Disinfection of biological fluids using asymmetric cyanine dyes
AssigneeAmerican National Red Cross
InventorStephen J. Wagner
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Abstract
Asymmetric cyanine dyes of Formula I bind nucleic acid but not red blood cell membrane, and function as photosensitizers when rigidly bound but not when free in solution. Unbound dye thus causes minimal oxidative damage. The dyes do not substantially accumulate in red blood cells, thereby minimizing hemolysis due to oxidative damage. Biological fluids can be disinfected by mixing the fluid with these asymmetric cyanine dye that binds to nucleic acid, irradiating the mixture, and recovering clinically significant components from the biological fluid and/or assaying the fluid for pathogens.
Claims24
A method for disinfecting a biological fluid containing red blood cells comprising:
- (a) creating a mixture of the biological fluid and a nucleic acid binding, cell-membrane-permeable, asymmetric cyanine dye;
- (b) irradiating the resulting mixture to achieve a viral inactivation capacity corresponding to at least about 7 Log10 VSV;
- and
- (c) assaying the biological fluid for a pathogen;
- wherein the asymmetric cyanine dye has the structure of Formula I:
- where:
- R1, R2, and R3 are saturated or unsaturated hydrocarbons of C6 or fewer;
- R4 and R5 are the same or different and are selected from saturated or unsaturated hydrocarbons, acyl, aryl, alcohol, ester, aldehyde, ketone and amine of C4 or fewer, any of which may be further substituted with a halogen, or R4 and/or R5 is itself a halogen;
- n is 0-5;
- m is 0-4;
- p is 0-4;
- and the ring W is a fused, bicyclic heteroaryl moiety.
A method for disinfecting a biological fluid containing red blood cells comprising:
- (a) creating a mixture of the biological fluid containing red blood cells and a nucleic acid binding, cell-membrane-permeable asymmetric cyanine dye;
- (b) irradiating the resulting mixture to achieve a viral inactivation capacity corresponding to at least about 7 Log 10VSV and less than 2% hemolysis on storage at 42 days following irradiation;
- and
- (c) recovering intact red blood cells from the mixture;
- wherein the asymmetric cyanine dye has the structure of Formula I:
- where:
- R1, R2 and R3 are saturated or unsaturated hydrocarbons of C6 or fewer;
- R4 and R5 are the same or different and are selected from saturated or unsaturated hydrocarbons, acyl, alcohol, ester, aldehyde and amine of C4 or fewer, any of which may be further substituted with a halogen, or R4 and/or R5 is itself a halogen;
- n is 0-5;
- m is 0-4;
- p is 0-4;
- and the ring W is a fused, bicyclic heteroaryl moiety.
A method for disinfecting a biological fluid containing red blood cells comprising:
- (a) creating a mixture of the biological fluid and a nucleic acid binding, cell-membrane-permeable, asymmetric cyanine dye;
- (b) irradiating the resulting mixture with white light to achieve:
- (i) viral inactivation corresponding to at least about 7 Log10 VSV;
- and
- (ii) less than 2% hemolysis on storage at 42 days following irradiation;
- and
- (c) assaying the biological fluid for a pathogen;
- wherein the asymmetric cyanine dye has the structure of Formula I:
- where:
- R1, R2, and R3 are saturated or unsaturated hydrocarbons of C6 or fewer;
- R4 and R5 are the same or different and are selected from saturated or unsaturated hydrocarbons, acyl, aryl, alcohol, ester, aldehyde, ketone and amine of C4 or fewer, any of which may be further substituted with a halogen, or R4 and/or R5 is itself a halogen;
- n is 0-5;
- m is 0-4;
- p is 0-4;
- and the ring W is a fused, bicyclic heteroaryl moiety;
- and
- wherein the asymmetric cyanine dye produces singlet oxygen upon irradiation with white light only when intercalated with a nucleic acid molecule.
Dependencies are inferred from the claim text.