Non-covalent patterned chemical features and use thereof in maldi-based quality control

Abstract

The present application provides arrays for use in immunosignaturing and quality control of such arrays. Also disclosed are peptide arrays and uses thereof for diagnostics, therapeutics and research.

What is claimed is: 
     
         1 . An array of compounds, wherein a defined area of the array is designated for quality control analysis of the array, the defined area of the array comprising unique compounds on separate features of the array, wherein the unique compounds are capable of being released from the surface of the array without diffusion of the compounds outside of a boundary of the feature. 
     
     
         2 . The array of  claim 1 , wherein the compounds are not covalently bound to the surface of the array. 
     
     
         3 . The array of  claim 1 , wherein the compounds are covalently bound to the surface of the array. 
     
     
         4 . The array of any of  claims 1 - 3 , wherein the array comprises a monolayer of greater than about 100 compounds per cm 2 . 
     
     
         5 . The array of any of  claims 1 - 3 , wherein the array comprises a monolayer of greater than about 1,000 compounds per cm 2 . 
     
     
         6 . The array of any of  claims 1 - 3 , wherein the array comprises a monolayer of greater than about 5,000 compounds per cm 2 . 
     
     
         7 . The array of any of  claims 1 - 6 , wherein the compounds are bound to the surface of the array via a linker. 
     
     
         8 . The array of  claim 6 , wherein the linker is cleavable between the molecule and the surface of the array. 
     
     
         9 . The array of  claim 6  or  7 , wherein the linker is acid labile, base labile or light labile. 
     
     
         10 . The array of any one of  claims 6 - 8 , wherein said linker comprises a compound selected from the group of hydroxymethylbenzoic acid (HMBA), hydroxymethylphenylacetic acid (HMPAA), hydroxymethylphenoxyacetic acid (HMPOA), 4-(4-hydroxymethyl-3-methoxyphenoxyl)-butyric acid (HMPB), carboxyproanesulfonamide (CPSA), sulfamoylbenzoic acid (SABA) (and other safety-catch linkers), p-{(R,S)-a-[1-(9H-Fluoren-9-yl)-methoxyformamido]-2,4-dimethoxybenzyl}-phenoxyacetic acid, and variants thereof. 
     
     
         11 . The array of any of  claims 1 - 9 , wherein the compounds to be measured are coupled to a permanently ionized group. 
     
     
         12 . The array of  claim 10 , wherein the compound is triphenylphosphine (TPP) or tris(2,4,6-trimethoxyphenyl)phosphine (TMPP). 
     
     
         13 . The array of claim of any of  claims 1 - 12 , wherein the unique compounds are released under a volatile, nebulized or sublimated gas phase, or under a liquid phase wherein droplets of the liquid have a diameter comparable to the array feature size and pitch. 
     
     
         14 . The array of any of  claims 1 - 13 , wherein the compounds are peptides or nucleic acids. 
     
     
         15 . A method for evaluating the quality of an array, the method comprising assigning quality control features on the surface of the array;
 generating unique compounds on each control feature;   releasing the compounds from the surface of the array without diffusion of the compounds outside of a boundary of the feature; and   analyzing the compounds for sequence fidelity using matrix assisted laser desorption/ionization—time of flight analysis.   
     
     
         16 . The method of  claim 15 , wherein the array comprises a monolayer of greater than about 100 compounds per cm 2 . 
     
     
         17 . The method of  claim 15 , wherein the array comprises a monolayer of greater than about 1,000 compounds per cm 2 . 
     
     
         18 . The method of  claim 15 , wherein the array comprises a monolayer of greater than about 5,000 compounds per cm 2 . 
     
     
         19 . The method of any of  claims 15 - 18 , wherein the compounds are not covalently bound to the surface upon generation on the array. 
     
     
         20 . The method of any of  claims 15 - 18 , wherein the compounds are covalently bound to the surface upon generation on the array. 
     
     
         21 . The method of any of  claims 15 - 20 , wherein the compounds are initially bound to the surface of the array via a linker. 
     
     
         22 . The method of  claim 21 , wherein the linker is cleavable between the molecule and the surface of the array. 
     
     
         23 . The method of  claim 21  or  22 , wherein the linker is acid labile, base labile or light labile. 
     
     
         24 . The method of any one of  claims 21 - 23 , wherein the linker comprises a compound selected from the group of hydroxymethylbenzoic acid (HMBA), hydroxymethylphenylacetic acid (HMPAA), hydroxymethylphenoxyacetic acid (HMPOA), 4-(4-hydroxymethyl-3-methoxyphenoxyl)-butyric acid (HMPB), carboxyproanesulfonamide (CPSA), sulfamoylbenzoic acid (SABA) (and other safety-catch linkers), p-{(R,S)-a-[1-(9H-Fluoren-9-yl)-methoxyformamido]-2,4-dimethoxybenzyl}-phenoxyacetic acid, and variants thereof. 
     
     
         25 . The method of any of  claims 15 - 24 , wherein the compounds to be measured are coupled to a permanently ionized group. 
     
     
         26 . The method of  claim 25 , wherein the compound is triphenylphosphine (TPP) or tris(2,4,6-trimethoxyphenyl)phosphine (TMPP). 
     
     
         27 . The method of any of  claims 15 - 26 , wherein the unique compounds are released under a volatile, nebulized or sublimated gas phase, or under a liquid phase wherein droplets of the liquid have a diameter comparable to the array feature size and pitch. 
     
     
         28 . The method of  claims 15 - 27 , wherein the compounds are peptides or nucleic acids. 
     
     
         29 . A method for evaluating the quality of an array, the method comprising
 a. assigning quality control features on the surface of the array, wherein each feature contains a linker peptide for each synthesis step to be performed;   b. initiating photolithography on one of the features of step (a) containing a linker peptide;   c. initiating an amino acid coupling reaction to the linker peptide on the feature; and   d. determining the identity of the amino acid coupled, if any, to the linker peptide;   wherein if the linker peptide in step (c) was not deprotected, no amino acid would be coupled to the linker peptide and the event would be registered as a deletion of an amino acid, and wherein if the amino acid in step (c) failed to couple to the linker peptide, a substitution event would be registered.   
     
     
         30 . The method of  claim 29 , wherein the array comprises a monolayer of greater than about 100 compounds per cm 2 . 
     
     
         31 . The method of  claim 29 , wherein the array comprises a monolayer of greater than about 1,000 compounds per cm 2 . 
     
     
         32 . The method of  claim 29 , wherein the array comprises a monolayer of greater than about 5,000 compounds per cm 2 . 
     
     
         33 . The method of any of  claims 30 - 32 , wherein the linker peptides are not covalently bound to the surface upon generation on the array. 
     
     
         34 . The method of any of  claims 30 - 32 , wherein the linker peptides are covalently bound to the surface upon generation on the array. 
     
     
         35 . The method of any of  claim 29 , wherein the compounds to be measured are coupled to a permanently ionized group. 
     
     
         36 . The method of  claim 29 , wherein the compound is triphenylphosphine (TPP) or tris(2,4,6-trimethoxyphenyl)phosphine (TMPP). 
     
     
         37 . The method of any of  claims 29 - 36 , wherein the unique compounds are released under a volatile, nebulized or sublimated gas phase, or under a liquid phase wherein droplets of the liquid have a diameter comparable to the array feature size and pitch. 
     
     
         38 . A method of monitoring coupling of amino acid to a feature on an array, the method comprising:
 a. Obtaining a spectra of the feature using matrix assisted laser desorption/ionization-time of flight analysis, wherein each feature contains a linker peptide for each synthesis step to be performed;   b. Determining the identity of each amino acid incorporated for ach synthesis step based on the spectra;   c. Repeating steps (a) and (b) for each synthesis step to be performed.   
     
     
         39 . The method of  claim 38 , the method further comprising calculating a cycle substitution score for each feature for each synthesis step, wherein the calculating is performed by a computer program having computer-executable code encoded therein, the computer executable code adapted to perform the calculating. 
     
     
         40 . The method of  claim 39 , the method further comprising calculating an average cycle substitute score for a plurality of features for each synthesis step, wherein the calculating is performed by a computer program having computer-executable code encoded therein, the computer executable code adapted to perform the calculating. 
     
     
         41 . The method of  claim 38 , the method further comprising calculating a cycle deletion score for each feature for each synthesis step, wherein the calculating is performed by a computer program having computer-executable code encoded therein, the computer executable code adapted to perform the calculating. 
     
     
         42 . The method of  claim 39 , the method further comprising calculating an average cycle eletion score for a plurality of features for each synthesis step, wherein the calculating is performed by a computer program having computer-executable code encoded therein, the computer executable code adapted to perform the calculating. 
     
     
         43 . The method of any of  claims 39 - 42 , wherein the calculated score is compared to a threshold value for a quality control determination, wherein the calculating is performed by a computer program having computer-executable code encoded therein, the computer executable code adapted to perform the calculating.