US2010041016A1PendingUtilityA1

Methods for detecting organisms and enzymatic reactions using raman spectroscopy and aromatic compounds comprising phosphate

Assignee: SWORD DIAGNOSTICS INCPriority: Oct 17, 2005Filed: Feb 17, 2009Published: Feb 18, 2010
Est. expiryOct 17, 2025(expired)· nominal 20-yr term from priority
G01N 33/56938G01N 33/581C12Q 1/28G01N 21/65G01N 33/58G01N 33/56916G01N 33/56983G01N 2333/55G01N 33/56911C12Q 1/42
54
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Claims

Abstract

The present disclosure provides systems for the rapid and sensitive detection of organisms and molecules in samples. Reactants that produce Raman-active products are used in combination with Raman light scattering. Such compounds may comprise phosphates permitting the detection of phosphatases. The present disclosure can also be used to measure enzyme-kinetics.

Claims

exact text as granted — not AI-modified
1 . A method for detecting the activity of at least one enzyme in a sample comprising:
 a) preparing a mixture comprising the sample and at least one aromatic compound comprising at least one phosphate group;   b) incubating the mixture to form at least one Raman-active product;
 i) optionally adding an oxidizing agent; and 
 ii) optionally adding a base; 
   c) detecting the at least one Raman-active product with Raman spectroscopy.   
     
     
         2 . The method of  claim 1 , wherein the at least one aromatic compound comprises: 
       
         
           
           
               
               
           
         
       
       wherein
 X is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, PO 4 , and COOH; 
 Y is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, and COOH; and 
 Z is chosen from H, OH, Cl, Br, NH 2 , SO 3 H, PO 4 , and COOH. 
 
     
     
         3 . The method of  claim 1 , wherein the at least one aromatic compound comprises: 
       
         
           
           
               
               
           
         
       
       wherein
 X is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, PO 4 , and COOH; 
 Y is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, and COOH; and 
 Z is chosen from H, OH, Cl, Br, NH 2 , SO 3 H, PO 4 , and COOH. 
 
     
     
         4 . The method of  claim 1 , wherein the at least one aromatic compound comprises: 
       
         
           
           
               
               
           
         
       
       wherein
 X is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, PO 4 , and COOH; and 
 Y is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, and COOH. 
 
     
     
         5 . The method of  claim 1 , wherein the at least one aromatic compound comprises: 
       
         
           
           
               
               
           
         
       
       wherein
 X is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, PO 4 , and COOH; and 
 Y is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, and COOH. 
 
     
     
         6 . The method of  claim 1 , wherein the at least one aromatic compound comprises: 
       
         
           
           
               
               
           
         
       
       wherein each of X, Y, Z, and W are each independently chosen from H and OH. 
     
     
         7 . The method of  claim 1 , wherein the at least one enzyme comprises a phosphatase. 
     
     
         8 . The method of  claim 7 , wherein the phosphatase is alkaline phosphatase. 
     
     
         9 . The method of  claim 8 , wherein the alkaline phosphatase is conjugated to an antibody. 
     
     
         10 . The method of  claim 1 , wherein the at least one aromatic compound comprises 4-amino-1-phenyl-1-phosphate. 
     
     
         11 . The method of  claim 1 , wherein the at least one aromatic compound comprises 4-hydroxy-1-naphthyl-1-phosphate. 
     
     
         12 . The method of  claim 1 , wherein the at least one aromatic compound comprises 4-amino-1-naphthyl-1-phosphate. 
     
     
         13 . The method of  claim 1 , wherein the at least one aromatic compound comprises hydroquinone diphosphate. 
     
     
         14 . The method of  claim 1 , wherein the base is sodium hydroxide. 
     
     
         15 . The method of  claim 1 , wherein the oxidizing agent is sodium metaperiodate. 
     
     
         16 . The method of  claim 1 , wherein the Raman spectroscopy is resonant Raman spectroscopy. 
     
     
         17 . A method for detecting at least one target in a sample comprising:
 a) preparing a mixture comprising the at least one target;   b) incubating the mixture with at least one ligand specific for the at least one target, wherein the at least one ligand comprises a phosphatase;   c) providing to the mixture at least one aromatic compound comprising a phosphate;   d) incubating the mixture to form at least one Raman-active product;
 i) optionally adding an oxidizing agent; and 
 ii) optionally adding a base; and 
   e) detecting the at least one Raman-active product with Raman spectroscopy.   
     
     
         18 . The method of  claim 17 , wherein the at least one aromatic compound is the aromatic compound of  claim 2 . 
     
     
         19 . The method of  claim 17 , wherein the at least one aromatic compound is the aromatic compound of  claim 3 . 
     
     
         20 . The method of  claim 17 , wherein the at least one aromatic compound is the aromatic compound of  claim 4 . 
     
     
         21 . The method of  claim 17 , wherein the at least one aromatic compound is the aromatic compound of  claim 5 . 
     
     
         22 . The method of  claim 17 , wherein the at least one aromatic compound is the aromatic compound of  claim 6 . 
     
     
         23 . The method of  claim 17 , wherein the Raman spectroscopy is resonance Raman Spectroscopy. 
     
     
         24 . The method of  claim 17 , wherein the at least one target is an organism. 
     
     
         25 . The method of  claim 24 , wherein the organism is chosen from  E. coli, Listeria, Salmonella, Vibrio, Camphelbacter, Staphylococcus , HIV, Hepatitis, Adenovirus, Rhino virus, and Human papilloma virus. 
     
     
         26 . The method of  claim 17 , wherein the target is chosen from protein, amino acids, nucleic acids, nucleotides, carbohydrates, metabolites, hormones, and metabolic intermediates. 
     
     
         27 . The method of  claim 26 , wherein the protein is chosen from IL-2, C-reactive protein, Tumor Necrosis Factor Receptor II, and Human Cardiac Troponin I. 
     
     
         28 . The method of  claim 17 , wherein the at least one ligand is an antibody. 
     
     
         29 . A kit for detecting at least one enzyme activity comprising:
 a) at least one aromatic compound comprising a phosphate;   b) optionally an oxidizing agent;   c) optionally a base; and   d) optionally suitable buffers for the at least one enzyme.   
     
     
         30 . An aromatic compound comprising: 
       
         
           
           
               
               
           
         
       
       wherein
 X is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, PO 4 , and COOH; 
 Y is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, COOH; and 
 Z is chosen from H, OH, Cl, Br, NH 2 , SO 3 H, PO 4 , and COOH. 
 
     
     
         31 . (canceled) 
     
     
         32 . An aromatic compound comprising: 
       
         
           
           
               
               
           
         
       
       wherein
 X is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, PO 4 , and COOH; and 
 Y is chosen from H, OH, Cl, Br, NO 2 , NH 2 , SO 3 H, and COOH. 
 
     
     
         33 - 34 . (canceled) 
     
     
         35 . An aromatic compound comprising: 
       
         
           
           
               
               
           
         
       
       wherein each of X, Y, Z, and W are each independently chosen from H and OH.

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