US2021072255A1PendingUtilityA1

System and method for protein corona sensor array for early detection of diseases

Assignee: BRIGHAM & WOMENS HOSPITAL INCPriority: Dec 16, 2016Filed: Nov 16, 2020Published: Mar 11, 2021
Est. expiryDec 16, 2036(~10.4 yrs left)· nominal 20-yr term from priority
G01N 33/57585G01N 33/6848G01N 33/5432G06F 2218/20G06N 5/01G06N 7/01G06F 2218/12G06F 18/24G06N 3/09G16B 40/20G01N 33/54326G01N 33/6842G06N 20/20G06N 3/04G06N 3/08G01N 2570/00G01N 33/553B82Y 30/00G16B 40/30G01N 2800/2821G01N 33/6845G01N 33/6803G01N 33/587G01N 33/586G01N 33/54346G16B 20/00C01P 2004/64B82Y 35/00C01G 49/02G06K 9/00563G06K 9/6267
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Claims

Abstract

The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

Claims

exact text as granted — not AI-modified
1 . A system, comprising:
 a communication interface that receives, over a communication network, proteomic data, wherein the proteomic data is from an array comprising physiochemically distinct types of particles exposed to a protein solution; and   a computer in communication with the communication interface, wherein the computer comprises a computer processor and a computer readable medium comprising machine-executable code that, upon execution by the computer processor, implements a method comprising:
 receiving, over the communication network, the proteomic data derived from the array comprising the physiochemically distinct types of particles, 
 combining the proteomic data from the array to generate a biomolecule fingerprint for the sample, and 
 assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. 
   
     
     
         2 . The system of  claim 1 , wherein the proteomic data comprise mass spectra. 
     
     
         3 . The system of  claim 1 , further comprising a mass spectrometer that generates the proteomic data from the array. 
     
     
         4 . The system of  claim 3 , wherein the mass spectrometer transmits the proteomic data over the communication network. 
     
     
         5 . The system of  claim 1 , wherein the physiochemically distinct types of particles of the array yield different mass spectral patterns. 
     
     
         6 . The system of  claim 1 , wherein the particles comprise metal particles. 
     
     
         7 . The system of  claim 6 , wherein the metal particles comprise metal nanoparticles. 
     
     
         8 . The system of  claim 7 , wherein the metal nanoparticles comprise iron oxide. 
     
     
         9 . The system of  claim 1 , wherein the particles comprise an oxide, a carbide, a nitride, lipid, or a liposome. 
     
     
         10 . The method of  claim 1 , wherein the biological state is a healthy biological state or a diseased biological state, and wherein assigning the label to the biomolecule fingerprint comprises applying an algorithm trained with training proteomic data derived from biomolecule coronas of physiochemically distinct types of particles incubated in (i) healthy biological samples or (ii) diseased biological samples. 
     
     
         11 . The system of  claim 10 , wherein the diseased biological state is a cancer, cardiovascular disease, endocrine disease, inflammatory disease, or neurological disease. 
     
     
         12 . The system of  claim 10 , wherein the diseased biological state is a cancer selected from the group consisting of lung cancer, pancreas cancer, myeloma, myeloid leukemia, meningioma, glioblastoma, breast cancer, esophageal squamous cell carcinoma, gastric adenocarcinoma, prostate, bladder, ovarian, thyroid, and neuroendocrine cancer. 
     
     
         13 . The system of  claim 12 , wherein the cancer is lung cancer. 
     
     
         14 . The system of  claim 12 , wherein the cancer is lung cancer and the particles comprise iron oxide particles. 
     
     
         15 . The system of  claim 1 , wherein the protein solution comprises proteins at a concentration of 100 ng/mL or less. 
     
     
         16 . The system of  claim 1 , wherein the physiochemically distinct types of particles comprise distinct electric charges. 
     
     
         17 . The system of  claim 1 , wherein the physiochemically distinct types of particles comprise metal particles with distinct electric charges. 
     
     
         18 . The system of  claim 1 , wherein the protein solution is a biological sample. 
     
     
         19 . The system of  claim 18 , wherein the biological sample is a plasma sample. 
     
     
         20 . The system of  claim 1 , wherein the biomolecule fingerprint is indicative of the diseased biological state with an accuracy or sensitivity of 75% or greater. 
     
     
         21 . The system of  claim 1 , wherein generating the biomolecule fingerprint comprises decomposing the proteomic data to yield a plurality of variables, wherein a variable from among the plurality of variables comprises a combination of protein abundances from at least two particles from among the physiochemically distinct groups of particles. 
     
     
         22 . The system of  claim 1 , wherein assigning the label to the biomolecule fingerprint comprises applying an algorithm to assign the label to the biomolecule fingerprint. 
     
     
         23 . The system of  claim 1 , wherein assigning the label to the biomolecule fingerprint comprises applying a trained algorithm derived using random forest classification or regression. 
     
     
         24 . The system of  claim 1 , further comprising an output device configured to output information regarding the label; or a server adapted to transmit the information regarding the label through a network. 
     
     
         25 . A method comprising using the label assigned by the system of  claim 10  in a treatment of the diseased biological state. 
     
     
         26 . A method for assaying a biological sample, comprising:
 (a) contacting the biological sample with a plurality of particles comprising different particle types to permit biomolecules of the biological sample to bind to the plurality of particles and form coronas around the plurality of particles, wherein the coronas corresponding to the different of particle types (i) differ based on particle type, and (ii) comprise overlapping and distinct proteins;   (b) separating at least a subset of the plurality of particles comprising the coronas from the biological sample by removing the subset of the plurality of particles thereby producing a subset of proteins from the biological sample;   (c) assaying the subset of proteins of (b) with an instrument to detect, in the subset, proteins in the biological sample at concentrations across a broad dynamic range, thereby assaying the biological sample.   
     
     
         27 . A method for partitioning of proteins from a biological sample, comprising:
 incubating the biological sample with a plurality of different sensor elements to form of protein coronas around the plurality of sensor elements,
 wherein the plurality of different sensor elements are configured to enrich low abundance proteins in the biological sample, 
 wherein affinity of proteins in the biological sample for a surface of a first sensor element in the plurality of sensor elements differs from a second sensor element in the plurality of sensor elements such that protein coronas differently form around sensor elements of the plurality of sensor elements having different surface properties, wherein the protein coronas comprise:
 (i) a high abundance protein in the biological sample, and 
 (ii) a low abundance protein present at a concentration of less than 100 ng/ml in the biological sample, and 
 
 wherein the high abundance protein and the low abundance protein are present in different relative quantities in the protein coronas corresponding to the sensor elements having different surface properties; and 
   collecting the protein coronas, thereby partitioning the proteins from the biological sample.   
     
     
         28 . A detection method, comprising:
 (a) contacting a biological sample obtained from a subject with physiochemically distinct groups of metal particles to form biomolecule coronas corresponding to the physiochemically distinct groups of metal particles;   (b) detecting, by mass spectrometry, proteins of the biomolecule coronas corresponding to the physiochemically distinct groups of metal particles; and   (c) identifying a biomolecule fingerprint associated with the biological sample based on the detected proteins.

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