SYSTEM AND SENSOR ARRAY
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.
1 - 29 . (canceled)
30 . A method for assaying a biological sample, comprising:
(a) incubating the biological sample with a plurality of sensor elements comprising different physiochemical properties to adsorb a plurality of biomolecules on surfaces of the plurality of sensor elements, wherein at least a first subset of the sensor elements comprises a first physiochemical property and at least a second subset of the sensor elements comprises a second physiochemical property,
(b) separating at least a portion of the plurality of biomolecules from the sensor elements to provide a plurality of separated biomolecules; and
(c) performing mass spectrometry on the plurality of separated biomolecules to detect the at least a portion of the plurality of separated biomolecules,
wherein the at least a portion of the plurality of separated biomolecules are present in the biological sample at concentrations across a dynamic range exceeding a detection limit of a mass spectrometer used for performing liquid chromatography-tandem mass spectrometry on at least a portion of the biological sample.
31 . The method of claim 30 , wherein the incubating is performed for at least 10 minutes.
32 . The method of claim 30 , wherein the sensor elements are disposed on an array.
33 . The method of claim 30 , wherein the plurality of biomolecules forms a layer on the sensor elements that is at least 15 nm thick.
34 . The method of claim 30 , wherein the plurality of biomolecules comprises at least 500 different biomolecules.
35 . The method of claim 30 , wherein a first sensor element of the sensor elements comprises a positive zeta potential when the first sensor element is in contact with the biological sample, and wherein a second sensor element of the sensor elements comprises a negative zeta potential when the second sensor element is in contact with the biological sample.
36 . The method of claim 35 , wherein a surface of the first sensor element comprises a first functional group and wherein a surface of the second sensor element comprises a second functional group, wherein the first functional group is different from the second functional group.
37 . The method of claim 35 , wherein the first functional group is selected from the group consisting of aminopropyl, amine, boronic acid, carboxylic acid, methyl, N-succinimidyl ester, polyethylene glycol, streptavidin, methyl ether, triethoxylpropylaminosilane, thiol, citrate, lipoic acid, polyethylene imine, hydroxyl, and any combination thereof; or
wherein the second functional group is selected from the group consisting of aminopropyl, amine, boronic acid, carboxylic acid, methyl, N-succinimidyl ester, polyethylene glycol, streptavidin, methyl ether, triethoxylpropylaminosilane, thiol, citrate, lipoic acid, polyethylene imine, hydroxyl, and any combination thereof.
38 . The method of claim 36 , wherein the first functional group is amine and the second functional group is carboxylic acid.
39 . The method of claim 30 , wherein a surface of a first sensor element of the sensor elements is polymeric and a surface of a second sensor element of the sensor elements is non-polymeric.
40 . The method of claim 30 , wherein the sensor elements are nanoscale sensor elements.
41 . The method of claim 30 , wherein the sensor elements are particles.
42 . A method for assaying a biological sample, comprising:
(a) contacting the biological sample with a plurality of sensor elements to generate a plurality of protein coronas on the plurality of sensor elements,
wherein the plurality of sensor elements comprise a first sensor element and a second sensor element,
wherein the first sensor element has a different surface functional group, a different zeta potential, or a different hydrophobicity compared to the second sensor element,
wherein the protein corona formed on the first sensor element has a different composition compared to the protein corona formed on the second sensor element;
(b) separating at least a subset of the protein coronas from the plurality of sensor elements, thereby producing a subset of proteins,
(c) performing mass spectrometry on the subset of proteins of (b) to generate a plurality of mass spectra of at least a portion of the subset of proteins; and
(d) generating a plurality of protein identifications based on the plurality of mass spectra of the at least a portion of the subset of proteins.
43 . The method of claim 42 , wherein a protein identification of the plurality of protein identifications is for a protein present in the biological sample at a concentration of less than 100 ng/ml.
44 . The method of claim 42 , wherein a protein identification of the plurality of protein identifications is for a protein present in the biological sample at a concentration of less than 10 ng/ml.
45 . The method of claim 42 , further comprising assaying a plurality of biological samples comprising (i) a first subset of biological samples associated with a disease and (ii) a second subset of biological samples for control.
46 . The method of claim 42 , wherein the different physiochemical properties comprise different surface functional groups, different zeta potentials, and different hydrophobicities.
47 . A method for assaying a biological sample, comprising:
(a) contacting the biological sample with a plurality of sensor elements to generate a plurality of protein coronas around the plurality of sensor elements,
wherein compositions of the plurality of protein coronas differ from one another based at least in part on a physiochemical property of a sensor element of the plurality of sensor elements;
(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) proteolytically fragmenting the subset of proteins to generate a plurality of peptides;
(d) performing liquid chromatography-tandem mass spectrometry using the plurality of peptides to generate a plurality of mass spectra of at least a subset of the plurality of peptides;
(e) generating a plurality of protein identifications based on the plurality of mass spectra of the at least a subset of the plurality of peptides,
wherein protein identifications of the plurality of protein identifications are for proteins that are present in the biological sample at concentrations across a dynamic range exceeding a detection limit of a mass spectrometer used for performing liquid chromatography-tandem mass spectrometry on at least a portion of the biological sample.
48 . The method of claim 47 , wherein the biological sample is selected from: blood, plasma, serum, and combinations thereof.
49 . The method of claim 48 , wherein at least one surface element of the plurality of surface elements enriches for a protein other than albumin such that a ratio of an amount of albumin to an amount of a protein X that binds to the at least one surface element is less than a ratio of an amount of albumin to an amount of the protein X in the biological sample.