APPARATUS AND METHOD FOR TESTING INTEGRITY OF AN ULTRAFILTER MEMBRANE

Abstract

An apparatus for an extracorporeal treatment of blood has a supply line, a waste line, and an ultrafilter inserted in the supply line. An air inlet line is connected to a first chamber of the ultrafilter. A pressure sensor is configured for detecting pressure in the waste line or a second chamber of the ultrafilter. A controller is configured to perform an integrity test procedure for detecting when an ultrafilter membrane of the ultrafilter has multiple or single fiber breaks. A method of testing the ultrafilter is also disclosed.

Claims

1. A method for testing an integrity of a semipermeable membrane of an ultrafilter of an extracorporeal blood treatment apparatus, the extracorporeal treatment apparatus comprising: a supply line including an inlet end connected to a source of treatment liquid and an outlet end connected to an inlet port of a blood treatment device, wherein the ultrafilter is inserted in the supply line and the semipermeable membrane divides the ultrafilter into a first chamber and a second chamber, the ultrafilter including a first port connecting a first tract of the supply line to the first chamber, and a second port connecting the second chamber to a second tract of the supply line; a waste line including an inlet end connected to an outlet port of the blood treatment device and an outlet end connected to a discharge of used treatment liquid; an air inlet line connected to the first chamber of the ultrafilter or to the first tract of the supply line; at least one waste pump located on the waste line; and at least one pressure sensor configured to detect a pressure in one of: the second chamber of the ultrafilter, the second tract of the supply line, or the waste line, wherein the method comprises: filling the first chamber of the ultrafilter with air through the air inlet line, verifying when, while the waste pump is running, the pressure sensed by the at least one pressure sensor reaches a set negative pressure threshold (Pt), and determining that the ultrafilter semipermeable membrane has a multi-fiber break when the sensed pressure does not reach the set negative pressure threshold (Pt) within a set time interval (T), the pressure being considered relative to atmospheric pressure present in a location where the extracorporeal blood treatment apparatus operates.

2. The method of claim 1 wherein, after filling the first chamber with air, the waste pump is operated to make pressure in the second chamber more negative or to create a negative pressure in the second chamber.

3. The method according to claim 1, wherein verifying the measured pressure does not reach the set negative pressure threshold (Pt) comprises detecting pressure by the pressure sensor after expiration of the set time interval (T).

4. The method according to claim 1, wherein verifying the measured pressure does not reach the set negative pressure threshold (Pt) comprises detecting pressure by the pressure sensor and measuring an actual time interval at which the negative pressure threshold (Pt) is reached.

5. The method according to claim 1, wherein filling the first chamber with air comprises opening an air valve or operating an air pump located on the air inlet line.

6. The method according to claim 1, wherein operating the waste pump causes extracting or continuing to extract liquid from the second chamber of the ultrafilter, and wherein operating the waste pump after filling the first chamber with air makes pressure in the second chamber more negative or creates a negative pressure in the second chamber.

7. A method for testing an integrity of a semipermeable membrane of an ultrafilter, wherein the semipermeable membrane separates the ultrafilter into a first and a second chamber, the method comprising: emptying the first chamber of the ultrafilter from liquid and filling the first chamber with air; after the first chamber has been filled with air, extracting or continuing to extract liquid from the second chamber of the ultrafilter; verifying, while extracting liquid from the second chamber of the ultrafilter, when the pressure in the second chamber of the ultrafilter reaches a set negative pressure threshold (Pt); determining that the semipermeable membrane has a multi-fiber break when the pressure in the second chamber during the step of extracting liquid does not reach the set negative pressure threshold (Pt) within a set time interval (T), wherein the pressure in the second chamber is considered relative to atmospheric pressure present in a location where the ultrafilter operates.

8. The method according to claim 7, wherein verifying the measured pressure does not reach the set negative pressure threshold (Pt) comprises detecting the pressure in one of: the second chamber of the ultrafilter, or a line connected to the second chamber of the ultrafilter, after expiration of the set time interval (T).

9. The method according to claim 7, wherein verifying the measured pressure does not reach the set negative pressure threshold (Pt) comprises detecting the pressure in one of: the second chamber of the ultrafilter, and a line connected to the second chamber of the ultrafilter; and measuring an actual time interval at which the negative pressure threshold (Pt) is reached.

10. The method according to claim 7, wherein an air inlet line is connected to the first chamber of the ultrafilter, and wherein the steps of emptying the first chamber of the ultrafilter from liquid and filling the first chamber with air comprise opening an air valve or operating an air pump located on the air inlet line.

11. The method according to claim 7, wherein extracting or continuing to extract liquid from the second chamber of the ultrafilter after filling the first chamber with air makes pressure in the second chamber more negative or creates a negative pressure in the second chamber.

12. The method according to claim 7, wherein: the ultrafilter is inserted in a supply line including an inlet end connected to a source of treatment liquid and an outlet end connected to an inlet port of a blood treatment device, the ultrafilter having a first port connecting a first tract of the supply line to the first chamber of the same ultrafilter, and a second port connecting the second chamber of the ultrafilter to a second tract of the supply line; a waste line including an inlet end is connected to an outlet port of the blood treatment device and an outlet end is connected to a discharge of used treatment liquid; a waste pump is positioned on the waste line; and an air inlet line is connected to the first chamber of the ultrafilter or to the first tract of the supply line, wherein said step of extracting liquid from the second chamber is achieved by operating the waste pump, and wherein said step of verifying takes place while the waste pump is running.

13. A method for testing an integrity of a semipermeable membrane of an ultrafilter of an extracorporeal blood treatment apparatus, the extracorporeal treatment apparatus comprising: a supply line including an inlet end connected to a source of treatment liquid and an outlet end connected to an inlet port of a blood treatment device, wherein the ultrafilter is inserted in the supply line and the semipermeable membrane divides the ultrafilter into a first chamber and a second chamber, the ultrafilter including a first port connecting a first tract of the supply line to the first chamber, and a second port connecting the second chamber to a second tract of the supply line; a waste line including an inlet end connected to an outlet port of the blood treatment device and an outlet end connected to a discharge of used treatment liquid; and a waste pump located on the waste line, the method comprising the following steps: emptying the first chamber of the ultrafilter from liquid and filling the first chamber with air, operating the waste pump to extract or to continue extracting liquid from the second chamber of the ultrafilter, verifying, while the waste pump is operating, when the pressure in the second chamber of the ultrafilter reaches a set negative pressure threshold (Pt), and determining that the semipermeable membrane has a fiber break when, while operating the waste pump, the pressure in the second chamber does not reach the set negative pressure threshold (Pt) within a set time interval (T), the pressure being considered relative to atmospheric pressure present in a location where the extracorporeal blood treatment apparatus operates.

14. The method according to claim 13, wherein verifying the measured pressure does not reach the set negative pressure threshold (Pt) comprises detecting the pressure in one of: the second chamber of the ultrafilter, or a line connected to the second chamber of the ultrafilter, after expiration of the set time interval (T).

15. The method according to claim 13, wherein verifying the measured pressure does not reach the set negative pressure threshold (Pt) comprises detecting pressure in one of: the second chamber of the ultrafilter, or a line connected to the second chamber of the ultrafilter; and and measuring an actual time interval at which the negative pressure threshold (Pt) is reached.

16. The method according to claim 13, wherein an air inlet line is connected to the first chamber of the ultrafilter, and wherein the steps of emptying the first chamber of the ultrafilter from liquid and filling the first chamber with air comprise opening an air valve or operating an air pump located on the air inlet line.

17. The method according to claim 13, wherein operating the waste pump to extract or to continue extracting liquid from the second chamber of the ultrafilter takes place until after the first chamber has been filled with air.

18. The method according to claim 17, wherein operating the waste pump after filling the first chamber with air makes pressure in the second chamber more negative or creates a negative pressure in the second chamber.

19. The method according to claim 16, wherein the method further includes: while filling the first chamber of the ultrafilter with air, operating the waste pump based on a first set negative pressure value (P1), which is a desired set value to be reached by the pressure sensed by the at least one pressure sensor; and after the step of filling the first chamber of the ultrafilter with air, once the first chamber has been emptied from liquid and filled with air, operating the waste pump based on a second set negative pressure value (P2), which is a desired set value to be reached by the pressure sensed by the at least one pressure sensor and which is more negative than the first pressure value, wherein the set negative pressure threshold (Pt), which is checked during the verifying step, has a negative value intermediate between the first set pressure value (P1) and the second set pressure value (P2).

20. The method according to claim 19, wherein: the first set pressure value (P1) is selected in a pressure range between -150 mmHg and -450 mmHg; and the second set pressure value (P2) is selected in a pressure range between -300 mmHg and -700 mmHg, with the condition that the second pressure value be at least 100 mmHg more negative than the first set pressure value.

Description

DESCRIPTION OF THE DRAWINGS

[0232] Aspects of the invention are shown in the attached drawings, which are provided by way of non-limiting example, wherein:

[0233] FIG. 1 shows a schematic layout of a dialysis apparatus implementing aspects of the invention;

[0234] FIG. 2 shows a schematic layout of a hemodiafiltration apparatus implementing aspects of the invention;

[0235] FIG. 3 shows a block diagram of a method of testing the integrity of an ultrafilter membrane of an ultrafilter, according to aspects of the invention; and

[0236] FIG. 4 shows a block diagram of a method of testing the integrity of an ultrafilter membrane of an auxiliary ultrafilter, according to other aspects of the invention.

DEFINITIONS

[0237] In the present description and claims the following definitions are adopted: [0238] checking integrity of the ultrafilter (or of the auxiliary ultrafilter) semipermeable membrane means checking that the semipermeable membrane does not present one or more breaks in correspondence of any fiber forming the semipermeable membrane structure which could compromise the ability of the semipermeable membrane to properly separate undesired particles such as pollutants, bacteria, endotoxins, from liquid to be filtered; in case of ultrafilter semipermeable membranes formed by a bundle of hollow fibers, checking integrity of the ultrafilter (or of the auxiliary ultrafilter) semipermeable membrane means checking that the tubular wall of all fibers forming the ultrafilter membrane are intact and that therefore the membrane does not present one or more breaks at any fiber tubular wall; [0239] single fiber break means a break compromising the membrane integrity and affecting a single fiber of the ultrafilter membrane; [0240] multi-fiber break or multi-fiber break problem or multi-fiber breaks means a plurality of breaks, i.e.: breaks affecting two or more fibers and compromising the membrane integrity.

CONVENTIONS

[0241] In the present description and claims the following conventions are adopted: [0242] the terms downstream and upstream respectively refer to the downstream or upstream position of a component with respect to another component relative to the direction of a fluid flow in a line during normal use of the apparatus; [0243] each pressure value represents the difference between an absolute pressure value and the absolute value of the atmospheric pressure in the ambient where the apparatus is placed; thus, assuming the absolute value of ambient pressure at the apparatus is 760 mmHg, a negative pressure value of for example -300 mmHg represents an absolute pressure value which is = 760 - 300 mmHg = 460 mmHg, i.e., 300 mmHg below the absolute value of the pressure present in the environment surrounding the apparatus.

DETAILED DESCRIPTION

[0244] An apparatus 1 for extracorporeal treatment of blood - which may implement innovative aspects of the invention - is shown in FIGS. 1 and 2. In particular, the apparatus 1 of FIG. 1 is a dialysis apparatus, while the apparatus 1 of FIG. 2 is a hemodiafiltration apparatus.

[0245] The apparatus 1 of FIGS. 1 and 2 includes hydraulic circuit 100 comprising a supply line 2 having an inlet end 3 connectable to a source of treatment liquid. The source of treatment liquid is not shown and may for example be tap water or water coming from a centralized water preparation system. The supply line extends from the inlet end 3 to an outlet end 4 connectable to an inlet port of a blood treatment device 5. For example, in the example of FIG. 1 the blood treatment device 5 comprises a dialyzer, while in the example of FIG. 2 the blood treatment device 5 comprises a hemofilter or a hemodiafilter. Note that the specific nature of the blood treatment device is not relevant to the present invention. The blood treatment device 5 of FIGS. 1 and 2 has a blood chamber 6 and a liquid chamber 7 separated by a semi-permeable membrane 8: the outlet end 4 of the supply line 2 is connected to an inlet of the liquid chamber 7 of the blood treatment device 5. On the other end, the blood chamber 6 is connected to an extracorporeal blood circuit 9 comprising a blood withdrawal line 11 having an end connected with an inlet to the blood chamber 6 and a blood return line 10 having an end connected to an outlet of the blood chamber 6. A blood pump 12 may operate on the extracorporeal blood circuit 9 to pump blood from a patient into the blood withdrawal line, through the blood chamber, into the blood return line and back to the patient. The hydraulic circuit 100 of the apparatus 1 of FIGS. 1 and 2 further comprises a waste line 13 having an inlet end 14 connected to an outlet port the liquid chamber 7 of the blood treatment device 7 and an outlet end 15 connected to a discharge of used treatment liquid. As shown in FIGS. 1 and 2 the supply line 2 and the waste line 13 are configurable according to a normal configuration, where the outlet end 4 of the supply line 2 is connected to the liquid chamber 7 and in fluid communication with the inlet end 14 of the waste line 13. The supply line 2 and the waste line 13 are also configurable according to a by-pass configuration, where the supply line is in fluid communication with the waste line via a bypass line 16 (see dashed line 16 in FIGS. 1 and 2) bypassing the blood treatment device 5 and connecting the outlet end of the supply line with the inlet end of the waste line. The switch from the normal to the bypass configuration may for example be obtained thanks to appropriate valves 17 and 18 or other valves which may be present in the circuit 100. As visible in FIGS. 1 and 2, the apparatus 1 comprises an ultrafilter 19 inserted in the supply line 2 and having a respective semipermeable membrane 20 dividing the ultrafilter into a first chamber 21 and a second chamber 22; the ultrafilter 19 is used for a plurality of treatments and is periodically changed: the ultrafilter 19 may be subject to the integrity test described below to make sure about integrity of the filter membrane before the start of each new treatment; the ultrafilter 19 also presents a first port 23 connecting a first tract 24 of the supply line 2 to the first chamber 21: basically the first tract 24 extends from inlet end 3 to the first port 23 of the ultrafilter 19; the ultrafilter 19 also presents a second port 25 connecting the second chamber 22 to a second tract 26 of the supply line extending from the second port 25 to the outlet end 4 of the supply line. The ultrafilter 19 may also present a third port 27 connecting the first chamber 21 to a flushing line 28 connectable to the waste line 13: in the examples of FIGS. 1 and 2, the flushing line 28 has at least a valve 29 for selectively opening and closing the flushing line and thus selectively forming or stopping a fluid communication between the first chamber 21 and the waste line 13.

[0246] The apparatus 1 also includes an air inlet line 30: the air inlet line of the example of FIGS. 1 and 2 is connected to the first tract 24 of the supply line 2 at air injection point 33 and presents an air inlet valve 31, which may be selectively opened or closed to respectively allow or prevent admission of air into the supply line 2 and towards the ultrafilter 19; note that instead or in addition to the air valve 31 an occlusive air pump may be used in order to selectively control admission of air into the air inlet line 30. Alternatively, the air inlet line 30 may be directly connected to the first chamber 21 of the ultrafilter 19. As shown in FIGS. 1 and 2, the apparatus 1 further comprises a fresh fluid pump 32 on the supply line 2 and a waste pump 34 on the waste line 13. In the examples shown, the fresh fluid pump 32 is positioned on the first tract 24 of the supply line 2, downstream to air injection point 33 and upstream the ultrafilter 19. Note that in the examples shown a three-way valve 35 may be positioned at the end of a further by-pass line 36 connecting the waste line 13 and the supply line 2: specifically, the three way valve 35 is positioned between the fresh fluid pump 32 and the ultrafilter 19, while the further by-pass line 36 extends between the three-way valve 35 and a junction point 37 in the-waste line 13, positioned between the waste pump 34 and the outlet end 15 of the waste line.

[0247] Also note that the apparatus 1 may comprise an auxiliary waste pump 38 operative on the waste line 13 and positioned between the waste pump 34 and the outlet end 15 of the waste line. Additionally, a general water inlet valve 39, operable to selectively open and close admission of fresh liquid (fresh water) into the supply line 2, may be present at the inlet end 3 of the supply line 2, and a general waste outlet valve 40, operable to selectively open and close discharge of waste liquid out of the waste line 13 may be present at the outlet end of waste line 13.

[0248] The apparatus 1 of FIGS. 1 and 2 furthermore comprises one or more pressure sensors as described below. In greater detail, at least one pressure sensor 41 is configured for directly or indirectly detecting pressure in the second chamber of the ultrafilter. At this purpose, the pressure sensor 41 may be directly connected to the second chamber 22 of the ultrafilter 19 or it may be positioned on the second tract 26 of the supply line or on the waste line in correspondence of the tract of waste line extending between the inlet end 14 and the waste pump 34. As shown in FIGS. 1 and 2, the apparatus may include an auxiliary waste pump 38 and, in this case, an auxiliary pressure sensor 42 is positioned on the waste line between the waste pump 34 and the auxiliary waste pump 38.

[0249] Again with reference to FIGS. 1 and 2 the apparatus may include an optional water inlet ultrafilter 43, which is operative on the supply line immediately downstream the water inlet valve 39: also the water inlet ultrafilter 43 may be periodically changed and, in the example herein described, is not subject to any integrity test procedure.

[0250] Finally, the apparatus of FIGS. 1 and 2 includes a controller 50. The controller 50 is connected to the valves, pumps and pressure sensors described above and configured to control operation of the apparatus 1. In detail, the controller 50 is connected to the air valve 31, the waste pump 34, (if present) the waste pump 38, the pressure sensor 41 and (if present) the auxiliary pressure sensor 42. The controller 50 may be connected to a user interface 51 and be configured to receive inputs from an operator and then perform execution of an extracorporeal blood treatment based on the operator’s input: the present disclosure does not provide further details on the controller role in the handling of the blood treatment as this is not relevant to the present invention.

[0251] A safety pressure sensor 90 is located between fresh fluid pump 32 and three-way valve 35. The controller may be configured to stop operation of fresh fluid pump 32 once the pressure difference between pressure detected by sensor 41 and pressure detected by safety pressure sensor 90 exceeds an identified safety threshold to prevent from pressurize air in chamber 21. Of course pressure ratio between pressure detected by sensor 41 and pressure detected by safety pressure sensor 90 may be used in place of pressure difference.

[0252] At the beginning of each new treatment, or periodically every given number of treatments, the controller 50 is configured to automatically (or upon operator’s request) execute an ultrafilter integrity test procedure as herein described in further detail. Note that before initiating the ultrafilter integrity test procedure, the controller 50 may also be configured or programmed to execute a number of per se known phases such as coordinating the filling and flushing of the hydraulic circuit and operate valves 17 and 18 to put the hydraulic circuit and in particular the supply line and the waste line in a by-pass configuration (see dash lines in FIGS. 1 and 2 by-passing the blood treatment device 5).

[0253] With the supply line and waste line in the by-pass configuration, the controller 50 is configured or programmed to execute an integrity test procedure for checking whether the membrane 20 of the ultrafilter 19 is intact or not.

[0254] With reference now to the flowchart of FIG. 3, the integrity test procedure comprises the following steps.

[0255] Initially, the controller 50 causes filling with air of the first chamber 21 of the ultrafilter 19 (step 110 in FIG. 3): this is achieved by opening the air valve 31 (or possibly operating the air pump 31) and creating a suction of air towards said first chamber of the ultrafilter. In order to create an air flow through the air inlet line 30 and towards the ultrafilter first chamber 21, the fresh fluid pump 32 and the waste pump 34 are is also operated, for example when opening the air valve or even before opening the air valve 31 (or in case an air pump 31 is used when operating or before operating the air pump 31). For example, the fresh fluid pump 32 may be operated at a given angular speed while the waste pump 34 may be operated in closed loop based on a first set pressure P1 which is a desired value to be sensed at the pressure sensor 41. In an example, the waste pump 34 may be operated in closed loop with the first set pressure P1 at pressure sensor 41 set equal to - 350 mmHg as control loop parameter (i.e. 350 mmHg below the atmospheric pressure present in the ambient where the apparatus is installed). In a case like in FIGS. 1 and 2 where two pumps are present in the waste line 13, then both waste pump 34 and auxiliary waste pump 38 may (during this phase) be operated in closed loop based on the first set desired pressure P1 to be sensed at the pressure sensor 41 for pump 34 and to be sensed at auxiliary pressure sensor 42 for pump 38. The first set pressure value P1 (e.g., - 350 mmHg) is in this case the same for both pumps.

[0256] After filling the first chamber with air, the controller 50 is configured to form a negative pressure or further increase the value of negative pressure in the second chamber of the ultrafilter (step 111 in FIG. 3 - as always negative pressure is intended relative to the atmospheric pressure present in the ambient where the machine operates; therefore increasing the value of the negative pressure means making the pressure further below the atmospheric pressure present in the environment where the apparatus is installed) by continuing to operate the waste pump, or the waste pumps if two waste pumps are present. In greater detail, after said step of filling the first chamber of the ultrafilter, i.e., once the first chamber has been completely emptied from liquid and filled with air, the controller 50 controls operation of the waste pump 34 in closed loop based on a second set negative pressure value P2 (e.g., -600 mmHg), which shall be reached by pressure sensed by the pressure sensor 41 and which is more negative than the first pressure value P1 (again relative to ambient pressure present where the apparatus is installed). In a case like in FIGS. 1 and 2 where two pumps are present in the waste line 13, then both waste pump 34 and auxiliary waste pump 38 may (during this phase) be operated in closed loop based on second set negative pressure value P2 to be sensed at the pressure sensor 41 for pump 34 and to be sensed at auxiliary pressure sensor 42 for pump 38.

[0257] For example, the first set pressure value P1 may be selected in a pressure range between -150 and -450 mm Hg, while the second set pressure value P2 may be selected in the range between -300 and - 700 mm Hg (with the condition that the second pressure value be at least 100 mm Hg more negative than the first set pressure value).

[0258] More in general, the first set pressure value P1 may be selected in a pressure range allowing to drain the ultrafilter at moderate flow rates in order to avoid excessive stress on the membrane; the second set pressure value P2 may be selected such as to have an appreciable delta pressure with no residual flow, thus avoiding excessive stresses on the membrane and degasification that could cause exceeding the membrane bubble point (thus resulting into possible false alarms).

[0259] After the above described two steps, the controller provides for verifying (step 112 in FIG. 3), while the waste pump 34 is running (or both the waste pump 34 and the waste pump 38 are still running), if the pressure sensed by the pressure sensor 41 reaches a set negative pressure threshold Pt, for then determining (step 113) that the ultrafilter semipermeable membrane has a multi-fiber break if the pressure sensed by the pressure sensor 41 during the verification step does not reach the set negative pressure threshold Pt within a set time interval T. This verification step may include checking pressure at the pressure sensor 41 after expiration of time interval T; alternatively one may envisage to measure the time interval at which the negative pressure threshold Pt is reached. In any case, if in this step the threshold pressure Pt is not reached or reached too late, the controller 50 concludes that there is a multi-fiber break problem for the membrane of the ultrafilter 19. The set negative pressure threshold has a negative value intermediate between said first set pressure value and said second set pressure value. For example if the first pressure value is set at -350 mm Hg and the second pressure value is set at - 600 mm Hg, the pressure threshold may be equal to - 500 mm Hg. The set pressure threshold has a negative value aimed at identifying multi-fiber breaks, thus providing an early detection.

[0260] The time interval (i.e., the interval by which the pressure sensed by the pressure sensor 41 should reach the set negative pressure threshold to exclude a multi-fiber break of the ultrafilter membrane) is counted by the controller starting from the moment at which the controller imposes the second negative pressure as setting to control the waste pump 34 (or to both waste pumps 34 and 38). This time interval lasts 10 to 60 seconds, for example 30 seconds.

[0261] According to aspects of the invention, the integrity test procedure may further comprise the following additional steps which the controller is configured to execute after steps 110 to 113 described above.

[0262] In detail, at step 114 the controller is configured to command the appropriate components for hydraulically isolating the ultrafilter: as it is known to the skilled person hydraulic isolation of the ultrafilter may take place in different ways depending upon the specific design of the hydraulic circuit 100. For example, with reference to FIG. 1, the controller may command closure of at least valves 29, 40 and 35 (or other equivalent valves blocking flow to the first chamber 21) and stop of the pumps 32, 34 and 38. Then, the controller (step 115 in FIG. 3) is configured for receiving pressure values detected by the pressure sensor 41 at the end of a given transitory period after having hydraulically isolated the ultrafilter; subsequently, the controller is configured for verifying (step 116) if two stability conditions (116a, 116b) are met, namely that the pressure values detected by pressure sensor 41 at the end of the transitory period be below an auxiliary negative pressure threshold Pt2 (for example below -350 mmHg, again relative to atmospheric pressure present in the ambient where the machine is installed), and that the variation by unit of time (dP/dt) of the pressure values detected by the at least one pressure sensor 41 at the end of the transitory period be sufficiently small and specifically be below a set pressure differential OP, for example below a value comprised between 3 to 6 mmHg, and in a presently preferred variant below 4 mmHg/s. Note that in a preferred embodiment the auxiliary negative pressure threshold Pt2 is less negative than the pressure threshold Pt (relative to atmospheric pressure present in the ambient where the machine is installed, thus Pt2 is closer than Pt to atmospheric pressure). Furthermore, the set pressure differential AP is chosen at a value suitable to detect multi-fiber breaks; in addition and in accordance with a further aspect, the controller 50 may be configured to sample the dP/dt values giving more weight to pressure values at the beginning of the detection phase when delta pressure is at its highest values (for example using a low-pass filter). The controller 50 (step 121) is configured for then determining that the semipermeable membrane of the ultrafilter 19 has a multi-fiber break if the two conditions (steps 116a, 116b) are not both met.

[0263] The integrity test procedure may also comprise the following further steps (steps 117-120 in FIG. 3) which the controller is configured to execute in order to determine if the membrane 20 of the ultrafilter 21 has a single fiber break. The further steps 117-120 described below are, in one aspect of the invention, executed after having verified that membrane 20 of the same ultrafilter 21 has no multi-fiber breaks (steps 110-113 and steps 114-116). In other words, the check for a possible single fiber break may be made as last check, thereby avoiding to carry out unnecessary steps if it is concluded that there is a higher ranking problem, namely a multi-fiber break. According to this aspect, the integrity test procedure, may therefore be configured to hydraulically isolate the (or maintain hydraulic isolation of) ultrafilter 19 and then receiving pressure values detected by the pressure sensor 41 during a further test interval after said transitory period following hydraulic isolation of the ultrafilter. In other words, while steps 114-115 are executed after hydraulic isolation of the ultrafilter but during pressure stabilization, the following steps are executed after having waited a relatively long time interval (longer than said transitory period) after which it is expected that, absent fiber integrity problems, pressure should be highly stable. Thus, the controller 50 is configured, after waiting for expiration of the transitory period and during the further test interval, for verifying if a variation by unit of time (dP/dt) of said pressure values detected by the pressure sensor 41 during the further test interval remains below a further set pressure differential Op2 during at least a portion lasting n seconds of the further test interval (step 117). The further set pressure differential Op2 may be in the range between 1 and 3 mmHg and in a specific example it may be equal to 2 mmHg. More in general, the further set pressure differential Op2 is set in order to detect a single broken fiber (Op2 may in practice be a fraction, e.g., 50% compared to said set pressure differential AP). The test interval is relatively short and may last 5 to 30 seconds, for instance 10 seconds; therefore, the controller checks if dp/dt stays below for example 2 mmHg during a portion of e.g., 4 seconds of the test interval (step 117) and also checks expiration of the test interval (118); the controller is configured to then establish that the membrane of the ultrafilter has a single-fiber break (step 119) if the check of step 117 is not positively passed before expiration of the test interval (step 118), i.e., before expiration of the 10 seconds in this example. Otherwise, if before expiration of the test interval, dp/dt stays below Op2 (in this example below 2 mmHg) for n seconds (in this example for consecutive 4 seconds) , then it is determined that the ultrafilter membrane is intact (step 120).

[0264] The apparatus of FIG. 2 has, in addition to the ultrafilter 20, an auxiliary ultrafilter 70 inserted in the second tract 26 of the supply line 2. The auxiliary ultrafilter 70 is used for a plurality of treatments and is periodically changed: for this reason also ultrafilter 70 may be subject to the integrity test described below to make sure about integrity of the filter membrane before the start of each new treatment. The auxiliary ultrafilter 70 has a semipermeable membrane 71 dividing the auxiliary ultrafilter into a respective first chamber 72 and a respective second chamber 73: the auxiliary ultrafilter may be structurally identical to the ultrafilter 20. The auxiliary ultrafilter 70 presents a first port 74 connecting, via first portion 26a of second tract 26, the first chamber 72 to second port 25 of the ultrafilter 19 second chamber 22. The auxiliary ultrafilter 70 also includes a respective second port 75 connecting the second chamber 73 of the auxiliary ultrafilter 70 to a second portion 26b of the second tract 26 of the supply line 2. It should be noted that in the non-limiting example of FIG. 2, an infusion line 81 may depart from the second portion 26b of the second tract 26 of line 2: in particular in the example of FIG. 2, infusion line 81 departs from bifurcation point 80 and may lead to an infusion port 83, which may be present on an accessible portion of the apparatus 1 (for example on the apparatus front panel), to which one or more replacement fluid lines 84 and 85 may be connected. Replacement fluid lines 84 and 85 shown in FIG. 2 thereby bring to the extracorporeal blood circuit fresh fluid filtered through the ultrafilters 21 and 70. An auxiliary air inlet line 76 is connected to the first chamber 72 of the auxiliary ultrafilter 70 or to the first portion 26a of the second tract of the supply line: the air inlet line 76 is provided with a respective auxiliary air valve 77 (or with an auxiliary occlusive air pump) in order to selectively open and close admission of air via the air inlet line 76 under the control of controller 50 and allow air filling of the first chamber of the auxiliary ultrafilter during execution of the integrity test procedure of the semipermeable membrane 71. In the alternative embodiment of FIG. 2, pressure sensor 41 may be configured for detecting pressure in one of the second chamber of the ultrafilter, the second portion of the second tract of the supply line, or the waste line (this last alternative is shown in FIG. 2). An auxiliary flush line 86 connects a third port 87 of the first chamber of the auxiliary ultrafilter 70 to the waste line, and an auxiliary flush valve 88 is positioned on the flush line 86 to selectively open and close the first chamber of the auxiliary ultrafilter 70 to the waste line.

[0265] The controller 50 is configured to carry out, with the supply line and the waste line in by-pass configuration, an auxiliary integrity test procedure on the auxiliary ultrafilter 70. The auxiliary test procedure on the ultrafilter is also represented in FIG. 4: in any case most steps of the auxiliary test procedure are similar to those of the test procedure conducted on the ultrafilter 20.

[0266] In particular, according to the auxiliary integrity test procedure, the controller 50 initially causes filling with air of the first chamber 72 of the ultrafilter 70 (step 110 in FIG. 4): this is achieved by opening the air valve 77 (or activating an air pump on the auxiliary air inlet line) and creating a suction of air towards said first chamber of the ultrafilter. In order to create an air flow through the air inlet line 76 and towards the ultrafilter first chamber 72, the waste pump 34 or the waste pumps 34 and 38 is/are operated, for example when opening the air valve or even before opening the air valve 77 (in case an occlusive air pump is used in place of the air valve the pump 34 or the pumps 34 and 38 may be operated in synchronism with the occlusive air pump or even before starting operation of the occlusive air pump). The waste pump 34 may be operated in closed loop based on a first set pressure P1′ which is a desired value to be sensed at the pressure sensor 41. In an example, the waste pump 34 may be operated in closed loop with the first set pressure P1′ at pressure sensor 41 set equal to - 300 mmHg as control loop parameter. In a case like in FIG. 2, where two pumps are present in the waste line 13, then both waste pump 34 and auxiliary waste pump 38 may (during this phase) be operated in closed loop based on the first set desired pressure P1′ to be sensed at the pressure sensor 41 for pump 34 and to be sensed at auxiliary pressure sensor 42 for pump 38. The first set pressure value P1′ (e.g., - 300 mmHg) may be the same for both pumps.

[0267] In case pressure sensor 41 immediately reaches the P1′ first set pressure value, thus causing the waste pump 34 (and if present also pump 38) to decelerate or stop without removing the water supposed to be still present in chamber 72, this identifies that the chamber 72 is in reality already empty. Thus, the controller 50 may also be configured, in accordance with an ancillary aspect, to check a time related parameter (step 130) such as the time necessary to reach the first pressure value P1′ or the pump rotation frequency of waste pump 34 (and/or 38), or the pump rotation period of pump 34 (and/or 38), and compare this detected time related parameter with a corresponding reference threshold, assigning the identification of a multi-fiber break problem in membrane 20 of ultrafilter 19 if the check on the time related parameter is not passed (step 131). In practice, if the time necessary to reach the first pressure value P1′ is too short, or if the frequency of one or both the waste pumps is too high, or if the pump rotation period of one or both the waste pumps is too small, then it is concluded that there is a multi-fiber break of the membrane 19 of ultrafilter 20, which for some reason was not detected before. Then, after filling the first chamber 72 with air, the controller 50 is configured to form a negative pressure or increase the negative pressure in the second chamber 73 of the ultrafilter (step 111 in FIG. 4 - negative pressure is intended relative to the atmospheric pressure present in the ambient where the machine operates; therefore increasing the value of the negative pressure means making the pressure further below the atmospheric pressure present in the environment where the apparatus is installed) by continuing to operate the waste pump or the waste pumps if two waste pumps are present. In greater detail, after said step of filling the first chamber of the ultrafilter with air, i.e., once the first chamber has been completely emptied from liquid and filled with air, the controller 50 controls operation of the waste pump 34 in closed loop based on a second set negative pressure value P2′ (e.g., - 600 mmHg), which shall be reached by pressure sensed by the pressure sensor 41 and which is more negative than the first pressure value P1′. In a case like in FIG. 2 where two pumps are present in the waste line 13, then both waste pump 34 and auxiliary waste pump 38 may (during this phase) be operated in closed loop based on second set negative pressure value P2′ to be sensed at the pressure sensor 41 for pump 34 and to be sensed at auxiliary pressure sensor 42 for pump 38.

[0268] The first set pressure value P1′ may be selected in a pressure range between -150 and -450 mm Hg, while the second set pressure value P2′ may be selected in the range between - 300 and - 700 mm Hg (with the condition that the second pressure value be at least 100 mm Hg more negative than the first set pressure value).

[0269] More in general, the first set pressure value P1′ may be selected in a pressure range allowing to drain the ultrafilter at moderate flow rate in order to avoid excessive stress on the membrane; the second set pressure value P2′ may be selected to form a sufficient delta pressure with no residual flow, also avoiding excessive stress on the membrane and degasification that could cause exceeding the membrane bubble point exceeding. At the end of the draining phase of ultrafilter 70, the controller may be configured to put first port 74 in communication with line 15, for example by opening an ancillary by-pass valve 91 placed on a line connecting the first tract 26a with the waste line 15. The controller opens the ancillary by-pass valve 91 for a short time frame (e.g., 1 to 5 seconds) to ensure the complete draining of the ultrafilter 70 from top to bottom.

[0270] After the above described two steps, the controller provides for verifying (step 112 in FIG. 3), while the waste pump 34 is running (or both the waste pump 34 and the waste pump 38 are still running), if the pressure sensed by the pressure sensor 41 reaches a set negative pressure threshold Pt′, for then determining (step 113) that the ultrafilter membrane 71 has a multi-fiber break if the pressure sensed by the pressure sensor 41 during the verification step does not reach the set negative pressure threshold Pt′ within a set time interval T′. This verification step may include checking pressure at the pressure sensor 41 after expiration of time interval T′; alternatively, one may envisage to measure the time interval at which the negative pressure threshold Pt′ is reached. In any case, if in this step the threshold pressure Pt′ is not reached or reached too late, the controller 50 concludes that there is a multi-fiber break problem for the semipermeable membrane 71 of the ultrafilter 70. The set negative pressure threshold Pt′ has a negative value intermediate between said first set pressure value P1′ and said second set pressure value P2′. For example if the first pressure value P1′ is set at -300 mm Hg and the second pressure value P2′ at - 600 mm Hg, the pressure threshold Pt′ may be equal to - 450 mm Hg. In more general terms, the pressure threshold Pt′ may be selected to have a value which is a negative value intermediate between said first set pressure value P1′ and said second set pressure value P2′ and which aims at early identification of multi-fiber breaks.

[0271] The set time interval T′ (i.e., the interval by which the pressure sensed by the pressure sensor 41 should reach the set negative pressure threshold Pt′ to exclude a multi-fiber break of the ultrafilter membrane) is counted by the controller starting from the moment at which the controller imposes the second negative pressure P2′ as setting to control the waste pump 34 (or to both waste pumps 34 and 38). This time interval T′ may last 10 to 60 seconds, for example of 30 seconds.

[0272] According to aspects of the invention, the auxiliary integrity test procedure may further comprise the following additional steps which the controller 50 is configured to execute after steps 110 to 113 described above.

[0273] In detail, at step 114 the controller 50 is configured to command the appropriate components to hydraulically isolating the ultrafilter 70: for example, with reference to FIG. 2, the controller may command closure of valves 35, 40 and 88 (and possibly also valve 77) and stop of the pumps 32, 34 and 38. Then, the controller (step 115 in FIG. 4) is configured for receiving pressure values detected by the pressure sensor 41 at the end of a given transitory period after having hydraulically isolated the auxiliary ultrafilter 70; subsequently, the controller 50 is configured for verifying (step 116) if two stability conditions (116a, 116b) are met, namely that the pressure values detected by pressure sensor 41 at the end of the transitory period be below an auxiliary negative pressure threshold Pt2′ (for example below -350 mmHg), and that the variation by unit of time (dP/dt) of the pressure values detected by pressure sensor 41 at the end of the transitory period be sufficiently small and specifically be below a set pressure differential ΔP′, for example below 4 mmHg/s. Note that in a preferred embodiment the auxiliary negative pressure threshold Pt2′ is less negative than the pressure threshold Pt′ and the set pressure differential ΔP′ is set in order to detect multi-fiber breaks (example 4 mmHg); in addition and in accordance with a further aspect, the controller 50 may be configured to sample the dP/dt values giving more weight to pressure values at the beginning of the detection phase when delta pressure is at its highest values (for example using a low-pass filter). The controller 50 (step 121) is configured for then determining that the membrane of the ultrafilter 19 has a multi-fiber break if the two conditions (steps 116a, 116b) are not both met.

[0274] The auxiliary integrity test procedure on ultrafilter 70 may also comprise the following further steps which the controller is configured to execute in order to determine if the membrane 71 has a single fiber break. The further steps described below are, in one aspect of the invention, executed after having verified that membrane 70 of the same ultrafilter 71 has no multi-fiber breaks (steps 110-113 and steps 114-116). In other words, the check for a possible single fiber break may be made as last check on the ultrafilter 70, thereby avoiding to carry out unnecessary steps if it is concluded that there is a higher ranking problem, namely a multi-fiber break. According to this aspect, the integrity test procedure, may therefore be configured to hydraulically isolate (or maintain hydraulic isolation of) the auxiliary ultrafilter 70 and then receiving pressure values detected by the pressure sensor 41 during a further test interval after the transitory period following hydraulic isolation of the ultrafilter 70. In other words, while steps 114-115 are executed after hydraulic isolation of the ultrafilter 70 but during pressure stabilization, the following steps are executed after having waited a relatively long transitory period after which it is expected that - absent fiber integrity problems - pressure should be highly stable. Thus, the controller 50 is configured, after waiting for expiration of the transitory period, for verifying if a variation by unit of time (dP/dt) of said pressure values detected by the pressure sensor 41 during the further test interval remains below a further set pressure differential Δp2′ during at least a portion lasting n seconds of the further test interval (step 117). The further set pressure differential Δp2′ may be in the range between 1 and 3 mmHg and in a specific example it may be equal to 2 mmHg. More in general, the further set pressure differential Δp2′ is set in order to detect a single broken fiber (Δp2′ may in practice be a fraction, e.g., 50% compared to said set pressure differential ΔP′). The test interval is relatively short and may last 5 to 30 seconds, for instance 10 seconds; therefore, the controller checks if dp/dt stays below for example 2 mmHg during a portion of e.g., 4 seconds of the test interval (step 117) and also checks expiration of the test interval (118); the controller is configured to then establish that the membrane of the auxiliary ultrafilter 70 has a single-fiber break (step 119) if the check of step 117 is not positively passed before expiration of the test interval (step 118), i.e., before expiration of the 10 seconds in this example. Otherwise, if before expiration of the test interval, dp/dt stays below Δp2′ (in this example below 2 mmHg) for n seconds (in this example for consecutive 4 seconds), then it is determined that the auxiliary ultrafilter membrane is intact (step 120).

Controller 50

[0275] As already indicated the apparatus according to the invention makes use of at least one controller 50. This controller may comprise a digital processor (CPU) with memory (or memories), an analogical type circuit, or a combination of one or more digital processing units with one or more analogical processing circuits. In the present description and in the claims it is indicated that the controller is “configured” or “programmed” to execute certain steps: this may be achieved in practice by any means which allow configuring or programming the controller. For instance, in case of a controller comprising one or more CPUs, one or more programs are stored in an appropriate memory: the program or programs containing instructions which, when executed by the controller, cause the controller to execute the steps described and/or claimed in connection with the controller. Alternatively, if the controller is of an analogical type, then the circuitry of the controller is designed to include circuitry configured, in use, to process electric signals such as to execute the controller steps herein disclosed.

Method of Testing the Integrity of an Ultrafilter Semipermeable Membrane

[0276] The invention also concerns a method of testing the integrity of an ultrafilter membrane of an ultrafilter. The ultrafilter may be part of an extracorporeal blood treatment apparatus. For instance, the method may be used for testing the integrity of the membrane of one or all the ultrafilters described above in connection with the apparatus of FIG. 1 or the apparatus of FIG. 2. In accordance with one aspect, the method described below may be implemented by any apparatus 1 described above or claimed in any one of the appended claims.

[0277] The method of the invention detects if the ultrafilter membrane is subject to multi-fiber breaks or to a single fiber break. The method comprises executing the following steps (please refer again to FIG. 3 and to FIG. 4): [0278] step 110: emptying the first chamber of the ultrafilter from liquid and filling the first chamber with air, [0279] step 111: after the first chamber has been filled with air, continue extracting liquid from the second chamber of the ultrafilter, [0280] step 112: verifying, while extracting liquid from the second chamber of the ultrafilter, if the pressure in the ultrafilter second chamber reaches a set negative pressure threshold, [0281] step 113: determining that the ultrafilter semipermeable membrane has a multi-fiber break if the pressure in the second chamber during the step of extracting liquid does not reach said set negative pressure threshold within a set time interval. The set time interval of said verifying step is a set time interval calculated from start of the step of extraction of liquid from the second chamber, or calculated from end of filling with air the first chamber of the ultrafilter under test.

[0282] After conclusion of steps 110-113, if no multi-fiber break has been detected the method continues with the following further steps: [0283] step 114: hydraulically isolating the ultrafilter; [0284] step 115: waiting a given transitory period; [0285] step 116: verifying if two stability conditions are met, one stability condition checking the ability to reach a certain negative pressure, while the other condition checking the stability of pressure.

[0286] In greater detail step 116 comprises the following sub-steps: [0287] sub-step 116a: verifying if the values of pressure in the second chamber of the ultrafilter at the end of the transitory period are below an auxiliary negative pressure threshold, for example below -300 or below -350 mmHg, and [0288] sub-step 116b: verifying if the variation by unit of time (dP/dt) of the pressure values in the second chamber of the ultrafilter at the end of the transitory period is below a set pressure differential, for example below 4 mmHg/s.

[0289] If the verifications of sub-steps 116a and 116b are not both positively passed, the method determines that the membrane of the ultrafilter has a multi-fiber break. In other words, it is sufficient that one of the two conditions of sub-steps 116a, 116b not be met to conclude for the presence of a multi-fiber break.

[0290] Finally, after conclusion of steps 110-113, and in one aspect, after conclusion also of steps 114-116, the method provides for a sequence of steps, namely steps 117-120) aimed at determining the possible presence in the membrane of a single fiber break. In particular, the method may comprise the following additional steps: [0291] step 118: monitoring expiration of a further test time interval after said given transitory period; [0292] step 117: verifying if a variation by unit of time dP/dt of values of pressure during the further test interval after said given transitory period remains below a further set pressure differential; for example it may be checked if dP/dt during the further test interval remains below 2 mmHg/s, for at least a portion of said further test interval, for example for 4 s in the first 10s of the further test interval.

[0293] Then, at step 119, it is determined that the membrane of the ultrafilter has a single-fiber break if the above last condition is not met. If, instead, the above last condition is met, the method provides for informing an operator or for issuing a corresponding signal to the controller of the apparatus 1 (step 120) .

[0294] If the above test method is applied to an ultrafilter (for example the auxiliary ultrafilter 70 of FIG. 2) having the first chamber connected with the second chamber of another already tested ultrafilter (for example ultrafilter 19 in FIG. 2), the behavior of the draining pump 34 (and 38) may be monitored and used to identify a multi-broken fiber in the membrane of the first ultrafilter, causing the first chamber of the ultrafilter under testing to be empty when expected to be still full of liquid (steps 130, 131). For example, the method may include to check a time related parameter (step 130) such as the time necessary to reach P1′ or the pump rotation frequency, or the pump rotation period, and compare this detected time related parameter with a corresponding reference threshold, assigning the identification of a multi-fiber break problem in the membrane of ultrafilter 19 if the check on the time related parameter is not passed (step 131).

[0295] Finally, according to aspects of the invention, a method of testing ultrafilters may use only steps 110, 111 and 114 to 120 (without steps 112-113) to identify whether an hydraulically isolated ultrafilter has a single fiber break or a multiple fiber break, in particular by first creating a negative pressure in the second chamber of the ultrafilter (e.g., executing steps 110 and 111 described above) and then detecting the behavior of derivative dp/dt to decide whether the ultrafilter membrane is intact or has a single fiber break or multiple fiber breaks, as described above in connection with steps 116a and 116b and with steps 117 and 118, and as indicated in aspects from 53rd to 81st of the summary section.

[0296] While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and the scope of the appended claims.