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:
measuring protein coronas formed from contacting particles with a biological sample wherein a subset of proteins in the biological sample are detected with an instrument to measure the subset of the proteins across a dynamic range of more than 6 orders of magnitude in the biological sample by:
(a) contacting the particles with the biological sample that comprises the subset of the proteins to allow the protein coronas to form on surfaces of the particles;
(b) separating the particles comprising the protein coronas from the biological sample by isolating the particles from the biological sample, thereby separating the subset of the proteins from the biological sample;
(c) preparing the protein coronas for detecting the proteins; and
(d) detecting the proteins.
31 . The method of claim 30 , wherein the particles comprise silica.
32 . The method of claim 31 , wherein the particles comprise carboxylate or carboxylic acid surface modifications.
33 . The method of claim 32 , wherein the particles comprise iron oxide.
34 . The method of claim 33 , wherein the particles comprise microparticles.
35 . The method of claim 34 , wherein the particles comprise a negative surface charge.
36 . The method of claim 33 , wherein the contacting is performed to obtain the protein coronas on the particles in the same biological sample at about the same time.
37 . The method of claim 33 , wherein the contacting is performed at a temperature between 10° C. and 40° C. for 15 to 60 minutes.
38 . The method of claim 37 , wherein the preparing comprises reducing and alkylating the proteins.
39 . The method of claim 38 , wherein the preparing comprises digesting the proteins to produce digested peptides.
40 . The method of claim 39 , wherein the detecting the proteins comprises detecting the digested peptides.
41 . The method of claim 40 , wherein the biological sample comprises plasma or serum.
42 . The method of claim 41 , wherein the biological sample comprises plasma.
43 . The method of claim 42 , wherein the contacting concentrates a first protein that comprises less than 100 ng/mg in the biological sample.
44 . The method of claim 43 , wherein the contacting concentrates a second protein that comprises less than 10 ng/mg in the biological sample.
45 . The method of claim 44 , wherein the contacting concentrates a third protein that is present in a sub-nanogram range in the biological sample.
46 . The method of claim 45 , wherein the detecting comprises detecting the first protein, the second protein, and the third protein.
47 . The method of claim 39 , wherein the preparing comprises purifying the digested peptides using solid phase extraction.
48 . The method of claim 30 , wherein the detecting comprises performing mass spectrometry.
49 . The method of claim 48 , wherein the mass spectrometry comprises LC-MS/MS.
50 . The method of claim 30 , wherein a dynamic range limitation of the instrument is 4-6 orders of magnitude.
51 . The method of claim 30 , wherein the particles comprise polyethylene imine, microparticles, ammonium group functionalizations, or ammonium group functionalizations with a positive surface charge.
52 . The method of claim 30 , wherein the particles vary in sizes including from about 1000 nm to about 5000 nm.
53 . The method of claim 30 , wherein the particles vary in sizes including from about 1000 nm to about 10000 nm.
54 . The method of claim 30 , wherein the particles comprise a first particle that is no more than about 3 μm and a second particle that is at least about 4 μm.
55 . The method of claim 30 , wherein proteins across a dynamic range of ten orders of magnitude are detected using mass spectrometry.