Abstract:
A method and an apparatus for treatment of a first liquid which is a plasma of human blood comprising cyclically feeding the first liquid and a second liquid to the treatment device, and measuring a component of the first and second liquids so that a ratio between the first and second liquids are determined by a measuring arrangement. The first and second liquids are transferred to predetermined collection points by initiating and terminating a collection of the first liquid during one of the feeding cycles based on the ratio between the first and second liquids. The volume of at least the first liquid conveyed to the treatment device is measured during one of the cycles by a volume measuring arrangement. A theoretical time is determined between the initiating and terminating of the collection of the first liquid.

Description:
TECHNICAL FIELD 
     The present invention relates to a system for treatment of a first liquid in a treatment arrangement which is arranged to be filled alternately by said liquid and a second liquid, whereby the two liquids are periodically mixed with each other and means are arranged for measuring the content of respective liquids in order to convey, depending on the measured value, the principal component of the first liquid to a collection point therefor and the principal component of the second liquid to a second collection point, whereby the collection of the first liquid is initiated at a first mixing ratio and terminated at a second mixing ratio. These two mixing ratios are hereby preferably identical, though they can also be different. 
     The system according to the invention is primarily intended for treatment of a biological liquid, preferably blood plasma or whole blood. 
     Many sicknesses are a result of the body&#39;s immune system becoming unbalanced, whereby undesirable fractions are formed in the blood. For example, in haemophilia antibodies against factor VIII or factor IX can be formed, which normally control the blood&#39;s coagulation. 
     An object of the present invention is to remove such undesired fractions. Another object is to segregate the removed fractions for further use. For example, the antibodies against said factor VIII or factor IX can themselves be attached to a column for removal of the actual factor VIII or factor IX from other liquids such as blood or plasma from blood donors. 
     Should it be desired to remove said actual antibodies against factor VIII or factor IX, according to the invention a column is used with factor VIII or factor IX attached to a carrier. Alternatively, protein A or protein G, for example, can be attached to the carrier and have an ability to themselves attach to, amongst others, various different types of IgG. It should also be clear for the skilled man that the invention may also be used in connection with many other adsorption substances. 
     BACKGROUND ART 
     The invention can be said to be a direct further development of the art which is described in U.S. Pat. No. 4,708,714. The content of this patent is therefore included in the present description. 
     The known art is primarily intended for treatment of blood plasma which is alternately mixed with another liquid and whereby the mixture ratio is measured optically. Certain difficulties have manifested themselves through operation in the measuring instrument and also through variations in optical absorbency in the plasma during patient treatment. Variations can be caused by, for example, the patient eating. Employed measuring instruments have therefore often had to be recalibrated. Because of the measuring errors an unnecessarily large quantity of plasma has sometimes been discarded instead of being returned to the patient. 
     The present invention has therefore as its object to minimize the plasma loss in the system according to the American patent and simultaneously provide a safe, preferably automatic, calibration of measuring instruments used therefore. 
     DESCRIPTION OF THE INVENTION 
     The above-mentioned problems are solved according to the invention with help of a system of the above mentioned type which is characterized by means for measuring the quantity of the liquid conveyed to the treatment arrangement during one cycle and by means for theoretically calculating with help of said measured value the time instance at which the collection of the first liquid is to be terminated. If the invention is hereby applied to the technique described in the American patent, it becomes possible to return substantially the same volume to the patient as was taken from the patient and this with minimal plasma loss. 
     The system according to the invention is preferably provided with means for comparing the measured value for the mixing ratio between the two liquids at said theoretically calculated time instance with a desired value for the time instance when collection of the first liquid is to cease. In this way, it is possible to prolong the collection of the first liquid if the measured value shows that the mixture still contains a high content of the first liquid. 
     The system according to the invention can alternatively be provided with means for comparing the measured value for the mixing ratio between the two liquids at said theoretically calculated time instance with the measured value of the mixture ratio at the time instance when collection of the first liquid was started. These two values will often be identical, though they can also be in a certain proportion to each other. Preferably, means are hereby arranged to allow the measured values for the mixing ratio at the start and end respectively of the collection of the first liquid during a work cycle to control the value for the mixing ratio at the start of the next work cycle. Should it be desired, for example, to start and cease collection of the first liquid at identical mixture ratios, for example 50%, then the mean value of the two measured values during one work cycle can be allowed to dictate when the collection during the next work cycle will commence. 
     The system according to the invention is preferably provided with means for measuring said mixing ratio at a time instance or during a time period when only the first liquid is at the measuring site, for use of this measured value in calibrating the measuring arrangement. The measured value should hereby show 100% for the first liquid. If this is not the case, then calibration should be carried out. In practice, however, calibration of the system according to the invention occurs first if the measured value deviates more than a certain percentage, for example more than 2% or 5%. The calibration can be carried out either automatically or manually. 
     A further improved calibration is achieved if the system according to the invention is provided with means for measuring the mixing ratio at a time instance, or during a time period, when only the second liquid is at the measuring site, for use of this measured value for calibration of the measuring device. The measured value for the mixing ratio should hereby show 0% for the first liquid. If this is not the case, then calibration should be carried out. Even in this case, in practice a calibration according to the invention occurs only if the measured value deviates more than a certain percentage, for example 2% or 5%. 
     Preferably the calibration is arranged to take place first before the subsequent cycle for simplification of the comparison between values measured during one cycle. Alternatively, however, the calibration can be arranged to take place substantially immediately for quick attainment of the correct measured values. 
     As mentioned above, the system according to the invention is primarily intended to be used for treatment of a biological liquid, preferably blood plasma, whereby said treatment arrangement comprises an adsorption column for removal of non-desirable substances, such as anti-bodies, from the biological liquid. Preferably two columns are hereby used in parallel for alternate adsorption and elution of adsorbed substances, as described in said above mentioned American patent. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 shows schematically a block diagram of a system according to the invention. 
     FIG. 2 shows a time diagram for a work cycle in the system according to FIG. 1. 
     FIG. 3 shows a similar diagram for a part of the work cycle, though here a measured detector value is compared with the pumped volume of liquid. 
    
    
     BEST MODE OF CARRYING OUT THE INVENTION 
     Two columns A and B are shown in FIG. 1 which are intended to alternately adsorb undesired substances from plasma which, with help of a pump PP, is pumped from a source P for such plasma. The source can, for example, be connected via a plasma filter directly to a patient. 
     The plasma is supplied via a valve V2 either to a drop chamber ADA connected before the column A or to a drop chamber ADB connected before the column B. Both the drop chambers are provided with pressure measuring means PRA and PRB respectively, which, together with the pump PP and the valve V2, are connected to a microprocessor MC. A valve V1 and two pumps PA and PB are also connected to this microprocessor. With help of the valve V1 and the pump PB a buffer can be pumped from a source B of such a liquid to the column which is temporarily not being used for adsorption. In this way, plasma is displaced in said column which is controlled with help of preferably optical measuring means PDA and PDB. When the plasma is totally displaced, a second pump PA is instead connected which pumps an elution liquid, for example an acid, from a source AC for said liquid. The hereby eluted fraction is also controlled with help of the measuring means PDA and PDB, which are also connected to the microprocessor MC. The same applies for the subsequent valves V3 and V4. With help of these valves, the pumped liquid can thereafter be pumped to either a more accurate protein content measurer, for example a UV-measurer, or to a pH-measurer pHP. Both these measurers UV and pHP respectively are connected to the microprocessor MC. The pumped liquid thereafter reaches two valves V5 and V6, which are also connected to the microprocessor MC. Depending on the measured values from the two latter-mentioned measuring means, respective liquids are then conveyed either to a collection point F for the eluted fraction or to a collection point P&#39; for the plasma or to a drain or to other collection point W. The collection point P&#39; can, of course, be a patient who is under treatment with help of the system according to the invention. 
     In FIG. 2 there is shown a time cycle for plasma treatment, which is possible to implement with help of the system shown in FIG. 1. If we imagine that the time cycle concerns the column A, then the point a denotes the instance when the valve V2 begins to permit plasma to flow in the direction towards column A. The point b denotes the instance when the plasma reaches the measuring device PDA. The point c denotes the instance when the valve V3 begins to allow the flow of the plasma mixture towards the measurer pHP for further conveyance to the valve V6 and the collection point P&#39; for plasma. Should an unsuitable pH value be measured, the plasma mixture is instead conveyed via valve V6 to the collection point W, for example a sink. At the point d the measurer PDA shows a measured value which corresponds to 100% plasma. This measured value is suitably integrated in the microprocessor MC during a certain time period, for example up to the point e. The hereby integrated value is then used for calibration of the measuring means PDA. This calibration can either occur directly or first just before commencement of the next cycle. During the collection time for the plasma P, the volume of the liquid pumped to the column A is measured. This can be achieved, for example, by counting the number of pump revolutions of the pump PP. Just before the end of the collection period, however, the valves V1 and V2 change over and from this time instance the number of pump revolutions for the pump PB is instead calculated. The pumped quantity is stored in the microprocessor MC which, at the same time, calculates a theoretical time instance at which the collection of plasma is to be interrupted. At this time instance, which in FIG. 2 is denoted by f, the plasma collection can be interrupted. Preferably, however, the hereby measured value for the mixture ratio is compared with a desired value and if the first mentioned value is too high, the collection period can be prolonged, for example up to the point g. The hereby measured value of the mixture ratio is suitably used for control of the starting of the collection during the next work cycle. 
     The point h denotes the desired mixing ratio at the interruption of the plasma collection. This value is suitably the same for the points c and h, for example 50% plasma. 
     At the point i the measuring means PDA shows a measured value which corresponds to 0% plasma. At, or just after, this point the pump PB is stopped and the pump PA is instead activated which pumps elution liquid via the valve V1 and the drop chamber ADA to the column A. At the point j the measuring means PDA shows that the eluted fraction has reached the measuring means and at the point k the same measuring means shows that fraction no longer reaches it. The eluted fraction is collected via the valve V3, the measurer UV and the valve V5 at the collection point F therefor. The collection can hereby already begin before the point j and be interrupted after the point k. This means only that the fraction will be somewhat more diluted by either elution liquid from the source AC or buffer liquid from the source B. The point a then denotes the commencement of a new work cycle for the column A. The column B&#39;s work cycle is identical to that of column A, but commences with the changeover of valves V1 and V2 and, more precisely, at the point a&#39;. 
     The above described zero-calibration can occur either between the points i and j or between the points k and a. 
     The points a-i also appear in FIG. 3, which shows the measured value in either of the measuring means PDA or PDB in comparison with the volume pumped during a certain time period to either of the columns A and B. If it should be the column A, then the point a denotes the time instance when valve V2 switches over and begins to direct plasma towards the column A and the point i denotes the time instance when the measurer PDA can no longer detect any plasma in the pumped liquid. 
     FIG. 3 displays three curves, whereby the curve I denotes an ideal curve with a substantially correctly adjusted measuring device PDA during the whole time, whereby the plasma collection is started at the point c at the mixing ratio 50% and is interrupted at the point h at the same mixing ratio. 
     According to the curve II, the measurer PDA instead shows a maximum mixing ratio of 120% plasma depending on, for example, operation of the measuring device or the fact that the patient has eaten. This is discovered at the measuring instance e and the measured value is used for calibration of the measurer PDA either directly or just before the next work cycle. 
     According to the curve III, the measurer PDA in the same way shows a mixing ratio of 80%, when the value should instead be 100%. The measuring device is therefore calibrated in the other way. 
     FIG. 3 shows that with the correct measured values for the measurer PDA, plasma is collected during the whole time that the mixture contains more than 50% plasma. Should, however, the curve II be followed, plasma is collected already at the mixture ratio 50:120 and is interrupted, if the mixture ratio is allowed so to determine, at the same mixture ratio. This is not so important for the patient, but may give rise to a certain increase in the patient&#39;s weight. 
     Should, however, the curve III be followed, the plasma collection commences first with the mixture ratio 50:80 and is interrupted at the same mixture ratio. This is on the condition that the measured value is also allowed to interrupt the plasma collection. This condition is more dangerous since the patient can hereby lose a considerable quantity of plasma and can receive a lack of, for example, albumin. 
     According to the invention, however, the measured value of the mixture ratio is not allowed to interrupt the plasma collection on its own. Instead, this is interrupted, as described above, firstly depending on the liquid volume pumped to the adsorption column and secondly on the measured value at a theoretically calculated time instance at which the desired quantity of liquid has been pumped to the adsorption column. 
     Naturally, the invention is not restricted to solely the above described embodiment, but can be varied within the scope of the appended claims. For example, the time and volume conditions shown in FIGS. 2 and 3 can be varied within wide limits depending on the type of treatment.