Device for detecting misfolded proteins and methods of use thereof

Abstract

The present invention relates to diagnostic devices as well as methods of using these devices for detecting proteins of interest associated with diseases or disorders in mammals. In particular, the proteins of interest may be misfolded proteins associated with certain misfolded-protein disorders in mammals including those mammals suspected of or at risk of having such disorders.

What is claimed is: 
     
         1 . A diagnostic test strip for detection of at least one protein in a biological sample of a mammal, said diagnostic test strip comprising:
 a) at least one sample receiving material, wherein said sample receiving material is capable of receiving a biological sample;   b) at least one trap, wherein said trap is able to separate a detection reagent bound to said at least one protein in said biological sample from a detection reagent that is not bound to said at least one protein in said biological sample; and   c) a display strip.   
     
     
         2 . The diagnostic test strip of  claim 1 , wherein said at least one sample receiving material, at least one trap and said display strip are in contact in sequence. 
     
     
         3 . The diagnostic test strip of  claim 2 , wherein said at least one sample receiving pad abuts said at least one trip and said at least one trap abuts said display strip. 
     
     
         4 . The diagnostic test strip of  claim 2 , wherein said at least one sample receiving material overlaps with said at least one trap and said at least one trap overlaps with said display strip. 
     
     
         5 . The diagnostic test strip of  claim 4 , wherein said at least one sample receiving pad comprises a first sample receiving pad and a second sample receiving pad. 
     
     
         6 . The diagnostic test strip of  claim 4 , wherein said at least one trap comprises a first trap and a second trap. 
     
     
         7 . The diagnostic test strip of  claim 6 , wherein said at least on sample receiving material overlaps with said first trap, said first trap overlaps with said second trap, and said second trap overlaps with said display strip. 
     
     
         8 . The diagnostic test strip of  claim 2 , wherein at said least one trap comprises a first trap, a second trap and a third trap. 
     
     
         9 . The diagnostic test strip of  claim 1 , wherein said test strip further comprises a control reagent. 
     
     
         10 . A housing or cassette encasing a device, wherein said device comprises said diagnostic test strip of  claim 1 . 
     
     
         11 . The housing or cassette of  claim 10 , wherein said housing or cassette further comprises a well for application of said biological sample. 
     
     
         12 . The housing or cassette of  claim 10 , wherein said housing or cassette further comprises a window for reading results. 
     
     
         13 . A kit comprising a device, wherein said device comprises said diagnostic test strip of  claim 1 . 
     
     
         14 . The kit of  claim 13 , wherein said kit further comprises instructions for use. 
     
     
         15 . The kit of  claim 13 , wherein said kit further comprises a sample applicator. 
     
     
         16 . The kit of  claim 13 , wherein said kit further comprises a calibrator or control reagent. 
     
     
         17 . The kit of  claim 13 , wherein said kit further comprises a detection reagent. 
     
     
         18 . The kit of  claim 17 , wherein said detection reagent is selected from the group consisting of an azo dye, Thioflavin T and an analog of an azo dye. 
     
     
         19 . The kit of  claim 18 , wherein said azo dye is Congo Red. 
     
     
         20 . The diagnostic test strip of  claim 1 , wherein said at least one sample receiving material comprises a material selected from the group consisting of nitrocellulose, cellulose, a glass fiber, a cotton, a woven mesh, a nonwoven material, a porous plastic, a polymer and a polyester. 
     
     
         21 . The diagnostic test strip of  claim 1 , wherein said at least one trap comprises a material selected from the group consisting of nitrocellulose, cellulose, a glass fiber, a cotton/glass fiber, a woven mesh, a nonwoven material, a polymer and a polysulfone. 
     
     
         22 . The diagnostic test strip of  claim 1 , wherein said display strip comprises a material selected from the group consisting of nitrocellulose, a chromatographic paper, a polysulfone and cellulose. 
     
     
         23 . The diagnostic test strip of  claim 1 , wherein said at least one protein is selected from the group consisting of a misfolded protein, a protein aggregate, a supramolecular protein aggregate, a fragment of a misfolded protein, a fragment of a protein aggregate, a fragment of a supramolecular protein aggregate, and mixtures thereof. 
     
     
         24 . The diagnostic test strip of  claim 23 , wherein said misfolded protein is selected from the group consisting of alpha-1 antitrypsin (SerpinA1), ceruloplasmin, heavy-chain IgG, light-chain IgG, interferon-inducible protein 6-16 (IF 16-6, G1P3), albumin, fragments thereof, and mixtures thereof. 
     
     
         25 . The diagnostic test strip of  claim 1 , wherein said at least one protein is congophilic. 
     
     
         26 . The diagnostic test strip of  claim 1 , wherein said trap permits flow of detection reagent bound to said at least one protein in said biological sample through said trap. 
     
     
         27 . The diagnostic test strip of  claim 1 , wherein said trap retains, retards the flow of or binds said unbound detection reagent. 
     
     
         28 . The diagnostic test strip of  claim 1 , wherein said display strip is configured to contain said biological sample after said biological sample flows through said trap. 
     
     
         29 . The diagnostic test strip of  claim 1 , wherein said display strip displays detection reagent if said at least one protein is present in said biological sample. 
     
     
         30 . A kit for detection of at least one protein in a biological sample of a mammal, said kit comprising:
 a) a sample receiving material, wherein said sample receiving material is capable of receiving a biological sample;   b) a trap, wherein said trap is in contact with said sample receiving material and wherein said trap is able to separate a detection reagent bound to said at least one protein in said biological sample from a detection reagent that is not bound to said at least one protein in said biological sample, whereby said detection reagent bound to said at least one protein in said biological sample is able to flow through said trap, and whereby said detection reagent that is not bound to said at least one protein in said biological sample is captured by said trap;   c) a display strip, wherein said display strip is in contact with said trap, and wherein said display strip is configured to contain said biological sample after said biological sample flows through said trap, wherein said sample receiving material, said trap, and said display strip are configured to be in contact in sequence; and   d) a detection reagent, wherein said detection reagent is reactive with said at least one protein in said biological sample.   
     
     
         31 . The kit of  claim 30 , wherein said display strip exhibits said detection reagent if said at least one protein is present in said biological sample. 
     
     
         32 . The kit of  claim 30 , wherein said detection reagent binds to at least one protein selected from the group consisting of a misfolded protein, a protein aggregate, a supramolecular protein aggregate, a fragment of a misfolded protein, a fragment of a protein aggregate, a fragment of a supramolecular protein aggregate, and mixtures thereof. 
     
     
         33 . The kit of  claim 30 , wherein said detection reagent is selected from the group consisting of an azo dye, Thioflavin T and an analog of an azo dye. 
     
     
         34 . The kit of  claim 33 , wherein said azo dye is Congo Red. 
     
     
         35 . The kit of  claim 30 , wherein said kit further comprises instructions for use. 
     
     
         36 . The kit of  claim 30 , wherein said kit further comprises a sample applicator. 
     
     
         37 . The kit of  claim 30 , wherein said kit further comprises a calibrator or control reagent.