Inactivation of pathogens in ex vivo blood products in storage bags using visible light

Abstract

Disclosed herein are methods and devices for the inactivation of pathogens (e.g., bacteria, viruses, etc.) in ex vivo stored blood products, such as plasma and/or platelets, by means of directing visible light radiation from an illuminating device into blood product storage containers in order to achieve effective pathogen inactivation without the presence of an added photosensitising agent in the blood product. An exemplary apparatus includes a control unit that operates a light source that emits light in the wavelength region of about 380-500 nm which is directed onto blood product storage bags at sufficient intensity to penetrate the bag material and the opaque blood product therein in order to inactivate pathogens in the blood product but at dose levels that cause no significant detrimental effects on the blood product.

1 . An apparatus for inactivating pathogens in ex vivo stored blood products, comprising:
 a treatment chamber configured to receive at least one sealed container storing a blood product; and   a light source operable to emit light that is directed to a blood product storage container in the treatment chamber, the emitted light having a wavelength and intensity sufficient to penetrate through a wall of the container and into the blood product, such that the irradiance of the light reaching the blood product inside the wall of the container is sufficient to inactivate pathogens in the blood product without the presence of an added photosensitizing agent in the blood product and without a detrimental effect on the blood product such that the blood product is suitable for future medical use.   
     
     
         2 . The apparatus of  claim 1 , wherein at least 50% of the light emitted by the light source has a wavelength in a range from 380 nm to 500 nm. 
     
     
         3 . The apparatus of  claim 1 , wherein at least 50% of the light emitted by the light source has a wavelength in a range from 400 nm to 420 nm. 
     
     
         4 . The apparatus of  claim 1 , wherein the light emitted by the light source has a wavelength spectrum centered on or around about 405 nm. 
     
     
         5 . The apparatus of  claim 1 , wherein the light reaching the blood product has a wavelength and intensity sufficient to inactivate bacteria, viruses, and fungi present in an ex vivo blood product stored in a sealed container. 
     
     
         6 . The apparatus of  claim 1 , further comprising an agitation mechanism positioned within or coupled to the treatment chamber and configured to agitate a blood product stored in a container within the treatment chamber while the blood product is irradiated with light. 
     
     
         7 . The apparatus of  claim 6 , wherein the agitation mechanism comprises a oscillating or vibrating tray on which a blood product storage container rests during treatment. 
     
     
         8 . The apparatus of  claim 6 , wherein the apparatus comprises at least two independent agitation mechanisms. 
     
     
         9 . The apparatus of  claim 6 , wherein the agitation mechanism is operable to oscillate a blood product storage container at from 30 to 100 reciprocations per minute during treatment. 
     
     
         10 . The apparatus of  claim 1 , wherein the light source comprises at least a first light source and a second light source positioned on opposing walls of the treatment chamber, the first light source being positioned to direct light at a first surface of a blood product storage container, and the second light source being configured to direct light at a second surface of the blood product storage container that is opposite from the first surface. 
     
     
         11 . The apparatus of  claim 1 , wherein the apparatus comprises a temperature control system operable to maintain the air temperature within the treatment chamber within a predetermined range during treatment. 
     
     
         12 . The apparatus of  claim 1 , wherein walls of the treatment chamber comprise reflective surfaces configured to reflect light having wavelengths between 380 nm and 500 nm. 
     
     
         13 . The apparatus of  claim 1 , further comprising a lens configured to focus or direct light from the light source to a particular region of the treatment chamber. 
     
     
         14 . The apparatus of  claim 1 , further comprising a diffuser configured to diffuse light from the light source or blend light from more than one light source. 
     
     
         15 . The apparatus of  claim 1 , wherein the light source is operable to emit light with an intensity low enough that light reaching a blood product has an irradiance of 3 mW/cm 2  or less. 
     
     
         16 . The apparatus of  claim 1 , wherein the light source is operable to emit light with an intensity high enough that light reaching a blood product has an irradiance of 80 mW/cm 2  or greater. 
     
     
         17 . The apparatus of  claim 1 , wherein the light source is operable to emit light with an intensity such that light reaching a blood has an irradiance in a range from 3 mW/cm 2  to 80 mW/cm 2 . 
     
     
         18 . The apparatus of  claim 1 , further comprising a control system operable to vary the intensity of light emitted from the light source during treatment. 
     
     
         19 . The apparatus of  claim 1 , wherein the treatment chamber comprises a hanging mechanism for holding blood product storage containers in a suspended or hanging orientation during treatment. 
     
     
         20 . The apparatus of  claim 1 , further comprising a heat sink or a cooling fan arranged to dissipate heat produced by the light source during treatment. 
     
     
         21 . A method for inactivating pathogens in ex vivo stored blood products, comprising:
 providing a sealed storage container containing an ex vivo blood product without an added photosensitizing agent present in the blood product, the storage container comprising at least one wall that is at least partially transmissive to light having wavelengths from 380 nm to 500 nm; and   irradiating at least one wall of the sealed storage container with light of sufficient intensity and wavelength to penetrate through the at least one wall of the sealed storage container and enter into the blood product, and doing so for sufficient duration to inactivate pathogens in the blood product without causing a substantial detrimental effect on the blood product such that the blood product is suitable for future medical use.   
     
     
         22 . The method of  claim 21 , wherein storage container is a blood product transfusion bag. 
     
     
         23 . The method of  claim 21 , wherein the storage container comprises PVC. 
     
     
         24 . The method of  claim 21 , wherein at least 50% of the light emitted by the light source has a wavelength in a range from 380 nm to 500 nm. 
     
     
         25 . The method of  claim 21 , wherein at least 50% of the light emitted by the light source has a wavelength in a range from 380 nm to 420 nm. 
     
     
         26 . The method of  claim 21 , wherein the light emitted by the light source has a wavelength spectrum centered on or around about 405 nm. 
     
     
         27 . The method of  claim 21 , wherein the light reaching the blood product has an irradiance of from 3 mW/cm 2  to 80 mW/cm 2 . 
     
     
         28 . The method of  claim 21 , wherein the light reaching the blood product has an irradiance of 3 mW/cm 2  or less. 
     
     
         29 . The method of  claim 21 , wherein the light reaching the blood product has an irradiance of 80 mW/cm 2  or greater. 
     
     
         30 . The method of  claim 21 , further comprising agitating the storage container during the irradiation such that the contained blood product moves within the storage container. 
     
     
         31 . The method of  claim 30 , wherein agitating comprising causing the storage container to reciprocate at from 30 to 100 reciprocations per minute. 
     
     
         32 . The method of  claim 21 , wherein the irradiating comprises adjusting the intensity of the light emitted by the light source during the treatment. 
     
     
         33 . The method of  claim 21 , wherein the irradiating comprises irradiating the storage container from at least two different directions simultaneously. 
     
     
         34 . The method of  claim 21 , further comprising circulating air around the storage container during the irradiating to maintain a desired temperature range for the storage container and the blood product. 
     
     
         35 . The method of  claim 21 , wherein the irradiating has a duration of at least one hour. 
     
     
         36 . The method of  claim 21 , wherein the irradiating has a duration of at least two hours. 
     
     
         37 . A method comprising using light having a wavelength of between 380 nm and 500 nm for deactivating pathogens in stored blood products. 
     
     
         38 . The method of  claim 37 , wherein deactivating pathogens in stored blood produces comprises deactivating virus contamination in stored blood products.