초록 ▼

A collection container and method for collecting a predetermined volume of a biological sample, and particularly a whole blood sample, includes an effective amount of at least one stabilizing agent. The stabilizing agent is able to stabilize nucleic acids in the biological sample at the point of col

A collection container and method for collecting a predetermined volume of a biological sample, and particularly a whole blood sample, includes an effective amount of at least one stabilizing agent. The stabilizing agent is able to stabilize nucleic acids in the biological sample at the point of collection to prevent enzymatic degradation of the nucleic acids. The stabilizing agents include cationic compounds, detergents, particularly cationic detergents, chaotropic salts, ribonuclease inhibitors, chelating agents, and mixtures thereof.

대표청구항 ▼

A collection container and method for collecting a predetermined volume of a biological sample, and particularly a whole blood sample, includes an effective amount of at least one stabilizing agent. The stabilizing agent is able to stabilize nucleic acids in the biological sample at the point of col

A collection container and method for collecting a predetermined volume of a biological sample, and particularly a whole blood sample, includes an effective amount of at least one stabilizing agent. The stabilizing agent is able to stabilize nucleic acids in the biological sample at the point of collection to prevent enzymatic degradation of the nucleic acids. The stabilizing agents include cationic compounds, detergents, particularly cationic detergents, chaotropic salts, ribonuclease inhibitors, chelating agents, and mixtures thereof. re, feed rate, substrate content, co-substrate content, nutrient feed or pressure, removal of conversion products or other solid or liquid components, or combination of any of the foregoing. 3. The process according to claims 1 or 2, wherein said reconditioning step is performed on a part of said solution or different parts of said solution are subjected to different reconditioning steps. 4. The process according to claim 1, wherein said carrier particles comprise a porous material. 5. The process according to claim 1, wherein said process is a continuous conversion process performed successively in one or more columns packed with said carrier. 6. The process according to claim 4 or 5, wherein said solution is recirculated through one or more of said columns. 7. The process according to claim 4 or 5, wherein said solution is fed successively through a series of said columns. 8. The process according to claim 4, wherein said carrier comprises an inert material selected from the group consisting of porous glass beads, porous silicate beads and active charcoal. 9. The process according to claim 4, wherein said carrier comprises a weakly basic anion exchange substance in the form of a substantially non-compressible porous particulate solid material. 10. The process according to claim 1, wherein said micro-organisms are selected from the group consisting of Leuconostoc pseudomesenteroides, Aspergillus candidus, Zygosaccharomyces rouxii, Candida versatilis, Lactobacillus fermentum, Lactobacillus cellobiosus, Lactobacillus brevis, Lactobacillus buchneri, Leuconostoc mesenteroides and Leuconostoc oenos. 11. The process according to claim 9, wherein said micro-organism is Leuconostoc pseudomesenteroides (ATCC 12291). 12. The process according to claim 1, wherein said reconditioning step comprises adjusting the pH of said solution to a value above about 4. 13. The process according to claim 1, wherein said reconditioning step comprises adjusting the pH of said solution to a value between about pH 4.5 and 6.5. 14. The process according to claim 1, wherein said reconditioning step comprises adjusting the pH to a value of about pH 5. 15. The process according to any one of claims 12, 13 and 14, wherein the pH of said solution is adjusted by adding a base selected from the group consisting of an alkali hydroxide and ammonium hydroxide or by adding a buffering substance. 16. The process according to any one of claims 12, 13 and 14, wherein the pH of said solution is adjusted by removing acid formed during the conversion. 17. The process according to claim 16, wherein carbonic acid formed by dissolution of carbon dioxide produced during the conversion is removed by reducing the pressure of said solution. 18. The process according to claim 1, wherein said reconditioning step comprises adjusting the temperature of said solution to about 20 to 35° C. 19. The process according to claim 1, wherein said reconditioning step comprises adjusting the volumetric flow rate of said solution to a value of about 2 to 20 bed volumes per hour. 20. The process according to claim 1, wherein said reconditioning step comprises adjusting the substrate fructose content of said solution to about 7 to 200 g/l. 21. The process according to claim 1, wherein said reconditioning step comprises adding a co-substrate to said solution to about 4 to 100 g/l. 22. The process according to claim 1, wherein said reconditioning step comprises adding nutrients to said solution. 23. The process according to claim 22, wherein said nutrients are selected from the group consisting of yeast extract, tryptone, Na2HPO4,magnesium sulphate, manganese sulphate and mixtures thereof. 24. The process according to claim 1, wherein said reconditioning step comprises recovering mannitol between successive conversion steps. 25. The process according to claim 24, wherein said reconditioning step comprises returning any substrate remaining in the mother liquor after final mann itol recovery to said solution. 26. The process according to claim 24, wherein said reconditioning step comprises recovery of acids from said solution by chromatography or ion exchange. 27. The process according to claim 25, wherein said reconditioning step comprises returning at least a part of said mother liquor to said solution. 28. The process according to claim 1, wherein said reconditioning step comprises removing solid or liquid components contained in said solution by one or more processes selected from the group consisting of filtration, precipitation, elution, membrane filtration, electrodialysis, and fractional distillation. 29. The process according to claim 6, wherein said solution is recirculated through said column until the volumetric production rate of mannitol per column volume in said column has decreased to a predetermined threshold value. 30. The process according to claim 1, wherein said solution contains as a co-substrate an assimilable hexose sugar, selected from the group consisting of glucose, an oligo- or poly-saccharide hydrolyzable to a hexose sugar, and a mixture thereof. 31. The process according to claim 30, wherein said solution contains a mixture of fructose and glucose. 32. The process according to claim 31, wherein said solution comprises isomerized glucose, inverted molasses, beet or cane molasses, thin or thick juices or fractions thereof. 33. The process according to claim 31, wherein the glucose in said solution is simultaneously enzymatically isomerized in the process. 34. The process according to claim 1, wherein said solution contains glucose or mannose as said substrate convertible into mannitol. 35. The process according to claim 1, wherein the carrier is regenerated by removal of the micro-organism cells, washing and reloading with fresh viable micro-organism cells. 36. The process according to claim 1, wherein said mannitol is recovered from the final converted solution by crystallization. 37. The process according to claim 36, wherein lactic acid or acetic acid contained in the mother liquor after mannitol separation are recovered by chromatography or ion exchange. 38. The process according to claim 1, wherein the conversion is performed until about 80% to about 90% or more of the fructose in said solution has been converted to mannitol. 39. The process according to claim 18, wherein said reconditioning step comprises adjusting the temperature of said solution to about 25 to 30° C. 40. The process according to claim 19, wherein said reconditioning step comprises adjusting the volumetric flow rate of said solution to a value of about 10 to about 20 bed volumes per hour. 41. The process according to claim 20, wherein said reconditioning step comprises adjusting the substrate fructose content of said solution to about 15 to 160 g/l. 42. The process according to claim 41, wherein said reconditioning step comprises adjusting the substrate fructose content of said solution to about 50 to 150 g/l. 43. The process according to claim 21, wherein said reconditioning step comprises adding a co-substrate to said solution to about 8 to 80 g/l. 44. The process according to claim 43, wherein said reconditioning step comprises adding a co-substrate to said solution to about 25 to 75 g/l. 45. The process according to claim 26, wherein said reconditioning step comprises returning at least a part of said recovered acid to said solution. 46. The process according to claim 33, wherein glucose in said solution is separately enzymatically isomerized in the process. 47. The process according to claim 31, wherein glucose in said solution is sequentially enzymatically isomerized. 48. The process according to claim 9, wherein said carrier comprises a weakly basic anion exchanger containing diethylaminoethyl (DEAE) modified cellulose adherently bound by agglomeration with polystyrene. ing water insoluble matrices, having amino groups and being selected from the group consisting of test tubes, microtiter plates, microscope slides, beads, membranes, resins, and filters, with a cyclobutene carboxylic acid derivative, selected from the group consisting of cyclobutene carboxylic acid diester, cyclobutene carboxylic acid halide, cyclobutene carboxylic acid ester halide, cyclobutene carboxylic acid dialkoxyester, and cyclobutene carboxylic acid imidazole, as an activating compound in methanol in the presence of triethylamine to form active matrices with active groups; b) dissolving a protein containing at least one primary or secondary amino group and adding the protein to the activated matrices; c) incubating the activated matrices and the protein of step b) at a pH of 7-10 and a temperature of +4° C. to +60° C. in an aqueous buffer system, free of primary and secondary amines, to thereby immobilize the protein of step b) on the matrices. 2. A method according to claim 1, further including the steps of: d) reacting the matrices of step c) with a cyclobutene carboxylic acid derivative, selected from the group consisting of cyclobutene carboxylic acid diester, cyclobutene carboxylic acid halide, cyclobutene carboxylic acid ester halide, cyclobutene carboxylic acid dialkoxyester, and cyclobutene carboxylic acid imidazole, as an activating compound in methanol in the presence of triethylamine to reactivate the matrices with active groups; e) dissolving a protein containing at least one primary or secondary amino group and adding the protein to the reactivated matrices of step d); f) incubating the reactivated matrices and the protein of step e) at a pH of 7-10 and a temperature of +4° C. to +60° C. in an aqueous buffer system, free of primary and secondary amines, to thereby immobilize the compound of step e) at the active groups of the reactivated matrices. 3. A method according to claim 1, wherein the matrices consist of cellulose, polystyrene, polypropylene, polycarbonate or glass. 4. A method according to claim 1, further including the step of reacting the product of step c), having unreacted active groups, with a low molecular weight compound, having active amino groups and containing positively charged, negatively charged, hydrophobic, hydrophilic or amphipathic groups, in an aqueous buffer system, free of primary and secondary amines, at a pH of 7-10 for modulating the biochemical, immunochemical or enzymatic reaction or activity of the matrices. 5. A method for immobilizing biornolecules and affinity ligands, said method comprising the steps of: a) dissolving a protein containing at least one primary or a secondary amino group; b) reacting the protein of step a) with a cyclobutene carboxylic acid derivative, selected from the group consisting of cyclobutene carboxylic acid diester, cyclobutene carboxylic acid halide, cyclobutene carboxylic acid ester halide, cyclobutene carboxylic acid dialkoxyester, and cyclobutene carboxylic acid imidazole, in methanol in the presence of triethylamine; c) adding the product of step b) to water insoluble matrices, having amino groups and being selected from the group consisting of test tubes, microtiter plates, microscope slides, beads, membranes, resins, and filters; d) incubating the matrices and the product of step b) at a pH of 7-10 and a temperature of +4° C. to +60° C. in an aqueous buffer system, free of primary and secondary amines, to thereby immobilize the compound of step a) on the matrices. 6. A method according to claim 5, further including the steps of: e) reacting the matrices of step d) with a cyclobutene carboxylic acid derivative, selected from the group consisting of cyclobutene carboxylic acid diester, cyclobutene carboxylic acid halide, cyclobutene carboxylic acid ester halide, cyclobutene carboxylic acid dialkoxyester, and cyclobutene carboxylic acid imidazole, as an activating compound in methanol in the presence of triethyl