Systems and methods for sample preparation, data generation, and protein corona analysis
Inventors
Manning, William • Kim, Young • Kwan-Leong, Brandon • Liou, Hope • Zhao, Xiaoyan • Hornburg, Daniel • Goldberg, Martin
Assignees
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Publication Number
US-12050222-B2
Publication Date
2024-07-30
Expiration Date
Abstract
Systems and methods for automated sample preparation and processing of protein corona are described herein, as well as its application in the discovery of advanced diagnostic tools as well as therapeutic agents.
Core Innovation
The invention describes an automated system for preparing a biological sample for mass spectrometry analysis using a plurality of magnetic particles comprising at least one physicochemical property. The system uses a sensing unit having a magnetic sensor array with at least two partitions, where the partitions comprise the plurality of magnetic particles and where the magnetic particles are configured to bind a population of proteins comprising at least 300 protein groups within the biological sample. The magnetic sensor array is transferred to a support that immobilizes the plurality of magnetic particles while the system performs subsequent preparation steps.
The automated system further includes a fluid transfer unit comprising a multichannel fluid transfer instrument, a sample storage unit, a reagent storage unit, and a waste unit, together with a magnetized support comprising a magnetic source. The control unit with one or more processors performs incubating the biological sample with the magnetic sensor array under conditions sufficient to bind the population of proteins comprising at least 300 protein groups, applying the magnetized support to separate unbound sample from the magnetic particles, and separating unbound components within the partition from the population of proteins and the plurality of magnetic particles.
The preparation for mass spectrometry comprises preparing the population of proteins by incubating a digestion solution with the population of proteins and the plurality of magnetic particles. In addition, the magnetic particles are characterized by a polydispersity index and physicochemical properties configured for binding, and the system is configured to immobilize the plurality of magnetic particles when the magnetic sensor array is transferred to the support.
Claims Coverage
The document includes three independent claims. Each independent claim centers on an automated system that binds a target protein population using a partitioned magnetic sensor array and magnetically separates unbound components, followed by digestion solution incubation to prepare proteins for mass spectrometry.
Automated magnetic particle system with partitioned magnetic sensor array for binding at least 300 protein groups
A system for preparing a biological sample for mass spectrometry analysis using a plurality of magnetic particles comprising at least one physicochemical property, with a sensing unit including a magnetic sensor array having at least two partitions that comprise the plurality of magnetic particles, wherein the magnetic particles are configured to bind a population of proteins comprising at least 300 protein groups, and where the support is configured to immobilize the plurality of magnetic particles when the magnetic sensor array is transferred to the support.
Automated workflow with magnetic separation and digestion solution incubation
A control unit programmed to perform incubating the biological sample with the plurality of magnetic particles of the magnetic sensor array under conditions sufficient to bind the population of proteins comprising at least 300 protein groups, applying the magnetized support to the magnetic sensor array to separate unbound sample from the plurality of magnetic particles, separating unbound components within the partition from the population of proteins and the plurality of magnetic particles, and preparing the population of proteins for mass spectrometry by incubating a digestion solution with the population of proteins and the plurality of magnetic particles.
Magnetic particles with specified coating and polydispersity index
The plurality of magnetic particles comprises a poly(N-(3-(dimethylamino)propyl) methacrylamide) coating in one claim family, and polydispersity index ranges are recited as dependent refinements, including a polydispersity index of at least 0.5 and a polydispersity index of 0.01 to 0.1.
The core claim coverage combines an automated system architecture with a partitioned magnetic sensor array, magnetized support, and a workflow that binds at least 300 protein groups, separates unbound components, and prepares proteins for mass spectrometry by incubating a digestion solution with the proteins and magnetic particles. Dependent refinements further specify magnetic particle coating and polydispersity index.
Stated Advantages
Enables high-throughput detection, diagnosis, and prognosis of disease states using protein biomolecule fingerprinting.
Supports identification and enrichment of proteins across very large dynamic ranges.
Emphasizes detection across early, intermediate, and late cancer stages.
Documented Applications
High-throughput detection, diagnosis, and prognosis of disease states, with emphasis on early, intermediate, and late cancer stages.
Disease category coverage explicitly includes cancer and other disease categories such as cardiovascular, endocrine, inflammatory, neurological, and neurodegenerative diseases.
Example cancer detection concept including patient-specific fingerprints based on varying particle charge and combined cross-particle relationships.
Mass spectrometry analysis workflows using automated preparation of biological samples, including plasma and serum in the provided partial description.
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