NMR device for detection of analytes

• US 20090134869A1
• Filed: 09/02/2008
• Published: 05/28/2009
• Est. Priority Date: 08/31/2005
• Status: Active Grant

• Current Assignee: T2 Biosystems, Inc
• Original Assignee: T2 Biosystems, Inc
• Inventors: Lee, W. David
• Granted Patent: US 8,102,176 B2
• Time in Patent Office: Days
• US Class Current: 324/309
• CPC Class Codes: G01N 24/08 by using nuclear magnetic resonance G01N24/12 takes precedence
• CPC Class Codes: G01N 24/088 Assessment or manipulation of a chemical or biochemical reaction, e.g. verification whether a chemical reaction occurred or whether a ligand binds to a receptor in drug screening or assessing reaction kinetics
• CPC Class Codes: G01R 33/281 Means for the use of in vitro contrast agents G01R33/282 takes precedence; involving use of a contrast agent in MR imaging G01R33/5601; in vivo contrast agents A61K49/0002
• CPC Class Codes: G01R 33/285 Invasive instruments, e.g. catheters or biopsy needles, specially adapted for tracking, guiding or visualization by NMR
• CPC Class Codes: G01R 33/302 Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips
• CPC Class Codes: G01R 33/34007 Manufacture of RF coils, e.g. using printed circuit board technology; additional hardware for providing mechanical support to the RF coil assembly or to part thereof, e.g. a support for moving the coil assembly relative to the remainder of the MR system
• CPC Class Codes: G01R 33/34053 Solenoid coils; Toroidal coils
• CPC Class Codes: G01R 33/34061 Helmholtz coils
• CPC Class Codes: G01R 33/34069 Saddle coils
• CPC Class Codes: G01R 33/34084 implantable coils or coils being geometrically adaptable to the sample, e.g. flexible coils or coils comprising mutually movable parts
• CPC Class Codes: G01R 33/341 comprising surface coils
• CPC Class Codes: G01R 33/44 using nuclear magnetic resonance [NMR] G01R33/24, G01R33/62 take precedence
• CPC Class Codes: G01R 33/465 applied to biological material, e.g. in vitro testing
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent

Abstract

This invention relates generally to detection devices having one or more small wells each surrounded by, or in close proximity to, an NMR micro coil, each well containing a liquid sample with magnetic nanoparticles that self-assemble or disperse in the presence of a target analyte, thereby altering the measured NMR properties of the liquid sample. The device may be used, for example, as a portable unit for point of care diagnosis and/or field use, or the device may be implanted for continuous or intermittent monitoring of one or more biological species of interest in a patient.

Claims

1-46. -46. (canceled)

47. A device for detection of an analyte, said device comprising a plurality of wells for holding a liquid sample comprising magnetic particles and said analyte, said magnetic particles having binding moieties linked thereto, and, for each of said wells:

an RF coil disposed about said well, said RF coil configured to detect an echo response produced by exposing said liquid sample in said well to a bias magnetic field created using one or more magnets and an RF excitation.

49. The device of claim 47, wherein said wells are arranged in an array.

50. The device of claim 49, wherein said array is substantially two-dimensional.

51. The device of claim 49, wherein said array is three-dimensional.

52. The device of claim 47, configured to allow distribution of liquid into said plurality of wells.

62. The device of claim 47, wherein a substrate defines said plurality of wells, and wherein each of said RF coils is integrated with said substrate and is disposed about its respective well.

48. (canceled)

53-61. -61. (canceled)

63-71. -71. (canceled)

72. A device comprising:

a support defining one or more wells for holding a liquid sample; and

disposed on said support, for reconstitution within said one or more wells, dried superparamagnetic particles having binding moieties linked thereto, wherein said binding moieties are operative to alter an aggregation of said magnetic particles in said liquid sample as a function of the presence or concentration of an analyte in said liquid sample.

74. The device of claim 72, wherein said support defines an array of said wells.

75. The device of claim 72, wherein said device is a component of an analyte detection system.

80. The device of claim 72, wherein said analyte comprises at least one of the following:

a protein, a peptide, a polypeptide, an amino acid, a nucleic acid, an oligonucleotide, a therapeutic agent, a metobolite of a therapeutic agent, RNA, DNA, an antibody, an organism, bacteria, a carbohydrate, a polysaccharide, a virus, and glucose.

81. The device of claim 72, wherein said binding moieties comprise at least one of the following:

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, bacteria, a virus, and a polysaccharide.

73. (canceled)

76. The device of claim 73, further comprising an RF excitation coil for transmitting said RF excitation, wherein said RF excitation coil is separate from said one or more RF coils disposed about said one or more wells.

77. The device of claim 73, wherein for each of said one or more wells, said well and said RF coil disposed about said well are configured to provide a filling factor of at least about 0.7.

78. The device of claim 73, wherein, for each of said one or more wells, said respective RF coil is disposed within one centimeter of the electrical element in communication with said RF coil.

79. The device of claim 73, wherein said electrical element is configured to do at least one of the following:

(i) amplify said signal;

(ii) rectify said signal; and

(iii) digitize said signal.

82. The device of claim 73, further comprising a reader configured to receive, for each of said wells, said signal corresponding to said echo response from said respective well.

83. A device comprising a support defining one or more wells for holding a liquid sample, said sample comprising magnetic particles and an analyte, said magnetic particles having binding moieties linked thereto, wherein said binding moieties are operative to alter an aggregation of said magnetic particles in said liquid sample as a function of the presence or concentration of said analyte in said liquid sample, and wherein at least one of said wells has a varying cross section such that, in the presence of a magnetic field, aggregations of said particles move from an area of larger cross section to an area of smaller cross section, thereby concentrating said analyte carried with said aggregations.

84. The device of claim 83, comprising, for each of said one or more wells, an RF coil disposed about said well and an electrical element in communication with said RF coil, wherein said RF coil is configured to detect an echo response produced by exposing said liquid sample in said well to a bias magnetic field created using one or more magnets and an RF excitation, wherein said electrical element is configured to at least partially condition a signal corresponding to said echo response.

85. The device of claim 83, wherein at least one of said binding moieties is operative to bind to at least one of the following:

(i) said analyte;

(ii) another of said binding moieties; and

(iii) an aggregation-inducing molecule in said liquid sample,

thereby producing said aggregations.

86. The device of claim 83, wherein said binding moieties comprise at least one of the following:

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, and bacteria.

87. The device of claim 83, wherein said analyte comprises at least one of the following:

a protein, a peptide, a polypeptide, an amino acid, a nucleic acid, an oligonucleotide, a therapeutic agent, a metabolite of a therapeutic agent, RNA, DNA, an antibody, an organism, a virus, bacteria, a carbohydrate, a polysaccharide, and glucose.

88. A device for detection of an analyte, the device comprising:

a support defining a well for holding a liquid sample comprising magnetic particles and said analyte, said magnetic particles having binding moieties linked thereto; and

an RF coil disposed about said liquid sample, said RF coil configured to detect an echo response produced by exposing said liquid sample to a bias magnetic field created using one or more magnets and an RF excitation, said well and said RF coil configured to provide a filling factor of at least about 0.1.

89-90. -90. (canceled)

91. A device for detection of an analyte, the device comprising:

a support defining a well for holding a liquid sample comprising magnetic particles and said analyte, said magnetic particles having binding moieties linked thereto; and

an RF coil disposed about said liquid sample, said RF coil configured to detect an echo response produced by exposing said liquid sample to a bias magnetic field created using one or more magnets and an RF excitation, wherein at least one of the following is less than about 1 mL;

(i) the volume circumscribed by said RF coil; and

(ii) the volume of said liquid sample.

92. (canceled)

93. A device for detection of an analyte, the device comprising:

a support defining a well for holding a liquid sample comprising magnetic particles and said analyte, said magnetic particles having binding moieties linked thereto;

an RF coil disposed about said liquid sample, said RF coil configured to detect an echo response produced by exposing said liquid sample to a bias magnetic field created using one or more magnets and an RF excitation; and

an electrical element in communication with said RF coil, said electrical element configured to at least partially condition a signal corresponding to said echo response, wherein said RF coil is disposed sufficiently close to said electrical element to provide a Q factor of at least 1.

95. The device of claim 93, wherein said RF coil is integrated with a substrate and disposed about said well.

96. The device of claim 93, wherein said RF coil is disposed within one centimeter of said electrical element.

94. (canceled)

97. (canceled)

98. A method of measuring one or more analytes in a sample comprising:

obtaining a sample for measuring one or more analytes; and

measuring the presence of the one or more analytes in the sample using a device for detection of an analyte, the device comprising;

a support defining one or more wells for holding a sample and magnetic particles, the magnetic particles having binding moieties linked thereto, wherein said binding moieties are operative to alter an aggregation phenomena of the magnetic particles in the sample as a function of the presence or concentration of analyte in said sample; and

an RF coil disposed about each of the one or more wells, said RF coil configured to detect an echo response produced by exposing the sample to a bias magnetic field created using one or more magnets and an RF excitation;

wherein an echo response detected from the sample exposed to the bias magnetic field and RF excitation is indicative of detection of the one or more analytes in the sample, thereby measuring the presence of the one or more analytes.

99. The method of claim 98, wherein said one or more analytes comprise a plurality of biologically active substances.

100. The method of claim 98, wherein said sample comprises at least one of the following:

a research sample, a cell sample, and an organism-derived sample.

101. The method of claim 98, wherein said method is performed in vivo.

102. The method of claim 98, wherein said measuring step comprises determining the concentration of said one or more analytes.

104. The method of claim 98, wherein said measuring step comprises continuously monitoring said one or more analytes.

105. The method of claim 98, wherein said measuring step comprises semi-continuously monitoring said one or more analytes.

106. The method of claim 98, wherein said measuring step comprises continuously monitoring said one or more analytes in vivo.

103. (canceled)