MXPA97005405A - Assay system in the line of farmaco in therapy out of the cue - Google Patents

Abstract

A preferred patient blood treatment system and method for photoactivating contact reagents with a patient's blood gets a well-mixed and accurate drug concentration in out-of-body therapy, the preferred drug delivery system of the present invention comprises specially designed components and a microprocessor control system that includes a syringe pump, a drug mixer and a reaction chamber, wherein the microprocessor control system monitors the patient's blood flow and regulates the components of the system to supply the desired concentration of drug to the reaction chamber, maximizing the effectiveness of the therapy outside the body

Description

ASSAY SYSTEM IN THE DRUG LINE OF THERAPY OUT OF THE BODY BACKGROUND OF THE INVENTION This invention relates to the field of treatment outside the body of fluids and particularly blood, wherein drugs or other biological solutions, such as solutions of monoclonal antibodies, need to be added to speeds accurately controlled, including at speeds that respond to other information and / or conditions throughout the out-of-body treatment. Very par ticularly, it refers to cell treatments with photoactivable compounds and radiation, and specifically to clinically useful systems for the treatment outside the body of blood cells, especially leukocytes, with ultraviolet radiation. It is well known that a number of pathological states of the human being can be characterized by the overproduction of certain types of leukocytes, including lymphocytes, in Or comparison with other populations of cells that normally comprise whole blood. Excessive or abnormal lymphocyte populations result in numerous adverse effects to patients including functional impairment of body organs, autoimmune diseases mediated by leukocytes and disorders related to leukemia, many of which often produce a fatal condition at the end.

For better results in chemotherapy outside the body, it is necessary to deliver drug molecules to a target site in the blood at a desired drug concentration. For example, in photochemotherapy outside the body (totopheresis) the patient orally to capsules of crystalline 8-ethoxypsoralen ("8-MOP.) Two (2) hours later when the concentration of 8-M0P in the patient's blood is At a higher level, peripheral blood is withdrawn from the patient, anticoagulated, and pumped into a centrifuge bowl where it is separated into three layers: plasma, curdled lymph, and layers of packed red cells.The layers of plasma and lymph curd they are separated from the bowl See, for example, U.S. Patent No. 4,568,328 of Kmg, U.S. Patent No. 4,573,960 of Goss, and U.S. Patent No. 4,623,328 of Hartranft The collected curd lymph is mixed with plasma and saline normal and recirculated through a photoactivation chamber (photoceptor) where the blood cells in the circulating solution are exposed to UVA irradiation in the presence of the photoactivatable drug, 8-MOP molecules. You immediately leave the patient. In this therapy, the concentration of drug in the patient's blood is one of the most important parameters. Inter- and intra-patient variation in the biodisponibility of 8-MOP is extremely high, however, and in some individuals, such as urernic patients, the bioavailability of 8-MOP is close to zero. Therefore, it is very difficult to give patients - consistent and optimal therapy. Several methods are currently used to deliver drugs in liquid form to an out-of-body circuit, but none of them can achieve the goal satisfactorily. Among the most common methods used today is injecting a precalculated amount of liquid drug into a part of a blood circuit outside the body, such as a drip chamber or blood bag, and mixing it manually. Another common approach is to drip the drug into the drip chamber. These methods are not very precise, thus making it difficult to control the concentration of drugs during the treatment process outside the body. Another method that is currently used imparts a drug solution to the blood circuit by means of a syringe pump. In that method the rate of injection of the drug can be controlled with precision but it is independent of the flow velocity of the blood. In this way, the concentration of drug in the blood circuit or in the reaction chamber varies as the blood flow rate changes in the circuit outside the body. Another commonly used method uses a peristaltic drug assortment pump, such as a hepapna pump, which is dependent on the speed of the blood pump. This method has limited applications for several reasons. First, in blood supply from the peripheral circuit of the patient to the circuit outside the body should remain substantially constant throughout the treatment, however, if the blood supply goes through, which often happens during the treatment due to the movement of the needle or other reasons, negative pressure can develop inside the circuit outside the body, endangering the patient. For this reason, most dialysis patients need to have an implanted fistula as a blood supply. This method also requires the use of a tube of elastic pump, such as silicon or PVC, which in many cases adsorbs drug molecules.In the aforementioned method, no attempt is made to achieve good mixing of the drug. As the flow is laminar in most of the blood circuit outside the body, any current of liquid drug injected into the bloodstream requires a quantity of substantial time or flow distance to achieve good mixing The known methods for out-of-body therapy keep the lymph portion curdled from the patient's blood in all treatment cycles of a therapy assignment, and therefore no return portion of the patient's curdling lymph to the latter until the cessation of treatment ends, in order to minimize the time during which a patient is In curdled lymph, it is convenient to have an out-of-body treatment system that returns whole blood (including curdled lymph) to the patient at the end of each treatment cycle in the transfer of blood. Therefore, an object of the present invention it is to overcome the above disadvantages by providing systems and methods to increase the effectiveness of out-of-body treatment and to increase patient safety thereby also raising the comfort level of the patient and also achieving acceptable regulatory standards. Another related object is to provide adequately automated systems and methods that can be monitored and operated by less trained personnel thus reducing treatment costs in accordance with the recently established fiscal policies. Another related object is to provide systems and methods for use in out-of-body treatment where the drug concentration is regulated and supplied to a reaction chamber, as it is used in chemotherapy outside the body, to maximize the effectiveness of said therapy. Another related object is to provide an out-of-body treatment system that returns whole blood to the patient at the end of each treatment cycle in the therapy assignment. Another related object is to provide a treatment system outside the body that achieves a complete and uniform mixing of a drug stocked with blood flow in a circuit outside the body.

Another related object is to provide a treatment system outside the body that is capable of detecting blood loss in the circuit outside the body. Another related object is to provide a treatment system outside the body that is capable of detecting the presence of air in the circuit outside the body. Another related object is to provide an out-of-body treatment system that includes a syringe pump and a pressure pad detector that prevents a drug in the syringe from passing into the blood circuit when there is negative pressure in the blood line.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a block diagram illustrating an out-of-body online drug treatment system operating in accordance with a preferred embodiment of the present invention. Figure 2 is a block diagram illustrating the operation of the system of Figure 1 according to a preferred embodiment of the present invention. Figure 2A is a block diagram illustrating the operation of the system of Figure 1 according to a further preferred embodiment of the present invention. Figure 3 is a block diagram illustrating the operation of blood pumps and syringes according to a preferred embodiment of the present invention. Figures 4 and 4A is a block diagram illustrating the operation of a system for controlling the irradiation time of blood contained in a centrifuge treatment chamber according to a preferred embodiment of the present invention. Figure 5 is a block diagram of a system for detecting re in the blood circuit of a bleeding out of body system in accordance with a preferred embodiment of the present invention. Figure 6 is a side view of a drug mixer for blending a drug solution with the blood of a patient within a blood circuit outside the body according to a preferred embodiment of the present invention. Figure 7 is a block diagram of a system for detecting blood loss from the blood circuit of an out-of-body blood treatment system in accordance with a preferred embodiment of the present invention. Figure 8 is a block diagram of a system for monitoring the status of irradiation lamps located within a centrifuge chamber according to a preferred embodiment of the present invention. Figures 9 and 9A are front views of a syringe pump according to a preferred embodiment of the present invention.

BRIEF DESCRIPTION OF THE INVENTION The present invention is directed to a method and apparatus for the forceful treatment of the body in line of a patient's blood. The whole blood is initially obtained from the patient and mixed with a drug solution to form a mixture of drug solution with whole blood. A quantity of treated whole blood is formed by supplying the mixture of drug solution and whole blood to a centrifuge chamber and exposing the whole blood drug solution to radiation. The amount of whole blood treated is then emptied from the centrifuge chamber, stored in a return storage medium, and reinfused into the patient. The process is repeated successively from the initial obtaining stage during a plurality of cycles. In a preferred embodiment, the treatment procedure is accelerated after the first volume of whole blood has been rated, simultaneously collecting whole blood from the patient while at the same time treating the volume of whole blood that was obtained from the patient in the cycle. previous. In accordance with another aspect of the present invention, a continuous flow of blood obtained from a patient in a rotating centrifuge chamber is provided. Upon receipt of the blood flow obtained from the patient by means of the centrifugal rotating chamber, the blood commonly contained in the rotating centrifuge chamber is irradiated with light. When the blood is irradiated in the center rotating chamber, it changes in the volume of blood contained in the centrifugal spinning chamber and the cumulative energy of light applied to the blood in the chamber is monitored over time. A value of the remaining irradiation time is determined according to the changes in the volume of blood commonly contained in the rotating centrifuge chamber and the cumulative light energy value. c, and make an ermination to see if the irradiation step is finished, comparing the value of the remaining irradiation time with a predetermined constant .. If the comparison of the value of the irradiation time remaining with the predetermined constant does not indicate that the irradiation step is finished, then new remaining irradiation time values are determined successively until a comparison of the remaining irradiation time value with the prede rmin constant * indicates that the irradiation step is finished. In accordance with a further aspect of the present invention, there is provided an online system and method for dispensing a predetermined concentration of a drug solution into the blood of a patient outside the cell. Essentially, blood is drawn from the patient and supplied to a blood supply. Then, the extracted blood is pumped from the blood reservoir into a blood line at a first pumping speed. The level of blood in the reservoir is detected based on the blood extracted commonly remaining in the blood reservoir to determine a level of blood deposition detected. The first pump speed is adjusted in response to the level of the detected blood vessel. A medical solution is pumped into the blood line at a second pump speed that is adjusted in response to the first pump speed. The blood drawn in the blood line is mixed with the medical solution in the blood line, and then the patient is returned. In accordance with another aspect of the present invention, an improved syringe pump is provided for use in an in-line system for dispensing a predetermined concentration of a drug solution into the blood of a patient out of the body. The syringe pump includes a mounting block for rigidly receiving a body portion of a syringe, the syringe is filled with a medicament solution and coupled with a blood route in the on-line system. A thrust block is slidably secured to the mounting block, the thrust block has an open plunger lock to secure an upper end of a plunger portion of the syringe to the thrust block. Drive means, coupled to the mounting block and the thrust block, are provided to drive the thrust block towards the mounting block in response to a control signal. The opening of the plunger lock in the push block is configured to prevent the online system from removing drug solution from the syringe when there is negative pressure in the blood path. In accordance with another aspect of the present invention, a blood loss detector is provided for use in connection with an in-line system for treating blood of a patient that includes a reaction chamber to treat the patient's blood outside of the body. , the reaction chamber has a drain line to remove blood from the system in line. A first conductor tube having a first end coupled to the drain line is provided. An insulating block having a first channel for receiving a second end of the first conductive tube is also provided. The insulating block also includes a second channel for receiving a first end of a second conductor tube. The first and second channels are connected in the insulating block by means of a hollow fluid bridge to transport fluid from the second end of the first conductor tube to the first end of the second conductor tube. Detection means are provided to signal the presence of a connection When the electrical between the first and second conductive tubes when the blood of a patient flows through the fluid bridge, thereby indicating a loss of blood from the circuit outside the body in accordance with a further aspect of the present invention, a detector is provided. of air to be used in connection to an online system to treat a patient's blood outside the body. First and second oscillators are placed on opposite sides of a bleeding line to transport the patient's blood through the in-line system. A signal transmitter is coupled to the first oscillator, and a signal receiver is coupled to the second oscillator. A microprocessor is coupled to the signal transmitter and the signal receiver. The microprocessor includes comparison means for comparing signals transmitted by the signal transmitter to signals received by the signal receiver. The microprocessor also includes means for detecting air, sensitive to the means of comparison, to signal the presence of air in the blood transmission line. In accordance with a further aspect of the present invention, there is provided an improved method and apparatus for mixing first and second fluids that move in a combined laminar flow within a single fluid transmission line. The combined laminar flow is directed towards a fluid mixer through an entrance door to the mixer. Then, the combined laminar flow passes through a mesh material located within the fluid mixer, thereby forming a mixture of the first and second fluids.

DETAILED DESCRIPTION OF THE PREFERRED MODALITY Referring now to Figure 1, a stepped diagram of an in-line out-of-body i-arrhythmic treatment system 100 operating in accordance with a preferred embodiment of the present invention is shown. FU system 100 operates of forms that are performed in a repetitive manner for a plurality of cycles during a treatment session, in the obtaining mode, system 100 obtains whole blood from patient 10, adds a controlled amount Precisely of medicament solution to the whole blood through a syringe pump 50, and supplies the mixture of medicament solution and whole blood to the reaction chamber 85 for processing. After the blood in the reaction chamber 85 has been treated, the system 100 is diverted to a return ear, during which the treated blood is pumped by means of the blood pump 30 into the return bag 60. When the contents of the reaction chamber 85 have been pumped into the return bowl 60, the system 100 is diverted towards a reinfusion time during which the whole blood treated from the return bag 60 is returned to the patient 10 by pressure of gravity. In a first embodiment (shown in Figure 2), the system 100 cycles successively through its three modes ten times during a treatment session. In each of said cycles, as little as 150 rnl of whole blood can be obtained, treated and returned (or re-infused) in the patient 10. In alternative embodiments of the system shown in Figure 2, an operator can vary both the number of cycles of treatment as the volume of whole blood that is treated in each cycle. As shown in Figure 2, system 100 is preferably primed with a saline solution before the initiation of the treatment session. In a second preferred embodiment (shown in Figure 2A), system 100 repeats its three modes ten times during a treatment session. Nevertheless, in contrast to the system of the figure? , in this embodiment the treatment procedure is rushed after the first volume of blood in was obtained, treated and emptied into the return bag 60. In the system of figure 2A, after the first volume of Whole blood has been obtained, treated and emptied into the return bag 60, a second volume of blood is collected from the patient 10, mixed with a medicament solution and supplied to the reaction chamber 85. Then, the second volume of blood in the reaction chamber 85 is treated while at the same time the blood in the return bag 60 (of the previous treatment cycle) is simultaneously reinfused to the patient 10. It was found that the total treatment time for a patient could be reduced by effecting the treatment and reinfusion steps simultaneously. In addition, it was found that blood line 12 was less prone to coagulate when the treatment and reinfusion steps were performed simultaneously since this reduced the time that blood line 12 is stagnant or inactive. As was the case with the system of FIG. 2, in the system of FIG. 2, as little as 150 ml of whole blood can be collected, treated, and the patient left in each treatment cycle. However, in alternative embodiments, an operator may vary both the number of treatment cycles or the volume of whole blood that is treated in each cycle. As discussed in more detail below, the blood flow through the entire system 100 is controlled precisely throughout the treatment session by means of the crossprocessor controller 45 which controls both the flow rate and the blood direction in the circuit outside the body. Among other devices, the microprocessor controller 45 is coupled to both the blood pump 80 and the syringe pump 50, as well as the solenoid-operated jaws 65, 70, 75. During the method of obtaining the system 100, the pump of blood 80 pumps whole blood from the pressure pad reservoir 35 into the reaction chamber 85. When the whole blood flows out of the pressure bearing reservoir 35, the syringe pump 50 injects a medicament solution into the blood circuit to a controlled speed. In the obtaining mode, the microprocessor controller 45 controls the direction of flow of the whole blood in the circuit outside the body by placing the jaws 65, 70 in a closed position, while the jaw 75 is placed in an open position. During the return mode of the system 100, the direction of the blood pump 80 is reversed, and the blood pump 80 pumps the whole blood treated from the reaction chamber 85 to the return bowl 60. In the return, the microprocessor controller 45 controls the direction of the treated blood in the circuit outside the body by opening the jaw 70, keeping the jaws 65, 75 in a closed position. Finally, during the reinfusion mode, the treated blood from the return bag 60 flows by gravity first to the pressure bearing reservoir 35, and then back to the patient. In the preferred embodiment, the same needle was used to collect blood from patient 10 in the obtaining mode as for reinfusion of the treated blood to the patient. In the reinfusion mode, the controller 45 of the microprocessor controls the blood flow in the circuit outside the body by opening the fastener 65, at the same time keeping the fasteners 70, 75 in a closed position. Against this view of the operation of the present invention, the details of the system 100 will be described more fully below. Referring once again to Figure 1, during the procurement mode, whole blood is withdrawn from patient 10 through a needle and provided to system 100 through disposable blood tube 12. The patient's blood flows preferably by gravity in the pressure pad reservoir 35. Before reaching the pressure pad reservoir 35, the blood of the patient is anticoagulated by an anticoagulation pump 15, which supplies hepapna from the bag 20 to the patient's blood. The whole blood in the pressure pad reservoir 35 is pumped into the reaction chamber 85 by the blood pump 80 at a rate controlled by the controller 45 of the microprocessor. During the obtaining mode, the pressure pad detector 40 continuously detects the blood level in the reservoir 35 and generates a representative signal of the reservoir level to the controller-45 of the initiator processor. If the blood level in the reservoir 35 falls below the predetermined threshold, the pump speed of the pump 00 is reduced to (eg until said time as the blood level in the reservoir 35 exceeds the predetermined minimum level. purpose behind the speed reduction of the pump 80 when it is ba or the blood level in the reservoir 35, is to ensure that the blood flow of the patient 10 is driven completely by gravity and that the blood is never pumped out of the patient by the blood pump 80. The pad detector 40 can be made of any different type of detector such as electromechanical, optical, ultrasonic, or piezoelectric detector or, in an alternate embodiment, the pump speed of the pump 80 can Gradually lower as the blood level in the pressure pad reservoir decreases As the pump 80 pumps the whole blood from the pressure pad reservoir 35 into the reaction chamber 85 during the obtaining mode, a liquid drug is pumped into the blood circuit of the syringe pump 50 at a rate controlled by the controller 45 of the microprocessor. In the calculation of the syringe pump speed, the microprocessor controller 45 actually enslaves the pumping speed of the syringe pump 50 to the pumping speed of the blood pump 80, so that the syringe pump 50 injects drug solution in the blood circuit only when the blood pump 80 is in an on state. Also, as described more fully afterwards together <In Figure 3, the syringe pump 50 operates at an increased pumping rate during the first cycle of a treatment session in order to compensate for the drug absorption by the tube and other materials forming the system. After injection by the syringe pump 50 of the drug solution in the out-of-body circuit, the blood stream, combined with the liquid drug assortment, flows in a specially designed drug mixer 55 wherein the two unmixed streams Relatively (i.e., the whole blood stream and the drug solution stream) are divided and mixed to form a mixture of whole blood drug solution which is pumped by the pump 80 into the reaction chamber 85. Other details of the drug mixer 55 are set forth below in conjunction with the description of Figure 6. In a preferred embodiment of the present invention, a photoactivatable agent, such as no psoralen, and still more preferred 8-methoxypsoralen, in liquid form is injected into the blood circuit by the syringe pump 50 during the method of obtaining the system 100, although other solutions can also be used of drugs or biologics, such as rnonoclonal antibody solutions or other photoac ivable agents. Also in a preferred embodiment, the reaction chamber 85 constitutes a rotating centrifuge that includes within it a photo-activation system for irradiating the mixture of whole blood drug solution with UV light as it rotates centrifugally. A preferred reaction chamber 85 including a photo-activation system within it is illustrated and operates substantially as shown and described in US Pat. No. 4,921,473, the description of said patent is incorporated herein by r ferenci. Although in the preferred modality of the system 100, the whole blood of a patient 10 is obtained and provided to the system for treatment and then re-infused into the patient, it will be understood by those skilled in the art that blood provided from other sources, such as, for example, a center The donor (not shown) may be provided to the system 100 for treatment. Where blood obtained from a donor center is provided to the system 100 for treatment, the treated blood can be infused directly into a patient by the system 100 or obtained in a container (not shown) and infused into a patient at a later time. Furthermore, although in the preferred embodiment, the system 100 operates to treat whole blood, it will be understood by those skilled in the art that blood formed from the fractional components of the whole blood can also be treated by the 100 system. Refer now to Figure 3, there is shown a flow diagram illustrating a system 300 for operating the blood pump 80 and syringe pump 50 in accordance with a preferred embodiment of the present invention. When the system 100 is operating in its obtaining mode, the operating speed of the blood pump 80 is set such that the pumping speed is less than the bleeding flow of the patient 10 to the pressure pad reservoir. 35. Accordingly, during normal operation, the pressure pad reservoir 35 must remain completely filled with the patient's blood. However, if the patient's blood flow to the pressure pad reservoir 35 decreases for any reason, the volume of blood within the pressure pad reservoir 35 may decrease over time causing the pressure pad reservoir to collapse. 35. This undesirable situation is prevented by the pad detector 40 which detects the level of the blood in the pressure pad reservoir 35 and signals this condition to the controller 45 of the microprocessor. If the blood level in the pressure pad reservoir 35 decreases, the microprocessor control system 45 decreases the blood pumping rates of the pumps 50 and 80. This feedback mechanism helps the patient 10 to receive uninterrupted treatment and more insurance. The operation of the realization system described generally in the immediately preceding paragraph is illustrated in more detail as the realization system 300 in FIG. 3. Still referring to FIG. 3, the system 300 begins in step 310 controlling the pressure pad detector 40 to determine the blood level in the reservoir 35. A control signal representative of the blood level in the reservoir is then provided to the microprocessor controller 45 by the detector 45. In step 320 , the controller 45 of the microprocessor determines, in response to the control signal received from the detector 40, whether the blood level in the pressure pad reservoir 35 has fallen below a predetermined level, thus indicating that the reservoir has collapsed. pressure pad 35. If a determination is made that the pressure pad reservoir 35 has collapsed, then the processing proceeds to step 330, wherein the microprocessor 45 sends control signals to the pumps 50 and 80 using both pumps to an OFF state. Alternatively, if a determination is made in step 320 that the pressure pad reservoir 35 has not collapsed, then the processing proceeds to step 340, wherein the microprocessor 45 sends a control signal to the pump 80 by adjusting said pump. to an on state. Then, in step 350, the controller 45 of the microprocessor determines whether the system 100 is operating in the first cycle of a treatment session. If the system 100 is in the first cycle of the treatment session, the controller 45 of the microprocessor sends a signal to the syringe pump 50 by turning said pump to an on state and adjusting its pump speed to a first speed (Rll. Alternatively, if the system 100 is not in the first cycle of the treatment session, the microprocessor controller 45 sends a control signal to the inga pump 50 by turning said pump to an on state and adjusting its pump speed to a second one. speed (R2) that is less than (Rl). In the preferred embodiment, an increased pumping rate (Rl) is used in the first cycle to compensate for the drug absorption rate of the tube and other materials that make up system 100. After adjusting the pumping speed of the syringe pump 50, the processing proceeds to step 380, wherein the controller 45 of the microprocessor determines whether the volume of the whole blood to be treated in the current cycle has been provided to the reaction chamber 85 by the pump 80. controller 40 of the microprocessor determines whether the cycle volume has been reached by repeatedly controlling the state and pumping speed of the blood pump 80 during the procurement mode. If the cycle volume has not been reached, the system 300 returns to step 310 and the procedure described above is repeated; otherwise, the processing proceeds to step 390. In step 390, the controller 45 of the microprocessor sends control signals to the pumps 50 and 80 by setting both pumps to a OFF state. Referring now to FIGS. 4, 4A, there is shown a flow diagram illustrating the operation of an irradiation time control system 400 for controlling the irradiation time of the blood contained in the reaction chamber 85 during the mode of treatment of the system 100 in accordance with a preferred embodiment of the present invention. During < > In this manner, a continuous flow of blood obtained from patient 10 is mixed with a solution of medicament and provided to reaction chamber 85 by blood pump 80. As previously mentioned, in the preferred embodiment , the reaction chamber 85 is a centrifuge illustrating an internal photoactivation system for irradiating the patient's blood with UV light. In the present invention, system 100 does not wait until the entire blood cycle volume (described in connection with step 350 above) is received in the centrifuge chamber before beginning to irradiate the patient's blood with UV light. Instead, on a continuous basis as the blood is received in the chamber 85 during the treatment mode, the blood is separated into its constituent parts by the rotating centrifuge and then irradiated by the UV lights placed inside the chamber. centrifuge. By separating and irradiating the patient's blood on a continuous basis during the obtaining mode, the present invention minimizes the treatment time for the patient 10. The operation of the time control system The irradiation generally described in FIG. immediately preceding paragraph, is illustrated in detail as system 400 in figure 4. Still referring to figure 4, system 400 starts at the beginning of the treatment period in step 405 by initiating a remaining irradiation time value (Ti) at a seed value (Ts) »The remaining irradiation time value is a test value that is incremented and decreased repeatedly, and that represents the time remaining (in seconds) during which the blood in chamber 85 is undergo UV light before returning and re-infusing said blood into the patient. The seed value (Ts) is adjusted to compensate for the fact that the UV light of the photoactivation system can not penetrate whole blood, but said light can only penetrate through a layer of wet lymph coating. Since it takes approximately 2-3 minutes for the whole blood to be received in a rotating centrifuge to separate into its constituent parts, any UV applied to the blood during these initial 2-3 minutes is useless for purposes of treating the blood. Therefore, in the preferred embodiment, T «is preferably set between 120-180 seconds in the initialization step 405, the time marker Tprew is set to zero, and a volume marker Vpr« v is set to zero., By setting Tprtv and Vprtv to zero, the micialization step 405 means that the irradiation step starts at time zero with the camera 85 in an empty state. After step 405, a determination is made in step '+10 with respect to the common volume of blood (VCOmun) in chamber 05. Since blood is continuously being pumped into chamber 85 at least during part of the treatment mode, the value of Vcomún will vary with time. The microprocessor controller 45 determines the temperature by monitoring the state and speed of the pump 80 through each cycle of processing. In step 415, a change in blood volume (deltaV) is determined by differentiating V Omún and VP r e v, and in step 420 replacing V r. with Vcomún. In step 425, the time has elapsed since the irradiation step initialization (Tcomún) has been saved. In step 430, a change in elapsed time (deltaT) is determined by differentiating Tcomun and Tprev, and in step 435 Tprßv is substituted with Tcomún- In step 440, the cumulative value of light energy (UV cum), which represents the total light energy provided to the blood in chamber 85 during the treatment cycle, is calculated. In order to determine this cumulative value of light energy, the microprocessor controller 45 monitors the state (on / off) of the ultraviolet lamps in the chamber 85 during the treatment cycle. In addition, the microprocessor controller 45 maintains a current record of the age (used in hours) of each focus in the camera 85 and adjusts the cumulative value of luminous enrichment by the fact that the light energy emitted by each focus decreases as the Although Figure 4, the steps to determine deltaV (steps 410, 415, 420), deltaT (steps 425, 430, 435) and UVC um (step 440) are shown in parallel, these values can also be determined sequentially. In the preferred embodiment of system 400, deltaV is determined 40 times per second, while deltaT and UVCum are determined 5 times per second. Frequent calculations of these value-s are important to ensure that the transition from Ti to zero is abducted at once. In step 445, after the calculation of deltaV, deltaT and UVcum, Vcomún is compared with a threshold (V m) representing the minimum volume of blood that activates the terms deltaV and deltaT during the calculation of Ti in step 485 (described later). If V common is greater than or equal to Vmi n, then step 450 adjusts the rate constants for the first (A) and second (B) irradiation time to one. If Vcomun is not greater than or equal to Vmin .. then in step 455 UVcum is compared to a threshold (UVm? N). If UVCum is greater than or equal to UVmin, then in step 460 the constants A and B of the first and second irradiation time calculation are set to zero and one respectively; otherwise, in step 465, in the constants A and B of calculation of the first and second irradiation time, both are set to zero. A preferred value of UVmln is 300. In step 470, the system 400 determines (or confirms) whether the ultraviolet lights in the camera 85 are in the on state. A preferred circuit for determining the state of the ultraviolet lights in the camera 85 is described below in connection with Figure 8. If the step 470 determines that the ultraviolet lights are in the on state, then a third of the constant of calculation of the irradiation time (U) was adjusted to one in step 475; from otr < Thus, the third constant of the calculation of time of u ation (U) is set to zero. After the determination of the three constants of the irradiation time calculation, the processor controller 45 updates the value of Ti according to equation (1) below: Ti = Ti + (A * C * deltaV) - (B * U * deltaT) (l) wherein, C is a constant representing the number of seconds of the irradiation time to be added to the remaining irradiation time Ti as each millimeter of blood is added to chamber 85. In step 490, IT is compared to a threshold of zero. If Ti is not greater than zero, this indicates that the irradiation step is over; otherwise, the procedure is repeated as shown in Figure 4 until Ti reaches or falls below the threshold of zero. Referring once again to Figure 1, the preferred embodiment of the 100 mc system includes a multitude of 2H detectors. air 25, 30 to detect the presence of air in the circuit outside the body. In the preferred embodiment, if air is detected in system 100, an alarm is generated that immediately informs an operator that air has been detected. Referred now to Figure 5, a block diagram of a detector 25, 10 is shown. The first and second oscillators 505, 510 are placed on opposite sides of the transmission line 12 of the blood to transport the patient's blood through the blood. s of the online system. The first and second crystal oscillators 505, 510 are held in place by the air detector assembly block 515 having cavities that are adapted to receive the oscillators 505, 510. A signal transducer 520 is electrically coupled to the first oscillator 505 and a signal receiver 525 is electrically coupled to the second oscillator 510. The microprocessor controller 505 is coupled to the signal transmitter 520 and the signal receiver 525. The icroprocessor controller 45 includes comparison means to periodically compare the transmitted signals by the signal transmitter 520 with the signals received by the signal receiver 525. Since the transmitter 520 repeatedly broadcasts the same signal, the unexpected changes of the signals received by the receiver 525 indicate the presence of air in the tube 12. The microprocessor controller 45 includes air detection means, sensitive to the comparison means, to indicate with signals the presence of air in the blood transfer line when there is an unexpected change in the signal received by the receiver 525. In the preferred embodiment of the present invention, the operation of each air detector 25, 30 is subjected to to test periodically to verify that it is functioning properly. In particular, with periodic basis, the signal transmitter 520 is turned off and any signal received by the receiver 525 is monitored by the microprocessor controller 45. If an unexpected signal, during this verification test, is received by the receiver 525, it is condition would indicate that the air detector is not operating properly either because the output of the transponder 520 is jammed or for some other reason. In the preferred embodiment, if the icroprocessor controller 45 deems that an air detector is not functioning properly, an alarm is sounded by signaling the state of the system to an operator. Although in Figure 1, the air detectors 25, 30 are placed adjacent to an anticoagulation pump 15 and a mixer 55, respectively, it will be understood by the expectations of the art that the detectors 25, 30 may be placed throughout the system 100. It will also be understood by those skilled in the art that air detectors 25, 30 may be used to detect the presence of air in fluid circuits other than blood circuits outside the body. Referring to time to Figure 6, a side view of a drug mixer 55 for mixing a drug solution with a patient's blood within a blood circuit outside the body is shown according to the preferred embodiment of the present invention. . The mixer 55 is formed of a sealed hollow chamber 610 with an opening 600 for receiving the unmixed fluids and an opening 650 for drawing out the mixed fluids. The interior of the 610 chamber is divided into the compartments 620 and 630 by a 640 mesh bag that is attached in a circular fashion along the length of the interior.; -o opening 660 to the interior- of the hollow chamber 610. During the operation of the fluid eraser 55, the first and second fluids that move in a combined laminar flow within a single fluid transfer line are provided to the mixer 55 through the inlet port 600. The combined laminar flow is then passed through the 640 mesh bag placed within the fluid mixer, thereby forming a mixture of the first and second fluids. The 640 mesh bag achieves efficient mixing of the first and second fluids by interrupting the combined laminar flow of these fluids. When the mixer 55 is used to mix the blood with other solutions, the 640 mesh preferably has a hole size between 100 and 600 microns. It will be understood by those skilled in the art that the mixer 55 can be used to mix different fluids of blood, and can be used in different applications of blood circuits outside the body.

In the preferred embodiment of the present invention, the system 100 includes means for detecting blood loss of the circuit outside the body. Such blood loss could occur - for example, if a hole or crack is formed in the treatment center chamber, or if an overflow condition develops within the centrifuge chamber. When the LOO system detects that blood is being lost from the circuit outside the body, an alarm is triggered signaling this event to an operator. Referring now to Figure 7, a block diagram of a preferred system 700 for detecting blood loss from system 100 is shown according to the preferred embodiment of the present invention. In the preferred embodiment, the reaction chamber 85 includes an outer housing (not shown) for detecting any leakage or overflow of the reaction chamber. The lowermost portion of this outer housing is connected to a drain line 710 to remove any blood that leaks or spills into the outer housing. In the system 700, a first electrically conductive tube 720 having a first end coupled to a drain line 710 is provided. An insulating block 730 having a first hollow channel 735 for receiving a second end of the first conductive tube 710 is also provided. The insulating block 730 is not electrically conductive. The insulating block 730 further includes a second hollow channel 740 for receiving an end prirner of a second conductive tube 750. The hollow channels-second and second 735, 740 are connected in the insulating block 730 by a hollow fluid bridge 755? to? to convey fluid from the second end of the first conductive tube 720 to the first end of the second electrically conductive tube 750. A comparator circuit 760 is provided to detect the presence of an electrical connection between the first and second conductive tubes 720, 750. Since the conductivity of the blood flow through the hollow fluid bridge 755 is sufficient to form an electrical connection between the first and second conduits 720, 750, the comparator circuit 760 will detect an electrical connection between the conductive tubes whenever blood flows through the hollow fluid bridge 755, thus signaling a loss of blood from the circuit outside the body. The output of the comparator circuit 760 is coupled to a latch relay circuit 770 which causes the closing of the blood pump 80 and the sound of an audible alarm whenever an electrical connection is detected between the first and second conductive tubes 720, 750 As discussed above in connection with the Figure 4, in year 470 of system 400, the present invention repeatedly repeats the state (on / off) of ultraviolet irradiation lamps within reaction chamber 85. Referring now to Figure 8, a diagram is shown circuitry of a preferred system 800 for monitoring the status of an irradiation lamp 810 positioned within a centrifuge chamber according to the preferred embodiment of the present invention. In the system 800, a sine wave generator 820 and a resistor 330 are placed in series with an irradiation lamp 810. When the lamp 810 is in an energized state, a voltage is generated across the resistor 830, thus causing a logic signal 0 at the output of circuit 840. Alternatively, when lamp 810 is in an off state, no volatility is generated through resistor 830 and the output of circuit 840 will be a logic signal 1. Fn The preferred embodiment of In the present invention, 3 separate irradiation lamps are located within the chamber 85, and a separate system 800 is coupled to each of these lamps, so that the status of each lamp can be monitored separately during the procedure. of the treatment. Finally, referring now to figures 9, 9A, front views of a preferred embodiment of the syringe pump 50 according to the present invention are shown. The syringe pump 50 includes a mounting block 900 for rigidly receiving a portion of the body of a syringe 910. The syringe 910 is preferably a glass syringe and filled with a medicament solution. The syringe 910 is coupled (at the syringe tip 910) to the blood circuit outside the body. A push block 930 is slidably secured to the mounting block 900 by a pair of metal rods 940, 950 located on opposite sides of the plunger portion 960 of the syringe 910. In the preferred embodiment, the push block 930 includes a plunger fastening opening 970 for securing the upper end of the piston portion 960 to the thrust block 930. The opening (plunger holder 970 in the thrust block 930 is configured to prevent the in-line system from extracting the Solution of the syringe drug 910 when this negative pressure in the blood path connected to the tip 920 is expelled. Impulse means (not shown, but located behind the blocks 900, 930 in FIGS. 9, 9A), coupled to the Mounting block 900 and push block 930 are provided to carry thrust block 930 to mounting block 900 in response to a control signal provided by the microprocessor controller 45. This is communicate the control pulse to the means whether syringe pump 50 should be pumping at rate Rl or R2 speed, or if the pump 50 should be in an off state. In the preferred embodiment, the drive means used to bring the push block 930 to the mounting block 900 is a worm push mechanism. In the preferred embodiment of the present invention, the syringe pump 50 includes a safety latch 980 which prevents the system 100 from operating, unless the syringe 910 has been installed in the mounting block 910. Figure 9 shows the latch. 980 security in its open position; and Figure 9A shows the safety lock 980 in its closed or locked position. A control signal prevents the operation of the present invention provided that the lock 980 is in the open position. Those skilled in the art will understand that the syringe pump 50 can be used to accurately deliver controlled amounts of fluids apart from medicament solutions and in environments away from blood circuits outside the body. In addition, those skilled in the art will also understand that the system 100 has applications in dynamic liquid mixing environments including any bleeding out of body, where the drug solution or any biological solution, such as solutions of monoclonal antibodies, they need to be added in the blood or other circuit at precisely controlled rate and be well mixed before entering the treatment chamber. The present invention may be expressed in other specific forms without departing from the spirit or essential attributes of the invention. Accordingly, reference should be made to the appended claims, rather than to the above specification, as indicated by the scope of the invention. 16 FIGURE 2 100 MSTFMA PRIMER 101 OBTAINING-BLOOD TREATMENT 102 SANGREST RETURN 103 BLOOD RE-INFRONED FIGURE 2A 200 SYSTEM PRIMER 201 OBTAINING-TRAIL 202 BLOOD RETURN 203 GETTING BLOOD 204 TREATMENT BLOOD R 205 RETURN DF BLOOD 206 RF- BLOOD INFUSION

Claims (38)

NOVELTY OF THE INVENTION CLAIMS

1. - An online method for treating blood outside the body, comprising the steps of: (A) obtaining blood from a blood stream; (B) mixing said obtained blood with a medicament solution and thereby forming a mixture of blood-drug solution; (C) a quantity of treated blood was introduced by introducing said blood mixture-drug solution into a treatment chamber and exposing said mixture of blood-drug solution to radiation; and (D) emptying said amount of treated blood from said treatment chamber and storing said amount of treated blood in a return storage container.

2. The method of claim 1, wherein said source of blood is a patient, further comprising the step of: (E) remfunding said amount of blood treated in said patient.

3. The method of claim 2, further comprising the step of: (F) repeating steps (A) - (E) a plurality of times during a single treatment session of said patient.

4. The method of claim 3, wherein a single needle is used to obtain the blood of said patient in step (A) and to reinfuse said amount of blood treated in said relative in step (E).

5. The method of claim 4, wherein said treatment chamber is a centrifuge chamber.

6. The method of claim 5, wherein said step of obtaining blood from said patient further comprises the steps of: (1) opening a blood for the patient located along a path of blood transmission between said Patient and said song of centrifuge; (2) closing a return clamp located along said blood transmission path between said centrifuge chamber and said return storage container; and (3) closing a reinfusion clamp located along said blood transmission path between said return storage container and said patient.

7. The method of claim 6, wherein said step of emptying said amount of treated blood from said centrum chamber further comprises the steps of: (1) closing said patient's clamp located along said route of blood transmission between said patient and said centrifuge chamber; and (2) opening said return clamp located along said blood transmission path between said centrifuge chamber and said return storage container.

8. The method of claim 7, wherein said step of reinfunding said amount of blood treatment treated in said patient further comprises the steps of: (1) closing said return clamp located along said transmission a blood between said centrifuge chamber and said return storage container; and (2) closing said patient clamp located along said blood transmission path between said centrifuge chamber and said patient.

9. The method of claim 3, wherein a quantity of treated blood formed during a previous cycle is remunded in said patient during step (0).

10. The method of claim 1, wherein said blood is whole blood.

11. The method of claim 1, wherein said blood represents a fractional component of whole blood.

12. An online method for treating blood outside the body, comprising the steps of: (A) continuously providing a blood flow obtained from a patient in a rotating centrifuge chamber; (B) and irradiating with blood light commonly contained in said rotating centrifuge chamber as said blood flow obtained from said patient is being received by said rotary centrifuge chamber; (C) monitoring, during said irradiation step, a change in blood volume contained in said rotating centrifuge chamber for a period; (D) moni ore, during said step of irradiation, a cumulative value of light energy representing total light energy provided to the blood in said rotating centrifuge chamber during said irradiation step; (E) determining, during said irradiation step, a remaining value of irradiation time in accordance with said change in blood volume commonly contained in said rotating centrifuge chamber and said cumulative value of light energy; (F) determining whether said irradiation step concludes by comparing said remaining value of irradiation time with a predetermined constant; (G),? said comparison of said remaining value of irradiation time with said predetermined constant in step (F) does not indicate that said irradiation step has concluded, then repeated steps (C) ~ (F) until said comparison of said remaining value of irradiation time with said predetermined constant in step (F) does not indicate that said irradiation step has ended; and (H) returning said blood contained in said centrifuge to said patient after said irradiation step has concluded.

13. - The method of claim 12, further comprising the steps of initiating said remaining value of irradiation time and a previous volume value before said irradiation step.

14. The method of confomi ad with claim 13, wherein step (C) comprises the steps of: (1) determining a common volume of blood contained in said rotating centrifuge chamber at the end of said period of time; (2) determining said change in blood volume by differentiating said common volume and said previous volume value; and (3) replacing said previous volume value with said common volume.

15.- The method according to the claim 14, further comprising the step of monitoring, during said irradiation step, whether the lights in said rotating centrifugal chamber are in an on state.

16. The method according to claim 15, wherein step (F) comprises the steps of: (1) comparing said common volume with a predetermined volume threshold; (2) comparing said cumulative light energy value with a predetermined light energy threshold; (3) initiating first and second radiation time constants to zero; (4) if said common volume is equal to or exceeds the predetermined volume threshold, scheduling said first and second irradiation time constants to one another, if said cumulative luminous energy-value is equal to or exceeds said threshold of light energy predetermined then programming said second irradiation time constant to one otherwise, if said cumulative luminous energy value is equal to or exceeds said predetermined light energy threshold then programming said second irradiation time constant to one; and (5) adjusting said remaining irradiation time in accordance with said change in blood volume, said first and second irradiation time constants and said monitoring of said lights in said rotating centrifugal chamber.

17. An online method for supplying out of the body a predetermined concentration of a medicinal solution within the blood of a patient, comprising the steps of: (A) extracting blood from said patient and introducing said extracted blood into a reservoir of blood; (B) pumping-said blood drawn from said blood reservoir into a blood line at a first pumping rate; (C) detecting a level of blood deposit in response to said extracted blood remaining in said blood pool to determine a detected level of blood deposit; (D) adjusting said first pumping rate in response to said detected level of blood deposition; (E) pumping said medicinal solution into said blood line at a second pumping rate; (F) adjusting said second pumping rate in response to said first pumping speed; (G) mixing said blood drawn in said blood line with said medicinal solution in said blood line; and (H) returning said extracted blood to said patient after said mixing step.

18.- The method of compliance with the claim 17, further comprising the step of delivering said extracted blood and said medicinal solution to a reaction chamber after said mixing step and before said extracted blood is returned to said patient.

19. - The method according to claim 17, further comprising the step of repeating steps (A) - (H) during a plurality of treatment cycles, and wherein said second pump speed is adjusted upwardly during a first cycle of treatment to compensate for a drug absorption rate associated with said line of san re.

20. The method according to claim 17, wherein said second pumping speed depends on said first pumping speed.

21. The method of compliance with the claim 17, wherein said mixing step is achieved only by the simultaneous flow of said extracted blood and said medicinal solution in said blood line.

22. The method according to the claim 18, wherein said reaction chamber is a photo-activation chamber.

23. The method according to claim 22, wherein said medicinal solution contains a psoralen.

24.- The method of compliance with the claim 17, in which a syringe pump is used to pump said medicinal solution, inside said blood line in step (E).

25. In an online system for supplying out of the body a predetermined concentration of a medicinal solution in the blood of a patient, a syringe pump comprising: (A) a mounting block for rigidly receiving a portion of the body of a patient; a syringe, said syringe being filled with said medicinal solution and being coupled to a blood path in said on-line system; (B) a thrust block slidably secured to said mounting block, said thrust block having a plunger fastening opening for securing an upper end of a plunger portion of said syringe to said thrust block; (C) driving means, coupled to said mounting block and said thrust block, for driving said thrust block toward said mounting block in response to a control signal; and wherein said plunger clamping opening prevents said in-line system from deviating from said medical solution of said syringe when there is a negative pressure in said blood path.

26. The syringe pump according to claim 25, further comprising first and second bars positioned on opposite sides of said syringe to ensure said thrust block slidable to said mounting block.

27. The syringe pump according to claim 25, further comprising a microprocessor controller for providing said control signal to said driving means.

28. The syringe pump according to claim 25, wherein said driving means is 4F > formed from a worm driver.

29. The syringe pump according to claim 25, further comprising a safety to prevent the operation of said system in line in the absence of said body portion of said syringe that is positioned in said assembly block.

30.- In an online system for treating a patient's blood outside the body, said system includes a reaction chamber to process said patient's blood, a reaction chamber, and a drain line to remove the blood. of said on-line system, a blood loss detector comprising: (A) first and second electrically conductive tubes, said first conductive tube having a first end coupled to said drainage line; (B) an insulator block having a first channel for receiving a second end of said first conductor tube, said insulator block having a second channel for receiving a first end of said second conductor tube, said first and second channels being connected in said b) The fluid by means of a fluid bridge to carry fluid from said second end of said first conductor tube to said first end of said second conductor tube; (C) detection means for signaling the presence of an electrical connection between said first and second conductive tubes when said patient's blood flows through said fluid bridge.

31. The blood loss detector according to claim 30, further characterized in that said detection means comprise a comparator having first and second comparator inputs, said first comparator input being electrically connected to said first conductive tube. , said second * comparator input- being electrically connected to said second conductor tube.

32. The blood loss detector according to claim 31, wherein said first comparator input is coupled to a positive voltage source and said second comparator input is coupled to ground.

33 .- Fn an online system to treat outside the body of a patient's blood, said system includes a blood transmission line to transport said patient's blood through said system, a detector of ai e comprising: ( A) first and second oscillators positioned on opposite sides of said transmission line; (B) a signal-transmitter coupled to said first oscillator; (C) a signal receiver coupled to said second oscillator; (D) a microprocessor - coupled to said signal transmitter and said signal receiver, said microprocessor includes comparison means for comparing the signals transmitted by said signal transmitter with signals received by said signal receiver, said microprocessor also includes detection means of air that respond to said comparative means, to signal the presence of air in said transmission line.

34. The air detector according to claim 33, said microprocessor further comprising means for periodically testing said signal transmitter and said signal receiver, periodically turning off said signal transmitter and monitoring signals received by said signal receiver.

35. The air detector according to claim 33, wherein said first and second oscillators are cpstaL oscillators.

36.- A method for mixing first and second fluids that move in a combined laminar flow within a single fluid transmission line, comprising the steps: (A) providing said combined laminar flow to a fluid mixer before a mixer inlet port; (B) passing said combined laminar flow through a mesh material positioned within said fluid mixer and there forming a mixture of said first and second fluids; and (C) outputs said mixture of said first and second fluids from an outlet port of the mixer.

37. The method according to claim 36, wherein said first fluid is whole blood and said second fluid is a medicinal solution.

38. The method according to claim 37, wherein said mesh has a hole size between 100 and 600 microns.