Abstract: The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy of drugs are also discussed.

Abstract: A laser ablation cell (1) comprises a flow channel (11) having an essentially constant cross-sectional area so as to ensure a strictly laminar flow in the flow channel. A sample chamber (21) is provided adjacent to a lateral opening (14) of the flow channel. A laser beam (41) enters the sample chamber (21) through a lateral window (16) and impinges on a surface (24) of a sample (23) to ablate material from the sample. The sample may be positioned in such a distance from the flow channel that the laser-generated aerosol mass distribution has its center within the flow channel. This leads to short aerosol washout times. The laser ablation cell is particularly well suited for aerosol generation in inductively coupled plasma mass spectrometry (ICPMS), including imaging applications.

Abstract: The disclosure provides biomarker panels, methods and kits for determining the probability for preeclampsia in a pregnant female. The present disclosure is based, in part, on the discovery that certain proteins and peptides in biological samples obtained from a pregnant female are differentially expressed in pregnant females that have an increased risk of developing in the future or presently suffering from preeclampsia relative to matched controls. The present disclosure is further based, in part, on the unexepected discovery that panels combining one or more of these proteins and peptides can be utilized in methods of determining the probability for preeclampsia in a pregnant female with relatively high sensitivity and specificity. These proteins and peptides dislosed herein serve as biomarkers for classifying test samples, predicting a probability of preeclampsia, monitoring of progress of preeclampsia in a pregnant female, either individually or in a panel of biomarkers.

Abstract: The invention provides a liquid cell for an atomic force microscope. The liquid cell includes a liquid cell housing with an internal cavity to contain a fluid, a plurality of conductive feedthroughs traversing the liquid cell housing between the internal cavity and a dry side of the liquid cell, a cantilevered probe coupled to the liquid cell housing, and a piezoelectric drive element disposed on the cantilevered probe. The cantilevered probe is actuated when a drive voltage is applied to the piezoelectric drive element through at least one of the conductive feedthroughs. A method of imaging an object in a liquid medium and a method of sensing a target species with the liquid cell are also disclosed.

Abstract: The disclosure provides biomarker panels, methods and kits for determining the probability for preterm birth in a pregnant female. The present disclosure is based, in part, on the discovery that certain proteins and peptides in biological samples obtained from a pregnant female are differentially expressed in pregnant females that have an increased risk of developing in the future or presently suffering from preterm birth relative to matched controls. The present disclosure is further based, in part, on the unexepected discovery that panels combining one or more of these proteins and peptides can be utilized in methods of determining the probability for preterm birth in a pregnant female with relatively high sensitivity and specificity. These proteins and peptides disclosed herein serve as biomarkers for classifying test samples, predicting a probability of preterm birth, monitoring of progress of preterm birth in a pregnant female, either individually or in a panel of biomarkers.

Abstract: The invention generally relates to methods for sample multiplexing. In certain embodiments, methods of the invention obtaining a plurality of different reactant molecules, attaching a unique identifier to the reactant molecules, and forming a droplet including the reactant molecules.

Abstract: The invention includes methods and apparatus for isolating and recovering mutations, especially rare and unknown mutations, without amplifying the sample. In particular, using the disclosed methods, it is possible to separate heteroduplexed nucleic acid strand pair from homoduplexed nucleic acid strand pairs having similar sequences and being at a much higher concentration. Once the heteroduplexed nucleic acids are isolated and recovered, it is straightforward to analyze the sequences of the heteroduplexed nucleic acids, e.g., using sequencing or hybrid assays.

Abstract: System, including methods, apparatus, and compositions, for performing a multiplexed digital assay of at least three targets. In an exemplary method, partitions may be formed each including a portion of a same sample. The sample may include a first target that is a reference sequence, a second target that is a variant sequence from a gene of interest, and a third target that is a normal sequence from the gene of interest. The target may be amplified in the partitions and amplification data may be collected. A level of the second target may be determined. A copy number of the third target may be determined from a level of the first target and a level of the third target.

Abstract: Isolated, Chlamydia-specific, IL-13 expressing CD8+ T cell clones are provided for understanding the biology of Chlamydia infection and screening of therapeutics. Furthermore, methods are provided for isolating CD8+ T cells comprising the steps of infecting or identifying a naturally infected mammal with at least one species of Chlamydia causing bacteria, allowing the bacteria to clear or for a T cell immune response to the natural infection, collecting immune splenocytes from the mammal, providing at least one antigen from a Chlamydia-specific bacteria, and expanding and depleting the CD4+ T cell population or purifying the CD8 T cell population to isolate IL-13 expressing CD8+ T cell clones.

Abstract: A method for selecting combinations of drugs for treatment of diseases that arise from deranged signaling pathways is disclosed. The method involves measuring the activity states for signaling proteins in a diseased cell and determining whether the activity states are different from the activity states observed for a reference cell such as a normal cell. Based on the observed differences, combinations of two or more drugs are selected to reduce these differences. Treatment of a subject with the combinations restores the activity states of the signaling proteins of the deranged disease-associated signaling pathways toward the activity states observed in the reference cell. Since the diseased cell and the reference cell can both be obtained from the same subject, combinations of drugs that specifically target patient-specific signaling derangements is possible.

Abstract: A mechanism is provided for utilizing a nanodevice to distinguish molecules with different structure. The molecules translocate through or across a nanochannel filled with a electrolyte solution. An electrical signal through the nanochannel is measured for every translocation event. Inner surfaces of the nanochannel include a functional layer, which is a coating to functionalize the nanochannel, in which the functional layer is configured to interact with predetermined ones of the molecules during translocation events. It is determined that a combination of at least two different molecules is formed based on predetermined ones of the molecules interacting with the functional layer to change the electrical signal and/or change a translocation time for the translocation event.

Abstract: The invention provides a high-throughput method for quantitating plant seed proteins, e.g. seed allergens. Such method involves obtaining a protein sample from the seed; analyzing the sample using mass spectrometry with a set of pre-designed internal standard peptides that are specific to the plant allergens; and monitoring frequencies and intensities of resulting spectra to obtain relative and absolute allergen contents in the seed. The invention also provides a system for high-throughput profiling of plant seed allergens. Such system comprises a set of pre-designed internal standard peptides that are specific to the plant seed allergens and one or more mass spectrometers.

Abstract: Biomarkers for pre-Diabetes, Diabetes and/or a Diabetes related conditions, and methods of their use, including the biomarkers in Tables 1 and 2 such as peroxiredoxin-2, complement C1q subcomponent subunit B, sulfhydryl oxidase 1 and apolipoprotein A-IV.

Abstract: A system for detecting an array of samples having detectable samples and at least one reference sample is provided. The system comprises an electromagnetic radiation source, a sensing surface comprising a plurality of sample fields, wherein the plurality of sample fields comprise at least one reference field, a phase difference generator configured to introduce differences in pathlengths of one or more samples in the array of samples, and an imaging spectrometer configured to image one or more samples in the array of samples.

Abstract: A method and a device for analyzing a liquid is provided, in which the liquid is distributed to a plurality of containers, and which enables the rapid and inexpensive performing of a multitude of analyses in liquids, in particular DNA analyses, in micro-arrays. The liquid is supplied to a transparent analytical plate which includes a matrix with a plurality of at least unilaterally closed receptacle chambers arranged adjacent to each other. Axially-displaceable plungers are moved towards walls of the receptacle chambers and the analytical plates are transported towards the plungers using a transport apparatus. The liquid can be distributed into the receptacle chambers using mobile elements of the analytical plate, and the elements may be moved by the plungers. At least one axially displaceable plunger may be heated to a preset temperature value and impart this temperature to the accommodating chamber.

Abstract: The present invention relates to methods and products associated with in vivo enzyme profiling. In particular, the invention relates to methods of in vivo processing of exogenous molecules followed by detection of signature molecules as representative of the presence of active enzymes associated with diseases or conditions. The invention also relates to products, kits, and databases for use in the methods of the invention.

Abstract: Disclosed is a prediction method of glomerular filtration rate (GFR) from urine samples after kidney transplantation to provide an information needed for predict renal function after the transplantation, more particularly to a prediction method of glomerular filtration rate (GFR) from urine samples after kidney transplantation, which comprises detecting metabolic profiles of five biomarkers, 5a-androst-3-en-17-one (AS), glycocholic acid (GC), sphingosine (SG), tryptophan (TR) and histidine (HT), from urine samples of patients. Glomerular filtration rate (GFR) after kidney transplantation can be predicted more rapidly and precisely to provide an information needed for predict renal function after the transplantation by using five metabolites as biomarkers. The method provides more specific, sensitive, and reliable biomarkers that monitor clinical outcomes and adverse renal events after kidney transplantation, such as rejection, drug toxicity, delayed graft function, and infection.

Abstract: The present Invention provides a method for diagnosing and/or prognosing Parkinson's disease dementia (PDD) comprising the step of detecting O-glycosylation. in a protein comprising a Ser/Thr motive, in particular Serpin A1, and/or the level of sialic acid on a protein comprising a Ser/Thr motive, in particular Serpin A1. Further, the present invention relates to a molecule for detecting O-linked glycomoieties in a protein comprising a Ser/Thr motive, in particular Serpin A1, and/or glycosylated i so forms of a Ser/Thr motive comprising protein, in particular Serpin A1, for use in the diagnosis and/or prognosis of Parkinson's disease dementia (PDD), Furthermore, the present invention relates to means for diagnosing and/or prognosing Parkinson's disease dementia (PDD) and a kit for diagnosing and/or prognosing Parkinson's disease dementia (PDD).

Abstract: The present invention relates generally to methods for identifying drug side effects by detecting perturbations in organ-specific molecular blood fingerprints. The invention further relates to methods for identifying drug-specific organ-specific molecular blood fingerprints. As such, the present invention provides compositions comprising organ-specific proteins, detection reagents for detecting such proteins, and panels and arrays for determining organ-specific molecular blood fingerprints.

Abstract: A method of analyzing molecules using a nanopore array including a plurality of cells included on a chip is disclosed. Nanopores are caused to be formed in at least a portion of the plurality of the cells. A first physical measurement of the nanopores is evaluated. It is determined whether to cause the molecules to interact with the nanopores. At least a portion of the nanopores is caused to interact with the molecules. A second physical measurement of the nanopores that indicates a property of the molecules is evaluated. It is determined whether to cause the nanopores to be reformed so that the cells may be reused to interact with additional molecules.

Abstract: Panels, kits, and methods for diagnosing or predicting the likelihood of occurrence of preterm birth (PTB) in a subject are disclosed. An exemplary panel includes at least one of a first marker from a first group of markers and a second marker from a second group of markers. A significant decrease in the first marker and a significant increase in the second marker measured in a sample taken from a subject during the second trimester of pregnancy are diagnostic or predictive of an increased risk of preterm birth for the subject.

Abstract: Specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-4 Protein (HER4) protein are provided that are particularly advantageous for quantifying the HER4 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.

Abstract: Compositions and methods which indicate an increased risk for pancreatic carcinoma in a test subject are disclosed.

Abstract: The present invention relates to methods for improving the folding stability of antibodies, to antibodies with improved folding stability, nucleic acid and vectors encoding such antibodies, and to uses of such antibodies, nucleic acid and vectors.

Abstract: The invention relates to a spatially encoded polymer matrix in the form of a bead or a granule for combinatorial solid phase synthesis, assaying, functional proteomics and diagnostic use. Compositions of such beads or granules are also provided. Each beaded polymer matrix of the composition comprises a plurality of spatially immobilized particles. The spatial immobilization of the particles confers on each beaded polymer matrix a “fingerprint” which enables identification of unique beads in a population of beads. The unique identification of individual beads makes it possible to perform combinatorial chemistry strategies while logging individual chemical transformation. Also provided are methods for detection of relative positions in space of particles, methods for generating matrices, methods for distance matrix determination, methods for identifying individual matrices and devices for recording and storing images of matrices.

Abstract: Specific peptides, and derived ionization characteristics of the peptides, from the Fatty acid synthase (FASN) protein are provided that are particularly advantageous for quantifying the FASN protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.

Abstract: A group of polypeptides that are modulated in a psoriatic sample as compared to a normal sample is provided. These polypeptides can be used as biomarkers for diagnosis and monitoring treatment of psoriasis.

Abstract: Nanochannel arrays that enable high-throughput macromolecular analysis are disclosed. Also disclosed are methods of preparing nanochannel arrays and nanofluidic chips. Methods of analyzing macromolecules, such as entire strands of genomic DNA, are also disclosed, as well as systems for carrying out these methods.

Abstract: The invention relates to a method of differentially diagnosing schizophrenia, bipolar disorder and major depressive disorder.

Abstract: The invention relates to a method of differential diagnosis of schizophrenia or other psychotic disorder from a further psychiatric disorder.

Abstract: An apparatus for glycan analysis is disclosed. The apparatus includes a plurality of loading wells adapted to receive a plurality of samples; a plurality of capillaries arranged in correspondence with the loading wells, each of the capillaries including a first portion including a stacking gel and a second portion including a resolving gel; and a plurality of eluting wells arranged in correspondence with the capillaries and adapted to receive a portion of the samples having traversed the capillaries.

Abstract: System, including methods and apparatus, for detection of spaced droplets.

Abstract: Compositions, methods and related uses are provided relating to cleaving modified DNA. For example, a set of DNA fragments obtainable by enzymatic cleavage of a large DNA is described where at least 50% are similarly sized and have a centrally positioned modified nucleotide. In addition, an enzyme preparation is provided that includes one or more enzymes that recognize a modified nucleotide in a DNA and cleave the DNA at a site that is at a non-random distance from the modified nucleotide. The one or more enzymes are further characterized by an N-terminal conserved domain with greater than 90% amino acid sequence homology to WXD(X)10YXGD. The related uses include creating a methylome, methods of purifying DNA fragments containing a modified nucleotide and diagnostic applications.

Abstract: A method for assessing the state of Alzheimer's disease in patients is disclosed. A method for monitoring the progression of Alzheimer's disease in patients is also disclosed. The method applies detection of specific peptide markers, e.g., using mass spectrometric analysis.

Abstract: The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; (b) expressing the genetic elements to produce their respective gene products within the microcapsules; (c) sorting the genetic elements which produce the gene product having the desired activity using a change in the optical properties of the genetic elements. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention.

Abstract: Inhibitors of the tmRNA pathway have antibacterial activity with broad species specificity, including B. anthracis and other pathogens of military and civilian interest. Identified cyclic or linear peptides are further selected by in vivo selection methods, kill bacterial pathogens when added exogenously, and/or eliminate plasmids carrying antibiotic resistance or virulence genes. The molecular target of each cyclic peptide is in the tmRNA pathway and the tmRNA pathway is inhibited in vitro and in vivo by the addition of the peptides.

Abstract: The present invention, provides a flow cytometry apparatus for the detection of particles from a plurality of samples comprising: means for moving a plurality of samples comprising particles from a plurality of respective source wells into a fluid flow stream; means for introducing a separation gas between each of the plurality of samples in the fluid flow stream; and means for selectively analyzing each of the plurality of samples for the particles. The present invention also provides a flow cytometry method employing such an apparatus.

Abstract: A marker for determining sensitivity of a patient to an anti-cancer agent, and novel cancer therapeutic means employing the marker, wherein the marker for determining sensitivity to an anti-cancer agent is a protein or a fragment, where in the protein or a fragment thereof exhibits a peak at m/z of 5,300 to 5,400, a peak at m/z of 6,130 to 6,230, a peak at m/z of 7,000 to 7,080 a peak at m/z of 7,840 to 7,920, a peak at m/z of 8,920 to 9,000, a peak at m/z of 12,440 to 12,560, a peak at m/z of 17,100 to 17,270, a peak at m/z of 18,290 to 18,470, a peak at m/z of 24,660 to 24,750, a peak at m/z of 35,980 to 36,290, a peak at m/z of 8,650 to 8,750, a peak at m/z of 9,100 to 9,200, a peak at m/z of 11,760 to 11,890, the peaks being determined by means of a mass spectrometer.

Abstract: Methods and systems for discovering drug candidates are disclosed. Methods and systems can include generating libraries of potential drug candidates (e.g., libraries of peptides) that can be screened to identify sub-libraries of potential drug candidates (e.g., sub-libraries of peptides) having selected pharmacological properties. Methods of making and using peptide libraries are also provided. D-amino acid chlorotoxins and D-amino acid chlorotoxin variants are also provided.

Abstract: The present invention concerns means and methods for predicting the risk of a subject to suffer from liver damage. In particular, it pertains to a method for predicting the risk of a subject to suffer from liver damage caused by acetaminophen comprising determining the amount of putrescine in a blood, serum or plasma sample that has been obtained from the subject after administration of acetaminophen, and comparing the determined amount to a reference, whereby the risk of the subject to suffer from liver damage caused by acetaminophen is predicted. Also provided are devices for carrying out the aforementioned methods.

Abstract: A method for identifying differentially expressed genes including the following steps: measure gene expression levels of test samples and control samples; estimate variances of noise in the test samples and in the control samples; based on the measured expression levels and the estimated variances of noise, derive a probability density function (PDF) for predicting the true value of each expression level measurement; normalize the PDFs; based on the normalized PDFs of the gene under test, derive a test-group PDF for predicting the gene's mean expression level in the test samples and derive a control-group PDF for predicting the gene's mean expression level in the control samples; based on the test-group PDF and the control-group PDF of the gene under test, derive a final PDF for predicting the gene's fold-change; use the final PDF to test whether the gene is differentially expressed.

Abstract: System, including methods and apparatus, for performing a multiplexed digital assay.

Abstract: The present disclosure relates to a panel of metabolite species that is useful for forecasting the outcome of preoperative chemotherapy for the treatment of breast cancer, including methods for identifying and using such metabolite species that can be measured in biological samples taken before treatment. In preferred embodiments, a method of forecasting a treatment outcome before subjecting a breast cancer patient to preoperative chemotherapy is disclosed that includes measuring the concentration of at least one metabolite species in a sample of a biofluid taken from the breast cancer patient before preoperative chemotherapy treatment.

Abstract: Methods of inhibiting S. aureus propagation, and screening for compounds that inhibit S. aureus propagation, are described. A method of inhibiting S. aureus propagation comprises either inhibiting or stabilizing ribosomal binding of a specific S. aureus tRNA in the S. aureus by an amount sufficient to inhibit S. aureus protein expression. A method of screening for compounds useful for inhibiting S. aureus propagation comprises contacting a specific S. aureus tRNA to a ribosome that binds that tRNA in the presence of the test compound and an mRNA that codes for methionine and arginine (i.e., includes the sequence AUGAGA), and then determining whether the compound inhibits the binding of that tRNA.

Abstract: The present invention relates to a method of qualifying prostate cancer status in a subject comprising: (a) measuring at least one of the disclosed biomarkers in a sample from the subject and (b) correlating the measurement with prostate cancer status. The invention further relates to kits for qualifying prostate cancer status in a subject.

Abstract: A method and a device for detecting the presence of a predetermined substance, in which a quantum dot is produced on a substrate. The quantum dot emits a radiation at a predetermined wavelength, and is covered with a surface layer to which the predetermined substance attaches. A deviation of the value of a parameter related to the radiation is produced when the predetermined substance attaches to the surface layer. This deviation can be detected to thereby sense the presence of the predetermined substance.

Abstract: Methods and kits for characterizing the risk of developing cardiovascular disease are described. The methods include determining the levels of a plurality of risk predictors selected from the group consisting of B-type natriuretic peptide (BNP), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) predictors in a biological sample from a subject. The levels of the plurality of risk predictors are then compared to corresponding control values to obtain a risk predictor differential for each risk predictor. The plurality of risk predictor differentials are then added to provide a cardiac biomarker score, and the cardiac biomarker score is compared to a reference biomarker score. A positive difference between the cardiac biomarker score and the reference biomarker score indicates the subject has an increased risk of developing cardiovascular disease compared to the risk of a reference population. The methods can be used for risk stratification.

Abstract: The present invention relates generally to methods for identifying and using organ-specific proteins and transcripts. The present invention further provides compositions comprising organ-specific proteins and transcripts encoding the same, detection reagents for detecting such proteins and transcripts, and diagnostic panels, kits and arrays for measuring organ-specific proteins/transcripts in blood, biological tissue or other biological fluid.

Abstract: Analyte arrays such as solutes in a slab-shaped gel following electrophoresis, and particularly arrays that are in excess of 3 cm square and up to 25 cm square and higher, are imaged at distances of 5 cm or less by either forming sub-images of the entire array and stitching together the sub-images by computer-based stitching technology, or by using an array of thin-film photoresponsive elements that is coextensive with the analyte array to form a single image of the array.

Abstract: A method and apparatus for simultaneously determining multiple different biological molecule types in a sample include labeling each different biological molecule type in a biological sample with a unique combination of a plurality of labels. Each different biological molecule type is selected from a population of M different biological molecules types. The plurality of labels is selected from a population of L different labels; and, M is greater than L. Measurements are obtained of relative abundances of the L different labels in the sample. Relative abundance of up to M different biological molecule types in the sample are determined based on the measurements and a method of compressed sensing.