WO2023039625A1 - Capteurs colorimétriques permettant la détection de contaminants chimiques et biologiques - Google Patents
Capteurs colorimétriques permettant la détection de contaminants chimiques et biologiques Download PDFInfo
- Publication number
- WO2023039625A1 WO2023039625A1 PCT/AU2021/051069 AU2021051069W WO2023039625A1 WO 2023039625 A1 WO2023039625 A1 WO 2023039625A1 AU 2021051069 W AU2021051069 W AU 2021051069W WO 2023039625 A1 WO2023039625 A1 WO 2023039625A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- colorimetric sensor
- cooh
- phospholipid
- target analyte
- formulation
- Prior art date
Links
- 238000001514 detection method Methods 0.000 title claims abstract description 52
- 239000000126 substance Substances 0.000 title abstract description 17
- 239000000356 contaminant Substances 0.000 title abstract description 13
- LLCSWKVOHICRDD-UHFFFAOYSA-N buta-1,3-diyne Chemical group C#CC#C LLCSWKVOHICRDD-UHFFFAOYSA-N 0.000 claims abstract description 121
- 239000000203 mixture Substances 0.000 claims abstract description 116
- 238000009472 formulation Methods 0.000 claims abstract description 83
- 238000000034 method Methods 0.000 claims abstract description 72
- 229920000642 polymer Polymers 0.000 claims abstract description 10
- 229920000015 polydiacetylene Polymers 0.000 claims description 259
- 239000002502 liposome Substances 0.000 claims description 224
- 150000003904 phospholipids Chemical class 0.000 claims description 137
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 101
- 239000000178 monomer Substances 0.000 claims description 101
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 90
- 239000012491 analyte Substances 0.000 claims description 88
- 239000002904 solvent Substances 0.000 claims description 67
- 230000008859 change Effects 0.000 claims description 64
- 239000000499 gel Substances 0.000 claims description 52
- 230000015572 biosynthetic process Effects 0.000 claims description 50
- 235000012000 cholesterol Nutrition 0.000 claims description 45
- 241000894006 Bacteria Species 0.000 claims description 39
- 239000000017 hydrogel Substances 0.000 claims description 36
- 235000013305 food Nutrition 0.000 claims description 35
- 239000000523 sample Substances 0.000 claims description 35
- 239000003228 hemolysin Substances 0.000 claims description 34
- 239000003053 toxin Substances 0.000 claims description 32
- 231100000765 toxin Toxicity 0.000 claims description 30
- 108700012359 toxins Proteins 0.000 claims description 30
- -1 poly(vinyl alcohol) Polymers 0.000 claims description 19
- 229920000936 Agarose Polymers 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 230000004044 response Effects 0.000 claims description 17
- 239000010409 thin film Substances 0.000 claims description 17
- 239000010408 film Substances 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 15
- 235000021588 free fatty acids Nutrition 0.000 claims description 15
- 230000036571 hydration Effects 0.000 claims description 15
- 238000006703 hydration reaction Methods 0.000 claims description 15
- 238000002347 injection Methods 0.000 claims description 15
- 239000007924 injection Substances 0.000 claims description 15
- 239000000758 substrate Substances 0.000 claims description 15
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 11
- 238000012544 monitoring process Methods 0.000 claims description 10
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 claims description 9
- 239000011159 matrix material Substances 0.000 claims description 9
- 230000035945 sensitivity Effects 0.000 claims description 9
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 8
- 229940072056 alginate Drugs 0.000 claims description 8
- 235000010443 alginic acid Nutrition 0.000 claims description 8
- 229920000615 alginic acid Polymers 0.000 claims description 8
- 125000002091 cationic group Chemical group 0.000 claims description 8
- 239000011521 glass Substances 0.000 claims description 8
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 8
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 7
- 230000001580 bacterial effect Effects 0.000 claims description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims description 6
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 239000000123 paper Substances 0.000 claims description 6
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- PAZGBAOHGQRCBP-DDDNOICHSA-N 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C/CCCCCCCC PAZGBAOHGQRCBP-DDDNOICHSA-N 0.000 claims description 5
- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical class NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 claims description 5
- 239000007853 buffer solution Substances 0.000 claims description 5
- 239000000976 ink Substances 0.000 claims description 5
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 5
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 5
- 229940067605 phosphatidylethanolamines Drugs 0.000 claims description 5
- 150000008106 phosphatidylserines Chemical class 0.000 claims description 5
- 125000002525 phosphocholine group Chemical class OP(=O)(OCC[N+](C)(C)C)O* 0.000 claims description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- 229920001661 Chitosan Polymers 0.000 claims description 4
- 244000007835 Cyamopsis tetragonoloba Species 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 4
- 230000009089 cytolysis Effects 0.000 claims description 4
- 239000005022 packaging material Substances 0.000 claims description 4
- 229920001277 pectin Polymers 0.000 claims description 4
- 239000001814 pectin Substances 0.000 claims description 4
- 235000010987 pectin Nutrition 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- MWRBNPKJOOWZPW-NYVOMTAGSA-N 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-NYVOMTAGSA-N 0.000 claims description 2
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 claims 2
- 239000012071 phase Substances 0.000 abstract description 12
- 239000007791 liquid phase Substances 0.000 abstract description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 60
- 230000008570 general process Effects 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- 238000003786 synthesis reaction Methods 0.000 description 43
- 235000013336 milk Nutrition 0.000 description 32
- 239000008267 milk Substances 0.000 description 32
- 210000004080 milk Anatomy 0.000 description 32
- 239000000243 solution Substances 0.000 description 31
- 239000000047 product Substances 0.000 description 28
- 239000012528 membrane Substances 0.000 description 21
- 125000000217 alkyl group Chemical group 0.000 description 20
- 150000002632 lipids Chemical class 0.000 description 17
- 244000052769 pathogen Species 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 12
- 241000191967 Staphylococcus aureus Species 0.000 description 10
- 230000001717 pathogenic effect Effects 0.000 description 10
- 208000031462 Bovine Mastitis Diseases 0.000 description 9
- 235000013350 formula milk Nutrition 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 238000003860 storage Methods 0.000 description 9
- DIEDVCMBPCRJFQ-UHFFFAOYSA-N 10,12-tricosadiynoic acid Chemical compound CCCCCCCCCCC#CC#CCCCCCCCCC(O)=O DIEDVCMBPCRJFQ-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000004215 Carbon black (E152) Substances 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- IQQJOZKPAQNXRX-UHFFFAOYSA-N henicosa-8,10-diynoic acid Chemical compound CCCCCCCCCCC#CC#CCCCCCCC(O)=O IQQJOZKPAQNXRX-UHFFFAOYSA-N 0.000 description 8
- RGDYQXRADMTROD-UHFFFAOYSA-N heptadeca-4,6-diynoic acid Chemical compound CCCCCCCCCCC#CC#CCCC(O)=O RGDYQXRADMTROD-UHFFFAOYSA-N 0.000 description 8
- RPTNONNBJKKVEV-UHFFFAOYSA-N hexadeca-5,7-diynoic acid Chemical compound CCCCCCCCC#CC#CCCCC(O)=O RPTNONNBJKKVEV-UHFFFAOYSA-N 0.000 description 8
- 229930195733 hydrocarbon Natural products 0.000 description 8
- 238000010348 incorporation Methods 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 208000004396 mastitis Diseases 0.000 description 8
- STCGDIJOEZNVHP-UHFFFAOYSA-N nonadeca-6,8-diynoic acid Chemical compound CCCCCCCCCCC#CC#CCCCCC(O)=O STCGDIJOEZNVHP-UHFFFAOYSA-N 0.000 description 8
- WNNYSRHBDYRXCH-UHFFFAOYSA-N octadeca-10,12-diynoic acid Chemical compound CCCCCC#CC#CCCCCCCCCC(O)=O WNNYSRHBDYRXCH-UHFFFAOYSA-N 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 238000004806 packaging method and process Methods 0.000 description 8
- ZPUDRBWHCWYMQS-UHFFFAOYSA-N pentacosa-10,12-diynoic acid Chemical compound CCCCCCCCCCCCC#CC#CCCCCCCCCC(O)=O ZPUDRBWHCWYMQS-UHFFFAOYSA-N 0.000 description 8
- ISQNNNPGHIZKAR-UHFFFAOYSA-N tricosa-6,8-diynoic acid Chemical compound C(CCCCC#CC#CCCCCCCCCCCCCCC)(=O)O ISQNNNPGHIZKAR-UHFFFAOYSA-N 0.000 description 8
- 125000003342 alkenyl group Chemical group 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 230000007704 transition Effects 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 229920006008 lipopolysaccharide Polymers 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 101710092462 Alpha-hemolysin Proteins 0.000 description 5
- 101710179002 Hemolytic toxin Proteins 0.000 description 5
- 244000052616 bacterial pathogen Species 0.000 description 5
- 239000000090 biomarker Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000007613 environmental effect Effects 0.000 description 5
- 239000003925 fat Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000004627 transmission electron microscopy Methods 0.000 description 5
- 101710164436 Listeriolysin O Proteins 0.000 description 4
- 238000003917 TEM image Methods 0.000 description 4
- 238000007259 addition reaction Methods 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 230000002949 hemolytic effect Effects 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000004310 lactic acid Substances 0.000 description 4
- 235000014655 lactic acid Nutrition 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000000527 sonication Methods 0.000 description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 description 4
- 238000001429 visible spectrum Methods 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000002296 dynamic light scattering Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000031700 light absorption Effects 0.000 description 3
- 230000004130 lipolysis Effects 0.000 description 3
- 235000013372 meat Nutrition 0.000 description 3
- 238000001000 micrograph Methods 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000003495 polar organic solvent Substances 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000005057 refrigeration Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical group SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108010006464 Hemolysin Proteins Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000004847 absorption spectroscopy Methods 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000012062 aqueous buffer Substances 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 239000006161 blood agar Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 125000004982 dihaloalkyl group Chemical group 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 239000010794 food waste Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 244000144980 herd Species 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 125000006682 monohaloalkyl group Chemical group 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 125000004385 trihaloalkyl group Chemical group 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- 239000000304 virulence factor Substances 0.000 description 2
- 230000007923 virulence factor Effects 0.000 description 2
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 1
- 101710197219 Alpha-toxin Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010073306 Exposure to radiation Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 101710124951 Phospholipase C Proteins 0.000 description 1
- 101000606032 Pomacea maculata Perivitellin-2 31 kDa subunit Proteins 0.000 description 1
- 101000606027 Pomacea maculata Perivitellin-2 67 kDa subunit Proteins 0.000 description 1
- 241000589970 Spirochaetales Species 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 239000002776 alpha toxin Substances 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 235000010633 broth Nutrition 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 239000011111 cardboard Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 235000016213 coffee Nutrition 0.000 description 1
- 235000013353 coffee beverage Nutrition 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 229920000547 conjugated polymer Polymers 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 125000006001 difluoroethyl group Chemical group 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000002095 exotoxin Substances 0.000 description 1
- 231100000776 exotoxin Toxicity 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000005817 fluorobutyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000021485 packed food Nutrition 0.000 description 1
- 239000011087 paperboard Substances 0.000 description 1
- 238000006552 photochemical reaction Methods 0.000 description 1
- 238000012123 point-of-care testing Methods 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001690 polydopamine Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 235000015067 sauces Nutrition 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 230000003201 sucrolytic effect Effects 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000012855 volatile organic compound Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000000733 zeta-potential measurement Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D4/00—Coating compositions, e.g. paints, varnishes or lacquers, based on organic non-macromolecular compounds having at least one polymerisable carbon-to-carbon unsaturated bond ; Coating compositions, based on monomers of macromolecular compounds of groups C09D183/00 - C09D183/16
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F138/00—Homopolymers of compounds having one or more carbon-to-carbon triple bonds
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
- G01N33/5432—Liposomes or microcapsules
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/49—Phosphorus-containing compounds
- C08K5/51—Phosphorus bound to oxygen
- C08K5/52—Phosphorus bound to oxygen only
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L49/00—Compositions of homopolymers or copolymers of compounds having one or more carbon-to-carbon triple bonds; Compositions of derivatives of such polymers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/02—Food
- G01N33/025—Fruits or vegetables
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/02—Food
- G01N33/04—Dairy products
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/02—Food
- G01N33/12—Meat; Fish
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/02—Food
- G01N33/14—Beverages
Definitions
- the present disclosure generally relates to a colorimetric sensor formulation for the detection of chemical and biological contaminants both in liquid phase and vapour phase.
- the present disclosure generally relates to a colorimetric sensor formulation comprising a diacetylene polymer composition, and methods for detection of a chemical and biological contaminant using such formulations, including various applications thereof.
- Bacterial infections have a large impact on health. Many potentially infectious bacteria can survive on surfaces for considerable amounts of time, and they can be transmitted to humans through air, water, food, or living vectors. The ability to detect infectious bacteria in the environment easily and quickly without the need of specialised high-cost equipment is critical to improve the health being of the general public.
- Polydiacetylene is a conjugated polymer that has been identified as a building block for the construction of colorimetric biosensors for the detection of pathogens.
- PDA is constructed from amphiphilic diacetylene monomers that selfassemble into vesicles in aqueous solution. These vesicles can be photopolymerised with 254 nm UV light via an addition reaction between diacetylene groups on neighbouring monomers. This produces a conjugated network that is responsible for the unique optical properties of PDA.
- PDA vesicles can be functionalised to detect an array of different analytes via incorporation of recognition elements into or onto the vesicle membrane.
- Chemical recognition of analytes or stimulus from environmental sources such as temperature or force can induce structural perturbations in the PDA membrane. This results in a change of the effective conjugation length and a shift in the characteristic maximum absorbance from 640 nm to 540 nm which corresponds to a visible blue to red colour change.
- the present disclosure is directed to a colorimetric sensor formulation, the process for preparing such a formulation, and use thereof, which may at least partially overcome at least one of the abovementioned disadvantages or provide the consumer with a useful or commercial choice.
- a colorimetric sensor formulation for detection of a target analyte comprising: i) a polydiacetylene composition comprising at least one diacetylene monomer of Formula 1
- R 1 is selected from Ci-20-alkyl or C2-20- alkenyl
- R 2 is selected from Ci-20-alkyl-COOH or C2-20-alkenyl-COOH, in which each Ci-20-alkyl-COOH or C2-io-alkenyl-COOH are optionally substituted (for example optionally substituted with at least one NH2, SH, or a mixture thereof); n is an integer of 1-5; and
- the at least one phospholipid molecule is incorporated into the polydiacetylene composition to form a polydiacetylene liposome comprising a recognition element;
- the recognition element is the phospholipid molecule and has a binding affinity for the target analyte; and - the polydiacetylene liposome exhibits a colour change when contacted with the target analyte.
- R 1 may be selected from Ci-20-alkyl.
- R 2 may be selected from Ci-20-alkyl-COOH.
- n may be 1 or 2.
- R 1 may be selected from Ci-14-alkyl;
- R 2 may be selected from Ci-s-alkyl- COOH; and
- n may be 1 or 2.
- R 1 may be selected from: pentadecyl, tetradecyl, tridecyl, dodecyl, undecyl, decyl, nonyl, octyl, heptyl, hexyl, pentyl, butyl or propyl.
- R 2 may be selected from: octyl-COOH, heptyl-COOH, hexyl-COOH, pentyl-COOH, butyl-COOH, propyl-COOH, ethyl-COOH or methyl-COOH.
- R 1 may be selected from: tetradecyl, decyl, octyl, or pentyl;
- R 2 may be selected from octyl-COOH, hexyl-COOH, butyl-COOH, propyl-COOH or ethyl-COOH; and
- n may be 1.
- the phospholipid may be selected from: phosphocholines, phosphoethanolamines, phosphatidylethanolamines, phosphatidylserines, phosphatidylglycerols, and combinations thereof.
- the phospholipid may be selected from: l,2-dimyristoyl-sn-glycero-3 -phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero- 3 -phosphocholine (DOPC), l-pahmtoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), l,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), l -pahnitoyl-2-olcoyl-.w- glycero-3-phospho-(l'-rac-glycerol) (POPG).
- the phospholipid may be 1,2- dimyristoyl-sn-glycer
- the polydiacetylene liposome may be unilamellar. In an embodiment, the polydiacetylene liposome may not encapsulate a probe.
- the ratio of the diacetylene monomer : phospholipid may be in a range between about 1:1 to about 10:1.
- the ratio of the diacetylene monomer : phospholipid may be about 3 :2 or about 4: 1.
- the ratio of the diacetylene monomer : phospholipid may be about 4:1.
- the colorimetric sensor formulation may further comprise cholesterol incorporated into the polydiacetylene liposome to detect the target analyte.
- the ratio of diacetylene monomer : phospholipid : cholesterol may be in a range between about 1:1:1 to about 10:1:1.
- the ratio of diacetylene monomer : phospholipid : cholesterol may be 5:2:3 or about 5:2:3.
- the polydiacetylene liposome may be dispersed in an aqueous solution.
- the aqueous solution may be selected from water or a buffer system.
- the pH of the aqueous solution may be in a range of between about 6 and 8.
- the polydiacetylene liposome may be coated on a substrate or incorporated into a matrix.
- the substrate may be selected from: glass, gels, films and paper, and the matrix may be selected from: ink, gels, films and packaging material.
- the colorimetric sensor formulation may further comprise a gel carrier for formation of a solid reservoir.
- the polydiacetylene liposome may be in the form of a hydrogel disc.
- the solid reservoir may encapsulate a perishable consumable product to provide a quality tag for contactless monitoring of food.
- the gel carrier is a crosslinkable polymer.
- the gel carrier may be selected from: agarose, alginate, poly(vinyl alcohol), pectin, carboxy methyl cellulose, hyaluronates, chitosan, cationic guar, cationic starch, or combinations thereof.
- the gel carrier may be selected from: agarose, alginate, poly(vinyl alcohol), or combinations thereof.
- the gel carrier may be agarose.
- the polydiacetylene liposome may be prepared using a thin-film hydration method or a solvent injection method.
- the colorimetric sensor formulation may have a detection limit of at least 3 pg/mL and may be capable of detecting the target analyte at concentrations of less than about 25 pg/mL.
- the target analyte may be bacteria, directly detected or detected through the emitted toxins.
- the target analyte may be food spoilage bacteria and/or metabolic bacteria.
- a colorimetric sensor system for detection of a target analyte comprising:
- a colorimetric sensor system for detection of a target analyte comprising:
- a colorimetric sensor kit comprising one or more vessels, wherein each of the one or more vessels comprises a colorimetric sensor formulation according to any one or more embodiments or examples thereof as described herein to detect a specific target analyte.
- the one or more vessels may be a two-part vessel system to enable the colorimetric sensor formulation to be separated from a target analyte until ready for use.
- a colorimetric sensor tag for detection of a target analyte comprising the colorimetric sensor formulation of any one or more embodiments or examples thereof as described herein in the form of a hydrogel, wherein the hydrogel encapsulates a perishable consumable product to provide the tag for contactless monitoring of food.
- the colorimetric sensor tag may be configured to be attached to an article.
- a method for detection of a target analyte comprising: a) obtaining a colorimetric sensor formulation according to any one or more embodiments or examples thereof as described herein, or a colorimetric sensor system according to any one or more embodiments or examples thereof as described herein, or a colorimetric sensor kit according to any one or more embodiments or examples thereof as described herein; b) contacting the colorimetric sensor with a sample suspected of containing a target analyte; and c) observing a colour change if the target analyte is present.
- the target analyte may be bacteria, directly detected or detected through the emitted toxins.
- the target analyte may be a-hemolysin.
- a method for detection of a target analyte comprising: al) obtaining a colorimetric sensor tag according to any one or more embodiments or examples thereof as described herein; and bl) observing a colour change if the target analyte is present.
- the target analyte may be a product of bacterial lysis such as free fatty acid.
- the observable colour change may occur in less than about 60 minutes of contacting the sensor with the sample suspected of containing an target analyte.
- the observable colour change may occur in real-time.
- an article comprising: a colorimetric sensor according to any one or more embodiments or examples thereof as described herein, or a colorimetric sensor tag according to any one or more embodiments or examples thereof as described herein; and a perishable consumable product.
- Figure 2 is a TEM micrograph of PDA/DMPC particles formed via the solvent injection method.
- Figure 4 is a series of TEM micrographs of PDA particles (a) before and (b) after the addition of 12.5 pg/mL of a-hemolysin and of PDA/DMPC/Chol particles (c) before and (d) after the addition of 12.5 pg/mL of a-hemolysin.
- Figure 5 is a) digital colorimetric response and c), e) photographs of PDA/DMPC vesicles in refrigerated and unrefrigerated milk vs storage time, b) Digital colorimetric response and d), f) photographs of PDA/DMPC/agarose/milk gels both refrigerated and unrefrigerated vs storage time.
- Figure 6 is a) digital colorimetric response and c) photographs of dehydrated gels in refrigerated and unrefrigerated milk vs storage time, b) Digital colorimetric response and d) photographs of rehydrated gels both refrigerated and unrefrigerated vs storage time.
- Diacetylene monomers are the building blocks of polydiacetylenes which can be used to construct colorimetric biosensors.
- the PDA is chromatically robust and does not exhibit chromatic responses (false positives) in the reaction to a stimulus to which it is likely to be exposed to such as changes to milk composition and temperature fluctuations. It has been shown that the sensing features of a PDA can be tuned by manipulation of the structure of the monomers. The inventors have unexpectedly shown that changing the total alkyl chain length and the positioning of the diacetylene functional group can impact thermochromism and the chromatic response to a range of analytes.
- One or more advantages provided by the present disclosure is that relocating the diacetylene group of the diacetylene monomer towards the carboxylic acid head group may reduce its chromatic response to fluctuations in temperature and its chemical environment by increasing its association with strong hydrogen bonding on the carboxylic acid head groups of the membrane, stabilising the PDA’s conjugation. This effect may be desirable for point of care testing in complex samples.
- alkyl refers to a straight-chained or branched saturated monovalent hydrocarbon radical, wherein the alkyl may optionally be substituted. Unless otherwise indicated, the alkyl groups typically contain from 1 to 20 carbon atoms. The term “alkyl” also encompasses both linear and branched alkyl, unless otherwise specified.
- the alkyl is a linear saturated monovalent hydrocarbon radical that has 1 to 20 (Ci-20), 1 to 16 (Ci-ie), 1 to 14 (Ci-14), 1 to 12 (Ci-12), 1 to 10 (Ci- 10), 1 to 8 (C1-8), or 1 to 6 (C1-6) carbon atoms, or branched saturated monovalent hydrocarbon radical of 3 to 20 (C3-20), 3 to 16 (C3-16), 3 to 14 (C3-14), 3 to 12 (C3-12), 3 to 10 (C3-10), 3 to 8 (C3-8), or 3 to 6 (C3-6) carbon atoms.
- alkyl as used herein, may include, but are not limited to optionally substituted: methyl, ethyl, propyl, (including all isomeric forms), n-propyl, isopropyl, butyl, (including all isomeric forms), n-butyl, isobutyl, sec-butyl, /-butyl, (including all isomeric forms), and hexyl (including all isomeric forms), and the like.
- alkyl may include optionally substituted: pentadecyl, tetradecyl, tridecyl, dodecyl, undecyl, decyl, nonyl, octyl, heptyl, hexyl, pentyl, butyl or propyl.
- alkyl groups may be mono- or polyvalent.
- the alkyl groups may be optionally substituted and/or optionally interrupted by one or more heteroatoms.
- the alkyl groups may be referred to as “-alkyl” in relation to use as a bivalent or polyvalent linking group.
- alkenyl refers to a straight-chained or branched monovalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, four, or five, in another embodiment, one, carbon-carbon double bond(s). The alkenyl may be optionally substituted.
- alkenyl also embraces radicals having “czs” and “trans” configurations, or alternatively, “Z” and “E” configurations, as appreciated by those of ordinary skill in the art.
- alkenyl encompasses both linear and branched alkenyl, unless otherwise specified.
- C2-6 alkenyl refers to a linear unsaturated monovalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated monovalent hydrocarbon radical of 3 to 6 carbon atoms.
- the alkenyl is a linear monovalent hydrocarbon radical of 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2-6) carbon atoms, or a branched monovalent hydrocarbon radical of 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3- 10), or 3 to 6 (C3-6) carbon atoms.
- alkenyl groups include, but are not limited to optionally substituted: ethenyl, propen- 1-yl, propen-2-yl, allyl, butenyl, and 4- methylbutenyl.
- carboxyl represents a -CO2H moiety.
- halo or halogen, whether employed alone or in compound words such as haloalkyl, means fluorine, chlorine, bromine or iodine.
- hydroxyl represents a -OH moiety.
- haloalkyl means an alkyl group having at least one halogen substituent, the terms “alkyl” and “halogen” being understood to have the meanings outlined above.
- dihaloalkyl means an alkyl group having two halogen substituents
- trihaloalkyl means an alkyl group having three halogen substituents.
- Examples of monohaloalkyl groups include fluoromethyl, chloromethyl, bromomethyl, fluoromethyl, fluoropropyl and fluorobutyl groups; examples of dihaloalkyl groups include difluoromethyl and difluoroethyl groups; examples of trihaloalkyl groups include trifluoromethyl and trifluoroethyl groups.
- amino represents an -NH2 moiety
- alkylamino represents an -NHR or -NR2 group in which R is an alkyl group as defined supra. Examples include, without limitation, methylamino, ethylamino, n-propylamino, isopropylamino, and the different butylamino, pentylamino, hexylamino and higher isomers.
- thiol refers to any organosulphur group containing a sulphurhydryl moiety -SH, which includes a R-SH group where R is a moiety containing a carbon atom for coordination to the -SH moiety, for example an alkylsulphur group as defined supra.
- the thiol or mercapto group may be a sulphurhydryl moiety -SH.
- optionally substituted means that a functional group is either substituted or unsubstituted, at any available position.
- substituted as referred to above or herein may include, but is not limited to, groups or moieties such as halogen, hydroxyl, alkyl, amino, thiol, thio, mercapto, mercaptan, or haloalkyl.
- biological and chemical contaminant(s) refers to any material that can be detected by the colorimetric sensor of the present disclosure, for example, on surfaces, in water, food (e.g. milk, juice, meat, protein powder, baby powder, etc.), and the indoor air environment.
- materials include, but are not limited to, small molecules, pathogenic and non-pathogenic organisms, toxins, membrane receptors and fragments, volatile organic compounds, enzymes and enzyme substrates, antibodies, antigens, proteins, peptides, nucleic acids, and peptide nucleic acids.
- Target analyte refers to the material targeted for detection by the colorimetric sensor of the present disclosure, and may include, but are not limited to, microorganisms (bacteria, directly detected or detected through the emitted toxins or through their DNA, and viruses), free fatty acids, lactic acid, antibacterial and antiviral peptides.
- the “target analyte” is bacteria directly detected or detected through the emitted toxins.
- the colorimetric sensor advantageously allows selective detection of a- hemolysin, a hemolytic toxin excreted by Staphylococcus aureus.
- the colorimetric sensor advantageously allows selective detection of free fatty acids, a marker from fat rancidification by bacterial lipolysis of various perishable consumer products (e.g. milk, juice, meat, protein powder, baby powder, etc.).
- bacteria refers to all forms of microorganisms considered to be bacteria including, but not limited to, cocci, bacilli, spirilla, spirochetes, spheroplasts, protoplasts.
- bacteria as used herein, may refer to food spoilage bacteria and/or metabolic bacteria, and may include, but not limited to, proteolytic bacteria, lypolytic bacteria, and sucrolytic bacteria.
- the bacteria may be Staphylococcus aureus.
- phospholipid refers to any phospholipid molecule or assembly of phospholipid molecules with an affinity for a target contaminant and/or a probe. It will be appreciated that the phospholipid may be the recognition element.
- the terms “assembly,” or “self-assembly,” refers to any selfordering of diacetylene molecules and phospholipids prior to polymerisation.
- polydiacetylene liposome describes a spherical vesicle capable of turning a recognition event such as a covalent bond or a noncovalent interaction (e.g. electrostatic interaction, polar interaction, van der Waals forces) at the molecular level into an observable signal (e.g. blue to red colour transition).
- a recognition event such as a covalent bond or a noncovalent interaction (e.g. electrostatic interaction, polar interaction, van der Waals forces) at the molecular level into an observable signal (e.g. blue to red colour transition).
- Probe refers to a constituent that is capable of interacting with the target contaminant and/or the phospholipid. Accordingly, the probe is a type of “detectable binding reagent” i.e. an agent that specifically recognises and interacts or binds with an contaminant (i.e. the target analyte) and/or the phospholipid, wherein the probe has a property permitting detection when bound and is encapsulated by the colorimetric sensor (i.e. polydiacetylene vesicle).
- the colorimetric sensor i.e. polydiacetylene vesicle
- detectable binding agent physically interacts with the target contaminant or phospholipid to the substantial exclusion of other contaminants also present in the sample.
- the binding of a detectable binding reagent useful according to the present disclosure has stability permitting the measurement of the binding.
- covalent bond refers to the linkage of two atoms by the sharing of two electrons, one contributed by each of the atoms.
- the term “absorption” refers, in one sense, to the absorption of light. Light is absorbed if it is not reflected from or transmitted through the colorimetric sensor, as described herein. Sensors that appear coloured have selectively absorbed all wavelengths of white light except for those corresponding to the visible colours that are seen.
- the term “spectrum” refers to the distribution of light energies arranged in order of wavelength.
- visible spectrum refers to light radiation that contains wavelengths from approximately 360 nm to approximately 800 nm.
- UV irradiation refers to exposure to radiation with wavelengths less than that of visible light (i.e. less than approximately 360 nm) but greater than that of X-rays (i.e. greater than approximately 0.1 nm). UV radiation possesses greater energy than visible light and is therefore, more effective at inducing photochemical reactions.
- chromatic transition refers to the changes of molecules or material that result in an alteration of visible light absorption.
- chromatic transition refers to the change in light absorption of the colorimetric sensor, as described herein, whereby there is a detectable colour change associated with the transition. This detection can be accomplished through various means including, but not limited to, visual observation and spectrophotometry.
- substrate refers to a solid object or surface upon which the colorimetric sensor is layered or attached.
- Substrates include, but are not limited to, glass, gels, and filter paper, among others.
- the term “formation solvent” refers to any medium, although typically a volatile organic solvent, used to solubilise and distribute material to a desired location (e.g. to a surface for producing a film or to a drying receptacle to deposit the polydiacetylene liposome, as described herein, for drying).
- the term “tag” refers to any device that is portable and may be attached to an article (e.g. food packaging).
- article refers to any type of food packaging.
- the food packaging may be made of, but not limited to, paper and paperboard, rigid plastic and glass.
- the term “device” refers to any apparatus that may or may not be portable, and used as a means of colorimetric detection.
- the terms “positive”, “negative”, and “zwitterionic charge” refer to molecules or molecular groups that contain a net positive, negative, or neutral charge, respectively. Zwitterionic entities contain both positively and negatively charged atoms or groups whose charges cancel (i.e. whose net charge is 0).
- zn situ refers to processes, events, objects, or information that are present or take place within the context of their natural environment.
- aqueous refers to a liquid mixture containing water, among other components.
- the present disclosure relates to colorimetric polydiacetylene sensor formulation for the detection of chemical and biological contaminants both in liquid phase and vapour phase.
- the diacetylene compounds of the present disclosure can self-assemble in solution to form ordered vesicles that can be polymerised using any actinic radiation such as, for example, electromagnetic radiation in the UV or visible range of the electromagnetic spectrum.
- the polymerisation of the diacetylene compounds result in polymerisation reaction products that have a colour in the visible spectrum less than about 540 nanometers (nm).
- the polymerisation of the diacetylene compounds result in polymerisation reaction products that have a colour in the visible spectrum at least about 640 nm.
- the polymerisation of the diacetylene compounds result in polymerisation reaction products that have a colour in the visible spectrum may be in a range of between about 540 nm and about 640 nm. It will be appreciated that the colour of the diacetylene compounds and their polymerisation products will depend on their conformation and exposure to external factors.
- polymerisation of the diacetylene compounds, as disclosed herein result in meta-stable blue phase polymer networks that include a polydiacetylene backbone. These meta-stable blue phase polymer networks undergo a colour change from bluish to reddish-orange upon exposure to external factors such as heat, a change in solvent or counter ion, if available, or physical stress, for example.
- the ability of the diacetylene compounds and their polymerisation products disclosed herein to undergo a visible colour change upon exposure to physical stress make them ideal candidates for the preparation of sensing devices for detection of a target analyte.
- the polydiacetylene (PDA) vesicles can be functionalised to detect an array of different target analytes via incorporation of recognition elements into or onto the vesicle membrane.
- Chemical recognition of analytes and/or stimulus from environmental sources such as temperature or force can induce structural perturbations in the PDA membrane. This results in a change of the effective conjugation length and a shift in the characteristic maximum absorbance from 640 nm to 540 nm which corresponds to a visible blue to red colour change.
- the colorimetric sensor formulation may comprise diacetylene monomers and phospholipids that can detect bacteria using: a direct method wherein bacteria or their toxins interact with polydiacetylene/phospholipids and induce structural perturbations in polydiacetylene, leading to colorimetric changes from blue to red; and/or an indirect method wherein the by-products of bacteria metabolism, for example lactic acid or ammonia gas, react with chemically-modified polydiacetylene, and induce structural perturbations in polydiacetylene, leading to colorimetric changes from blue to red.
- a direct method wherein bacteria or their toxins interact with polydiacetylene/phospholipids and induce structural perturbations in polydiacetylene, leading to colorimetric changes from blue to red
- an indirect method wherein the by-products of bacteria metabolism, for example lactic acid or ammonia gas, react with chemically-modified polydiacetylene, and induce structural perturbations in polydiacetylene, leading to colorimetric
- the present disclosure provides a colorimetric sensor formulation for detection of a target analyte comprising: i) a polydiacetylene composition comprising at least one diacetylene monomer of Formula 1
- R 1 is selected from Ci-20-alkyl or C2-20- alkenyl
- R 2 is selected from Ci-20-alkyl-COOH or C2-20-alkenyl-COOH, in which each Ci-20-alkyl-COOH or C2-io-alkenyl-COOH are optionally substituted; n is an integer of 1-5; and
- the at least one phospholipid molecule is incorporated into the polydiacetylene composition to form a polydiacetylene liposome comprising a recognition element;
- the recognition element is the phospholipid molecule and has a binding affinity for the target analyte
- the polydiacetylene liposome exhibits a colour change when contacted with the target analyte.
- the polydiacetylene liposome may be unilamellar. In an embodiment, the polydiacetylene liposome may not encapsulate a probe.
- the polydiacetylene liposome may be dispersed in an aqueous solution.
- the aqueous solution may be selected from water or a buffer system.
- the pH of the aqueous solution may be in a range of between about 6 and 8.
- the polydiacetylene liposome may be coated on a substrate or incorporated into a matrix.
- the substrate may be selected from: glass, gels, films and paper, and the matrix may be selected from: ink, gels, films and packaging material.
- the polydiacetylene liposome may be prepared using a thin-film hydration method or a solvent injection method.
- the colorimetric sensor formulation may have a detection limit of at least 3 pg/mL and may be capable of detecting the target analyte at concentrations of less than about 25 pg/mL.
- the target analyte may be bacteria, directly detected or detected through the emitted toxins.
- the target analyte may be food spoilage bacteria and/or metabolic bacteria.
- the bacteria may be hemolytic bacteria.
- the bacteria may be a-hemolytic bacteria.
- diacetylene monomers can be manipulated to tune the sensitivity, specificity, and chromism of PDAs.
- a monomer that forms a PDA that is resistant to environmental stimulus is desirable.
- R 1 may be Ci-20-alkyl or C2-20-alkenyl. In an embodiment is from C1-20- alkyl. In another embodiment Ri is C2-20-alkenyl.
- R 1 may be a Ci-14-alkyl.
- R 1 may be selected from: pentadecyl, tetradecyl, tridecyl, dodecyl, undecyl, decyl, nonyl, octyl, heptyl, hexyl, pentyl, butyl or propyl.
- R 1 may be selected from: tetradecyl, decyl, octyl, or pentyl.
- R 2 is a Ci-20-alkyl-COOH or C2-20-alkenyl-COOH, in which each C1-20- alkyl-COOH or C2-io-alkenyl-COOH are optionally substituted.
- R 2 is an optionally substituted Ci-20-alkyl-COOH.
- R 2 is an optionally substituted C2-20-alkenyl-COOH.
- R 2 may be an optionally substituted Ci-s-alkyl-COOH.
- R 2 may be selected from an optionally substituted: octyl-COOH, heptyl-COOH, hexyl-COOH, pentyl-COOH, butyl-COOH, propyl-COOH, ethyl-COOH or methyl- COOH.
- R 2 is unsubstituted. In another embodiment, R 2 is substituted, for example R 2 is a Ci-20-alkyl-COOH or C2-20-alkenyl-COOH substituted with at least one NH2, SH, or a mixture thereof. Integer “n”
- n may be 1, 2, 3, 4 or 5. In an embodiment, n may be 1 or 2. In an embodiment, n is 1. In another embodiment, n is 2.
- -R 1 is Ci-i4-alkyl
- R 2 is an optionally substituted Ci-s-alkyl-COOH
- n is 1 or 2;
- R 1 is: tetradecyl, decyl, octyl, or pentyl;
- R 2 is an optionally substituted: octyl- COOH, hexyl-COOH, butyl-COOH, propyl-COOH or ethyl-COOH; and
- n is 1.
- the diacetylene monomer may be selected from the group consisting of 6,8-tricosadiynoic acid, 4,6-heptadecadiynoic acid, 5,7- hexadecadiynoic acid, 10,12-octadecadiynoic acid, 6,8-nonadecadiynoic acid, 8,10- henicosadiynoic acid, 10,12-tricosadiynoic acid, 10,12-pentacosadiynoic acid, or combinations thereof.
- the PDA liposomes may comprise a recognition element.
- the PDA can be functionalized with different recognition elements to act as a colorimetric sensor for temperature, pH, mechanical stress, proteins, bacteria, viruses, and other important target analytes.
- the recognition element may be the phospholipid molecule and has a binding affinity for a target analyte. It has been found that incorporation of phospholipids into the PDA membranes may increase membrane flexibility and may also increase the chromatic sensitivity of PDA sensors in response to stimuli as it can allow easier conformational and structural changes around the diacetylene functional group.
- a phospholipid can be added to the polydiacetylene composition either prior to or after polymerisation. Upon polymerisation or thereafter, the phospholipid is effectively incorporated within the polymer network such that interaction of the phospholipid with a target analyte results in a visible colour change due to the perturbation of the conjugated diacetylene polymer backbone.
- the phospholipid may be physically mixed and dispersed among the polydiacetylene assembly.
- the phospholipid may be covalently bonded to the polydiacetylene assembly.
- the phospholipid may be selected from: phosphocholines, phosphoethanolamines, phosphatidylethanolamines, phosphatidylserines, phosphatidylglycerols, and combinations thereof.
- the phospholipid may be selected from: l,2-dimyristoyl-5n-glycero-3- phosphocholine (DMPC), 1 ,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1- pahmtoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1 ,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE), l-palmitoyl-2-oleoyl-5n-glycero-3-phospho-(l'-rac- glycerol) (POPG).
- the phospholipid may be l,2-dimyristoyl-5n-glycero-3- phosphocholine (DMPC).
- the colorimetric sensor formulation may further comprise cholesterol incorporated into the polydiacetylene liposome to detect the target analyte.
- pathogenic bacteria produce a large variety of toxins and virulence factors.
- Hemolytic bacteria are pathogenic bacteria that produce pore-forming toxins, ultimately resulting in cell death by necrosis or apoptosis.
- incorporation of phospholipid and cholesterol in the PDA membrane may allow the selective detection of alpha-hemolysin, a hemolytic toxin excreted by Staphylococcus aureus, a predominant causative pathogen of bovine mastitis.
- the ratio of diacetylene monomer : phospholipid : cholesterol may be in a range between about 1 : 1 : 1 to about 10:1:1.
- the ratio of diacetylene monomer : phospholipid : cholesterol may be 5:2:3 or about 5:2:3. It will be appreciated that the present disclosure may mimic the composition (or ratio) of phospholipid : cholesterol in biological cells which may vary greatly.
- the ratio of phospholipid : cholesterol may be in a range that occurs in a biological cell membranes to detect membrane active toxins (e.g. a-hemolysin). Hydrogel
- a hydrogel may serve as a solid reservoir for the colorimetric sensor, as described herein, to advantageously transform the sensor formulation into a polydiacetylene solid sensor or colorimetric sensor tag.
- the colorimetric sensor formulation may further comprise a gel carrier for formation of a solid reservoir.
- the polydiacetylene liposome may be in the form of a hydrogel disc.
- the solid reservoir may encapsulate a perishable consumable product to provide a quality tag for contactless monitoring of food.
- the gel carrier may be a crosslinkable polymer.
- the gel carrier may be selected from: agarose, alginate, poly(vinyl alcohol), pectin, carboxy methyl cellulose, hyaluronates, chitosan, cationic guar, cationic starch, or combinations thereof.
- the gel carrier may be selected from: agarose, alginate, poly(vinyl alcohol), or combinations thereof.
- the gel carrier may be agarose.
- the inventors have advantageously developed a colorimetric sensor formulation for the selective detection of pathogenic bacteria (e.g. a-hemolysin) in complex samples (e.g. perishable consumable products such as milk).
- pathogenic bacteria e.g. a-hemolysin
- complex samples e.g. perishable consumable products such as milk.
- POC point-of-care
- a colorimetric sensor formulation for detection of a target analyte may comprise: i) a polydiacetylene composition comprising at least one diacetylene monomer of Formula 1
- R 1 is selected from Ci-20-alkyl or C2-20- alkenyl
- R 2 is selected from Ci-20-alkyl-COOH or C2-20-alkenyl-COOH, in which each Ci-20-alkyl-COOH or C2-io-alkenyl-COOH are optionally substituted
- n is an integer of 1 to 5;
- the at least one phospholipid molecule is incorporated into the polydiacetylene composition to form a polydiacetylene liposome comprising a recognition element;
- the recognition element is the phospholipid molecule and has a binding affinity for the target analyte
- the polydiacetylene liposome exhibits a colour change when contacted with the target analyte.
- R 1 may be selected from Ci-20-alkyl.
- R 2 may be selected from an optionally substituted Ci-20-alkyl-COOH.
- n may be 1 or 2.
- R 1 may be selected from Ci-14-alkyl
- R 2 may be selected from optionally substituted Ci-s-alkyl-COOH
- n may be 1 or 2.
- R 1 may be selected from: pentadecyl, tetradecyl, tridecyl, dodecyl, undecyl, decyl, nonyl, octyl, heptyl, hexyl, pentyl, butyl or propyl.
- R 2 may be selected from optionally substituted: octyl-COOH, heptyl-COOH, hexyl-COOH, pentyl-COOH, butyl-COOH, propyl-COOH, ethyl-COOH or methyl-COOH.
- R 1 may be selected from: tetradecyl, decyl, octyl, or pentyl
- R 2 may be selected from optionally substituted: octyl-COOH, hexyl-COOH, butyl-COOH, propyl-COOH or ethyl-COOH
- n may be 1.
- the diacetylene monomer may be selected from the group consisting of 6,8-tricosadiynoic acid, 4,6-heptadecadiynoic acid, 5,7- hexadecadiynoic acid, 10,12-octadecadiynoic acid, 6,8-nonadecadiynoic acid, 8,10- henicosadiynoic acid, 10,12-tricosadiynoic acid, 10,12-pentacosadiynoic acid, or combinations thereof.
- the phospholipid may be selected from: phosphocholines, phosphoethanolamines, phosphatidylethanolamines, phosphatidylserines, phosphatidylglycerols, and combinations thereof.
- the phospholipid may be selected from: l,2-dimyristoyl-sn-glycero-3 -phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero- 3 -phosphocholine (DOPC), 1 -pahmtoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), l,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), l -pahnitoyl-2-olcoyl-.w- glycero-3-phospho-(l'-rac-glycerol) (POPG).
- the phospholipid may be l,2-dimyristoyl-sn-
- the polydiacetylene liposome may be unilamellar. In one embodiment, the polydiacetylene liposome does not encapsulate a probe.
- the ratio of the diacetylene monomer : phospholipid may be in a range between about 1:1 to about 10:1.
- the ratio of the diacetylene monomer : phospholipid may be about 3 :2 or about 4: 1.
- the ratio of the diacetylene monomer : phospholipid may be about 4:1.
- the ratio of diacetylene monomer : phospholipid : cholesterol may be in a range between about 1:1:1 to about 10:1:1.
- the ratio of diacetylene monomer : phospholipid : cholesterol may be about 5:2:3. It will be appreciated that the present disclosure may mimic the composition (or ratio) of phospholipid : cholesterol in biological cells which may vary greatly.
- the ratio of phospholipid : cholesterol may be in a range that occurs in a biological cell membranes to detect membrane active toxins (e.g. a-hemolysin).
- the polydiacetylene liposome may be dispersed in an aqueous solution.
- the aqueous solution may be selected from water or a buffer system.
- the buffer system may be phosphate-buffered saline (PBS) or 4-(2- hydroxyethyl)-l -piperazineethanesulfonic acid (HEPES).
- PBS phosphate-buffered saline
- HEPES 4-(2- hydroxyethyl)-l -piperazineethanesulfonic acid
- the pH of the aqueous solution may be in a range of between about 6 and 8.
- the polydiacetylene liposome may be coated on a substrate or incorporated into a matrix.
- the substrate may be selected from: glass, gels, films and paper, and the matrix may be selected from: ink, gels, films and packaging material.
- the polydiacetylene liposome may be prepared using a thin- film hydration method or a solvent injection method.
- the target analyte may be bacteria, directly detected or detected through the emitted toxins.
- the target analyte may be food spoilage bacteria and/or metabolic bacteria.
- the target analyte is a-hemolysin. It will be appreciated that pathogenic bacteria produce a large variety of toxins and virulence factors. Hemolytic bacteria are pathogenic bacteria that produce pore-forming toxins, ultimately resulting in cell death by necrosis or apoptosis.
- incorporation of phospholipid and cholesterol in the PDA membrane may allow the selective detection of a-hemolysin, a hemolytic toxin excreted by Staphylococcus aureus, a predominant causative pathogen of bovine mastitis.
- the colorimetric sensor formulation may have a detection limit of at least 3 pg/mL and may be capable of detecting the target analyte at concentrations of less than about 25 pg/mL.
- the colour change may be attributed to pore formation in the PDA membrane and lysis of the vesicles due to the action of the Staphylococcus aureus a-hemolysin. This can be evidenced by vesicle membrane destruction in transmission electron microscopy micrographs of PDA vesicles before and after incubation with the toxin.
- the specificity of the sensor may be demonstrated by discrimination between a-hemolysin and other toxins and biomarkers for mastitis.
- the inventors have custom-designed a PDA sensor for point-of-care application in bovine milk samples which can selectively detect a- hemolysin, a hemolytic toxin excreted by Staphylococcus aureus, a predominant causative pathogen of bovine mastitis, using the PDA-based sensor, as described herein.
- the inventors have advantageously developed a colorimetric sensor tag for contactless monitoring of complex samples (e.g. perishable consumable products such as milk).
- complex samples e.g. perishable consumable products such as milk.
- the colorimetric sensor may find particular use as quality indicators in food packaging that could improve food management.
- a colorimetric sensor formulation for detection of a target analyte comprising: i) a polydiacetylene composition comprising at least one diacetylene monomer of Formula 1
- R 1 is selected from Ci-20-alkyl or C2-20- alkenyl
- R 2 is selected from Ci-20-alkyl-COOH or C2-20-alkenyl-COOH, in which each Ci-20-alkyl-COOH or C2-io-alkenyl-COOH are optionally substituted;
- n is an integer of 1 to 5;
- the at least one phospholipid molecule is incorporated into the polydiacetylene composition to form a polydiacetylene liposome comprising a recognition element;
- the recognition element is the phospholipid molecule and has a binding affinity for the target analyte
- polydiacetylene liposome exhibits a colour change when contacted with the target analyte.
- R 1 may be selected from Ci-20-alkyl.
- R 2 may be selected from an optionally substituted Ci-20-alkyl-COOH.
- n may be 1 or 2.
- R 1 may be selected from Ci-14-alkyl
- R 2 may be selected from optionally substituted Ci-s-alkyl-COOH
- n may be 1 or 2.
- R 1 may be selected from: pentadecyl, tetradecyl, tridecyl, dodecyl, undecyl, decyl, nonyl, octyl, heptyl, hexyl, pentyl, butyl or propyl.
- R 2 may be selected from optionally substituted: octyl-COOH, heptyl-COOH, hexyl-COOH, pentyl-COOH, butyl-COOH, propyl-COOH, ethyl-COOH or methyl-COOH.
- R 1 may be selected from: tetradecyl, decyl, octyl, or pentyl
- R 2 may be selected from optionally substituted: octyl-COOH, hexyl-COOH, butyl-COOH, propyl-COOH or ethyl-COOH
- n may be 1.
- the diacetylene monomer may be selected from the group consisting of 6,8-tricosadiynoic acid, 4,6-heptadecadiynoic acid, 5,7- hexadecadiynoic acid, 10,12-octadecadiynoic acid, 6,8-nonadecadiynoic acid, 8,10- henicosadiynoic acid, 10,12-tricosadiynoic acid, 10,12-pentacosadiynoic acid, or combinations thereof.
- the phospholipid may be selected from: phosphocholines, phosphoethanolamines, phosphatidylethanolamines, phosphatidylserines, phosphatidylglycerols, and combinations thereof.
- the phospholipid may be selected from: l,2-dimyristoyl-sn-glycero-3 -phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero- 3 -phosphocholine (DOPC), 1 -pahmtoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), l,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), l -pahnitoyl-2-olcoyl-.w- glycero-3-phospho-(l'-rac-glycerol) (POPG).
- the phospholipid may be l,2-dimyristoyl-sn-
- the polydiacetylene liposome may be unilamellar. In one embodiment, the polydiacetylene liposome does not encapsulate a probe.
- the ratio of the diacetylene monomer : phospholipid may be in a range between about 1:1 to about 10:1.
- the ratio of the diacetylene monomer : phospholipid may be about 3 :2 or about 4: 1.
- the ratio of the diacetylene monomer : phospholipid may be about 4:1.
- the polydiacetylene liposome may be in the form of a hydrogel disc.
- the gel carrier is a crosslinkable polymer.
- the gel carrier may be selected from: agarose, alginate, poly(vinyl alcohol), pectin, carboxy methyl cellulose, hyaluronates, chitosan, cationic guar, cationic starch, or combinations thereof.
- the gel carrier may be selected from: agarose, alginate, poly(vinyl alcohol), or combinations thereof.
- the gel carrier may be agarose.
- the polydiacetylene liposome may be prepared using a thin-film hydration method or a solvent injection method.
- the solid reservoir may encapsulate the perishable consumable product to provide a tag for contactless monitoring of the perishable consumable.
- the perishable consumable may be a food or drink product, optionally selected from: milk, juice, meat, coffee, sauce, broth, protein powder, and the like.
- the colorimetric sensor tag may be used to monitor the quality of fruit, vegetable, and animal products, and products that contain sugar, protein and fats (e.g. baby formula).
- the senor may be provided in a dehydrated form when not in use, optionally for storage and/or transportation.
- the colorimetric sensor tag can be attached to the external surface of an article (e.g. food packaging) to provide an indirect indication of food quality without the need for contact with the food product.
- the quality tags can be “switched” on and off using dehydration and rehydration methods, advantageously removing the need for in situ manufacturing and allowing storage before use.
- the target analyte may be a free fatty acid. It will be appreciated that free fatty acids are a product of microbial spoilage of perishable consumable products.
- the polydiacetylene liposome may prepared using a thin-film hydration method or a solvent injection method.
- a method to obtain polydiacetylene liposomes may involve dissolving diacetylene monomers and phospholipids in an organic solvent (e.g. chloroform) which is then evaporated to dryness (e.g. by nitrogen) leaving a thin lipid film.
- the dry lipid film is then hydrated in an appropriate amount of aqueous phase and the mixture is heated to above the phase transition temperature (T m ) of the lipids/lipid mixture and lipid film is allowed to “swell”.
- T m phase transition temperature
- the resulting liposomes which typically consist of multilamellar vesicles (MLV's) are dispersed by shaking the test tube.
- This preparation provides the basis for producing small unilamellar vesicles by methods such as sonication (Papahadjopoulos et al., 1967), extrusion as described by Cullis et al. in U.S. Pat. No.5, 008, 050, or high-pressure homogenisation.
- This process is the conventional method for synthesis of polydiacetylene liposomes and is known as the thin film hydration method (“Bangham method”) which was developed in 1965 for the production of liposomes.
- Another method which may be used to prepare the polydiacetylene liposomes, as described herein, may be the solvent injection method and may be a suitable alternative for the synthesis of the polydiacetylene liposomes.
- the diacetylene monomers may be dissolved in a polar solvent (e.g. ethanol).
- a polar solvent e.g. ethanol
- the diacetylene solvent solution is then slowly added to an aqueous medium at above the phase transition temperature of the monomer under vigorous stirring.
- the ethanol is evaporated, and the amphiphilic diacetylenes self-assemble into vesicles.
- Preparation of liposomes of phospholipids by the double emulsion method for encapsulating a water soluble compound, e.g. a protein, which does not have strong affinity to the liposome is described by Schneider in US 4,008,801 and US 4,224,179.
- the emulsion with liposomes containing the compound is prepared by the double emulsion method: A small volume of an aqueous solution with a water soluble compound e.g. a protein antigen and/or an immunostimulator is mixed with a larger volume organic solvent with the phospholipid dissolved. The formed emulsion is mixed with a larger volume aqueous solution and the organic solvents are removed with an airstream.
- a method described by Carmona-Ribeiro and Chaimovich involves injecting an organic e.g. chloroform, methanol, ethanol, solution of the desired lipids into an aqueous buffer where the lipids spontaneously forms liposomes as the solvent evaporates.
- the ethanol injection method for large scale manufacturing of liposomes has been evaluated in recent years (Wagner 2006, Justo 2010), and this manufacturing method was judged more feasible to large scale production than for example the lipid film method.
- the activity of the toxin results in pore formation in the lipid membrane and the dye is released from the liposome. This leads to an increase in fluorescent signal which provides a quantitative indication of the toxin concentration.
- this biosensor is faster and more portable than blood agar tests, encapsulation of the dye in the liposome for a signal transducer and the requirement of fluorometer adds complexity to the particle synthesis and signal reading.
- Electrochemical sensors have also been previously developed that convert the action of the toxin on endothelial cells coating an electrode into an electrical signal. Whilst, this sensor may exhibit good sensitivity (0.1 ng/mL), electrochemical transduction requires a digital signal display for use by untrained operators.
- the present disclosure provides for the incorporation of PDA into a membrane wherein the signal generated from a chemical recognition event is a colour change that is visible to the human eye. This advantageously removes the necessity for signal reading equipment such as fluorometers or voltammeters.
- the PDA systems as described herein, can offer new opportunities for mobilisation of alpha-toxin diagnostics and use by unskilled operators due to its convenient colour change.
- a method for detection of a target analyte may comprise: a) obtaining a colorimetric sensor formulation according to any one or more embodiments or examples thereof as described herein, or a colorimetric sensor system according to any one or more embodiments or examples thereof as described herein, or a colorimetric sensor kit according to any one or more embodiments or examples thereof as described herein; b) contacting the colorimetric sensor with a sample suspected of containing a target analyte; and c) observing a colour change if the target analyte is present.
- the target analyte may be bacteria, directly detected or detected through the emitted toxins.
- the target analyte may be a-hemolysin.
- a-hemolysin is a hemolytic toxin excreted by Staphylococcus aureus, a predominant causative pathogen of bovine mastitis.
- a method for detection of a target analyte may comprise: al) obtaining a colorimetric sensor tag according to any one or more embodiments or examples thereof as described herein; and bl) observing a colour change if the target analyte is present.
- the target analyte may be a product of bacterial lysis such as free fatty acid. It will be appreciated that free fatty acids are a product of microbial spoilage of perishable consumable products.
- the observable colour change may occur in less than about 60 minutes of contacting the sensor with the sample suspected of containing an target analyte. In an embodiment, the observable colour change may occur in less than about 60 minutes, about 45 minutes, about 30 minutes, about 15 minutes, about 10 minutes, about 5 minutes, or about 1 minute. For example, the observable colour change may occur in less than about 30 minutes. In a preferred example, the observable colour change may occur in less than about 15 minutes.
- the observable colour change may occur in realtime. It will be appreciated that the term “real-time” may refer to the actual time for which the observable colour change occurs, i.e. at the time the recognition event occurs.
- the present disclosure provides a colorimetric sensor formulation that can be amenable to a variety of applications that demand cost-effective, stable, accurate, consistent and quick diagnostics outside the laboratory setting. Applications include point-of-care (POC) testing, home testing diagnostics, and food processing.
- POC point-of-care
- a colorimetric sensor system for detection of a target analyte may comprise: (i) the colorimetric sensor formulation of any one or more embodiments or examples thereof as described herein; and
- a colorimetric sensor system for detection of a target analyte may comprise:
- the colorimetric sensor tag may comprise opaque materials such as food ingredients.
- software for the analysis of images of colorimetric sensors may include Python programming language and Digital Colorimetric Response (DCR) to observe the colour change.
- DCR Digital Colorimetric Response
- the colorimetric sensor formulation comprising the PDA vesicles can be obtained without the need to form a film by the conventional LB (Langmuir-Blodgett) process before transferring it onto an appropriate support.
- the polydiacetylene vesicles can be formed on a substrate using the known LB process as described in A. Ulman, An Introduction to Ultrathin Organic Films, Academic Press, New York (1991), pp. 101-219.
- the present disclosure can provide bio sensing capabilities in a matrix, such as ink.
- the sensors are self-contained and do not require additional instrumentation to convey a measurable result.
- use with other analytical instrumentation is possible to further enhance sensitivity, such as fluorescence with the fluorescent “red” phase developed after detection of the target analyte.
- the colorimetric sensor formulation as described herein may be in the form of a solution.
- the solution can be provided in a simple vial system, the targe analyte may be directly added to a vial containing a solution of the colorimetric sensor, as described herein, designed specifically to the target analyte of interest.
- the colorimetric sensor kit could comprise multiple vials in the kit, with each vial containing a colorimetric sensor formulation, as described herein, particular to different target analytes. For those applications in which the target analyte cannot be added directly to the colorimetric sensor formulation, a two-part vial system could be used.
- one compartment of the vial could contain reagents for sample preparation of the target analyte physically separated from the second compartment containing the colorimetric sensor formulation. Once sample preparation is complete, the physical barrier separating the compartments would be removed to allow the analyte to mix with the transducer for detection.
- a colorimetric sensor kit may comprise one or more vessels, wherein each of the one or more vessels comprises a colorimetric sensor formulation according to any one or more embodiments or examples thereof as described herein to detect a specific target analyte.
- the one or more vessels may be a two-part vessel system to enable the colorimetric sensor formulation to be separated from a target analyte until ready for use.
- bovine mastitis is a common herd disease typically caused by bacterial infection and is characterised by an inflammation of the mammary gland. It represents one of the most difficult veterinary diseases to control and is the most costly to the dairy industry. Animal welfare concerns, treatment costs, extreme antibiotic use, and the reduced milk yield associated with mastitis incur significant economic and environmental expenses. Early and more specific diagnosis has been identified as an opportunity to better direct herd management strategy and reduce costs.
- Standard bovine mastitis diagnostic techniques include a range of laboratory and farm-based approaches. Some methods evaluate milk characteristics such as somatic cell count, enzymatic activity, electrical conductivity, and pH. These can indicate mastitis quickly and at low cost, however they do not specify the causative pathogen. Viable pathogen-specific methods include cell culturing and DNA-based techniques (e.g. polymerase chain reaction). These are restricted to laboratory settings, require specialised equipment, and are time-consuming. It has been identified that PDA sensors may be a useful alternative for pathogen- specific diagnosis that exhibit the sensitivity and specificity of laboratory-based techniques with the rapidity, mobility, and price of existing non-specific farm-based methods. Previous efforts have aimed to develop sensors for pathogen-specific diagnosis tools for mastitis.
- Staphylococcus aureus is a gram-positive bacterium and is a predominant causative pathogen of mastitis
- a-hemolysin a-toxin
- the toxin is secreted by the bacteria as a water soluble monomer which binds to the membrane of a host cell and forms an oligomer containing seven subunits.
- the oligomerisation process forms a pore in the lipid bilayer of the host cell between 1-3 nm which allows the flow of cations, ATP, and small molecules ( ⁇ 4 kDa) to either side of the cell membrane.
- date marking tools such as use-by and sell-by dates
- shelf life estimates are static and do not adapt to variables such as storage conditions, leading to frequently invalid indications of food quality.
- shelf life estimates are overly conservative as they pre-empt poor storage conditions.
- Cautious date marking is understandable as poisoning from spoiled food is a serious public health concern that can precipitate economic and legal ramifications for food producers.
- increasing concerns over sustainable food production now means that food loss due to conservative date marking is unacceptable and an attractive avenue to address the global food waste crisis.
- Traditional sensors directly monitor the chemical constitution of a sample, deducing qualitative or quantitative information by specific detection of targeted markers. Although this approach works well in controlled laboratory settings, in out-of- lab applications it can be difficult to establish and maintain a reliable interface between a sample and the sensor. This is particularly true for sensors that are intended for incorporation into food packaging to indicate quality.
- the present inventors have advantageously prepared colorimetric sensor tags which can encapsulate a variety of perishable consumable products (e.g. milk).
- the colorimetric sensor tags as described herein, may be incorporated into, or retrofitted onto an article (e.g. food packaging) as quality tags for contactless monitoring of food to be consumed.
- an article e.g. packaged food product
- attaching the colorimetric sensor tags to an article may subject both the sensor and the consumable product to the same storage conditions and therefore the sensor tag may “spoil” or change in composition with the same kinetics as the food product being emulated.
- the colorimetric sensor tag can advantageously indirectly indicate the quality of the food by measuring the degree of the colour change of the quality tag. This removes the challenge of maintaining an interface between the food and sensor as it is no longer required.
- a colorimetric sensor tag for detection of a target analyte may comprise the colorimetric sensor formulation of any one or more embodiments or examples thereof as described herein in the form of a hydrogel, wherein the hydrogel encapsulates a perishable consumable product to provide the tag for contactless monitoring of food.
- the colorimetric sensor tag may be configured to be attached to an article.
- the article may be food packaging prepared from cardboard, aluminium, plastic, glass, and the like.
- DA diacetylene
- a solvent e.g. chloroform
- the DA monomer formed a thin film on the substrate.
- the thin film of DA monomer was hydrated with 10 mL of deionised water at 80 °C under probe sonication for 10 minutes utilising a Branson Digital Sonifier (250 W, 20 kHz) with a 1/8” diameter tapered circular tip (Branson 101-148-062). Hydration produced liposomes at a concentration of 1 mg/mL.
- the liposomes were left to anneal for 16 hours at 4 °C.
- the DA liposomes were then subjected to photopolymerisation to form polydiacetylene (PDA) liposomes by being exposed to 254 nm UV light to induce an addition reaction between diacetylene groups on neighbouring monomers.
- PDA vesicle size distribution and ( ⁇ -potential were measured using dynamic light scattering (DLS) using a Malvern Zetasizer Nano ZS.
- DLS dynamic light scattering
- the PDA sample was diluted in water by a factor of 10 (i.e. 0.1 mg/ml).
- the z-average size of the PDA liposomes ranged from about 100 nm to about 400 nm.
- the average ( ⁇ -potential of the PDA liposomes ranged between about - 30 mV to about -40 mV. Examples of the liposome sizes and zeta potentials are shown in Figure 1.
- Polydiacetylene liposome 1A may be prepared according to the general process prepared in Example 1, wherein the diacetylene monomer is 6,8-tricosadiynoic acid and the solvent is chloroform.
- the z-average size of PDA liposome 1A was 140.14 ⁇ 38.97 nm.
- Polydiacetylene liposome IB may be prepared according to the general process prepared in Example 1, wherein the diacetylene monomer is 10,12-tricosadiynoic acid and the solvent is chloroform.
- the z-average size of PDA liposome IB was 117.18 ⁇ 7.28 nm.
- Polydiacetylene liposome 1C may be prepared according to the general process prepared in Example 1, wherein the diacetylene monomer is 6,8-nonadecadiynoic acid and the solvent is chloroform.
- the z-average size of PDA liposome C was 325.50 ⁇ 42.80 nm.
- Polydiacetylene liposome ID may be prepared according to the general process prepared in Example 1, wherein the diacetylene monomer is 10,12-pentacosadiynoic acid and the solvent is chloroform.
- Polydiacetylene liposome IE may be prepared according to the general process prepared in Example 1, wherein the diacetylene monomer is 8,10-henicosadiynoic acid and the solvent is chloroform.
- Polydiacetylene liposome IF may be prepared according to the general process prepared in Example 1, wherein the diacetylene monomer is 10,12-octadecadiynoic acid and the solvent is chloroform.
- Polydiacetylene liposome 1G may be prepared according to the general process prepared in Example 1, wherein the diacetylene monomer is 4,6-heptadecadiynoic acid and the solvent is chloroform.
- Polydiacetylene liposome IH may be prepared according to the general process prepared in Example 1, wherein the diacetylene monomer is 5,7-hexadecadiynoic acid and the solvent is chloroform.
- DA monomer and a phospholipid e.g. l,2-dimyristoyl-5n-glycero-3- phosphocholine (DMPC)
- a solvent e.g. chloroform
- the solvent was evaporated by nitrogen for 60 minutes at room temperature (20 °C).
- the DA monomer and phospholipid formed a thin film on the substrate.
- the thin film of DA monomer and phospholipid was hydrated with 10 mL of deionised water at 80 °C under probe sonication for 10 minutes utilising a Branson Digital Sonifier (250 W, 20 kHz) with a 1/8” diameter tapered circular tip (Branson 101-148-062). Hydration produced liposomes at a concentration of 1 mg/mL. The liposomes were left to anneal for 16 hours at 4 °C. The DA/phospholipid liposomes were then subjected to photopolymerisation to form PDA/phospholipid liposomes by being exposed to 254 nm UV light to induce an addition reaction between diacetylene groups on neighbouring monomers.
- Polydiacetylene/phospholipid liposome 2A may be prepared according to the general process prepared in Example 2, wherein the diacetylene monomer is 6,8- tricosadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Example 2b Synthesis of polydiacetylene/phospholipid liposome 2B
- Polydiacetylene/phospholipid liposome 2B may be prepared according to the general process prepared in Example 2, wherein the diacetylene monomer is 10,12- tricosadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid liposome 2C may be prepared according to the general process prepared in Example 2, wherein the diacetylene monomer is 6,8- nonadecadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid liposome 2D may be prepared according to the general process prepared in Example 2, wherein the diacetylene monomer is 10,12- pentacosadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid liposome 2E may be prepared according to the general process prepared in Example 2, wherein the diacetylene monomer is 8,10- henicosadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid liposome 2F may be prepared according to the general process prepared in Example 2, wherein the diacetylene monomer is 10,12- octadecadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid liposome 2H may be prepared according to the general process prepared in Example 2, wherein the diacetylene monomer is 4,6- heptadecadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid liposome 2H may be prepared according to the general process prepared in Example li, wherein the diacetylene monomer is 5,7- hexadecadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Example 3 General process for the preparation of PDA/phospholipid/cholesterol liposomes via thin film hydration method
- DA monomer, a phospholipid (e.g. DMPC), and cholesterol were dissolved in 500 pL of a solvent (e.g. chloroform) at 25 °C, to produce a solution of DA monomer, phospholipid, and cholesterol in the solvent.
- a solvent e.g. chloroform
- the solvent was evaporated by nitrogen for 60 minutes at room temperature (20 °C).
- the DA monomer, phospholipid, and cholesterol formed a thin film on the substrate.
- the thin film of DA monomer, phospholipid, and cholesterol was hydrated with 10 mL of deionised water at 80 °C under probe sonication for 10 minutes utilising a Branson Digital Sonifier (250 W, 20 kHz) with a 1/8” diameter tapered circular tip (Branson 101- 148-062). Hydration produced liposomes at a concentration of 1 mg/mL. The liposomes were left to anneal for 16 hours at 4 °C. The DA/phospholipid/cholesterol liposomes were then subjected to photopolymerisation to form PDA/phospholipid/cholesterol liposomes by being exposed to 254 nm UV light to induce an addition reaction between diacetylene groups on neighbouring monomers.
- Polydiacetylene/phospholipid/cholesterol liposome 3A may be prepared according to the general process prepared in Example 3, wherein the diacetylene monomer is 6,8-tricosadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid/cholesterol liposome 3B may be prepared according to the general process prepared in Example 3, wherein the diacetylene monomer is 10,12-tricosadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid/cholesterol liposome 3C may be prepared according to the general process prepared in Example 3 wherein the diacetylene monomer is 6,8-nonadecadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid/cholesterol liposome 3D may be prepared according to the general process prepared in Example 3, wherein the diacetylene monomer is 10,12-pentacosadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid/cholesterol liposome 3E may be prepared according to the general process prepared in Example 3, wherein the diacetylene monomer is 8,10-henicosadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid/cholesterol liposome 3F may be prepared according to the general process prepared in Example 3, wherein the diacetylene monomer is 10,12-octadecadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid/cholesterol liposome 3G may be prepared according to the general process prepared in Example 3, wherein the diacetylene monomer is 4,6-heptadecadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- Polydiacetylene/phospholipid/cholesterol liposome 3H may be prepared according to the general process prepared in Example 3, wherein the diacetylene monomer is 5,7-hexadecadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- DA monomer (8 mg) was dissolved in 250 pl of polar organic solvent (e.g. ethanol), to produce a solution of DA monomer in solvent at a concentration of 32 mg/ml).
- the solution was injected into a vial containing 10 ml of water at flow rate of 100 pl/min. During the solution injection process, the solution was maintained at 80 °C under constant stirring at 300 rpm. After the injection step was complete, the DA/ethanol/water mixture was incubated for further 30 minutes at 80 °C to allow for ethanol evaporation. The self-assembled DA liposomes were allowed to cool to room temperature and then stored at 4 °C for 24 hours. Photo-induced polymerisation was carried out under 254 nm UV irradiation (UV lamp LF-206.LS, 6W, UVfTEC, UK) for 10 minutes to obtain blue-phase PDA liposomes.
- UV irradiation UV lamp LF-206.LS, 6W, UVfTEC, UK
- the data were analysed using the general purpose non-negative least squares (NNLS) fitting algorithm, with a size range analysis of 0.4-10000 nm.
- the liposomes’ size and standard deviation were calculated from the intensity distributions.
- Zeta potential measurements were collected using a disposable folded capillary cell (DTS1070), containing 0.6 ml of the sample without dilution.
- DTS1070 disposable folded capillary cell
- Different amphiphilic DA monomer building blocks self-assembled to form vesicles of a characteristic size with their diameters ranging from about 130 nm to about 800 nm and zeta-potentials ranging from about -25 mV to about -30 mV.
- Polydiacetylene liposome 4A may be prepared according to the general process prepared in Example 4, wherein the diacetylene monomer 10,12-pentacosadiynoic acid and the solvent is ethanol.
- the z-average size of PDA liposome 4A was 127.2 ⁇ 58.3 nm and the zeta potential was -32.2 ⁇ 8.6 mV.
- Polydiacetylene liposome 4B may be prepared according to the general process prepared in Example 4, wherein the diacetylene monomer is 10,12-tricosadiynoic acid and the solvent is ethanol.
- the z-average size of PDA liposome 4B was 184.1 ⁇ 59.9 nm and the zeta potential was -29.0 ⁇ 6.8 mV.
- Polydiacetylene liposome 4C may be prepared according to the general process prepared in Example 4, wherein the diacetylene monomer is 10,12-octadecadiynoic acid and the solvent is ethanol.
- the z-average size of PDA liposome 4C was 800.3 ⁇ 237.1 nm and the zeta potential was -26.9 ⁇ 7.5 mV.
- Example 4d Synthesis of polydiacetylene liposome 4D
- Polydiacetylene liposome 4D may be prepared according to the general process prepared in Example 4, wherein the diacetylene monomer is 8,10-henicosadiynoic acid and the solvent is ethanol.
- the z-average size of PDA liposome 2D was 281.9 + 91.3 nm and the zeta potential was -26.7 ⁇ 6.7 mV.
- Polydiacetylene liposome 4E may be prepared according to the general process prepared in Example 4, wherein the diacetylene monomer is 6,8-nonadecadiynoic acid and the solvent is ethanol.
- the z-average size of PDA liposome 4E was 456.1 + 130.7 and the zeta potential was -32.0 ⁇ 7.1 mV.
- Polydiacetylene liposome 4F may be prepared according to the general process prepared in Example 4, wherein the diacetylene monomer is 6,8-tricosadiynoic acid and the solvent is ethanol.
- Polydiacetylene liposome 4G may be prepared according to the general process prepared in Example 4, wherein the diacetylene monomer is 4,6-heptadecadiynoic acid and the solvent is ethanol.
- Polydiacetylene liposome 4H may be prepared according to the general process prepared in Example 4, wherein the diacetylene monomer is 5,7-hexadecadiynoic acid and the solvent is ethanol.
- DA monomer was dissolved in 250 pl of polar organic solvent (e.g. ethanol).
- 2 mg of phospholipid e.g DMPC
- 250 pl of polar organic solvent e.g. ethanol
- the mixed solution was then injected (100 pl/min for 5 min) via pipette into 10 ml of water which was being heated at 80 °C and mixed at 300 rpm in a thermomixer. After the injection step was complete, the solution containing self-assembled diacetylene/phospholipid vesicles was left at 80 °C for a further 30 minutes to allow evaporation of residual ethanol.
- the vial was then wrapped in foil and placed in the refrigerator at 4 °C for 24 hours to allow the vesicles to anneal.
- Photo-induced polymerisation was carried out under 254 nm UV irradiation (UV lamp LF-206.LS, 6W, UVITEC, UK) for 10 minutes at a distance of 15 cm from lamp base to solution surface was then performed to produce PDA/phospholipid liposomes.
- Polydiacetylene/phospholipid liposome 5A may be prepared according to the general process prepared in Example 5, wherein the diacetylene monomer is 6,8- tricosadiynoic acid, the phospholipid is DMPC, and the solvent is ethanol.
- Polydiacetylene/phospholipid liposome 5B may be prepared according to the general process prepared in Example 5, wherein the diacetylene monomer is 10,12- tricosadiynoic acid, the phospholipid is DMPC, and the solvent is chloroform.
- TEM micrographs were obtained using a JEOL 1400 TEM (JEOL, Akishima, Japan) operating at an accelerating voltage of 100 keV. Samples were ultra- sonicated, and then drop cast onto formv ar- supported copper grids (ProSciTech) without staining. The size and morphology of the nanoparticles were recorded using a Phurona CCD Camera (Emsis) and Radius software (Emsis). TEM analysis (Fig.2) confirmed that the particles were of the same morphology as PDA/DMPC vesicles constructed via the thin film hydration method as described in Example 1.
- Polydiacetylene/phospholipid liposome 5C may be prepared according to the general process prepared in Example 5, wherein the diacetylene monomer is 6,8- nonadecadiynoic acid, the phospholipid is DMPC, and the solvent is ethanol.
- Polydiacetylene/phospholipid liposome 2M may be prepared according to the general process prepared in Example 5, wherein the diacetylene monomer is 10,12- pentacosadiynoic acid, the phospholipid is DMPC, and the solvent is ethanol.
- Example 5e Synthesis of polydiacetylene/phospholipid liposome 5E
- Polydiacetylene/phospholipid liposome 5E may be prepared according to the general process prepared in Example 5, wherein the diacetylene monomer is 8,10- henicosadiynoic acid, the phospholipid is DMPC, and the solvent is ethanol.
- Polydiacetylene/phospholipid liposome 5F may be prepared according to the general process prepared in Example 5, wherein the diacetylene monomer is 10,12- octadecadiynoic acid, the phospholipid is DMPC, and the solvent is ethanol.
- Polydiacetylene/phospholipid liposome 5G may be prepared according to the general process prepared in Example 5, wherein the diacetylene monomer is 4,6- heptadecadiynoic acid, the phospholipid is DMPC, and the solvent is ethanol.
- Polydiacetylene/phospholipid liposome 5H may be prepared according to the general process prepared in Example 5, wherein the diacetylene monomer is 5,7- hexadecadiynoic acid, the phospholipid is DMPC, and the solvent is ethanol.
- Example 6 Detection of q-Hemolysin a-hemolysin powder was hydrated with 0.01 M phosphate buffered- saline (PBS) to make a 0.5 mg/mL stock solution. 100 pL of the polydiacetylene liposome 1A synthesised according to Example la was mixed with the stock a-hemolysin solution to produce a solution with final a-hemolysin concentration of 12.5 pg/mL.
- PBS phosphate buffered- saline
- Example 2a 100 pL of the polydiacetylene/phospholipid liposome 2A synthesised according to Example 2a was mixed with the stock a-hemolysin solution to produce a solution with final a-hemolysin concentration of 12.5 pg/mL.
- Example 3a 100 pL of the polydiacetylene/phospholipid/cholesterol liposome 3A synthesised according to Example 3a was mixed with the stock a-hemolysin solution to produce a solution with final a-hemolysin concentration of 12.5 pg/mL.
- Example 6a Liposomes synthesised according to Example 3a selectivity
- LPS lipopolysaccharide
- Liposomes synthesised according to Example 3a were incubated with 12.5 Listeriolysin O toxin (LLO) (100 pg/mL) and no colour change in the sensor was detected. This was surprising, however the action of pore-forming toxins is known to require specific lipid compositions or binding sites.
- LLO Listeriolysin O toxin
- Liposomes synthesised according to Example 3a were exposed to other known biomarkers for mastitis in bovine milk including FFA (octanoic acid, 0.5 pg/mL) and lactic acid (3 mM) and no colour change in the liposomes was observed.
- FFA octanoic acid, 0.5 pg/mL
- lactic acid 3 mM
- Example 6b Liposomes synthesised according to Example 3a morphology pre and post a-hemolysin incubation
- TEM micrographs were taken of liposomes synthesised according to Example la and Example 3a before and after the addition of alpha-hemolysin (12.5 pg/mL).
- polydiacetylene/phospholipid liposomes 5A-5H prepared according to examples 5a-5h are referred to as PDA based liposomes.
- a 6 wt% agarose solution was prepared by dissolving agarose (600 mg) in deionised water (10 ml) under constant stirring at 60 °C for 1 hour. 2 ml of the 6 wt% agarose solution was mixed with 2 ml of a perishable consumable product (e.g milk) and 2 ml of PDA based liposomes (1 mg/ml). The resultant mixture had a constitution of 0.33 mg/ml PDA based liposome, 33 vol% milk, and 2 wt% agarose. 400 pl of the mixture was cast into the cap of a glass vial and placed in the fridge for 1 hour to allow the gel to set forming the PDA based liposome hydrogels.
- a perishable consumable product e.g milk
- PDA based liposomes 1 mg/ml
- PDA based liposome hydrogel 7 A may be prepared according to the general process prepared in Example 7, wherein the PDA based liposome is prepared according to Example 5a.
- PDA based liposome hydrogel 7B may be prepared according to the general process prepared in Example 7, wherein the PDA based liposome is prepared according to Example 5b.
- PDA based liposome hydrogel 7C may be prepared according to the general process prepared in Example 7, wherein the PDA based liposome is prepared according to Example 5c.
- PDA based liposome hydrogel 7D may be prepared according to the general process prepared in Example 7, wherein the PDA based liposome is prepared according to Example 5d.
- PDA based liposome hydrogel 7E may be prepared according to the general process prepared in Example 7, wherein the PDA based liposome is prepared according to Example 5e.
- PDA based liposome hydrogel 7F may be prepared according to the general process prepared in Example 7, wherein the PDA based liposome is prepared according to Example 5f.
- PDA based liposome hydrogel 7G may be prepared according to the general process prepared in Example 7, wherein the PDA based liposome is prepared according to Example 5g.
- PDA based liposome hydrogel 7H may be prepared according to the general process prepared in Example 7, wherein the PDA based liposome is prepared according to Example 5h.
- Example 7b To make quality tags that mimic the spoilage kinetics of milk, two PDA based liposome hydrogel were generated according to Example 7b. To study the colour change behaviour of the hydrogels, one sample set was refrigerated at 4°C and the other was stored at 20 °C for a period of 48 hours.
- the blue to red colour change of the samples stored at 20 °C is due to the insertion of free fatty acids into the PDA membrane.
- Free fatty acids are a product of fat rancidification by bacterial lipolysis.
- the hydrogel acts as a quasi-liquid and does not impede or alter the spoilage of milk fats.
- the tags were first dehydrated in a vacuum to 13.8 ⁇ 1.4% of their original weight under refrigeration. The dehydrated tags were then subject to the same experimental conditions used to compare the spoilage kinetics of the PDA based liposome/milk solutions and PDA based liposome hydrogels (Fig. 5). One sample set of the dehydrated gels was refrigerated keeping the milk ingredients fresh. In parallel with this experiment, another sample set was stored at 20 °C, allowing the milk ingredients to spoil. Both the refrigerated and unrefrigerated dehydrated gels did not change colour over 48 hours (Fig. 6a, c).
- a set of dehydrated gels were then rehydrated to see if increasing the water content could “switch” the gels back “on”.
- the dehydrated gels were submerged in a small Petri dish containing 5 ml of water and left to soak for 6 hours under refrigeration.
- the gels were then weighed and found to have returned to 74.4 ⁇ 3.9% of their original weight before dehydration.
- the gels were then subject to refrigerated and unrefrigerated conditions for 48 hours.
- the rehydrated gels that were refrigerated remained blue for the 48 hour period. It was found that the encapsulated milk was not expected to spoil while refrigerated.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Polymers & Plastics (AREA)
- Endocrinology (AREA)
- Materials Engineering (AREA)
- Plasma & Fusion (AREA)
- Toxicology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/AU2021/051069 WO2023039625A1 (fr) | 2021-09-16 | 2021-09-16 | Capteurs colorimétriques permettant la détection de contaminants chimiques et biologiques |
AU2021464941A AU2021464941A1 (en) | 2021-09-16 | 2021-09-16 | Colorimetric sensors for detection of chemical and biological contaminants |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/AU2021/051069 WO2023039625A1 (fr) | 2021-09-16 | 2021-09-16 | Capteurs colorimétriques permettant la détection de contaminants chimiques et biologiques |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2023039625A1 true WO2023039625A1 (fr) | 2023-03-23 |
Family
ID=85601836
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/AU2021/051069 WO2023039625A1 (fr) | 2021-09-16 | 2021-09-16 | Capteurs colorimétriques permettant la détection de contaminants chimiques et biologiques |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU2021464941A1 (fr) |
WO (1) | WO2023039625A1 (fr) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060172371A1 (en) * | 2003-07-10 | 2006-08-03 | Ben-Gurion University Of The Negev Research And Development Authority | Polydiacetylene-containing solid colorimetric and/or fluorescent detector, method for its preparation and uses thereof |
WO2013049525A1 (fr) * | 2011-09-30 | 2013-04-04 | Cirle | Emballages ou autres matériaux comportant un biocapteur et leurs procédés d'utilisation |
-
2021
- 2021-09-16 AU AU2021464941A patent/AU2021464941A1/en active Pending
- 2021-09-16 WO PCT/AU2021/051069 patent/WO2023039625A1/fr active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060172371A1 (en) * | 2003-07-10 | 2006-08-03 | Ben-Gurion University Of The Negev Research And Development Authority | Polydiacetylene-containing solid colorimetric and/or fluorescent detector, method for its preparation and uses thereof |
WO2013049525A1 (fr) * | 2011-09-30 | 2013-04-04 | Cirle | Emballages ou autres matériaux comportant un biocapteur et leurs procédés d'utilisation |
Non-Patent Citations (3)
Title |
---|
WESTON MAX, CIFTCI MUSTAFA, KUCHEL RHIANNON P., BOYER CYRILLE, CHANDRAWATI RONA: "Polydiacetylene for the Detection of α-Hemolysin in Milk toward the Diagnosis of Bovine Mastitis", ACS APPLIED POLYMER MATERIALS, vol. 2, no. 11, 13 November 2020 (2020-11-13), pages 5238 - 5248, XP093049457, ISSN: 2637-6105, DOI: 10.1021/acsapm.0c00968 * |
WESTON, M. ET AL.: "Digital analysis of polydiacetylene quality tags for contactless monitoring of milk", ANALYTICA CHIMICA ACTA, vol. 1148, no. 238190, 5 January 2021 (2021-01-05), XP086471961, DOI: 10.1016/j.aca.2020.12.065 * |
ZHOU JIN, YAO DANYU, QIAN ZHIYONG, HOU SEN, LI LINHAO, JENKINS A. TOBIAS A., FAN YUBO: "Bacteria-responsive intelligent wound dressing: Simultaneous In situ detection and inhibition of bacterial infection for accelerated wound healing", BIOMATERIALS, ELSEVIER, AMSTERDAM, NL, vol. 161, 1 April 2018 (2018-04-01), AMSTERDAM, NL , pages 11 - 23, XP093049458, ISSN: 0142-9612, DOI: 10.1016/j.biomaterials.2018.01.024 * |
Also Published As
Publication number | Publication date |
---|---|
AU2021464941A1 (en) | 2024-04-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20080193967A1 (en) | Colorimetric Sensor Constructed Of Diacetylene Materials | |
Schlafer et al. | Confocal microscopy imaging of the biofilm matrix | |
Sutthasupa et al. | Colorimetric ammonia (NH3) sensor based on an alginate-methylcellulose blend hydrogel and the potential opportunity for the development of a minced pork spoilage indicator | |
Sträuber et al. | Viability states of bacteria—specific mechanisms of selected probes | |
Remis et al. | Bacterial social networks: structure and composition of M yxococcus xanthus outer membrane vesicle chains | |
Scheinpflug et al. | Measurement of cell membrane fluidity by Laurdan GP: fluorescence spectroscopy and microscopy | |
Jelinek et al. | Biomolecular sensing with colorimetric vesicles | |
Zafiu et al. | Liquid crystals as optical amplifiers for bacterial detection | |
Thet et al. | Visible, colorimetric dissemination between pathogenic strains of Staphylococcus aureus and Pseudomonas aeruginosa using fluorescent dye containing lipid vesicles | |
Jewell et al. | Clostridium perfringens α-toxin interaction with red cells and model membranes | |
Dou et al. | Biomimetic cell model for fluorometric and smartphone colorimetric dual-signal readout detection of bacterial toxin | |
Thet et al. | Photopolymerization of polydiacetylene in hybrid liposomes: effect of polymerization on stability and response to pathogenic bacterial toxins | |
Weston et al. | Polydiacetylene for the Detection of α-Hemolysin in Milk toward the Diagnosis of Bovine Mastitis | |
JP2011504236A (ja) | ジアセチレンを含むポリマーセンサーを用いる細菌試料の分析方法 | |
AU2021464941A1 (en) | Colorimetric sensors for detection of chemical and biological contaminants | |
Huang et al. | Ordered membrane domain-forming properties of the lipids of Borrelia burgdorferi | |
Krok et al. | Tunable biomimetic bacterial membranes from binary and ternary lipid mixtures and their application in antimicrobial testing | |
DE60314290T2 (de) | Aus polydiacetylen hergestellte kolorimetrische sensoren. | |
ES2878114T3 (es) | Detección de patógenos beta-hemolíticos | |
Heider et al. | Structural characterization of individual vesicles using fluorescence microscopy | |
Yadav et al. | Methods for Determination of Antimicrobial Activity of Bacteriocins of Lactic Acid Bacteria | |
Patil et al. | Mapping fusogenicity of ciprofloxacin-loaded liposomes with bacterial cells | |
Valenta et al. | Phloretin and 6-ketocholestanol: membrane interactions studied by a phospholipid/polydiacetylene colorimetric assay and differential scanning calorimetry | |
EP1186059B1 (fr) | Procédé de formation de monocouches | |
da Silva | NAMs' Membrane Permeabilization and Partition into Membrane Models |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21956972 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2021464941 Country of ref document: AU Ref document number: AU2021464941 Country of ref document: AU |
|
ENP | Entry into the national phase |
Ref document number: 2021464941 Country of ref document: AU Date of ref document: 20210916 Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |