Magnetic resonance system and method to detect and confirm analytes

Abstract

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.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

The details of the present invention, both as to its structure and operation, may be gleaned in part by study of the accompanying drawings, in which like reference numerals refer to like parts, and in which:

FIG. 1 is a schematic representation of a nanoparticle showing the applied magnetic field and the second magnetic field around the nanoparticle.

FIG. 2 is a graph of the net magnetic field surrounding the nanoparticle of FIG. 1.

FIG. 3 is a plot of the magnitude of the magnetic field gradient around the nanoparticle.

FIG. 4 is a plot of the field gradient magnitude along the axis of the particle.

FIG. 5 is a schematic representation of the mutual forces between nanoparticles in a magnetic field.

FIG. 6 is a schematic representation of the formation of a chain structure from nanoparticles and analyte.

FIG. 7 which is a functional block diagram of a magnetic resonance system.

FIGS. 8 a-d is a representation of four configurations of the antenna.

FIG. 9 is a schematic representation of one embodiment of a magnet.

FIG. 10 is a circuit diagram of a buffered oscillator.

FIG. 11 is a schematic illustration of an installation having one controller and multiple sensor units.

FIG. 12 is a schematic depiction of an analyzer system suitable for use with an HVAC system.

FIG. 13 is a representation of a concentrator magnet system.

FIG. 14 is a representation of an alternative concentrator magnet system.

FIG. 15 is a graph of magnetic resonance data with and without magnetic processing.

FIGS. 16 a-e depict an embodiment of a fixed installation system and three collector intakes.

FIG. 17 is a front perspective view of a hand-portable system.

FIG. 18 is a block diagram of a system adapted to a medical diagnostic application.

Claims

1. A method, for detecting an analyte, comprising the steps of: attaching nanoparticles to the analyte, thereby forming nanoparticle-analyte complexes;applying a magnetic field to the complexes in a known liquid, thereby magnetizing the nanoparticles;then, allowing the magnetic field to exert forces on the nanoparticles and allowing the nanoparticles to exert magnetic forces on each other;then, allowing the complexes to undergo motions responsive to the magnetic forces;allowing the complexes to undergo interactions, which interactions are enhanced by said motions;exciting magnetic resonance signals from a sample comprising the complexes and the known liquid;determining the T2 of the sample by analyzing the magnetic resonance signals; anddetermining whether the analyte is present in the sample by analyzing the determined T2 and a predetermined value.

2. The method of claim 1 wherein the analytes are selected from the group of molecules, molecular fragments, molecular complexes, viruses, cells, and bacteria.

3. The method of claim 1 wherein the interactions are molecular bonding reactions.

4. The method of claim 1 wherein the magnetic field is substantially uniform in a region occupied by the complexes.

5. The method of claim 1 wherein the magnetic field is substantially non-uniform in a region occupied by the complexes, and wherein the magnetic field is strongest in a subvolume of said region.

6. The method of claim 5 wherein the complexes have an initial concentration in the fluid medium; and wherein the magnetic field, in cooperation with the nanoparticles, urges the complexes to move toward the subvolume, thereby causing the complexes to have a concentration in the subvolume which is higher than the initial concentration; and wherein the interactions are accelerated due to the higher concentration of the complexes in the subvolume.

7. The method of claim 1 wherein pairs of the nanoparticles exert mutual magnetic forces on each other; and wherein the mutual magnetic forces urge the complexes to approach each other in alignment with the magnetic field, thereby causing the interactions to occur while the reactants are positioned in alignment with the magnetic field.

8. The method of claim 1 wherein the interactions produce a product comprising nanoparticles and analyte; and wherein the motions cause a particular form of the product to be produced.

9. The method of claim 8 wherein the particular form of the product is an extended and substantially linear chain.

10. The method of claim 1 wherein the interactions produce a product comprising nanoparticles and analyte; and wherein the motions suppress production of a particular form of the product.

11. The method of claim 10 wherein the particular form of the product is an agglomerate comprising a distributed accumulation of nanoparticles and analyte.

12. The method of claim 1 wherein the presence of the analyte is indicated by the determined T2 being greater than the predetermined value.

13. The method of claim 1 wherein the predetermined value is the T2 of the combination of the known liquid with the nanoparticles.

14. The method of claim 11 wherein the presence of the analyte is indicated by the determined T2 being less than the predetermined value.

15. The method of claim 1 further comprising measuring T2 of the known liquid and the nanoparticles.

16. The method of claim 1 wherein the T2 parameter is measured before the interactions undergo and again after the interactions undergo; and comparing the T2 values so obtained.

17. The method of claim 16 wherein an increase in T2 indicates that extended substantially linear chain structures have formed; and wherein a decrease in T2 indicates that distributed agglomerates have formed.

18. A method to detect DNA in a sample, comprising the steps of: binding nanoparticles to DNA probes having a sequence complementary to the DNA to create nanoparticle probes;mixing the sample with the nanoparticle probes in a fluid to form a fluid sample and to promote binding between the nanoparticle probes and DNA;measuring the magnetic resonance parameter T2 of the fluid sample;applying a substantially non-uniform magnetic field to the fluid sample, thereby magnetizing the nanoparticles,drawing the nanoparticles into a sub-volume of the fluid sample where the magnetic field is strongest;forming chain-like structures of nanoparticle probes and DNA in the sub-volume;re-mixing the fluid sample;measuring the magnetic resonance parameter T2 of the fluid sample; anddetermining whether the DNA is present by comparing the T2 measurements.

19. A method to detect DNA in a sample, comprising the steps of: binding nanoparticles to DNA probes having a sequence complementary to the DNA to create nanoparticle probes;mixing the sample with the nanoparticle probes in a fluid to form a fluid sample and to promote binding between the nanoparticle probes and DNA;measuring the magnetic resonance parameter T2 of the fluid sample;applying a substantially uniform magnetic field to the fluid sample, thereby magnetizing the nanoparticles, forming chain-like structures of nanoparticle probes and DNA;measuring the magnetic resonance parameter T2 of the fluid sample; anddetermining whether the DNA is present by comparing the T2 measurements.

20. A method, for detecting an analyte, comprising the steps of: binding analytes to paramagnetic nanoparticles to form nanoparticle-analyte complexes;placing the complexes in a known liquid in a non-uniform magnetic field thereby concentrating the complexes in a region of the non-uniform magnetic field having the strongest field;wherein the concentrating of the complexes enhances the process of the complexes binding to each other;exciting magnetic resonance signals from a sample comprising the complexes and the known liquid; anddetermining whether the analyte is present in the sample by analyzing one or more of the magnetic resonance signals.

21. A method, for detecting an analyte, comprising the steps of: binding analytes to paramagnetic nanoparticles to form nanoparticle-analyte complexes;placing the complexes in a known liquid in a uniform magnetic field thereby magnetizing the nanoparticles and producing dipole-dipole forces between the nanoparticles;wherein the forces enhance the process of the complexes binding to each other;exciting magnetic resonance signals from a sample comprising the complexes and the known liquid; anddetermining whether the analyte is present in the sample by analyzing one or more of the magnetic resonance signals.

22. A portable magnetic resonance system comprising: a magnet system having an upper permanent magnet and a lower permanent magnet which generate a magnetic field in a sample area located between the upper permanent magnet and the lower permanent magnet;a pulse generator configured to produce electromagnetic pulses at a selected frequency;a coil coupled to the pulse generator and configured to transmit the electromagnetic pulses generated by the pulse generator to the sample area and to receive responsive magnetic resonance signals from the sample area;a receiver coupled to the coil so as to receive the magnetic resonance signals from the coil and configured to convert the magnetic resonance signals into a digital form; anda controller in communication with the pulse generator and the receiver, and configured to control the operation of the pulse generator so as to cause the pulse generator to produce electromagnetic pulses at a selected frequency;said controller being further configured to receive the digital form of the magnetic resonance signals from the receiver caused by the electromagnetic pulses being transmitted to the sample area by the coil in the presence of the magnetic field, and to analyze the digital form of the magnetic resonance signals.

23. The system of claim 22 further comprising a concentrating magnet system which generates a non-uniform magnetic field in an area occupied by a sample.

24. The system of claim 22 further comprising a uniform magnet system which generates dipole-dipole forces between paramagnetic bodies placed within the uniform magnet system.

25. The system of claim 22 further comprising: a sample collector having a concentrator to collect sample material,a mixer configured to receive sample material from the concentrator and to mix sample material with a liquid,a fluidic transport system in communication with the mixer and extending into the sample area for transporting the sample material mixed with the liquid to the sample area.

26. A magnetic resonance system comprising: a concentrating magnet system which generates a non-uniform magnetic field in an area occupied by a sample;a magnetic resonance measurement device having a sample area; anda fluidic sample delivery system having a sample container and a delivery system for transporting liquid samples to the concentrating magnet system and the sample area.

27. A magnetic resonance system comprising: a magnet system which generates a magnetic field in an area occupied by a sample so as to magnetize paramagnetic bodies placed in the system and to generate dipole-dipole forces among those bodies;a magnetic resonance measurement device having a sample area; anda fluidic sample delivery system having a sample container and a delivery system for transporting liquid samples to the concentrating magnet system and the sample area.