Patent Application
20240277913
Extracorporeal fluid treatment typically involves the removal of fluid from a patient, treatment of the external/removed fluid, and return of the treated fluid into the patient in a continuous circuit or path. Blood is one body fluid for which conventional extracorporeal techniques have been developed. Using such techniques, blood is typically treated to extract materials from the blood and/or add materials to augment the blood prior to return of the treated blood to the patient. In some techniques, blood is removed from the patient in a continuous flow and introduced into a chamber containing a filtration unit where the blood flows past a semipermeable membrane. The semipermeable membrane allows only select material in the blood to pass through the membrane for removal from the blood (or removal of the material that does not pass therethrough) and/or allows material to pass through the semipermeable membrane and into the blood. After passage of material to and/or from the blood, the treated blood is discharged from the filtration unit for return to the patient. If material has been removed from the blood, the removed material is separately discharged from the filtration unit.
One ailment that includes pathogens within a mammal's blood that is not satisfactorily treated by conventional extracorporeal techniques is sepsis. Acute sepsis is a metastatic infection that arises when infectious microbes in the circulatory system overwhelm the immune system and the pathogenic microorganisms can no longer be removed from circulating blood (by the body) faster than they are proliferating. Sepsis thus originates as an isolated infection of pathogenic microorganisms that become mobile in the circulatory system. When bacteria or viruses are present in the bloodstream, the condition is known as bacteremia or viremia. Pathogenic fungi can also be present in the bloodstream. Sepsis is a constellation of symptoms secondary to the infection that manifest as disruptions in heart rate, respiratory rate and/or body temperature. Bacteremia is rarely associated with any signs or symptoms, and most pathogenic microorganisms are readily removed from circulation by the humoral immune system.
When pathogenic microbes begin to reproduce in the circulatory system and the body is unable to remove them at an adequate rate, septicemia develops, and a systemic inflammatory response is initiated. This syndrome, SIRS, is one of the primary disease patterns in sepsis. If acute sepsis worsens to the point of end-organ dysfunction (such as renal failure, liver dysfunction, altered mental status or heart damage), the condition is referred to as “severe sepsis.” Once severe sepsis worsens to the point where blood pressure can no longer be maintained by the body with intravenous fluid intervention alone, then the criteria for “septic shock” are met. Precipitating infections which may lead to septic shock, if severe enough, include appendicitis, pneumonia, bacteremia, diverticulitis, pyelonephritis, meningitis, pancreatitis, and necrotizing fasciitis, for example.
It has been reported that acute sepsis kills approximately 120,000-200,000 people annually in the United States. Statistics have shown that sepsis is the second leading cause of death in non-coronary ICU patients. Overall, sepsis is the tenth most common cause of death in the United States and accounts for as much as 25% of ICU bed utilization, according to some reports. In fact, it has been said that the medical specialty practice of Critical Care Management was specifically developed as a result of septic mortality rates. According to some reports, overall sepsis mortality is in the range of 40-44%, with mortality rates rising to between 70-90% when sepsis proceeds to severe septicemia or septic shock (i.e., proceeds to organ dysfunction, hypotension, or hypo-perfusion, or to hypotension despite adequate fluid resuscitation, respectively).
Septic shock, the most severe manifestation of sepsis, is a clinical syndrome that results, at least in part, from an activated systemic host inflammatory response to infection leading to cardiovascular collapse. Septic shock has become increasingly common in the North American population, potentially because of an increasing population of at risk elderly individuals (many of whom have chronic debilitating disease) and individuals with impaired immunity due to diseases (such as cancer and AIDS). According to some reports, about 750,000 cases of sepsis occur each year in the United States.
Common origins of infections that develop into sepsis include urinary tract infections, pneumonia, cellulitis, wounds and abscesses, sinusitis, meningitis, and surgical procedures to an infected area or the abdomen. The most common causative organisms associated with sepsis can include Gram-positive bacteria (e.g., Staphylococcus aureus, coagulase-negative Staphylococcus, Streptococcus pyogenes, Streptococcus pneumoniae, and enterococci), Gram-negative bacteria (e.g., Proteus, Serratia, Pseudomonas aeruginosa, Neisseria meningitudis, and Escherichia coli Klebsiella pneumoniae), anaerobic organisms and fungi (e.g., Candida albicans).
The progression from sepsis to septic shock follows the significant increase in serum levels of TNF-a, IFN-a, IL-1B, IL-8, and IL-6. Shock is a condition defined by inadequate tissue perfusion, such as resulting from vasodilation due to increased cytokine levels and intravascular fluid shifting. Increase in TNF-a levels is believed to be responsible for the onset of disseminated intravascular coagulation (DIC). These conditions, together with renal and liver failure, can cause cardiac collapse and respiratory failure (ARDS).
The signs and symptoms of sepsis vary according to the associated underlying disease/infection process(es). However, most symptomology is universal. Sepsis is typically preceded by a period of altered mental status (e.g., for approximately 24 hours) before other signs develop. Fatigue, malaise, myalgia, nausea, and vomiting are common early signs. Fever typically initially develops, but often declines to hypothermia in late stages. Elevated heart rate and respiratory rate typically develop as blood pressure becomes erratic. Blood pressure often eventually declines dramatically as plasma shifts and vasodilation worsens. Impaired renal function is typically evident with decreased urinary output, as is liver failure with jaundice.
No universally effective, curative treatments currently exist for sepsis, severe septicemia, and septic shock. Some supportive measures, such as antibiotics, vasopressor agents and various endogenous strategies associated with attempts at blood “purification,” are associated with some degree of lower mortality in patients with sepsis (primarily with treatments utilizing polymyxin B). For example, antibiotics are often inadequate to combat the overwhelming invasion of bacteria or other infectious microorganisms associated with the more severe manifestations of sepsis. In addition, antibiotic resistant strains of bacteria are prevalent, limiting the effectiveness of antibiotic treatment. Vasopressor agents may support hypotension associated with cardiovascular collapse, but fail to treat the infectious microorganisms. Current attempts at blood purification, which include hemoperfusion, plasma exchange, and hemofiltration with hemoperfusion, inadequately remove the infectious microorganisms associated with sepsis, severe septicemia, and septic shock. As such, despite all current treatment approaches, mortality from all manifestations and degrees of severity of sepsis remains unacceptably high.
While certain aspects of conventional technologies have been discussed to facilitate disclosure of Applicant's disclosure, the Applicant in no way disclaims these technical aspects, and it is contemplated that their disclosure may encompass one or more conventional technical aspects. In this specification, where a document, act or item of knowledge is referred to or discussed, this reference or discussion is not an admission that the document, act or item of knowledge or any combination thereof was, at the priority date, publicly available, known to the public, part of common general knowledge, or otherwise constitutes prior art under the applicable statutory provisions: or is known to be relevant to an attempt to solve any problem with which this specification is concerned.
The present disclosure describes a system and method for disinfecting blood utilizing multiple wavelengths of light. In various embodiments, the systems and methods are particularly advantageous for treatment and/or prevention of sepsis. The present disclosure may address one or more of the problems and deficiencies of the art discussed above. However, it is contemplated that the disclosure may prove useful in addressing other problems and deficiencies in a number of technical areas. Therefore, the claims should not necessarily be construed as limited to addressing any of the particular problems or deficiencies discussed herein.
In some embodiments, the disinfection systems and methods of the present disclosure comprise an extracorporeal device designed to address pathogenic microbial infection associated with sepsis (including severe sepsis and septic shock) by externally reducing or eliminating the presence of the infectious microorganisms associated with the condition(s) in a mammal's blood. The systems and methods also provide an effective and unique stand-alone or adjunctive therapeutic intervention to standard measures used in the treatment of sepsis (including severe sepsis and septic shock), such as compared to anti-infective drug therapy, to combat the overwhelming infectious process characteristic of the condition wherein infecting microbial organisms can no longer be removed from circulating blood faster than they are proliferating.
In some embodiments, the disinfection systems and methods of the present disclosure comprise a blood pump with a built in or attached microbicidal lighting device intended to expose a blood flow of mammalian blood at sufficient intensity and duration that is effective in reducing or eliminating or slowing the proliferation of a broad range of infectious sources, such as infectious sources known to be associated with sepsis (e.g., severe sepsis and/or septic shock).
In some embodiments, the device may include an attached or incorporated filter designed to remove one or more unwanted by-product of disinfection or one or more toxins released by an infectious microorganisms from the blood before returning the blood to the patient's body, and/or an attached or incorporated infusion component to that restores or supplements one or more component into the blood that is/may be affected by the microbicidal process and/or by the infectious agents/microorganisms.
In some embodiments, the device may include an optical element associated with the lighting device configured to scatter, direct, or combine light from one or more irradiation sources resulting in uniform intensity of the light incident on the blood. In some embodiments, the device may include one or more reflectors configured to reflect stray light back into a treatment pathway of the blood and/or to improve uniformity of irradiation. In some embodiments, the device may include a cooling device (such as a heatsink, waterblock, peltier cooling system, heatpipe, or phase change material element) associated with the lighting device and configured to dissipate heat from the lighting device to maintain the temperature of the lighting device below a predefined temperature such that the lighting device is prevented from heating the treated blood above a predefined temperature, or to maintain a preferred operating temperature for the light engine, such as to maximize efficiency, prevent damage, or maintain a characterized light output.
In some embodiments, the disinfection systems and methods of the present disclosure may include a blood pump with a built in or attached microbicidal lighting device intended to expose blood flow at sufficient intensity and duration (i.e., total dose) that is effective in reducing or eliminating or slowing the proliferation of a broad range of infectious sources, such as those associated with sepsis (including severe sepsis and/or septic shock).
In one embodiment, the device may include an attached or built in filter designed to remove any potential toxins released by the microorganisms and/or unwanted by-products of disinfection before returning the patient's blood to their body, and/or an attached or incorporated infusion component configured to restore or supplement one or more blood components of the treated blood that is negatively affected by the treatment proves (e.g., negatively affected by the microbicidal light).
All aspects, examples and features mentioned below can be combined in any technically possible way.
An aspect of the disclosure provides an extracorporeal blood disinfection system, comprising: an input tube forming a flowpath for the flow of infected blood from a mammalian patient: a disinfection unit including a microbicidal light emitting device configured to emit a plurality of light emissions, each light emission having a wavelength within the range of about 380 nm to about 800 nm: a treatment flowpath in communication with the input tube that is substantially transparent to the emitted light of the microbicidal light emitting device for receiving at least a portion of the flow of the infected blood therethrough, wherein the microbicidal light emitting device effectuates a dose of the plurality of light emissions to the infected blood flowing through the treatment flowpath to disinfect the blood; and an output tube in fluid communication with the treatment flowpath forming a flowpath for the flow of the disinfected blood from the disinfection unit back to the patient.
Another aspect of the disclosure includes any of the preceding aspects, and further comprising a pump configured to at least one of: provide the flow of infected blood from the patient through the input tube: pass the blood from the input tube through the treatment flowpath; and provide the flow of disinfected blood to the patient through the output tube.
Another aspect of the disclosure includes any of the preceding aspects, and the disinfection unit further comprises a thermal management device associated with the microbicidal light emitting device and configured to maintain the blood within the treatment pathway above a blood temperature set point.
Another aspect of the disclosure includes any of the preceding aspects, and the thermal management device includes a treatment flowpath coolant flowpath thermally coupled with the treatment flowpath, the treatment flowpath coolant flowpath including one or more channels configured to allow a coolant to flow therethrough.
Another aspect of the disclosure includes any of the preceding aspects, and the treatment flowpath coolant flowpath is optically transparent, thermally coupled with the treatment flowpath, and thermally isolated from the microbicidal light emitting device.
Another aspect of the disclosure includes any of the preceding aspects, and further comprising a blood temperature sensor configured to measure a blood temperature of the blood, wherein the thermal management device controls a temperature of the coolant based on the blood temperature.
Another aspect of the disclosure includes any of the preceding aspects, and further comprising a heat exchanger configured to control the temperature of the coolant based on the blood temperature.
Another aspect of the disclosure includes any of the preceding aspects, and the thermal management device controls a blood flow rate generated by the pump based on the blood temperature.
Another aspect of the disclosure includes any of the preceding aspects, and further comprising a fault detection system configured generate an alarm in response to at least one of: the blood temperature exceeding a blood temperature set point: a temperature of the microbicidal light emitting device being outside of an allowable range; and detection of an air bubble in the treatment flowpath.
Another aspect of the disclosure includes any of the preceding aspects, and the disinfection unit further comprises a thermal management device associated with the microbicidal light emitting device configured to dissipate heat from the microbicidal light emitting device to maintain the temperature of at least a portion thereof below a predefined temperature such that the microbicidal light emitting device is prevented from heating the blood within the treatment pathway above a blood temperature set point.
Another aspect of the disclosure includes any of the preceding aspects, and further comprising an insulating layer between the microbicidal light emitting device and the treatment flowpath.
Another aspect of the disclosure includes any of the preceding aspects, and the insulating layer is optically transparent, and resistant to conductive heat transfer.
Another aspect of the disclosure includes any of the preceding aspects, and the insulating layer includes one of: air, a vacuum, a gas, aerogels, a material configured to trap air pockets, such as but not limited to, glass wool, and a polymeric material.
Another aspect of the disclosure includes any of the preceding aspects, and the insulating layer includes an optical diffuser.
Another aspect of the disclosure includes any of the preceding aspects, and the insulating layer includes a surface that reflects or resists transmission of infrared thermal energy.
Another aspect of the disclosure includes any of the preceding aspects, and the insulating layer includes at least one optical feature to direct the plurality of light emissions.
Another aspect of the disclosure includes any of the preceding aspects, and the dose of light is effective in at least one of: eliminating pathogenic microorganisms from the infected blood; partially reducing the number of the pathogenic microorganisms in the infected blood; and reducing the rate of proliferation of the pathogenic microorganisms in the infected blood.
Another aspect of the disclosure includes any of the preceding aspects, and the pathogenic microorganisms comprise microorganisms associated with at least one of sepsis, severe sepsis, and septic shock.
Another aspect of the disclosure includes any of the preceding aspects, and the pathogenic microorganisms comprise at least one of bacteria, fungi, yeast, and a combination thereof.
Another aspect of the disclosure includes any of the preceding aspects, and the pathogenic microorganisms comprise at least one of gram positive bacteria, gram negative bacteria, bacterial endospores, yeast, filamentous fungi, and a combination thereof.
Another aspect of the disclosure includes any of the preceding aspects, and the pathogenic microorganisms comprise at least one of Staphylococcus aureus, Clostridium perfringens, Clostridium difficile, Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus hyicus, Streptococcus pyogenes, Listeria monocytogenes, Bacillus cereus, Mycobacterium terrae, Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Salmonella enteritidis, Shigella sonnei, Serratia spp, Bacillus cereus, Clostridium difficile, Aspergillus niger, Candida albicans, Saccharomyces cerevisiae and a combination thereof.
Another aspect of the disclosure includes any of the preceding aspects, and the plurality of light emissions includes light within at least two ranges of: about 380 nm to about 420 nm; about 400 nm to about 415 nm: about 405 nm; about 500 nm to about 700 nm; about 500 nm to about 520 nm: about 530 nm to about 555 nm, about 565 nm to about 590 nm and about 615 nm to about 645 nm.
Another aspect of the disclosure includes any of the preceding aspects, and the mammalian patient is a human patient.
Two or more aspects described in this disclosure, including those described in this summary section, may be combined to form implementations not specifically described herein.
The details of one or more implementations are set forth in the accompanying drawings and the description below. Other features, objects and advantages will be apparent from the description and drawings, and from the claims.
The present disclosure will hereinafter be described in conjunction with the following drawing figures, which are not necessarily drawn to scale for ease of understanding, wherein the same reference numerals retain their designation and meaning for the same or like elements throughout the various drawings, and wherein:
It is noted that the drawings of the disclosure are not necessarily to scale. The drawings are intended to depict only typical aspects of the disclosure and therefore should not be considered as limiting the scope of the disclosure. In the drawings, like numbering represents like elements between the drawings.
Aspects of the present disclosure and certain features, advantages, and details thereof, are explained more fully below with reference to the non-limiting embodiments illustrated in the accompanying drawings. Descriptions of well-known materials, fabrication tools, processing techniques, etc., are omitted so as to not unnecessarily obscure the details of the disclosure. It should be understood, however, that the detailed description and the specific example(s), while indicating embodiments of the present disclosure, are given by way of illustration only, and are not by way of limitation. Various substitutions, modifications, additions and/or arrangements within the spirit and/or scope of the underlying inventive concepts will be apparent to those skilled in the art from this disclosure.
Approximating language, as used herein throughout disclosure, may be applied to modify any quantitative representation that could permissibly vary without resulting in a change in the basic function to which it is related. Accordingly, a value modified by a term or terms, such as “about” or “substantially,” is not limited to the precise value specified. For example, these terms can refer to less than or equal to +5%, such as less than or equal to +2%, such as less than or equal to #1%, such as less than or equal to +0.5%, such as less than or equal to +0.2%, such as less than or equal to +0.1%, such as less than or equal to +0.05%. In some instances, the approximating language may correspond to the precision of an instrument for measuring the value.
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The extracorporeal disinfection device 14 may expose a blood flow to such light wavelengths at sufficient intensity and duration that the light is effective in reducing or eliminating or slowing the proliferation of a broad range of infectious sources, such as infectious sources known to be associated with sepsis (e.g., severe sepsis) and/or septic shock. In some embodiments, the dose of light emitted from the at least one microbicidal lighting device of the systems and methods may be configured to destroy, eradicate and/or reduce the number of harmful pathogenic microorganisms, or reduce of the rate of proliferation thereof, within the blood or blood portion/derivative that are associated with sepsis (including severe sepsis and septic shock). For example, in some embodiments, the dose of light emitted from the at least one microbicidal lighting device may be configured to destroy, eradicate and/or reduce the number of at least the pathogenic microorganisms listed below in TABLE 1, or reduce of the rate of proliferation thereof, within the treated blood.
Acinetobacter
Staphylococcus
Bacillus
Aspergillus
baumannii
aureus (incl. MRSA)
cereus
niger
Pseudomonas
Clostridium
Clostridium
Candida
aeruginosa
perfringens
difficile
albicans
Klebsiella
Clostridium difficile
Saccharomyces
pneumoniae
cerevisiae
Proteus vulgaris
Enterococcus faecalis
Escherichia coli
Staphylococcus
epidermidis (CONS)
Salmonella
Staphylococcus hyicus
enteritidis
Shigella sonnei
Staphylococcus
pyogenes
Serratia spp
Listeria
monocytogenes
Bacillus cereus
Mycobacterium
terrae
Continuing with
System 10 and/or the extracorporeal disinfection device 14 itself is configured such that the microbicidal light emitting device 24 externally (with respect to the patient 11) effectuates a dose of the emitted light to the infected blood flowing through the treatment flowpath 22 that reduces or eliminates the presence of infectious microorganisms in the blood that are commonly associated with sepsis, severe sepsis and/or septic shock to address a pathogenic microbial infection of the patient 11 that is leading to, or could/would lead to, sepsis, severe sepsis and/or septic. The system 10 and treatment method associated therewith may thereby provide a stand-alone or adjunctive therapeutic intervention to standard measures used in the treatment of sepsis, severe sepsis and/or septic shock to combat the overwhelming infectious process characteristic of the conditions where infecting microbial organisms can no longer be removed from circulating blood by the body's natural processes faster than they are proliferating. For example, the system 10 and treatment method associated therewith may be utilized in conjunction with an anti-infective drug therapy.
In some embodiments, the microbicidal lighting device 24 of the extracorporeal disinfection device 14 of the disinfection system 10 is configured to emit light in the 380-420 nm (violet) range. In some such embodiments, the light spectrum emitted from the microbicidal lighting device 24 may thereby be configured as bactericidal, but yet safe for processing the blood of a patient 11 without critically damaging the blood when infecting microbial organisms can no longer be removed from circulating blood by the patient 11 faster than they are proliferating. As noted above, the light emitted from the microbicidal lighting device 24 is of wavelengths that may be selectively absorbed by single cell organisms (e.g., non-mammalian cells) (such as by the porphyrin thereof, for example), and may not be absorbed by mammalian multi-cell organisms (as they are void, or at least substantially void, of porphyrin, for example). In some embodiments, system 10 is configured to effectuate a dose of the light emitted from the microbicidal light emitting device 24 to the infected blood of the patient 11 flowing through the treatment flowpath 22 that destroys, eradicates and/or reduces the number of harmful pathogenic microorganisms, or reduces the rate of proliferation thereof, within the blood or blood products/derivatives, such as those that cause sepsis (e.g., tend to cause, known to cause or may cause sepsis). For example, in some embodiments, the system 10 is configured to effectuate a dose of the light emitted from the microbicidal light emitting device 24 to the infected blood of the patient 11 flowing through the treatment flowpath 22 that destroys, eradicates and/or reduces, or reduces the rate of the proliferation of, infectious microorganisms in the blood that (can or likely) cause, for example, UTI, pneumonia, cellulitis, wounds and abscesses, sinusitis and/or meningitis. In some embodiments, the system 10 is configured to effectuate a dose of the light emitted from the microbicidal light emitting device 24 to the infected blood of the patient 11 flowing through the treatment flowpath 22 that destroys, eradicates and/or reduces, or reduces the rate of the proliferation of, for example, gram-positive bacteria (e.g., Staphylococcus aureus, coagulase-negative Staphylococcus, Streptococcus pyogenes, Streptococcus pneumoniae, and enterococci), gram-negative bacteria (e.g., Proteus, Serratia, Pseudomonas aeruginosa, Neisseria meningitidis, Escherichia coli Klebsiella pneumoniae), anaerobic organisms, fungi (e.g., Candida albicans) and/or combinations thereof.
The system 10 may thereby be configured to effectuate a dose of the light emitted from the microbicidal light emitting device 24 to the infected blood of the patient 11 flowing through the treatment flowpath 22 effective in at least one of: selectively eliminating pathogenic microorganisms from the infected blood: selectively partially reducing the number of the pathogenic microorganisms in the infected blood; and selectively reducing the rate of proliferation of the pathogenic microorganisms in the infected blood. The pathogenic microorganisms may comprise microorganisms associated with at least one of sepsis, severe sepsis, and septic shock to treat and/or prevent at least one of sepsis, severe sepsis, and septic shock. For example, in some embodiments, the pathogenic microorganisms may comprise at least one of bacteria, fungi, yeast and a combination thereof. In some such embodiments, the pathogenic microorganisms may comprise at least one of gram positive bacteria, gram negative bacteria, bacterial endospores, yeast, filamentous fungi, and a combination thereof. In some such embodiments, the pathogenic microorganisms may comprise at least one of Staphylococcus aureus, Clostridium perfringens, Clostridium difficile, Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus hyicus, Streptococcus pyogenes, Listeria monocytogenes, Bacillus cereus, Mycobacterium terrae, Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Salmonella enteritidis, Shigella sonnei, Serratia spp. Bacillus cereus, Clostridium difficile, Aspergillus niger, Candida albicans, Saccharomyces cerevisiae and a combination thereof.
In some embodiments, the microbicidal light emitting device 24 of the extracorporeal disinfection device 14 is configured to emit light within the range of about 380 nm to about 420) nm. In some embodiments, the microbicidal light emitting device 24 of the extracorporeal disinfection device 14 is configured to emit light within the range of about 400 nm to about 415 nm. In some such embodiments, the microbicidal light emitting device 24 of the extracorporeal disinfection device 14 is configured to emit light of about 405 nm. In some embodiments, the microbicidal light emitting device 24 of the extracorporeal disinfection device 14 is configured to emit light within the range about 500 nm to about 700 nm.
In some embodiments, the microbicidal light emitting device 24 of the extracorporeal disinfection device 14 is configured to emit light within the range of at least one of about 500 nm to about 520 nm, about 530) nm to about 555 nm, about 565 nm to about 590) nm and about 615 nm to about 645 nm. In some such embodiments, the microbicidal light emitting device 24 of the extracorporeal disinfection device 14 is configured to emit light within the range of about 500 nm to about 520 nm, within the range of about 530 nm to about 555 nm, within the range of about 565 nm to about 590 nm and/or within the range of about 615 nm to about 645 nm. The light emitted from the microbicidal lighting device 24 may thereby be of one or more wavelengths that may be selectively absorbed by single cell organisms (e.g., non-mammalian cells) (such as by the porphyrin thereof, for example), as opposed to being absorbed by mammalian multi-cell organisms (as they are void, or at least substantially void, of porphyrin, for example).
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The input tube 12 and the output tube 16 may each comprise any tube, hose or other mechanism that forms at least one sterile hollow flow channel for the passage of the flow of blood from the patient 11 therethrough. The input tube 12 and the output tube 16 may each comprise any biologically- or blood-compatible extracorporeal tube or like member. In some embodiments, the input tube 12 and the output tube 16 may be formed of a biologically- or blood-compatible material, such as PVC, polyurethane, ethylene vinyl acetate (EVA), polyacrylonitrile (pAN), silicone, a thermoplastic elastomer (TPE) or a combination thereof, for example.
In some embodiments, the input tube 12 and/or the output tube 16 may include at least a portion that is transparent or translucent such that the flow of blood therethrough is visible to the naked eye. In some embodiments, the input tube 12 and/or the output tube 16 may be flexible to form a flexible flowpath extending between and connecting the patient 11 and the system 10. In one embodiment, the input tube 12 and the output tube 16 are thin, flexible, plastic hoses.
In some embodiments, the input tube 12 is a continuous integral tube, and the output tube 16 is a continuous integral tube that is separate and distinct from the input tube 12 but in fluid communication with the input tube 12. In some other embodiments, the input tube 12 and the output tube 16 are portions of a single continuous integral tube. In some other embodiments, at least one of the input tube 12 and the output tube 16 are formed of a plurality of interconnected tubes (in fluid communication).
The input tube 12 and/or the output tube 16 may be fluidically coupled to a blood vessel (e.g., vein or artery) of the patient for the flow of blood therefrom or thereto, respectively. The input tube 12 and the output tube 16 may be fluidly coupled to the same blood vessel of the patient 11 (e.g., different portions thereof), or fluidly coupled to different blood vessels of the patient 11. In some embodiments, the input tube 12 and/or the output tube 16 may be fluidly coupled to a blood vessel of the patient 11 via a needle or catheter, for example.
The input tube 12 and the output tube 16 may form an internal passageway that allows for the flow of the blood therethrough. For example, the cross-sectional size and shape of the internal passageways formed by the input tube 12 and the output tube 16 may be configured to allow the blood to flow therethrough without clogging or clotting of the blood (which may be related, at least in part, to the pressure and/or flow rate of the blood within the tube via the at least one pump 20). In some such embodiments, the input tube 12 and the output tube 16 may form an internal passageway with a minimum internal cross-sectional area of at least about 1.25 square millimeters (mm2). As a further example, the surface finish and/or material of the internal passageway of the input tube 12 and the output tube 16 may be configured to allow the blood to flow therethrough without clogging or clotting of the blood (which may be related, at least in part, to the pressure and/or flow rate of the blood within the tube via the at least one pump 20). For example, the internal surfaces of the input tube 12 and the output tube 16 that form the internal passageways thereof may be substantially smooth (e.g., comprise a surface roughness of 0.5 micrometer (μm) Ra or less) and/or include an low friction and/or hydrophobic substance (e.g., polytetrafluoroethylene, fluorinated ethylene propylene, manganese oxide polystyrene nano-composites, zinc oxide polystyrene nano-composites, fluorinated silanes and silica nano-coatings).
The extracorporeal blood pump 20 may be configured to draw a flow of blood from the patient 11 via the input tube 12 and to pass a flow of blood from the patient 11 through at least the extracorporeal disinfection device 14 (and any other potential component of the system 10, as described further below) and back into the patient 11 via an output passageway, tube or flow 16, at least in part. The extracorporeal blood pump 20 may comprise any biologically- or blood-compatible extracorporeal pump mechanism effective to form a flow of the infected blood from the patient 11 via the input tube 12, through at least the extracorporeal disinfection device 14, and back to (and into) the patient 11 via the output tube 16. For example, the extracorporeal blood pump 20 may comprise a centrifugal extracorporeal blood pump, a roller extracorporeal blood, a pulsatile tube compression extracorporeal pump, a ventricular extracorporeal pump or another pump type or pump configuration (such as another peristaltic pump configuration). However, it is noted that any blood pump may be utilized.
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In some embodiments, the filter 38 may be positioned upstream of the extracorporeal disinfection device 14 to remove or otherwise filter out at least one substance from the untreated blood flowing through the input tube 12. In some embodiments, at least a first filter 38 may positioned upstream of the extracorporeal disinfection device 14 to remove or otherwise filter out at least one substance from the untreated blood flowing through the input tube 12, and at least a second filter 38 may positioned downstream of the extracorporeal disinfection device 14 to remove or otherwise filter out at least one substance from the treated blood flowing through the output tube 16.
In some embodiments, the filter 38 may comprise a filter medium that defines a plurality of passageways therethrough of a particular size or ranges of sizes. The filter may thereby be configured to prevent components or portions of the flow of blood from flowing therethrough that are larger than the size(s) of the passageways to filter out the components or portions from the blood. As another example, the filter 38 may comprise a substance that binds, bonds or otherwise couples to one or more components or portions of the flow of blood flowing therethrough or thereover. The filter may thereby be configured to prevent components or portions of the flow of blood from flowing therethrough or thereover that bind to the substance to filter out the components or portions from the blood. In some embodiments, the filter 38 may comprise aluminosilicates, molecular sieves, activated charcoal, silicalite, zeolite, composite materials comprising a selective molecular absorber (such as above) and a binder agent, such as a polymer, zeolite-polymer composites, nanofiber mesh, semipermeable membrane (e.g., that is selective to molecules based on size), synthetic ion channel membranes (e.g., that is selective to molecules based on size and/or polarity/solubility) or a combination thereof as filter media.
In some embodiments, filter 38 may comprise elements coated in a chemical binder agent. This binder agent may comprise a compound that selectively binds to components of pathogenic or single celled organisms, a compound that selectively bonds to endotoxins, or a compound that binds to other undesirable toxins found within the patient blood. The filter may comprise a binder agent such as polymyxin B (PMX), immobilized onto fibers or other physical structures that present a large surface area to the treatment blood flow, and contained within a cartridge, tube, reservoir, or other physical enclosure that directs the treatment blood flow.
In some embodiments, filter 38 may comprise one or more different filter components connected serially such that each sequential filter component removes a different toxin or detrimental byproduct from the blood. For example, filter 38 may comprise first a PMX binding component, and a secondly a synthetic ion channel membrane component. In other configurations, multiple filter components may be connected in parallel to increase overall flow through the system or to decrease pressure drop across the filter 38.
As shown in
In some embodiments, the manifold 34 may be in fluid communication with a supply of treatment or infusion material 35 configured to treat the treated/disinfected blood. The manifold 34 may thereby introduce the treatment material 35 into the flow of treated/disinfected blood flowing through the output tube 16. In one embodiment, the dose of light from the extracorporeal disinfection device 14 may degrade at least one constituent part or substance of the pre-treated/infected blood, and the treatment or infusion material 35 may comprise the at least one constituent part or component of the infected blood in a non-degraded state and/or comprises a substance that treats the degraded at least one constituent part or substance of the infected blood.
As also shown in
In some embodiments, the disinfection system 10 may be designed to meet a determined minimum rate of disinfection, dosage, or other treatment criteria set by the operator. The rate of disinfection is determined by a number of factors, including the characteristics of the substrate (blood), the specific pathogen(s) involved, the wavelengths of light utilized, the relative ratios between energy at said wavelengths, the optical transmission of the irradiation chamber and other elements of the system, the geometry of the irradiation chamber, and the rate of flow through the system.
Some of these are ‘external factors’ are not attempted to be controlled directly by the system, but rather compensated for. For example, the optical transmission of the blood is known to vary between patients with different health conditions. For example, iron deficiency anemia can result in increased transmission of wavelengths in the 600-800 nm range, while dehydration can result in decreased transmission of the same range. Drugs can also impact the optical characteristics of patient blood, especially drugs intended for use in photodynamic therapy or that otherwise function as a photosensitizing agent. The physical characteristics of the blood also play an important role as a limiting factor in the geometry of the irradiation chamber and other extracorporeal loop components. TABLE 2 lists sample transmission data for a healthy human male at various wavelengths, expressed as a percentage of 400 nm transmission in the same sample. This data illustrates that 630 nm and 660 nm light are transmitted substantially better than 400 nm through the 0.02 mm and thicker sample depths.
Some patient health conditions can change the viscosity of blood, or the likelihood of clotting.
An embodiment of this technology includes the use of an anticoagulant agent such as heparin (UFH), low molecular weight heparin (LMWH), argatroban, regional citrate (RCA), or other agents to prevent clotting within the system. Unless contraindicated by specific health conditions, UFH is preferred and approved for related uses (dialysis) in the United States by the Food and Drug Administration (FDA) because it offers safe reduction of clotting risk with a short half-life. Use of UFH or other short half-life anticoagulant agents requires continued or periodic administration of the agent during extracorporeal treatment to maintain the anti-clotting effects, whereas some other agents such as LMWH may be administered before treatment, and the effects last throughout treatment without additional agent administered.
Table 3 lists weighting factors for reactive oxygen species (ROS) production at various wavelengths in a sample bacterium, normalized to 400 nm.
Table 3 can be used with the equation created herein for ‘Effective Delivered Disinfection’ (EDD)—power disinfection dosage in 405 nm light equivalent ROS production of a multiband disinfection treatment. EDD allows for the comparison of the overall efficacy of a multiband light to a 405 nm light for disinfection, accounting for wavelength specific attenuation within a 3-dimensional volume of blood of arbitrary geometry.
Where: L(x,y,z,λ)=energy delivered within a body of fluid S at point (x,y,z) and wavelength λ; and D(λ)=weighting factor.
This equation serves to sum up all light energy within the irradiation chamber, at all depths after any attenuation, and after correction for relative efficacy vs 405 nm. The result is the effective dosage/irradiation level in units that match L( ) either power or energy.
This form of the equation assumes each light source s creates a uniform light distribution, and there are an arbitrary number of sources s. The distance d is from the surface of the irradiation chamber, and all points where d=0 may be nonplanar in some configurations (such as with a round tube profile irradiation chamber).
The output from this form of the equation is the effective dosage/irradiation level in units that match L( ) either power or energy.
The equation for Effective Delivered Disinfection Ratio (EDDratio) can be used to compare the relative efficacy of a system versus using 400 nm light alone. This is useful for evaluating the suitability of a given spectrum to a given treatment pathway geometry and allowing for optimization of a multiband disinfection system. For a given overall output power, any EDDratio over 1.0 indicates improved performance over using 400 nm light alone. A preferred embodiment of the disclosure utilizes a multiband spectrum where EDDratio exceeds 1.25. In certain embodiments, disinfection unit 14 has an effective delivered dosage ratio greater than 1.0. In certain embodiments, disinfection unit 14 has an effective delivered dosage of greater than 4 Watts. EDD represents a minimum effective dosage, regardless of irradiation chamber geometry and wavelengths selected. The EDD ratio >1 means that, with a given geometry, the effective delivered dosage of multiband energy to bacterial cells is greater than the dosage would be using pure 405 nm light in that same geometry chamber.
The extracorporeal disinfection device 14 may be configured in a variety of differing configurations that effectuate a dose of the light emitted by the microbicidal light emitting device 24 to the infected blood flowing through the treatment flowpath 22 that disinfects the blood, such as a dose that is effective in at least one of eliminating pathogenic microorganisms from the infected blood, partially reducing the number of the pathogenic microorganisms in the infected blood, and reducing the rate of proliferation of the pathogenic microorganisms in the infected blood, as described above.
For example, as shown in
As also shown in
In some embodiments, the light emitting devices 26 are provided in a helical arrangement as shown in
Another illustrative extracorporeal disinfection device 114 is illustrated in
As shown in
In some embodiments, the open structure may be configured with internal mirrored or reflective surfaces or material that reflect the light emitted from the plurality of light emitting devices 126. The mirrored or reflective surfaces of the open structure may be configured to reflect the light emitted from the plurality of light emitting devices 126 inwardly into the interior of the inner cavity and the coiled (e.g., helical) treatment flowpath 122 therein. In this way, light emitted from the plurality of light emitting devices 126 that passes or is not incident on the coiled treatment flowpath 122 may reflect off one or more of the mirrored or reflective surfaces and, ultimately, act on the treatment flowpath 122 (i.e., become incident on the flow of blood therethrough).
In some embodiments, the light emitting devices 126 are provided in a helical arrangement as shown in
Another illustrative extracorporeal disinfection device 214 is illustrated in
As also shown in
In some embodiments, the light emitting devices 226 are provided in a regular pattern on the emitter plate, as shown in
Another illustrative extracorporeal disinfection device 314 is illustrated in
Another embodiment of an extracorporeal blood disinfection system 410 with an extracorporeal disinfection device 414 according to the present disclosure is shown in
As shown in
In some embodiments, the printed circuit board 427 may be built on, incorporate, or be coupled to a thermally conductive substrate 440 (e.g., a metal or ceramic substrate) to enhance thermal conduction of the circuit board 437 (which may be or comprise fiberglass, for example) and/or the light emitting devices 426, as shown in
In some embodiments, the extracorporeal disinfection device 414 includes an optical diffuser 428 associated with the microbicidal light emitting device 424, as shown in
Another embodiment of the extracorporeal disinfection device 414, the light emitting devices 426 may be attached to a substrate 440, illustrated in
In another embodiment, the light emitting devices may comprise one or more laser sources, illustrated in
Another embodiment of an extracorporeal blood disinfection system 510 with an extracorporeal disinfection device 514 according to the present disclosure is shown in
In some embodiments, the emitter shaft 527 may include a central thermal management device. The emitter shaft 527 may be surrounded with outward facing light emitting device 526 as described above with respect to
The at least one light emitting device 526 may thereby be positioned at an axial end portion of the emitter shaft 527, as shown in
It is noted that the location of the at least one light emitting device 526 at the end of the emitter shaft 527 spaced from the helical coiled treatment pathway 522 limits or attenuates the amount of incidental conduction of thermal energy into the blood flowing through the helical coiled treatment pathway 522 channel from the at least one light emitting device 526. To further limit or prevent the ability or effect of the at least one light emitting device 526 from heating up the blood flowing through the helical coiled treatment pathway 522, the extracorporeal disinfection device 514 may include a heatsink 540 coupled to the at least one light emitting device 526 to remove heat (or exchange heat) therefrom, as shown in
Another embodiment of an extracorporeal blood disinfection system 610 with an extracorporeal disinfection device 614 according to the present disclosure is shown in
As shown in
In some implementations of the disclosure, a further improved thermal management system is provided. Maintaining the blood at normal body temperature (approximately 37 degrees Celsius) is critical to patient safety during extracorporeal disinfection. In some configurations, cooling the light emitter using a passive device such as a heatsink is adequate. In higher light output emitters, lower efficiency emitters, or emitters that produce a larger amount of heat, active cooling of the emitter may improve performance (e.g., adding a fan to force air onto the emitter heatsink). Cooling the emitter to a further degree may be necessary if the desired optical flux is substantially higher, for example, if the surface area of the irradiation chamber is decreased to minimize extracorporeal blood volume, or for use in portable systems. This further improved cooling of the emitter can be accomplished using chilled air (cooled below ambient operating temperature), liquid cooling (using a high thermal capacity fluid in a heat exchanger to remove heat from the emitter), chilled liquid cooling (using fluid that is cooled to below ambient operating temperature), thermoelectric cooling (such as a peltier heat pump) or other cooling methods that can dissipate the increased thermal load. Even with improved thermal management of the emitter, the blood may still increase in temperature beyond an acceptable range (e.g., 36.5-37.5° C.). This temperature increase may be due to radiative thermal energy from the emitter that is not removed by the emitter thermal management system, conducted thermal energy from the emitter, and/or thermal energy released as a byproduct of the cells in the blood absorbing the disinfecting and other wavelengths of light from the emitter.
The blood temperature set point is the target temperature or temperature range for the blood to remain in during treatment. This set point may be input by the device operator, preset at the factory, or determined based on device operating mode. The irradiation set point is a maximum allowable temperature for the emitter and is typically preset (not operator adjustable). The maximum emitter temperature may be limited by the technology used for the emitter, insulation characteristics between the emitter and treatment flowpath, and design of the thermal management system. In some implementations, it may be preferable to utilize a higher irradiation set point temperature, to enable a smaller form factor (e.g., for a field portable extracorporeal disinfection unit) with a likely effect of reducing the operating lifespan of the emitter.
The sensor signal processor 922 is a microcontroller, logic circuit, computer, FPGA, or other device that serves to read input signals from the blood temperature sensor 930, emitter temperature detector 944, an irradiation set point 931, a blood flow set point 933, and an irradiation dosage sensor 935, and other sensors and dynamically adjust various outputs in a closed loop control scheme. In this example, the blood temperature sensor 924 and treatment path temperature regulation 926 are accomplished with a closed loop control scheme, and the emitter is cooled with an open loop scheme, with fault detection. In this system, the sensor signal processor 922 continuously or repeatedly compares the current blood temperature sensor 928 value to the blood temperature setpoint value and enables the treatment path heater 928 or treatment path chiller 932 in order to maintain the target set point temperature. If the blood temperature sensor returns a value outside the acceptable range, the device may be configured to activate an alarm 934 and optionally halt operation. The sensor signal processor 922 may alter the speed of the blood pump 936 to mitigate a minor fault (e.g., temporarily increase blood pump 936 speed in a minor blood temperature sensor over temperature event) in addition to activating the appropriate treatment path thermal management elements. In the event of a serious fault (temperature reading is significantly outside of safe operating range and continued use could cause immediate patient harm), a fault signal processor 940 may be used to immediately cease blood flow by activating a venous clamp 942 or other element to rapidly halt operation. Typically, detection of a serious fault would activate an alarm 934 and require intervention by the device operator to continue device operation. Other faults that may activate the fault signal processor include but are not limited to emitter temperature detector 944 out of allowable range (i.e. emitter is overheating and continued operation may damage the emitter), detection of an air bubble by air bubble detector 946 in the treatment flowpath 22, or activation of other sensors that are designed for detecting abnormal conditions that may be detrimental to the patient 10. In some embodiments, the fault signal processor 940 may be a part of the same processor as the sensor signal processor 922.
Not all elements are required in a commercial implementation of the disclosure—some elements may be replaced by characterization of a design. For example, an emitter cooling system may consist of a passive heatsink 1010 (
Terminology used herein is for the purpose of describing particular examples only and is not intended to be limiting. As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, references to “one example” are not intended to be interpreted as excluding the existence of additional examples that also incorporate the recited features. Moreover, unless explicitly stated to the contrary, the terms “comprising” (and any form of “comprise,” such as “comprises” and “comprising”), “have” (and any form of “have,” such as “has” and “having”), “include” (and any form of “include,” such as “includes” and “including”), and “contain” (and any form of “contain,” such as “contains” and “containing”) are used as open-ended linking verbs. As a result, any examples that “comprises,” “has,” “includes” or “contains” one or more step or element possesses such one or more step or element, but is not limited to possessing only such one or more step or element. As used herein, the terms “may” and “may be” indicate a possibility of an occurrence within a set of circumstances: a possession of a specified property, characteristic or function; and/or qualify another verb by expressing one or more of an ability, capability, or possibility associated with the qualified verb. Accordingly, usage of “may” and “may be” indicates that a modified term is apparently appropriate, capable, or suitable for an indicated capacity, function, or usage, while taking into account that in some circumstances the modified term may sometimes not be appropriate, capable, or suitable. For example, in some circumstances, an event or capacity can be expected, while in other circumstances the event or capacity cannot occur—this distinction is captured by the terms “may” and “may be.” As used herein, the terms “comprising.”” has.” “including.” “containing,” and other grammatical variants thereof encompass the terms “consisting of” and “consisting essentially of.”
The phrase “consisting essentially of” or grammatical variants thereof when used herein are to be taken as specifying the stated features, integers, steps or components but do not preclude the addition of one or more additional features, integers, steps, components or groups thereof but only if the additional features, integers, steps, components or groups thereof do not materially alter the basic and novel characteristics of the claimed compositions or methods.
All publications cited in this specification are herein incorporated by reference as if each individual publication were specifically and individually indicated to be incorporated by reference herein as though fully set forth.
Subject matter incorporated by reference is not considered to be an alternative to any claim limitations, unless otherwise explicitly indicated.
Where one or more ranges are referred to throughout this specification, each range is intended to be a shorthand format for presenting information, where the range is understood to encompass each discrete point within the range as if the same were fully set forth herein.
While several aspects and embodiments of the present disclosure have been described and depicted herein, alternative aspects and embodiments may be affected by those skilled in the art to accomplish the same objectives. Accordingly, this disclosure and the appended claims are intended to cover all such further and alternative aspects and embodiments as fall within the true spirit and scope of the disclosure.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US22/28314 | 5/9/2022 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63189748 | May 2021 | US |
