Abstract: A system and method is provided for validating the manufacturing process for the production of complex biological compositions, and particularly for providing process validation information for evaluation by a federal regulatory agency. The system and method continuously and chronologically assess the concentration of proteoforms within the biological composition as it is being produced in a fermentor. Samples from the fermentor are analyzed in a pre-selected array of analysis columns, with data generated by the columns being accumulated and evaluated, and particularly compared with data from previous stages in the production process. A continuous process validation system includes top-down and bottom-up analysis sectors, each including a plurality of different analysis columns that can be selected by the controller for a particular biological composition and a particular production process.

Abstract: The present invention relates to methods for continuous or near-continuous separation and purification of samples, particularly biological samples, to reduce the number or volume of non-targeted analytes in those samples to enable improved mass spectrometric analysis of analytes of interest, and apparatuses for conducting those methods, utilizing a transport agent with a core domain and a binding domain, the transport agent exceeding 200 kiloDaltons or 10 nm, and the binding domain targeted to the analytes of interest, in conjunction with size-exclusion based chromatography to separate the transport agent-analyte of interest complex from non-targeted analytes that are not bound, or are only non-specifically bound, to the transport agent.

Abstract: The present invention relates to methods for continuous or near-continuous separation and purification of samples, particularly biological samples, to reduce the number or volume of non-targeted analytes in those samples to enable improved mass spectrometric analysis of analytes of interest, and apparatuses for conducting those methods, utilizing a transport agent with a core domain and a binding domain, the transport agent exceeding 200 kiloDaltons or 10 nm, and the binding domain targeted to the analytes of interest, in conjunction with size-exclusion based chromatography to separate the transport agent-analyte of interest complex from non-targeted analytes that are not bound, or are only non-specifically bound, to the transport agent.

Abstract: The present invention relates to methods for continuous or near-continuous separation and purification of samples, particularly biological samples, to reduce the number or volume of non-targeted analytes in those samples to enable improved mass spectrometric analysis of analytes of interest, and apparatuses for conducting those methods, utilizing a transport agent with a core domain and a binding domain, the transport agent exceeding 200 kiloDaltons or 10 nm, and the binding domain targeted to the analytes of interest, in conjunction with size-exclusion based chromatography to separate the transport agent-analyte of interest complex from non-targeted analytes that are not bound, or are only non-specifically bound, to the transport agent.

Abstract: The invention relates to a device for the rapid simultaneous collection, and, optionally, treatment or standardization, of multiple aliquots of a liquid biological sample such as blood from a single source drop or sample portion, the device comprising device comprising a cover, a spreading layer comprising a macroporous membrane adjacent to the cover, where the spreading layer comprises a transport portion and at least one accumulation portion in fluid connection with the transport portion, and at least one collection portion in fluid connection with each accumulation portion.

Abstract: The present invention relates to methods for continuous or near-continuous separation and purification of samples, particularly biological samples, to reduce the number or volume of non-targeted analytes in those samples to enable improved mass spectrometric analysis of analytes of interest, and apparatuses for conducting those methods, utilizing a transport agent with a core domain and a binding domain, the transport agent exceeding 200 kiloDaltons or 10 nm, and the binding domain targeted to the analytes of interest, in conjunction with size-exclusion based chromatography to separate the transport agent-analyte of interest complex from non-targeted analytes that are not bound, or are only non-specifically bound, to the transport agent.

Abstract: The present invention comprises methods for determining the presence, amount, or concentration of analytes of interest including Vitamin D and other secosteroids from biological samples, through derivatization, with improved speed and ease of analysis and improved sensitivity to mass spectrometry. In a preferred embodiment, the present invention comprises methods for determining the presence, amount, or concentration of analytes of interest, including Vitamin D and other secosteroids from whole human blood, through derivatization, and using a plasma collection device to facilitate collection, separation, and preparation of the sample for derivatization and analysis.

Abstract: The present invention comprises methods for determining the presence, amount, or concentration of analytes of interest including Vitamin D and other secosteroids from biological samples, through derivatization, with improved speed and ease of analysis and improved sensitivity to mass spectrometry. In a preferred embodiment, the present invention comprises methods for determining the presence, amount, or concentration of analytes of interest, including Vitamin D and other secosteroids from whole human blood, through derivatization, and using a plasma collection device to facilitate collection, separation, and preparation of the sample for derivatization and analysis.

Abstract: The present invention provides compositions and methods for enhanced detection and quantification of amino acids by derivatization. Also provided are compositions and methods for enhanced detection and quantification of peptides by derivatization.

Abstract: The present invention comprises a diagnostic platform. The platform has a substrate having plurality of hydrophobic wells formed thereon. The hydrophobic wells are directly printed onto the substrate in a test pattern and are adapted to contain a biological sample for conducting a diagnostic assay to identify analytes within the biological sample. The test pattern is divided into equally sized quadrants, each containing an equal number of hydrophobic wells. The hydrophobic wells may be in a single or double well arrangement, as well as may be connected by at least one microfluidic channel.

Abstract: A sample holder comprises a substrate microfabricated to define a multiplicity of microscopic islands defining sample support surfaces. At least one sump separates adjacent island surfaces and inhibits transport of samples between adjacent island surfaces.

Abstract: A method of probing a plurality of analyzer molecules distributed about a detection platform is disclosed. The method includes contacting a test sample to the plurality of analyzer molecules, scanning the plurality of analyzer molecules at a rate relating to a carrier frequency signal, and detecting the presence or absence of a biological molecule based at least in part upon the presence or absence of a signal substantially at a sideband of the carrier frequency signal. A molecule detection platform including a substrate and a plurality of targets positioned about the substrate is also disclosed. Specific analyzer molecules adapted to bind a specific analyte are immobilized about a first set of the targets. Nonspecific analyzer molecules are immobilized about a second set of the targets. The targets positioned about the substrate along at least a segment of a scanning pathway alternate between at least one of the first set and at least one of the second set.

Abstract: A planar array having plurality of biological recognition molecules including at least two types of biological recognition molecules distributed about a substrate is disclosed. A first type of biological recognition molecules is distributed according to a first frequency and a second type of biological recognition molecules is distributed according to a second frequency. Another planar array having a plurality of biological recognition molecules including at least two kinds of biological recognition molecules is disclosed. The recognition molecules are distributed about a substrate with first kind of biological recognition molecules distributed at a first height or depth relative to a surface of the substrate and a second kind of biological recognition molecules distributed at a second height or depth relative to the surface.

Abstract: A phase contrast quadrature interferometric method for determining the presence or absence of a target analyte in a sample. The method comprises using a laser beam having a wavelength ? and a waist wo to probe at least a portion of a substrate having a reflecting surface that has been exposed to the sample. The reflecting surface includes at least a first region having a layer of recognition molecules specific to the target analyte and a second region that does not include a layer of recognition molecules specific to the target analyte. The method further comprises measuring a time dependent intensity on a photodetector of a substantially only first quadrature at one of a pair of quadrature angles ?q of a reflected diffraction signal of the probe beam while probing the first region and the second region. An apparatus for phase-contrast quadrature interferometric detection of the presence or absence of a target molecule on a planar array, comprises a laser source for generating a probe beam.

Abstract: A device for identifying analytes in a biological sample, including a substrate configured to bind the analyte and a detection system to determine the presence or absence of the analyte in the biological sample.

Abstract: An apparatus for assessing topology of a surface of a target. The apparatus includes an optical source for generating a probe laser beam. The apparatus also includes means for scanning the probe laser beam across at least a portion of the surface of the target. The apparatus further includes a beamsplitter for redirecting a return signal toward means for detecting the return signal in a substantially quadrature condition, the return signal resulting from reflection of the probe laser beam off the surface of the target. A quadrature interferometric method for determining the presence or absence of a target analyte in a sample. The method comprises generating a laser probe beam having a wavelength ? and a waist wo to probe at least a portion of a substrate having a reflecting surface that has been exposed to the sample.

Abstract: The invention provides novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics. Specifically, the claimed multi-dimensional methods involve combining a solution of heterogeneous ligands with the target of interest to screen the ligands on the basis of one or more binding characteristics. Ligands having the first binding characteristic bind to the target of interest thereby to form a target/ligand complex. The complex then optionally is separated from the unbound components using any of a variety of separation techniques, e.g., size exclusion. At least one of the complex or unbound components then is introduced to a second “dimension”. The second dimension is capable of separating components based upon a second binding characteristic. One then elutes the ligand having the desired binding characteristics.

Abstract: The invention provides novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics. Specifically, the claimed multi-dimensional methods involve combining a solution of heterogeneous ligands with the target of interest to screen the ligands on the basis of one or more binding characteristics. Ligands having the first binding characteristic bind to the target of interest thereby to form a target/ligand complex. The complex then optionally is separated from the unbound components using any of a variety of separation techniques, e.g., size exclusion. At least one of the complex or unbound components then is introduced to a second “dimension”. The second dimension is capable of separating components based upon a second binding characteristic. One then elutes the ligand having the desired binding characteristics.

Abstract: The invention provides novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics. Specifically, the claimed multi-dimensional methods involve combining a solution of heterogeneous ligands with the target of interest to screen the ligands on the basis of one or more binding characteristics. Ligands having the first binding characteristic bind to the target of interest thereby to form a target/ligand complex. The complex then optionally is separated from the unbound components using any of a variety of separation techniques, e.g., size exclusion. At least one of the complex or unbound components then is introduced to a second “dimension”. The second dimension is capable of separating components based upon a second binding characteristic. One then elutes the ligand having the desired binding characteristics.

Abstract: The present invention relates to an in situ micromachined mixer for microfluidic analytical systems. In a preferred embodiment, a 100 pL mixer for liquids transported by electroosmotic flow (EOF) is described. Mixing was achieved in multiple intersecting channels with a bimodal width distribution and varying lengths. Five &mgr;m width channels ran parallel to the direction of flow whereas larger 27 &mgr;m width channels ran back and forth through the network at a 45° angle. All channels were approximately 10 &mgr;m deep. It was observed that little mixing of confluent streams occurred in the 100 &mgr;m wide mixer inlet channel where mixing would be achieved almost exclusively by diffusion. In contrast, mixing was complete after passage through the channel network in the ≈200 &mgr;m length mixer. Solvent composition was altered by varying the voltage on solvent reservoirs. The high efficiency attained in this mixer was attributed to the presence of a 2 pL vortex in the center of the mixer.