Abstract: A technique for sequencing nucleic acids in an automated or semi-automated manner is disclosed. Sample arrays of a multitude of nucleic acid sites are processed in multiple cycles to add nucleotides to the material to be sequenced, detect the nucleotides added to sites, and to de-block the added nucleotides of blocking agents and tags used to identify the last added nucleotide. Multiple parameters of the system are monitored to enable diagnosis and correction of problems as they occur during sequencing of the samples. Quality control routines are run during sequencing to determine quality of samples, and quality of the data collected.

Abstract: A technique for sequencing nucleic acids in an automated or semi-automated manner is disclosed. Sample arrays of a multitude of nucleic acid sites are processed in multiple cycles to add nucleotides to the material to be sequenced, detect the nucleotides added to sites, and to de-block the added nucleotides of blocking agents and tags used to identify the last added nucleotide. Multiple parameters of the system are monitored to enable diagnosis and correction of problems as they occur during sequencing of the samples. Quality control routines are run during sequencing to determine quality of samples, and quality of the data collected.

Abstract: Methods for obtaining nucleic acid sequence information including the steps of (a) providing a first sequencing reagent to a target nucleic acid in the presence of a polymerase, wherein the first sequencing reagent includes at least two different nucleotide monomers and no more than three nucleotide monomers, wherein the nucleotide monomers are simultaneously in the presence of the target nucleic acid, (b) providing a second sequencing reagent to the target nucleic acid, wherein the second sequencing reagent comprises one or more nucleotide monomers, at least one of the one or more nucleotide monomers being different from the nucleotide monomers present in the first sequencing reagent, and wherein the second sequencing reagent is provided subsequent to providing the first sequencing reagent, and optionally (c) repeating (a) and (b) for said target nucleic acid, whereby sequence information for at least a portion of the target nucleic acid is obtained.

Abstract: The invention provides a method for preparing and analysing a population of fragmented polynucleotide sequences having a substantially uniform size. The method can include steps of (a) binding at least one protection molecule to at least one polynucleotide sequence; (b) cleaving the at least one polynucleotide sequence to generate a plurality of polynucleotide fragment sequences of substantially uniform size; (c) amplifying the polynucleotide fragments; and (d) determining a sequence characteristic of a plurality of the polynucleotide fragments.

Abstract: The present invention provides methods for creating an array of features on a surface based on content transferred from a plurality of beads to the surface. Nucleic acid content can be transferred using a method including the steps of (a) providing a surface having one or more primer oligonucleotides attached to the surface; (b) providing a pool of beads, wherein beads in the pool have a plurality of templates attached thereto, the plurality comprising multiple copies of a single nucleic acid template sequence; (c) arraying the beads onto the surface by hybridizing the templates to the primer oligonucleotides; and (d) extending the primers to produce copies of the templates attached to the surface.

Abstract: The invention provides imaging apparatus and methods useful for obtaining a high resolution image of a sample at rapid scan rates. A rectangular detector array having a horizontal dimension that is longer than the vertical dimension can be used along with imaging optics positioned to direct a rectangular image of a portion of a sample to the rectangular detector array. A scanning device can be configured to scan the sample in a scan-axis dimension, wherein the vertical dimension for the rectangular detector array and the shorter of the two rectangular dimensions for the image are in the scan-axis dimension, and wherein the vertical dimension for the rectangular detector array is short enough to achieve confocality in a single axis.

Abstract: A prism for use in scanning applications such as total internal reflection microscopy in which the prism is translated relative to an incident light beam. A geometry is disclosed which cancels walk of the beam footprint at the base of the prism. Walk of the beam footprint due to irregularities in a largely planar sample surface located at the prism base are cancelled by coupling movement of the incident light beam to movement of the sample in the field of view of an objective lens, for example as part of an autofocus arrangement.

Abstract: The invention provides a method of modifying a phosphomonoester moiety of a target compound. The method can include the steps of (a) providing a target compound having an electrophilic moiety and a phosphomonoester moiety; (b) contacting the target compound with a first carbodiimide compound under conditions for preferential addition of the first carbodiimide compound to the electrophilic moiety over the phosphomonoester moiety, thereby forming an electrophile-protected target compound; and (c) contacting the electrophile-protected target compound with a second carbodiimide compound and a nucleophilic compound under conditions for addition of the nucleophilic compound to the phosphomonoester.

Abstract: The invention provides imaging apparatus and methods useful for obtaining a high resolution image of a sample at rapid scan rates. A rectangular detector array having a horizontal dimension that is longer than the vertical dimension can be used along with imaging optics positioned to direct a rectangular image of a portion of a sample to the rectangular detector array. A scanning device can be configured to scan the sample in a scan-axis dimension, wherein the vertical dimension for the rectangular detector array and the shorter of the two rectangular dimensions for the image are in the scan-axis dimension, and wherein the vertical dimension for the rectangular detector array is short enough to achieve confocality in a single axis.

Abstract: The invention provides a method of modifying a phosphomonoester moiety of a target compound. The method can include the steps of (a) providing a target compound having an electrophilic moiety and a phosphomonoester moiety; (b) contacting the target compound with a first carbodiimide compound under conditions for preferential addition of the first carbodiimide compound to the electrophilic moiety over the phosphomonoester moiety, thereby forming an electrophile-protected target compound; and (c) contacting the electrophile-protected target compound with a second carbodiimide compound and a nucleophilic compound under conditions for addition of the nucleophilic compound to the phosphomonoester.

Abstract: The invention provides imaging apparatus and methods useful for obtaining a high resolution image of a sample at rapid scan rates. A rectangular detector array having a horizontal dimension that is longer than the vertical dimension can be used along with imaging optics positioned to direct a rectangular image of a portion of a sample to the rectangular detector array. A scanning device can be configured to scan the sample in a scan-axis dimension, wherein the vertical dimension for the rectangular detector array and the shorter of the two rectangular dimensions for the image are in the scan-axis dimension, and wherein the vertical dimension for the rectangular detector array is short enough to achieve confocality in a single axis.

Abstract: The invention provides imaging apparatus and methods useful for obtaining a high resolution image of a sample at rapid scan rates. A rectangular detector array having a horizontal dimension that is longer than the vertical dimension can be used along with imaging optics positioned to direct a rectangular image of a portion of a sample to the rectangular detector array. A scanning device can be configured to scan the sample in a scan-axis dimension, wherein the vertical dimension for the rectangular detector array and the shorter of the two rectangular dimensions for the image are in the scan-axis dimension, and wherein the vertical dimension for the rectangular detector array is short enough to achieve confocality in a single axis.

Abstract: The invention provides a method of determining activity of a protease.

Abstract: An abrasive jet apparatus is provided which includes an abrasive dispenser defining a compartment for storing a granular abrasive material and at least one metering orifice disposed in open communication therewith for dispensing the granular abrasive material. The apparatus also includes a shutter assembly disposed adjacent the metering orifice, which includes a shutter member angularly displaceable between first and second positions relative to the metering orifice. The shutter member has formed therethrough at least one shutter opening which in the first position is substantially fully aligned with the metering orifice, and in the second position is substantially fully offset therefrom. The apparatus further includes a position actuator operatively coupled to the shutter mechanism for reversibly displacing the shutter member to the first and second positions and a plurality of intermediate positions therebetween for occluding a selective portion of the metering orifice.

Abstract: Described herein are systems and methods for normalizing data without the use of external controls. Also described herein are systems and methods for analyzing cluster data, such as genotyping data, using an artificial neural network.

Abstract: The invention provides an apparatus and method for transferring a plurality of samples from an array of source sample locations to an array of destination sample locations. An apparatus or method of the invention are useful for reformatting samples in cases where the array of source sample locations differs in shape or orientation from the array of destination sample locations. The invention can be used to transfer fluid samples in the absence of an externally applied force. Because active automation is not required for transferring samples, the invention provides the advantage of a compact and efficient format for liquid handling.

Abstract: The invention relates to compositions and methods for decoding microsphere array sensors.