Magnetic resonance system and method to detect and confirm analytes
A system and method are provided to detect target analytes based on magnetic resonance measurements. Magnetic structures produce distinct magnetic field regions having a size comparable to the analyte. When the analyte is bound in those regions, magnetic resonance signals from the sample are changed, leading to detection of the analyte.
1. A method, for detecting an analyte, comprising the steps of:
a) mixing a sample containing the analyte with paramagnetic nanoparticles comprising an analyte binding agent, in a known liquid comprising non-zero-spin nuclei, thereby forming a mixture,
wherein the analyte binding agent can bind to the analyte in the known liquid to form paramagnetic nanoparticle-analyte complexes;
b) enhancing binding of the paramagnetic nanoparticles comprising an analyte binding agent to the analyte in the mixture by applying an external, non-uniform magnetic field that varies throughout the volume of the known liquid and has maximal field strength in a subvolume of the known liquid,
wherein the paramagnetic nanoparticles and paramagnetic nanoparticle-analyte complexes are drawn into the subvolume by the non-uniform magnetic field, thereby concentrating the paramagnetic nanoparticles and paramagnetic nanoparticle analyte complexes and enhancing interactions therebetween, except that the non-uniform magnetic field is not applied when the T2 magnetic resonance spin relaxation property measurement is being made; and
c) measuring a magnetic resonance spin relaxation property of the mixture by:
i) applying an external uniform magnetic field to the mixture;
ii) applying one or more radio frequency energy pulses to the mixture in the uniform magnetic field to reorient the bulk magnetization vector of the non-zero spin nuclei in the mixture; and
iii) detecting the magnetic resonance spin relaxation property of the mixture, wherein the magnetic resonance spin relaxation property is the spin-spin relaxation time (T2);
wherein a change in T2 in the presence of the analyte compared to the T2 of a negative control mixture that does not include analyte indicates the presence of analyte in the sample,
thereby detecting the analyte.
2. The method of claim 1 , wherein the analyte is selected from the group of molecules, molecular fragments, molecular complexes, viruses, cells, and bacteria.
3. The method of claim 1 , wherein the interactions produce at least one paramagnetic nanoparticle-analyte complex bound to another paramagnetic nanoparticle-analyte complex.
4. The method of claim 1 , wherein the T2 of the negative control is a value predetermined from a mixture of the known liquid with the nanoparticles.
5. The method of claim 1 further comprising collecting an airborne sample comprising analyte and air; concentrating the analyte into a liquid form; and mixing the concentrated analyte with the paramagnetic nanoparticles and the known liquid.
6. The method of claim 5 wherein the known liquid is water.
7. The method of claim 1 wherein the interactions are selected from the group consisting of an antibody binding with a protein, DNA bonding with complimentary DNA, an antibody binding to an antigen, an oligonucleotide binding with an RNA, a DNA-aptamer binding to a target protein, a DNA-aptamer binding to a target bacteria, a DNA-aptamer binding to a target virus, a DNA-aptamer binding to a target yeast, a DNA-aptamer binding to a target fungus, a protein binding to a target protein, a protein binding to a target bacteria, a protein binding to a target virus, a protein binding to a target yeast, a protein binding to a target fungus, a peptide binding to a target protein, a peptide binding to a target bacteria, a peptide binding to a target virus, a peptide binding to a target yeast, a peptide binding to a target fungus, and a pseudopeptide composed of unnatural amino acids binding with a target, a small molecule binding to a target.
8. The method of claim 1 , wherein the external, non-uniform magnetic field is applied through a permanent magnet.
9. The method of claim 8 , where the external, non-uniform magnetic field has a field strength in the range of 0.01 Tesla to 20 Tesla.
10. The method of claim 1 , wherein the non-zero-spin nuclei are hydrogen atoms.
11. The method of claim 1 , wherein the paramagnetic nanoparticles have an overall diameter of 50 nm.