Method and apparatus for sterilizing a dialyzer

Abstract

An apparatus for sterilizing a dialyzer for extracorporeal blood treatment includes a pulsed electric field generator arranged for generating a pulsed electric field penetrating the dialyzer received between a first electrode and a second electrode, when a pulsed electric voltage is applied between the first electrode and the second electrode of the generator. A method of sterilizing a dialyzer for extracorporeal blood treatment adapted to be executed using the apparatus incorporates, in a process for preparing or manufacturing the dialyzer, at least the steps of generating a pulsed electric field using a predetermined number of electric pulses of defined electric voltage, defined pulse duration and defined pulse-off time between the pulses, and applying the pulsed electric field to the dialyzer.

Claims

1. An apparatus for sterilizing a dialyzer for extracorporeal blood treatment, the apparatus comprising: a dialyzer having a liquid channel therein; a first electrode and a second electrode adapted to receive the dialyzer there between, wherein the liquid channel is electrically insulated from the first electrode and the second electrode; and a pulsed electric field generator coupled to the first and the second electrode, the pulsed electric field generator configured to generate a pulsed electric field that penetrates the dialyzer received between the first electrode and the second electrode by applying a pulsed electric voltage between the first electrode and the second electrode.

2. The apparatus according to claim 1, wherein the pulsed electric field generator includes a first section adapted to be disposed on a first end face of the dialyzer and a second section adapted to be disposed opposite to the first section on a second end face of the dialyzer.

3. The apparatus according to claim 2, wherein the first electrode is arranged in the first section and the second electrode is arranged in the second section so that the pulsed electric field penetrates at least one hollow fiber bundle accommodated in the dialyzer in the longitudinal direction thereof.

4. The apparatus according to claim 2, wherein: the liquid channel opens into the dialyzer and towards an outside of the pulsed electric field generator, and extends through each of the first section and the second section of the pulsed electric field generator; wherein the first electrode and the second electrode have a hollow cylindrical shape, the first section of the pulsed electric field generator includes a first electric insulator in which the first electrode is received, and the second section of the pulsed electric field generator includes a second electric insulator in which the second electrode is received.

5. The apparatus according to claim 4, wherein the liquid channel opening into the dialyzer extends in a direction of a longitudinal axis of the dialyzer through the electric insulator and through the hollow cylindrical shape of at least one of the first electrode or the second electrode.

6. The apparatus according to claim 2, further comprising: a liquid channel opening into the dialyzer and toward the outside of the pulsed electric field generator that extends through each of the first section and the second section of the pulsed electric field generator; wherein the first electrode and the second electrode are disk shapes, the first section of the pulsed electric field generator includes a first electric insulator in which the first electrode is received, and the second section of the pulsed electric field generator includes a second electric insulator in which the second electrode is received.

7. The apparatus according to claim 6, wherein the liquid channel opening into the dialyzer extends along a first length in the direction of a longitudinal axis of the dialyzer and along a second length in the direction of a transverse axis of the dialyzer between the dialyzer and the first electrode through the first electric insulator.

8. The apparatus according to claim 1, wherein the pulsed electric field generator can be fixed to the dialyzer in a fluid-tight manner by a screw-on thread arrangement.

9. The apparatus according to claim 1, wherein the pulsed electric field generator and the dialyzer are connectable in a fluid-tight manner via a sealing face surrounding a hollow fiber bundle of the dialyzer in an area of a cut face of the hollow fiber bundle on an inside of a wall of the dialyzer and via an elevation adapted to be pressed against the sealing face.

10. The apparatus according to claim 1, wherein the pulsed electric field generator includes a first section and a second section which are arranged opposite to each other along a longitudinal side of the dialyzer, and the first electrode is arranged in the first section and the second electrode is arranged in the second section so that the pulsed electric field penetrates at least a hollow fiber bundle accommodated in the dialyzer in the transverse direction thereof.

11. The apparatus according to claim 10, wherein the first electrode and the second electrode are each plate-shaped and are arranged parallel to each other.

12. The apparatus according to claim 10, wherein the first electrode and the second electrode are curved following a circumference of the dialyzer.

13. An apparatus for sterilizing a dialyzer for extracorporeal blood treatment, the apparatus comprising: a dialyzer; a first electrode and a second electrode adapted to receive the dialyzer there between; and a pulsed electric field generator coupled to the first electrode and the second electrode, the pulsed electric field generator configured to generate a pulsed electric field that penetrates the dialyzer received between the first electrode and the second electrode by applying a pulsed electric voltage between the first electrode and the second electrode; wherein: the pulsed electric field generator includes a first section adapted to be disposed on a first end face of the dialyzer and a second section adapted to be disposed opposite to the first section on a second end face of the dialyzer, a liquid channel opening into the dialyzer and towards an outside of the pulsed electric field generator extends through each of the first section and the second section of the pulsed electric field generator, and the first electrode and the second electrode have a hollow cylindrical shape, the first section of the pulsed electric field generator includes a first electric insulator in which the first electrode is received, and the second section of the pulsed electric field generator includes a second electric insulator in which the second electrode is received.

14. An apparatus for sterilizing a dialyzer for extracorporeal blood treatment, the apparatus comprising: a dialyzer; a first electrode and a second electrode adapted to receive the dialyzer there between; and a pulsed electric field generator coupled to the first electrode and the second electrode, the pulsed electric field generator configured to generate a pulsed electric field that penetrates the dialyzer received between the first electrode and the second electrode by applying a pulsed electric voltage between the first electrode and the second electrode; wherein: the pulsed electric field generator includes a first section adapted to be disposed on a first end face of the dialyzer and a second section adapted to be disposed opposite to the first section on a second end face of the dialyzer, a liquid channel opening into the dialyzer and toward the outside of the pulsed electric field generator that extends through each of the first section and the second section of the pulsed electric field generator, and the first electrode and the second electrode are disk shapes, the first section of the pulsed electric field generator includes a first electric insulator in which the first electrode is received, and the second section of the pulsed electric field generator includes a second electric insulator in which the second electrode is received.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The invention is best understood from the following detailed description when read in connection with the accompanying drawings. Included in the drawings are the following figures:

(2) FIG. 1 schematically shows a sectional view of a dialyzer including a PEF unit, a top-side liquid inlet and, respectively, liquid outlet and electrodes on an end face of the dialyzer according to a first embodiment of the invention;

(3) FIG. 2 schematically shows a sectional view of a dialyzer including a PEF unit and a lateral liquid inlet and, respectively, liquid outlet according to a second embodiment of the invention;

(4) FIG. 3 schematically shows a modification of the first and second embodiments including an alternative sealing of a liquid-filled chamber of the dialyzer according to a third embodiment;

(5) FIG. 4 schematically shows a sectional view of a dialyzer including a PEF unit, a top-side liquid inlet and, respectively, liquid outlet and electrodes along the longitudinal sides of the dialyzer according to a fourth embodiment of the invention; and

(6) FIG. 5 schematically shows a top view onto a dialyzer including a PEF unit and a curved electrode contour according to a fifth embodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

(7) It is noted that in the drawings like or equally acting elements and components are denoted with like reference numerals and are not redundantly described.

(8) FIG. 1 schematically shows a sectional view of a dialyzer 1 including a PEF unit 4, a top-side liquid inlet and, respectively, liquid outlet 3 and at least two electrodes 2 on an end face of the dialyzer according to a first embodiment. A laterally arranged plug located in the dialysis solution nozzle is denoted with reference numeral 5.

(9) The PEF unit 4 is a unit for generating a pulsed electric field which is arranged to generate a pulsed electric field penetrating the (liquid-filled) dialyzer 1 in a predetermined manner by applying electric pulses of predetermined form, duration and/or signal intensity (voltage) with the electrodes 2.

(10) The dialyzer 1 is filled with a liquid, preferably purified or distilled water of predetermined purity. The predetermined purity is useful, as in the case of an impure solution or liquid an undesired dielectric breakdown may occur when the pulsed electric field is applied. Various additives may be added to the liquid, such as chorine-containing substances for increasing the sterilizing effect and thus reduction of the sterilizing time. In this context, the related increase in the conductivity of the liquid has to be considered and has to be taken into account when defining the required electric field intensity. In the case of excessive electric conductivity of the liquid, a dielectric breakdown may occur which in turn may entail impairment or damage of the dialyzer and/or of the PEF unit.

(11) An electrode 2 is arranged on each side of the dialyzer 1 via the end or cut face thereof and is accommodated in the PEF (pulsed electric field) unit 4.

(12) In other words, the dialyzer 1 includes on its respective other end face not shown in FIG. 1 an at least functionally mirror-inverted arrangement having a first top-side electrode 2 and a corresponding second bottom-side electrode (not shown). Hereinafter, therefore the electrodes 2 of the pair of electrodes on the dialyzer 1 are described in the singular form and it is understood that the description nevertheless relates to both electrodes 2 of the pair of electrodes on the dialyzer 1.

(13) In this embodiment, the electrode 2 has an annular or (hollow) cylindrical shape the diameter of which preferably corresponds at least to the diameter of the hollow fiber bundle (potted with polyurethane (PUR), for example) inside the dialyzer 1 so that, when an electric voltage is applied to the electrode 2, a homogenous electric field forms inside the dialyzer 1 between the first top-side electrode 2 and the second bottom-side electrode (not shown).

(14) The electrode 2 is provided with a respective insulation 6 that fills, for example, a remaining recess of the PEF unit 4. In addition, the electrode 2 includes a hole, preferably in the form of a central bore, through which liquid can be introduced and discharged during a filling and/or flushing process. The electrode 2 and the insulation 6 in this embodiment form a unit together with e.g. an outer sheath of the PEF unit 4. The PEF unit 4 may as well be a PEF adapter.

(15) The PEF unit 4 or the PEF adapter, respectively, allows for sealing the liquid-filled chamber toward the housing of the dialyzer 1. For this purpose, the PEF unit 4 preferably includes a female thread which as to its design and dimensioning corresponds to the thread of a blood cap for the dialyzer 1.

(16) At the beginning of a sterilizing treatment, a PEF unit 4 is screwed onto each of the two (end) faces of the dialyzer 1 (without blood caps). As an additional sealing measure, an O-ring may be provided analogously to the sealing of blood caps. The production process of the dialyzer 1 may expediently take place such that the assembly of blood cap follows sterilization.

(17) In the further sterilizing treatment, the dialyzer 1 is filled with liquid and upon reaching a predetermined filling level it is uncoupled from the liquid supply.

(18) After that, the PEF treatment is carried out. In the PEF treatment, a defined number of electric pulses of defined field intensity (or voltage), defined pulse duration and defined pulse-off time between the pulses is applied to the dialyzer 1, or the liquid provided in the dialyzer, respectively, via the electrodes 2 along the longitudinal direction of the dialyzer.

(19) The electric pulses are generated by a technology for generating high-frequency pulses of high electric voltage known per se (e.g. with a Marx generator). The technology known per se therefore will not be redundantly described here.

(20) After PEF treatment as described before, preferably a dwell time is provided during which reactive substance generated by the voltage pulses (reactive oxygen species, elementary chlorine (when chloric compounds are added to the liquid) etc.) can be active so as to increase the effect of sterilization. Subsequently, the dialyzer 1 is flushed with distilled or purified water so as to remove residues such as e.g. killed microorganisms, added substances and the like.

(21) In conformity with the first embodiment, PEF sterilization may be incorporated in the production process of a dialyzer 1 as described below.

(22) After initiating steps, the dialyzer can be cut including a check of the cut faces. After that, the dialyzer 1 (without blood caps) can be connected to a device for checking fiber integrity (not shown) and appropriate test steps can be carried out. Then the connection of the dialyzer (without blood caps) to an apparatus for PEF sterilization may be provided and the sterilization may be carried out. Furthermore, the dialyzer 1 (without blood caps) then can be connected to a device for drying the dialyzer 1 and the dialyzer 1 can be dried.

(23) Finally, sterilized blood and protective caps are attached to the dialyzer 1. For ensuring the sterility of the blood chamber the insides of blood caps and protective caps as well as the O-ring preferably have to be superficially sterilized. Further steps of a regular production process for completing the dialyzer 1 may follow.

(24) Preferably, the process steps of the fiber integrity test, of PEF sterilization and of drying can be carried out in a combined manner.

(25) Moreover, the liquid present in the dialyzer 1 can be circulated during the PEF treatment so as to distribute sterilizing substances formed, such as reactive oxygen species, elementary chlorine and the like, evenly over all areas and/or hollow fibers of the dialyzer 1.

(26) In a modification, the PEF treatment can further be carried out in intervals, and accordingly, periods and times or intervals of the PEF treatment and periods and times or intervals in which the liquid is circulated may alternate.

(27) FIG. 2 schematically shows a sectional view of a dialyzer 1 comprising a PEF unit 4, an insulation 6 and a lateral liquid inlet and, respectively, liquid outlet 3 according to a second embodiment of the invention. The plug 5 in the dialysis solution nozzle, too, is provided on a sidewall of the dialyzer 1.

(28) The second embodiment of the dialyzer 1 comprising the PEF unit 4 differs from that of the first embodiment in that the liquid can be introduced to and discharged from the dialyzer through a channel opening laterally below the electrode 2 in an opening or, respectively, in the liquid inlet or liquid outlet 3 in the insulation 6 and therefore the electrode 2 is disk-shaped, i.e. it has no central bore.

(29) The preceding description of the first embodiment is fully applicable to the second embodiment as well.

(30) FIG. 3 schematically illustrates a modification of the first and second embodiments with alternative sealing of the liquid-filled chamber of the dialyzer 1 according to a third embodiment.

(31) In the third embodiment, the arrangement of the PEF unit 4 on the dialyzer 1 and the sealing of the liquid-filled chamber on the transition between the PEF unit 4 and the dialyzer 1 are not carried out, other than in the first and second embodiments, with a thread but by pressing a hollow cylinder (not shown) of thin wall thickness onto the area between the housing and the fiber-containing cut face 8 of the dialyzer 1.

(32) For this purpose, the area between the housing and the fiber-containing cut face of the dialyzer 1 may be in the form of a sealing face 7, and the hollow cylinder may be provided in the PEF unit 4 for this purpose.

(33) The preceding description of the first and second embodiments is fully applicable to the third embodiment, too.

(34) FIG. 4 schematically illustrates a sectional view of a dialyzer 1 comprising a PEF unit 4, a top-side liquid inlet and, respectively, liquid outlet and electrodes 2 at a predetermined distance on the outside along the longitudinal sides of the dialyzer 1 in accordance with a fourth embodiment of the invention.

(35) In the fourth embodiment, the electrodes 2 are not arranged, in contrast to the first to third embodiments, on the respective end faces of the dialyzer 1 but in the form of parallel plates on or along the longitudinal sides thereof. The electrodes 2 therefore generate pulsation along the transverse direction of the dialyzer 1 in this embodiment.

(36) In simulations of the electric field forming in this case it can be demonstrated that with electrodes 2 in the form of flat plates an approximately homogenous electric field forms therebetween and the electric field intensity decreases in the respective marginal areas only. Said decrease may be compensated, however, by dimensioning the electrodes 2 to be slightly larger than the cross-sectional area of the dialyzer 1, as illustrated in FIG. 4.

(37) FIG. 5 schematically illustrates a top view onto a dialyzer 1 comprising a PEF unit 4 and curved electrodes 2 according to a fifth embodiment. The fifth embodiment constitutes a modification of the fourth embodiment in which the electrodes 2 arranged on the outside are curved corresponding to the periphery and/or the radius of the dialyzer 1 and are arranged at a predetermined distance from the circumferential wall of the dialyzer 1.

(38) When designing the electrodes 2 in the form of curved plates, in the space between the electrodes 2 in which the dialyzer 1 is located areas of high field intensity and areas of lower field intensity may occur. Therefore, it is possible that the effect of sterilization is not evenly distributed throughout the entire dialysis volume. Such uneven distribution of the effect of sterilization may be counteracted in a minimizing and/or compensating manner by reducing the inhomogeneity of the electric field with a further adapted and/or specific formation of the electrodes 2 and/or time variation of locally forming field maximums and field minimums to generate field-induced turbulence.

(39) The foregoing description of the first and second embodiments is fully applicable to the fourth and fifth embodiments, too.

(40) The PEF unit 4 according to the first to third embodiments and, respectively, the electrodes 2 according to the fourth and fifth embodiments currently are not provided to be permanently maintained on a dialyzer intended for practical use, but are used during a manufacturing process of the dialyzer 1 merely temporarily for sterilization thereof and especially for removal of germs already present in the dialyzer 1.

(41) Therefore, in the third embodiment it is sufficient to press the PEF unit 4 (adapter) against a support area sealing in a predetermined manner on the dialyzer 1. It is thus understood that in the afore-described embodiments fastening devices, pressing devices, holding fixtures and the like may be expertly provided additionally or alternatively to described embodiments so as to maintain components involved in performed process steps and embodiments in situ and fluid-tight in a predetermined manner, without any detailed description of such devices and means being required.

(42) Moreover, in the fourth and fifth embodiments, the plate-shaped electrodes 2 and, respectively, the curved or bent electrodes 2 may be arranged and dimensioned so that during the PEF process steps the dialyzer 1 can be guided between the electrodes 2 in an automated manner and, after a predetermined dwell time, can be guided out of the electrode space. Therefore, predetermined clearances between the electrodes 2 or a predetermined positioning of the dialyzer 1 between the electrodes 2 may be provided, as it is indicated, for example, in FIG. 4 and FIG. 5 by the position of the dialysis fluid nozzle relative to the electrodes 2.

(43) It is noted that, due to the lack of physical contact of the PEF unit 4 and the liquid, the electric insulation 6 in the fourth and fifth embodiments may be omitted, where appropriate.

(44) As described in the foregoing, an apparatus for sterilizing a dialyzer for extracorporeal blood treatment comprises a unit for generating a pulsed electric field which is arranged for generating a pulsed electric field penetrating the dialyzer received between the first electrode and the second electrode of the unit, when a pulsed electric voltage is applied between a first electrode and a second electrode.

(45) Accordingly, the unit for generating a pulsed electric field (PEF unit 4) may include a first section disposed on a first end face of the dialyzer and a second section disposed opposite to the first section on a second end face of the dialyzer, and the first electrode may be arranged in the first section and the second electrode may be arranged in the second section so that the pulsed electric field penetrates at least one hollow fiber bundle accommodated in the dialyzer in the longitudinal direction thereof.

(46) In accordance with the first embodiment as afore-described, the first electrode and the second electrode may be produced in hollow cylindrical shape, the first section of the unit for generating a pulsed electric field may include an electric insulator in which the first electrode is accommodated, the second section of the unit for generating a pulsed electric field may include an electric insulator in which the second electrode is accommodated, and a liquid channel opening into the dialyzer and toward the outside of the unit for generating a pulsed electric field may extend through each of the first section and the second section of the unit for generating a pulsed electric field.

(47) In accordance with the first embodiment, furthermore the liquid channel opening into the dialyzer may extend in the direction of the longitudinal axis of the dialyzer through the insulator and through the hollow cylinder of the electrode. The liquid channel in this case may be insulated against the electrode by the insulator.

(48) In accordance with the second embodiment as afore-described, the first electrode and the second electrode may be produced in disk shape, the first section of the unit for generating a pulsed electric field may include an electric insulator in which the first electrode is accommodated, the second section of the unit for generating a pulsed electric field may include an electric insulator in which the second electrode is accommodated, and a liquid channel opening into the dialyzer and toward the outside of the unit for generating a pulsed electric field may extend through each of the first and second sections of the unit for generating a pulsed electric field.

(49) In accordance with the second embodiment, in the foregoing alternative the liquid channel opening into the dialyzer may further extend through the insulator between the dialyzer and the electrode along a first length in the direction of the longitudinal axis of the dialyzer and along a second length in the direction of the transverse axis of the dialyzer.

(50) In accordance with the first and second embodiments, the unit for generating a pulsed electric field can be fixed in a fluid-tight manner to the dialyzer with a screw-on thread arrangement.

(51) In accordance with the third embodiment as afore-described, alternatively the unit for generating a pulsed electric field and the dialyzer may be adapted to be connected or coupled in a fluid-tight manner via a sealing face surrounding the hollow fiber bundle on the inside of the wall of the dialyzer in the area of a cut face of the hollow fiber bundle and via an elevation adapted to be pressed against the sealing face.

(52) In accordance with the fourth embodiment as afore-described, the unit for generating a pulsed electric field may include a first section and a second section which are arranged so as to face each other along the longitudinal side of the dialyzer, and the first electrode may be arranged in the first section and the second electrode may be arranged in the second section so that the pulsed electric field penetrates the hollow fiber bundle accommodated in the dialyzer in the transverse direction thereof. Preferably, in the fourth embodiment the first electrode and the second electrode are flatly plate-shaped and are arranged in parallel to each other.

(53) In accordance with the fifth embodiment as afore-described, the first electrode and the second electrode may be curved following the circumference of the dialyzer.

(54) In a method for sterilizing a dialyzer for extracorporeal blood treatment, during a process for preparing or manufacturing the dialyzer the following steps are carried out: generating a pulsed electric field with a predetermined number of electric pulses of defined electric voltage, defined pulse duration and defined pulse-off time between the pulses, and applying the pulsed electric field to the dialyzer.

(55) Prior to generating the pulsed electric field, a unit for generating a pulsed electric field may be arranged on both sides of the dialyzer and the dialyzer may be filled with a predetermined liquid prior to generating the pulsed electric field. After switching off or removing said pulsed electric field it may be provided to allow a predetermined exposure time for reactive substances generated by the electric pulses to expire, and then flushing of the dialyzer may be carried out to remove residues of the sterilization process. Preferably, the afore-mentioned method is carried out by an apparatus of any one of the afore-described embodiments.

(56) As described before, an apparatus for sterilizing a dialyzer for extracorporeal blood treatment comprises a unit for generating a pulsed electric field which is arranged for generating a pulsed electric field penetrating the dialyzer received between the first electrode and the second electrode, when a pulsed electric voltage is applied between a first electrode and a second electrode of the unit. A method for sterilizing a dialyzer for extracorporeal blood treatment adapted to be executed using said apparatus incorporates, in a process for preparing or manufacturing the dialyzer, at least the steps of generating a pulsed electric field with a predetermined number of electric pulses of defined electric voltage, defined pulse duration and defined pulse-off time between the pulses, and applying the pulsed electric field to the dialyzer.

(57) The invention has been described in the foregoing by way of preferred embodiments. It is understood that details of the described preferred embodiments do not restrict the invention per se and various changes, modifications and/or equivalents obvious to those skilled in the art may result all of which as such are within the scope of the invention defined by the attached claims.