Abstract: Described herein is a method for adding a counter sequence to the individual polynucleotide molecules of an initial nucleic acid sample. After addition of the counter sequence, the sample may be amplified and the number of initial target molecules in the sample can be estimated by counting the number of counter sequences associated with the amplified target molecules.

Abstract: Modified silica particles are provided. Aspects of the particles include an outer layer that is composed of organically-modified silica comprising a siloxane-linked hydrophilic group, such as a charged functional group or a polar neutral functional group. The modified silica particles can form the basis of a variety of chromatography support materials. Also provided are methods of preparing the subject particles. Aspects of the methods include contacting silica particles with water, an ionic fluoride and an organosilane reagent comprising a hydrophilic moiety to produce modified silica particles wherein the hydrophilic moiety of the organosilane reagent is incorporated into an outer layer of the silica particles. Chromatography supports and kits including the subject particles and methods of using the same are also provided.

Abstract: The present disclosure generally relates to improved methods for separating and analyzing compounds by liquid chromatography, particularly when coupled with mass spectrometry. The methods include the addition of an additive to a mobile phase carrying a sample. The mobile phase additive may be effective for improving peak shapes of targeted analytes in acquired data, and/or eliminating or at least reducing ion suppression. The methods are particularly suited for anionic compounds such as phosphorylated compounds.

Abstract: Paraffin-embedded tissue, which may be disposed on a solid substrate, is prepared by a dry technique that removes paraffin from tissue without adding any liquid to the tissue, thereby rendering the tissue substantially free of paraffin. The dry technique may entail applying heat energy to the tissue effective to melt the paraffin and thereby render it flowable, and applying an electric field. The electric field is effective to impart electrical charge to the paraffin and to move the paraffin out from the tissue due to electrical charge repulsion or attraction, which may be assisted by moving an electrode utilized to generate the electric field relative to the paraffin. The electric field, or both the electric field and the heat energy, may be applied until the tissue is substantially free of paraffin.

Abstract: Aspects of the present disclosure provide methods for determining the eligibility of a subject having a malignancy for treatment with an anti-PD therapeutic agent based on a Combined Positive Score (CPS) for a tumor tissue sample from the subject. Compositions and kits or performing the disclosed methods are also provided.

Abstract: The present invention relates to MHC-peptide complexes and uses thereof in the diagnosis of, treatment of or vaccination against a disease in an individual. More specifically the invention discloses MHC complexes comprising Mycobacterium tuberculosis antigenic peptides and uses there of.

Abstract: A secondary electron multiplier includes: a conversion dynode for emitting a secondary electron in response to an incident ion; a plurality of dynodes configured to have multi-stages from second to final stages for receiving the secondary electron; and a first voltage applying device for applying a first negative voltage to the conversion dynode and sequentially dividing the first negative voltage to apply to each of the second-stage and subsequent dynodes, wherein the secondary electron multiplier is configured to sequentially multiply the emitted secondary electron by the second-stage and subsequent dynodes. In the secondary electron multiplier, any of the second-stage and subsequent dynodes have a second voltage applying device for applying a second negative voltage. The secondary electron multiplier has an improved ion detection efficiency without a large reduction of a usable period thereof, thereby enhancing the sensitivity of a mass spectrometer.

Abstract: The present invention provides a method for making a large nucleic acid having a defined sequence in vivo. The method combines recombineering techniques with a CRISPR/Cas system to permit multiple insertions of defined sequences into a target nucleic acid at one time, double stranded cleavage of target nucleic acids in which the defined sequences were not successfully inserted, and selection of successful recombinant cells. The method further includes repeating the process one or more times, using a successful recombinant from one round as the host cell for the next round.

Abstract: An ATR scanner and method for calibrating the same are disclosed. The scanner includes an ATR objective having a reflecting face and an optical port adapted to receive a first light beam, and to focus the first light beam to a point, at a location on the reflecting face such that the first light beam is reflected by the reflecting face and no portion of the first light beam strikes the reflecting face at an angle greater than the critical angle. A detector measures an intensity of light reflected from the reflecting face. A controller controls the location of the focal point and determines an intensity of light that was incident on the reflecting face as a function of the position on the reflecting face and an intensity of light that was reflected from the reflecting face as a function of position on the reflecting face.

Abstract: A method of deprotecting a solid support bound polynucleotide comprising at least one 2?-protected ribonucleotide in which a step of contacting the polynucleotide with a composition comprising a diamine is performed under conditions sufficient to deprotect and cleave the polynucleotide which remains retained on the solid support.

Abstract: A method for sequencing a nucleic acid is provided. In certain embodiments the method comprises obtaining a duplex comprising a nucleic acid and a primer, wherein the primer has a nuclease resistant 3? end, combining the duplex with a chain terminator nucleotide and a proof-reading polymerase to produce a reaction in which the polymerase idles on the added chain terminator nucleotide, identifying the chain terminator nucleotide added to the end of the primer; and adding a nuclease-resistant nucleotide to the end of the primer after the polymerase has idled on and removed the added chain terminator nucleotide, thereby producing a duplex comprising the template and an extended primer that has a nuclease resistant 3? end.

Abstract: A piston member for a high-pressure pump for pumping fluid in a sample separation apparatus, wherein the piston member comprises a piston configured for being mountable to reciprocate in a piston chamber for displacing fluid, and a sealing for sealing between the piston member and the piston chamber when the piston member is mounted in the piston chamber to reciprocate, wherein the sealing is mounted on the piston so as to reciprocate together with the piston.

Abstract: In a mass spectrometer or gas chromatograph/mass spectrometer system, one or more different conditioning gases are added to condition or modify one or more surfaces or regions of the ion source. The conditioning gas(es) may be added directly into the ion source. The conditioning gas may be added off-line, when the mass spectrometer is not analyzing a sample.

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 method for fragmenting a genome is provided. In certain embodiments, the method comprises: (a) combining a genomic sample containing genomic DNA with a plurality of Cas9-gRNA complexes, wherein the Cas9-gRNA complexes comprise a Cas9 protein and a set of at least 10 Cas9-associated guide RNAs that are complementary to different, pre-defined, sites in a genome, to produce a reaction mixture; and (b) incubating the reaction mixture to produce at least 5 fragments of the genomic DNA. Also provided is a composition comprising at least 100 Cas9-associated guide RNAs that are each complementary to a different, pre-defined, site in a genome. Kits for performing the method are also provided. In addition, other methods, compositions and kits for manipulating nucleic acids are also provided.

Abstract: Aspects of the present disclosure include a system for analytical sample preparation. In some embodiments, the system includes a container having disposed therein an analytical sample treatment composition including ?-cyclodextrin and/or an ?-cyclodextrin co-polymer. Also provided is a method of reducing matrix effects in an analytical sample. In some embodiments, the method includes: contacting a sample including a matrix-interfering agent and an analyte with a cyclodextrin composition to produce a matrix-cyclodextrin complex, wherein the cyclodextrin composition comprises an ?-cyclodextrin and/or an ?-cyclodextrin co-polymer; separating the complex from the contacted sample to produce a matrix-reduced composition; and detecting the analyte in the matrix-reduced composition. Kits and compositions for use in the subject systems and methods are also provided.

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: 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: Provided herein, among other things, are compositions for improving signal-to-noise in hybridization to oligonucleotide arrays. In some embodiments, the composition may comprise a population of indexing oligonucleotides of formula X-Y, where the sequences of region X hybridize to an array and the sequences of region Y hybridize to distinct sites within a genomic region, transcript, set of transcripts, or complement of the same. Use of these oligonucleotides increases signal, reduces background and smoothens array hybridization analyses. Methods and kits that employ the compositions are also provided.

Abstract: In one embodiment, a high voltage power supply includes a DC voltage input, a converter for converting a DC voltage at the DC voltage input to an AC voltage, a booster for boosting the AC voltage to a boosted AC voltage, a rectifier in DC isolation from the DC voltage input, the rectifier operable to convert the boosted AC voltage to a high DC voltage at an isolated rectifier output, a high voltage DC output for outputting the high DC voltage, a voltage control input, and an error circuit coupled to the voltage control input and operable to reduce variation in the high DC voltage by driving a return side of the isolated rectifier output in response to feedback based on the high DC voltage.