Systems and methods for processing biological fluids

CN116571191BActive Publication Date: 2026-09-08CERUS CORP
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Patent Information

Application Number
CN202310382666.7
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2017-12-29
Filing Date
2018-12-28
Publication Date
2026-09-08
Estimated Expiration
2038-12-28

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Abstract

The present invention provides systems and methods for processing biological fluids, for example, to inactivate pathogens.
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Description

[0001] This application is a divisional application of Chinese Patent Application No. 201880084617.2, filed on December 28, 2018, entitled "System and Method for Processing Biological Fluids".

[0002] Cross-references to related applications

[0003] This application claims priority to U.S. Provisional Patent Application No. 62 / 612,314, filed December 29, 2017, the disclosure of which is incorporated herein by reference in its entirety. Background Technology

[0004] This disclosure generally relates to systems and methods for treating biological fluids with light, including treating mixtures of biological fluids and photochemical agents.

[0005] Systems and methods for treating biological fluids with light are well known. For example, U.S. Patents 7,459,695, 6,986,867, and 5,593,823 describe systems for treating biological fluids with light to inactivate pathogens in the biological fluid. Specifically, such systems include a treatment chamber having drawers for introducing the biological fluid into the treatment chamber and a light source within the treatment chamber for irradiating the biological fluid. The light source emits light within a selected wavelength range, which effectively inactivates pathogens in the biological fluid, particularly by photochemical inactivation. Other systems and methods for treating biological fluids with light may include, for example, the systems and methods described in U.S. Patents 6,843,961, 7,829,867, 9,320,817, and 8,778,263, and Schlenke, 2014, Transfus. Med. Hemother. 41:309-325.

[0006] For systems and methods that light-treat biological fluids (such as blood products, including, for example, platelets and plasma), it is important to ensure that the blood products are free of pathogens to minimize the risk of infection to individuals receiving the blood products. The ability to test for pathogens in blood is limited by the pathogen being tested and the sensitivity of the assay. As an alternative to or supplement to testing for pathogens, methods for inactivating pathogens using various compound-based (e.g., chemical, photochemical) inactivation methods are known in the art (e.g., disclosed in Schlenke et al., Transfus Med Hemother, 2014, 41, 309-325 and Prowse, Vox Sanguinis, 2013, 104, 183-199). Photochemical pathogen inactivation systems based on psoralen and ultraviolet light for treating blood products include commercially available... The Cerus Corporation uses amotosalen and irradiates it with ultraviolet A light, followed by treatment with a compound adsorption device (CAD) to remove residual amotosalen and its photoproducts.

[0007] While previous systems and methods for treating biological fluids have generally been satisfactory, there is a desire to develop improved systems and methods for treating biological fluids more effectively, for example, by reducing the levels of pathogen-inactivating compounds after photochemical treatment (e.g., photoconversion) while maintaining or enhancing pathogen inactivation, and / or by improving the properties (e.g., quality) of the treated biological fluid, for example, by minimizing the damage that may be caused to the biological fluid by various parameters of the treatment process. Furthermore, it may be desirable to improve the monitoring and control of various parameters of the treatment process. Summary of the Invention

[0008] Systems and methods for processing biological fluids with light are provided. In one exemplary embodiment, the processing system may include a processing chamber for receiving the biological fluid and one or more photosensors configured to detect light in the processing chamber. A first light source array may be positioned to illuminate the biological fluid in the processing chamber. The first light source array may include one or more light source channels illuminating the biological fluid with light of a selected peak wavelength. For example, a first light source channel may emit light of a first peak wavelength, and a second light source channel may emit light of a second peak wavelength that differs from the first peak wavelength by at least 5 nanometers. In other instances, the one or more light source channels may emit light of a first peak wavelength with a full-width half-maximum (FWHM) emission bandwidth of less than 20 nanometers.

[0009] This document provides a system for processing biological fluids, the system comprising: a processing chamber for receiving biological fluid (e.g., biological fluid in a container); one or more sensors configured to detect (e.g., measure) light (e.g., light intensity) in the processing chamber; and a first light source array positioned to irradiate the biological fluid in the processing chamber (e.g., positioned towards the biological fluid), wherein the first light source array includes a first light source channel configured to emit ultraviolet light having a first peak wavelength and a second light source channel configured to emit light having a second peak wavelength, wherein the second peak wavelength differs from the first peak wavelength by at least 5 nanometers.

[0010] In some embodiments, the first light source array includes a plurality of light source groups, wherein each light source group in the first light source array includes a first light source channel configured to emit ultraviolet light having a first peak wavelength and a second light source channel configured to emit light having a second peak wavelength. In some embodiments, the first light source channel and / or the second light source channel are configured to emit ultraviolet light. In some embodiments, the first peak wavelength is in the ultraviolet A spectrum (e.g., 315-400 nm). In some embodiments, the first light source channel is configured to emit ultraviolet light having a first peak wavelength of about 315 nm to about 350 nm. In some embodiments, the first peak wavelength is about 315 nm to about 335 nm. In some embodiments, the first peak wavelength is about 330 nm to about 350 nm. In some embodiments, the first peak wavelength is in the ultraviolet A spectrum (e.g., 315-400 nm), and the second peak wavelength is in the ultraviolet C spectrum (e.g., 100-280 nm, 200-280 nm, 240-280 nm). In some embodiments, the first peak wavelength is in the ultraviolet A spectrum (e.g., 315-400 nm), and the second peak wavelength is in the ultraviolet B spectrum (e.g., 280-315 nm). In some embodiments, the first peak wavelength is in the ultraviolet A spectrum (e.g., 315-400 nm), and the second peak wavelength is in the ultraviolet A spectrum. In some embodiments, the first peak wavelength is in the ultraviolet A spectrum, and the second peak wavelength is in the visible light spectrum (e.g., 400-800 nm). In some embodiments, the first peak wavelength is in the ultraviolet B spectrum, and the second peak wavelength is in the ultraviolet C spectrum. In some embodiments, the first peak wavelength is in the ultraviolet B spectrum, and the second peak wavelength is in the visible light spectrum. In some embodiments, the first peak wavelength is in the ultraviolet C spectrum, and the second peak wavelength is in the visible light spectrum. In some embodiments, the first light source channel and the second light source channel include one or more (e.g., multiple) light-emitting diodes (LEDs). In some implementations, the light intensity at 50% of the maximum peak intensity of the light emitted by the first light source channel is within a spectral width of less than 20 nanometers of the first peak wavelength (e.g., no more than 10 nanometers larger than the first peak wavelength, no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller than the first peak wavelength, and within 10 nanometers larger than the first peak wavelength).In some embodiments, the full width at half maximum (FWHM) spectral width (e.g., bandwidth) of the light emitted by the first light source channel (e.g., the spectral bandwidth at maximum peak intensity) is within 20 nanometers of the first peak wavelength (e.g., no more than 10 nanometers larger than the first peak wavelength, no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller than the first peak wavelength, within 10 nanometers larger than the first peak wavelength). In some embodiments, the first array includes the sole / only light source of the processing chamber, which is positioned to irradiate the biofluid in the processing chamber. In some embodiments, the system further includes a first platform (e.g., tray, trough, plate, table) placed in the processing chamber, the first platform being configured to hold the biofluid (e.g., a container for one or more biofluids). In some embodiments, one or more sensors configured to detect light in the processing chamber are placed on or within the first platform. In some embodiments, the system further includes a heat exchanger thermally connected to the first light source array. In some embodiments, the first platform is placed above the first light source array, and wherein the first light source array faces the first platform. In some implementations, the first platform is placed below the first light source array, and the first light source array faces the first platform.

[0011] In some embodiments, the light sources of the first light source array are positioned in a non-uniformly distributed manner on the array. In some embodiments, the first array includes an inner region having a first light source density and an outer region having a second light source density, wherein the first light source density is different from the second light source density. In some embodiments, the first array includes a continuous inner region containing a midpoint of the first array and a continuous outer region surrounding the inner region, wherein the inner region occupies less than 50% of the surface area of ​​the first array (e.g., less than 40%, 30%, 20%, 10%, 10%-50%, 20%-40%, 10%-20%), and wherein the outer region occupies the remaining percentage of the surface area of ​​the first array (e.g., 50%, 60%, 70%, 80%, 90%). In some embodiments, the first array includes a continuous inner region containing a midpoint of the first array and a continuous outer region surrounding the inner region, wherein the inner region occupies more than 50% of the surface area of ​​the first array (e.g., more than 60%, 70%, 80%, 90%, 50%-90%, 60%-80%), and wherein the outer region occupies the remaining percentage of the surface area of ​​the first array (e.g., less than 50%, 40%, 30%, 20%, 10%, 10%-50%, 20%-40%, 10%-20%). In some embodiments, the outer region includes a first region containing the outer edge of the first array, wherein no light source is placed in the first region. In some embodiments, the density of a first light source located in the outer region is greater than the density of a second light source located in the inner region. In some embodiments, the density of a first light source located in the outer region is less than the density of a second light source located in the inner region. In some embodiments, the first array is configured such that the light source is placed at a greater density in the outer 50% surface area of ​​the array than the light source density near the midpoint of the array (e.g., the inner 10% or 20% of the surface area). In some embodiments, the first array includes a first region of light sources and a second region of light sources, the former configured to irradiate a first biological fluid (e.g., a first container with biological fluid) in the processing chamber, and the latter configured to irradiate a second biological fluid (e.g., a second container with biological fluid) in the processing chamber. In some embodiments, the first light source density located in the first region of the first array and the second light source density located in the second region of the first array are each greater than the light source density located outside the first and second regions of the first array. In some embodiments, the first array includes a first region of light sources and a second region of light sources, the former configured to irradiate a first biological fluid (e.g., a first container with biological fluid) in the processing chamber, and the latter configured to irradiate a second biological fluid (e.g., a second container with biological fluid) in the processing chamber.In some embodiments, the first light source density located in the first region of the array and the second light source density located in the second region of the array are each greater than the light source density outside the first and second regions of the array. In some embodiments, the first array is configured such that the light source irradiates the biofluid in the processing chamber with an irradiance difference of less than 25% across the surface of the biofluid facing the first array (e.g., the fluid container, a cross-section of the fluid container). In some embodiments, the first array is configured such that the light source irradiates any 5 cm of the biofluid in the processing chamber (e.g., the container with biofluid) with an integral irradiance (averaged over surface area) of less than 25% compared to the cross-section of the entire biofluid (e.g., the container with biofluid). 2 The area.

[0012] In some embodiments, the first light source array further includes a third light source channel configured to emit light of a third peak wavelength (e.g., wherein each of the first, second, and third peak wavelengths differs from the other by at least 5 nanometers). In some embodiments, each of the plurality of light source groups further includes a third light source channel configured to emit light of a third peak wavelength. In some embodiments, each of the plurality of light source groups further includes a third light source channel configured to emit light of a third peak wavelength and a fourth light source channel configured to emit light of a fourth peak wavelength. In some embodiments, the first light source array further includes a third light source channel configured to emit light of a third peak wavelength and a fourth light source channel configured to emit light of a fourth peak wavelength. In some embodiments, each of the first, second, third, and fourth peak wavelengths differs from the other by at least 5 nanometers. In some embodiments, the first peak wavelength is equal to the third peak wavelength, and wherein the second peak wavelength is equal to the fourth peak wavelength. In some embodiments, the system further includes a barrier (e.g., a light barrier, a protective barrier) placed in the processing chamber between the first light source array and the first platform. In some embodiments, the system further includes a barrier (e.g., a light barrier, a protective barrier) placed within the processing chamber between the first light source array and the biological fluid (e.g., biological fluid in a container). In some embodiments, the barrier is a light barrier (e.g., a filter) configured to reduce (e.g., minimize, attenuate, block) the transmission of light with wavelengths smaller than those in the UVA spectrum. In some embodiments, the barrier is a light barrier configured to reduce the transmission of light with wavelengths smaller than those in the UVB spectrum. In some embodiments, the barrier is a light barrier (e.g., a filter) configured to reduce (e.g., minimize, attenuate, block) the transmission of light with wavelengths at least 20 nm smaller than the first peak wavelength and / or another peak wavelength (e.g., at least 20 nm smaller than the second, third, or fourth peak wavelength) (e.g., at least 25 nm smaller, at least 30 nm smaller). In some embodiments, the barrier is a light barrier (e.g., a filter) configured to reduce the transmission of light with wavelengths at least 20 nm larger than the first peak wavelength and / or another peak wavelength (e.g., at least 20 nm larger than the second, third, or fourth peak wavelength) (e.g., at least 25 nm larger, at least 30 nm larger). In some embodiments, the barrier is transparent to light with wavelengths within 30 nm of the first peak wavelength (e.g., within 15 nm smaller and larger than the first peak wavelength; or no more than 15 nm larger and no more than 15 nm smaller than the first peak wavelength). In some embodiments, one or more sensors configured to detect light in the processing chamber are placed on or within the barrier.In some implementations, the first platform and the first light source array are configured to translate relative to each other to change the distance between the first light source array and the first platform.

[0013] In some embodiments, the first platform includes a first compartment and a second compartment separate from the first compartment. In some embodiments, the first platform is configured to separately hold a first container having at least a first biological fluid and a second container having a second biological fluid. In some embodiments, the first platform is transparent to light with wavelengths within 100 nm (e.g., 75 nm, 50 nm, 40 nm, 30 nm, 20 nm) of the first peak wavelength and / or another peak wavelength (e.g., a second, third, or fourth peak wavelength). In some embodiments, the first platform is transparent to ultraviolet light (e.g., UV-A, UV-B, and / or UV-C). In some embodiments, the first platform is movable in a sliding manner (e.g., in a drawer configuration) for introducing and removing the biological fluid (e.g., a container having the biological fluid) into and out of the compartment. In some embodiments, one or more of the plurality of inner surfaces of the processing compartment are configured to absorb light. In some embodiments, each of the plurality of inner surfaces of the processing compartment is configured to absorb light. In some embodiments, one or more of the plurality of inner surfaces of the processing compartment are configured to reflect light. In some implementations, each of the plurality of inner surfaces of the processing chamber is configured to reflect light.

[0014] In some embodiments, the system (e.g., a first platform) is configured to agitate the biofluid during processing. In some embodiments, the first platform is configured to move (e.g., orbital movement, reciprocating movement, controlled movement, movement at a specified rate) to agitate the biofluid during processing.

[0015] In some embodiments, the system further includes one or more thermal sensors placed in the processing chamber, and / or one or more airflow sensors placed in the processing chamber. In some embodiments, the one or more sensors are placed on the first light source array. In some embodiments, the system further includes one or more sensors (e.g., in contact with / on the platform) for detecting the presence and / or type of biological fluid (e.g., a container containing biological fluid) in the chamber.

[0016] In some embodiments, the light sources of the first light source array are connected in series. In some embodiments, the light sources of the first light source array are connected in parallel. In some embodiments, a first group of light sources in the first light source array is connected in parallel, and a second group of light sources in the first light source array is connected in series. In some embodiments, the light sources of the first light source array are connected by a combination of parallel and series circuits.

[0017] In some embodiments, the system further includes a second light source array facing in the opposite direction to the first light source array, wherein each light source in the second light source array includes a third light source channel configured to emit light having the first peak wavelength and a fourth light source channel configured to emit light having the second peak wavelength. In some embodiments, the first and second light source arrays are configured to translate relative to each other to change the distance between the first and second light source arrays. In some embodiments, the system further includes a first platform placed in the processing chamber between the first and second light source arrays, the first platform being configured to carry the biofluid (e.g., a container with the biofluid). In some embodiments, the system further includes a barrier placed in the processing chamber between the second light source array and the first platform.

[0018] In some embodiments, the system further includes a second light source array facing the same direction as the first light source array, wherein each light source in the second light source array includes a third light source channel configured to emit light having the first peak wavelength and a fourth light source channel configured to emit light having the second peak wavelength, and wherein the first light source array and the second light source array define a first region between the first light source array and the second light source array. In some embodiments, the system further includes a first platform placed in the processing chamber within the first region, the first platform being configured to carry a first biological fluid; and a second platform placed in the processing chamber outside the first region, the second platform being configured to carry a second biological fluid, wherein the second light source array faces the second platform. In some embodiments, the system further includes a barrier placed in the processing chamber outside the first region and between the second light source array and the second platform. In some embodiments, the first array includes a single light source for the processing chamber, which is positioned to irradiate the biological fluid in the first region of the processing chamber. In some embodiments, a first set of light sources of the first light source array is arranged on a first panel, and wherein a second set of light sources of the first light source array is arranged on a second panel placed adjacent to the first panel. In some embodiments, a first set of light sources of the second light source array is arranged on a first panel, and a second set of light sources of the second light source array is arranged on a second panel adjacent to the first panel. In some embodiments, the first panel and the second panel are configured to translate relative to each other to change the distance between the first panel and the second panel. In some embodiments, the first set of light sources is connected in series, the second set of light sources is connected in series, and the first panel and the second panel are connected in parallel.

[0019] In some embodiments, the system further includes control circuitry (e.g., control circuitry operatively coupled (wireless or wired) to the processing chamber and operatively coupled to one or more arrays). In some embodiments, the control circuitry is configured to adjust or set a first peak wavelength of light emitted by each first light source channel and to adjust or set a second peak wavelength of light emitted by each second light source channel. In some embodiments, the control circuitry is configured to adjust or set the intensity of each light source (e.g., each light source independently) of the first light source array. In some embodiments, the control circuitry is configured to adjust or set a first light intensity emitted by each first light source channel and to adjust or set a second light intensity emitted by each second light source channel. In some embodiments, the control circuitry is configured to adjust or set the light emission duration from each light source (e.g., each light source independently) of the first light source array. In some embodiments, the control circuitry is configured to adjust or set a first light emission duration from each first light source channel and to adjust or set a second light emission duration from each second light source channel.

[0020] In some embodiments, the control circuit adjusts or sets the first peak wavelength and the second peak wavelength of the light based at least in part on a first set of parameters detected by at least one sensor (e.g., a light sensor, an air flow sensor, a thermal sensor, a sensor for detecting the presence or properties of a biological fluid, a sensor for detecting photochemical compounds, a sensor positioned to detect the fluid depth of the biological fluid). In some embodiments, the control circuit adjusts or sets the first peak wavelength and the second peak wavelength of the light based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light. In some embodiments, the control circuit is configured to adjust or set the light emission duration of each light source from the first light source array based at least in part on a first set of parameters detected by at least one sensor (e.g., a light sensor, an air flow sensor, a thermal sensor, a sensor for detecting the presence or properties of a biological fluid, a sensor for detecting photochemical compounds, a sensor positioned to detect the fluid depth of the biological fluid). In some embodiments, the control circuit is configured to adjust or set the light emission duration of each light source from the first light source array based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light. In some embodiments, the control circuitry is configured to adjust or set the light emission intensity of each light source from the first light source array based at least in part on a first set of parameters detected by at least one sensor (e.g., a light sensor, an airflow sensor, a thermal sensor, a sensor for detecting the presence or properties of a biological fluid, a sensor for detecting photochemical compounds, a sensor positioned to detect the fluid depth of the biological fluid). In some embodiments, the control circuitry is configured to adjust or set the light emission intensity of each light source from the first light source array based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light.

[0021] In some embodiments, the system further includes a depth sensor configured to detect a first depth of a first portion of the biofluid placed in the processing chamber. In some embodiments, the control circuitry is configured to adjust or set the intensity of light emitted by a first light source channel facing the biofluid based on the depth of the biofluid. In some embodiments, the control circuitry is configured to adjust or set the intensity of light emitted by a second light source channel facing the biofluid based on the depth of the biofluid. In some embodiments, the control circuitry is configured to adjust or set a first light intensity emitted by each first light source channel facing the first portion of the biofluid based on the depth of the first portion of the biofluid, and to adjust or set a second light intensity emitted by each second light source channel facing the second portion of the biofluid based on the depth of the second portion of the biofluid. In some embodiments, the system further includes one or more depth sensors placed in the processing chamber, the one or more depth sensors being configured to detect the depth of the first portion of the biofluid and the depth of the second portion of the biofluid.

[0022] In some embodiments, the system further includes a first container placed inside the processing chamber (e.g., a processing container) for receiving and processing the biological fluid, wherein the first container is adapted to be connected to a source container of the biological fluid, and wherein the first container is adapted to be connected to a second container for receiving the biological fluid from the first container.

[0023] This document further provides a system for processing biological fluids, the system comprising: a processing chamber for receiving biological fluid (e.g., biological fluid in a container); one or more sensors configured to detect (e.g., measure) light (e.g., light intensity) in the processing chamber; and a first light source array positioned to irradiate the biological fluid in the processing chamber (e.g., positioned facing the biological fluid), wherein each light source in the first light source array includes a first light source channel configured to emit ultraviolet light having a first peak wavelength (e.g., 315 to 400 nm) in the ultraviolet A, ultraviolet B, and / or ultraviolet C spectra, wherein the full width at half maximum (FWHM) spectral bandwidth (e.g., spectral bandwidth at maximum peak intensity) of the light emitted by the first light source channel is less than 20 nm (e.g., within 10 nm smaller than the first peak wavelength, within 10 nm larger than the first peak wavelength; not exceeding 10 nm larger than the first peak wavelength, and not exceeding 10 nm smaller than the first peak wavelength).

[0024] In some embodiments, each light source in the first light source array includes a first light source channel configured to emit ultraviolet light with a first peak wavelength between about 315 nm and about 350 nm. In some embodiments, each light source in the first light source array includes a first light source channel configured to emit ultraviolet light with a first peak wavelength between about 315 nm and about 335 nm (e.g., between about 320 nm and about 330 nm, or about 325 nm). In some embodiments, each light source in the first light source array includes a first light source channel configured to emit ultraviolet light with a first peak wavelength between about 330 nm and about 350 nm (e.g., between about 335 nm and about 345 nm, or about 340 nm). In some embodiments, 50% of the maximum peak intensity of the light emitted by the first light source channel is within 10 nanometers of the first peak wavelength. In some embodiments, the light intensity at 50% of the maximum peak intensity of the light emitted by the first light source channel is (e.g., limited to) a spectral width of less than 20 nanometers (e.g., no more than 10 nanometers larger than the first peak wavelength, no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller than the first peak wavelength, and within 10 nanometers larger than the first peak wavelength). In some embodiments, the first light source array further includes a second light source channel configured to emit light (e.g., ultraviolet light) having a second peak wavelength. In some embodiments, the second peak wavelength differs from the first peak wavelength by at least 5 nanometers. In some embodiments, the second peak wavelength is located in the ultraviolet A spectrum (e.g., 315-400 nm), ultraviolet B spectrum (e.g., 280-315 nm), ultraviolet C spectrum (e.g., 100-280 nm, 200-280 nm, 240-280 nm), or visible light spectrum (e.g., 400-800 nm). In some embodiments, 50% of the maximum peak intensity of the light emitted by the second light source channel is within 10 nanometers of the second peak wavelength (e.g., no more than 10 nanometers larger than the second peak wavelength and no more than 10 nanometers smaller than the second peak wavelength; within 10 nanometers smaller than the second peak wavelength and within 10 nanometers larger than the second peak wavelength). In some embodiments, the full width at half maximum (FWHM) spectral bandwidth (e.g., the spectral bandwidth at maximum peak intensity) of the light emitted by the second light source channel is less than 20 nanometers (e.g., no more than 10 nanometers larger than the second peak wavelength and no more than 10 nanometers smaller than the second peak wavelength; within 10 nanometers smaller than the second peak wavelength and within 10 nanometers larger than the second peak wavelength).In some embodiments, the first light source array includes a plurality of light source groups, and each light source group of the first light source array includes a first light source channel configured to emit ultraviolet light having a first peak wavelength and a second light source channel configured to emit light (e.g., ultraviolet light) having a second peak wavelength. In some embodiments, the first light source channel includes one or more (e.g., multiple) LEDs. In some embodiments, the second light source channel includes one or more (e.g., multiple) LEDs.

[0025] In some embodiments, the system further includes a first platform (e.g., tray, trough, plate, table) placed in the processing chamber, the first platform being configured to hold the biological fluid (e.g., a container for one or more biological fluids). In some embodiments, the system further includes a heat exchanger thermally connected to the first light source array. In some embodiments, the first platform is placed above the first light source array, and wherein the first light source array faces the first platform. In some embodiments, the first platform is placed below the first light source array, and wherein the first light source array faces the first platform. In some embodiments, one or more sensors configured to detect light in the processing chamber are placed on or within the first platform.

[0026] In some embodiments, the light sources of the first light source array are positioned in a non-uniformly distributed manner on the array. In some embodiments, the first array includes an inner region having a first light source density and an outer region having a second light source density, wherein the first light source density is different from the second light source density. In some embodiments, the first array includes a continuous inner region containing a midpoint of the first array and a continuous outer region surrounding the inner region, wherein the inner region occupies less than 50% of the surface area of ​​the first array (e.g., less than 40%, 30%, 20%, 10%, 10%-50%, 20%-40%, 10%-20%), and wherein the outer region occupies the remaining percentage of the surface area of ​​the first array (e.g., 50%, 60%, 70%, 80%, 90%). In some embodiments, the first array includes a continuous inner region containing a midpoint of the first array and a continuous outer region surrounding the inner region, wherein the inner region occupies more than 50% of the surface area of ​​the first array (e.g., more than 60%, 70%, 80%, 90%, 50%-90%, 60%-80%), and wherein the outer region occupies the remaining percentage of the surface area of ​​the first array (e.g., less than 50%, 40%, 30%, 20%, 10%, 10%-50%, 20%-40%, 10%-20%). In some embodiments, a first light source density located in the outer region is greater than a second light source density located in the inner region. In some embodiments, a first light source density located in the outer region is less than a second light source density located in the inner region. In some embodiments, the outer region includes a first region containing the outer edge of the first array, wherein no light source is placed in the first region. In some embodiments, the first array includes a first region of light source and a second region of light source, the former configured to irradiate a first biofluid (e.g., a first container having biofluid) in the processing chamber, and the latter configured to irradiate a second biofluid (e.g., a second container having biofluid) in the processing chamber. In some embodiments, the first light source density located in the first region of the first array and the second light source density located in the second region of the first array are each greater than the light source density located outside the first and second regions of the first array. In some embodiments, the first array is configured such that the light source irradiates the biofluid in the processing chamber with an irradiance difference of less than 25% across the surface of the biofluid facing the first array (e.g., the fluid container, a cross-section of the fluid container). In some embodiments, the first array is configured such that the light source irradiates any 5 cm of the biofluid in the processing chamber (e.g., the container having biofluid) with an integral or average irradiance difference of less than 25% over the entire cross-section of the biofluid (e.g., the container having biofluid).2 The area.

[0027] In some embodiments, the first light source array further includes a third light source channel configured to emit light at a third peak wavelength (e.g., wherein each of the first, second, and third peak wavelengths differs from the other by at least 5 nanometers). In some embodiments, each of the plurality of light source groups further includes a third light source channel configured to emit light at a third peak wavelength.

[0028] In some embodiments, each of the plurality of light source groups further includes a third light source channel configured to emit light of a third peak wavelength and a fourth light source channel configured to emit light of a fourth peak wavelength. In some embodiments, the first light source array further includes a third light source channel configured to emit light of a third peak wavelength and a fourth light source channel configured to emit light of a fourth peak wavelength. In some embodiments, each of the first, second, third, and fourth peak wavelengths differs from the other by at least 5 nanometers. In some embodiments, the first peak wavelength is equal to the third peak wavelength, and wherein the second peak wavelength is equal to the fourth peak wavelength.

[0029] In some embodiments, the system further includes a barrier (e.g., a light barrier, a protective barrier) placed within the processing chamber between the first light source array and the first platform. In some embodiments, the system further includes a barrier (e.g., a light barrier, a protective barrier) placed within the processing chamber between the first light source array and the biological fluid (e.g., biological fluid in a container). In some embodiments, the barrier is a light barrier (e.g., a filter) configured to reduce (e.g., minimize, attenuate, block) the transmission of light with wavelengths smaller than those in the UVA spectrum. In some embodiments, the barrier is a light barrier configured to reduce the transmission of light with wavelengths smaller than those in the UVB spectrum. In some embodiments, the barrier is a light barrier (e.g., a filter) configured to reduce (e.g., minimize, attenuate, block) the transmission of light with wavelengths at least 20 nm smaller than the first peak wavelength and / or another peak wavelength (e.g., at least 20 nm smaller than the second, third, or fourth peak wavelength) (e.g., at least 25 nm smaller, at least 30 nm smaller). In some embodiments, the barrier is a light barrier (e.g., a filter) configured to reduce the transmission of light with wavelengths at least 20 nm larger than the first peak wavelength and / or another peak wavelength (e.g., at least 20 nm larger than the second, third, or fourth peak wavelength) (e.g., at least 25 nm larger, at least 30 nm larger). In some embodiments, the barrier is transparent to light with wavelengths within 30 nm of the first peak wavelength (e.g., within 15 nm smaller and larger than the first peak wavelength; not exceeding 15 nm larger and not exceeding 15 nm smaller than the first peak wavelength). In some embodiments, one or more sensors configured to detect light in the processing chamber are placed on or within the barrier. In some embodiments, the first platform and the first light source array are configured to translate relative to each other to change the distance between the first light source array and the first platform.

[0030] In some embodiments, the first platform includes a first compartment and a second compartment separate from the first compartment. In some embodiments, the first platform is configured to separately hold a first container having at least a first biological fluid and a second container having a second biological fluid. In some embodiments, the first platform is transparent to light with wavelengths within 100 nm (e.g., 75 nm, 50 nm, 40 nm, 30 nm, 20 nm) of the first peak wavelength and / or another peak wavelength (e.g., a second, third, or fourth peak wavelength). In some embodiments, the first platform is transparent to ultraviolet light (e.g., UV-A, UV-B, and / or UV-C). In some embodiments, the first platform is slidable (e.g., in a drawer configuration) for introducing and removing the biological fluid (e.g., a container having the biological fluid) into and out of the compartment. In some embodiments, one or more inner surfaces of the processing compartment (e.g., multiple inner surfaces of the processing compartment) are configured to absorb light. In some embodiments, each of the multiple inner surfaces of the processing compartment is configured to absorb light. In some embodiments, one or more inner surfaces of the processing chamber (e.g., multiple inner surfaces of the processing chamber) are configured to reflect light. In some embodiments, each inner surface of the processing chamber is configured to reflect light.

[0031] In some embodiments, the system (e.g., a first platform) is configured to agitate the biofluid during processing. In some embodiments, the first platform is configured to move (e.g., orbital movement, reciprocating movement, controlled movement, movement at a specified rate) to agitate the biofluid during processing.

[0032] In some embodiments, the system further includes one or more thermal sensors placed in the processing chamber, and / or one or more airflow sensors placed in the processing chamber. In some embodiments, the one or more sensors are placed on the first light source array. In some embodiments, the system further includes one or more sensors (e.g., in contact with / on the platform) for detecting the presence and / or type of biological fluid (e.g., a container containing biological fluid) in the chamber.

[0033] In some embodiments, the light sources of the first light source array are connected in series. In some embodiments, the light sources of the first light source array are connected in parallel. In some embodiments, a first group of light sources in the first light source array is connected in parallel, and a second group of light sources in the first light source array is connected in series. In some embodiments, the light sources of the first light source array are connected by a combination of parallel and series circuits.

[0034] In some embodiments, the system further includes a second light source array facing in the opposite direction to the first light source array, wherein each light source in the second light source array includes a third light source channel configured to emit light having the first peak wavelength and a fourth light source channel configured to emit light having the second peak wavelength. In some embodiments, the first and second light source arrays are configured to translate relative to each other to change the distance between the first and second light source arrays. In some embodiments, the system further includes a first platform placed in the processing chamber between the first and second light source arrays, the first platform being configured to carry the biofluid (e.g., a container with the biofluid). In some embodiments, the system further includes a barrier placed in the processing chamber between the second light source array and the first platform.

[0035] In some embodiments, the system further includes a second light source array facing the same direction as the first light source array, wherein each light source in the second light source array includes a third light source channel configured to emit light having the first peak wavelength and a fourth light source channel configured to emit light having the second peak wavelength, and wherein the first light source array and the second light source array define a first region between the first light source array and the second light source array. In some embodiments, the system further includes a first platform placed in the processing chamber within the first region, the first platform being configured to carry a first biological fluid; and a second platform placed in the processing chamber outside the first region, the second platform being configured to carry a second biological fluid, wherein the second light source array faces the second platform. In some embodiments, the system further includes a barrier placed in the processing chamber outside the first region and between the second light source array and the second platform. In some embodiments, the first array includes a single light source for the processing chamber, which is positioned to irradiate the biological fluid in the first region of the processing chamber. In some embodiments, a first set of light sources of the first light source array is arranged on a first panel, and wherein a second set of light sources of the first light source array is arranged on a second panel placed adjacent to the first panel. In some embodiments, a first set of light sources of the second light source array is arranged on a first panel, and a second set of light sources of the second light source array is arranged on a second panel adjacent to the first panel. In some embodiments, the first panel and the second panel are configured to translate relative to each other to change the distance between the first panel and the second panel. In some embodiments, the first set of light sources is connected in series, the second set of light sources is connected in series, and the first panel and the second panel are connected in parallel.

[0036] In some embodiments, the system further includes control circuitry (e.g., control circuitry operatively coupled (wireless or wired) to the processing chamber and operatively coupled to one or more arrays). In some embodiments, the control circuitry is configured to adjust or set the first peak wavelength of light emitted by each light source (e.g., each light source independently) of the first light source array. In some embodiments, the control circuitry is configured to adjust or set the first peak wavelength of light emitted by each first light source channel and to adjust the second peak wavelength of light emitted by each second light source channel. In some embodiments, the control circuitry is configured to adjust or set the intensity of each light source (e.g., each light source independently) of the first light source array. In some embodiments, the control circuitry is configured to adjust or set the first light intensity emitted by each first light source channel and to adjust or set the second light intensity emitted by each second light source channel. In some embodiments, the control circuitry is configured to adjust or set the light emission duration from each light source (e.g., each light source independently) of the first light source array. In some embodiments, the control circuitry is configured to adjust or set the first light emission duration from each first light source channel and to adjust or set the second light emission duration from each second light source channel.

[0037] In some embodiments, the control circuitry is configured to adjust or set the first peak wavelength of light from each light source of the first light source array based at least in part on a first set of parameters detected by at least one sensor (e.g., a light sensor, an airflow sensor, a thermal sensor, a sensor for detecting the presence or properties of a biological fluid, a sensor for detecting photochemical compounds, a sensor positioned to detect the fluid depth of the biological fluid). In some embodiments, the control circuitry is configured to adjust or set the first peak wavelength of light from each light source of the first light source array based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light. In some embodiments, the control circuitry adjusts or sets both the first peak wavelength and the second peak wavelength of light based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light. In some embodiments, the control circuitry is configured to adjust or set the light emission duration of each light source from the first light source array based at least in part on a first set of parameters detected by at least one sensor (e.g., a light sensor, an airflow sensor, a thermal sensor, a sensor for detecting the presence or properties of a biological fluid, a sensor for detecting photochemical compounds, a sensor positioned to detect the fluid depth of the biological fluid). In some embodiments, the control circuitry is configured to adjust or set the light emission duration of each light source from the first light source array based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light. In some embodiments, the control circuitry is configured to adjust or set the light emission intensity of each light source from the first light source array based at least in part on a first set of parameters detected by at least one sensor (e.g., a light sensor, an airflow sensor, a thermal sensor, a sensor for detecting the presence or properties of a biological fluid, a sensor for detecting photochemical compounds, a sensor positioned to detect the fluid depth of the biological fluid). In some implementations, the control circuitry is configured to adjust or set the light emission intensity of each light source from the first light source array based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light.

[0038] In some embodiments, the system further includes a depth sensor configured to detect a first depth of a first portion of the biofluid placed in the processing chamber. In some embodiments, the control circuitry is configured to adjust or set the intensity of light emitted by a first light source channel facing the biofluid based on the depth of the biofluid. In some embodiments, the control circuitry is configured to adjust or set the intensity of light emitted by a second light source channel facing the biofluid based on the depth of the biofluid. In some embodiments, the control circuitry is configured to adjust or set the intensity of a first light emitted by each first light source channel facing the first portion of the biofluid based on the depth of the first portion of the biofluid, and to adjust or set the intensity of a second light emitted by each second light source channel facing the second portion of the biofluid based on the depth of the second portion of the biofluid. In some embodiments, the system further includes one or more depth sensors placed in the processing chamber, the one or more depth sensors being configured to detect the depth of the first portion of the biofluid and the depth of the second portion of the biofluid.

[0039] In some embodiments, the system further includes a first container placed inside the processing chamber (e.g., a processing container) for receiving and processing the biological fluid, wherein the first container is adapted to be connected to a source container of the biological fluid, and wherein the first container is adapted to be connected to a second container for receiving the biological fluid from the first container.

[0040] This document further provides a method for treating a biological fluid (e.g., inactivating pathogens in the biological fluid), the method comprising: providing a biological fluid infused with a pathogen inactivating compound (e.g., a photochemical agent); irradiating (e.g., exposing) the biological fluid with ultraviolet light of a first peak wavelength; and irradiating (e.g., exposing) the biological fluid with light of a second peak wavelength (e.g., ultraviolet light), wherein the first peak wavelength differs from the second peak wavelength by at least 5 nm, and wherein the duration and intensity of irradiation of the biological fluid are sufficient to inactivate pathogens in the biological fluid.

[0041] In some embodiments, ultraviolet light of the first peak wavelength is provided by a first light source (e.g., within a processing chamber), and light of the second peak wavelength is provided by a second light source (e.g., within a processing chamber). In some embodiments, 50% of the maximum peak intensity of the light emitted by the first light source is within 10 nanometers of the first peak wavelength (e.g., no more than 10 nanometers larger than the first peak wavelength, no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller than the first peak wavelength, and within 10 nanometers larger than the first peak wavelength). In some embodiments, the full width at half maximum (FWHM) spectral bandwidth (e.g., the spectral bandwidth at maximum peak intensity) of the light emitted by the first light source is less than 20 nanometers (e.g., no more than 10 nanometers larger than the first peak wavelength, no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller than the first peak wavelength, and within 10 nanometers larger than the first peak wavelength). In some embodiments, the ultraviolet light of the first peak wavelength is in the ultraviolet A spectrum (e.g., 315 to 400 nanometers). In some embodiments, the light with the second peak wavelength is in the ultraviolet B spectrum (e.g., 280-315 nm), the ultraviolet C spectrum (e.g., 100-280 nm, 200-280 nm, 240-280 nm), or the visible light spectrum (e.g., 400-800 nm). In some embodiments, the first peak wavelength is in the ultraviolet A spectrum (e.g., 315-400 nm), and the second peak wavelength is in the ultraviolet C spectrum (e.g., 100-280 nm, 200-280 nm, 240-280 nm). In some embodiments, the first peak wavelength is in the ultraviolet A spectrum (e.g., 315-400 nm), and the second peak wavelength is in the ultraviolet B spectrum (e.g., 280-315 nm). In some embodiments, the first peak wavelength is in the ultraviolet A spectrum (e.g., 315-400 nm), and the second peak wavelength is in the ultraviolet A spectrum. In some embodiments, the first peak wavelength is in the ultraviolet A spectrum, and the second peak wavelength is in the visible light spectrum (e.g., 400-800 nm). In some embodiments, the first peak wavelength is in the ultraviolet B spectrum, and the second peak wavelength is in the ultraviolet C spectrum. In some embodiments, the first peak wavelength is in the ultraviolet B spectrum, and the second peak wavelength is in the visible light spectrum. In some embodiments, the first peak wavelength is in the ultraviolet C spectrum, and the second peak wavelength is in the visible light spectrum. In some embodiments, irradiation of the biofluid with ultraviolet light of the first peak wavelength and irradiation of the biofluid with light of the second peak wavelength are performed sequentially or simultaneously.In some embodiments, irradiating the biological fluid with ultraviolet light of the first peak wavelength includes irradiating the biological fluid with ultraviolet light of the first peak wavelength for a first duration, and wherein irradiating the biological fluid with light of the second peak wavelength includes irradiating the biological fluid with light of the second peak wavelength for a second duration. In some embodiments, the first duration and the second duration are different. In some embodiments, the first duration and the second duration are equal. In some embodiments, irradiating the biological fluid with ultraviolet light of the first peak wavelength is performed by a first set of light sources, wherein irradiating the biological fluid with light of the second peak wavelength is performed by a second set of light sources, and wherein the first and second sets of light sources are arranged on a light source array. In some embodiments, the first and second light sources include LEDs. In some embodiments, the pathogen inactivating compound is a photoactive pathogen inactivating compound selected from psoralen, isorhodazine, phosphonazine, phthalocyanine, phenothiazine, porphyrin, and cyanine 540. In some embodiments, the pathogen inactivating compound is psoralen (e.g., amtoxalin).

[0042] This document further provides a method for treating a biological fluid (e.g., inactivating pathogens in the biological fluid), comprising: providing a biological fluid infused with a pathogen inactivating compound (e.g., a photochemical agent); and irradiating (e.g., exposing) the biological fluid with ultraviolet light of a first peak wavelength provided by a first ultraviolet light source (e.g., in a treatment chamber), wherein the full width at half maximum (FWHM) spectral bandwidth (e.g., spectral bandwidth at maximum peak intensity) of the ultraviolet light emitted by the first ultraviolet light source is less than 20 nanometers (e.g., no more than 10 nanometers larger than the first peak wavelength, no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller than the first peak wavelength, within 10 nanometers larger than the first peak wavelength), and wherein the duration and intensity of irradiation of the biological fluid are sufficient to inactivate pathogens in the biological fluid.

[0043] In some embodiments, the first peak wavelength of ultraviolet light is in the ultraviolet A spectrum (e.g., 315 to 400 nm). In some embodiments, the first peak wavelength is between 330 nm and 350 nm (e.g., 340 nm + 5 nm). In some embodiments, the first peak wavelength of ultraviolet light is in the ultraviolet B spectrum (e.g., 280–315 nm). In some embodiments, the first peak wavelength of ultraviolet light is in the ultraviolet C spectrum (e.g., 100–280 nm, 200–280 nm, 240–280 nm). In some embodiments, the first light source comprises an LED. In some embodiments, irradiating the biofluid with ultraviolet light of the first peak wavelength is performed using the first ultraviolet light source as the sole light source for irradiating the biofluid in the processing chamber. In some embodiments, the first light source comprises the sole ultraviolet light source for irradiating the biofluid in the processing chamber during processing. In some embodiments, the biofluid is within a container, and the irradiation of the biofluid with ultraviolet light of the first peak wavelength is performed by a first set of light sources arranged on a light source array, the first set of light sources facing only one side of the container. In some embodiments, the biofluid is contained within a container, and the irradiation of the biofluid with ultraviolet light of the first peak wavelength is performed by a first set of light sources arranged on a light source array (e.g., in a processing chamber), wherein during processing, the array is positioned facing (e.g., irradiating) one side of the biofluid container. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from psoralen, isorhodazine, phosphatrazine, phthalocyanine, phenothiazine, porphyrin, and benzoin 540. In some embodiments, the pathogen-inactivating compound is psoralen (e.g., amtoxalin).

[0044] This document further provides a method for treating a biological fluid (e.g., inactivating pathogens in the biological fluid), comprising: introducing a biological fluid (e.g., a biological fluid in a container) infused with a pathogen inactivating compound (e.g., a photochemical agent) into a treatment chamber, the treatment chamber including one or more photosensors configured to detect (e.g., measure) light (e.g., light intensity) in the treatment chamber and a first light source array configured to irradiate the biological fluid in the treatment chamber, wherein each light source of the first light source array includes either a first light source channel configured to emit ultraviolet light having a first peak wavelength or a second light source channel configured to emit light (e.g., ultraviolet light) having a second peak wavelength, the first peak wavelength differing from the second peak wavelength by at least 5 nanometers; and irradiating the biological fluid by emitting light having the first peak wavelength from each first light source channel and light having the second peak wavelength from each second light source channel, the duration and intensity of irradiation being sufficient to inactivate pathogens in the biological fluid.

[0045] In some embodiments, the method further includes determining a set of characteristics of the biofluid; determining a treatment profile based on the set of characteristics of the biofluid; and adjusting or setting a set of parameters of the treatment chamber according to the treatment profile.

[0046] In some embodiments, irradiation of the biological fluid is performed according to the treatment profile. In some embodiments, the duration and intensity sufficient to inactivate the pathogen are determined by the treatment profile. In some embodiments, the first light source array comprises a plurality of light source groups, wherein each light source group of the first light source array includes a first light source channel configured to emit ultraviolet light having the first peak wavelength and a second light source channel configured to emit light having the second peak wavelength. In some embodiments, 50% of the maximum peak intensity of the light emitted by the first light source channel is within 10 nanometers of the first peak wavelength (e.g., no more than 10 nanometers larger than the first peak wavelength, no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller than the first peak wavelength, within 10 nanometers larger than the first peak wavelength). In some embodiments, the full width at half maximum (FWHM) spectral bandwidth (e.g., the spectral bandwidth at maximum peak intensity) of the light emitted by the first light source channel is less than 20 nanometers (e.g., no more than 10 nanometers larger than the first peak wavelength, no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller than the first peak wavelength, within 10 nanometers larger than the first peak wavelength). In some embodiments, the set of characteristics of the biofluid includes at least one of the following: the volume of the biofluid, the type of the biofluid, or the temperature of the biofluid. In some embodiments, determining the processing profile based on the set of characteristics includes determining the first peak wavelength and the second peak wavelength. In some embodiments, determining the processing profile based on the set of characteristics includes determining a first intensity of ultraviolet light having the first peak wavelength and a second intensity of light having the second peak wavelength. In some embodiments, determining the processing profile based on the set of characteristics includes determining a first emission duration of ultraviolet light having the first peak wavelength and a second emission duration of light having the second peak wavelength. In some embodiments, the processing chamber further includes a first platform placed within the processing chamber, the first platform carrying the biofluid (e.g., one or more biofluid containers). In some embodiments, the processing chamber further includes a heat exchanger thermally connected to the first light source array. In some embodiments, adjusting or setting the set of parameters of the processing chamber includes adjusting or setting the distance between the first light source array and the first platform. In some embodiments, adjusting or setting the set of parameters of the processing chamber includes adjusting or setting the temperature of the processing chamber. In some embodiments, the method further includes agitating the biofluid. In some implementations, adjusting or setting the set of parameters of the treatment chamber includes adjusting or setting parameters associated with agitating the biofluid.

[0047] This document further provides a method for treating biological fluids (e.g., inactivating pathogens in biological fluids), comprising: introducing the biological fluid (e.g., biological fluid in a container) incorporating a pathogen-inactivating compound (e.g., a photochemical agent) into a treatment chamber, the treatment chamber including one or more photosensors configured to detect (e.g., measure) light (e.g., light intensity) in the treatment chamber and a first light source array configured to irradiate the biological fluid in the treatment chamber, wherein each light source in the first light source array includes a light source configured to emit light having a first peak wavelength in a UV A, UV B, and / or UV C spectrum. In the first source channel of ultraviolet light, the full width at half maximum (FWHM) spectral bandwidth (e.g., spectral bandwidth at maximum peak intensity) of the light emitted by the first source channel is less than 20 nanometers (e.g., no more than 10 nanometers larger than the first peak wavelength, no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller than the first peak wavelength, and within 10 nanometers larger than the first peak wavelength); and the biological fluid is irradiated by emitting light having the first peak wavelength from each of the first source channels, the first duration and first intensity of irradiation being sufficient to inactivate pathogens in the biological fluid.

[0048] In some embodiments, each light source in the first light source array includes a first light source channel configured to emit ultraviolet light with a first peak wavelength between about 330 nm and about 350 nm (e.g., between about 335 nm and about 345 nm or about 340 nm). In some embodiments, the method further includes determining a set of characteristics of the biological fluid; determining a treatment profile based on the set of characteristics of the biological fluid; and adjusting or setting a set of parameters of the treatment chamber according to the treatment profile. In some embodiments, irradiation of the biological fluid is performed according to the treatment profile. In some embodiments, a first duration and a first intensity sufficient to inactivate the pathogen are determined by the treatment profile. In some embodiments, 50% of the maximum peak intensity of the light emitted by the first light source channel is within 20 nm of the first peak wavelength (e.g., within 10 nm less than the first peak wavelength and within 10 nm greater than the first peak wavelength). In some embodiments, each light source in the first light source array further includes a second light source channel configured to emit light with a second peak wavelength. In some embodiments, the second peak wavelength differs from the first peak wavelength by at least 5 nm. In some embodiments, 50% of the maximum peak intensity of the light emitted by the second light source channel is within 10 nanometers of the second peak wavelength (e.g., no more than 10 nanometers larger and no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller and no more than 10 nanometers larger than the second peak wavelength). In some embodiments, the full width at half maximum (FWHM) spectral bandwidth (e.g., the spectral bandwidth at maximum peak intensity) of the light emitted by the second light source channel is less than 20 nanometers (e.g., no more than 10 nanometers larger and no more than 10 nanometers smaller than the first peak wavelength; within 10 nanometers smaller and no more than 10 nanometers larger than the second peak wavelength). In some embodiments, the first light source array comprises a plurality of light source groups, and each light source group of the first light source array comprises a first light source channel configured to emit ultraviolet light having the first peak wavelength and a second light source channel configured to emit ultraviolet light having the second peak wavelength. In some embodiments, the set of characteristics of the biological fluid includes at least one of the following: the volume of the biological fluid, the type of the biological fluid, or the temperature of the biological fluid. In some embodiments, determining the processing profile based on the set of features includes determining the first peak wavelength. In some embodiments, determining the processing profile based on the set of features includes determining the first intensity of light having the first peak wavelength. In some embodiments, determining the processing profile based on the set of features includes determining the first duration of emitting light having the first peak wavelength.In some embodiments, the processing chamber further includes a first platform disposed within the processing chamber, the first platform carrying the biofluid (e.g., one or more biofluid containers). In some embodiments, the processing chamber further includes a heat exchanger thermally connected to the first light source array. In some embodiments, adjusting or setting the set of parameters of the processing chamber includes adjusting or setting the distance between the first light source array and the first platform. In some embodiments, adjusting or setting the set of parameters of the processing chamber includes adjusting or setting the temperature of the processing chamber. In some embodiments, the method further includes agitating the biofluid. In some embodiments, adjusting or setting the set of parameters of the processing chamber includes adjusting or setting parameters associated with agitating the biofluid.

[0049] In some embodiments of any of the above-described embodiments, the treatment method is sufficient to inactivate at least 1 log (e.g., at least 2 log, at least 3 log, at least 4 log) of pathogens in the biofluid. In some embodiments, the treatment method is sufficient to inactivate at least 1 log (e.g., at least 2 log, at least 3 log, at least 4 log) of pathogens in the biofluid, and the biofluid is suitable for infusion into a subject after irradiation without further treatment to remove residual pathogen-inactivating compounds or their photoproducts. In some embodiments, irradiation of the biofluid mixed with the pathogen-inactivating compound reduces the concentration of the pathogen-inactivating compound after irradiation to 5 μM or lower (e.g., 4 μM or lower, 3 μM or lower, 2 μM or lower, 1 μM or lower, 0.5 μM or lower). In some embodiments, the biofluid contains 5 μM or less (e.g., 4 μM or less, 3 μM or less, 2 μM or less, 1 μM or less, 0.5 μM or less) of pathogen-inactivating compound after irradiation (e.g., without further treatment to remove residual pathogen-inactivating compound, such as before any subsequent compound removal step, e.g., before subjecting the biofluid to CAD). In some embodiments, the concentration of the pathogen-inactivating compound co-incorporated with the biofluid before irradiation is at least 10 μM (e.g., at least 15 μM, at least 20 μM, at least 30 μM, at least 40 μM, at least 50 μM, at least 60 μM, at least 70 μM, at least 80 μM, at least 90 μM, at least 100 μM, at least 110 μM, at least 120 μM, at least 130 μM, at least 140 μM, or at least 150 μM). In some embodiments, the concentration of the pathogen-inactivating compound incorporated with the biofluid prior to irradiation is about 10 μM to about 1500 μM, about 10 μM to about 1000 μM, about 10 μM to about 500 μM, about 10 μM to about 250 μM, about 10 μM to about 200 μM, about 10 μM to about 150 μM, about 15 μM to about 150 μM, or about 15 μM to about 130 μM. M, about 15 μM to about 110 μM, about 15 μM to about 90 μM, about 30 μM to about 150 μM, about 30 μM to about 130 μM, about 30 μM to about 110 μM, about 30 μM to about 90 μM, about 30 μM to about 60 μM, about 60 μM to about 150 μM, about 60 μM to about 130 μM, about 60 μM to about 110 μM, or about 60 μM to about 90 μM.In some embodiments, the concentration of the pathogen-inactivating compound mixed with the biological fluid prior to irradiation is about 10 μM, about 15 μM, about 20 μM, about 25 μM, about 30 μM, about 35 μM, about 40 μM, about 45 μM, about 50 μM, about 55 μM, about 60 μM, about 65 μM, about 70 μM, about 75 μM, about 80 μM, about 85 μM, about 90 μM, about 95 μM, about 100 μM, about 110 μM, about 120 μM, about 130 μM, about 140 μM, or about 150 μM. In some embodiments, the concentration of the pathogen-inactivating compound mixed with the biofluid after irradiation is at most one-third (e.g., at most one-quarter, at most one-fifth, at most one-tenth or less) of the concentration of the pathogen-inactivating compound mixed with the biofluid before irradiation (e.g., without further treatment to remove residual pathogen-inactivating compounds, such as before any subsequent compound removal step, such as subjecting the biofluid to CAD).

[0050] This document further provides pathogen-inactivated biofluids prepared by methods according to any of the above embodiments. In some embodiments, the biofluid contains 5 μM or less (e.g., 4 μM or less, 3 μM or less, 2 μM or less, 1 μM or less, 0.5 μM or less) of a pathogen-inactivating compound after irradiation (e.g., prior to any subsequent compound removal step).

[0051] This document further provides a method for treating a biological fluid, comprising: providing a biological fluid incorporating a photoactive pathogen inactivating compound; and irradiating the biological fluid with ultraviolet light emitted by one or more first light sources having a first peak wavelength of about 315 nm to about 350 nm, wherein each of the one or more first light sources emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nm, and wherein the duration and intensity of irradiation of the biological fluid are sufficient to inactivate pathogens in the biological fluid.

[0052] In some embodiments, the first peak wavelength is about 315 to about 335 nm. In some embodiments, the first peak wavelength is about 330 nm to about 350 nm. In some embodiments, the first peak wavelength is the peak wavelength of one of the group of one or more first light sources. In some embodiments, the first peak wavelength is the peak wavelength of each of the group of one or more first light sources. In some embodiments, the first peak wavelength is the average peak wavelength of the group of one or more first light sources.

[0053] In some embodiments, the method further includes irradiating the biofluid with ultraviolet light having a second peak wavelength emitted by one or more second light sources, wherein each of the one or more second light sources emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nm, and wherein the second peak wavelength differs from the first peak wavelength by at least 5 nm. In some embodiments, the second peak wavelength is the peak wavelength of one of the one or more second light sources. In some embodiments, the second peak wavelength is the peak wavelength of each of the plurality of second light sources. In some embodiments, the second peak wavelength is the average peak wavelength of the one or more second light sources.

[0054] In some embodiments, the group of one or more first light sources includes one or more LEDs. In some embodiments, the biofluid is contained within a container, and the group of one or more first light sources is arranged as a light source array, the group of one or more first light sources facing only one side of the container. In some embodiments, the photoactive pathogen inactivating compound is psoralen. In some embodiments, the photoactive pathogen inactivating compound is amtoxalin.

[0055] In some embodiments, the method further includes, prior to irradiating the biofluid with ultraviolet light having the first peak wavelength: introducing the biofluid, infused with the photoactive pathogen inactivating compound, into a processing chamber, the processing chamber including one or more photosensors configured to detect light in the processing chamber and a first light source array configured to irradiate the biofluid in the processing chamber, wherein the first light source array includes a first light source channel, the first light source channel including the set of one or more first light sources, wherein irradiating the biofluid includes emitting light having the first peak wavelength from the first light source channel, the first duration and first intensity of irradiation being sufficient to inactivate pathogens in the biofluid. In some embodiments, each light source of the first light source channel is configured to emit ultraviolet light with a first peak wavelength between about 315 nm and about 350 nm. In some embodiments, the method further includes: determining a set of characteristics of the biofluid; determining a processing profile based on the set of characteristics of the biofluid; and adjusting or setting a set of parameters of the processing chamber according to the processing profile. In some embodiments, irradiation of the biofluid is performed according to the processing profile, and the first duration and first intensity sufficient to inactivate the pathogen are determined by the processing profile. In some embodiments, the first light source array includes a second light source channel configured to emit light at a second peak wavelength. In some embodiments, the second peak wavelength differs from the first peak wavelength by at least 5 nm. In some embodiments, the second peak wavelength is in the ultraviolet A, ultraviolet B, or ultraviolet C spectrum. In some embodiments, the second light source channel includes a group of one or more second light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nm. In some embodiments, the set of characteristics of the biofluid includes one or more of the following: the volume of the biofluid, the type of the biofluid, and the temperature of the biofluid. In some embodiments, determining the processing profile based on the set of characteristics of the biofluid includes determining the first intensity of light having the first peak wavelength or determining the first duration of emitting light having the first peak wavelength. In some embodiments, the processing chamber further includes a first platform placed in the processing chamber, the first platform carrying the biofluid. In some embodiments, adjusting or setting the set of parameters of the processing chamber includes adjusting or setting the distance between the first light source array and the first platform.

[0056] In some embodiments, the method further includes agitating the biofluid. In some embodiments, the total dose of ultraviolet light irradiating the biofluid is approximately 0.5 J / cm². 2 Approximately 50 J / cm2 In some embodiments, the total dose of ultraviolet light irradiating the biological fluid emitted by the group of one or more first light sources is approximately 0.5 J / cm². 2 Approximately 50 J / cm 2In some embodiments, the treatment method is sufficient to inactivate at least 1 log of pathogens present in the biofluid, and the biofluid is suitable for infusion into a subject after irradiation without further treatment to remove residual pathogen-inactivating compounds or one or more photoproducts thereof. In some embodiments, the treatment method is sufficient to inactivate at least 1 log (e.g., at least 2 log, at least 3 log, at least 4 log) of pathogens present in the biofluid, and the biofluid is suitable for infusion into a subject after irradiation without subjecting the biofluid to a compound removal step (e.g., subjecting the biofluid to CAD) to remove residual pathogen-inactivating compounds or one or more photoproducts thereof. In some embodiments, the treatment method is sufficient to inactivate at least 1 log (e.g., at least 2 log, at least 3 log, at least 4 log) of pathogens present in the biofluid, and the biofluid contains 5 μM or less (e.g., 4 μM or less, 3 μM or less, 2 μM or less, 1 μM or less, 0.5 μM or less) of the pathogen-inactivating compound after irradiation. In some embodiments, the treatment method is sufficient to inactivate at least 1 log (e.g., at least 2 log, at least 3 log, at least 4 log) of pathogens present in the biofluid, and the biofluid contains 2 μM or less of the pathogen-inactivating compound after irradiation. In some embodiments, the concentration of the pathogen-inactivating compound incorporated with the biofluid before irradiation is at least about 10 μM (e.g., at least about 30 μM, at least about 60 μM, at least about 90 μM, at least about 110 μM). In some embodiments, the concentration of the pathogen-inactivating compound incorporated with the biofluid before irradiation is about 15 μM to about 150 μM (e.g., about 30 μM to about 110 μM, about 60 μM to about 90 μM, about 75 μM). In some embodiments, the concentration of the pathogen-inactivating compound incorporated with the biofluid after irradiation is at most one-third of the concentration of the pathogen-inactivating compound incorporated with the biofluid before irradiation. In some embodiments, the treatment method is sufficient to inactivate at least 4 logs of pathogens present in the biofluid. In some embodiments, the treatment method is sufficient to inactivate at least about 4 logs of pathogens present, wherein the concentration of the pathogen-inactivating compound incorporated with the biofluid before irradiation is about 30 μM to about 110 μM, and wherein the biofluid contains about 5 μM or less of PIC after irradiation. In some embodiments, the treatment method is sufficient to inactivate at least about 4 logs of pathogens present, wherein the concentration of the pathogen-inactivating compound incorporated with the biofluid before irradiation is about 30 μM to about 110 μM, and wherein the biofluid contains about 2 μM or less of PIC after irradiation.In some implementations, the biofluid retains sufficient biological activity after irradiation to make it suitable for infusion into a subject.

[0057] In some embodiments, the biofluid comprises a blood product. In some embodiments, the biofluid comprises a plasma composition. In some embodiments, the concentration of fibrinogen in the irradiated plasma composition is at least 70% of the concentration of fibrinogen in the plasma composition before irradiation. In some embodiments, the concentration of factor VIII in the irradiated plasma composition is at least 70% of the concentration of factor VIII in the plasma composition before irradiation. In some embodiments, the concentrations of factors II, V, X, XI, protein C, and / or S in the irradiated plasma composition are at least 70% of the concentrations of the corresponding factors II, V, X, XI, C, and / or S in the plasma composition before irradiation.

[0058] In some embodiments, the biofluid comprises a platelet composition. In some embodiments, the biofluid further comprises a platelet additive solution. In some embodiments, the amount of platelets in the irradiated platelet composition is at least 80% platelet recovery. In some embodiments, the platelet recovery of the irradiated platelet composition is at least 80% (e.g., at least 80% of the platelet composition before irradiation). In some embodiments, the pH of the irradiated (e.g., post-treatment) platelet composition at 22°C is at least 6.2 (e.g., at least 6.4 after 5 days or 7 days after irradiation). In some embodiments, the method includes incubating the biofluid with the photoactive pathogen inactivating compound for a period of 30 minutes to 24 hours (e.g., about 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours, 24 hours) prior to irradiation.

[0059] This document further provides pathogen-inactivated biofluids prepared by methods according to any of the above embodiments. In some embodiments, the pathogen-inactivated biofluid contains 5 μM or less of the pathogen-inactivating compound. In some embodiments, the pathogen-inactivated biofluid contains 2 μM or less of the pathogen-inactivating compound.

[0060] This document further provides a system for processing biological fluids, the system comprising: a processing chamber configured to receive biological fluids; one or more sensors configured to detect light in the processing chamber; and a first light source array positioned to irradiate the biological fluids in the processing chamber, wherein the first light source array includes a first light source channel configured to emit ultraviolet light with a first peak wavelength of about 315 nm to about 350 nm, and wherein the first light source channel includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nm.

[0061] In some embodiments, the first peak wavelength of the first array is from about 315 nm to about 335 nm. In some embodiments, the first peak wavelength of the first array is from about 330 nm to about 350 nm. In some embodiments, the first peak wavelength of the first array is the average peak wavelength of the one or more light sources in the first light source channel. In some embodiments, the one or more light sources in the first light source channel include one or more light-emitting diodes (LEDs). In some embodiments, the first light source array further includes a second light source channel configured to emit light having a second peak wavelength of the first array, wherein the second light source channel includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nm, and wherein the second peak wavelength of the first array differs from the first peak wavelength of the first array by at least 5 nm. In some embodiments, the second peak wavelength of the first array is in the ultraviolet A, ultraviolet B, or ultraviolet C spectrum. In some embodiments, the second light source channel includes one or more LEDs.

[0062] In some embodiments, the light sources of the first light source array are positioned in a non-uniformly distributed manner across the array. In some embodiments, the system is configured to agitate the biofluid during treatment. In some embodiments, the first light source array comprises two or more light source panels. In some embodiments, the first array is configured such that the light sources of the first array irradiate the biofluid in the treatment chamber with an irradiance difference of less than 25% across the surface of the biofluid facing the first array.

[0063] In some embodiments, the system further includes a first platform disposed within the processing chamber, the first platform being configured to carry the biofluid. In some embodiments, the first platform and the first light source array are configured to translate relative to each other to change the distance between the first light source array and the first platform. In some embodiments, the first platform can slide to introduce and remove the biofluid from the processing chamber. In some embodiments, the first platform is configured to separately hold a first container having at least the biofluid as a first container of biofluid and a second container having a second container of biofluid. In some embodiments, one or more of the one or more sensors are attached to or placed therein on the first platform.

[0064] In some embodiments, the system further includes a barrier placed within the processing chamber between the first light source array and the biological fluid. In some embodiments, the barrier placed within the processing chamber between the first light source array and the biological fluid is transparent to light with wavelengths within 30 nm of the first peak wavelength of the first array. In some embodiments, one or more of the one or more sensors are attached to or disposed therein by the barrier placed within the processing chamber between the first light source array and the biological fluid. In some embodiments, the first array includes a first region of light sources and a second region of light sources, the former configured to irradiate the biological fluid as a first irradiated biological fluid in the processing chamber, and the latter configured to irradiate a second irradiated biological fluid in the processing chamber.

[0065] In some embodiments, the system further includes control circuitry. In some embodiments, the control circuitry is configured to adjust or set the intensity or duration of light emission from each light source of the first light source array. In some embodiments, the control circuitry is configured to adjust or set the intensity or duration of light emission from each light source of the first light source array based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light. In some embodiments, the system further includes one or more sensors configured to detect the presence of biological fluid within the processing chamber.

[0066] In some embodiments, the system further includes a second light source array facing in the opposite direction to the first light source array, wherein the second light source array includes a first light source channel configured to emit light at a first peak wavelength of the second array, and wherein the first light source channel of the second array includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers. In some embodiments, the first peak wavelength of the second array is substantially the same as the first peak wavelength of the first array. In some embodiments, the second light source array includes a second light source channel configured to emit light at a second peak wavelength of the second array, wherein the second light source channel of the second array includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers, and wherein the second peak wavelength of the second array differs from the first peak wavelength of the second array by at least 5 nanometers. In some embodiments, the first light source array and the second light source array are configured to translate relative to each other to change the distance between the first light source array and the second light source array. In some embodiments, the system further includes a second light source array oriented in the same direction as the first light source array, wherein the second light source array includes a first light source channel configured to emit light of a first peak wavelength of the second array, and wherein the first light source array and the second light source array define a first region between the first light source array and the second light source array, and wherein the first light source channel of the second array includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers.

[0067] In some embodiments, the system further includes a first platform placed in the processing chamber between the first light source array and the second light source array, the first platform being configured to carry the biofluid. In some embodiments, the system further includes: a first platform placed in the processing chamber in the first region, the first platform being configured to carry the biofluid as a first carrier of biofluid; and a second platform placed in the processing chamber outside the first region, the second platform being configured to carry a second carrier of biofluid, wherein the second light source array faces the second platform. In some embodiments, one or more of the one or more sensors are attached to or placed therein on the second platform.

[0068] In some embodiments, the system further includes a barrier placed within the processing chamber between the second light source array and the biological fluid. In some embodiments, the barrier placed within the processing chamber between the second light source array and the biological fluid is transparent to light with wavelengths within 30 nm of the first peak wavelength of the first array. In some embodiments, one or more of the one or more sensors are attached to or placed within the barrier placed within the processing chamber between the second light source array and the biological fluid.

[0069] In some embodiments, the system further includes control circuitry configured to adjust or set the intensity or duration of light emission from each light source of the second light source array. In some embodiments, the control circuitry is configured to adjust or set the intensity or duration of light emission from each light source of the second light source array based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light. In some embodiments, the control circuitry is configured to a) determine a set of characteristics of the biofluid; b) determine a treatment profile based on the set of characteristics of the biofluid; c) adjust or set a set of parameters of the treatment chamber according to the treatment profile; and d) irradiate the biofluid according to the treatment profile.

[0070] In some embodiments, the system is configured to irradiate the biofluid infused with a photoactive pathogen inactivating compound, the duration and intensity of which are sufficient to inactivate pathogens present in the biofluid. In some embodiments, the system is configured to irradiate the biofluid infused with a photoactive pathogen inactivating compound, the duration and intensity of which are sufficient to inactivate at least 1 log of pathogens present in the biofluid, and the biofluid is suitable for infusion into a subject after irradiation without further processing to remove residual photoactive pathogen inactivating compound or one or more of its photoproducts. In some embodiments, the system is configured to irradiate the biofluid infused with a photoactive pathogen inactivating compound, the duration and intensity of which are sufficient to inactivate at least 1 log of pathogens present in the biofluid, and the biofluid contains 5 μM or less of the photoactive pathogen inactivating compound after irradiation. In some embodiments, the system is configured to irradiate the biofluid mixed with a photoactive pathogen inactivating compound, the duration and intensity of which are sufficient to reduce the concentration of the photoactive pathogen inactivating compound mixed with the biofluid to at most one-third relative to the concentration of the photoactive pathogen inactivating compound mixed with the biofluid before irradiation. In some embodiments, the system is configured to irradiate the biofluid mixed with the photoactive pathogen inactivating compound, the duration and intensity of which are sufficient to inactivate at least 4 log of pathogens present in the biofluid.

[0071] In some embodiments, the biofluid comprises blood products. In some embodiments, the biofluid comprises a plasma composition. In some embodiments, the biofluid comprises a platelet composition. In some embodiments, the biofluid further comprises a platelet additive solution. In some embodiments, the pathogen-inactivating compound is psoralen. In some embodiments, the photoactive pathogen-inactivating compound is amtoxalin. Attached Figure Description

[0072] Figure 1A-1E A perspective view showing an exemplary system for processing biological fluids.

[0073] Figure 2A-2D An exemplary light source array configuration is shown.

[0074] Figure 3 This is a perspective view of an exemplary system for processing biological fluids, which includes a light source array having multiple light source panels.

[0075] Figure 4 This is a perspective view of an exemplary system for processing biological fluids, which includes opposing arrays of light sources facing a platform for processing biological fluids.

[0076] Figure 5 This is a perspective view of an exemplary system for processing biological fluids, which includes multiple light source arrays facing the same direction.

[0077] Figures 6A-6B This is a perspective view of an exemplary system for processing biological fluids, which includes an array of light sources facing a platform for processing biological fluids.

[0078] Figures 7A-7B This is a flowchart describing an exemplary method for processing biological fluids.

[0079] Figure 8A An exemplary spectral output of the light source is shown, indicating the wavelength of the maximum peak intensity, 50% of the maximum peak intensity, and the full width at half maximum peak intensity.

[0080] Figure 8B Exemplary spectral outputs from three light sources with different wavelengths and wavelength distributions at their maximum peak intensity are shown.

[0081] Figure 9 Exemplary spectral outputs of a broadband fluorescent lamp UV light source and a narrowband LED UV light source are shown. Detailed Implementation

[0082] The following description is provided to enable those skilled in the art to make and utilize various embodiments. The descriptions of specific systems, apparatuses, methods, and applications are provided only as examples. Various modifications to the embodiments described herein will be apparent to those skilled in the art, and the general principles established herein can be applied to other embodiments and applications without departing from the spirit and scope of the various embodiments. Therefore, the various embodiments are not intended to be limited to the embodiments described and shown herein, but are accorded the scope consistent with the claims.

[0083] Biological fluids (such as blood and blood products) may contain one or more contaminating pathogens due to an infected donor or the introduction of one or more pathogens during processing. Therefore, it is desirable to subject such biological fluids to treatment processes that reduce the risk of contamination (e.g., pathogen inactivation, pathogen reduction). Ideally, this process results in the inactivation of a wide range of pathogens (e.g., viruses, bacteria, parasites) that may be present in the biological fluid. The treatment process may also inactivate other unwanted substances, such as cells (e.g., white blood cells) and nucleic acids that may be present in the biological fluid.

[0084] Advantageously, the methods and systems disclosed herein unexpectedly provide higher levels of viral and / or bacterial inactivation (e.g., photochemical inactivation), with more efficient photoconversion of pathogen-inactivating compounds such as psoralen (e.g., S-59). In some embodiments, the methods and systems are sufficient to inactivate at least 1 log (at least 2 log, at least 3 log, at least 4 log) of pathogens in a biological fluid and provide a pathogen-inactivated biological fluid (e.g., a blood product) wherein the pathogen-inactivating compound undergoes sufficient photoconversion after irradiation, making the biological fluid suitable for infusion into a subject without further processing to remove residual pathogen-inactivating compounds or their photoproducts.

[0085] In some embodiments, the photoconversion of the pathogen-inactivating compound (e.g., S-59) is determined as a percentage (e.g., concentration, weight %) of the compound retained after irradiation relative to the amount (e.g., concentration, weight %) of the input pathogen-inactivating compound. In some embodiments, the percentage of the compound retained after irradiation is less than about 40%, less than about 35%, less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, or less than about 5%. In some embodiments, the photoconversion of the pathogen-inactivating compound is determined as the concentration (e.g., μM concentration) of the residual pathogen-inactivating compound retained after irradiation.

[0086] Figure 1A This is a perspective view of an exemplary system 100 for processing biological fluids. As used herein, "biological fluid" means any fluid found in or derived from an organism (e.g., human, animal, plant, microorganism) or containing one or more components found in, isolated from, or derived from an organism (e.g., biological products), including synthetic forms thereof. Biological fluids may include, but are not limited to, blood and blood products, vaccines, cells (e.g., primary cells, cell lines, cell cultures), natural and recombinant proteins (e.g., therapeutic agents, antibodies), bacterial cultures, viral suspensions, etc. As used herein, "blood products" means blood (e.g., whole blood) or components or derivatives of blood, such as red blood cells, white blood cells, platelets, plasma, cryoprecipitate, and hypothermic anemic (e.g., hypothermic reduced) plasma, or combinations of one or more such components isolated from blood. In some embodiments, biological fluids may further include non-biological fluids, such as physiological solutions (e.g., diluent solutions), including but not limited to saline, buffer solutions, nutrient solutions, platelet additive solutions (PAS), and / or anticoagulant solutions. In some embodiments, the biofluid comprises a volume of about 50 mL to about 1000 mL (e.g., about 100 mL to about 750 mL, about 200 mL to about 600 mL, about 100 mL, about 200 mL, about 300 mL, about 400 mL, about 500 mL, about 600 mL).

[0087] In some embodiments, the treatment system 100 can be used to inactivate one or more pathogens in a biological fluid, preferably a biological fluid mixed with one or more pathogen inactivating compounds (e.g., the photoactive pathogen inactivating compound psoralen). Specifically, the treatment system 100 can irradiate a mixture of one or more pathogen inactivating compounds and the biological fluid with light of certain wavelengths (e.g., ultraviolet light) to induce a photochemical reaction and inactivate pathogens, such as viruses, bacteria, parasites, and other contaminants that may be present in the biological fluid, such as cellular contaminants (e.g., leukocytes). In some embodiments, the treatment system 100 can irradiate a mixture of one or more pathogen inactivating compounds and a biological fluid with a volume of about 50 mL to about 1000 mL (e.g., about 100 mL to about 750 mL).

[0088] In some embodiments, after the processing system 100 irradiates a mixture of one or more pathogen-inactivating compounds and a biofluid with light of certain wavelengths (e.g., about 315 nm to about 350 nm, about 315 nm to about 335 nm, about 330 nm to about 350 nm) (e.g., ultraviolet light, ultraviolet A light) to induce a photochemical reaction and inactivate the pathogen, the biofluid is suitable for infusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual components that can be used for photochemical inactivation of pathogens, such as pathogen-inactivating compounds (PICs) or their photoproducts. In some embodiments, after the processing system 100 irradiates a mixture of one or more pathogen-inactivating compounds and a biofluid with light of certain wavelengths (e.g., about 315 nm to about 350 nm, about 315 nm to about 335 nm, about 330 nm to about 350 nm) (e.g., ultraviolet light) to induce a photochemical reaction and inactivate the pathogen, the biofluid contains less than 5 μM of PIC (e.g., less than 2 μM of PIC).

[0089] The term "pathogen inactivating compound" means any suitable compound, such as a small organic compound, that can be used to inactivate pathogens that may be present in biological fluids (e.g., blood or blood products). Pathogen inactivating compounds that are "photoactive," "photoactivated," "photochemical," or "photosensitizer" compounds are suitable compounds that require a certain level of light to adequately inactivate pathogens. Such compounds are preferred in inactivating pathogens in biological products because they provide control over the inactivation process. In some embodiments, the pathogen inactivating compound is selected from psoralen, isorhodazine, phosphonazine, phthalocyanine, phenothiazine, porphyrin, and phthalocyanine 540. In some embodiments, the pathogen inactivating compound is psoralen. In some embodiments, the pathogen inactivating compound is amtoxalin (e.g., S-59). Such photoactivated or photochemical pathogen inactivating compounds as described herein may include, but are not limited to, psoralen, isorhodazine, phosphonazine, phthalocyanine, phenothiazine, and porphyrin, wherein these terms should be understood to cover the general category of compounds, i.e., the core compound and its suitable derivatives. For example, psoralen is typically described as the psoralen core compound and any of its derivatives (e.g., amtosalin), isochorazine is typically described as the isochorazine core and any of its derivatives (e.g., riboflavin), and so on. These derivatives include the core compound structure and any additional substituents on the core. The description of these compounds includes any of their salts.

[0090] The term "amtosalicyline" refers to the compound 3-(2-aminoethoxymethyl)-2,5,9-trimethylfurano[3,2-g]chromone-7-one and any salt thereof. This compound may also be referred to as 4'-(4-amino-2-oxa)butyl-4,5',8-trimethylpsoralen. In the cases where the methods of this disclosure include the addition of amtosalicyline HCl (an HCl salt of amtosalicyline), the removal of this compound from biological fluids such as blood products (e.g., platelet compositions, platelet units, plasma compositions, whole blood compositions, plasma compositions) is not limited to the removal of amtosalicyline HCl, as amtosalicyline may exist in solution as other salts or as a free base. As used in the methods described herein, removal of amtosalicyline means the removal of the compound in any form, such as as a free base or as any salt, as measured by the assays described herein.

[0091] In some embodiments, the pathogen-inactivating compound is a 4-primary amino-substituted psoralen, which is a psoralen compound in which an NH2 group is linked to the 4' position of psoralen via a hydrocarbon chain of 2 to 20 carbons, wherein 0 to 6 of these carbons are independently substituted with NH or O, and each substitution site is separated from each other by at least two carbons and from psoralen by at least one carbon. The 4'-primary amino-substituted psoralen may have further substitutions at the 4, 5', and 8 positions of psoralen, including but not limited to the following groups: H and (CH2). n CH3, where n = 0-6. In some embodiments, the 4'-primary amino-substituted psoralen comprises: a) a substituent R1 on the 4' carbon atom, selected from: -(CH2) u -NH2、-(CH2) w -R2-(CH2) z -NH2、-(CH2) w -R2-(CH2) x -R3-(CH2) z -NH2 and -(CH2) w -R2-(CH2) x -R3-(CH2) y -R4-(CH2) z -NH2; wherein R2, R3, and R4 are independently selected from O and NH, where u is an integer from 1 to 10, w is an integer from 1 to 5, x is an integer from 2 to 5, y is an integer from 2 to 5, and z is an integer from 2 to 6; and b) the substituents R5, R6, and R7 on the 4th, 5', and 8th carbon atoms, respectively, are independently selected from H and (CH2). v CH3, where v is an integer from 0 to 5; or a salt thereof.

[0092] In some embodiments, the pathogen-inactivating compound is a 5-primary amino-substituted psoralen, which is a psoralen compound in which an NH2 group is linked to the 5' position of psoralen via a hydrocarbon chain of 1 to 20 carbons, wherein 0 to 6 of these carbons are independently substituted with NH or O, and each substitution site is separated from each other by at least two carbons and from psoralen by at least one carbon. The 5'-primary amino-substituted psoralen may have further substitutions at the 4, 4', and 8 positions of psoralen, including but not limited to the following groups: H and (CH2). n CH3, where n = 0-6. In some embodiments, the 5'-primary amino-substituted psoralen comprises: a) a substituent R1 on the 5' carbon atom, selected from: -(CH2) u -NH2、-(CH2) w -R2-(CH2) z -NH2、-(CH2)w -R2-(CH2) x -R3-(CH2) z -NH2 and -(CH2) w -R2-(CH2) x -R3-(CH2) y -R4-(CH2) z -NH2; wherein R2, R3, and R4 are independently selected from O and NH, and wherein u is an integer from 1 to 10, w is an integer from 1 to 5, x is an integer from 2 to 5, y is an integer from 2 to 5, and z is an integer from 2 to 6; and b) the substituents R5, R6, and R7 on the 4th, 4', and 8th carbon atoms, respectively, are independently selected from H and (CH2). v CH3, where v is an integer from 0 to 5, where R1 is selected from -(CH2). u When -NH2 is present, R7 is (CH2). v CH3, wherein R5, R6, and R7 are (CH3) 2 ) v When CH3, u is an integer from 3 to 10; or a salt thereof. Exemplary psoralen is described, for example, in U.S. Patent No. 5,593,823.

[0093] In some embodiments, a biofluid (e.g., a platelet composition) is co-infused with a pathogen-inactivating compound (PIC) in a platelet additive solution (PAS). In some embodiments, the PIC is co-infused with the PAS prior to co-infusion with the biofluid. Platelet additive solutions are known in the art, for example, as described by Alhumaidan et al. and Ringwald et al. (Alhumaidan, H. and Sweeney, J., J Clin Apheresis, 27:93-98 (2012); Ringwald et al., Transfusion Medicine Reviews, 20:158-64 (2006)), which are incorporated herein by reference in their entirety. In some embodiments, the platelet additive solution (PAS) comprises one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate. In some embodiments, the platelet additive solution (PAS) is a PAS approved by a regulatory or certification body generally accepted in the art.

[0094] In some implementations, the platelet additive solution (PAS) contains one or more of sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, sodium phosphate, sodium gluconate, glucose, and sodium bicarbonate.

[0095] In some embodiments, PAS comprises chloride, citrate, phosphate, and potassium. In some embodiments, PAS comprises chloride, citrate, and acetate. In some embodiments, PAS comprises chloride, citrate, phosphate, and acetate. In some embodiments, PAS comprises chloride, citrate, acetate, magnesium, potassium, and gluconate. In some embodiments, PAS comprises chloride, citrate, phosphate, acetate, magnesium, and potassium. In some embodiments, PAS comprises chloride, acetate, magnesium, potassium, and gluconate. In some embodiments, PAS comprises chloride, citrate, phosphate, acetate, magnesium, potassium, and glucose.

[0096] In some embodiments, PAS comprises sodium chloride, sodium acetate, potassium chloride, magnesium chloride, and sodium gluconate. In some embodiments, PAS comprises sodium chloride, sodium acetate, and sodium citrate. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, and sodium phosphate. In some embodiments, PAS comprises sodium chloride, sodium citrate, sodium phosphate, and potassium chloride. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, and sodium phosphate. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, and sodium gluconate. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, sodium phosphate, glucose, and sodium bicarbonate. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, glucose, and sodium bicarbonate.

[0097] In some embodiments, PAS is PAS-I. In some embodiments, PAS is PlasmaLyte. In some embodiments, PAS is PAS-II. In some embodiments, PAS is T-Sol. In some embodiments, PAS is PAS-III. In some embodiments, PAS is Intersol. In some embodiments, PAS is PAS-IIIM SSP. In some embodiments, PAS is ComposolPAS-G. In some embodiments, PAS is M-Sol. In some embodiments, PAS is Isoplate. In some embodiments, PAS is PAS-A. In some embodiments, PAS is PAS-B. In some embodiments, PAS is PAS-C. In some embodiments, PAS is PAS-D. In some embodiments, PAS is PAS-E. In some embodiments, PAS is PAS-F. In some embodiments, PAS is PAS-G.

[0098] In some embodiments, a biological fluid (e.g., a plasma composition, a platelet composition, or a platelet composition in PAS) is incubated with a photoactive pathogen inactivating compound for a period of time from 30 minutes to 24 hours (e.g., 2 hours to 24 hours, 4 hours to 24 hours, 8 hours to 24 hours, or 12 hours to 24 hours) before irradiation.

[0099] Biofluids, such as blood products including whole blood, red blood cells, and platelet-containing and plasma-containing blood products (e.g., platelet compositions, plasma compositions), may contain pathogens or may be contaminated with pathogens during processing. Therefore, it is desirable to subject such biofluids (e.g., blood products) to pathogen inactivation treatment to reduce the risk of infusion-related disease transmission. Various treatments and methods have been employed to reduce the risk of infusion-related disease transmission from blood products (such as platelet-containing and plasma-containing blood products). In addition to pathogen screening and detection and subsequent removal of contaminated blood products, methods including treatments to inactivate any present pathogens (i.e., pathogen inactivation) may be employed. Ideally, this method results in the inactivation of a wide range of pathogens that may be present in the blood products, such as viruses, bacteria, and parasites. For example, pathogen inactivation may involve the addition of low molecular weight compounds that inactivate various pathogens, with preferred methods involving the addition of photosensitizers (e.g., photoactive compounds, photochemical), which, when activated by irradiation with light of a suitable wavelength, will inactivate a variety of pathogens that may be present. Two commercially available preferred methods include adding amtoxalin or riboflavin to blood products (e.g., platelets, plasma) followed by UV irradiation. Other methods include UV irradiation without the addition of photosensitizers (e.g., UV sterilization), and irradiation with other photoactive compounds, including psoralen derivatives other than amtoxalin, isorhodiazines other than riboflavin, phosphatazines, dyes such as phthalocyanine, phenothiazine dyes (e.g., methylene blue, azure B, azure C, thionine, toluidine blue), porphyrin derivatives (e.g., diheptoporphyrin ether, heptoporphyrin derivatives, benzo[a]porphyrin derivatives, alkyl-substituted thiazolines), and phthalocyanine 540 (Prodouz et al., Blood Cells 1992, 18(1):101-14; Sofer, Gail, BioPharm, August 2002). Other pathogen inactivation systems include, for example, those described in International Application Publication No. WO2012071135, WO2012018484, WO2003090794, WO2003049784, WO1998018908, WO1998030327, WO1996008965, WO1996039815, WO1996039820, WO1996040857, WO1993000005, U.S. Patent Application No. US20050202395, and U.S. Patents Nos. 8,296,071 and 6,548,242, the contents of which relate to pathogen inactivation in blood products are hereby incorporated by reference. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from psoralen, isorhodoxime, isorhodoxime, phthalocyanine, phenothiazine, porphyrin, and quinoline 540. In some embodiments, the pathogen-inactivating compound is psoralen.In some implementations, the pathogen-inactivating compound is amtoxalin. When pathogen inactivation is carried out by adding a compound to a biological fluid, such as a blood product (e.g., platelets, plasma), it is desirable in some cases to remove any residual pathogen-inactivating compound or its byproducts (e.g., photoproducts, degradation products), for example, through more efficient photoconversion by the pathogen-inactivating compound.

[0100] Some methods for removing pathogen-inactivating compounds or their byproducts include the use of pathogen-inactivating compound removal devices, such as devices for reducing the concentration of pathogen-inactivating compounds, like small organic compounds and their byproducts, in biological fluids while substantially maintaining the desired bioactivity of the biological fluid, including compound adsorption devices (CAD). In some embodiments, the removal device includes porous adsorbent particles in an amount sufficient to reduce the pathogen-inactivating compound to below the desired concentration, wherein the adsorbent particles have an affinity for the pathogen-inactivating compound. A variety of adsorbent particles are known, generally including particles made of any natural or synthetic material capable of interacting with the compound to be removed, including particles made of natural materials such as activated carbon, silica, diatomaceous earth, and cellulose, and synthetic materials such as hydrophobic resins, hydrophilic resins, or ion exchange resins. Such synthetic resins include, for example, carbonaceous materials, polystyrene, polyacrylic acid, polyacrylates, cation exchange resins, and polystyrene-divinylbenzene. Detailed descriptions of such removal devices and adsorbent particles can be found in international applications WO1996040857, WO1998030327, WO1999034914 and WO2003078023, and include, for example, Amberlite (Rohm and Haas) XAD-2, XAD-4, XAD-7, XAD-16, XAD-18, XAD-1180, XAD-1600, XAD-2000, XAD-2010; Amberchrom (Toso Haas) CG-71m, CG-71c, CG-161m, CG161c; Diaion Sepabeads (Mitsubishi Chemicals) HP20, SP206, SP207, SP850, HP2MG, HP20SS, SP20MS; Dowex (Dow Optipore (Chemical) XUS-40285, XUS-40323, XUS-43493 (also known as Optipore V493 (dry form) or Optipore L493 (hydrated form)), Optipore V503, Optipore SD-2; HypersolMacronet (Purolite) MN-100, MN-102, MN-150, MN-152, MN-170, MN-200, MN-202, MN-250, MN-252, MN-270, MN-300, MN-400, MN-500, MN-502; Purosorb (Purolite) PAD 350, PAD 400, PAD428, PAD 500, PAD 550, PAD 600, PAD 700, PAD 900 and PAD 950.Materials used to form the immobilization matrix typically include low-melting-point polymers such as nylon, polyester, polyethylene, polyamide, polyolefin, polyvinyl alcohol, ethylene vinyl acetate, or polysulfone. In one example, a removal device for amtosalin-inactivated blood products is commercially available, including, for example, a removal device containing Hypersol Macronet MN-200 adsorbent housed within a sintered matrix, wherein the sintered matrix comprises PL2410 plastic as a binder.

[0101] Inactivating pathogens in biological fluids may require satisfying various treatment parameters, including the treatment profile of the biological fluid. Therefore, the systems and methods discussed herein can be controlled and used to treat one or more biological fluids according to one or more corresponding treatment profiles. As used herein, a treatment profile of a biological fluid refers to a set of treatment parameters required to inactivate one or more types of pathogens present in the biological fluid. Such parameters may include, but are not limited to, one or more peak wavelengths of light applied to the biological fluid (e.g., one or more peak wavelengths of light irradiating the biological fluid), the duration of light applied to the biological fluid at one or more peak wavelengths, the intensity of light applied to one or more portions of the biological fluid at one or more peak wavelengths, the energy dose of light applied to one or more portions of the biological fluid at one or more peak wavelengths, the angle of incidence of light applied to the biological fluid, the temperature during treatment of the biological fluid, the method of agitation / mixing of the biological fluid, the duration of agitation or mixing of the biological fluid, the distance between light sources applied to the biological fluid, and the type of biological fluid, etc. As described herein, a “peak wavelength” of a light source refers to the wavelength at which the light emitted by the light source is at its maximum intensity. Figure 8A An exemplary spectral output 802 of the light source is shown (e.g., a spectral curve). A vertical solid line 804 identifies the wavelength of maximum peak intensity (e.g., peak wavelength), and a horizontal dashed line 806 represents 50% of the maximum peak intensity. Vertical dashed lines 812 and 814 identify points 816 and 818 located at half-maximum on either side of the peak, representing the full width (e.g., bandwidth) along the wavelength axis between these points (e.g., FWHM, 20 nm full width, 10 nm from peak half-width). The spectral curve includes, for example,... Figure 8B The spectral curves 850, 860, and 870 shown from light sources with similar peak intensities may have symmetrical (B) or asymmetrical (A, C) wavelength distributions, as well as peak wavelengths for different light sources. An exemplary difference 885 in peak wavelengths (e.g., >5 nm) is also described.

[0102] Pathogens inactivated by the systems and methods of this disclosure may include, for example, any number of viruses, bacteria, and / or parasites. Exemplary pathogens may include enveloped viruses, non-enveloped viruses, DNA viruses, such as viruses of the Papillomaviridae, Parvoviridae, Herpesviridae, Poxviridae, Hepatoviridae, and Polyomaviridae families; RNA viruses, such as reoviridae, Parvoviridae, Caliciviridae, Capoviridae, Arenaviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, Bunyaviridae, Rhabdoviridae, Filoviridae, Coronaviridae, Astroviridae, Bonaviridae, Arterioviridae, and hepatitis viruses. Viruses of the family Retroviridae, including human immunodeficiency virus (e.g., HIV-1), HTLV-1, HTLV-2, adenovirus, hepatitis A virus, hepatitis B virus, hepatitis C virus, yellow fever virus, Zika virus, hepatitis D virus, hepatitis E virus, West Nile virus, Lassa virus, Ebola virus, Marburg virus, alphaviruses (e.g., flexovirus), Epstein-Barr virus, dengue virus, cytomegalovirus, BK virus, influenza virus, bluetongue virus, and / or adenovirus. Exemplary pathogens may include Gram-positive bacteria, Gram-negative bacteria, anaerobic bacteria, Escherichia coli (e.g., *Escherichia coli*), Yersinia spp. (e.g., *Yersinia enterocolitica*), Klebsiella spp. (e.g., *Klebsiella pneumoniae*), Serratia spp. (e.g., *Serratia marcescens*), Staphylococcus spp. (e.g., *Staphylococcus epidermidis*, *Staphylococcus aureus*), Streptococcus spp. (e.g., *Streptococcus pyogenes*), Bacillus spp. (e.g., *Bacillus cactus*), and Clostridium spp. (e.g., *Aeromonas vaginalis*). Examples of pathogens include *Clostridium*, *Propionibacterium* (e.g., *Propionibacterium acnes*), *Treponema* (e.g., *Treponema pallidum*), *Borrelia* (e.g., *Borrelia burgdorferi*), *Listeria* (e.g., *Listeria monocytogenes*), *Pseudomonas* (e.g., *Pseudomonas aeruginosa*), *Haemophilus* (e.g., *Haemophilus parainfluenzae*), *Rickettsia* (e.g., *Rickettsia rickettsia*), *Anaplasma* (e.g., *Anaplasma phagocytosus*), and *Acinetobacter* (e.g., *Acinetobacter baumannii*). Exemplary pathogens may also include parasites such as *Plasmodium* (e.g., *Plasmodium falciparum*), *Babesia* (e.g., *Babesia microsporum*), *Trypanosoma* (e.g., *Trypanosoma krusei*), and *Leishmania* (e.g., *Leishmania brasiliensis*). Additionally, the systems and methods of this disclosure can inactivate one or more unwanted cell types, such as leukocytes, in biological fluids. It should be understood that treating biological fluids to inactivate potential pathogens does not necessarily inactivate all potential pathogens, but it significantly reduces the amount of pathogens, thereby significantly reducing the risks associated with the presence of pathogens (e.g., infusion-related diseases caused by blood products, infusion-transmitted infections caused by blood products).Pathogen inactivation can be determined by measuring the number of infectious pathogens (e.g., viral particles, bacteria) in a given volume, and is typically expressed as a log reduction in pathogen infectivity or a log reduction in titer. Methods for measuring the log reduction in titer and assessing pathogen inactivation levels are well known in the art. When testing an inactivation process against multiple pathogens, a reduction in titer for a specific pathogen is at least about 1 log, at least about 2 log, at least about 3 log, at least about 4 log, or at least about 5 log or more. Such pathogen-inactivated biofluids, in addition to being used to treat (e.g., infusion, therapy) subjects in need, can be further processed for other uses, such as further processing to provide products derived from the biofluid, for example, platelet lysate products from pathogen-inactivated platelet preparations or cryoprecipitants from pathogen-inactivated plasma preparations.

[0103] Turning Figure 1A An exemplary system 100 for processing biological fluids includes a processing chamber 102 for receiving one or more biological fluids 108 and 110, and a light source array 104 positioned to irradiate the one or more biological fluids 108 and 110. In some embodiments, the light source array 104 may include a single light source in the chamber 102 positioned to irradiate the one or more biological fluids 108 and 110. (The following is a continuation of the previous paragraph...) Figure 3-5 In other embodiments described, multiple light source arrays may be used to illuminate one or more biological fluids placed in chamber 102 of various embodiments. As described herein, "light source array" means one or more light sources arranged on any two-dimensional or three-dimensional surface (e.g., continuous surface, discontinuous surface).

[0104] One or more light source channels 106 are included in the light source array 104. Each light source channel 106 may be a group of one or more light sources having the same wavelength (e.g., peak wavelength). In an exemplary group, one light source may have a peak wavelength. In another exemplary group, two light sources may have the same peak wavelength as each other. In yet another exemplary group, each of the multiple light sources may have a different peak wavelength than each other. In a further exemplary group, a first subgroup of one or more light sources may have a single peak wavelength, and a second subgroup of one or more light sources may have different peak wavelengths. Within a light source channel having multiple light sources, all light sources may have corresponding peak wavelengths, all of which are within the wavelength range of the light source channel (e.g., the range of 1-20 nm; e.g., 1 nm, 2 nm, 3 nm, 4 nm, 5 nm or greater, greater than and / or less than a specific wavelength). For example, in some embodiments, within a light source channel having multiple light sources, all light sources may have peak wavelengths within the range given in this disclosure, e.g., about 315 nm to about 350 nm (e.g., about 315 nm to about 335 nm, about 330 nm to about 350 nm). In light source channel 106, each light source can be any light source that provides light with desired characteristics (e.g., peak wavelength, spectral bandwidth), including but not limited to solid-state lamps (SSL), light-emitting diodes (LEDs), organic light-emitting diodes (OLEDs), polymer light-emitting diodes (PLEDs), and laser diodes. The light source channels 106 of the light source array 104 can be connected in series, in parallel, or a combination of series and parallel circuits. In light source channels 106 with multiple light sources, these light sources can be controlled together or separately.

[0105] Each light source channel 106 may be tilted (e.g., tilted in an adjustable manner) relative to the normal direction (e.g., perpendicular to the surface) of the surface on which each light source channel 106 is arranged. For example, each light source channel 106 may be tilted at an angle >0° to about 50° relative to the normal direction of the surface 124 defined by the plane of the light source array 104, such as about 45°, 40°, 35°, 30°, 25°, 20°, 15°, 10°, 5°, 4°, 3°, 2° or about 1°, or <50°, <45°, <40°, <35°, <30°, <25°, <20°, <15°, <10°, <5°, <4°, <3°, <2° or <1°. Each light source channel 106 (e.g., a light source therein) may be tilted independently, such that one or more light source channels 106 (e.g., multiple light sources therein) are tilted at an angle different from one or more other light source channels 106 (e.g., multiple light sources therein). It is desirable to tilt one or more light source channels 106 to control the intensity and / or angle of incidence of the light illuminating the biological fluids 108 and 110.

[0106] Each light source channel 106 can be adjusted or configured to emit light of different intensities (e.g., adjusting the light dose, adjusting the energy dose), with one or more peak wavelengths of light applied to one or more portions of the biological fluid at said intensities. For example, each light source channel can emit light at a maximum intensity (e.g., 100%) or less than a maximum intensity (e.g., about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, or less).

[0107] Each light source channel 106 can emit various types of light. For example, each light source channel can emit ultraviolet light, ultraviolet A light, ultraviolet B light, ultraviolet C light, and / or visible light. In addition, each light source channel 106 can emit light with various peak wavelengths. For example, the emitted peak wavelengths can be in the ultraviolet A spectrum (e.g., 315-400 nm), ultraviolet B spectrum (e.g., 280-315 nm), ultraviolet C spectrum (e.g., 100-280 nm, 200-280 nm, 240-280 nm) or visible light spectrum (e.g., 400-800 nm). In some embodiments, the emitted peak wavelengths may be between about 240 nm and about 250 nm, between about 245 nm and about 255 nm, between about 250 nm and about 260 nm, between about 255 nm and about 265 nm, between about 260 nm and about 270 nm, between about 265 nm and about 275 nm, between about 270 nm and about 280 nm, or between about 275 nm and about 285 nm. In some embodiments, the emitted peak wavelengths may be between about 280 nm and about 290 nm, between about 285 nm and about 295 nm, between about 290 nm and about 300 nm, between about 300 nm and about 310 nm, between about 305 nm and about 315 nm, or between about 310 nm and about 320 nm. In some implementations, the emitted peak wavelengths may be between approximately 315 nm and approximately 325 nm, between approximately 320 nm and approximately 330 nm, between approximately 325 nm and approximately 335 nm, between approximately 330 nm and approximately 340 nm, between approximately 335 nm and approximately 345 nm, between approximately 340 nm and approximately 350 nm, between approximately 345 nm and approximately 355 nm, between approximately 350 nm and approximately 360 nm, between approximately 355 nm and approximately 365 nm, between approximately 360 nm and approximately 370 nm, between approximately 365 nm and approximately 375 nm, between approximately 370 nm and approximately 380 nm, between approximately 375 nm and approximately 385 nm, between approximately 380 nm and approximately 390 nm, between approximately 385 nm and approximately 395 nm, and between approximately 390 nm and approximately 400 nm. In some implementations, the peak wavelength of the emission can be approximately 240 nm, approximately 245 nm, approximately 250 nm, approximately 255 nm, approximately 260 nm, approximately 265 nm, approximately 270 nm, approximately 275 nm, approximately 280 nm, approximately 285 nm, approximately 290 nm, approximately 295 nm, approximately 300 nm, approximately 305 nm, approximately 310 nm, approximately 315 nm, approximately 320 nm, approximately 325 nm, approximately 330 nm, approximately 335 nm, approximately 340 nm, approximately 345 nm, approximately 350 nm, approximately 355 nm, approximately 360 nm, approximately 365 nm, approximately 370 nm, approximately 375 nm, approximately 380 nm, approximately 385 nm, approximately 390 nm, approximately 395 nm, or approximately 400 nm.In some embodiments, the peak wavelength of the emission may be between about 255 nm and about 275 nm (e.g., between about 260 nm and about 270 nm, 265 nm). In some embodiments, the peak wavelength of the emission may be between about 275 nm and about 295 nm (e.g., between about 280 nm and about 290 nm, 285 nm). In some embodiments, the peak wavelength of the emission may be between about 300 nm and about 320 nm (e.g., between about 305 nm and about 315 nm, 310 nm). In some embodiments, the peak wavelength of the emission may be between about 315 nm and about 335 nm (e.g., between about 320 nm and about 330 nm, 325 nm). In some embodiments, the peak wavelength of the emission may be between about 330 nm and about 350 nm (e.g., between about 335 nm and about 345 nm, 340 nm). In some embodiments, the peak wavelength of the emission may be between about 355 nm and about 375 nm (e.g., between about 360 nm and about 370 nm, 365 nm). In some embodiments, the peak wavelength of the emission may be between about 375 nm and about 395 nm (e.g., between about 380 nm and about 390 nm, 385 nm). In some embodiments, the peak wavelength of the emission may be in (1) a UV-A spectrum (e.g., 315-400 nm); and (2) a UV-B spectrum (e.g., 280-315 nm) or a UV-C spectrum (e.g., 100-280 nm, 200-280 nm, 240-280 nm). In some embodiments, the peak wavelength of the emission is in the UV-A spectrum between about 315 nm and about 350 nm (e.g., between about 320 nm and about 345 nm, between about 315 nm and about 335 nm, between about 330 nm and about 350 nm).

[0108] In some embodiments, all light source channels 106 of the light source array 104 may emit a peak wavelength that is substantially the same (e.g., within a variance of ±1 nm, ±2 nm, ±3 nm, ±4 nm, ±5 nm). A light source channel may include multiple light sources with different peak wavelengths (e.g., measured peak wavelengths) within a range of variability. In some embodiments, the average peak wavelength of multiple light sources spanning a single light source channel may be the same as a specific peak wavelength of a particular light source within that single light source channel. In other embodiments, the average peak wavelength of multiple light sources spanning a single light source channel may differ from all specific peak wavelengths of each light source within that single light source channel (e.g., by about 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, or more). In some embodiments, some light source channels may emit light at a first peak wavelength, and other light source channels may emit light at a second peak wavelength. The first peak wavelength may differ from the second peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. For example, in a non-limiting embodiment, the first light source channel may emit light with a peak wavelength in the UV A spectrum as described above (e.g., between about 330 nm and about 350 nm), and the second light source channel may emit light with a peak wavelength in the UV C spectrum as described above (e.g., between about 250 nm and about 260 nm, or between about 260 nm and about 270 nm) or in the UV B spectrum as described above (e.g., between about 305 nm and about 315 nm). In another non-limiting embodiment, the first light source channel may emit light with a peak wavelength in the UV A spectrum as described above (e.g., between about 330 nm and about 350 nm), and the second light source channel may emit light with a peak wavelength also in the UV A spectrum as described above (e.g., between about 315 nm and about 335 nm, or between about 355 nm and about 375 nm). In some embodiments, the first peak wavelength is the average peak wavelength of one or more light sources in the first light source channel. In some embodiments, the light source array 104 may include first, second, and third light source channels, each emitting light at a first, second, and third peak wavelength, respectively. In some embodiments, the first peak wavelength may differ from the second peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more, and / or the second peak wavelength may differ from the third peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. Alternatively, each of the first, second, and third peak wavelengths may differ from each other by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. In some embodiments, the light source array may include first, second, third, and fourth light source channels, each emitting light at a first, second, third, and fourth peak wavelength, respectively.In some implementations, at least two, at least three, or at least four of the first, second, third, and fourth peak wavelengths may differ from each other by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. Alternatively, each of the first, second, third, and fourth peak wavelengths may differ from each other by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. Alternatively, the first peak wavelength may be substantially the same as the third peak wavelength (e.g., equal to the third peak wavelength within a variance of +1 nm, +2 nm, +3 nm, +4 nm, or +5 nm), the second peak wavelength may be substantially the same as the fourth peak wavelength (e.g., equal to the fourth peak wavelength), and the first peak wavelength may differ from the second peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm.

[0109] In some embodiments, each light source channel 106 may emit light with a narrow spectral bandwidth. For example, the full width at half maximum (FWHM) spectral bandwidth (e.g., the spectral bandwidth at maximum peak intensity) of the light emitted by each light source channel 106 may be less than 20 nm, less than 18 nm, less than 16 nm, less than 14 nm, less than 12 nm, less than 10 nm, less than 9 nm, less than 8 nm, less than 7 nm, less than 6 nm, or less than 5 nm. In some embodiments, the full width at half maximum (FWHM) spectral bandwidth of the light emitted by each light source channel is within 10 nm smaller than the peak wavelength and / or within 10 nm larger than the peak wavelength (e.g., no more than 10 nm larger and no more than 10 nm smaller than the peak wavelength). In some embodiments, the full width at half maximum (FWHM) spectral bandwidth of the light emitted by each light source channel may be greater than 1 nm, greater than 2 nm, greater than 3 nm, or greater than 4 nm or larger. In other examples, 50% of the maximum peak intensity of the light emitted by each light source channel is within 10 nm, 9 nm, 8 nm, 7 nm, 6 nm, 5 nm, 4 nm, or 3 nm of the peak wavelength (e.g., no more than 10 nm larger or smaller than the peak wavelength; no more than 10 nm smaller or larger than the peak wavelength). In other examples, the light intensity at 50% of the maximum peak intensity of the light emitted by each light source channel is within a spectral width of less than 20 nm, less than 18 nm, less than 16 nm, less than 14 nm, less than 12 nm, less than 10 nm, less than 9 nm, less than 8 nm, less than 7 nm, less than 6 nm, or less than 5 nm (e.g., no more than 10 nm larger or smaller than the peak wavelength; no more than 10 nm smaller or larger than the peak wavelength). Commercially available LEDs and laser diodes are non-limiting examples of light sources that can provide such narrow spectral bandwidth illumination at the peak wavelengths discussed above.

[0110] Achieving narrow spectral bandwidth irradiation of biological fluids at various selected peak wavelengths can advantageously maximize the efficiency of photochemical reactions and / or pathogen inactivation, while minimizing unnecessary exposure of the biological fluid to light that may affect (e.g., reduce, weaken, or impair) its biological functions and / or desired properties (e.g., quality). Furthermore, maximizing the efficiency of the photochemical process can subsequently reduce the amount of pathogen-inactivating compounds required and / or reduce or eliminate the need to remove (e.g., adsorb) unreacted pathogen-inactivating compounds and / or photoproducts from the biological fluid after pathogen inactivation treatment.

[0111] Furthermore, irradiating biofluids with narrow spectral bands at one or more peak wavelengths can yield unexpected advantages and results. For example, when biofluids mixed with the psoralen pathogen-inactivating compound amtoxalin are irradiated with, for example, narrow spectral band UVA light from LEDs (e.g., peak wavelengths of approximately 315-350 nm, approximately 315-335 nm, approximately 330-350 nm, approximately 325 nm, approximately 340 nm, and approximately 365 nm), the results are comparable to those obtained by irradiating the same fluid mixture with a broader spectral bandwidth UVA fluorescent lamp (e.g., typically in the 320-400 nm range, with a peak wavelength of approximately 352 nm). Compared to the blood system (Cerus Corporation), an increased level of photoconversion can be observed. Furthermore, when a narrow-bandwidth UVA light with a selected peak wavelength is applied to a biofluid infused with pathogen inactivation, an improved level of pathogen inactivation (e.g., a reduced log of pathogen increase, a wider spectrum) and / or improved distribution of photoproducts can be achieved compared to existing biofluid treatment systems using wider-spectrum UVA sources. Further, such improvements can be achieved while maintaining the desired functions and / or properties of the biofluid after treatment with pathogen inactivation compounds and narrow-bandwidth light, compared to biofluids treated with existing wider-spectrum irradiation sources.

[0112] Given the various advantages and unintended results of treating (e.g., photochemically treating) biological fluids with narrow-bandwidth light sources as presented herein, it is desirable to control various parameters of the light source capable of emitting such narrow-bandwidth light. Therefore, the peak wavelength of emission, the spectral bandwidth of emission, the tilt angle, the duration of emission, and the intensity of emission for each light source channel 106 can be adjusted or set.

[0113] The various light source channel parameters can be adjusted via control circuitry 126, which is operatively linked (e.g., communicatively linked) to processing chamber 102, light source array 104, and / or computer system 128. As used herein, “operatively linked” means any wired or wireless connection between two or more components that enables the two or more components to exchange information, control commands, and / or control signals. As will be discussed in more detail below, control circuitry 126 can receive control commands and / or control signals from computer system 128 and transmit control commands and / or control signals to the various components of processing chamber 102 to adjust or set various parameters associated with the various components of chamber 102. It is preferable to adjust the various parameters of chamber 102 to ensure that the processing parameters of the chamber conform to the processing profile of one or more biological fluids 108 and 110. It should be appreciated that in some instances, the control circuitry 126 and / or the functionality of control circuitry 126 may be included within computer system 128. In some instances, control circuitry 126 may include the functionality of computer system 128. In some instances, the control circuitry 126 may be structurally attached to the processing chamber 102 (e.g., attached to the outside, top, and / or bottom of the processing chamber 102). In some instances, the control circuitry 126 may be integrated with the processing chamber 102 (e.g., located inside the processing chamber 102 or forming part of the structure of the processing chamber 102).

[0114] Now, additional or optional components of the steering system 100, Figure 1B The display light source array 104 may be thermally coupled to a heat exchanger 122 (e.g., a radiator, finned radiator, or heat exchanger operatively coupled to and controlled by control circuitry 126). The heat exchanger 122 may extract heat from the array 104 facing one or more biological fluids 108 and 110, thereby minimizing the exposure of the biological fluids 108 and 110 to heat energy (e.g., heat energy that may impair biological function). Further control of the temperature of chamber 102 and / or the temperature of one or more biological fluids 108 and 110 may be provided by a heating / cooling unit 114, operatively coupled to and controlled by control circuitry 126, and configured to regulate or set the temperature of chamber 102. The heating / cooling unit 114 may be any suitable technology known in the art, such as a fan, heat pump, Peltier cooler, and / or heat pipe. The heating / cooling unit 114 may be external to, internal to, and / or integrated with chamber 102.

[0115] Processing chamber 102 may further include a plurality of inner surfaces configured to absorb light (e.g., each configured to absorb light). For example, processing chamber 102 may include a top wall 116, a bottom wall 118, and four side walls 120a-d, which are made of or coated with a material that substantially absorbs certain wavelengths of light (e.g., black plastic, black silicate, black paint). As used herein, “substantially absorbs” means that more than 50%, 60%, 70%, 80%, or 90% or more of the light incident on the surface is not reflected (absorbed) by the surface. For example, each wall 116, 118, and 120a-d may substantially absorb ultraviolet light, ultraviolet A light, ultraviolet B light, ultraviolet C light, visible light, or light with wavelengths less than 500 nm, 450 nm, 400 nm, 375 nm, 350 nm, 325 nm, 300 nm, 280 nm, or 260 nm.

[0116] In some instances, the wavelength of light substantially absorbed by the multiple inner surfaces of the processing chamber 102 may depend on one or more peak wavelengths of light emitted by one or more light sources 106 of the light source array 104. For example, walls 116, 118, and 120a-d can absorb light with wavelengths equal to the peak wavelengths of light emitted by one or more light sources 106 of the light source array 104. The walls can absorb light with wavelengths within 100 nm, 75 nm, 50 nm, 40 nm, 30 nm, 20 nm, or 10 nm of the peak wavelengths of light emitted by one or more light sources 106.

[0117] Alternatively or additionally, in some embodiments, the processing chamber 102 may further include one or more inner surfaces configured to reflect light (e.g., each configured to reflect light). For example, the processing chamber 102 may include a top wall 116, a bottom wall 118, and four side walls 120a-d, any or all of which are made of or coated with a material that substantially reflects light of certain wavelengths. As used herein, “substantially reflective” means that more than 50%, 60%, 70%, 80%, or 90% or more of the light incident on the surface is reflected by the surface. For example, each wall 116, 118, and 120a-d may substantially reflect ultraviolet light, ultraviolet A light, ultraviolet B light, ultraviolet C light, visible light, or light with wavelengths less than 500 nm, 450 nm, 400 nm, 375 nm, 350 nm, 325 nm, 300 nm, 280 nm, or 260 nm.

[0118] Biofluid Container

[0119] like Figure 1CAs shown, biofluids 108 and 110 may be contained in biofluid containers 130 and 132, respectively. Containers 130 and 132 may include identifiers (e.g., barcode 134, RFID, tags) for identifying the contained biofluids. In one example, biofluid containers 130 and 132 may be made of any translucent or transparent or otherwise substantially transparent material (e.g., transparent for the ultraviolet peak wavelength provided herein), which may also be sterilizable and / or flexible. When the biofluid contains blood or blood products, the biofluid container may include a blood-compatible material, such as polymeric materials used in the art for blood product bags (e.g., plasma bags, platelet bags).

[0120] In some embodiments, the biofluid container may be a separate container (e.g., container 130) not connected to other containers. In some embodiments, the biofluid container may be connected to one or more other containers (e.g., storage containers) and / or compound adsorption devices. In some embodiments, such biofluid containers may be inserted into a treatment chamber to expose the biofluid to a desired amount of light, and then removed after such light exposure. In other embodiments, multiple containers may be used to allow the biofluid to flow in and out of the treatment chamber 102. In particular, the treatment chamber may include a treatment container 132 placed within the treatment chamber for receiving and treating the biofluid. The treatment container 132 may be adapted to be connected to a source container and an outlet container, the former placed outside the treatment chamber and the latter placed outside chamber 102, for receiving the treated biofluid from the treatment container 132. The connection between the source container, the treatment container 132, and the outlet container may be via piping. A pump may be operatively attached to or otherwise connected to one or more of the source container, piping, treatment container 132, and outlet container to transfer the biofluid 110 between the containers. The pump is operatively connected to the control circuit 126, and the control circuit 126 can control the volumetric flow rate of the biological fluid between the containers by controlling the pump.

[0121] Platform for carrying biological fluids

[0122] like Figure 1CAs shown, the processing chamber 102 may further include a platform 144 configured to hold one or more biological fluids 108 and 110 (e.g., containers of biological fluids). The platform 144 may be a tray, trough, or any other support suitable for holding biological fluids or containers of biological fluids. The platform 144 may be positioned in a "drawer configuration" such that it can be manually moved in and out of the chamber 102 in a sliding manner. The platform 144 may be moved in a sliding manner by any suitable actuator such as a motor or servo mechanism. The platform 144 carrying the biological fluids 108 and 110 may be positioned above the light source array 104, with the light source array 104 facing the platform 144. However, in other embodiments, the platform 104 carrying one or more biological fluids may be positioned below the light source array 104, with the light source array 104 facing the platform 144. In other embodiments, the light sources may be arranged in an array parallel to one of the side walls 120a-d of the processing chamber 102 to provide illumination of the one or more biological fluids 108 and 110 from various sides.

[0123] In some embodiments, platform 144 may include (e.g., via partition wall 150) a first compartment 146 and a second compartment 148 separated from each other. The first compartment 146 may be configured to hold a first biofluid 108, and the second compartment may be configured to hold a second biofluid 110. The first biofluid 108 may be a biofluid of the same or different type as the second biofluid 110. In other embodiments, platform 144 may include (e.g., via partition walls) more than two compartments, each separated from each other. Each compartment may be configured to hold a biofluid independently.

[0124] In embodiments where platform 144 is configured to hold two or more biological fluids, two or more different biological fluids requiring different treatment profiles can be treated in a single treatment chamber. For example, as Figure 1C As shown, the first set of light sources 152 facing the first biological fluid 108 can be controlled to emit light according to the processing status of the first biological fluid 108, and the second set of light sources 154 facing the second biological fluid 110 can be controlled to emit light according to the processing status of the second biological fluid 110.

[0125] In some embodiments, platform 144 may be translucent or transparent to light of selected wavelengths. Specifically, platform 144 may be made of materials such as plastic or glass to achieve translucency or transparency at selected wavelengths. These selected wavelengths can be determined by the peak wavelength of light emitted by one or more light source channels 106 of light source array 104. For example, the platform may be translucent or transparent to light with wavelengths within 200 nm, 150 nm, 100 nm, 75 nm, 40 nm, 30 nm, or 20 nm of the peak wavelength of light emitted by the light source channels of array 104. In other embodiments, platform 144 may be translucent or transparent to specific types of light. For example, platform 144 may be transparent to light in the ultraviolet, ultraviolet A, ultraviolet B, ultraviolet C, and / or visible light spectra.

[0126] In the example where platform 144 is divided into multiple compartments, each compartment can be translucent or transparent for the selected wavelength of light described above. In other words, each of the multiple compartments of platform 144 can be made of a different material to provide the desired translucency or transparency. For example, as... Figure 1C As shown, in an embodiment where platform 144 includes a first compartment 146 and a second compartment 148, the first compartment 146 may be translucent or transparent for light of a first selected wavelength range, while the second compartment 148 may be translucent or transparent for light of a second selected wavelength range.

[0127] Platform 144 and light source array 104 can be translated relative to each other to increase or decrease the distance 156 between light source array 104 and platform 144. In one example, the distance 156 can be adjusted or set within a range of 0-19 cm. Control circuitry 126, operatively coupled to platform 144 and / or light source array 104, controls this translation. For example, actuators (e.g., motors, servo mechanisms, etc.) control the displacement and orientation of platform 144 and / or light source array 104, and control circuitry 126 can control the relative positioning of platform 144 and light source array 104 by controlling the actuators. Further, control circuitry 126 can independently control the movement of light source array 104 and platform 144. Preferably, the distance 156 between platform 144 and light source array 104 can be changed to alter the dose of light energy incident on one or more biological fluids 108 and 110 (e.g., change the light intensity) and / or the degree of heat transfer between light source array 104 and one or more biological fluids 108 and 110.

[0128] In some embodiments, it is desirable to agitate one or more biological fluids 108 and 110 before, during, and / or after irradiation. Specifically, the biological fluids are agitated such that they are sufficiently and uniformly exposed to the emitted light and / or any pathogen-inactivating compounds. Therefore, platform 144 may be configured to agitate one or more biological fluids 108 and 110 carried by platform 144. Specifically, platform 144 may vibrate (e.g., by a vibrating motor attached to or integrated with platform 144), move in an orbital motion (e.g., by a motor or servo mechanism that moves platform 144 along a preset trajectory or displacement path), or move in a reciprocating motion at a specified frequency (e.g., from one side to the other) (e.g., by a reciprocating motor). The frequency, initiation, and type of such agitation may be based on commands and / or control signals from control circuitry 126, which are received by any suitable electromechanical drive mechanism attached to or integrated with platform 144.

[0129] barrier

[0130] The processing chamber 102 may further include a barrier 158 placed between the light source array 104 and one or more biological fluids 108 and 110. For example, the barrier 158 may be placed between the light source array 104 and the platform 144. The barrier 158 may be a protective barrier, such as one that separates one or more biological fluids 108 and 110 from the light source array 104 to reduce the possibility of contamination and / or the need to clean the light source array 104. Alternatively or additionally, the barrier 158 may be a filter that transmits or attenuates the transmission of certain wavelengths of light. The barrier 158 may be made of a material such as plastic or glass to transmit or attenuate the transmission of all or some wavelengths of light. The thickness of the barrier 158 may be, for example, in the range of 1-10 mm.

[0131] In some instances, barrier 158 may be configured to transmit at least 50%, 60%, 70%, 80%, 90%, 95%, 97%, or 99% or more of a desired wavelength (e.g., the wavelength of light emitted by light source channel 106, the wavelength of light that photoactivates a specific pathogen inactivation compound). In some instances, barrier 158 may be configured to reduce the transmission of light with wavelengths less than a certain wavelength, such as wavelengths less than 320 nm, 310 nm, 300 nm, 290 nm, 280 nm, 270 nm, 260 nm, 250 nm, or 240 nm. In other embodiments, barrier 158 may be configured to reduce the transmission of light with wavelengths greater than a certain wavelength (e.g., greater than 350 nm, greater than 370 nm, greater than 400 nm, or greater). As used herein, “reduce” may mean less than 50%, 40%, 30%, 20%, 10%, 5%, 4%, 3%, 2%, or 1% of light transmitted through barrier 158.

[0132] In some instances, one or more wavelengths of light transmitted or attenuated by the light barrier 158 may depend on one or more wavelengths of light emitted by the light source channel 106. For example, the barrier 158 may be configured to attenuate the transmission of light with wavelengths at least 5 nm, 10 nm, 20 nm, 25 nm, or 30 nm or more larger or smaller than the peak wavelength of the light emitted by the light source channel 106. The barrier may be configured to be translucent or transparent for light with wavelengths within 5 nm, 10 nm, 15 nm, 20 nm, 25 nm, or 30 nm of the peak wavelength of the light emitted by the light source channel 106 of the light source array 104.

[0133] In some instances, barrier 158 may be divided into multiple sections, each of which may reduce and / or reduce the transmission of light having any of the aforementioned wavelengths to a different level. In other words, each of the multiple sections of barrier 158 may be made of different or the same material to provide the desired transmission or reduction and / or reduction to different levels of transmission or reduction of light of certain wavelengths. For example, in an embodiment where barrier 158 includes a first section 160 and a second section 162, the first section 160, positioned below the first compartment 146 of platform 144, may reduce the transmission of light in a selected wavelength range, while the second section 162, positioned below the second compartment 148 of platform 144, may reduce the transmission of light in another selected wavelength range.

[0134] In embodiments where platform 144 and / or barrier 158 are selectively translucent or transparent and selectively attenuate and / or attenuate light of selected wavelengths to different levels, one or more biofluids 108 and 110 may be irradiated only substantially with light of wavelengths appropriate to their respective treatment profiles. Thus, wavelength-selective irradiation can lead to more efficient photochemical reactions and therefore more effective pathogen inactivation. Furthermore, exposure of one or more biofluids 108 and 110 to unfavorable wavelengths of light that may impair biological function can be minimized.

[0135] Light source array configuration

[0136] Turning Figure 2A-2D An exemplary light source array configuration of light source array 104 will now be described.

[0137] Figure 2A An exemplary light source array configuration is shown, wherein light sources 202 are positioned in a distributed manner across light source array 200. Specifically, light sources 202 may be positioned as a group 204 of light sources. Each light source 202 belonging to the same light source channel may emit light of the same wavelength (e.g., peak wavelength) in the visible or ultraviolet spectrum (e.g., ultraviolet A, ultraviolet B, or ultraviolet C spectrum). In other words, each light source channel may be a group of one or more light sources 202 having the same wavelength. Figure 2AAs shown, each group of light sources may include two or more (e.g., three or more, four or more, five or more, six or more) light sources 202. In some instances, the two or more light sources 202 may emit light whose peak wavelengths differ from each other by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. In other instances, the two or more light sources 202 may include one or more pairs (e.g., two or more pairs, three or more pairs) of light sources. For example, as... Figure 2A As shown, each light source group 204 may include four light sources 202. A first pair of light sources in a common light source channel may emit light with a first peak wavelength, and a second pair of light sources in another common light source channel may emit light with a second peak wavelength that differs from the first peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. Alternatively, a first pair of light sources (e.g., the first and second light sources of the first and second light source channels, respectively) may emit light with a first peak wavelength, and another light source (e.g., the third light source of the third light source channel) may emit light with a second peak wavelength, and yet another light source (e.g., the fourth light source of the fourth light source channel) may emit light with a third peak wavelength, wherein the first peak wavelength differs from the second peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more, and the second peak wavelength differs from the third peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. Alternatively, a first light source (e.g., a first light source in a first light source channel) may emit light having a first peak wavelength, another light source (e.g., a second light source in a second light source channel) may emit light having a second peak wavelength, yet another light source (e.g., a third light source in a third light source channel) may emit light having a third peak wavelength, and yet another light source (e.g., a fourth light source in a fourth light source channel) may emit light having a fourth peak wavelength, wherein the first peak wavelength differs from the second peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more, and the second peak wavelength differs from the third peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more, and the third peak wavelength differs from the fourth peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more.

[0138] Figure 2BAnother exemplary light source array configuration is shown, wherein light sources 208 (e.g., within the same light source channel) are positioned in a distributed manner across light source array 206. Specifically, light source array 206 may include an inner region 210 and an outer region 212. The inner region 210 may occupy less than 50% (e.g., less than 40%, less than 30%, less than 20%, less than 10%) of the surface area of ​​array 206, while the outer region may occupy the remaining percentage (e.g., 50%-90% or more) of the surface area of ​​array 206. Alternatively, the inner region 210 may occupy less than 90% (e.g., less than 80%, less than 70%, less than 60%) of the surface area of ​​array 206, while the outer region may occupy the remaining percentage (e.g., 10%-50% or more) of the surface area of ​​array 206. The density of light sources 208 placed in the inner region 210 (e.g., within the same light source channel) may be greater than the density of light sources 208 placed in the outer region 212 (e.g., within the same light source channel). In other embodiments, such as Figure 2D As shown, the density of light sources 208 placed in the inner region 210 (e.g., within the same light source channel) of the light source array 216 may be less than the density of light sources 208 placed in the outer region 212 (e.g., within the same light source channel). In these examples, the density of light sources placed in the inner region 210 and the density of light sources placed in the outer region 212 may differ by at least 1.2 times, 1.5 times, 2 times, 2.5 times, 3.0 times, or more (e.g., as shown). Figure 2B The density is higher in the inner region than in the outer region, such as Figure 2D The density is higher in the outer regions compared to the inner regions.

[0139] like Figure 2B and Figure 2D As shown, in some embodiments, the light source 208 is not placed on (e.g., nearby) one or more outer edges 214 of the array 206. In other embodiments, the light source 208 may be placed on (e.g., nearby) one or more outer edges 214.

[0140] Figure 2CAnother exemplary light source array configuration is shown, wherein the light source array 216 includes a first region 218 and a second region 220 separated by a third region 222. The density of light sources 224 placed in the first region 218 and the second region 220 may each be greater than the density of light sources placed in regions outside the first region 218 and the second region 220 (e.g., the third region 222, for example, a third region excluding light sources). In some embodiments, the third region does indeed include one or more light sources. Such a light source array configuration is desirable in embodiments of the processing chamber 102 discussed above, which include a first biological fluid 108 and a second biological fluid 110. In particular, the light sources placed in the first region 218 may be oriented towards the first biological fluid 108, and the light sources placed in the second region 220 may be oriented towards the second biological fluid 110. The light sources in the first region 218 may illuminate the first biological fluid 108 according to the processing profile of the first biological fluid 108, and the light sources in the second region 220 may illuminate the second biological fluid 110 according to the processing profile of the second biological fluid 110. In regions that do not face either the first or second biological fluid (e.g., third region 222), no light source or a low-density light source may be placed. For example, if the third region 222 faces the partition wall 150 of platform 144, a light source may not be needed in the third region. Alternatively, the third region 222 may include a light source that is tilted toward the first or second biological fluid, or both.

[0141] On a given array of light sources, the light sources can be placed in a uniform distribution. For example, Figure 2A This can be understood as a group 204 of light sources (e.g., sixteen groups 204 of light sources) uniformly distributed on a light source array 200. For the light source array 200, there may be four light source channels, each including a light source 202 at the same corresponding position in each group 204. Therefore, each group 204 may include four light sources, each from four different light source channels. Alternatively, the positioning of the light sources and the arrangement of the light source channels on a given light source array can provide a non-uniform distribution. The light sources themselves can be placed in a non-uniform manner. The light sources of a given light source channel can be placed in a non-uniform manner. One or more light sources of the "light source array" can be arranged in any positioning manner (e.g., straight lines, curves, (multi) rows and (multi) columns, regular patterns, irregular spacing, etc.). A uniform distribution can be provided by a regular pattern and spacing of light sources uniformly applied throughout the array, such as... Figure 2A As illustrated in the example. Non-uniform distribution can be provided, for example, by irregular patterns and spacing of light sources applied throughout the array, such as by... Figure 2B and Figure 2D The inner and outer regions with different light source densities are illustrated in the figure.

[0142] The various light source configurations discussed above are desirable for irradiating various biological fluids requiring different treatment profiles. Furthermore, these configurations are desirable for achieving substantially uniform irradiation of the surface of the biological fluid or the surface of the biological fluid container. For example, Figure 2A-2D The image illustrates various configurations for arranging light sources for an array, and Figure 4 and Figure 6B Various configurations of the distance between the light source and the biological fluid are illustrated. The surface of the biological fluid may be defined by, for example, the surface of the biological fluid container holding the fluid or a plane intersecting any portion of the biological fluid. In one example, the light source of the light source array 104 may be configured (e.g., placed in the array) such that the light source irradiates the biological fluid with an irradiance difference of less than 25% (e.g., less than 20%, less than 15%, less than 10%) across the surface of the biological fluid 108 facing the light source array 104. In other words, the light intensity on any portion of the surface of the biological fluid 108 facing the light source array 104 may differ from the light intensity on any other portion of the surface of the biological fluid 108 facing the light source array 104 by less than 25% (e.g., less than 20%, less than 15%, less than 10%).

[0143] In another example, the light source of the light source array 104 can be configured such that the light source illuminates any 5 square centimeter area of ​​the surface of the biofluid 108 with an irradiance that differs from the average integrated irradiance across the entire surface of the biofluid 108 by less than 25% (e.g., less than 20%, less than 15%, less than 10%). In other words, the light intensity received within any 5 square centimeter area of ​​the surface of the biofluid 108 facing the array 104 can differ from the total light intensity received by the surface of the biofluid 108 facing the array 104 (averaged over the surface area) by less than 25% (e.g., less than 20%, less than 15%, less than 10%).

[0144] Turn now Figure 3-6B Further embodiments of exemplary light source array configurations in a processing system for processing one or more biological fluids are described.

[0145] Figure 3 Showing a perspective view of an exemplary system 300 for processing biological fluids, the system includes a light source array configuration comprising multiple light source panels 302 and 304 in a processing chamber 308. Although Figure 3 Only two light source panels are described in this document, but in other instances, the light source array may include more than two (e.g., three, four, five or more) light source panels. The processing chamber 308 is operatively connected to a control circuit 306, which is capable of adjusting or setting various parameters of the processing chamber 308, such as adjusting or setting parameters of the light sources within the processing chamber (e.g., peak wavelength of emission, spectral bandwidth of emission, tilt angle, duration of emission, intensity of emission).

[0146] Each light source panel 302 and 304 can be independently removed from the processing chamber 308 (e.g., from a light source array) and operatively connected to the control circuitry 306. Each light source panel 302 and 304 may include light source arrays, such as 310 and 312. The control circuitry 306 can adjust or set various parameters of each light source 314 of each light source panel 302 and 304. For example, the control circuitry can adjust or set the peak wavelength, spectral bandwidth, intensity, duration, and tilt angle of emission of each light source 314 of each light source panel 302 and 304. Further, each of the respective light source arrays 310 and 312 can be independently configured using the above-mentioned parameters. Figure 2A-2D The various light source distributions discussed are configured.

[0147] Each light source 314 of each light source array 310 and 312 arranged on panels 302 and 304 respectively can be connected in series within each panel. Each panel 302 and 304 can be connected to other panels in parallel.

[0148] In some embodiments, control circuitry 306 can adjust or set the positions of light source panels 302 and 304 within processing chamber 308. Specifically, control circuitry 306 can send control commands and / or control signals to, for example, motors, servo mechanisms, or any suitable electromechanical drive mechanisms attached to or integrated with each light source panel 302 and 304, causing the panels to translate relative to each other to increase or decrease the distance between light source panels 302 and 304. For example, first light source panel 302 can translate parallel to the plane of first light source panel 302, and second light source panel 304 can translate parallel to the plane of second light source panel 304. First light source panel 302 can be translated to increase or decrease a first distance 318 between the bottom plane 316 of processing chamber 308 and first light source panel 302. Similarly, second light source panel 304 can also be translated to increase or decrease a second distance 320 between the bottom plane 316 and second light source panel 304.

[0149] In some embodiments, processing chamber 308 may include platform 322 (e.g., a platform including one or more compartments). The light source panels in the plurality of light source panels in the light source array may face each compartment, for example, directly aligned without lateral offset. For example, as... Figure 3 As shown, platform 322 may include a first compartment 324 and a second compartment 326 separated from each other by a partition wall 328. The first compartment 324 may be configured to hold a first biological fluid 330, and the second compartment may be configured to hold a second biological fluid 332. A first light source panel 302 may face the first compartment 324, and a second light source panel 304 may face the second compartment 326.

[0150] In instances where multiple types of biological fluids need to be treated in chamber 308, it is preferable to configure chamber 308 to include multiple independently controllable light source panels. For example, if the first biological fluid 330 and the second biological fluid 332 are of different types, the required treatment profiles for the first and second biological fluids may differ. To achieve these different treatment profiles, the first panel 302 facing the first biological fluid 330 and the second panel 304 facing the second biological fluid 332 can be independently configured and controlled by control circuitry 306. For example, control circuitry 306 can set or adjust the light source configuration on the first panel 302 and / or the light source configuration on the light panel 304 to be different from each other. Furthermore, control circuitry 306 can set or adjust the distance between the first panel 302 and the first biological fluid 330 and / or the distance between the second panel 304 and the second biological fluid 332 to be different from each other. Furthermore, the control circuit 306 can set or adjust the light emission characteristics of the first panel 302 (e.g., duration, wavelength, intensity, spatial pattern, and temporal pattern of light emission) and / or the light emission characteristics of the second panel 304 to be different from each other.

[0151] Figure 4 A perspective view of an exemplary system 400 for processing one or more biological fluids 406 and 408 is shown, comprising opposing light source arrays 402 and 404 disposed within a processing chamber 412. The opposing light source arrays 402 and 404 may each be thermally connected to heat exchangers 414 and 416, respectively. The processing chamber 412 may include a platform 410 disposed between the opposing light source arrays 402 and 404, the platform being configured to hold one or more biological fluids 406 and 408. Providing illumination to the biological fluids 406 and 408 from opposing sides is desirable, for example, for more uniform illumination of the biological fluids.

[0152] The processing chamber 412, the opposing light source arrays 402 and 404, the heat exchangers 414 and 416, and the platform 410 can each be operatively connected to the control circuit 418, which can adjust or set their respective parameters.

[0153] The first relative light source array 402 may include a first light source array channel 420, and the second relative light source array 404 may include a second light source array channel (not shown). Each light source channel 420 of the first relative light source array 402 and each light source channel of the second relative light source array 404 may be configured to emit light of the various peak wavelengths discussed above.

[0154] In some embodiments, one or more wavelengths of light emitted by the first opposing light source array 402 may be the same as one or more wavelengths of light emitted by the second opposing light source array 404. For example, the first and second light source channels of the first opposing array 402 may respectively emit light with a first peak wavelength and a second peak wavelength that differs from the first wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. The third and fourth light source channels of the second opposing array 404 may respectively emit light with wavelengths that are the same as (e.g., equal to) the first and second peak wavelengths.

[0155] In some embodiments, all light sources of the first opposing array 402 may emit light with a single peak wavelength (e.g., a first peak wavelength). All light sources of the second opposing array 404 may also emit light with a single peak wavelength (e.g., a first peak wavelength). The peak wavelength of the light emitted by all light sources of the first opposing array 402 may be the same as (e.g., equal to) the peak wavelength of the light emitted by all light sources of the second opposing array 404. Alternatively, the peak wavelength of the light emitted by all light sources of the first opposing array 402 may differ from the peak wavelength of the light emitted by all light sources of the second opposing array 404 by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more.

[0156] In some implementations, the first relative array 402, the second relative array 404, and the platform 410 can all be configured to translate relative to each other to increase or decrease the distances 422, 424, and 426 between any of the following pairs: the first relative array 402, the second relative array 404, and the platform 410. This translation can be achieved by any number of actuators (e.g., motors, servo mechanisms, etc.) controlled by control circuitry 418, which can individually control the translation of the first relative array 402, the second relative array 404, and the platform 410.

[0157] Figure 5 The diagram shows a perspective view of an exemplary system 500 including a processing chamber 502 and multiple light source arrays 504 and 506 facing the same direction. Light source arrays 504 and 506 may each be thermally connected to heat exchangers 508 and 510, respectively. The processing chamber 502 may optionally include multiple platforms 512 and 514, each configured to carry one or more (e.g., multiple) biological fluids 516. This configuration of system 500 provides separate processing areas within the processing chamber 502, each with a separate inlet (e.g., a separate opening, a separate sliding drawer) for processing multiple biological fluids. This configuration is desirable for high-throughput processing of biological fluids and / or for processing biological fluids (e.g., different biological fluids) under different conditions or at different times (e.g., non-parallel processing cycles).

[0158] Each of the processing chamber 502, the multiple light source arrays 504 and 506, the heat exchangers 508 and 510, and the platforms 512 and 514 is operatively connected (directly or indirectly) to the control circuit 518, which can adjust or set various parameters of them.

[0159] like Figure 5 As shown, the first light source array 504 may face the same direction as the second light source array 506. A first platform 512 may be placed in a first region 520 between the first light source array 504 and the second light source array 506. The first light source array 504 may include the sole light source for the processing chamber 502 to irradiate one or more biological fluids in the first region 520. For example, the processing chamber 502 may be configured (e.g., with opaque partition walls) such that light from the second light source array 506 may not irradiate region 520. The second platform 514 may be placed in a second region 522 outside the first region 520 (e.g., above the second light source array 506). The second light source array 506 may face the second platform 514. The second light source array 506 may be the sole light source for the processing chamber 502 to irradiate one or more biological fluids in the second region 522. For example, the processing chamber 502 may be configured (e.g., with opaque partition walls) such that light from the first light source array 504 may not irradiate region 522.

[0160] Processing chamber 502 may optionally include a third and a fourth light source array (not shown) facing the same direction as the first and second light source arrays 504 and 506. The third light source array may face a third platform (not shown) positioned between the third and fourth light source arrays (e.g., in a third region). The fourth light source array may face a fourth platform (not shown). Those skilled in the art will understand that processing chamber 502 may extend to accommodate any number of light source arrays facing the same direction and any number of platforms. Each additional light source array may provide an additional region (not shown), for example, each additional light source array providing a single light source for illuminating one or more biological fluids in its respective region. Similarly, each individual processing area within the processing chamber may have a separate entrance (e.g., a separate, sliding drawer) for independently processing multiple biological fluids.

[0161] The first light source array 504 may include one or more light source channels 524, and the second light source array 506 may include one or more light source channels 526. Each light source channel 524 of the first light source array 504 and each light source channel 526 of the second light source array 506 may be configured to emit light of the various peak wavelengths discussed above.

[0162] In some embodiments, light source arrays 504 and 506 may emit light with the same peak wavelength. This is desirable in instances where multiple biological fluids 516 requiring the same treatment profile (e.g., the same type of biological fluid) are to be treated in chamber 502 or treated with light of the same peak wavelength. For example, the first and second light source channels of the first light source array 504 may emit light with a first peak wavelength and a second peak wavelength that differs from the first wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, or 20 nm or more. The third and fourth light source channels of the second light source array 506 may emit light with wavelengths that are the same as (e.g., equal to) the first and second peak wavelengths.

[0163] In some embodiments, all light source channels 524 of the first light source array 504 may emit light with a single peak wavelength (e.g., a first peak wavelength). All light source channels 526 of the second light source array 506 may also emit light with a single peak wavelength (e.g., a first peak wavelength). The peak wavelength of the light emitted by all light source channels 524 of the first light source array 504 may be the same as (e.g., equal to) the peak wavelength of the light emitted by all light source channels 526 of the second light source array 506. Alternatively, the peak wavelength of the light emitted by all light source channels 524 of the first light source array 504 may differ from the peak wavelength of the light emitted by all light source channels 526 of the second light source array 506 by at least (e.g., more than) 5 nm, 10 nm, 15 nm, and 20 nm or more.

[0164] In some embodiments, each of the light source arrays 504 and 506 and each of the platforms 512 and 514 can be translated relative to each other to increase or decrease the distance between any pair of light source arrays 504 and 506 and platforms 512 and 514. This translation can be achieved by any number of actuators (e.g., motors, servo mechanisms, etc.) controlled by control circuitry 518, which can individually control the translation of each of the light source arrays 504 and 506 and each of the platforms 512 and 514. Similarly, additional light source arrays and platforms (e.g., third and fourth light source arrays, third and fourth platforms, not shown) can be translated relative to each other by any number of actuators (e.g., motors, servo mechanisms, etc.) controlled by control circuitry 518.

[0165] Figure 6AA perspective view of an exemplary system 600 for processing one or more biological fluids 606 and 608 is shown, including a light source array 604 disposed in a processing chamber 612. The light source array 604 faces a platform 610 for the biological fluids. The light source array 604 may be thermally coupled to a heat exchanger 616. The processing chamber 612 may include the platform 610 disposed below the light source array 604, the platform being configured to hold one or more biological fluids 606 and 608. The processing chamber 612, the light source array 604, the heat exchanger 616, and the platform 610 may each be operatively coupled to a control circuit 618, which may adjust or set their respective parameters. Figure 6B The exemplary system 600 may also include a barrier 658 and various sensors 612, 666, 668, and 680 within a processing chamber 612. The barrier 658 is positioned between the light source array 604 and one or more biological fluids 606 and 608, and the barrier 658 may have the aforementioned features... Figure 1D Any of the features discussed in barrier 158. Sensors 612, 666, 668 may be attached to or placed in platform 610. Sensor 680 may be attached to (e.g., above or below) barrier 658 or placed therein.

[0166] The light source array 604 may include an array of light source channels. Each light source channel of the light source array 604 may be configured to emit light of various peak wavelengths discussed above, and may be arranged in various arrangements of light sources and light source channels discussed above.

[0167] Both the light source array 604 and the platform 610 can be configured to translate relative to each other to increase or decrease the distance 626 between them, as discussed in the translations above. The platform 610 can be lowered to the bottom of the processing chamber 612, and the processing chamber 612 can be raised from or flush with an external bottom surface (e.g., floor, ground, tabletop, etc.) (e.g., via any structural base, including any components such as sensors or circuitry). The light source array 604 can be raised to the top of the processing chamber 612. Figure 6BIn this configuration, the light source array 604, barrier 658, and platform 610 can all be configured to translate relative to each other to increase or decrease the distances 626, 682, and 684 between any pair of the following: light source array 604, barrier 658, and platform 610. This translation can be achieved by any number of actuators (e.g., motors, servo mechanisms, etc.) controlled by control circuitry 618, which can individually control the translation of light source array 604, barrier 658, and platform 610. In some embodiments, one or both of the light source array 604, barrier 658, and platform 610 can be fixedly positioned within processing chamber 612. For example, barrier 658 can be fixedly positioned within processing chamber 612. As another example, barrier 658 and light source array 604 can be fixedly positioned relative to each other within processing chamber 612 at a fixed distance 682, wherein platform 610 can be configured to translate to increase or decrease distances 626 and 684. As another example, barrier 658 and platform 610 can be fixedly positioned relative to each other in processing chamber 612 at a fixed distance 684, wherein light source array 604 can be configured to translate to increase or decrease the distances 626 and 682.

[0168] Figures 6A-6B The system 600 in the middle can be similar to many other methods. Figure 1A-1E System 100, including, for example, system 600 and system 100, both provide irradiation to the biological fluid on one side: for example, irradiation on one side of the container of the biological fluid, irradiation on one side of the platform. Figures 6A-6B The system 600 in the middle can be different in many ways. Figure 1A-1E System 100 includes, for example, system 600 providing illumination to the biological fluid from above (e.g., above the container of the biological fluid, above the platform), but system 100 provides illumination from below (e.g., below the container of the biological fluid, below the platform).

[0169] Figures 6A-6B The system 600 in the middle can be similar to many other methods. Figure 4 System 400, including, for example, system 600, provides illumination light to the biological fluid from above (e.g., above the container of the biological fluid, above the platform). Figures 6A-6B The system 600 in the middle can be different in many ways. Figure 4 The system 400, including, for example, system 600, provides irradiation to the biological fluid on one side, but not on the opposite side as in system 400.

[0170] For any number of reasons, it is desirable to provide illumination to the biofluids 606 and 608 from above. For example, biofluids 606 and 608 may be stationary and passively resting on platform 610 due to downward gravity (e.g., in a container, in a tank, on a tray). Therefore, light can be used to illuminate biofluids 606 and 608 from above platform 610, and it may not be necessary for light to pass through platform 610 to reach biofluids 606 and 608. Loss and / or dispersion of illumination light energy due to platform 610 can be avoided. Furthermore, platform 610 may not need to be transparent or translucent to the illumination light. Platform 610 may be formed from materials and / or designed to be opaque to the illumination light.

[0171] sensor

[0172] Exemplary implementations of the systems discussed above may include one or more sensors of various types implemented for their respective processing chambers. (Go to...) Figure 1E Each of the types of sensors discussed below (directly or indirectly) is operatively connected to control circuitry 126 and / or computer system 128. Although the following is combined with... Figure 1E Various sensors have been described, but those skilled in the art will understand that this description also applies to any other implementation of the systems described above, such as... Figure 6B The various sensors shown are illustrated.

[0173] Various sensors that can be implemented in processing chamber 102 include:

[0174] ● One or more light sensors 112 are configured to measure light intensity at various locations within the processing chamber and / or incident on various locations of one or more biological fluids 108 and 110.

[0175] ●One or more air flow sensors 164

[0176] ●One or more thermal sensors 166 are used to measure the temperature of the processing chamber 102 and / or the temperature of one or more biological fluids 108 and 110.

[0177] ● One or more sensors 168 or 172 are used to detect the presence of one or more biological fluids 108 and 110 (e.g., pressure sensors, optical retroreflection sensors, optical transmission sensors, tag readers, barcode scanners, RFID sensors, etc.).

[0178] ● One or more sensors 172 are used to detect the type of one or more biological fluids 108 and 110 (e.g., tag readers, barcode scanners, RFID sensors).

[0179] ● One or more sensors 174 are used to detect the properties of biological fluids (e.g., transmittance) (e.g., optical sensors, spectral sensors).

[0180] ● One or more sensors 174 are used to detect photochemical compounds (e.g., fluorescence spectra) in biological fluids, and

[0181] ● One or more sensors 174 (e.g., ultrasonic sensors) are positioned to detect the fluid depth of a portion (e.g., each portion) of one or more biological fluids 108 and 110.

[0182] Any of these various sensors can be placed in any location (e.g., outside the processing chamber, inside the processing chamber, or as part of the structure forming the processing chamber) for implementation in conjunction with the various embodiments of the processing chamber discussed above. For example, one or more light sensors 112, one or more thermal sensors 166, and one or more airflow sensors 164 can be placed on the light source array 104. Figure 1E As shown, in an embodiment including a processing chamber 102 with a platform 144, one or more light sensors 112 and one or more sensors 168 for detecting the presence of one or more biological fluids 108 and 110 may be placed on the platform 144. Figure 6B As shown, in an embodiment of the processing chamber 612 including platform 610 and barrier 658, one or more light sensors 612, one or more thermal sensors 666, and one or more sensors 668 for detecting the presence of one or more biological fluids 606 and 608 may be attached to or placed therein on platform 610. Sensors 680 representing any of the various sensors discussed above may be attached to or placed therein on barrier 658.

[0183] System control and user input

[0184] The mechanisms for controlling, regulating, or setting various parameters of the components of the various embodiments of the biological fluid treatment system will now be described. Although the mechanisms for controlling, regulating, or setting various parameters of the components of the treatment system 100 are discussed below, those skilled in the art will understand that the following description is also applicable to regulating various parameters of various other embodiments of the treatment system discussed above.

[0185] In some implementations, various parameters of the components of the processing system 100 may be dynamically or automatically adjusted or set based on feedback received at control circuitry 126 and / or computer system 128 from one or more of various types of sensors. Alternatively, the various parameters of the components of the processing system 100 may be adjusted or set based on user input at computer system 128.

[0186] Computer system 128 is operatively coupled (directly or indirectly) to control circuitry 126 and / or to any of the various sensors discussed above. The computer system may include one or more processors 176, memory 178, input / output (I / O) interface 180, and user interface (UI) 182. The one or more processors 176 may be one or more of any type of general-purpose computer processor. Memory or computer-readable medium 178 may include one or more readily available memories such as random access memory (RAM), read-only memory (ROM), floppy disk, hard disk, optical storage media (e.g., optical disc or digital video disc), flash drive, or any other form of digital storage (local or remote). In some instances, the non-transitory computer-readable storage medium of memory 178 may be used to store instructions for irradiating one or more biological fluids according to one or more treatment profiles, as will be referenced below. Figures 7A-7B The flowchart will be discussed. Computer system 128 may include any type of computer, such as personal computer (PC), desktop computer, laptop computer, computer terminal, server computer, tablet computer, smartphone, personal digital assistant (PDA), etc. In some instances, control circuitry 126 and / or the functionality of control circuitry 126 may be included within computer system 128.

[0187] The control circuit 126 can be implemented as any suitable logic circuit capable of cooperating with the control functions described herein. Such control functions can be provided by executing instructions implemented in a software program. Suitable logic circuitry may include a processor-readable medium storing the instructions implemented in the software program and a processor that performs the control functions when the instructions are executed. Alternatively, such control functions can be provided by a corresponding logic design implemented in hardware logic circuitry, such as a programmable logic device or application-specific integrated circuit that implements the logic design providing the control functions of the control circuit 126. Furthermore, such control functions can be provided by combining a processor running software with an implementation of hardware logic circuitry. In some instances, the control circuit 126 may include the computer system 128 and / or the functions of the computer system 128.

[0188] At UI 182, the user can input one or more characteristics from a set of features for one or more biofluids 108 and 110. Alternatively, one or more characteristics from a set of features for one or more biofluids can be determined based on feedback input from one or more sensors used in the processing chamber 102 to the computer system 128 and / or control circuitry 126. Features from a set of features for the biofluids may include, for example, the type of biofluid (e.g., blood products such as plasma, platelets, red blood cells; cells such as eukaryotic cells; proteins such as antibodies; vaccines), photochemical agents in the biofluid (e.g., type, volume, concentration), the volume of the biofluid, the transmittance of the biofluid, the type and / or shape of the container carrying the biofluid, and the temperature of the biofluid.

[0189] At UI 182, the user can input one or more parameters, including a treatment profile of one or more biological fluids 108 and 110. Alternatively, computer system 128 can automatically determine one or more parameters of a treatment profile of one or more biological fluids 108 and 110 based on a corresponding set of characteristics of one or more biological fluids 108 and 110. In particular, memory 178 can store a computer program including instructions that map one or more characteristics of the biological fluid to one or more parameters of the treatment profile for each biological fluid. The instructions that map one or more characteristics of the biological fluid to one or more parameters of the treatment profile for each biological fluid can be implemented as a set of user-programmable rules.

[0190] Computer system 128 may send control commands and / or control signals to control circuitry 126 to adjust or set various parameters of processing chamber 102. In some embodiments, various parameters of processing chamber 102 may be adjusted or set based on the processing profile of one or more biological fluids 108 and 110 placed in the processing chamber. Alternatively, various parameters of processing chamber 102 may be adjusted or set based on feedback from various sensors placed within processing chamber 102.

[0191] Control circuit 126 can adjust or set the peak wavelength of the light emitted by each light source channel 106. Control circuit 126 can adjust or set the intensity of the light emitted by each light source channel 106. Specifically, control circuit 126 can adjust or set the intensity of the light emitted by each light source channel 106 from a "off" state (0% intensity) to a maximum intensity state (100% intensity) in 0.4% increments. Control circuit 126 can adjust or set the tilt angle of each light source channel 106 by physically reorienting the light source channel 106 or by tuning the output direction of the light source channel 106. For example, the control circuit can adjust or set the tilt angle of each light source channel relative to the normal direction (e.g., perpendicular) of the surface on which each light source channel is arranged to be 0° to 5°. Control circuit 126 can adjust or set the emission duration of the light emitted by each light source channel 106. Control circuit 126 can adjust or set the emission spectral bandwidth of the light emitted by each light source channel 106. Any of these parameters can be adjusted or set based on a set of parameters received from, for example, one or more optical sensors 112 placed in the processing chamber 102 and / or any other various sensors placed in the processing chamber 102.

[0192] Enabling individual control over one or more of the following parameters—emission peak wavelength, emission duration, emission intensity, and emission angle—of light emitted from each light source channel 106 allows for programming and control of the optical properties of light emitted by the light source array 104, which vary with time and / or space. These optical properties can be important processing parameters in the processing profile of the biological fluid and can be programmed by the user on the computer system 128 and stored in the memory 178. The optical properties of one or more biological fluids can be automatically determined on the computer system 128 based on a corresponding set of characteristics of one or more biological fluids.

[0193] In one set of exemplary optical characteristics, all light sources of the light source array 104 can be simultaneously turned on and off at a user-adjustable frequency to generate a gated output mode. In another set of exemplary optical characteristics, the intensity of light emitted by each light source channel can be adjusted over time to generate a sinusoidal intensity output mode. In yet another set of exemplary optical characteristics, the first set of light sources 152 of the light source array 104 can irradiate the portion of the first biofluid 108 facing the first set of light sources 152 at a first intensity, and the second set of light sources 154 of the light source array 104 can irradiate the second biofluid 110 facing the second set of light sources 154 at a second intensity.

[0194] Before irradiating one or more biological fluids 108 and 110 in the treatment chamber 102, various parameters of the treatment chamber 102 may be adjusted by the control circuit 126. Such initial adjustments by the control circuit 126 may include, for example, instructing or controlling the heating / cooling unit 114 to adjust or set the temperature of the treatment chamber 102, instructing or controlling the light source array 104 to move closer to or further away from one or more biological fluids 108 and 110, instructing or controlling the pump 142 to flow biological fluids from the source container 136 to the treatment container 132, instructing or controlling the platform 144 to agitate one or more biological fluids 108 and 110, and instructing or controlling each light source channel 106 to adjust the light intensity from an "off" state or set it to an initial intensity state.

[0195] Various parameters can also be adjusted by control circuitry 126 while one or more biofluids 108 and 110 are being irradiated. Such adjustments can be made dynamically by control circuitry 126 based on feedback received from the various sensors discussed above at computer system 128 and / or control circuitry 126. Specifically, memory 178 can store a set of user-programmable rules that map inputs from various sensors to desired adjustments of various components of processing chamber 102. Enabling dynamic feedback responses to data received from various sensors advantageously allows control circuitry 126 to rapidly correct processing parameters that deviate from the intended processing profile of the one or more biofluids 108 and 110 being processed. This, in turn, can provide improved inactivation of pathogens in the one or more biofluids being processed while minimizing exposure of the one or more biofluids to processing chamber conditions that may affect (e.g., reduce, weaken, damage) the biological function and / or desired properties of the biofluids.

[0196] An example is now described of how various parameters of the processing chamber 102 are dynamically controlled by the control circuit 126 based on feedback from various sensors.

[0197] In some instances, the light intensity emitted by each light source channel 106 can be adjusted by control circuitry 126 based on data received by computer system 128 from one or more light sensors 112. For example, if one or more light sensors 114 detect that the light intensity incident on a portion of the biofluid 108 is greater than or less than a threshold, control circuitry 126 can reduce or increase the light intensity of one or more light sources of the light source array 104 facing that portion of the biofluid 108, respectively. Alternatively, control circuitry 126 can increase or decrease the distance 156 between the platform 144 carrying the biofluid 108 and the light source array 104 to change the light intensity incident on that portion of the biofluid 108. The threshold intensity value can be based on, for example, one or more of the following: the depth of that portion of the biofluid 108, the type of biofluid 108, the transmittance of the biofluid 108, the transmittance of the container carrying the biofluid 108, and the type of pathogen inactivation compound mixed with the biofluid 108. The threshold intensity value may be specified in the processing profile of the biofluid 108 and / or a set of characteristics of the biofluid 108. Suitable light sensors are well known in the art, such as photodiodes whose spectral response range corresponds to (e.g., including) the wavelength of the light source provided herein (e.g., photodiodes with a spectral response range of 210-390 nm). Exemplary photodiodes may include silicon photodiodes, silicon carbide photodiodes, or other suitable photodiodes such as GaAsP photodiodes, GaP photodiodes, and GaN photodiodes.

[0198] In some instances, the intensity of light emitted by each light source channel 106 of the light source array 104 can be adjusted or set by control circuitry 126 based on depth data received by computer system 128 from one or more depth sensors 174. In embodiments where the container 130 carrying the biological fluid 108 may have variations in depth (e.g., maximum depth) and / or non-uniform depth (e.g., blood bags) due to different volumes of the biological fluid (e.g., volumes smaller than the capacity of the container carrying the biological fluid), enabling depth-dependent intensity control is desirable. Specifically, due to the characteristic central bulge of blood bags, the central portion of the biological fluid in a blood bag may be deeper than the peripheral portion. Therefore, the irradiation intensity required to adequately inactivate pathogens in the central region of the biological fluid may be greater than that required to adequately inactivate pathogens in the peripheral region. Thus, one or more depth sensors 174 can detect this variation in fluid depth across container 130, and control circuitry 126 can adjust or set the emission intensity of each light source facing such portions of the biological fluid 108 based on the detected depth of each portion. Alternatively or additionally, the depth of a container with a specific capacity (e.g., 1000 mL) containing a volume of biological fluid smaller than its container capacity (e.g., 300 mL) may be less than the depth of a biological fluid with a volume closer to its container capacity (e.g., 900 mL). Therefore, the irradiation intensity required to adequately inactivate pathogens in a larger volume of biological fluid may be greater than the irradiation intensity required to adequately inactivate pathogens in a smaller volume of biological fluid contained in a container of similar size. Therefore, one or more depth sensors 174 may detect the fluid depth in container 130, and control circuitry 126 may adjust or set the emission intensity of each light source facing the biological fluid 108 based on the detected depth.

[0199] In instances where the biofluid is to be continuously or periodically agitated during treatment, depth-dependent intensity control and dynamic intensity adjustment by control circuitry 126 may also be important. Specifically, in embodiments where biofluid 108 is agitated during treatment, the biofluid 108 may produce sloshing or undulation, which can result in standard undulation patterns. This movement can cause depth variations across different portions of the biofluid 108, thereby altering the light energy dose sufficient to inactivate pathogens within such portions. Therefore, based on feedback from one or more depth sensors 174, control circuitry 126 can dynamically adjust or set the intensity of light emitted by one or more light source channels 106. For example, the intensity of light emitted by one or more light source channels facing that portion of the biofluid 108 may be dynamically increased or decreased by control circuitry 126 based on whether the depth of a portion of the biofluid 108 detected by one or more depth sensors 174 is greater than or less than a threshold depth. The threshold depth may be specified in the treatment profile of the biofluid 108 and / or a set of characteristics of the biofluid 108. Alternatively, a standard fluctuation pattern can be determined based on variables such as the volume of the biological fluid, the type of biological fluid, the size of the container, the shape of the container, the agitation speed, the agitation mode, and the agitation stroke length, and the computer system 128 can send control commands and / or control signals to the control circuit 126 to adjust or set the intensity of light emitted by one or more light source channels using user-programmable rules based on such fluctuation patterns.

[0200] In some instances, the temperature of the processing chamber 102 and / or the temperatures of one or more biofluids 108 and 110 can be adjusted or set by control circuitry 126 based on data received from one or more thermal sensors 166 at computer system 128. Suitable thermal sensors are well known in the art, such as the LM74 temperature sensor (Texas Instruments, Inc.). For example, if the temperature of the biofluid 108 detected by one or more thermal sensors 166 exceeds a threshold temperature, control circuitry 108 can adjust or set various operating parameters of the processing chamber 102 to reduce the temperature of the biofluid 108. For example, control circuitry 108 can increase the distance 156 between the light source array 104 and the biofluid 108, and / or instruct or control heating / cooling unit 114 to reduce the temperature of the processing chamber 102. Alternatively, control circuitry 126 can instruct or control heat exchanger 122 to increase the heat transfer rate between the light source array 104 and heat exchanger 122.

[0201] While specific examples of how feedback from various sensors can enable control circuitry 126 to adjust or set various parameters of the components of processing chamber 102 have been discussed above, these examples are not intended to be limiting. It should be understood that control circuitry 126 can adjust or set any of the adjustable parameters of possible components of the various embodiments of the processing system discussed above, based on feedback data detected by any of the various sensors discussed above and / or based on any user input provided at UI 182 of computer system 128.

[0202] Methods for treating biological fluids

[0203] The following discusses various methods for treating biological fluids to adequately inactivate one or more pathogens present in the biological fluid. These methods can be carried out using various embodiments of the systems discussed above. However, the methods described below do not necessarily require the use of the systems discussed above, but can be carried out using any system capable of performing these methods.

[0204] Figures 7A-7B This is a flowchart illustrating a method 700 for processing biological fluids according to certain embodiments. In various embodiments, some operations in the method may be combined and / or the order of some operations may be changed. Figures 7A-7B The order shown is different. Additionally, in some embodiments, operations shown in individual blocks / figures and / or discussed in conjunction with individual methods can be combined to form other methods, and operations shown in the same block / figure and / or discussed in conjunction with the same method can be divided into different methods.

[0205] exist Figure 7A Step 702 may provide or receive a biofluid (hereinafter referred to as "biofluid") infused with one or more pathogen inactivation compounds. In embodiments where a treatment chamber (such as chamber 102) is used to treat the biofluid, step 702 may include an optional step 703 of introducing or receiving the biofluid by the treatment chamber 102. For example, refer to Figure 1C In an embodiment where the processing chamber 102 includes a slidably movable platform 144, the slidably movable platform 144 can slide out of the processing chamber, on which biological fluid 108 (e.g., biological fluid in a container) can be placed, and the platform can slide back into the processing chamber 102.

[0206] In another instance, in an embodiment that includes multiple containers 132, 136 and 138, optional step 703 may include allowing biofluid 110 to flow from source container 136 into treatment chamber 102.

[0207] In optional step 704, a set of characteristics of the biological fluid can be determined. The determination of one or more characteristics of the biological fluid can be based on user input at computer system 128 and / or on feedback from the various types of sensors discussed above. For example, in an embodiment where processing chamber 102 includes one or more biological fluid type sensors 170, the type of biological fluid can be determined.

[0208] In another example, a barcode scanner 172 can be used to determine a set of characteristics of the biofluid. Specifically, the barcode sensor 172 can scan the barcode 134 on the biofluid container 130 to determine the identifier of the biofluid 108 and transmit this identifier to the computer system 128. The computer system 128 can then determine a set of characteristics of the biofluid 108 based on a list stored in memory 178 that associates the identifiers of one or more biofluids with their corresponding set of characteristics.

[0209] In optional step 706, a treatment profile of the biological fluid may be determined. Determining the treatment profile may include determining any one or more parameters that constitute the treatment profile discussed above. For example, determining the treatment profile may include determining one or more peak wavelengths of light to be used to irradiate the biological fluid. Determining the treatment profile may include determining one or more luminescence intensities at one or more peak wavelengths. Determining the treatment profile may include determining one or more emission durations at one or more peak wavelengths.

[0210] In some instances, determining the treatment profile of a biological fluid can be based on a set of characteristics of the biological fluid. For example, after computer system 128 has determined a set of characteristics of the biological fluid, computer system 128 can use a set of programmable rules to determine the treatment profile of the biological fluid. This set of programmable rules can determine one or more parameters of the treatment profile based on one or more of the characteristics of the biological fluid. For example, the programmable rules can match a certain type of photochemical agent with a certain peak wavelength of light, a certain emission duration, and a certain emission intensity of that peak wavelength of light sufficient to inactivate pathogens in the biological fluid mixed with the photochemical agent. In another instance, the programmable rules can match the depth of a portion of the biological fluid with a certain light intensity sufficient to inactivate pathogens in that portion of the biological fluid.

[0211] In other instances, the user may input one or more parameters of the processing profile at computer system 128.

[0212] Turning Figure 7BIn an example where the processing chamber 102 is used to process biological fluids, in optional step 708, a set of parameters of the processing chamber 102 can be adjusted or set by the control circuitry 126 based on the processing profile. The parameters in this set that can be adjusted or set based on the processing profile may include whether the biological fluid is agitated, one or more parameters related to the agitation of the biological fluid (e.g., the frequency and type of agitation), the temperature of the processing chamber 102, and the distance between the light source array 104 and the platform 144.

[0213] In step 710, the duration and intensity (e.g., providing a light dose, providing a total light dose) of irradiating the biological fluid (e.g., a biological fluid incorporating a photoactive pathogen inactivation compound) are sufficient to inactivate one or more pathogens in the biological fluid. In some embodiments, the irradiation of the biological fluid is performed according to the treatment profile.

[0214] In some instances, step 710 may include step 711, wherein the biological fluid is irradiated with light of a first peak wavelength and with light of a second peak wavelength. In some embodiments of any method provided herein, the first peak wavelength may differ from the second peak wavelength by at least (e.g., more than) 5 nm, 10 nm, 15 nm, 20 nm, or 25 nm or more. In some embodiments of any method provided herein, the light of the second peak wavelength is emitted by one or more second light sources, each emitting light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nm, and wherein the second peak wavelength differs from the first peak wavelength by at least 5 nm, such as at least one of 10 nm, 15 nm, 20 nm, or 25 nm. The first peak wavelength may be in the visible or ultraviolet spectrum, for example, ultraviolet A, ultraviolet B, or ultraviolet C. Similarly, the second peak wavelength may be in the visible or ultraviolet spectrum, for example, ultraviolet A, ultraviolet B, or ultraviolet C. In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 240 nm and about 250 nm, between about 245 nm and about 255 nm, between about 250 nm and about 260 nm, between about 255 nm and about 265 nm, between about 260 nm and about 270 nm, between about 265 nm and about 275 nm, between about 270 nm and about 280 nm, or between about 275 nm and about 285 nm. In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 280 nm and about 290 nm, between about 285 nm and about 295 nm, between about 290 nm and about 300 nm, between about 300 nm and about 310 nm, between about 305 nm and about 315 nm, or between about 310 nm and about 320 nm. In some implementations, the first peak wavelength and / or the second peak wavelength may be between about 315 nm and about 325 nm, between about 320 nm and about 330 nm, between about 325 nm and about 335 nm, between about 330 nm and about 340 nm, between about 335 nm and about 345 nm, between about 340 nm and about 350 nm, between about 345 nm and about 355 nm, between about 350 nm and about 360 nm, between about 355 nm and about 365 nm, between about 360 nm and about 370 nm, between about 365 nm and about 375 nm, between about 370 nm and about 380 nm, between about 375 nm and about 385 nm, between about 380 nm and about 390 nm, between about 385 nm and about 395 nm, or between about 390 nm and about 400 nm.In some implementations, the first peak wavelength and / or the second peak wavelength may be about 240 nm, about 245 nm, about 250 nm, about 255 nm, about 260 nm, about 265 nm, about 270 nm, about 275 nm, about 280 nm, about 285 nm, about 290 nm, about 295 nm, about 300 nm, about 305 nm, about 310 nm, about 315 nm, about 320 nm, about 325 nm, about 330 nm, about 335 nm, about 340 nm, about 345 nm, about 350 nm, about 355 nm, about 360 nm, about 365 nm, about 370 nm, about 375 nm, about 380 nm, about 385 nm, about 390 nm, about 395 nm, or about 400 nm. In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 255 nm and about 275 nm (e.g., between about 260 nm and about 270 nm, 265 nm). In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 275 nm and about 295 nm (e.g., between about 280 nm and about 290 nm, 285 nm). In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 300 nm and about 320 nm (e.g., between about 305 nm and about 315 nm, 310 nm). In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 315 nm and about 335 nm (e.g., between about 320 nm and about 330 nm, 325 nm). In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 330 nm and about 350 nm (e.g., between about 335 nm and about 345 nm, 340 nm). In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 355 nm and about 375 nm (e.g., between about 360 nm and about 370 nm, 365 nm). In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 375 nm and about 395 nm (e.g., between about 380 nm and about 390 nm, 385 nm). In some embodiments, the first peak wavelength and / or the second peak wavelength may be between about 315 nm and about 350 nm.

[0215] In some embodiments of any of the methods provided herein, the total dose of ultraviolet light irradiating the biological fluid emitted by one or more first light sources is approximately 0.5 J / cm². 2 Approximately 50 J / cm 2 Such as any of the following: approximately 0.5 J / cm 2 Approximately 10 J / cm 2 Approximately 0.5 J / cm 2 Approximately 15 J / cm 2Approximately 0.5 J / cm 2 Approximately 25 J / cm 2 Approximately 1 J / cm 2 Approximately 10 J / cm 2 Approximately 1 J / cm 2 Approximately 15 J / cm 2 Approximately 1 J / cm 2 Approximately 25 J / cm 2 Approximately 3J / cm 2 Approximately 10 J / cm 2 Approximately 3J / cm 2 Approximately 15 J / cm 2 Approximately 3J / cm 2 Approximately 25 J / cm 2 Approximately 5 J / cm 2 Approximately 10 J / cm 2 Approximately 5 J / cm 2 Approximately 15 J / cm 2 Approximately 5 J / cm 2 Approximately 25 J / cm 2 Approximately 10 J / cm 2 Approximately 30 J / cm 2 Approximately 10 J / cm 2 Approximately 20 J / cm 2 Approximately 15 J / cm 2 Approximately 50 J / cm 2 Approximately 15 J / cm 2 Approximately 35 J / cm 2 Approximately 20 J / cm 2 Approximately 30 J / cm 2 Approximately 25 J / cm 2 Approximately 50 J / cm 2 Approximately 30 J / cm 2 Approximately 40 J / cm 2 or about 40J / cm 2 Approximately 50 J / cm 2 In some embodiments, the total dose of ultraviolet light irradiating the biological fluid emitted by one or more first light sources is approximately 0.5 J / cm². 2 Or more, such as about any of the following: 1 J / cm 2 or more, 2J / cm 2 or more, 3J / cm 2 or more, 4J / cm 2 or more, 5J / cm 2 or more, 6J / cm 2 or more, 7J / cm 2 or more, 8J / cm 2or more, 9J / cm 2 or more, 10J / cm 2 or more, 15J / cm 2 or more, 20J / cm 2 or more, 25J / cm 2 or more, 30J / cm 2 or more, 35J / cm 2 or more, 40J / cm 2 or more, 45J / cm 2 or more or 50 J / cm 2 Or more. In some embodiments, the total dose of ultraviolet light irradiating the biological fluid emitted by one or more first light sources is less than about 50 J / cm². 2 Less than approximately 40 J / cm 2 Less than approximately 30 J / cm 2 Less than approximately 25 J / cm 2 Less than approximately 20 J / cm 2 Less than approximately 15 J / cm 2 or less than about 10 J / cm 2 In some embodiments, the duration and intensity of irradiation of the biological fluid are sufficient to provide a total dose of ultraviolet light irradiating the biological fluid (e.g., the aforementioned total dose) (e.g., any suitable combination of duration and intensity sufficient to provide a total dose of ultraviolet light). In some embodiments, the intensity is between 1 mW / cm². 2 With 1000mW / cm 2 Between (e.g., 1mW / cm) 2 With 100mW / cm 2 (between). In some implementations, the duration is between 1 second and 2 hours (e.g., between 1 minute and 60 minutes).

[0216] In some embodiments of any of the methods provided herein, light at a first peak wavelength and light at a second peak wavelength may be provided by a first light source and a second light source, respectively. The first light source and / or the second light source may be, for example, a solid-state lamp (SSL), a light-emitting diode (LED), an organic light-emitting diode (OLED), a polymer light-emitting diode (PLED), or a laser diode. In some instances, the first and second light sources may be included in light source channels 106 of the light source array 104.

[0217] In some embodiments of any of the methods provided herein, the first and second light sources may emit light with narrow spectral bandwidths. In some instances, the full width at half maximum (FWHM) spectral bandwidth (e.g., the spectral bandwidth at maximum peak intensity) of the light emitted by the first and / or second light sources may be less than 20 nm, less than 18 nm, less than 16 nm, less than 14 nm, less than 12 nm, less than 10 nm, less than 9 nm, less than 8 nm, less than 7 nm, less than 6 nm, or less than 5 nm. In some embodiments, the full width at half maximum (FWHM) spectral bandwidth of the light emitted by the first and / or second light sources is within 10 nm smaller and within 10 nm larger than the peak wavelengths of the first and / or second light sources, respectively (e.g., no more than 10 nm larger and no more than 10 nm smaller than the peak wavelengths of the first and / or second light sources, respectively). In some embodiments, the full width at half maximum (FWHM) spectral bandwidth of the light emitted by the first and / or second light sources may be greater than 1 nm, greater than 2 nm, greater than 3 nm, or greater than 4 nm or larger. In other instances, the light intensity at 50% of the maximum peak intensity of the light emitted by the first and / or second light source may be within 10 nanometers of the peak wavelength of the light emitted by the first and / or second light source.

[0218] In some instances, the biological fluid is irradiated sequentially with light of a first peak wavelength and then with light of a second peak wavelength. In other instances, the biological fluid is irradiated simultaneously with light of the first peak wavelength and light of the second peak wavelength. In still other instances, the irradiation of the biological fluid with light of the first peak wavelength and with light of the second peak wavelength partially overlap (e.g., irradiation with light of the first peak wavelength only for a period of time (from a light source in the processing chamber), followed by irradiation with light of both the first and second peak wavelengths for a period of time, followed by irradiation with light of the second peak wavelength only for a period of time (from a light source in the processing chamber).

[0219] In some embodiments of any of the methods provided herein, irradiating the biological fluid with light of a first peak wavelength can be performed for a first duration, and irradiating the biological fluid with light of a second peak wavelength can be performed for a second duration. The first duration may be equal to or different from the second duration. In some instances, the first duration may be at least 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 times or more of the second duration. In other instances, the second duration may be at least 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10 times or more of the first duration.

[0220] In some instances, the biological fluid may be irradiated with light of a first peak wavelength and a second peak wavelength, depending on the processing profile. For example, the processing profile may specify the light characteristics used to irradiate the biological fluid. An exemplary processing profile may specify that the biological fluid is first irradiated with light of the first peak wavelength at a first intensity for a first duration, and then irradiated with light of the second peak wavelength at a second intensity for a second duration. Another exemplary processing profile may specify that the biological fluid is irradiated with light of the first peak wavelength at a first intensity for a first duration, and simultaneously (e.g., at least partially overlapping) irradiated with light of the second peak wavelength at a second intensity for a second duration. In some embodiments, the processing profile may specify one or more agitation conditions to be applied before, during, and / or after irradiating the biological fluid. An exemplary processing profile may specify one or more agitation conditions to be applied before, during, and / or after irradiating the biological fluid with light of the first peak wavelength, and one or more agitation conditions to be applied before, during, and / or after irradiating the biological fluid with light of the second peak wavelength.

[0221] In some embodiments of any of the methods provided herein, the biological fluid may be irradiated with light of a single peak wavelength (e.g., a first peak wavelength). In some instances, step 710 may include step 712, wherein the biological fluid may be irradiated with light of a single peak wavelength (e.g., a first peak wavelength). The single peak wavelength (e.g., the first peak wavelength) may be in the visible or ultraviolet spectrum, ultraviolet A spectrum, ultraviolet B spectrum, or ultraviolet C spectrum. In other instances, the single peak wavelength (e.g., the first peak wavelength) may be between about 240 nm and about 250 nm, between about 245 nm and about 255 nm, between about 250 nm and about 260 nm, between about 255 nm and about 265 nm, between about 260 nm and about 270 nm, between about 265 nm and about 275 nm, between about 270 nm and about 280 nm, or between about 275 nm and about 285 nm. In some implementations, a single peak wavelength (e.g., a first peak wavelength) may be between about 280 nm and about 290 nm, between about 285 nm and about 295 nm, between about 290 nm and about 300 nm, between about 300 nm and about 310 nm, between about 305 nm and about 315 nm, or between about 310 nm and about 320 nm. In some implementations, a single peak wavelength (e.g., a first peak wavelength) may be between about 315 nm and about 325 nm, between about 320 nm and about 330 nm, between about 325 nm and about 335 nm, between about 330 nm and about 340 nm, between about 335 nm and about 345 nm, between about 340 nm and about 350 nm, between about 345 nm and about 355 nm, between about 350 nm and about 360 nm, between about 355 nm and about 365 nm, between about 360 nm and about 370 nm, between about 365 nm and about 375 nm, between about 370 nm and about 380 nm, between about 375 nm and about 385 nm, between about 380 nm and about 390 nm, between about 385 nm and about 395 nm, and between about 390 nm and about 400 nm. In some implementations, the single peak wavelength (e.g., the first peak wavelength) can be about 240 nm, about 245 nm, about 250 nm, about 255 nm, about 260 nm, about 265 nm, about 270 nm, about 275 nm, about 280 nm, about 285 nm, about 290 nm, about 295 nm, about 300 nm, about 305 nm, about 310 nm, about 315 nm, about 320 nm, about 325 nm, about 330 nm, about 335 nm, about 340 nm, about 345 nm, about 350 nm, about 355 nm, about 360 nm, about 365 nm, about 370 nm, about 375 nm, about 380 nm, about 385 nm, about 390 nm, about 395 nm, or about 400 nm.In some embodiments, a single peak wavelength (e.g., a first peak wavelength) may be between about 255 nm and about 275 nm (e.g., between about 260 nm and about 270 nm, 265 nm). In some embodiments, a single peak wavelength (e.g., a first peak wavelength) may be between about 275 nm and about 295 nm (e.g., between about 280 nm and about 290 nm, 285 nm). In some embodiments, a single peak wavelength (e.g., a first peak wavelength) may be between about 300 nm and about 320 nm (e.g., between about 305 nm and about 315 nm, 310 nm). In some embodiments, a single peak wavelength (e.g., a first peak wavelength) may be between about 315 nm and about 335 nm (e.g., between about 320 nm and about 330 nm, 325 nm). In some embodiments, a single peak wavelength (e.g., a first peak wavelength) may be between about 330 nm and about 350 nm (e.g., between about 335 nm and about 345 nm, 340 nm). In some embodiments, a single peak wavelength (e.g., a first peak wavelength) may be between about 355 nm and about 375 nm (e.g., between about 360 nm and about 370 nm, 365 nm). In some embodiments, a single peak wavelength (e.g., a first peak wavelength) may be between about 375 nm and about 395 nm (e.g., between about 380 nm and about 390 nm, 385 nm). In some embodiments, a single peak wavelength (e.g., a first peak wavelength) may be between 315 nm and about 350 nm.

[0222] In some embodiments of any of the methods provided herein, light of a single peak wavelength (e.g., a first peak wavelength) may be provided by a first light source. In some instances, the first light source may be the sole light source in the processing chamber 102 used to irradiate the biological fluid. The first light source may be, for example, a solid-state lamp (SSL), a light-emitting diode (LED), an organic light-emitting diode (OLED), a polymer light-emitting diode (PLED), or a laser diode. For example, the first light source may be included in the light source channel 106 of the light source array 104. Figure 1A-1E As shown, the light source channel 106 may face only one side of the container 130 that carries the biological fluid 108.

[0223] The first light source can emit light with a narrow spectral bandwidth. Specifically, the light intensity at 50% of the maximum peak intensity emitted by the first light source can be emitted at a wavelength less than 10, 20, 30, or 40 nanometers different from the peak wavelength of the light emitted by the first light source. In other examples, the full width at half maximum (FWHM) spectral bandwidth of the light emitted by the first light source can be less than 20 nm, 18 nm, 16 nm, 14 nm, 12 nm, 10 nm, 9 nm, 8 nm, 7 nm, 6 nm, 5 nm, or less than 5 nm.

[0224] In some embodiments of any of the methods provided herein, the treatment method is sufficient to inactivate at least about 1 log of pathogen present (e.g., when present), such as at least about 2 log, 3 log, 4 log, 5 log, 6 log, 7 log, 8 log, 9 log, or 10 log (e.g., after the admixture has been exposed to light sufficient to photochemically inactivate the pathogen). In some embodiments, the treatment method is sufficient to inactivate at least about 1 log of pathogen present (e.g., when present), such as at least about 2 log, 3 log, 4 log, 5 log, 6 log, 7 log, 8 log, 9 log, or 10 log, and wherein the biofluid contains about 5 μM or less PIC after irradiation, such as a concentration of about 4 μM or less, 3 μM or less, 2 μM or less, or 1 μM or less. In some embodiments, the treatment method is sufficient to inactivate at least about 1 log of pathogen present (e.g., when present), such as at least about 2 log, 3 log, 4 log, 5 log, 6 log, 7 log, 8 log, 9 log, or 10 log, wherein the concentration of the pathogen inactivating compound mixed with the biofluid prior to irradiation is about 15 μM to about 150 μM, and wherein the biofluid contains about 5 μM or less of PIC after irradiation, such as a concentration of about 4 μM or less, 3 μM or less, 2 μM or less, or 1 μM or less. In some embodiments, the treatment method is sufficient to inactivate at least about 1 log of pathogen present (e.g., when present), such as at least about 2 log, 3 log, 4 log, 5 log, 6 log, 7 log, 8 log, 9 log, or 10 log, wherein the concentration of the pathogen-inactivating compound incorporated with the biofluid prior to irradiation is about 15 μM to about 150 μM (e.g., about 30 μM to about 110 μM, about 60 μM to about 90 μM, about 75 μM), and wherein the total dose of ultraviolet light irradiating the biofluid is about 0.5 J / cm². 2 Approximately 50 J / cm 2 (For example, about 3J / cm) 2 Approximately 15 J / cm 2The biofluid contains, after irradiation, about 5 μM or less of a PIC, such as about 4 μM or less, 3 μM or less, 2 μM or less, or 1 μM or less. In some embodiments, the treatment method is sufficient to inactivate at least about 4 log of pathogens present (e.g., when present), wherein the concentration of the pathogen-inactivating compound co-incorporated with the biofluid prior to irradiation is about 30 μM to about 110 μM, and wherein the biofluid contains about 5 μM of a PIC after irradiation. In some embodiments of any of the foregoing methods, the biofluid is suitable for infusion into a subject after irradiation without further treatment to remove residual pathogen-inactivating compounds or one or more of their photoproducts.

[0225] In some embodiments of any of the methods provided herein, the biofluid includes blood products. In some embodiments, the biofluid includes a whole blood composition. In some embodiments, the biofluid includes a red blood cell composition. In some embodiments, the biofluid includes a platelet composition (e.g., platelets). In some embodiments, the biofluid includes a plasma composition (e.g., plasma). In some embodiments, the biofluid includes a platelet composition (e.g., platelets) and a plasma composition (e.g., plasma). In some embodiments, the biofluid (e.g., a platelet composition) includes a platelet additive solution. In some embodiments, the biofluid is a platelet composition comprising a platelet additive solution and plasma (e.g., about 5 to 50% plasma and about 95 to 50% additive solution; about 30 to 50% plasma and about 70 to 50% platelet additive solution). For example, in some embodiments, the processing method includes preparing a platelet composition suitable for individual transfusion using the systems and methods disclosed herein.

[0226] In some embodiments of any of the methods provided herein, the treatment methods described herein are sufficient to inactivate at least 1 log (e.g., at least 2 log, 3 log, 4 log or more) of pathogens (e.g., when present), wherein the biofluid is suitable for infusion into a subject after irradiation without further treatment to remove residual PIC or its photoproducts. In some embodiments, the treatment methods are sufficient to inactivate at least 1 log (e.g., at least 2 log, 3 log, 4 log or more) of pathogens (e.g., when present), wherein the platelet composition contains 5 μM or less of PIC after irradiation. In some embodiments, the concentration of PIC in the mixture prior to irradiation is at least 10 μM. In some embodiments, the concentration of PIC in the mixture prior to irradiation is at least 30 μM, at least 50 μM, at least 70 μM, at least 90 μM, or at least 110 μM or higher. In some embodiments, the concentration of PIC in the mixture prior to irradiation is between about 15 μM and about 150 μM. In some embodiments, the concentration of PIC in the admixture prior to irradiation is between about 15 μM and about 110 μM, about 30 μM and about 110 μM, about 60 μM and about 110 μM, about 30 μM and about 90 μM, or about 60 μM and about 90 μM. In some embodiments, the concentration of PIC in the admixture prior to irradiation is about 75 μM. In some embodiments, the methods for treating biological fluids disclosed herein do not include subjecting the biological fluid to further treatment, such as exposure to a compound adsorption device (CAD), after irradiation with a duration and intensity sufficient to inactivate one or more pathogens present in the biological fluid. In some embodiments, the methods for processing biological fluids disclosed herein do not include subjecting the biological fluid to further treatment, such as exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts after irradiation of the biological fluid for a duration and intensity sufficient to inactivate one or more pathogens present in the biological fluid (e.g., when present), wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 log of pathogens), and wherein the biological fluid is suitable for infusion into a subject after irradiation according to the methods disclosed herein. In some embodiments, after irradiation of a biological sample according to the methods disclosed herein, the biological sample contains less than 5 μM of PIC (e.g., less than 2 μM of PIC).

[0227] In some embodiments of any of the methods provided herein, the processing method includes obtaining PIC at a desired (e.g., standardized) concentration or premixing it with a platelet additive solution (PAS), and then metering the PIC / PAS solution into the platelet formulation, thereby allowing, for example (i) improved processing flexibility and control, (ii) improved pathogen inactivation, including, for example, allowing a reduction in the amount of PIC used for pathogen inactivation, (iii) reduced processing steps, such as eliminating the need for further treatment with a compound absorption device (CAD) to remove residual PIC or its photoproducts prior to administration to an individual, and / or (iv) improved platelet quality.

[0228] In some embodiments of any of the methods provided herein, the treatment further includes, prior to irradiation, incubating the biological fluid with the photoactive pathogen inactivating compound for a period of 30 minutes to 24 hours (e.g., 2 hours to 24 hours, 4 hours to 24 hours, 8 hours to 24 hours, 12 hours to 24 hours).

[0229] As used herein, unless otherwise indicated, the singular forms “a (kind)” and “the (represented)” include plural references.

[0230] It should be understood that the aspects and implementation schemes of the disclosed content provided herein include the following: "includes aspects and implementation schemes", "consisting of aspects and implementation schemes", and "consisting substantially of aspects and implementation schemes".

[0231] It's important to understand that when a range is provided "between" two numerical values, the endpoints of that range are included. For example, the range "between x and y" or "between approximately x and approximately y" includes the values ​​x and y.

[0232] The present disclosure is further illustrated by the following examples, which should not be construed as limiting the scope or substance of the disclosure to the specific procedures described herein.

[0233] Example

[0234] Example 1. A system for processing biological fluids

[0235] An exemplary system for processing biological fluids is configured to house two opposing arrays of light sources facing each other within a processing chamber, each comprising a group of 72 groups with four LED channels, each group including LEDs with wavelengths of both 340 nm and 365 nm (see example...). Figure 2A The system also includes a glass platform placed between the two arrays to irradiate the biofluid containers placed on the platform with ultraviolet light from opposite sides of the containers (see, for example...). Figure 4The system control provides for the adjustment of the LEDs, and the treatment of biological fluid samples with light from either a 340nm or 365nm LED, or with light of both 340nm and 365nm wavelengths simultaneously or sequentially, controlling the timing (e.g., duration) and intensity of the irradiation by the LEDs.

[0236] Example 2. Photochemical transformation of pathogen inactivating compounds

[0237] Studies using the system disclosed herein were conducted to determine the photochemical conversion efficiency of pathogen-inactivating compounds. The photochemical agent amtoxalin (also known as S-59) is a commercially available medical device for the pathogen inactivation treatment of plasma and platelet blood components. The psoralen pathogen-inactivating compound used in the blood system (Cerus Corporation). To determine the photochemical conversion efficiency of amtoxalin after treatment with the LED-based irradiation device described in Example 1 and the distribution of the present photoproducts, various wavelengths and light sources were studied and compared. Narrow-bandwidth 340nm wavelength LEDs (Example 1 device), narrow-bandwidth 365nm wavelength LEDs (Example 1 device), and commercially available fluorescent UVA bulbs were used. Irradiation is performed using a blood system irradiation device (INT-100). The bulb in the INT-100 device produces a broad bandwidth of irradiation across the entire UVA spectrum (see, for example...). Figure 9 Furthermore, the filters in the INT-100 device attenuate light wavelengths below 320nm, thus generating UVA irradiation of approximately 320-400nm with a peak wavelength of approximately 352nm, as shown in spectral curve 902. Figure 9 Exemplary narrow bandwidth peaks (not to scale) for 340nm and 365nm LEDs are also described, compared as spectral curves 904 and 906, respectively. For the purpose of using data from the prototype system described in Examples 1-9 herein, the unit of light dose is joules (J) / cm². 2 ±25%.

[0238] For the study, three different suspension media units were prepared: 100% plasma, platelet additive solution (PAS III), or a combination of plasma and PAS III at a 35% / 65% ratio. Amtoxapine (S-59) was added to each type of unit at a concentration of 150 μM, followed by exposure to approximately 6.4 J / cm² using an LED-based device from 340 nm or 365 nm (for all unit types). 2 UV light dose (100% plasma): approximately 3.6 J / cm² 2 UV light dose (PAS + plasma) or approximately 3 J / cm 2The UV light dose (PAS) or approximately 6.4 J / cm² from the INT-100 device (for plasma or PAS units only) is required. 2 UV light irradiation. As previously described (Schlenke et al., 2008, Transfusion, 48:697-705), samples before and after irradiation were analyzed by HPLC to determine the efficiency of S-59 photoconversion and the distribution of photoproducts.

[0239] For plasma, PAS, or PAS+plasma (65 / 35) units, the percentage of residual S-59 after irradiation is shown in Table 1 below. It is worth noting that this was achieved using a 340 nm wavelength LED at approximately 6.4 J / cm². 2 Irradiation with S-59 produces significantly greater S-59 light conversion in each type of medium than irradiation with a similar light dose from a 365nm LED or INT-100.

[0240] Table 1: Optical conversion of S-59 (percentage of remaining input to S-59).

[0241]

[0242] In addition, HPLC analysis of the irradiated samples was used to determine the area counts and relative levels of residual S-59 and photoproducts after various treatment conditions. Table 2 below shows the differences in the distribution of the resulting photoproducts observed for irradiation at 340 nm, 365 nm, and INT-100 nm.

[0243] Table 2: Photoproducts after irradiation.

[0244]

[0245] Example 3. Inactivation of the virus

[0246] The photochemical inactivation of viruses in human donor plasma was then evaluated using the irradiation apparatus of this disclosure. Pathogen inactivation studies were conducted in plasma spiked with rod-shaped vesicular stomatitis virus (VSV) and subsequently treated with ammoniated aminotoxalin and UVA light, using either narrow-spectrum 340 nm and 365 nm LED devices or broad-spectrum INT-100 devices described in Examples 1 and 2.

[0247] The ABO-matched plasma pool was aseptically divided into three equal volumes of approximately 500 mL each, with each unit inoculated with VSV. The VSV-spiked plasma units were then individually compared with commercially available... The blood system processing unit was connected, mixed with 150 μM amtoxapine, and transferred to an irradiation container. Samples were collected from each unit before UV irradiation to determine the pre-treatment viral titer. The VSV-containing plasma units were then subjected to ~6.4 joules / cm² using an INT-100 device or a 340 nm or 365 nm LED as the light source. 2 UVA irradiation (see, for example, Example 2). Samples were collected after irradiation, and the viral titer after treatment was determined by plaque assay of BHK cells.

[0248] Table 3 below shows the virus titer results of the samples before and after treatment, as well as the obtained virus inactivation level (log inactivation).

[0249] Table 3: Virus inactivation

[0250]

[0251] These data demonstrate a striking difference in the levels of photochemical inactivation. The use of amtoxapine and narrow-band UVA irradiation as a light source resulted in significantly higher levels of virus inactivation compared to narrow-band UVA irradiation from a 365nm LED and broadband UVA irradiation from an INT-100 device. The inactivation levels from the 365nm LED were comparable to those from the INT-100 device.

[0252] Virus inactivation and photoconversion

[0253] Another study compared VSV inactivation in 220 mL or 350 mL volumes with a lower 30 μM dose of amtoxarine (S-59) and UVA light, as well as using a 340 nm LED or INT-100 irradiation device. Plasma was pooled to at least 1140 mL and inoculated with a 1:100 final dilution of VSV stock solution. The VSV-spiked plasma pool was then divided into four units: two 220 mL units and two 350 mL units. Each unit was inoculated with approximately 30 μM amtoxarine, and control samples were collected to determine the VSV titer and amtoxarine concentration before UVA exposure. One 220 mL unit and one 350 mL unit were exposed to ~3.0 J / cm² using an INT100 irradiator. 2 UVA, while simultaneously using a 340nm LED irradiator to subject another 220mL and 350mL unit to ~3.0J / cm². 2 UVA. After photochemical treatment, samples were collected from each unit to determine VSV titers and amtoxapine concentrations following UVA exposure. VSV titers (log) were determined using standard plaque assays. 10 The concentration of amtoxapine (μM) was determined by HPLC, as shown in Table 3b below as the average of two replicate experiments.

[0254] Table 3b: Virus inactivation and photoconversion of amtosalicylate.

[0255]

[0256] These data also indicate that the virus inactivation levels using amtoxapine and UVA irradiation with a 340nm LED as the light source are higher than those using broadband UVA irradiation from the INT-100 device. Furthermore, the photoconversion level of amtoxapine using the 340nm device is significantly higher than that using the INT-100 device, resulting in levels below 1 μM after photochemical treatment in the 220 mL unit and close to 2 μM in the 350 mL unit.

[0257] Further photochemical inactivation studies were conducted on other viruses. Caliciviruses used as hepatitis E virus models, such as feline calicivirus (FCV), have previously been shown to exhibit high resistance to photochemical inactivation with amtoxalin (S-59), with a titer reduction of only about 1.7–2.4 log10 (Irsch et al., Transfus Med Hemother, 38:19–31 (2011)). Studies were conducted to evaluate the inactivation level of FCV in platelet preparations. More specifically, two platelet units prepared in 35% plasma / 65% platelet additive solution (PAS) were pooled to produce a combined volume of approximately 400 mL containing approximately 3.8 x 10⁻⁶ FCV. 11 Platelets were collected and inoculated with feline calicivirus (FCV) stock solution at a final dilution of 1:100. The FCV-spiked platelets were then divided into ten smaller units, each approximately 28.5 mL. Nine of these units were assigned to amtoxapine "dose" groups, each containing three units, to which one of three different concentrations of amtoxapine was added: 90 μM, 30 μM, or 15 μM. Samples were collected from each unit before irradiation. Within each dose group, the units were incubated at room temperature for 4 hours, 8 hours, or 24 hours (T = 4 hours, 8 hours, 24 hours) and then subjected to approximately 3 J / cm² using the aforementioned apparatus. 2 The cells were irradiated with 340 nm UVA light. For the remaining cells, 150 μM amtoxapine was added, and the control samples before irradiation were used for analysis. The cells were then immediately (T=0) exposed to 340 nm UVA light, unintentionally receiving more than twice the light dose of the other nine samples. After UVA treatment, samples from all cells, along with the control samples before irradiation, were collected to determine FCV titers (by standard plaque assay) and amtoxapine concentrations (by HPLC). The data are shown in Table 3c below.

[0258] Table 3c: Virus inactivation and photoconversion of amtosalicylate.

[0259]

[0260] As these data demonstrate, the S-59 photochemical inactivation level of FCV using the 340 nm LED irradiation device of this disclosure is higher than the level reported by Irsch (ibid.) with 150 μM S-59 and broad-spectrum UV-A light. Furthermore, incubating FCV-containing platelets with S-59 for a period of time (e.g., pre-incubation) before irradiation with the LED device resulted in even higher FCV inactivation levels, even at lower input concentrations of the S-59 pathogen-inactivating compound. Specifically, pre-incubation for 4, 8, or 24 hours at 90 μM and 30 μM S-59 concentrations, and pre-incubation for 8 or 24 hours at 15 μM S-59 concentrations, resulted in at least 4 log FCV inactivation with the LED device. For 150 μM S-59 without pre-incubation, 2.5 log inactivation was obtained. FCV inactivation greater than 5.6 log was achieved under several conditions, reflecting inactivation below the detection limit of the dilution tested in plaque assays. Furthermore, HPLC analysis to determine the amount (e.g., concentration) of residual S-59 in the samples after UVA irradiation and photoconversion showed that the residual S-59 concentration was reduced to less than 5 μM for pathogen inactivation, and in many cases to less than 2 μM or less than 1 μM. These data demonstrate that pathogen inactivation treatment conditions based on the methods presented herein can be achieved, resulting in high levels of viral inactivation (e.g., >4 log, >5.6 log) and effective S-59 photoconversion with low levels of residual S-59 concentration.

[0261] Side-to-side contrast irradiation

[0262] Follow-up studies will be conducted to evaluate pathogen inactivation by irradiation from LED arrays placed above and below the biofluid container (e.g., bilateral irradiation) or from LED arrays placed only above the biofluid container (e.g., unilateral irradiation).

[0263] Platelet units were prepared using 35% plasma / 65% PAS, with a volume of approximately 370 mL and containing approximately 5.2 x 10⁻⁶ platelets. 11 Platelets were collected and inoculated with FCV stock solution at a final dilution of 1:100. The FCV-spiked platelets were then divided into ten smaller units, each approximately 28.5 mL. Nine of these units were assigned to the amtoxapine "dose" groups: two units with 150 μM amtoxapine, four units with 30 μM amtoxapine, and four units with 15 μM amtoxapine. The 30 μM and 15 μM dose groups were incubated at room temperature for 8 hours or 24 hours (T = 8 hours, 24 hours), and pre-irradiation samples were collected from each unit. The units were then subjected to approximately 3 J / cm² using the aforementioned device, delivered from either the upper or lower LED arrays or only from the upper LED array. 2The cells were irradiated with 340 nm UVA light. For 150 μM cells, a control sample was taken before irradiation for analysis, and then the cells were immediately irradiated with 340 nm UVA light with either a top + bottom (2 sides) LED configuration or a top (1 side) LED configuration only (T = 0). After UVA treatment, samples from all cells, along with the control sample before irradiation, were collected for determining FCV titers by standard plaque assays and for determining amtoxapine concentrations by HPLC. The data are shown in Table 3d below.

[0264] Table 3d: Virus inactivation and photoconversion of amtosalicylate.

[0265]

[0266] As these data demonstrate, incubating FCV-containing platelets with S-59 (e.g., 8 hours, 24 hours) followed by LED irradiation resulted in high levels of FCV inactivation, even with low input concentrations of the S-59 pathogen-inactivating compound. Inactivation levels greater than 150 μM S-59 were again observed. Furthermore, the inactivation levels were generally comparable regardless of whether the FCV-containing platelets were irradiated from both sides or only from one side with 340 nm LED irradiation. HPLC analysis also again showed efficient photoconversion, achieving very low residual S-59 levels (e.g., <1 μM) after photochemical treatment with either one or both sides of LED irradiation.

[0267] Example 4: Inactivation of bacteria

[0268] The systematic review of this disclosure uses photochemical treatment to inactivate bacteria in human plasma. Pathogen inactivation studies were conducted in human donor plasma spiked with the bacteria *Escherichia coli*, and subsequently treated with amtoxaridine and UVA light using the LED-based system described in Example 1 or the INT-100 device used for comparison.

[0269] More specifically, approximately 3000 mL of fractionated plasma (FFP) was aseptically divided into five equal volumes of approximately 585 mL each. Each unit was inoculated with an overnight culture of ~6 log CFU / mL of E. coli. The E. coli-spiked plasma units were then each inoculated with one of three concentrations (150 μM for two units, 15 μM for two units, and 1.5 μM for one unit) of the pathogen-inactivating compound amtoxalin (S-59). The blood system processing apparatus was mixed in with the irradiation container. Samples were collected from each unit prior to UV irradiation to determine the pre-processing bacterial titer. The remaining E. coli-spiked plasma was then subjected to UVA irradiation, with units containing 150 μm and 15 μm amtoxapine irradiated using a commercially available wideband INT-100 device at ~3 J / cm². 2Irradiation with light dose, or irradiation of units containing 150μm, 15μm, and 1.5μm amtoxalin with a narrow-band 340nm LED light source (Example 1 device), followed by exposure to UVA light once (~3J / cm). 2 ), twice (~6J / cm) 2 ) or three times (~9J / cm) 2 The results are shown in the table below. Samples were collected for each treatment condition to determine the bacterial titer after treatment using the standard colony-forming unit assay.

[0270] Table 4 below shows the bacterial titer results before and after UVA treatment, as well as the obtained bacterial inactivation level (log reduction). Additionally, the light conversion efficiency of amtoxalin (S-59) was determined and is shown as the percentage of S-59 remaining after each indicated treatment condition. LOQ indicates the limit of quantitation.

[0271] Table 4: Bacterial inactivation and S-59 transformation

[0272]

[0273] These data indicate that using amtoxarine and narrowband UVA irradiation as the light source achieves a relatively high level of bacterial photochemical inactivation compared to wider INT-100 irradiation. Furthermore, bacterial reductions of more than 4 log were achieved using commercially approved concentrations of 150 μM amtoxarine and significantly lower concentrations of 15 μM. In addition, the use of LED-based irradiation devices in these studies significantly improved the efficiency of S-59 photoconversion, resulting in much lower S-59 levels in the treated materials.

[0274] In another study, four plasma units were prepared from ~220 mL or ~350 mL of pooled plasma. Each unit was inoculated with an overnight culture of ~6 log CFU / mL of E. coli. The E. coli-spiked plasma units were then each inoculated with 15 μM of the pathogen-inactivating compound amtoxalin (S-59). The blood system processing unit was mixed in with the irradiated container. Samples were collected from each unit prior to UV irradiation to determine the pre-treatment bacterial titer. The remaining E. coli-spiked plasma was then subjected to ~6.4 J / cm³ using a narrow-bandwidth 340 nm LED device or a commercially available INT-100 device. 2 UVA irradiation with light dose.

[0275] Bacterial titers were analyzed before and after UVA treatment to determine the level of bacterial inactivation, which is shown as a log reduction in Table 5 below. Additionally, S-59 photoconversion was determined by HPLC and is shown as the absolute concentration and residual percentage after each indicated treatment condition.

[0276] Table 5: Bacterial inactivation and S-59 transformation

[0277]

[0278] The data is the average of the two samples tested (n=2).

[0279] These data also indicate that using S-59 and narrowband UVA as the light source achieves a relatively high level of bacterial photochemical inactivation compared to the wider INT-100 irradiation. Furthermore, the use of an LED-based irradiation device significantly improved the efficiency of S-59 photoconversion, resulting in much lower S-59 levels in the treated material.

[0280] To confirm that the observed E. coli inactivation is a photochemical process requiring pathogen-inactivating compounds, rather than solely mediated by UVA light from the LED device, a control experiment was conducted using increased doses of 340nm LED irradiation without the administration of amtoxaridine. For this study, E. coli cultures were prepared and spiked into ~585 mL plasma units with a titer of ~6 log CFU / mL. The spiked plasma was then transferred to a... The plasma was placed in an irradiation bag of a blood system plasma processing device, and samples were taken before irradiation to determine the initial control titer. The bacterial-spiked plasma was then subjected to 340 nm irradiation, with samples taken after each energy dose indicated in Table 6 below for bacterial titer. The titers before and after irradiation, along with the calculated log reduction, are shown. No inactivation of *E. coli* was observed at different 340 nm UVA light dose levels in the absence of pathogen-inactivating compounds.

[0281] Table 6: Bacterial Inactivation

[0282]

[0283] Example 5. Treatment of platelets in plasma and additive solutions

[0284] Platelets collected in PAS / plasma (65% PAS III / 35% plasma) were aliquoted into three 285 mL units for study. Amtoxapine (S-59) was added to a concentration of 150 μM, and the units were irradiated once with a narrow-band 340 nm LED or 365 nm LED using the apparatus of Example 1 or the INT-100 apparatus (~3.6 J / cm²). 2 Total dose), twice (~7.2 J / cm) 2 Total dose) or three times (~10.8 J / cm) 2total dose). The efficiency of S-59 photoconversion and photoproduct formation after UVA irradiation was evaluated by HPLC as in the previous examples. The concentration of S-59 after irradiation for the INT-100 device (approximately 3.6, 7.2, 10.8 J / cm 2 ) was 32 μM, 11 μM and 5 μM, and for the 340 nm LED (approximately 3.6, 7.2, 10.8 J / cm 2 ) was 9 μM, 2 μM and 0.98 μM (<LOQ), and for the 365 nm LED (approximately 3.6, 7.2, 10.8 J / cm 2 ) was 42 μM, 15 μM and 7 μM. These data show that the degree of S-59 photoconversion is higher when using the narrow-band 340 nm LED irradiation device, and the residual S-59 level after two or three irradiations (e.g., approximately 7.2 or 10.8 J / cm 2 ) is equal to or lower than 2 μM.

[0285] HPLC analysis of the irradiated samples was performed to determine the area counts and relative levels of photoproducts produced from various treatment conditions. As shown in Tables 7-9 below, differences in the resulting photoproduct distribution were observed for 340 nm, 365 nm and INT-100 irradiation, and lower photoproduct levels were generally found after irradiation with narrow-band 340 nm wavelength light.

[0286] Table 7: Photoproducts from INT-100 Irradiation

[0287] INT 100 S-59 Peak B Peak C Peak D Peak E Peak G 0 1753 0 0 0 0 0 3.6 396 19 24 127 27 9 7.2 129 18 338 102 26 11 10.8 56 15 34 72 24 12

[0288] Table 8: Photoproducts from 340 nm Irradiation

[0289] 340nm S-59 Peak B Peak C Peak D Peak E Peak G 0 1826 0 0 0 0 0 3.6 106 4 29 93 28 5 7.2 24 2 27 33 25 5 10.8 11 3 23 13 22 5

[0290] Table 9: Photoproducts from 365 nm Irradiation

[0291] 365nm S-59 Peak B Peak C Peak D Peak E Peak G 0 1753 0 0 0 0 0 3.6 514 18 30 152 28 10 7.2 183 17 42 156 29 11 10.8 84 14 43 144 29 13

[0292] Liquid chromatography-mass spectrometry was also used to perform S-59 photoconversion and photoproduct analysis on platelets in PAS / plasma (65% PAS III / 35% plasma) treated with 150 μM amotosalen and irradiated once (approximately 3.6 J / cm 2 total dose), twice (approximately 7.2 J / cm 2 total dose) or three times (approximately 10.8 J / cm 2 total dose). The 340 nm LED and the broadband INT-100 device were compared. Since it is assumed that the mass spectrometric extinction coefficient of the photoproduct is the same as that of S-59, only the relative concentration difference (μM) between samples rather than the absolute concentration is compared in Table 9b below.

[0293] Table 9b: Photoproducts after irradiation

[0294]

[0295] In addition, after three UVA irradiations (˜10.8 J / cm 2 ), various measured values of platelet quality were evaluated immediately by standard methods to determine possible differences between light sources. As shown in Table 10 below, these platelet parameters remained similar under each irradiation condition.

[0296] Table 10: Platelet parameters after 3× irradiation

[0297] INT 100 340nm 365nm Platelet count <![CDATA[~1.2x10 6 / mL]]> <![CDATA[~1.2x10 6 / mL]]> <![CDATA[~1.2x10 6 / mL]]> pH (37℃) 6.60 6.61 6.74 Cracks (%) 2.25 2.36 1.72 <![CDATA[ATP mmol / x10 8 ]]> 4.1 4.0 4.8 % of residual S-59 3.1 0.5 4.9

[0298] Example 6: Treatment of apheresis-collected platelets in 100% plasma or plasma / PAS

[0299] Studies were conducted to evaluate the photoconversion of amotosalen and platelet function in platelets suspended in 100% plasma after 7 days (Day 3, Day 7) of photochemical treatment with different light doses using the 340 nm device of the present disclosure. Five apheresis platelet units in 100% plasma were pooled and divided into ˜285 mL units for the study. Amotosalen (S-59) was added to a concentration of 15 μM. Three of the units were irradiated with the narrow-band 340 nm LED device of Example 1 at one of three different light doses, at ˜3.6 J / cm 2 for one irradiation (1×), two irradiations (2×, ˜7.2 J / cm 2 ) or three irradiations (3×, ˜10.8 J / cm 2 ). Additional units were irradiated with the INT-100 device at ˜3.6 J / cm 2 for comparison or kept as untreated controls. S-59 photoconversion was assessed by HPLC after UVA irradiation as in previous examples. The S-59 concentration after irradiation was 4.11 μM for the INT-100 device, and was significantly lower with the 340 nm LED irradiation device: 0.86 μM (<LOQ) for the 1× light dose, 0.19 μM (<LOQ) for the 2× light dose, and 0.00 μM (<LOQ) for the 3× light dose, indicating a higher degree of photoconversion.

[0300] In addition, various biochemical and / or functional measurements of platelet quality were evaluated before and / or after UVA irradiation and on days 3, 5 and 7 after treatment. As shown in Tables 11-19 below, for platelet quality parameters, the results for the control, INT-100 and 340 nm test samples were generally similar, except for the 3× 340 nm dose for certain parameters.

[0301] Table 11: Platelet count (x10) 3 (cells / μL)

[0302] UVA before UVA after D3 D5 D7 Comparison 1425 1487 1436 1453 INT-100 1481 1415 1395 1400 1439 340nm(1x) 1453 1366 1391 1338 1391 340nm(2x) 1448 1301 1317 1370 1376 340nm(3x) 1452 1322 1372 1550 1474

[0303] Table 12: pH at 37°C

[0304] UVA before UVA after D3 D5 D7 Comparison 6.91 6.62 6.70 6.62 INT-100 6.87 6.89 6.82 6.67 6.54 340nm(lx) 6.90 6.89 6.84 6.70 6.58 340nm(2x) 6.90 6.89 6.86 6.72 6.56 340nm(3x) 6.87 6.87 6.56 5.57 5.49

[0305] Table 13: Adenosine triphosphate (ATP; mmol / 10) 8 (platelet count)

[0306]

[0307]

[0308] Table 14: pCO2 (mm Hg) at 37℃

[0309] UVA before UVA after D3 D5 D7 Comparison 87.7 59.1 27.1 29.1 INT-100 101.1 91.4 55.8 36.4 35.0 340nm(1x) 89.6 91.9 54.4 35.7 34.3 340nm(2x) 88.5 94.1 54.5 37.5 36.4 340nm(3x) 98.2 98.1 62.5 13.9 4.4

[0310] Table 15: pO2 (mm Hg) at 37℃

[0311] UVA before UVA after D3 D5 D7 Comparison 35.0 15.3 37.3 37.6 INT-100 98.4 36.4 18.9 20.1 19.7 340nm(1x) 41.8 14.3 11.8 22.5 16.6 340nm(2x) 45.9 14.2 14.8 15.3 14.1 340nm(3x) 90.9 19.7 27.7 159.5 178.6

[0312] Table 16: Lactate (mmol / L)

[0313] UVA after D3 D5 D7 Comparison 8.76 19.37 21.31 22.27 INT-100 8.85 14.71 20.18 23.31 340nm(1x) 9.05 15.17 19.81 21.83 340nm(2x) 8.77 14.55 19.06 22.13 340nm(3x) 9.48 20.42 36.09 36.36

[0314] Table 17: Glucose (mmol / L)

[0315] UVA after D3 D5 D7 Comparison 16.96 11.48 9.59 8.22 INT-100 17.24 13.11 10.26 8.19 340nm(1x) 17.45 13.49 10.27 8.32 340nm(2x) 16.98 13.63 10.69 8.34 340nm(3x) 16.77 10.87 1.33 0.43

[0316] Table 18: Platelet lysis (%)

[0317] UVA before UVA after D3 D5 D7 Comparison 4.30 5.01 6.73 5.63 INT-100 4.30 4.74 4.69 4.50 5.18 340nm(1x) 4.30 4.48 4.90 4.43 5.23 340nm(2x) 4.30 4.50 4.59 4.92 5.19 340nm(3x) 4.30 4.77 4.78 6.62 16.6

[0318] Table 19: LDH (LDH IU / 10) 11 (platelet count)

[0319] UVA before UVA after D3 D5 D7 Comparison 10.7 12.0 17.1 17.1 INT-100 10.3 11.5 11.9 11.6 12.6 340nm(1x) 10.5 11.3 12.1 12.1 13.1 340nm(2x) 10.5 12.1 12.1 13.0 13.2 340nm(3x) 10.5 12.1 11.6 16.0 33.7

[0320] Platelets treated with different concentrations of amtoxapine

[0321] The study aimed to evaluate the photoconversion of amtoxapine in platelets from 100% plasma after 7 days (day 3 and day 7) following photochemical treatment using the 340 nm device disclosed herein. Multiple donor platelet units (5 units, ~278-391 mL) in 100% plasma were collected and divided into 5 units of ~285 mL each, serving as either an untreated control or treated with different concentrations of amtoxapine under UV A irradiation using the 340 nm device. Amtoxapine was added to concentrations of 30, 60, 90, or 110 μM, and samples were then analyzed before irradiation (before UV exposure). The remaining units were treated with ~7.2 J / cm². 2 The samples were then subjected to irradiation. After irradiation (post-UV), the samples were processed and analyzed. The parameters shown in Tables 20-29 (left column) for the untreated control and amtoxaridine / UVA treated samples were measured using standard analytical methods known in the art, and residual amtoxaridine concentrations were determined by HPLC analysis.

[0322] Similar studies were conducted to evaluate the photoconversion of amtoxapine in platelets in platelet additive solutions (35% plasma / 65% PAS III) after 7 days (day 4 and day 7) following photochemical treatment using the 340 nm device disclosed herein. Multiple donor platelet units (6 units, ~202-318 mL) in plasma / PAS were collected and divided into five units of ~285 mL each as either untreated controls or treated with different concentrations of amtoxapine using UV-A irradiation with the 340 nm device. Amtoxapine was added to concentrations of 30, 60, 90, or 110 μM, and samples were then analyzed before irradiation (before UV exposure), with the remaining units treated at ~7.2 J / cm². 2 The samples were then subjected to irradiation. After irradiation (post-UV), the samples were processed and analyzed. The parameters shown in Tables 20-29 (right column) for the untreated control and amtoxaridine / UVA treated samples were also measured using standard analytical methods known in the art, and the residual amtoxaridine concentration was further determined by HPLC analysis.

[0323] Table 20: Platelet Count (x10) 3 (cells / μL)

[0324]

[0325] Table 21: pH at 37°C

[0326]

[0327] Table 22: pH at 22°C

[0328]

[0329]

[0330] Table 23: pCO2 (mm Hg) at 37℃

[0331]

[0332] Table 24: pO2 (mm Hg) at 37℃

[0333]

[0334] Table 25: Lactate (mmol / L)

[0335]

[0336] Table 26: Glucose (mmol / L)

[0337]

[0338]

[0339] Table 27: Platelet lysis (%)

[0340]

[0341] Table 28: LDH (LDH IU / 10) 11 (platelet count)

[0342]

[0343] Table 29: Amtoxalin Concentration (μM)

[0344]

[0345] These data show that, compared with untreated control platelets, platelet quality in 100% plasma or plasma + PAS was adequately maintained at a range of amtoxapine treatment concentrations (e.g., 30 μM to 110 μM), and that, in addition, post-treatment levels of amtoxapine could be reduced to <5 μM (including <1 μM) after irradiation with a 340 nm device.

[0346] Another study used a 340nm LED system or a commercially available INTERCEPT blood system with an INT-100 system for irradiation to further evaluate platelet quality after pathogen inactivation under conditions achieving <2μM residual amtoxarine treatment. Platelet units in 100% plasma were pooled into 750-900 mL units and then divided into multiple 250-300 mL units for treatment under one of three conditions: 1) 75μM infusion of amtoxarine, irradiated with a 340nm device at ~6.4 J / cm²; 2) 75μM infusion of amtoxarine, irradiated with a 340nm device at ~7.2 J / cm². 2 3) Irradiation; 150 μM amtoxapine infusion, administered via an INT-100 device at ~3.6 J / cm². 2 (For example, standard conditions used for this system) Irradiation. Units irradiated with INT-100 after treatment need to undergo CAD treatment to reduce residual amtoxalin, while CAD is not required for units irradiated with 340nm.

[0347] The parameters shown in Tables 30-34 below, including pCO2 and pO2 (blood gas analyzer), morphology (Kunicki score), P-selectin (flow cytometry), degree of shape change (agglutination meter), and hypotonic shock response (agglutination meter), were measured using standard analytical methods and other assays known in the art, and the concentration of residual amtoxapine was determined by HPLC analysis.

[0348] Table 30: pH

[0349]

[0350] Table 31: pCO2 and pO2 (mmHg)

[0351]

[0352] Table 32: P-selectin (CD62P) and degree of shape variation (ESC)

[0353]

[0354] Table 33: Hypoosmolar shock response (HSR) and its morphology

[0355]

[0356] Table 34: Amtoxapine Concentration

[0357]

[0358] These data show that platelet quality was adequately maintained under both amtoxalin treatment conditions with 340 nm irradiation, and the residual amtoxalin level was reduced to ~2 μM after treatment, requiring no further treatment to remove residual amtoxalin.

[0359] Example 7. Plasma Processing

[0360] The study aimed to evaluate the photoconversion of amtoxapine in whole blood plasma and the characteristics of the plasma after photochemical treatment using the broadband UVA device (INT-100) or 340 nm device disclosed herein. Multiple donor plasma units (3-4 units, ~250-350 mL each) were collected and divided into three units of ~285 mL each, serving as an untreated control or for amtoxapine treatment using the INT-100 or 340 nm device. This collection and division process was repeated four times, producing four replicates. Amtoxapine was added to a concentration of 50 μM, and the untreated (before UVA) sample was analyzed. The remaining units were treated at ~6.4 J / cm². 2 The samples were then subjected to irradiation. The irradiated (post-UVA) samples were then processed and analyzed. The parameters in Table 35 below were measured using standard analytical methods known in the art, and the residual ammonixapine concentration was further determined by HPLC analysis at 17.06 μM using an INT-100 instrument and 4.65 μM using a 340 nm instrument.

[0361] Table 35. Plasma parameters before and after irradiation

[0362]

[0363] These data show that the quality of photochemically treated plasma was adequately maintained compared to untreated control plasma, and that the post-treatment level of amtoxapine was reduced to <5 μM after irradiation with a 340 nm device instead of an INT-100 device.

[0364] Example 8. System for processing biological fluids

[0365] Another exemplary system for processing biological fluids is configured to provide a processing chamber within the device with interchangeable arrays of light sources, each array having an LED channel with a narrow bandwidth single peak wavelength (e.g., a first peak wavelength) of 265 nm, 280 nm, 310 nm, 325 nm, 340 nm, 365 nm, or 385 nm in the UVA, UVB, or UVC spectrum. This system includes a single array facing (e.g., relative to) a platform positioned to irradiate the biological fluid placed on the platform (see, for example...). Figure 5The system controls the LEDs during the processing of biological fluid samples, thereby controlling the timing and intensity of LED irradiation to achieve the desired UV light dose. As previously described, photochemical conversion, photoproduct formation, pathogen inactivation, and evaluation of plasma and / or platelet quality parameters are performed at each light source wavelength.

[0366] In a study using the device, the photochemical inactivation of various bacteria was tested on each of the aforementioned LEDs along with amtoxarin. The bacteria included *Escherichia coli* (Gram-negative), *Staphylococcus epidermidis* (Gram-positive), and *Propionibacterium acnes* (anaerobic). Because ultraviolet light in the UVC and UVB wavelength range has known bactericidal effects, the study was controlled to determine the total inactivation level for each LED wavelength, as well as the specific inactivation levels derived from UV light (without amtoxarin) or the photochemical treatment process itself.

[0367] Bacterial cultures were inoculated into plasma units at ~6 log CFU / mL, and samples were taken from these units to obtain initial bacterial titers using a standard colony-forming unit assay. The spiked plasma was then aliquoted into one of three control or treatment units. The amtosalin treatment groups included a 15 μM concentration against each of the three bacteria, and an additional 150 μM concentration treatment against Escherichia coli.

[0368] ●Plasma + Bacteria, without Irradiation

[0369] ●Plasma + bacteria, with irradiation

[0370] ●Plasma + bacteria + amtoxapine, with irradiation

[0371] Samples were taken and the bacterial titer of each spiked unit was determined before irradiation. The units were then aliquoted into six-well plates (2 mL / well) for irradiation. The plates were exposed to irradiation at 265 nm, 280 nm, 310 nm, 325 nm, 340 nm, 365 nm, or 385 nm. The light dose for *Escherichia coli* and *Staphylococcus epidermidis* was ~3 J / cm². 2 The light dose for Propionibacterium acnes is ~6.4 J / cm². 2 The bacterial titer after irradiation was then determined using the standard colony-forming unit assay. Tables 36-39 below show the total log reduction of bacteria, as well as the log reduction attributable to photochemical inactivation with amtoxaridine (S-59) or solely to UV light (without amtoxaridine). The residual post-irradiation amtoxaridine concentration in the samples was also determined using HPLC analysis, as previously described.

[0372] Table 36: Amtoxapine and UV light treatment of Escherichia coli (150 μM)

[0373]

[0374] Table 37: Escherichia coli (15 μM) treated with amtoxacillin and UV light

[0375]

[0376] Table 38: Staphylococcus epidermidis (15 μM) with amtoxacillin and UV light treatment

[0377]

[0378]

[0379] Table 39: Amoxicillin and UV light treatment for Propionibacterium acnes (15 μM)

[0380]

[0381] High levels of bacterial inactivation were observed. When comparing the effects of amtoxacillin + UV light versus UV light alone (without amtoxacillin), the data indicated that photochemical inactivation (amtoxacillin + UV light) was generally the highest for all three bacteria in the 325nm, 340nm, and 365nm UVA treatment groups. Photochemical inactivation in the 310nm amtoxacillin + UVB wavelength treatment group appeared to be more variable and at lower levels than amtoxacillin + 325nm, 340nm, or 365nm UVA light, with increased direct bactericidal effect observed from UVB light compared to UVA light. The 265nm and 280nm amtoxacillin + UVC treatment groups provided minimal inactivation attributable to amtoxacillin, with inactivation primarily derived from the direct bactericidal effect of UVC light. When post-treatment (post-UVA) analysis also takes into account residual amtoxalin levels, these data show that photochemical inactivation greater than 4 log can be achieved under amtoxalin +325 nm irradiation and amtoxalin +340 nm irradiation treatments, with residual amtoxalin below 5 μM.

[0382] Example 9. Pathogen inactivation using a combination of multiple wavelengths

[0383] Additionally, any two or more wavelengths of narrow-bandwidth light can be combined for evaluation, for example, using amtoxalin and sequentially or simultaneously using UV light at the first peak wavelength and UV light at the second peak wavelength for photochemical treatment of biological fluids. More specifically, in one example, an apparatus using amtoxalin and LEDs with the wavelengths described in Example 8 was used to evaluate pathogen inactivation of *Escherichia coli* (Gram-negative) and *Staphylococcus epidermidis* (Gram-positive) bacteria. Bacterial cultures were inoculated into plasma units at ~6 log CFU / mL, and samples were taken from these units to obtain initial bacterial titers using a standard colony-forming unit assay. Spiked plasma units were aliquoted into control (without amtoxalin + UV light) and treatment (with amtoxalin) conditions, with amtoxalin used at a concentration of 15 μM. Units were aliquoted into six-well plates (5 mL / well) for irradiation. Samples were taken before irradiation and the control bacterial titers were determined using a standard colony-forming unit assay. A combination of 265nm or 280nm UVC light dose and 325nm, 340nm or 365nm UVA light dose is used to subject the plate to two light doses sequentially, each of ~3J / cm. 2 Next, the bacterial titer after irradiation was determined, and the residual amtoxalin was analyzed. The data for the titer before irradiation, the titer after the first irradiation, the titer after the second irradiation, and the residual amtoxalin (S-59) after treatment (after the second irradiation) are shown in Tables 40-41 below.

[0384] Table 40: Amoxicillin and UV light treatment for Escherichia coli

[0385]

[0386] Table 41: Amtoxacillin and UV light treatment of Staphylococcus epidermidis

[0387]

[0388]

[0389] High levels of bacterial inactivation were observed. Similar pathogen inactivation studies were conducted using other bacteria identified as less sensitive to amtoxaridine / UV and / or UVC treatment. Additionally, similar studies were conducted with other combinations of sequential light doses, including combinations of 310 nm UVB light doses with 325 nm, 340 nm, or 365 nm UVA light doses (in any order), and combinations of 325 nm, 340 nm, or 365 nm UVA light doses followed by another different 325 nm, 340 nm, or 365 nm UVA light dose (in any order). Furthermore, similar studies can evaluate any of the above-described wavelength combinations using these or other devices disclosed herein, with simultaneous rather than sequential irradiation and / or with different containers (e.g., blood product bags).

[0390] While specific components, configurations, features, and functions have been provided above, those skilled in the art will understand that other variations are possible. Furthermore, although a feature may appear to be described in conjunction with a particular embodiment, those skilled in the art will recognize that various features of the described embodiments can be combined. Moreover, aspects described in conjunction with embodiments can be independent.

[0391] Although embodiments have been described in full with reference to the accompanying drawings, it should be noted that various changes and modifications will be apparent to those skilled in the art. Such changes and modifications should be understood to be included within the scope of the various embodiments defined by the appended claims.

[0392] By reading the foregoing description, variations of the embodiments provided herein will be apparent to those skilled in the art. It is anticipated that those skilled in the art will be able to appropriately employ such variations and implement the compositions, methods, and kits described herein in ways different from the specific description herein. Therefore, the systems and methods described herein include all modifications and equivalents of the subject matter recited in the appended claims as permitted by applicable law. Furthermore, unless otherwise stated herein or where the context clearly contradicts it, the specification covers any combination of the foregoing elements in all possible variations. The following are examples of specific embodiments of this disclosure. These examples are exemplary and not intended to limit the scope of the disclosure provided herein.

[0393] Implementation Scheme 1. A system for processing biological fluids, the system comprising:

[0394] A processing chamber for receiving biological fluids;

[0395] One or more sensors configured to detect light in the processing chamber; and

[0396] A first light source array is placed to irradiate the biological fluid in the processing chamber, wherein the first light source array includes a first light source channel and a second light source channel, the first light source channel being configured to emit ultraviolet light having a first peak wavelength, and the second light source channel being configured to emit light having a second peak wavelength, wherein the second peak wavelength differs from the first peak wavelength by at least 5 nanometers.

[0397] Implementation Scheme 2. In the system described in Implementation Scheme 1, the first light source array includes multiple light source groups, wherein each light source group of the first light source array includes a first light source of the first light source channel and a second light source of the second light source channel, the former being configured to emit ultraviolet light having the first peak wavelength and the latter being configured to emit light having the second peak wavelength.

[0398] Implementation Scheme 3. The system as described in Implementation Scheme 1 or Implementation Scheme 2, wherein the second light source channel is configured to emit ultraviolet light.

[0399] Implementation Scheme 4. The system of any one of Implementation Schemes 1-3, wherein the first peak wavelength is in the ultraviolet A spectrum.

[0400] Implementation Scheme 5. The system of any one of Implementation Schemes 1-4, wherein the first peak wavelength is in the ultraviolet A spectrum and the second peak wavelength is in the ultraviolet C spectrum.

[0401] Implementation Scheme 6. The system as described in any one of Implementation Schemes 1-5, wherein the first light source channel and the second light source channel comprise LEDs.

[0402] Implementation Scheme 7. The system of any one of Implementation Schemes 1-6, wherein the light intensity at 50% of the maximum peak intensity of the light emitted by the first light source channel is within a spectral width of less than 20 nanometers of the first peak wavelength.

[0403] Implementation Scheme 8. The system of any one of Implementation Schemes 1-6, wherein the full width at half maximum (FWHM) spectral width of the light emitted by the first light source channel is within 20 nanometers of the first peak wavelength.

[0404] Implementation Scheme 9. The system of any one of Implementation Schemes 1-8, further comprising a first platform placed in the processing chamber, the first platform being configured to carry the biofluid.

[0405] Implementation Scheme 10. The system of any one of Implementation Schemes 1-9, wherein the light sources of the first light source array are placed in a non-uniformly distributed manner on the array.

[0406] Implementation Scheme 11. The system of Implementation Scheme 10, wherein the first array includes a continuous inner region containing a midpoint of the first array and a continuous outer region surrounding the inner region, wherein the inner region occupies less than 50% of the surface area of ​​the first array, and wherein the outer region occupies the remaining percentage of the surface area of ​​the first array.

[0407] Implementation Scheme 12. The system as described in Implementation Scheme 11, wherein the density of a first light source located in the outer region is greater than the density of a second light source located in the inner region.

[0408] Implementation Scheme 13. The system of any one of Implementation Schemes 1-10, wherein the first array includes a first region of a light source and a second region of a light source, the former being configured to irradiate a first biological fluid in the processing chamber and the latter being configured to irradiate a second biological fluid in the processing chamber.

[0409] Implementation Scheme 14. The system of any one of Implementation Schemes 1-13, wherein the first array is configured such that the light source irradiates the biofluid in the processing chamber with an irradiance difference of less than 25% across the surface of the biofluid facing the first array.

[0410] Implementation Scheme 15. The system of any one of Implementation Schemes 1-14, wherein the first light source array further includes a third light source channel configured to emit light of a third peak wavelength.

[0411] Implementation Scheme 16. The system of any one of Implementation Schemes 1-15, wherein the first light source array further includes a third light source channel configured to emit light of a third peak wavelength and a fourth light source channel configured to emit light of a fourth peak wavelength.

[0412] Implementation Scheme 17. The system of any one of Implementation Schemes 1-16, further comprising a barrier placed in the processing chamber between the first light source array and the biofluid.

[0413] Implementation Scheme 18. The system as described in Implementation Scheme 17, wherein the barrier is transparent to light with wavelengths within 30 nm of the first peak wavelength.

[0414] Implementation Scheme 19. The system of any one of Implementation Schemes 9-18, wherein the first platform and the first light source array are configured to translate relative to each other to change the distance between the first light source array and the first platform.

[0415] Implementation Scheme 20. The system of any one of Implementation Schemes 9-19, wherein the first platform is configured to separately hold a first container having at least a first biological fluid and a second container having a second biological fluid.

[0416] Implementation Scheme 21. The system of any one of Implementation Schemes 9-20, wherein the first platform is movable in a sliding manner for introducing and removing the biofluid from the processing chamber.

[0417] Implementation Scheme 22. The system of any one of Implementation Schemes 1-21, wherein the system is configured to agitate the biofluid during processing.

[0418] Implementation Scheme 23. The system of any one of Implementation Schemes 1-22, further comprising one or more sensors for detecting the presence of biological fluid within the processing chamber.

[0419] Implementation Scheme 24. The system of any one of Implementation Schemes 1-23, further comprising a second light source array facing in the opposite direction to the first light source array, wherein the second light source array includes a third light source channel configured to emit light having the first peak wavelength and a fourth light source channel configured to emit light having the second peak wavelength.

[0420] Implementation Scheme 25. The system of Implementation Scheme 24, wherein the first light source array and the second light source array are configured to translate relative to each other to change the distance between the first light source array and the second light source array.

[0421] Implementation Scheme 26. The system as described in Implementation Scheme 24 or Implementation Scheme 25, further comprising a first platform placed in the processing chamber between the first light source array and the second light source array, the first platform being configured to carry the biological fluid.

[0422] Implementation Scheme 27. The system of any one of Implementation Schemes 1-23, further comprising a second light source array facing the same direction as the first light source array, wherein the second light source array includes a third light source channel configured to emit light having the first peak wavelength and a fourth light source channel configured to emit light having the second peak wavelength, and wherein the first light source array and the second light source array define a first region between the first light source array and the second light source array.

[0423] Implementation Scheme 28. The system as described in Implementation Scheme 27, further comprising:

[0424] A first platform is placed in the first area of ​​the processing chamber, the first platform being configured to carry a first biological fluid; and

[0425] A second platform is placed in the processing chamber outside the first area, the second platform being configured to carry a second biological fluid, wherein the second light source array faces the second platform.

[0426] Implementation Scheme 29. The system as described in any one of Implementation Schemes 1-28, further comprising control circuitry.

[0427] Implementation Scheme 30. The system as described in Implementation Scheme 29, wherein the control circuit is configured to adjust or set the intensity of each light source in the first light source array.

[0428] Implementation Scheme 31. The system as described in Implementation Scheme 29 or 30, wherein the control circuit is configured to adjust or set a first light intensity emitted by each first light source channel and to adjust or set a second light intensity emitted by each second light source channel.

[0429] Implementation Scheme 32. The system of any one of Implementation Schemes 29-31, wherein the control circuit is configured to adjust or set the light emission duration of each light source from the first light source array.

[0430] Implementation Scheme 33. The system of any one of Implementation Schemes 29-32, wherein the control circuit is configured to adjust or set the first light emission duration from each first light source channel and to adjust or set the second light emission duration from each second light source channel.

[0431] Implementation Scheme 34. The system of any one of Implementation Schemes 29-33, wherein the control circuit is configured to adjust or set the light emission dura...

Claims

1. A method for treating biological fluids, comprising: Provide a biofluid infused with a photoactive pathogen inactivating compound, wherein the photoactive pathogen inactivating compound is psoralen; and The biological fluid is irradiated with ultraviolet light having a first peak wavelength of 320 nm to 330 nm emitted by one or more first light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nm. The duration and intensity of irradiation of the biological fluid are sufficient to inactivate pathogens in the biological fluid.

2. The method of claim 1, wherein the first peak wavelength is 325±5 nm.

3. The method of claim 1 or 2, wherein the first peak wavelength is the peak wavelength of one of the group of one or more first light sources.

4. The method of claim 3, wherein the first peak wavelength is the peak wavelength of each of the plurality of first light sources in the group of one or more first light sources.

5. The method of claim 1 or 2, wherein the first peak wavelength is the average peak wavelength of the group of one or more first light sources.

6. The method of claim 1 or 2, further comprising irradiating the biological fluid with ultraviolet light having a second peak wavelength emitted by one or more second light sources, wherein each of the one or more second light sources emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers, and wherein the second peak wavelength differs from the first peak wavelength by at least 5 nm.

7. The method of claim 6, wherein the second peak wavelength is the peak wavelength of one of the group of one or more second light sources.

8. The method of claim 7, wherein the second peak wavelength is the peak wavelength of each of the plurality of second light sources in the group of one or more second light sources.

9. The method of claim 6, wherein the second peak wavelength is the average peak wavelength of the group of one or more second light sources.

10. The method of claim 1 or 2, wherein the group of one or more first light sources comprises one or more LEDs, and / or the group of one or more second light sources comprises one or more LEDs.

11. The method of claim 1 or 2, wherein the biological fluid is contained within a container, and wherein the group of one or more first light sources is arranged as a light source array, the group of one or more first light sources facing only one side of the container.

12. The method of claim 1 or 2, wherein the photoactive pathogen inactivating compound is amtoxalin.

13. The method of claim 1 or 2, further comprising, prior to irradiating the biological fluid with the ultraviolet light having the first peak wavelength: A biofluid infused with the photoactive pathogen inactivation compound is introduced into a processing chamber, the processing chamber including one or more photosensors configured to detect light in the processing chamber and a first light source array configured to irradiate the biofluid in the processing chamber, wherein the first light source array includes a first light source channel, the first light source channel including the set of one or more first light sources. Irradiating the biological fluid includes emitting light having the first peak wavelength from the first light source channel, wherein the first duration and the first intensity of the emission are sufficient to inactivate pathogens in the biological fluid.

14. The method of claim 13, wherein each light source of the first light source channel is configured to emit ultraviolet light having a first peak wavelength between 320 nm and 330 nm.

15. The method of claim 13, further comprising: Determine a set of characteristics of the biological fluid; The treatment profile is determined based on the set of characteristics of the biological fluid. and Adjust or set a set of parameters for the processing chamber according to the processing overview.

16. The method of claim 15, wherein irradiation of the biological fluid is performed according to the treatment profile, and wherein the first duration and the first intensity sufficient to inactivate the pathogen are determined by the treatment profile.

17. The method of claim 13, wherein the first light source array includes a second light source channel configured to emit light of a second peak wavelength.

18. The method of claim 17, wherein the second peak wavelength differs from the first peak wavelength by at least 5 nm.

19. The method of claim 17 or claim 18, wherein the second peak wavelength is in the ultraviolet A, ultraviolet B, or ultraviolet C spectrum.

20. The method of claim 19, wherein the second peak wavelength is 315 nm to 350 nm.

21. The method of claim 17, wherein the second light source channel comprises a group of one or more second light sources, each of the one or more second light sources emitting light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers, and / or the second light source channel comprises a group of one or more second light sources containing one or more LEDs.

22. The method of claim 15 or 16, wherein the set of characteristics of the biological fluid includes one or more of the following: the volume of the biological fluid, the type of the biological fluid, and the temperature of the biological fluid.

23. The method of claim 15 or 16, wherein determining the processing profile based on the set of characteristics of the biological fluid includes determining the first intensity of light having the first peak wavelength or determining the first duration of emitting light having the first peak wavelength.

24. The method of claim 13, wherein the processing chamber further comprises a first platform disposed within the processing chamber, the first platform carrying the biofluid.

25. The method of claim 15, wherein the processing chamber further includes a first platform positioned within the processing chamber, and adjusting or setting the set of parameters of the processing chamber includes adjusting or setting the distance between the first light source array and the first platform.

26. The method of claim 1 or 2, further comprising agitating the biofluid.

27. The method as described in claim 1 or 2, The duration of irradiation of the biological fluid is from 1 second to 2 hours; and / or The intensity of the irradiation of the biological fluid is 1 to 1000 mW / cm. 2 ; and / or The total dose of ultraviolet light irradiating the biological fluid was 0.5 J / cm. 2 Up to 50 J / cm 2 .

28. The method of claim 27, wherein the total dose of ultraviolet light irradiating the biological fluid emitted by the group of one or more first light sources is 0.5 J / cm². 2 Up to 50 J / cm 2 .

29. The method of claim 1 or 2, wherein the treatment method is sufficient to inactivate at least 1 log of pathogens present in the biofluid, and wherein the biofluid is suitable for infusion into a subject after irradiation without further treatment to remove residual pathogen-inactivating compounds or one or more of their photoproducts.

30. The method of claim 29, wherein the further treatment is subjecting the biofluid to a compound removal step.

31. The method of claim 1 or 2, wherein the treatment method is sufficient to inactivate at least 1 log of pathogens present in the biological fluid, and wherein the biological fluid contains 5 µM or less of the pathogen inactivating compound after irradiation.

32. The method of claim 1 or 2, wherein the treatment method is sufficient to inactivate at least 1 log of pathogens present in the biological fluid, and wherein the biological fluid contains 2 µM or less of the pathogen inactivating compound after irradiation.

33. The method of claim 1 or 2, wherein the concentration of the pathogen inactivating compound mixed with the biological fluid prior to irradiation is at least 10 µM.

34. The method of claim 1 or 2, wherein the concentration of the pathogen inactivating compound incorporated with the biological fluid prior to irradiation is from 15 µM to 150 µM.

35. The method of claim 1 or 2, wherein the concentration of the pathogen inactivating compound mixed with the biological fluid after irradiation is at most one-third of the concentration of the pathogen inactivating compound mixed with the biological fluid before irradiation.

36. The method of claim 1 or 2, wherein the treatment method is sufficient to inactivate at least 4 logs of pathogens present in the biological fluid.

37. The method of claim 1 or 2, wherein the biofluid retains sufficient biological activity after irradiation to make the biofluid suitable for infusion into the subject.

38. The method of claim 1 or 2, wherein the biofluid comprises blood products.

39. The method of claim 1 or 2, wherein the biofluid comprises a plasma composition.

40. The method of claim 39, wherein the concentration of fibrinogen in the plasma composition after irradiation is at least 70% of the concentration of fibrinogen in the plasma composition before irradiation.

41. The method of claim 39, wherein the concentration of factor VIII in the plasma composition after irradiation is at least 70% of the concentration of factor VIII in the plasma composition before irradiation.

42. The method of claim 1 or 2, wherein the biological fluid comprises a platelet composition.

43. The method of claim 42, wherein the biofluid further comprises a platelet additive solution.

44. The method of claim 42, wherein the amount of platelets in the platelet composition after irradiation is at least 80% platelet recovery.

45. The method of claim 42, wherein the platelet composition has a pH of at least 6.2 at 22°C after irradiation.

46. ​​The method of claim 1 or 2, wherein the method comprises incubating the biological fluid with the photoactive pathogen inactivating compound for a period of 30 minutes to 24 hours prior to irradiation.

47. A pathogen-inactivated biofluid prepared by any one of claims 1-46.

48. The pathogen-inactivating biofluid of claim 47, comprising 5 µM or less of the pathogen-inactivating compound.

49. The pathogen-inactivating biofluid of claim 47 or claim 48, comprising 2 µM or less of the pathogen-inactivating compound.

50. A system for processing biological fluids, the system comprising: A processing chamber configured to receive biological fluids; One or more sensors configured to detect light in the processing chamber; and A first light source array is placed to irradiate the biological fluid in the treatment chamber, wherein the first light source array includes a first light source channel configured to emit ultraviolet light with a first peak wavelength of 320 nm to 330 nm, wherein the first light source channel includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers.

51. The system of claim 50, wherein the first peak wavelength is 325±5 nm.

52. The system of claim 50, wherein the first peak wavelength of the first light source array is the average peak wavelength of the one or more light sources of the first light source channel, or wherein the first peak wavelength of the first light source array is the peak wavelength of one light source of the first light source channel.

53. The system of claim 52, wherein the first peak wavelength is the peak wavelength of each of the plurality of light sources in the first light source channel.

54. The system of claim 50 or 51, wherein the one or more light sources of the first light source channel comprise one or more light-emitting diodes.

55. The system of claim 50 or 51, wherein the first light source array further includes a second light source channel configured to emit light having a second peak wavelength of the first light source array, wherein the second light source channel includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers, and wherein the second peak wavelength of the first light source array differs from the first peak wavelength of the first light source array by at least 5 nanometers.

56. The system of claim 55, wherein the second peak wavelength of the first light source array is in the ultraviolet A, ultraviolet B, or ultraviolet C spectrum.

57. The system of claim 56, wherein the second peak wavelength of the first light source array is 315 nm to 350 nm.

58. The system of claim 55, wherein the second light source channel comprises one or more LEDs.

59. The system of claim 50 or 51, wherein the light sources of the first light source array are positioned in a non-uniformly distributed manner on the array.

60. The system of claim 50 or 51, wherein the system is configured to agitate the biofluid during processing.

61. The system of claim 50 or 51, wherein the first light source array comprises two or more light source panels.

62. The system of claim 50 or 51, wherein the first light source array is configured such that the light source of the first light source array irradiates the biological fluid in the processing chamber with an irradiance difference of less than 25% across the surface of the biological fluid facing the first light source array.

63. The system of claim 50 or 51, further comprising a first platform placed in the processing chamber, the first platform being configured to carry the biofluid.

64. The system of claim 63, wherein the first platform and the first light source array are configured to translate relative to each other to change the distance between the first light source array and the first platform.

65. The system of claim 63, wherein the first platform is movable in a sliding manner for introducing and removing the biofluid from the processing chamber.

66. The system of claim 63, wherein the first platform is configured to separately hold a first container having at least the biological fluid as a first biological fluid and a second container having a second biological fluid.

67. The system of claim 63, wherein one or more of the one or more sensors are attached to or placed on the first platform.

68. The system of claim 50 or 51, further comprising a barrier placed in the processing chamber between the first light source array and the biofluid.

69. The system of claim 68, wherein the barrier placed in the processing chamber between the first light source array and the biological fluid is transparent to light with wavelengths within 30 nm of the first peak wavelength of the first light source array.

70. The system of claim 68, wherein one or more of the one or more sensors are attached to or placed therein within the barrier positioned between the first light source array and the biofluid in the processing chamber.

71. The system of claim 50 or 51, wherein the first light source array comprises: A first region of the light source and a second region of the light source, the former being configured to irradiate the biological fluid in the processing chamber as a first irradiated biological fluid, and the latter being configured to irradiate the second irradiated biological fluid in the processing chamber.

72. The system of claim 50 or 51, further comprising control circuitry.

73. The system of claim 72, wherein the control circuitry is configured to adjust or set the intensity or duration of light emission from each light source of the first light source array.

74. The system of claim 73, wherein the control circuitry is configured to adjust or set the intensity or duration of light emission from each light source of the first light source array based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light.

75. The system of claim 50 or 51, further comprising one or more sensors configured to detect the presence of the biological fluid in the treatment room.

76. The system of claim 50 or 51, further comprising a second light source array facing in the opposite direction to the first light source array, wherein the second light source array includes a first light source channel configured to emit light of a first peak wavelength of the second light source array, and wherein the first light source channel of the second light source array includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers.

77. The system of claim 76, wherein the first peak wavelength of the second light source array is substantially the same as the first peak wavelength of the first light source array.

78. The system of claim 76, wherein the second light source array includes a second light source channel configured to emit light at a second peak wavelength of the second light source array, wherein the second light source channel of the second light source array includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers, and wherein the second peak wavelength of the second light source array differs from the first peak wavelength of the second light source array by at least 5 nanometers.

79. The system of claim 76, wherein the first light source array and the second light source array are configured to translate relative to each other to change the distance between the first light source array and the second light source array.

80. The system of claim 50 or 51, further comprising a second light source array facing the same direction as the first light source array, wherein the second light source array includes a first light source channel configured to emit light of a first peak wavelength of the second light source array, and wherein the first light source array and the second light source array define a first region between the first light source array and the second light source array, and wherein the first light source channel of the second light source array includes one or more light sources, each of which emits light with a full width at half maximum (FWHM) spectral bandwidth of less than 20 nanometers.

81. The system of claim 76, further comprising a first platform disposed in the processing chamber between the first light source array and the second light source array, the first platform being configured to carry the biological fluid.

82. The system of claim 80, further comprising: A first platform is placed in the first area of ​​the processing chamber, the first platform being configured to carry the biological fluid as a first carrier of the biological fluid; and A second platform is placed in the processing chamber outside the first area, the second platform being configured to carry a second carrier of biological fluid, wherein the second light source array faces the second platform.

83. The system of claim 82, wherein one or more of the one or more sensors are attached to or placed in the second platform.

84. The system of claim 76, further comprising a barrier placed in the processing chamber between the second light source array and the biological fluid.

85. The system of claim 84, wherein the barrier placed in the processing chamber between the second light source array and the biological fluid is transparent to light with wavelengths within 30 nm of the first peak wavelength of the first light source array.

86. The system of claim 84, wherein one or more of the one or more sensors are attached to or placed therein within the barrier positioned between the second light source array and the biological fluid in the processing chamber.

87. The system of claim 76, further comprising control circuitry configured to adjust or set the intensity or duration of light emission from each light source of the second light source array.

88. The system of claim 87, wherein the control circuitry is configured to adjust or set the intensity or duration of light emission from each light source of the second light source array based at least in part on a first set of parameters detected by at least one of the one or more sensors configured to detect light.

89. The system of claim 87, wherein the control circuitry comprises: Memory; One or more processors; and one or more programs, wherein the one or more programs are stored in memory and configured to be executed by the one or more processors, wherein when executed by the one or more processors, the one or more programs cause the processor to irradiate the biological fluid mixed with the pathogen inactivation compound by controlling a first light source array, a second light source array, or a combination of the first and second light source arrays to irradiate light for a duration and intensity sufficient to inactivate pathogens present in the biological fluid.

90. The system of claim 72, wherein the control circuit is configured to a) Determine a set of characteristics of the biological fluid; b) Determine the treatment profile based on the set of characteristics of the biological fluid; c) Adjust or set a set of parameters of the processing chamber according to the aforementioned processing overview; and d) Irradiate the biological fluid according to the treatment profile.

91. The system of claim 50 or 51, wherein the system is configured to irradiate the biofluid mixed with a photoactive pathogen inactivating compound, the duration and intensity of which are sufficient to inactivate pathogens present in the biofluid.

92. The system of claim 50 or 51, wherein the system is configured to irradiate the biofluid mixed with a photoactive pathogen inactivating compound, the duration and intensity of the irradiation being sufficient to inactivate at least 1 log of pathogens present in the biofluid, and wherein the biofluid is suitable for infusion into a subject after irradiation without further processing to remove residual photoactive pathogen inactivating compound or one or more of its photoproducts.

93. The system of claim 50 or 51, wherein the system is configured to irradiate the biofluid mixed with a photoactive pathogen inactivating compound, the duration and intensity of the irradiation being sufficient to inactivate at least 1 log of pathogens present in the biofluid, and wherein the biofluid contains 5 µM or less of the photoactive pathogen inactivating compound after irradiation.

94. The system of claim 50 or 51, wherein the system is configured to irradiate the biofluid mixed with a photoactive pathogen inactivating compound, the duration and intensity of the irradiation being sufficient to reduce the concentration of the photoactive pathogen inactivating compound mixed with the biofluid to at most 1 / 3 relative to the concentration of the photoactive pathogen inactivating compound mixed with the biofluid prior to irradiation.

95. The system of claim 50 or 51, wherein the system is configured to irradiate the biofluid mixed with a photoactive pathogen inactivating compound, the duration and intensity of which are sufficient to inactivate at least 4 logs of pathogens present in the biofluid.

96. The system of claim 50 or 51, wherein the biofluid comprises blood products.

97. The system of claim 50 or 51, wherein the biofluid comprises a plasma composition.

98. The system of claim 50 or 51, wherein the biofluid comprises a platelet composition.

99. The system of claim 98, wherein the biofluid further comprises a platelet additive solution.

100. The system of claim 91, wherein the photoactive pathogen inactivating compound is psoralen.

101. The system of claim 100, wherein the photoactive pathogen inactivating compound is amtoxalin.

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