated with the second electrodes. The first group and/or the second group has a geometric feature that progressively varies along the axial direction. The lens generates an axial potential profile that progressively changes along the axial direction, and thereby reduces geometrical aberrations. The lens may be part of a charged particle processing apparatus such as, for example, a mass spectrometer or an electron microscope.

Abstract: A vacuum pump includes a housing, a rotatable shaft extending in an axial direction within the housing, a first pumping arrangement including a first stator arrangement and a first rotor arrangement, and a second pumping arrangement including a second stator arrangement and a second rotor arrangement. The vacuum pump further includes a spacer arranged between the first pumping arrangement and the second pumping arrangement. The spacer is coupled between the first stator arrangement and the second stator arrangement and is configured to provide a defined elasticity in the axial direction allowing an elastic deformation of the spacer in the axial direction.

Abstract: A degasser for at least partially degassing a gas-containing liquid, in particular for a sample separation device, includes a circulation path along which the liquid can be circulated between a liquid accommodation volume and one of an inlet to a consumer unit consuming degassed liquid or a conduit leading to the inlet, a drive unit configured for circulating the liquid in the circulation path, and a filter in the circulation path for filtering particles or debris out of the liquid, wherein the liquid is forced through the filter by the drive unit. The drive unit includes a movable body, in particular a movable piston or a movable membrane, configured for at least partially degassing the liquid by generating a negative pressure in the liquid.

Abstract: Mutant polymerases are provided that have improved ability to incorporate modified nucleotides, including 3?-OH unblocked reversible terminators. The mutant polymerases may be used in a variety of applications, such as for polynucleotide sequencing, primer extension reactions, and template-independent enzymatic oligonucleotide synthesis.

Abstract: A fluid valve for a sample separation apparatus includes a first valve component and a second valve component, which are adjacent to one another and movable relative to one another. The valve components are configured such that, in at least one switching state, at least one switchable fluid channel is formed between the valve components, and at least one part of a surface of at least one of the first valve component and the second valve component is provided with a coating containing gold and/or platinum.

Abstract: Methods of inducing functional maturation of immature cardiomyocytes derived from induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) by electrically pacing the immature cardiomyocytes according to a pulse profile that induces maturation until the immature cardiomyocytes mature into functionally adult cardiomyocytes.

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: Provided herein are compositions and methods to assess the genomic landscape of fixed cells using light activated oligonucleotides that can be directed to the nucleus, mitochondria, or cytoplasm of fixed cells and that, upon activation, can be extended for in situ copying of nuclear single-stranded DNA (i.e., open chromatin), open mitochondrial DNA, and/or cytoplasmic RNA into barcoded complementary DNA. These methods also provide for gene specific 3D chromatin structural niche analysis.

Abstract: Methods and compositions are provided for amplifying a pool of oligonucleotides, such as dual guide oligonucleotide constructs comprising sequences encoding a first guide RNA segment and a sequence encoding a second guide RNA segment. An amplification mixture is formed comprising the pool of oligonucleotides, an amplification enzyme, deoxyribonucleotide triphosphates, and primers. The amplification mixture is thermocycled a sufficient number of times and under conditions to produce a library of oligonucleotide constructs. The present methods and compositions provide dual guide libraries, including libraries that are essentially free of scrambled library members.

Abstract: A method of optical analysis comprises receiving light at an optical spectrometer module from a light source, distributing the received light into two or more light beams with a light distribution component of the optical spectrometer module, concurrently exposing each of a reference and one or more test samples to one of the two or more light beams, and concurrently measuring a property of the light associated with each of the reference sample and one or more test samples with a corresponding detector.

Abstract: A fluid pump includes a pump head and a motor coupled by a drive shaft. The pump head includes a pump inlet, a pump outlet, and a pumping stage in which a movable pump element is driven by the drive shaft. The motor includes a motor rotor and a motor stator. A connector couples the motor rotor and the drive shaft. The connector includes a plate rotatable with the drive shaft, fan blades attached to the plate for establishing a flow of air for cooling the motor, and one or more counterweights attached to the plate for reducing or eliminating imbalance created by certain forces generated by the pump during operation.

Abstract: Systems, computer-readable media, and methods using mass spectrometry to analyze a sample are provided. For example, a method includes: acquiring a precursor ion spectrum; analyzing the precursor ion spectrum to identify precursor ions that preliminarily match one or more peptides that each belong to at least one protein of interest for the analysis; selecting each of the identified precursor ions in an order according to a ranking protocol for maximizing the number of proteins that are identified in the sample; for each selected precursor ion: acquiring a corresponding product ion spectrum, determining whether the acquired product ion spectrum matches one of the peptides that belong to the set of proteins of interest, and identifying a matched peptide as being present in the sample; and identifying proteins of interest that are present in the sample based on the peptides that are identified as being present in the sample.

Abstract: The present disclosure relates to methods and apparatus for measuring of multiple physiological properties of biological samples, such as measuring biological flux.

Abstract: A sample separation network includes a server node, a plurality of client nodes coupled with the server node, a plurality of sample separation devices coupled with the server node, wherein each of the sample separation devices includes device-specific control software configured for controlling specifically the respectively assigned sample separation device, wherein at least one of the server node and the client nodes includes generic control software configured for generically controlling sample separation devices in a non-device-specific way, and wherein at least one of the server node and the client nodes and the sample separation devices is configured for loading device-specific control software from a sample separation device to at least one of the server node and the client nodes upon connection of said sample separation device to the sample separation network.

Abstract: An apparatus for separating a fluidic sample includes a fluid drive arrangement including fluid drive units for driving a mobile phase along a flow path to a sample separation unit, a sample accommodation volume for accommodating the fluidic sample and selectively fluidically coupleable with or decoupleable from the flow path, and a control unit. The control unit is configured to control pressure decoupling of at least part of at least one of the fluid drive units from the flow path, and enable the partially pressure-decoupled fluid drive unit(s) to pressurize the sample accommodation volume before fluidically coupling the sample accommodation volume with the flow path and/or to de-pressurize the sample accommodation volume after fluidically coupling the sample accommodation volume with the flow path for preparing a subsequent intake of fluidic sample in the sample accommodation volume.

Abstract: A solvent supply system for supplying a composite includes a first supply path with a first pump unit, the first supply path being adapted for supplying a first solvent to a mixing unit, the first pump unit operating periodically, and a second supply path with a second pump unit, the second supply path being adapted for supplying a second solvent to the mixing unit, the second pump unit operating periodically. The mixing unit is adapted for mixing the first and the second solvent and for supplying a composite solvent. The solvent supply system further includes a control unit adapted for controlling operation of the first and the second pump unit.

Abstract: In an inductively coupled plasma-mass spectrometry (ICP-MS) system, ions are transmitted into a collision/reaction cell. A DC potential is applied at an exit of the cell at a first magnitude to generate a DC potential barrier effective to prevent the ions from exiting the cell. The DC potential barrier is maintained during a confinement period to perform an interaction. After the confinement period, analyte ions or product ions are transmitted to a mass spectrometer by switching the exit DC potential to a second magnitude effective to allow the analyte ions or product ions to pass through the cell exit as a pulse. The analyte ions or product ions are then counted during a measurement period. The interaction may be ion-molecule reactions or ion-molecule collisions.

Abstract: A sample dispatcher for a fluid separation apparatus includes a sampling path including a sampling volume, a sampling unit, and a retaining unit. The sampling unit receives a fluidic sample, and the sampling volume temporarily stores an amount of the received sample. The retaining unit receives and retains from the sampling volume at least a portion of the stored sample, and has different retention characteristics for different components of the sample. A switching unit is coupled to the sampling path, a sampling fluid drive, a mobile phase drive, and a separating device. In a feed injection configuration of the switching unit, the mobile phase drive, the separating device, and the sampling path are coupled together in a coupling point for combining a flow from the sampling fluid drive containing the fluidic sample retained by the retaining unit with a flow of the mobile phase from the mobile phase drive.