Abstract: An anti-immunoglobulin specific antibody (or fragment thereof), characterised that the antibody or fragment thereof comprises one or more non-disulphide cross-links between at least one heavy chain or fragment thereof and at least one light chain or fragment thereof of the antibody or fragment thereof. A method purifying an anti-immunoglobulin specific antibody (or fragment thereof), characterised that the antibody or fragment thereof comprises one or more non-disulphide cross-links between at least one heavy chain or fragment thereof and at least one light chain or fragment thereof of the antibody or fragment thereof.

Abstract: 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.

Abstract: An anti-immunoglobulin specific antibody (or fragment thereof), characterised that the antibody or fragment thereof comprises one or more non-disulphide cross-links between at least one heavy chain or fragment thereof and at least one light chain or fragment thereof of the antibody or fragment thereof. A method purifying an anti-immunoglobulin specific antibody (or fragment thereof), characterised that the antibody or fragment thereof comprises one or more non-disulphide cross-links between at least one heavy chain or fragment thereof and at least one light chain or fragment thereof of the antibody or fragment thereof.

Abstract: The application describes a method of quantifying a multimeric analyte in a sample comprising: (i) treating the multimeric analyte with a separating agent selected to convert at least a portion of the multimeric analyte into monomeric analyte; (ii) binding the analyte to an analyte-specific binding agent; (iii) comparing the amount of binding of the analyte to the analyte-specific binding agent to a calibration curve, wherein the calibration curve is obtained (i) by binding the analyte-specific binding agent to one or more predetermined amounts of separating agent treated analyte, prior to contacting with analyte-specific binding agent or (ii) by binding the analyte-specific binding agent to a predetermined amount of substantially monomeric analyte; and (iv) determining an amount of the multimeric analyte in the sample.

Abstract: A method for analyzing protein(s) in a sample using an immunoassay kit includes creating protein-reducing and/or protein-denaturing conditions by contacting the sample with a reducing and/or denaturing agent provided in the immunoassay kit, to provide a partially or fully denatured protein population. One or both of a presence and an amount of one or more protein-associated analytes are determined under the created protein-reducing and/or protein-denaturing conditions by contacting the partially or fully denatured protein population with one or more specific antibodies or binding fragments thereof provided in the immunoassay kit. The one or more specific antibodies or binding fragments thereof include one or more chemically-introduced non-disulfide cross-links between at least one heavy chain or binding fragment thereof and at least one light chain or binding fragment thereof.

Abstract: This invention provides a method of identifying or characterising an immune response in a subject comprising: (a) contacting a sample containing immunoglobulins from the subject with at least one antigen immobilised on a support; (b) washing unbound, non-antigen specific immunoglobulins from the support to leave antigen-specific immunoglobulins bound to the antigen on the support; (c) optionally eluting the antigen-specific immunoglobulins from the antigen on the support; and (d) subjecting the antigen-specific immunoglobulins to mass spectrometry to identify two or more different antigen specific immunoglobulin classes, subclasses and/or light chain types.

Abstract: The Invention provides a method of immunopurifying and characterising an analyte from a sample comprising: (i) providing a predetermined amount of a control substance bound to a substrate via a linkage cleavable by acidic pH and/or reducing agents and optionally additional analyte specific antibodies or fragments thereof bound to a substrate, wherein the control substance is specific for the analyte or is not specific for the analyte; (ii) allowing analyte when present in the sample to bind to the control substance or said optional additional analyte-specific antibodies or fragments, wherein the control substance bound to the substrate (i) may be provided after contacting the analyte with the optional additional analyte-specific antibodies (ii); (iii) washing unbound material away from the substrate; (iv) acid eluting the analyte bound thereto, from at least one substrate; (v) performing mass spectrometry to identify two or more peaks, at least one peak of which is associated with the presence of the analyte

Abstract: The application provides a method of identifying or monitoring a plasma cell associated disease, comprising purifying immunoglobulin free light chains (FLCs) from a sample from a subject with anti-FLC specific antibodies or fragments thereof and subjecting the purified sample to a mass spectrometry technique to identify the presence of one or more peaks corresponding to one or more monoclonal FLCs in the sample.

Abstract: Method of Detecting or Monitoring Minimal Residual Disease The application describes a method of identifying minimal residual disease (MRD) in a monoclonal gammopathy patient, comprising detecting the presence or absence of a monoclonal free light chain (FLC) in a sample from the patient by mass spectrometry (MS).

Abstract: 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.

Abstract: 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.

Abstract: This document relates to materials and methods for identifying and/or quantifying immunoglobulins from a biological sample without pre-purification of the immunoglobulins prior to ionization and detection using mass spectrometry. For example, a monoclonal light chain from a monoclonal immunoglobulin may be observed using matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry after diluting a sample containing the monoclonal immunoglobulin with an aqueous buffer containing acid and a reducing agent then mixing the sample with alpha-cyano-4-hydroxycinnamic acid matrix (CHCA). In another example, an intact monoclonal immunoglobulin may be observed in a sample using MALDI-TOF mass spectrometry after diluting the sample containing the monoclonal immunoglobulin with water then mixing the sample with CHCA matrix.

Abstract: The application provides a method of identifying or monitoring a plasma cell associated disease, comprising purifying immunoglobulin free light chains (FLCs) from a sample from a subject with anti-FLC specific antibodies or fragments thereof and subjecting the purified sample to a mass spectrometry technique to identify the presence of one or more peaks corresponding to one or more monoclonal FLCs in the sample.

Abstract: An anti-immunoglobulin specific antibody (or fragment thereof), characterised that the antibody or fragment thereof comprises one or more non-disulphide cross-links between at least one heavy chain or fragment thereof and at least one light chain or fragment thereof of the antibody or fragment thereof. A method purifying an anti-immunoglobulin specific antibody (or fragment thereof), characterised that the antibody or fragment thereof comprises one or more non-disulphide cross-links between at least one heavy chain or fragment thereof and at least one light chain or fragment thereof of the antibody or fragment thereof.

Abstract: The application describes a method of quantifying a multimeric analyte in a sample comprising: (i) treating the multimeric analyte with a separating agent selected to convert at least a portion of the multimeric analyte into monomeric analyte; (ii) binding the analyte to an analyte-specific binding agent; (iii) comparing the amount of binding of the analyte to the analyte-specific binding agent to a calibration curve, wherein the calibration curve is obtained (i) by binding the analyte-specific binding agent to one or more predetermined amounts of separating agent treated analyte, prior to contacting with analyte-specific binding agent or (ii) by binding the analyte-specific binding agent to a predetermined amount of substantially monomeric analyte; and (iv) determining an amount of the multimeric analyte in the sample.

Abstract: The invention provides an immunoassay kit providing an immunoassay kit comprising one or more analyte specific antibodies or fragments thereof, characterised that the antibody or fragment thereof comprises one or more non-disulphide cross-links between at least one heavy chain or fragment thereof and at least one light chain or fragment thereof of the analyte- specific antibodies or fragments thereof.

Abstract: The application discloses a method of determining the severity of symptoms in a patient comprising (i) producing a triage score, such as an early warning score (EWS) modified early warning score (MEWS), paediatric early warning score (PEWS), NHS early warning score (NEWS), simple clinical score (SCS), rapid emergency score (REMS) or mortality in emergency department sepsis score for the patient, (ii) measuring an amount of free light chains (FLC), preferably combined free light chains (cFLC), in a sample from the patient, and (iii) using the triage score and the amount of FLC measured to assess the severity of symptoms in the patient. This also allows patients to be triaged to provide better treatment of them.

Abstract: The invention provides a method for characterising a plasma cell associated disease in a patient comprising: (i) providing at least one sample from the patient; (ii) determining in the sample(s) two or more of; (a) the ?:? free light chain (FLC) ratio; (b) the ratio of ? light chains bound to a class of heavy chain:? light chain bound to the same class of heavy chain (HLC?:HLC ? ratio); (c) the total amount of FLC in the samples and (d) the total amount of ? light chains bound to the heavy chain class plus ? light chains bound to the same heavy chain class (total HLC); (iii) comparing each ratio or amount from (a) (b), (c) and/or (d) to predetermined values and assigning a score to each amount or ratio; and (iv) using the scores to characterise the plasma cell associated disease. Apparatus configured to carry out the method of the invention are also provided.

Abstract: The invention provides a method of estimating free light chain production (FLC) in a subject comprising (i) determining an amount of FLC in a sample from the subject; and (ii) correcting the amount of FLC in the sample for FLC cleared from the source of the sample by glomerular filtration and by reticuloendothelial (RE) clearance.

Abstract: A multiplexer (1) having M high frequency input channels (2) and N high frequency output channels (3). The multiplexer (1) comprises N routing control inputs (4); a detector (10) arranged to receive control signals on the or each control input (4), the control signals being indicative of a required connection between the multiplexer input channels (2) and output channels (3); and a decoder (11) arranged to decode the received control signals and generate switching control signals (8) to selectively connect the input channels (2) to the output channels (3) in response to the decoded control signals. The multiplexer (1) is integrated onto a single chip. A multiplexer apparatus comprising a pair of such multiplexers (1) mounted on a printed circuit board is also described. The multiplexers (1) are positioned on opposite sides of the printed circuit board, with one multiplexer (1) rotated 180° about a diagonal axis (20) relative to the other multiplexer (1).