Probes comprising metal nanoparticles, magnetic nanoparticles and target-specific fluorophores or binding sites

1 . A biosensor probe, comprising:

a core comprising a metal nanoparticle having a metal nanoparticle surface, the metal nanoparticle comprising a metal selected from gold, silver, copper, aluminum, and alloys thereof;

at least one magnetic nanoparticle associated with the core, the magnetic nanoparticle comprising iron, iron oxide, nickel, cobalt, or a combination thereof; and

at least one reporter molecule.

2 . The probe according to claim 1 , comprising a plurality of magnetic nanoparticles associated with the metal nanoparticle core, the plurality of magnetic nanoparticles covering greater than 0 to less than 50% of the metal nanoparticle core surface.

3 . The probe according to claim 2 , wherein the plurality of magnetic nanoparticles covers from 10% to 30% of the metal nanoparticle core surface.

4 . The probe according to claim 1 , further comprising at least one recognition receptor associated with the metal nanoparticle for recognizing a selected target.

5 . The probe according to claim 4 , wherein the recognition receptor is a peptide, a protein, a nucleic acid, a molecularly imprinted polymer, or any combination thereof.

6 . The probe according to claim 4 , wherein the recognition receptor is an antibody.

7 . The probe according to claim 4 , wherein the recognition receptor is single or double stranded RNA or DNA.

8 . The probe according to claim 4 , wherein the reporter molecule is associated with the recognition receptor.

9 . The probe according to claim 1 , wherein the reporter molecule is selected from a fluorescent tag, a Raman reporter, or a combination thereof.

10 . The probe according to claim 9 , wherein the reporter molecule is a fluorescent dye and the metal nanoparticle size is selected to create a plasmon resonance spectrum that matches the light excitation or dye emission wavelength of the fluorescent dye to thereby enhance the fluorescence or Raman signal of the fluorescent dye.

11 . The probe according to claim 1 , wherein the metal nanoparticle size is varied, a percentage of the metal nanoparticle surface that is covered by magnetic particles is varied, or both are varied, to reduce or eliminate unwanted scattering or absorption of light contributed by the MNP.

12 . A biosensor probe, comprising:

a core comprising a metal nanoparticle having a metal nanoparticle surface, the metal nanoparticle comprising a metal selected from gold, silver, copper, aluminum, and alloys thereof;

a plurality of magnetic nanoparticles associated with the core, the plurality of magnetic nanoparticles comprising iron, iron oxide, nickel, cobalt, or a combination thereof, and wherein the the plurality of magnetic nanoparticles covers greater than 0 to less than 50% of the metal nanoparticle core surface;

at least one recognition receptor associated with the metal nanoparticle for recognizing a selected target; and

at least one reporter molecule associated with the metal nanoparticle, wherein the reporter molecule is a fluorescent tag, a Raman reporter, or a combination thereof.

13 . A method, comprising:

providing a probe according to claim 1 ;

contacting a sample comprising a target of interest with the probe to form a probe-target composite;

concentrating probe-target composites using an applied magnetic field to form concentrated probe-target composites; and

detecting the concentrated probe-target composites.

14 . The method according to claim 13 , wherein a plurality of probes are concentrated on a surface.

15 . The method according to claim 13 , wherein concentrating the probe-target composites enhances a sensing signal from 5 to 10 times compared to detection without concentrating the probes.

16 . The method according to claim 13 , wherein the probes are concentrated on a surface comprising an anti-fouling agent selected from bovine serum albumin, casein, an alkylene glycol, zwitterionic molecules, and combinations thereof.

17 . The method according to claim 13 , wherein detecting comprises detecting a fluorescent signal, obtaining a Raman spectrum, or both.

18 . The method according to claim 13 , wherein the target is a virus.

19 . The method according to claim 13 , wherein the virus is SARS-COV-2 or a mutant strain thereof.

20 . The method according to claim 13 , comprising:

obtaining a sputum or blood sample from a subject; and

detecting interleukin-6 (IL-6), interleukin-2 (IL-2), interleukin-1β (IL-1β), or combinations thereof, in the sample at concentrations at least as low as 25 pg/ml.

21 . A method, comprising:

providing a biosensor probe according to claim 12 ;

contacting a sample comprising a target of interest with the biosensor probe to form a probe-target composite;

concentrating probe-target composites on a surface using an applied magnetic field to form concentrated probe-target composites, thereby enhancing a sensing signal from 5 to 10 times compared to detection without concentrating the probes, the surface comprising an anti-fouling agent selected from bovine serum albumin, casein, an alkylene glycol, zwitterionic molecules, and combinations thereof; and

detecting a fluorescent signal, obtaining a Raman spectrum, or both, from the concentrated probe-target composites.

22 . The biosensor probe of claim 12 , wherein the reporter molecule is a fluorescent dye and wherein the metal nanoparticle has a size selected to create a plasmon resonance spectrum that matches the light excitation or dye emission wavelength of the fluorescent dye to thereby enhance fluorescence or Raman signal of the fluorescent dye.