US2013273522A1PendingUtilityA1

Nmr systems and methods for the rapid detection of analytes

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Assignee: T2 BIOSYSTEMS INCPriority: Nov 16, 2010Filed: Mar 28, 2013Published: Oct 17, 2013
Est. expiryNov 16, 2030(~4.3 yrs left)· nominal 20-yr term from priority
Inventors:Thomas Jay Lowery, Jr.Mark John AudehJames Franklin ChepinVasiliki DemasRahul K. DhandaMarilyn Lee FritzemeierMatthew BlancoIsaac KohSonia KumarBrian M. MozeleskiLori Anne NeelyDaniella Lynn PlourdeCharles W. Rittershaus
C12Q 2563/155G01N 24/08C12Q 2565/633C12Q 1/6895G01R 33/302G01R 33/448G01R 33/465Y10T436/24C12Q 1/6816C12Q 2563/143C12Q 2600/156C12Q 2565/113G01N 27/745C12Q 2537/125
67
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Claims

Abstract

This invention features systems and methods for the detection of analytes, and their use in the treatment and diagnosis of disease.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of detecting an analyte in a sample, the method comprising:
 (a) obtaining a liquid sample suspected of having one or more analytes selected from GRO-alpha, High mobility group-box 1 protein (HMBG-1), IL-1 receptor, IL-1 receptor antagonist, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-18, macrophage inflammatory protein (MIP-1), macrophage migration inhibitory factor (MIF), osteopontin, RANTES (regulated on activation, normal T-cell expressed and secreted; or CCL5), TNF-α, C-reactive protein (CRP), CD64, monocyte chemotactic protein 1 (MCP-1), adenosine deaminase binding protein (ABP-26), inducible nitric oxide synthetase (iNOS), lipopolysaccharide binding protein, and procalcitonin;   (b) preparing an assay sample by combining with a portion of the liquid sample from 1×10 6  to 1×10 13  magnetic particles per milliliter of the liquid sample, wherein the magnetic particles have a mean diameter of from 150 nm to 1200 nm and a T 2  relaxivity per particle of from 1×10 8  to 1×10 12  mM −1 s −1 , and wherein the magnetic particles have binding moieties on their surfaces, the binding moieties operative to alter the specific aggregation of the magnetic particles in the presence of the one or more analytes;   (c) placing the assay sample in a device, the device comprising a support defining a well for holding the liquid sample comprising the magnetic particles and the one or more analytes, and 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;   (d) exposing the assay sample to the bias magnetic field and the RF pulse sequence;   (e) following step (d), measuring the signal produced by the assay sample; and   (f) on the basis of the result of step (e), detecting the analyte.   
     
     
         2 . The method of  claim 1 , wherein the one or more analytes is selected from GRO-alpha, high mobility group-box 1 protein (HMBG-1), IL-1 receptor, IL-1 receptor antagonist, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-18, macrophage inflammatory protein (MIP-1), macrophage migration inhibitory factor (MIF), osteopontin, RANTES (regulated on activation, normal T-cell expressed and secreted; or CCL5), TNF-α, C-reactive protein (CRP), CD64, and monocyte chemotactic protein 1 (MCP-1). 
     
     
         3 . The method of  claim 1 , wherein the method further comprises detecting the concentration of an antiviral agent, antibiotic agent, antifungal agent, or metabolite thereof, in the sample. 
     
     
         4 . The method of  claim 1 , wherein the method further comprises detecting the presence of a multivalent binding agent. 
     
     
         5 . The method of  claim 1 , wherein the method further comprises detecting the presence of one or more pathogen-associated analytes. 
     
     
         6 . The method of  claim 5 , wherein the one or more pathogen-associated analytes is a particular substance derived from a pathogen or a mixture derived from a pathogen. 
     
     
         7 . The method of  claim 6 , wherein the particular substance derived from a pathogen is a protein, nucleic acid, lipid, or polysaccharide. 
     
     
         8 . The method of  claim 6 , wherein the mixture derived from a pathogen comprises a whole cell or a whole virus. 
     
     
         9 . The method of  claim 6 , wherein the one or more pathogen-associated analytes is derived from a pathogen associated with sepsis selected from  Acinetobacter  sp.,  Aspergillus fumigatis, Bacteroides fragilis , blaSHV,  Burkholderia cepacia, Campylobacter jejuni/coli, Candida guilliermondii, Candida albicans, Candida glabrata, Candida krusei, Candida Lusitaniae, Candida parapsilosis, Candida tropicalis, Clostridium pefringens , coagulase-negative  Staphylococcus  sp.,  Enterobacter aeraogenes, Enterobacter cloacae , Enterobacteriaceae,  Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Haemophilus influenzae, Kingella kingae, Klebsiella oxytoca, Klebsiella pneumoniae, Listeria monocytogenes , MecA gene (Methicillin-resistant  Staphylococcus aureus  (MRSA)),  Morganella morganii, Neisseria meningitidis , non-meningitidis  Neisseria  sp.,  Prevotella buccae, Prevotella intermedia, Prevotella melaminogenica, Propionibacterium acnes, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enterica, Serratia marcescens, Staphylococcus aureus, Staphylococcus haemolyticus, Stenotrophomonas maltophilia, Staphylococcus saprophyticus, Streptococcus agalactie, Streptococcus bovis, Streptococcus dysgalactiae, Streptococcus mitis, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes , and  Streptococcus  sanguinis. 
     
     
         10 . The method of  claim 9 , wherein the pathogen associated with sepsis is a bacterium selected from the group consisting of  Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter  sp., and  Pseudomonas aeruginosa.    
     
     
         11 . The method of  claim 9 , wherein the pathogen associated with sepsis is a fungus selected from the group consisting of  Candida albicans, Candida glabrata, Candida krusei, Candida Lusitaniae, Candida parapsilosis , and  Candida tropicalis.    
     
     
         12 . The method of  claim 5 , wherein the one or more pathogen-associated analytes is derived from treatment-resistant strains of bacteria. 
     
     
         13 . The method of  claim 12 , wherein the treatment-resistant strains of bacteria are penicillin-resistant, methicillin-resistant, quinolone-resistant, macrolide-resistant, and/or vancomycin-resistant bacterial strains. 
     
     
         14 . The method of  claim 13 , wherein the methicillin-resistant bacterial strain is methicillin-resistant  Staphylococcus aureus  (MRSA). 
     
     
         15 . The method of  claim 13 , wherein the vancomycin-resistant bacterial strain is vancomycin-resistant  Enterococci.    
     
     
         16 . The method of  claim 1 , wherein the sample is derived from an immunocompromised subject. 
     
     
         17 . The method of  claim 1 , wherein the sample is derived from a subject suspected of having sepsis or septic shock. 
     
     
         18 . The method of  claim 1 , wherein the magnetic particles have a mean particle diameter between 150 and 699 nm. 
     
     
         19 . The method of  claim 18 , wherein the magnetic particles have a mean particle diameter between 150 and 250 nm. 
     
     
         20 . A method of detecting a pathogen-associated analyte in a sample, the method comprising:
 (a) obtaining a liquid sample suspected of having one or more pathogen-associated analytes;   (b) preparing an assay sample by combining with a portion of the liquid sample from 1×10 6  to 1×10 13  magnetic particles per milliliter of the liquid sample, wherein the magnetic particles have a mean diameter of from 150 nm to 1200 nm and a T 2  relaxivity per particle of from 1×10 8  to 1×10 12  mM −1 s −1 , and wherein the magnetic particles have binding moieties on their surfaces, the binding moieties operative to alter the specific aggregation of the magnetic particles in the presence of the one or more pathogen-associated analytes;   (c) placing the assay sample in a device, the device comprising a support defining a well for holding the liquid sample comprising the magnetic particles and the one or more pathogen-associated analytes, and 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;   (d) exposing the assay sample to the bias magnetic field and the RF pulse sequence;   (e) following step (d), measuring the signal produced by the assay sample; and   (f) on the basis of the result of step (e), detecting the pathogen-associated analyte.   
     
     
         21 . The method of  claim 20 , wherein the one or more pathogen-associated analytes is a particular substance derived from a pathogen or a mixture derived from a pathogen. 
     
     
         22 . The method of  claim 21 , wherein the particular substance derived from a pathogen is a protein, nucleic acid, lipid, or polysaccharide. 
     
     
         23 . The method of  claim 22 , wherein the particular substance derived from a pathogen is a nucleic acid. 
     
     
         24 . The method of  claim 23 , wherein the nucleic acid is the MecA gene. 
     
     
         25 . The method of  claim 23 , wherein the nucleic acid is a Van A gene or a Van B gene. 
     
     
         26 . The method of  claim 23 , wherein the nucleic acid is a blaSHV gene. 
     
     
         27 . The method of  claim 22 , wherein the particular substance derived from a pathogen is a protein. 
     
     
         28 . The method of  21 , wherein the mixture derived from a pathogen comprises a whole cell or a whole virus. 
     
     
         29 . The method of  claim 21 , wherein the one or more pathogen-associated analytes is derived from a pathogen associated with sepsis selected from  Acinetobacter  sp.,  Aspergillus fumigatis, Bacteroides fragilis , blaSHV,  Burkholderia cepacia, Campylobacter jejuni/coli, Candida guilliermondii, Candida albicans, Candida glabrata, Candida krusei, Candida Lusitaniae, Candida parapsilosis, Candida tropicalis, Clostridium pefringens , coagulase-negative  Staphylococcus  sp.,  Enterobacter aeraogenes, Enterobacter cloacae , Enterobacteriaceae,  Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Haemophilus influenzae, Kingella kingae, Klebsiella oxytoca, Klebsiella pneumoniae, Listeria monocytogenes , MecA gene (Methicillin-resistant  Staphylococcus aureus  (MRSA)),  Morganella morganii, Neisseria meningitidis , non-meningitidis  Neisseria  sp.,  Prevotella buccae, Prevotella intermedia, Prevotella melaminogenica, Propionibacterium acnes, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enterica, Serratia marcescens, Staphylococcus aureus, Staphylococcus haemolyticus, Stenotrophomonas maltophilia, Staphylococcus saprophyticus, Streptococcus agalactie, Streptococcus bovis, Streptococcus dysgalactiae, Streptococcus mitis, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes , and  Streptococcus sanguinis.    
     
     
         30 . The method of  claim 29 , wherein the pathogen associated with sepsis is a bacterium selected from the group consisting of  Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter  sp., and  Pseudomonas aeruginosa.    
     
     
         31 . The method of  claim 29 , wherein the pathogen associated with sepsis is a fungus selected from the group consisting of  Candida albicans, Candida glabrata, Candida krusei, Candida Lusitaniae, Candida parapsilosis , and  Candida tropicalis.    
     
     
         32 . The method of  claim 20 , wherein the one or more pathogen-associated analytes is derived from treatment-resistant strains of bacteria. 
     
     
         33 . The method of  claim 32 , wherein the treatment-resistant strains of bacteria are penicillin-resistant, methicillin-resistant, quinolone-resistant, macrolide-resistant, and/or vancomycin-resistant bacterial strains. 
     
     
         34 . The method of  claim 33 , wherein the methicillin-resistant bacterial strain is methicillin-resistant  Staphylococcus aureus  (MRSA). 
     
     
         35 . The method of  claim 33 , wherein the vancomycin-resistant bacterial strain is vancomycin-resistant  Enterococci.    
     
     
         36 . The method of  claim 20 , wherein the sample is derived from an immunocompromised subject. 
     
     
         37 . The method of  claim 20 , wherein the sample is derived from a subject suspected of having sepsis or septic shock. 
     
     
         38 . The method of  claim 23 , wherein the magnetic particles have a mean particle diameter between 700 and 900 nm. 
     
     
         39 . The method of  claim 38 , wherein the magnetic particles have a mean particle diameter between 700 and 850 nm. 
     
     
         40 . The method of  claim 27 , wherein the magnetic particles have a mean particle diameter between 150 and 699 nm. 
     
     
         41 . The method of  claim 40 , wherein the magnetic particles have a mean particle diameter between 150 and 250 nm.

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