Various embodiments of the present disclosure relate to a method for analyzing target compounds from a fluid or dried biological sample by using a microfluidic sample device including a hollow cartridge and an absorbent body unit.

The present invention provides a method for the determination of the monoisotopic mass of a macromolecule from a mass M.sub.mono spectrometry spectrum of said macromolecule based on the experimentally determined most abundant mass, with accuracy in the low parts-per-million (ppm) range. The method uses a simple, double-linear model for predicting the monoisotopic mass based on the experimentally determined most abundant mass, comprising the steps of (a) deriving the most abundant mass MMostAb from the spectrum; and (b) calculating the monoisotopic mass M.sub.Mono from the most abundant mass M.sub.MostAb, using M.sub.Mono=a+βM.sub.MOSTAB+ε; wherein β is a scalar slope obtainable by fitting the slope of monoisotopic mass versus most abundant mass for a plurality of macromolecules from a macromolecule database; and ε is a scalar residue of the form ε=ε.sub.int+s.sub.frac, ε.sub.int being an integer, and ε.sub.frac being a sawtooth function of M.sub.MostAb.

The use of mass defect signatures to impart milliDalton mass differences between isotopically labeled peptides at the MS.sup.1-level allows multiplex quantification without the increased mass spectral complexity that occurs with mass difference approaches. Provided herein is a mass defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), that is compact and easy to synthesize at high purity in few steps using commercially available starting materials. The multiplex DiPyrO tags are amine-reactive and can impart a mass difference onto labeled peptides and through calculated substitution of heavy isotopes. DiPyrO offers up to 10-plex quantification on current Orbitrap or FT-ICR platforms without increasing mass spectral complexity. The synthesis of the DiPyrO tag is provided along with viability of the DiPyrO tag for labeling complex proteomics samples using yeast extract digests and its effect on labeled peptides during LC-MS.sup.2 analysis. Labeling and quantification of glycans and metabolites using the DiPyrO tag is also demonstrated. ##STR00001##

The invention relates to a method for diagnosing a subject suffering from cancer, or a pre-disposition thereto. The method comprises detecting, in a bodily sample from a test subject, the concentration of a signature compound resulting from the metabolism of at least one sugar, and/or at least one amino acid or a precursor thereof, and/or at least one polyol present in a composition previously administered to the subject. The sugar is present in the composition at a concentration of more than 20,000 mg/100 ml, the amino acid or a precursor thereof is present in the composition at a concentration of at least 500 mg/ml, and the polyol is present in the composition at a concentration of more than 25,000 mg/100 ml. The method further comprises comparing this concentration with a reference for the concentration of the signature compound in an individual who does not suffer from cancer. In particular, an increase or decrease in the concentration of the signature compound compared to the reference, suggests that the subject is suffering from cancer, or has a pre-disposition thereto, or provides a negative prognosis of the subject's condition.

Provided are methods and compositions for identifying candidate agents for treatment of obesity, liver disease, and/or diabetes. Such methods include, e.g., contacting a mammalian cell or cell population with a test agent, and measuring an expression level and/or activity level of ClpP in the mammalian cell or in cells of the cell population. Also provided are methods and compositions for treating an individual (e.g., one who is obese and/or has diabetes). Treatment methods include administering an inhibitor of ClpP to the individual (e.g., to prevent or reduce weight gain, to increase insulin sensitivity, and/or to increase glucose tolerance).

The present invention relates to the high resolution imaging of samples using imaging mass spectrometry (IMS) and to the imaging of biological samples by imaging mass cytometry (IMC™) in which labelling atoms are detected by IMS. LA-ICP-MS (a form of IMS in which the sample is ablated by a laser, the ablated material is then ionised in an inductively coupled plasma before the ions are detected by mass spectrometry) has been used for analysis of various substances, such as mineral analysis of geological samples, analysis of archaeological samples, and imaging of biological substances. However, traditional LA-ICP-MS systems and methods may not provide high resolution. Described herein are methods and systems for high resolution IMS and IMC.

An elution buffer for eluting one or more predetermined analytes from one or more analyte-specific antibodies or fragments thereof or for eluting one or more predetermined antibodies or fragments from a target antigen, wherein: the elution buffer has a pH of 1 to 5; and the elution buffer comprises a predetermined amount of an acid stable mass spectrometry ionisation control protein. The use of the elution buffer in the detection and quantifying of analytes, for example by mass spectrometry is also described.

Disclosed herein are protease-based biological circuits for use in the diagnosis and treatment of disease and disorders characterized by aberrant protease signaling. An exemplary method of treating disease in a subject includes administering to the subject a plurality of therapeutic agent loaded-liposomes, wherein each of the liposomes comprises a different density of peptides surrounding the core and a different dose of the therapeutic agent, wherein the peptides comprise a cleavage site for a protease of interest, and wherein cleavage of the peptides open the liposome and release the therapeutic agent from within the liposome.

An integrated sample processing system including an analyzer and a mass spectrometer is disclosed. The integrated sample processing system can perform multiple different types of detection, thereby providing improved flexibility and better accuracy in processing samples. The detection systems in the sample processing system may include an optical detection system and a mass spectrometer.

The invention provides a method of quantifying the amount of kappa or lambda immunoglobulin light chain in a sample from a subject comprising: i. providing a sample from a subject; ii. mixing the sample with a predetermined amount of lambda light chain calibrator or kappa light chain calibrator to form a mixture; iii. performing mass spectrometry on the mixture; and iv quantifying one or both of a) the amount of lambda light chain in the sample by comparing the relative amount of lambda light chain in the mixture as determined by the mass spectrometry to the relative amount of calibrator kappa light chain in the mixture as determined by mass spectrometry; and/or b) the amount of kappa light chain in the sample by comparing the relative amount of kappa light chain in the mixture as determined by mass spectrometry to the relative amount of calibrator lambda light chain in the mixture as determined by mass spectrometry, most typically MALDI-TOF spectrometry or liquid chromatography-mass spectrometry.