Bibliographic Details
| Title: |
NMR SYSTEMS AND METHODS FOR THE RAPID DETECTION OF ANALYTES |
| Document Number: |
20120100546 |
| Publication Date: |
April 26, 2012 |
| Appl. No: |
12/910594 |
| Application Filed: |
October 22, 2010 |
| Abstract: |
This invention features systems and methods for the detection of analytes, and their use in the treatment and diagnosis of disease. |
| Inventors: |
Lowery, JR., Thomas Jay (Belmont, MA, US); Audeh, Mark John (Brighton, MA, US); Blanco, Matthew (Boston, MA, US); Chepin, James Franklin (Arlington, MA, US); Demas, Vasiliki (Arlington, MA, US); Dhanda, Rahul (Needham, MA, US); Fritzemeier, Marilyn Lee (Lexington, MA, US); Koh, Isaac (Arlington, MA, US); Kumar, Sonia (Cambridge, MA, US); Neely, Lori Anne (Reading, MA, US); Mozeleski, Brian (Knox, ME, US); Plourde, Daniella Lynn (Arlington, MA, US); Rittershaus, Charles William (Malden, MA, US); Wellman, Parris (Reading, MA, US) |
| Assignees: |
T2 Biosystems, Inc. (Cambridge, MA, US) |
| Claim: |
1-98. (canceled) |
| Claim: |
99. A composition comprising: (a) a liquid sample containing an analyte; and (b) within the liquid sample from 1×106 to 1×1013 magnetic particles per milliliter of the liquid sample, the magnetic particles having a mean diameter of from 150 nm to 950 nm, a T2 relaxivity per particle of from 1×104 to 1×1012 mM−1s−1, and binding moieties specific to the analyte are conjugated to their surface, wherein the analyte from the sample is bound to at least one of the binding moieties on at least one magnetic particle. |
| Claim: |
100. A composition comprising: (a) a liquid sample suspected of containing a Candida nucleic acid; and (b) within the liquid sample from 1×106 to 1×1013 magnetic particles per milliliter of the liquid sample, the magnetic particles having a mean diameter of from 700 nm to 1200 nm, a T2 relaxivity per particle of from 1×109 to 1×1012 mM−1s−1, and having a first probe and a second probe conjugated to their surface selected so that the first probe is operative to bind to a first segment of the Candida nucleic acid and the second probe is operative to bind to a second segment of the Candida nucleic acid. |
| Claim: |
101. A composition comprising: (a) a liquid sample suspected of containing creatinine; (b) within the liquid sample from 1×106 to 1×1013 magnetic particles per milliliter of the liquid sample, the magnetic particles having a mean diameter of from 150 nm to 699 nm, a T2 relaxivity per particle of from 1×108 to 1×1012 mM−1s−1, and creatinine antibodies conjugated to their surface; and (c) a multivalent binding agent bearing a plurality of creatinine conjugates designed to form aggregates with the population of magnetic particles in the absence of creatinine. |
| Claim: |
102. A composition comprising: (a) a liquid sample suspected of containing tacrolimus; (b) within the liquid sample from 1×106 to 1×1013 magnetic particles per milliliter of the liquid sample, the magnetic particles having a mean diameter of from 150 nm to 699 nm, a T2 relaxivity per particle of from 1×108 to 1×1012 and creatinine antibodies conjugated to their surface; and (c) a multivalent binding agent bearing a plurality of tacrolimus conjugates designed to form aggregates with the population of magnetic particles in the absence of tacrolimus. |
| Claim: |
103. The composition of any one of claims 100-102, wherein the liquid sample is derived from a whole blood sample. |
| Claim: |
104. The composition of claim 101 or 102, wherein the multivalent binding agent comprises a polymeric scaffold. |
| Claim: |
105. A composition, comprising: a) a whole blood sample, or a component thereof; b) a forward primer comprising the oligonucleotide sequence 5′-GGC ATG CCT GTT TGA GCG TC-3′; c) a reverse primer comprising the oligonucleotide sequence 5′-GCT TAT TGA TAT GCT TAA GTT CAG CGG GT-3′; d) a thermal stable polymerase; and e) deoxynucleotide triphosphates, buffer, and magnesium. |
| Claim: |
106. A composition, comprising: (a) a liquid sample containing one or more nucleic acid amplicons generated from an amplification reaction; and (b) within the liquid sample from 1×106 to 1×1013 magnetic particles per milliliter of the liquid sample, the magnetic particles having a mean diameter of from 150 nm to 1200 nm, a T2 relaxivity per particle of from 1×104 to 1×1012 mM−1s−1, and having a first probe and a second probe conjugated to their surface selected so that the first probe is operative to bind to a first segment of the nucleic acid amplicons and the second probe is operative to bind to a second segment of the nucleic acid amplicons. |
| Claim: |
107. A composition, comprising: (a) a liquid sample containing Candida nucleic acid amplicons generated from an amplification reaction; and (b) within the liquid sample from 1×106 to 1×1013 magnetic particles per milliliter of the liquid sample, the magnetic particles having a mean diameter of from 150 nm to 1200 nm, a T2 relaxivity per particle of from 1×104 to 1×1012 mM−1s−1 mM−1s−1, and having a first probe and a second probe conjugated to their surface selected so that the first probe is operative to bind to a first segment of the Candida nucleic acid amplicons and the second probe is operative to bind to a second segment of the Candida nucleic acid amplicons. |
| Claim: |
108. The composition of claim 107, wherein said magnetic particles have a mean diameter of from 700 nm to 1200 nm and a T2 relaxivity per particle of from 1×109 to 1×1012 mM−1s−1. |
| Claim: |
109. The composition of claim 107, the binding of the first probe to a first segment of the Candida amplicon and the binding of the second probe to a second segment of the Candida amplicon form magnetic particle-amplicon aggregates. |
| Claim: |
110. The composition of claim 107, wherein the Candida nucleic acid amplicons are amplified from Candida albicans, and wherein the first probe comprises the oligonucleotide sequence: [table included] and the second probe comprises the oligonucleotide sequence: [table included] |
| Claim: |
111. The composition of claim 107, wherein the Candida nucleic acid amplicons are amplified from Candida krusei, and wherein the first probe comprises the oligonucleotide sequence: [table included] and the second probe comprises the oligonucleotide sequence: [table included] |
| Claim: |
112. The composition of claim 107, wherein the Candida nucleic acid amplicons are amplified from Candida glabrata, and wherein the first probe comprises the oligonucleotide sequence: [table included] and the second probe comprises the oligonucleotide sequence: [table included] |
| Claim: |
113. The composition of claim 107, wherein the Candida nucleic acid amplicons are amplified from Candida parapsilosis or Candida tropicalis, and wherein the first probe comprises the oligonucleotide sequence: [table included] and the second probe comprises the oligonucleotide sequence: [table included] |
| Claim: |
114. A composition comprising: (a) a liquid sample containing nucleic acid amplicons generated from an amplification reaction; (b) within the liquid sample from 1×106 to 1×1013 magnetic particles per milliliter of the liquid sample, the magnetic particles having a mean diameter of from 150 nm to 1200 nm, a T2 relaxivity per particle of from 1×104 to 1×1012 mM−1s−1, and having a first probe and a second probe conjugated to their surface and selected to hybridize to a first segment and a second segment of the nucleic acid amplicons to form aggregates, the aggregates comprising the magnetic particles and the nucleic acid amplicons. |
| Claim: |
115. The composition of claim 114, wherein said magnetic particles have a mean diameter of from 700 nm to 1200 nm and a T2 relaxivity per particle of from 1×109 to 1×1012 mM−1s−1. |
| Claim: |
116. A composition comprising: (a) a liquid sample containing Candida nucleic acid amplicons generated from an amplification reaction; (b) within the liquid sample from 1×106 to 1×1013 magnetic particles per milliliter of the liquid sample, the magnetic particles having a mean diameter of from 150 nm to 1200 nm, a T2 relaxivity per particle of from 1×104 to 1×1012 mM−1s−1, and having a first probe and a second probe conjugated to their surface and selected to hybridize to a first segment and a second segment of the Candida nucleic acid amplicons to form aggregates, the aggregates comprising the magnetic particles and the Candida nucleic acid amplicons. |
| Claim: |
117. The composition of claim 116, wherein said magnetic particles have a mean diameter of from 700 nm to 1200 nm and a T2 relaxivity per particle of from 1×109 to 1×1012 mM−1s−1. |
| Claim: |
118. The aggregate of claim 116, wherein the Candida nucleic acid amplicons are amplified from Candida albicans, and wherein the first probe comprises the oligonucleotide sequence: [table included] and the second probe comprises the oligonucleotide sequence: [table included] |
| Claim: |
119. The aggregate of claim 116, wherein the Candida nucleic acid amplicons are amplified from Candida krusei, and wherein the first probe comprises the oligonucleotide sequence: [table included] and the second probe comprises the oligonucleotide sequence: [table included] |
| Claim: |
120. The aggregate of claim 116, wherein the Candida nucleic acid amplicons are amplified from Candida glabrata, and wherein the first probe comprises the oligonucleotide sequence: [table included] and the second probe comprises the oligonucleotide sequence: [table included] |
| Claim: |
121. The aggregate of claim 116, wherein the Candida nucleic acid amplicons are amplified from Candida parapsilosis or Candida tropicalis, and wherein the first probe comprises the oligonucleotide sequence: [table included] and the second probe comprises the oligonucleotide sequence: [table included] |
| Claim: |
122. A composition comprising: (a) a liquid sample optionally comprising an analyte; (b) within the liquid sample from 1×106 to 1×1013 magnetic particles per milliliter of the liquid sample, the magnetic particles having a mean diameter of from 150 nm to 699 nm, a T2 relaxivity per particle of from 1×108 to 1×1012 mM−1s−1, and binding moieties specific to the analyte are conjugated to their surface; and (c) within the liquid sample a multivalent binding agent bearing a plurality of analyte conjugates capable of forming aggregates with the population of magnetic particles in the absence of the analyte. |
| Claim: |
123. A method of detecting the presence of an analyte, comprising: (a) combining a liquid sample containing an analyte with a population of magnetic particles having a mean diameter of from 150 nm to 1200 nm and binding moieties specific to a first binding site on the analyte are conjugated to their surface; (b) exposing the sample to a magnetic field to capture or concentrate the magnetic particles and the analyte; (c) exposing the concentrated magnetic particles to a surface derivitized with ligands complementary to a second binding site on the analyte thereby forming magnetic particle-analyte-ligand complexes; (d) removing unbound magnetic particles to produce a population of analyte-bound magnetic particles; (e) placing the analyte-bound magnetic particles in a well having an RF coil disposed about the well, the RF coil configured to detect a signal produced by exposing the liquid sample to a bias magnetic field created using one or more magnets and an RF pulse sequence; (f) exposing the sample to a bias magnetic field and an RF pulse sequence; (g) following step (f), measuring the T2 relaxation signal; and (h) on the basis of the result of step (g), determining the concentration of analyte in the liquid sample. |
| Current U.S. Class: |
435/612 |
| Current International Class: |
01; 01; 12; 01; 12; 01 |
| Accession Number: |
edspap.20120100546 |
| Database: |
USPTO Patent Applications |
