Particle-based sensors and methods using particle-based sensors for detection of analytes
The disclosure relates to particle-based assays for the detection of analytes. Using various combinations of particular technologies, including gold nanorods, silver nanoparticles, gold/silver nanoshells, gold/silver nanocages and nanobubble detection, enhanced detection limits can be achieved across a large range of analytes.
1 . A method of detecting an analyte in a sample comprising:
(a) providing a binding agent comprising a gold nanoparticle, an antibody or analyte-binding fragment thereof that selectively binds to an analyte, wherein said antibody or analyte-binding fragment thereof is linked to said gold nanoparticle;
(b) contacting said binding agent with a sample containing or suspected of containing said analyte, wherein binding of said binding agent to said analyte induces nanoparticle aggregation;
(c) subjecting the product of step (b) to a laser, thereby inducing nanobubbles when nanoparticle aggregates are present; and
(d) detecting binding of said binding agent to said analyte by optical detection of nanobubbles,
wherein step (c) comprises optically detecting light amplitude and area under the curve.
2 . The method of claim 1 , wherein said detecting is quantitative or semi-quantitative.
3 . The method of claim 1 , wherein said detecting is non-quantitative.
4 . The method of claim 1 , wherein said analyte is a protein, peptide, oligonucleotide, polynucleotide, a lipid, or a carbohydrate.
5 . The method of claim 1 , wherein said analyte is a virus, a bacterium, a fungus, or a cell.
6 . The method of claim 1 , wherein said analyte is a non-biological chemical compound, or a metal ion.
7 . The method of claim 1 , wherein said antibody is a single chain antibody, bispecific antibody, or a polyvalent antibody.
8 . The method of claim 1 , wherein said antigen binding fragment is a Fab, a F(ab) 2 , a scFv or aptamer.
9 . The method of claim 1 , further comprising a control reaction where said binding agent is contacted with a second sample containing said analyte.
10 . The method of claim 1 , further comprising a control reaction where said binding agent is contacted with a second sample lacking said analyte.
11 . The method of claim 1 , wherein steps (b) and (c) are completed in less than one hour.
12 . The method of claim 1 , wherein the laser is nanosecond or picosecond laser.
13 . The method of claim 5 , wherein said virus is respiratory syncytial virus (RSV) or SARS-COV-2.
14 . The method of claim 1 , wherein step (d) employs a handheld optical detection device.
15 . The method of claim 1 , wherein said sample is a biological sample, an environmental sample, a food sample, or a drug sample.
16 . The method of claim 6 , wherein said non-biological chemical compound is a small molecule drug, a pesticide, a herbicide, a polymer, a toxin, an industrial by-product or waste product.
17 . The method of claim 6 , wherein said metal is a heavy metal ion.
18 . The method of claim 9 , wherein the amount of said analyte in said second sample is known.
19 . The method of claim 11 , wherein steps (b) and (c) are completed in about 30 minutes.