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. 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 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 dynamic range comprising at least 6 orders of magnitude, thereby assaying the biological sample.
2. The method of claim 1 , wherein the detecting of proteins in the biological sample comprises detecting a protein present in the sample at a concentration greater than 1 mg/ml and a protein present in the sample at a concentration of less than 10 ng/ml.
3. The method of claim 1 , wherein the plurality of particles comprise iron oxide.
4. The method of claim 1 , wherein the assaying is performed using gel-electrophoresis, liquid chromatography, mass spectrometry, nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, circular dichroism, Raman spectroscopy, or any combination thereof.
5. The method of claim 1 , wherein the dynamic range of the proteins detected exceeds a detection limit of the assaying.
6. The method of claim 1 , wherein the dynamic range of the proteins detected spans 6 or more orders of magnitude.
7. The method of claim 1 , wherein the detected proteins comprise proteins present in concentrations of 100 ng/ml or less in the biological sample.
8. The method of claim 1 , wherein the assaying comprises quantitative determination of the total protein adsorbed onto a particle from among the plurality of particles.
9. The method of claim 1 , wherein the assaying comprises quantitative determination of the relative amounts of different types of proteins adsorbed onto a particle from among the plurality of particles.
10. The method of claim 1 , wherein step (b) further comprises removing loosely attached proteins from the particles prior to (c).
11. The method of claim 1 , wherein a particle from among the plurality of particles forms a corona that is at least 15 nm thick.
12. The method of claim 1 , wherein the contacting in (a) is performed for at least 1 minute.
13. The method of claim 1 , wherein the assaying comprises detecting a protein from the corona of a first particle from among the plurality of particles and a protein from the corona of a second particle from among the plurality of particles at the same time, wherein the first particle and the second particle are different particle types.
14. The method of claim 13 , wherein the detecting is performed on an array.
15. The method of claim 1 , wherein the assaying comprises determining the quantity of a protein in the corona of a particle from among the plurality of particles.
16. The method of claim 1 , wherein the assaying comprises determining a ratio of two proteins in a corona of a particle from among the plurality of particles.
17. The method of claim 1 , wherein the assaying further comprises digesting the proteins.
18. The method of claim 1 , wherein the biological sample is divided into a plurality of sample volumes, wherein, in (a), contacting comprises separately incubating a particle of the plurality of particles with the biological sample in a sample volume of the plurality of sample volumes, such that one or more sample volume(s) of the plurality of sample volumes are incubated with a distinct particle type of the plurality of particles.
19. The method of claim 1 , wherein the contacting the biological samples further comprises contacting the biological sample under multiple conditions that differ by one or more of: incubation time, incubation temperature, or flow of the biological sample in contact with the plurality of particles.
20. The method of claim 1 , wherein the assaying comprises determining the conformational state of a protein from the biological sample.
21. The method of claim 1 , wherein the assaying comprises measuring an association between two different proteins in the biological sample.
22. The method of claim 1 , wherein the biological sample is selected from the group consisting of: blood, plasma, serum, lung lavage, menstrual blood, urine, processed tissue samples, amniotic fluid, cerebrospinal fluid, tears, saliva, sperm, chopped tissue, homogenized tissue, or any lysates or combinations thereof.
23. The method of claim 1 , wherein the coronas that form around the plurality of particles further comprise a species of biomolecules selected from the group consisting of polysaccharides, sugars, lipids, lipoproteins, metabolites, oligonucleotides, or any combination thereof.
24. The method of claim 1 , wherein at least one particle of the plurality of particles enriches for peptides other than albumin such that a ratio of an amount of albumin to a protein X that binds to the at least one particle is less than a ratio of an amount of albumin to the protein X in the biological sample.
25. The method of claim 1 , wherein the different particle types differ from each other by one or more physicochemical properties, wherein the one or more physicochemical properties are selected from the group consisting of: composition, size, surface charge, hydrophobicity, hydrophilicity, surface functionality, surface topography, surface curvature, shape, and any combination thereof.
26. The method of claim 25 , wherein the one or more physicochemical properties comprises surface functionality, wherein the surface functionality is selected from the group consisting of aminopropyl functionalization, amine functionalization, boronic acid functionalization, carboxylic acid functionalization, methyl functionalization, N-succinimidyl ester functionalization, polyethylene glycol PEG functionalization, streptavidin functionalization, methyl ether functionalization, triethoxylpropylaminosilane functionalization, thiol functionalization, citrate functionalization, lipoic acid functionalization, polyethylene imine functionalization, carboxyl functionalization, hydroxyl functionalization, and any combination thereof.
27. The method of claim 1 , wherein the assaying comprises detecting a signal from a particle from among the plurality of particles, wherein the signal is selected from the group consisting of a fluorescence signal, a luminescence signal, a charge-based signal, and a colorimetric signal.
28. The method of claim 1 , wherein the assaying comprises measuring the change in size of a particle of the plurality of particles following corona formation on said particle.
29. The method of claim 1 , further comprising centrifuging the biological sample and the plurality of particles prior to (b).