Reducing Intersample Analyte Variability in Complex Biological Matrices
AssigneeSomaLogic, Inc.
InventorsDaniel Drolet, David Astling, Ira von Carlowitz, Thomas Howard Hraha, Jan Hoh
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Abstract
Described herein are compositions and methods for reducing the variability of inter-sample analyte measurements from a biological matrix. In some embodiments, the present disclosure relates to methods for reducing the variability in the inter-sample levels of one or more proteins from a biological sample as measured by a proteomic assay.
Claims116
A method for preparing a plurality of biological samples for detecting a protein comprising:
- generating a plurality of test samples by performing a buffer exchange on the plurality of biological samples using a formulation comprising a buffering agent, one or more salts, a chelating agent and a nonionic surfactant, and
- generating a plurality of adjusted test samples by adjusting the total protein concentrations of a plurality of test samples, wherein the total protein concentration of each adjusted test sample is about the same;
- wherein the method does not comprise concentrating the total protein of the plurality of biological samples prior to performing the buffer exchange.
A method for preparing a biological sample for detecting a protein comprising:
- generating a test sample by performing a buffer exchange on the biological sample using a formulation comprising a buffering agent, one or more salts, a chelating agent and a nonionic surfactant;
- and
- generating an adjusted test sample by adjusting the total protein concentration of the test sample, wherein the total protein concentration in the adjusted test sample is from about 70 μg/mL to about 100 μg/mL.
A method for preparing a biological sample for detecting a protein comprising:
- generating a test sample by performing a buffer exchange on the biological sample using a formulation comprising a buffering agent, one or more salts, a chelating agent and a nonionic surfactant;
- determining the total protein concentration of the test sample;
- and
- generating an adjusted test sample by adjusting the total protein concentration of the test sample, wherein the total protein concentration in the adjusted test sample is from about 70 μg/mL to about 100 μg/mL.
A method of preparing a biological sample for detecting a protein comprising:
- generating a test sample by performing a buffer exchange on the biological sample using a formulation comprising a buffering agent, one or more salts, a chelating agent and a nonionic surfactant;
- determining the protein concentration of the test sample;
- and
- if the total protein concentration of the test sample is not in the range of from about 70 μg/mL to about 100 μg/mL, generating an adjusted test sample by adjusting the total protein concentration of the test sample, wherein the total protein concentration in the adjusted test sample is from about 70 μg/mL to about 100 μg/mL.
A test sample comprising a buffer-exchanged biological sample, wherein the test sample has a total protein concentration from about 70 μg/mL to about 100 μg/mL, and wherein the buffer-exchanged biological sample comprises a buffering agent, one or more salts, a chelating agent and a nonionic surfactant.
A method for detecting a target protein in a test sample comprising:
- a) contacting the test sample with at least one capture reagent, wherein the at least one capture reagent is capable of binding to the target protein to form a complex;
- b) incubating the test sample with the at least one capture reagent under conditions that allow for the complex to form;
- and
- c) determining the level of the target protein in the test sample by measuring the level of the at least one capture reagent, the complex, or the protein;
- wherein the level of the at least one capture reagent or the complex is a surrogate for the level of the target protein;
- wherein, the test sample is generated by performing a buffer exchange of a biological sample with a formulation comprising a buffering agent, a salt, a chelating agent and a nonionic surfactant;
- and
- wherein, the total protein concentration of the test sample is about 70 μg/mL to about less than 100 μg/mL.
A method for preparing a biological sample for detecting a protein comprising:
- generating a test sample by performing a buffer exchange on the biological sample using a formulation comprising a buffering agent, one or more salts, a chelating agent and a nonionic surfactant;
- and
- determining the total protein concentration of the biological sample or of the test sample;
- and
- adjusting the total protein concentration of the biological sample or of the test sample, wherein the method does not comprise concentrating the total protein of the biological sample prior to performing the buffer exchange,
- optionally wherein (i) the total protein concentration is adjusted before performing the buffer exchange or (ii) the total protein concentration is adjusted after performing the buffer exchange.
Dependencies are inferred from the claim text.