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1. AU2008343871 - Magnetic resonance system with implantable components and methods of use thereof

Anmerkung: Text basiert auf automatischer optischer Zeichenerkennung (OCR). Verwenden Sie bitte aus rechtlichen Gründen die PDF-Version.

[ EN ]
CLAIMS
What is claimed is:
1. A nuclear magnetic resonance system for measuring magnetic resonance signals from a sample contained in a sample volume in-vivo, the system comprising:
(a) a magnet or magnetic field generator positioned to provide a magnetic field in a sample volume, the magnetic field being suitable to allow measuring magnetic resonance signal;
(b) a probehead suitable for partial or complete implantation in a subject, the probehead comprising a radiofrequency circuit that includes a radiofrequency coil wound to form a space capable of accommodating a sample volume and a port, the port allowing a sample to enter the sample volume, wherein the sample volume contains magnetic particles and the port is adapted to allow an analyte to enter the sample volume and to prevent, partly or completely, the magnetic particles from leaving the sample volume; (c) an external coil for disposition outside the subject's body, wherein the external coil is suitable for inductive coupling to the radiofrequency circuit to form a radiofrequency resonant circuit; and
(d) a control unit for disposition outside the subject's body, wherein the control unit is connected to the external coil and comprises logic circuitry to control the radiofrequency resonant circuit and allows acquisition and processing of magnetic resonance signal received by the radiofrequency resonant circuit.
2.           A nuclear magnetic resonance system for measuring magnetic resonance relaxation signals from a sample contained in a sample volume in-vivo, the system comprising: (a) a permanent magnet or magnetic field generator for disposition outside a subject's body and near a sample volume to provide a magnetic field in a sample volume, the magnetic field being suitable to allow measuring magnetic resonance relaxation signal;
(b) a probehead suitable for partial or complete implantation in a subject, the probehead comprising a radiofrequency circuit that includes a radiofrequency coil wound to form a space capable of accommodating a sample volume and a port, the port allowing a sample to enter the sample volume; (c) an external coil for disposition outside the subject's body, wherein the external coil is suitable for inductive coupling to the radiofrequency circuit to form a radiofrequency resonant circuit; and
(d) a control unit for disposition outside the subject's body, wherein the control unit is connected to the external coil and comprises logic circuitry to control the radiofrequency resonant circuit and allows acquisition and processing of magnetic resonance relaxation signal received by the radiofrequency resonant circuit.
3.           A nuclear magnetic resonance system for measuring magnetic resonance relaxation signals from a sample contained in a sample volume in-vivo, the system comprising: (a) a probehead suitable for partial or complete implantation in a subject, the probehead comprising:
(al) a radiofrequency circuit that includes a capacitor and a radiofrequency coil wound to form a space capable of accommodating a sample volume and a port, the port allowing a sample to enter the sample volume;
(a2) a permanent magnet positioned near or around the radiofrequency coil to provide a magnetic field in the sample volume, the magnetic field being suitable to allow measuring magnetic resonance relaxation signal;
(b) an external coil for disposition outside the subject's body, wherein the external coil is suitable for inductive coupling to the radiofrequency circuit to form a radiofrequency resonant circuit; and
(c) a control unit for disposition outside the subject's body, wherein the control unit is connected to the external coil and comprises logic circuitry to control the radiofrequency resonant circuit and allows acquisition and processing of magnetic resonance relaxation signal received by the radiofrequency resonant circuit.
4.           A nuclear magnetic resonance system for measuring magnetic resonance relaxation signals from a sample contained in a sample volume in-vivo, the system comprising: (a) a permanent magnet or magnetic field generator for disposition outside a subject's body and near a sample volume to provide a magnetic field in a sample volume, the magnetic field being suitable to allow measuring magnetic resonance relaxation signal;
(b) a probehead suitable for partial or complete implantation in a subject, the probehead comprising a radiofrequency circuit that includes a radiofrequency coil wound to form a space capable of accommodating a sample volume and a port, the port allowing a sample to enter the sample volume, wherein the sample volume contains at least one sensor particle and the port is adapted to allow an analyte to enter the sample volume and to prevent, partly or completely, the one or more sensor particles from leaving the sample volume;
(c) an external coil for disposition outside the subject's body, wherein the external coil is suitable for inductive coupling to the radiofrequency circuit to form a radiofrequency resonant circuit; and
(d) a control unit for disposition outside the subject's body, wherein the control unit is connected to the external coil and comprises logic circuitry to control the radiofrequency resonant circuit and allows acquisition and processing of magnetic resonance relaxation signal received by the radiofrequency resonant circuit.
5.           A nuclear magnetic resonance system for measuring magnetic resonance relaxation signals from a sample contained in a sample volume in-vivo, the system comprising: (a) a probehead suitable for partial or complete implantation in a subject, the probehead comprising a probehead suitable for partial or complete implantation within a subject's body, the probehead comprising:
(al) a radiofrequency circuit that includes a capacitor and a radiofrequency coil wound to form a space capable of accommodating a sample volume and a port, the port allowing a sample to enter the sample volume, wherein the sample volume contains at least one sensor particle and the port is adapted to allow an analyte to enter the sample volume and to prevent, partly or completely, the one or more sensor particles from leaving the sample volume;
(a2) a permanent magnet positioned near or around the radiofrequency coil to provide a magnetic field in the sample volume, the magnetic field being suitable to allow measuring magnetic resonance relaxation signal;
(b) an external coil for disposition outside the subject's body, wherein the external coil is suitable for inductive coupling to the radiofrequency circuit to form a radiofrequency resonant circuit; and
(c) a control unit for disposition outside the subject's body, wherein the control unit is connected to the external coil and comprises logic circuitry to control the radiofrequency resonant circuit and allows acquisition and processing of magnetic resonance relaxation signals received by the radiofrequency resonant circuit.
6.           The system of any one of Claims 1-5, wherein the magnetic field is effectively static. 7. The system of any one of Claims 1-5, wherein the system is for measuring magnetic resonance relaxometry.
8.           The system of any one of Claims 1-5, wherein the radiofrequency circuit comprises a radiofrequency coil and a capacitor.
9.           The system of any one of Claims 1-5, wherein the radiofrequency coil has an associated detection volume and the sample volume overlaps completely with the detection volume.
10.         The system of any one of Claims 1-5, wherein the radiofrequency coil encompasses part of or effectively all of a sample volume and a port.
11.         The system of any one of Claims 1-5, wherein the magnet or magnetic field generator is single-sided.
12.         The system of any one of Claims 1-5, wherein the magnet or magnetic field generator is at least two-sided.
13.         The system of any one of Claims 1-2, and 4, wherein the magnet or magnetic field generator is adapted for disposition outside the subject's body.
14.        The system of any one of Claims 1-5, wherein power for operation of the radiofrequency circuit is-provided via electromagnetic coupling of the external coil with the radiofrequency circuit.
15.        The system of Claim 14, wherein the external coupled power source is the sole power source for the radiofrequency circuit.
16.         The system of any one of Claims 1-5 adapted for magnetic resonance relaxometry. 17. The system of any one of Claims 1-5, wherein the logic circuitry for processing the magnetic resonance signals is adapted to determine a magnetic resonance relaxation parameter.
18.        The system of Claim 17, wherein the magnetic resonance relaxation parameter is any of TI, T2, and/or Tirho.
19. The system of any one of Claims 1-5, wherein the logic circuitry for processing the magnetic resonance signals is adapted to determine one or a combination of signal intensity, signal lifetime, signal linewidth or signal integral.
20.         The system of any one of Claims 1-5, the radiofrequency circuit further comprising a reporter coil, wherein any coupling of the external coil to the radiofrequency circuit being inductive and substantially via the reporter coil.
21.         The system of Claim 1, wherein the probehead comprises the magnet or magnetic field generator.
22.         The system of Claim 1, wherein the radiofrequency circuit comprises a radiofrequency coil and a capacitor and the probehead comprises the magnet, the magnet being a permanent magnet with a position fixed relative to the position of the sample chamber.
23.         The system of Claim 22 further comprising (e) a detection device for determining the position of the probehead within the subject's body.
24.         The system of Claim 1, wherein the radiofrequency circuit comprises a radiofrequency coil and a capacitor, and the probehead comprises a permanent magnet near or around the radiofrequency coil.
25.         The system of any one of Claims lor 4-5, wherein a biosensor particle is a magnetic particle and at least part of the magnetic particles aggregate in the presence of an analyte to change a magnetic resonance signal of a sample
26.         The system of any one of Claims 1 or 4-5, wherein the particles are paramagnetic. 27. The system of any one of Claims 1 or 4-5, wherein the particles are superparamagnetic.
28.         The system of any one of Claims Ior 4-5, wherein at least one of the particles comprises a polymer matrix coating.
29.         The system of any one of Claims I or 4-5, wherein the magnetic particles have an average particle size of between about 1 nm and 5pim.
30. The system of any one of Claims 1 or 4-5, wherein the magnetic particles are functionalized with one or more binding moieties that bind to one or more target analytes.
31. The system of Claim 30, wherein at least one of the one or more binding moieties comprises at least one of an amino group, a carboxyl group, a sulfhydryl group, an amine group, an imine group, an epoxy group, a hydroxyl group, a thiol group, an acrylate group, or an isocyano group.
32.         The system of Claim 30, wherein at least one of the one or more binding moieties comprises at least one of an amino acid, a nucleic acid, an oligonucleotide, a therapeutic agent, a metabolite of a therapeutic agent, a peptide, a polypeptide, a protein, a carbohydrate, a polysaccharide, a virus, or a bacteria.
33.         The system of any one of Claims 1-5, wherein the probehead further comprises means allowing removing and/or loading a sample volume with sensor particles, and the port is adapted to allow an analyte to enter the sample volume and to prevent, partly or completely, the one or more particles from leaving the sample volume.
34.         The system of any one of Claims 1-5, wherein the probehead further comprises a magnetic field detector for detecting the strengths of the magnetic field within or adjacent to the sample volume, and
a transmitter for transmitting a signal indicative of the strength of the magnetic field; and
and the control unit further comprises a receiver for receiving the signal indicative of the strength of the magnetic field.
35.         The system of any one of Claims 1-5 further comprising (e) a device for determining the position of the probehead within the subject's body.
36.         The system of Claim 35, wherein the device of (e) is based on x-ray telemetric location determination, near IR telemetric location determination, ultrasonic telemetric location determination, or magnetic resonance telemetric location determination.
37.         The system of Claim 35, wherein the probehead further comprises a radiofrequency identification (RFID) emitter for emitting radiofrequency signals, and the means of (e) comprising (i) a radiofrequency receiver for receiving the emitted radiofrequency signals, and (ii) logic circuitry for determining the position of the sample volume from the received radiofrequency signals.
38.         The system of any one of Claims 1-5, wherein the probehead comprises a plurality of separate sample volumes and the radiofrequency circuit comprises at least one radiofrequency coil with an associated excitable volume and detection volume for each sample volume, wherein each of the sample volumes at least partly overlap with the excitable volume and detection volume.
39.         The system of any one of Claims 1-5, wherein the probehead comprises a plurality of separate sample volumes and the radiofrequency circuit comprises a separate radiofrequency coil for each sample volume, wherein each radiofrequency coil is independently connected to a switch and associated circuitry that allows wirelessly turning on or off each of the radiofrequency coils, and wherein each radiofrequency coil has an associated excitable volume and detection volume that at least partly overlaps with each corresponding sample volume.
40.         The system of any one of Claims 1-5, further comprising at least one further probehead suitable for partial or complete implantation in a subject, the probehead comprising a radiofrequency circuit that includes a radiofrequency coil wound to form a space capable of accommodating a sample volume and a port, the port allowing a sample to enter the sample volume, wherein the sample volume contains magnetic particles and the port is adapted to allow an analyte to enter the sample volume and to prevent, partly or completely, the magnetic particles from leaving the sample volume, and at least part the magnetic particles aggregate in the presence of analyte to change a magnetic resonance signal of a sample;
wherein the external coil is further adapted for inductive coupling to the radiofrequency circuit of a given probehead to form a radiofrequency resonant circuit to allow control with the control unit of the given probehead.
41.         The system of any one of Claims 1-5, wherein the sample volume and the detection volume overlap in a sample-detection volume, and the magnetic field within the sample-detection volume is inhomogeneous.
42.         The system of any one of Claims 1-5, wherein the sample volume and the detection volume overlap in a sample-detection volume, the magnetic field within the sample detection volume has a minimum magnetic field strength value, and the magnetic field varies by more than 0.5%, more than 1%, more than 2% , and/or more than 3% within the sample-detection volume with respect to the minimum magnetic field strength value.
43.         The system of any one of Claims 1-5, wherein the magnet or magnetic field generator is positioned relative to the radiofrequency coil such that its detection volume overlaps at least partly with an excitable volume.
44.         The system of any one of Claims 1-5, wherein the sample volume and the detection volume overlap in a sample-detection volume, and the magnetic field within the sample-detection volume exhibits a maximum variation selected from between about 1 ppm and about 10000 ppm; between about 1 ppm and about 2000 ppm; and between about 10 ppm and about 1000 ppm.
45.         The system of any one of Claims 1-44 wherein the probehead is adapted for partial or complete implantation in a subject and for monitoring an analyte to determine outcome of a surgery.
46.         The system of any one of Claims 1-45, wherein the one or more analytes are, independently, a therapeutic agent or a biomarker.
47.         The system of any one of Claims 1-46, wherein the probehead is biodegradable or bioinert after a period of time.
48.         The system of any one of Claims 1-46, wherein the probehead is coated with a coating suitable to prevent, partly or completely, biofouling or immune response against the probehead; and/or the probehead is partially or completely composed of biodegradable materials.
49.         The system of any one of Claims 1-48, wherein the magnetic resonance system further comprises a drug delivery unit, the delivery unit comprising a pharmaceutically active agent suitable for administration to the subject, and the control unit further comprising logic circuitry for controlling the drug delivery unit, wherein the pharmaceutically active agent is delivered to the subject in response to the determined magnetic resonance signal received.
50.         The system of any one of Claims 2 or 3 wherein the sensor particle comprises a responsive polymer and a sample characteristic comprises any one of a pH value, ionic strength, or the concentration or presence of an analyte, wherein a characteristic of the responsive polymer changes in response to changes in the sample characteristic, thereby altering a magnetic resonance signal sensed by the system.