ES2976019T3 - Non-invasive sensor to determine the heartbeat and/or cardiac rhythm in a segment of an extracorporeal blood circuit - Google Patents

Abstract

Noninvasive heartbeat sensor for determining a heart rate in a conduit of an extracorporeal blood treatment apparatus, comprising a source for directing an optical signal toward blood flowing in the segment; a detector for receiving an optical information signal comprising the signal emitted by said source after passing the blood, and outputting the respective output signal; a controller receiving the respective output signal and recovering a heartbeat frequency and a heart rate value, based on the output signal, wherein the information signal is altered by the disturbance of the blood flow generated partly by the flow impulses originated by the heart. (Automatic translation with Google Translate, no legal value)

Description

DESCRIPTION

Noninvasive sensor for determining heartbeat and/or heart rhythm in a segment of an extracorporeal blood circuit

Field of invention

The present disclosure belongs to the general field of signal processing and optical measurement of physical quantities. In detail, the invention relates to an apparatus and a sensor for determining at least the heartbeat and/or the heart rate.

Background of the technique

In renal care devices (hemodialysis for chronic renal care or acute renal failure treatments, or during extracorporeal plasma processing, e.g. hemodialysis, hemofiltration, hemodiafiltration, plasmapheresis, etc.) the patient's hemodynamic parameters are measured indirectly through the blood lines (e.g. mean arterial and venous pressures with semi-invasive sensors that are part of the blood line itself) or sporadically with a traditional inflatable cuff placed on the patient's arm. The use of a traditional inflatable cuff does not allow for continuous blood pressure reading, since its operation involves a temporary occlusion of the arteries and veins in the patient's arm. Furthermore, the measurement is quite uncomfortable and can be painful for the patient, so it is not acceptable to repeat the measurement continuously during a dialysis treatment. Blood pressure cuffs can also detect heartbeat and/or rhythm, but only during the measurement period (which lasts approximately 1 minute). The known semi-invasive pressure sensors are usually installed in the blood line, in a position close to the pump and away from the patient. These semi-invasive pressure sensors are usually equipped with membranes that come into contact with the blood or fluid circulating in the lines of the device. Therefore, special care must be taken in the design and in the materials chosen for their manufacture in order to reduce the risk of affecting the health of the patient being treated.

It has been observed that the pulse that the heart provides to the blood as it beats decreases in intensity and/or energy along the path from the fistula access to the conduit to the extracorporeal blood treatment apparatus.

Likewise, the pumps operatively driven in the apparatus typically produce unwanted pressure peaks (or flow peaks) in the blood or fluid circulating in the lines, as they are usually pulsating pumps, in particular peristaltic pumps. This worsens the accuracy and reliability of pressure readings because unwanted noise is always added to the desired signal; the pressure peaks (or flow peaks) provided by the pumps can sometimes be an order of magnitude greater than the magnitude of the heart pulses. The pressure peaks (or flow peaks) provided by the pump are related, in amplitude and/or frequency, to the flow rate of the pump itself. The higher the flow rate, the faster the pump rotates and, typically, the higher the frequency with which the peaks occur. This is particularly true for peristaltic pumps, whose operation leads to a discontinuous flow/pressure delivery in the conduits throughout the operating cycle, due to the cyclic compression of a conduit segment of a blood circuit which is plastically deformed due to the action of the pump rollers against a contrast wall.

It has further been observed that for typical flow rates involved in blood treatment, in particular dialysis processes performed through an extracorporeal blood treatment apparatus, the peak frequencies provided by the pump are very close to that of the heart rate, which normally, under resting conditions, lies between 50 bpm (or typically 60-70 bpm, the first number referring to well trained athletes) and 100 bpm, resulting in approximately peak frequencies lying between slightly less than 1 Hz and slightly less than 2 Hz. Therefore, the fundamental frequency of the peaks provided by the pump is substantially in close relationship with that of the heart beat and sometimes the frequency of the peaks provided by the pump may substantially overlap that of the heart beat, differing e.g. by a few tenths of a Hz. It seems clear that without appropriate procedures, heart rate readings can be substantially adversely affected by the pulses provided by the pump. Some treatments can lead to a reduction in the differential blood pressure between diastolic and systolic values, so that the effect of the pump pulses remains greater.

This harmful condition can be overcome by temporarily stopping the blood pump, i.e. the treatment processes for reading the pulses, but this has the disadvantage that it influences the proportion of purified blood sent to the patient, lengthens the treatment, requires a specific setting for the blood treatment device and in any case does not allow for continuous reliable monitoring, as the pump will be reactivated after a short period of time after the reading. Continuous monitoring of the heartbeat and/or rhythm is also possible by means of additional devices (e.g. wearable devices) added to the system and placed in close contact with the patient's body. Having an additional device in contact with the patient and connected to the machine for transmitting data brings the following disadvantages:

- user discomfort due to the added device (portable or not),

- reliability issue due to close connection with the patient's body, - need for an additional connectivity device to the machine and vice versa, leading to higher development and upgrading costs of existing machines.

WO2011/080194 discloses an apparatus for extracorporeal blood treatment configured to monitor fluid flow rate of a cardiovascular system of a patient. The apparatus comprises an extracorporeal blood circuit and a connection for connecting the extracorporeal blood circuit to the cardiovascular system. A monitoring device receives a time-dependent measurement signal from a venous pressure sensor in the blood circuit. The pressure sensor is arranged to detect pulses originating from the patient's heart, wherein the system further comprises a signal processor for processing the measurement signal and obtaining a pulse profile which is a temporal signal profile of the subject's pulse, and for calculating a fluid flow rate based on the temporal signal profile after filtering out pressure spikes/pulses from the blood pump.

US2018/078212 discloses a system and method for assessing a patient's respiratory health and indicating and characterizing respiratory stress. The device includes a sensor in communication with a patient to generate a biological signal having a time-domain waveform curve. The biological signal is processed and a waveform curve reflecting the patient's respiratory rate is calculated. A correlation between the waveform curve of the biological signal and the waveform curve of the respiratory rate is then determined and a respective correlation coefficient is determined. A frequency analysis is performed on the biological signal and a determination of a respiration metric is made that reflects the proportion of spectral components associated with the respiration component of the biological signal relative to the total spectral components of the biological signal. The correlation coefficient and the respiration metric are combined to form a respiratory stress metric for display to the user.

WO2018/112354 discloses a system and method for monitoring and determining patient parameters from the detected venous waveform. This document discloses the evaluation of a plurality of frequencies associated with local maxima of the peripheral venous pressure (PVP) signal in the frequency domain, including the heart rate (F1) and the harmonic frequency (FH) at a harmonic of the heart rate.

Regardless of the type of known sensor technique used for sensing, pump pressure or flow spikes greatly affect the reliability of the heartbeat and/or heart rhythm reading.

Description of the drawings

The above technical aspects and other relevant technical aspects of the disclosure will be described in the following part of this disclosure with the help of the attached figures where:

- Figures 1A and 1B show a schematic diagram of embodiments of a blood treatment apparatus that may be provided with the sensor of the present disclosure;

- Figure 2 shows an operating principle of the sensor of the present disclosure;

- Figure 3 shows a schematic view of the sensor according to the present disclosure;

- Figure 3a shows a perspective view of the sensor according to the present disclosure in an operational configuration in which its body is open to allow the extraction or introduction of a tube or conduit segment of a blood circuit into a cavity in which sensor elements are provided;

- Figure 3b shows a perspective view of a circuit configuration of a particular embodiment of the sensor according to the present disclosure;

- Figure 4 shows a schematic block diagram of the signal processing operations performed through the sensor object of the present disclosure;

- Figure 5 shows an example diagram of an electrical output signal provided by a sensing portion of the sensor according to the present disclosure;

- Figure 6 shows a frequency domain diagram showing the combined spectral peaks of the background noise, noise induced by the operation of at least one pump of the apparatus, and the peaks related to the actual blood pulses provided by the heart, as detected through the sensor of the present disclosure;

- Figure 7 shows a flow chart showing the steps of a method for detecting heartbeat and/or heart rate through the non-invasive sensor of the present disclosure;

- Figure 8 shows a combined diagram of a raw signal, corresponding to the output signal of a sensor detector according to the present disclosure, and of a square wave signal, associated with the pump, used to process the output signal;

- Figure 9 shows a combined diagram where the upper part represents a resulting signal, the product of the multiplication between the output signal and the square wave signal associated with the pump, and where the lower part represents an additional signal, corresponding to the previous signal, after having eliminated the average of the value of the parts not set to zero;

- Figure 10 shows a combined diagram in which the upper part represents a frequency domain spectrum of the pulses induced by the pump and by the heart, as read by the sensor according to the present disclosure, without the processing of the raw output signal as schematically shown in Figure 8 and Figure 9, and where the lower part represents the result of the processing of the detector output signal following the procedure of Figure 8 and Figure 9, where it can be observed how the maximum pulses related to the heart-induced blood pulses then have a significantly higher magnitude than before, being now comparable in amplitude to that of the pump;

- Figure 11 shows a schematic flow diagram of the method described in Figures 8, 9 and 10; and

- Figure 12 shows a schematic front view of a cabinet structure for the appliance of Figure 1A or 1B.

Detailed description

The present invention is defined in the appended claims.

The present disclosure first describes a non-invasive, reusable (i.e., non-disposable) heartbeat sensor whose operation takes advantage of optical radiation to detect flow disturbances in a fluid comprising blood flowing into a conduit, in particular a conduit or tube of a blood circuit configured to be installed in an extracorporeal blood treatment apparatus 1.

Definitions

For the purposes of this disclosure:

- "non-invasive" means any means, and in particular a sensor, which does not come into contact with the user's body, and in particular is not configured to be introduced into the user's body or come into contact, in particular direct contact, with a fluid of the user, specifically blood, which penetrates the duct segment to perform the detection for which it is designed;

- "flow disturbances" means a local variation in the flow or density or volume of a fluid, in particular, but not limited to, blood or fluids containing a significant proportion of blood; - "optical radiation" means any electromagnetic field radiation within the infrared, visible or ultraviolet radiation spectrum, that is to say any radiation with a vacuum wavelength substantially between 1000 pm (300 GHz, corresponding to far infrared) and 10 nm (3000 THz, corresponding to extreme UV) according to ISO 21348;

- "infrared radiation" means any radiation with a wavelength in vacuum between 0.7 pm and 1000 pm, and more particularly between 1 pm and 350 pm or between 790 nm and 820 nm, for example between 800 nm and 810 nm;

- "visible radiation" means any radiation whose wavelength in vacuum is substantially between 400 and 750 nm, and

- "red radiation" means any radiation whose wavelength in vacuum is substantially between 620 nm and 750 nm.

As disclosed above, the sensor according to the present disclosure is configured to be installed in an apparatus 1 for extracorporeal blood treatment that can be configured to perform one or more of the following treatments: hemodialysis (HD), hemofiltration with predilution (HFpre), hemofiltration with postdilution (HFpost), hemofiltration with both predilution and postdilution (HFpre-post), hemodiafiltration with predilution (HDFpre), hemodiafiltration with postdilution (HDFpost), hemodiafiltration with both predilution and postdilution (HDFprepost), ultrafiltration (UF), or that is configured to be installed in a segment 101 of a blood circuit suitable to be installed in said apparatus.

Brief description of the device

For the purposes of clarity of exposition and contextualization of the operation of the sensor disclosed herein, a brief description of the apparatus 1 is provided below.

Examples of an apparatus 1 for extracorporeal blood treatment, which may implement innovative aspects of the invention, are shown in Figures 1A and 1B. In the following description and in Figures 1A and 1B, the same components are identified with the same reference numbers.

The apparatus 1 includes at least one sensor 100 that can be configured to determine at least the heartbeat and/or the heart rate. As is evident from the following description, the sensor 100 can be placed in any position of the hydraulic circuit, and particularly in the blood circuit 60. Figure 1A shows an apparatus 1 suitable for chronic treatments and Figure 1B describes an apparatus suitable for administering acute treatments; both apparatuses are configured to administer any of the treatments such as ultrafiltration, hemodialysis and hemodiafiltration.

The apparatus 1 comprises a treatment unit 2 (such as a hemofilter, an ultrafilter, a hemodiafilter, a dialyzer, a plasma filter and the like) having a primary chamber 3 and a secondary chamber 4 separated by a semipermeable membrane 5; depending on the treatment, the membrane 5 of the treatment unit 2 can be selected to have different properties and performances. A blood collection line 6 is connected to an inlet of the primary chamber 3, and a blood return line 7 is connected to an outlet of the primary chamber 3. The blood collection line 6, the primary chamber 3 and the blood return line 7 are part of an extracorporeal blood circuit, which is globally identified with the reference numeral 60 in Figures 1A and 1B. In use, the blood collection line 6 and the blood return line 7 are connected to a needle or catheter or other access device (not shown) which is then placed in fluid communication with the patient's vascular system so that blood may be drawn through the blood collection line, circulated through the primary chamber, and then returned to the patient's vascular system through the blood return line. As marked in Figure 1B by the curved arrow F, the normal flow of fluid imposed by the blood pump 11 is from the arterial connector 40 to the venous connector 41; therefore, the words "downstream" and "upstream" will be referred to in consideration of such flow. Figure 1A shows the blood flow rate Qbent and its normal flow direction. In a non-limiting solution, the blood collection line 6 and the blood return line 7 are made of transparent plastic material, allowing for example to identify the fluid flow, the presence of bubbles or air inside or even obstructions (via dedicated sensors). At least the inner part of the blood collection line and the blood return line, and particularly any part of the disposable circuit described herein, are made of a material specifically conceived for medical applications, and in particular of a plastic material that is compatible and does not release substances when coming into contact with body fluids and/or lipids, e.g. drug lipids or nutrients. Said plastic may be, for example, PVC, in particular high-quality medical PVC. An air separator, such as a bubble trap 8 may be present in the blood return line; The extracorporeal blood circuit is supported by one or more supports provided, in a conventional manner, by the support structure 70a of the apparatus 1. For example, as shown in Figure 12, the extracorporeal blood circuit 60 may be supported by a support 71 holding the bubble trap, by a support 72 holding the treatment unit 2, and by a support 73 located in correspondence of the blood pump. A safety clamp 9, controlled by a control unit 10 may be present on the blood return line downstream of the bubble trap 8. A bubble sensor 8a, for example associated with the bubble trap 8 or coupled to a portion of the line 7 between the bubble trap 8 and the clamp 9 may be present: if present, the bubble sensor is connected to the control unit 10 and sends signals to the control unit for the control unit to cause the clamp 9 to be closed in case one or more bubbles above certain safety thresholds are detected. The blood flow through the blood lines may be controlled by a blood pump 11, for example a peristaltic blood pump, acting either on the blood withdrawal line (as shown in figure 1) or on the blood return line. An operator may enter a set value for the blood flow rate Qb: the control unit 10, during treatment, is configured to control the blood pump according to the set blood flow rate. It should be noted that the control unit 10 may also be connected to a user interface 12, for example a graphical user interface, which receives operator inputs (such as, but not limited to, the blood flow rate set point) and displays the outputs of the apparatus. For example, the graphical user interface 12 may include a touch screen for displaying results while allowing user input, or a display screen and physical keys for entering user input, or a combination thereof. One end of a spent dialysate line 13 configured to evacuate an effluent fluid from the secondary chamber 4 is connected to an outlet of the secondary chamber 4 and its other end is connected to a drain which may be a discharge line or an effluent fluid container 14 (dashed lines in FIGS. 1 and 2) which collects the fluid withdrawn from the secondary chamber. An effluent fluid pump 17 operates in the spent dialysate line 13 under the control of the control unit 10 to regulate the flow rate Qdout of effluent fluid through the spent dialysate line. The net ultrafiltration (i.e. the net fluid removed from the blood through the semipermeable membrane of the treatment unit 2 may be determined by the flow rate difference between a dialysis fluid pump 21, in the fresh dialysis fluid line 19, and the effluent fluid pump 17. Alternatively (or in combination), the apparatus may also include an ultrafiltration line 25 branching off from the spent dialysate line 13 and provided with a respective ultrafiltration pump 27, also controlled by the control unit 10 to cause a flow rate QF along the ultrafiltration line. The embodiments of Figures 1A and 1B feature a predilution fluid line 15 connected to the blood collection line: this line 15 supplies replacement fluid from an infusion fluid container 16 connected at one end of the predilution fluid line. Although Figure 1A shows a predilution fluid line 15, the apparatus may also include a dialysis fluid pump 21, in the fresh dialysis fluid line 19, and the effluent fluid pump 17. Although the apparatus of FIG. 1A may use the container 16 as a source of infusion fluid, this should not be interpreted in a limiting manner: in fact, alternatively, the infusion fluid may come from an in-line preparation section. Note that, alternatively to the pre-dilution fluid line, the apparatus of FIG. 1A may include a post-dilution fluid line (not shown in FIG. 1A) connecting an infusion fluid container, or an in-line preparation section of infusion solution, to the blood return line. Finally, as a further alternative (not shown in FIG. 1A), the apparatus may include a pre-dilution fluid line and a post-infusion fluid line: in this case, each infusion fluid line may be connected to a respective infusion fluid container or may receive infusion fluid from a same infusion fluid source, such as a same infusion liquid container or an in-line preparation section. In case the infusion liquid is prepared in-line, the source of infusion fluid may be an in-line preparation section forming part of the apparatus 1 (i.e. such as the in-line preparation section 200 described hereinafter) or a separate device analogous to section 200 and connected to the infusion line(s) and configured to supply fluid to the post-dilution and/or pre-dilution lines (see FIG. 1A). Also, an infusion pump 18 operates in the infusion line 15 to regulate the flow rate Qrepi through the infusion line 15. Note that in the case of two infusion lines (pre-dilution and post-dilution), each infusion line may be provided with a respective infusion pump. The apparatus of Figure 1A further includes a fluid preparation line 19 connected at one end to a water inlet and at its other end to the inlet of the secondary chamber 4 of the filtration unit, for supplying fresh treatment liquid to the secondary chamber 4. A dialysis fluid pump 21 operates in the fluid preparation line, under the control of said control unit 10, to supply fluid from a source of fresh treatment liquid (such as a container or the section 200 for preparing fresh dialysis liquid on-line) to the secondary chamber at a flow rate Qdent. In the example of Figure 1A, the line 19 connects the hemodialyzer or hemodiafilter 2 to the on-line preparation section 200, which is configured to prepare the dialysis liquid: the section 200 comprises a main line 201, the upstream end of which is designed to be connected to a water supply. A first secondary line 102 and a second secondary line 103 are connected to the main line 201 and are configured to at least supply the necessary amount of a regulator and the necessary amount of electrolyte. The first secondary line 102, which can return back to the main line 201, is configured to accommodate a first container 104, such as a bag or cartridge or other container, containing a regulator. The line 102 is further equipped with a first metering pump 105 for metering the regulator into the fresh treatment liquid: as shown in Figure 1A, the pump may be located downstream of the first vessel 104. The operation of the pump 105 may be controlled by the control unit 10 based on the comparison between: 1) a set point value for the regulator concentration of the solution forming at the junction of the main line 201 and the first secondary line 102, and 2) the value of the regulator concentration of this mixture measured through a first probe 106 located either in the first secondary line, downstream of the first vessel 104, or in the main line 201, immediately downstream of the junction between the main line 201 and the first secondary line 102. Likewise, the free end of the second secondary line 103 is intended to receive fluid from the second vessel 107 containing a concentrated saline solution, e.g. electrolytes such as sodium chloride, calcium chloride, magnesium chloride and potassium chloride. In a variant, the second secondary line 103 can also return to the main line 201. It is also possible to provide a plurality of independent second secondary lines 103 in case it is desired to feed electrolytes or independent electrolyte compositions from the respective containers. Note that the second secondary line 103 is equipped with a second dosing pump 108 for dosing electrolytes into the fresh treatment liquid; The operation of the second metering pump depends on the comparison between 1) a conductivity set point value or an electrolyte concentration set point value for the solution formed at the junction of the main line 201 with the second secondary line 103, and 2) the conductivity or electrolyte concentration value of this solution measured through a second probe 109 located either in the second secondary line, downstream of the second vessel 107, or in the main line 201, immediately downstream of the junction between the main line 201 and the secondary line 103. Note that the specific nature of the concentrates contained in vessels 104 and 107 may vary depending on the circumstances and the type of fresh treatment fluid to be prepared. Furthermore, the nature and position of the first and second probes may depend on the type of regulator used, the type of electrolyte concentrate(s) adopted and the specific configuration of the circuit formed by the main line and the secondary lines. Also, as already mentioned above, there may be more than two secondary lines, with respective concentrate containers and respective dosing pumps, in case it is necessary to add a plurality of different types of substances for the preparation of the fresh treatment fluid. The second probe is generally a conductivity meter configured to measure the conductivity Oent of the dialysis fluid upstream of the filtration unit 2. Of course, the conductivity Oent of the dialysis fluid is set by the operator or set and controlled by the apparatus during the treatment. Likewise, the apparatus includes an additional conductivity meter 112 placed on the spent dialysate line 13 to detect the conductivity Os of the dialysis fluid downstream of the filtration unit 2. Both conductivity meters 109 and 112 provide the respective measurement signal to the control unit 10 of the apparatus. Flow sensors 110, 111 (either volumetric or mass type) may be used to measure the flow rate in each of the lines. The flow sensors are connected to the control unit 10. In the example of Figure 1A, where the infusion line 15 and the ultrafiltration line 25 lead to a respective container or bag 16, 23, scales may be used to detect the amount of fluid administered or collected. For example, the apparatus of Figure 1A includes a first scale 33 that serves to provide weight information W<1> regarding the amount of fluid collected in the ultrafiltration vessel 23 and a second scale 34 that serves to provide weight information W<2> regarding the amount of fluid delivered from the infusion vessel 16. The embodiment of Figure 1B shows an alternative apparatus 1 designed to administer acute treatments such as hemodialysis, hemofiltration, hemodiafiltration and ultrafiltration. In the apparatus shown in Figure 1B, the same components described for the embodiment of Figure 1A are identified by the same reference numerals and, therefore, are not described again. Unlike the hemodiafiltration apparatus of Figure 1A, the apparatus of Figure 1B does not feature on-line fluid preparation since all fluids are prepackaged in sterile containers. The fresh dialysis fluid is contained in a fresh dialysis container 43. Furthermore, the fluid line 19 and the effluent line 13 are of the disposable type and are directly and immovably linked to the treatment unit 2. Accordingly, the dialysis pump 21 and the effluent pump 17 are peristaltic pumps (and not volumetric pumps according to the embodiment of Figure 1A). The embodiment of Figure 1B presents the predilution fluid line 15 connected to the blood collection line 6: this line 15 supplies replacement fluid from the infusion fluid container 16 connected at one end of the predilution fluid line. Furthermore, the apparatus may further comprise the infusion pump 18, which operates on the infusion line 15 to regulate the flow rate Qrep through the infusion line. Note that, alternatively or in combination with the pre-dilution fluid line, the apparatus may include a post-dilution fluid line 28 connecting an infusion fluid container 29 to the blood return line 7. Another pump 30, for example a peristaltic pump, may act under the control of the control unit 10 on the post-dilution fluid line 28 and thus also be part of a means for regulating the flow through the fluid lines. Additionally, the disposable circuit shown in Fig. 1B may feature an additional infusion line 31 connected, at one end, to the blood collection line 6 positioned upstream of the blood pump 11 and, at its other end, to another infusion fluid container 32, which, for example, may contain a drug or a regional anticoagulant such as a citrate solution. This additional infusion line is referred to herein as the pre-dilution infusion line 31 of the blood prepump. The regulating means comprises a pre-blood pump (PBP) 22, for example a peristaltic pump controlled by the control unit 10, which acts on a segment of the pre-dilution infusion line 31 of the pre-blood pump to regulate the infusion flow rate Qpbp of the pre-blood pump. The pump 22 is normally part of the apparatus 1 and is therefore not part of the disposable set. Alternatively or in combination with the above-mentioned fluid lines, the apparatus of Figure 1B may comprise one or more auxiliary lines 42, which are connected, at one end, to a blood withdrawal line 6. Figure 2 shows a single auxiliary line. Another pump, not shown in Figure 2, for example a peristaltic pump, may act under the control of the control circuit 10 in the auxiliary line and thus also be part of said means for regulating the flow through the fluid lines. In the embodiment of Figure 1A, the apparatus includes a first scale 33 operative to provide weight information W<1> with respect to the amount of fluid collected in the ultrafiltration vessel 23 and a second scale 34 operative to provide weight information W<1> with respect to the amount of fluid collected in the infusion fluid container 16. All of the scales are connected to the control unit 10 and provide such weight information Wi for the control unit to determine the actual amount of fluid in each vessel as well as the actual flow rate of fluid delivered or received into each vessel. Figure 1B further includes third, fourth, and fifth scales 35, 36, 37 for respectively sensing the weight of the fresh dialysis vessel 43, the citrate infusion vessel 32, and the post-infusion fluid container 29. In the example of Figure 1A, to monitor the fluid balance between the amount of fluid supplied to the secondary chamber 4 and the amount of fluid withdrawn from the secondary chamber, flow sensors 110, 111 positioned on the fresh dialysate line and the spent dialysate line 13 provide the control unit 10 with signals indicative of the fluid flow through the respective lines and the scale(s) provide weight information enabling the control unit to calculate the flow rate through the ultrafiltration line 25 and, if present, through the infusion line 15. The control unit is configured to control at least the pumps 17, 21 and 27 to ensure that a prescribed removal of fluid from the patient is achieved over the course of a prescribed treatment time, as required by the prescription provided to the control unit, e.g., via the user interface 12. Note that other fluid balancing systems may be used: for example, in case the apparatus includes a container as a source of fresh treatment fluid and a container for collecting waste (see Figure 1B), scales may be used to detect the amount of fluid delivered or collected by each container and then inform the control unit accordingly. As a further alternative, systems based on volumetric control may be used where the preparation line 19 and the spent dialysate line 13 are connected to a balance chamber system which ensures - at each instant - that the amount of fluid flowing into the line 19 is identical to the amount of fluid leaving the line 13. From a structural point of view, one or more of the containers 104, 107, 16, 23 may be disposable plastic containers. The blood lines 6, 7 and the filtration unit may also be disposable plastic components which may be assembled at the beginning of the treatment session and then disposed of at the end of the treatment session. Pumps, e.g. peristaltic pumps or positive displacement pumps, have been described as means of regulating the flow of fluid through each of the lines; however, it should be noted that alternatively other means of regulating flow may be adopted such as, for example, valves or combinations of valves and pumps. The scales may comprise piezoelectric sensors, strain gauges, spring sensors or any other type of transducer capable of sensing forces applied to them.

Sensor Description

The sensor according to the present disclosure exploits the variation in the physical properties of an optical radiation to detect alterations in the flow in a fluid comprising blood flowing towards the segment 101 of a tube or conduit for extracorporeal blood treatment. It follows that the segment 101 should provide a certain transparency to the wavelengths of optical radiation involved in the measurement. In particular, the sensor 100 object of the present disclosure makes it possible to detect variations in the concentration of blood and in particular of red blood cells over time, through which it is possible to identify a heartbeat and therefore a heart rhythm; in more detail, when irradiated with a suitable optical radiation, the transmission of the radiation through the blood varies according to its concentration, in particular as a function of the concentration of red blood cells, which in turn varies according to the flow peaks produced by the heartbeats. Thus, by counting the cadence of the flux peaks, i.e. the peaks (or correspondingly the decreases) in radiation transmission, it is possible to detect the heartbeats and therefore the frequency with which the heart beats.

The sensor 100 according to the present disclosure is non-invasive and allows continuous monitoring of the heartbeat that can last without significant interruption for any desired time, and for the entire duration of the blood treatment as required by the standard or acute therapy to which the patient is subjected. Since during normal operation no part of the sensor comes into contact with the user's blood, the sensor object of the present disclosure is reusable and therefore does not constitute a so-called disposable device. In this way, some processing intelligence can be arranged on board it, without involving relevant exchange costs, which would otherwise be present in any case where known sensors come into contact with blood. The sensor 100 is in particular placed on a segment of the blood circuit, specifically the blood extraction line 6 and/or the blood return line 7. More than one sensor 100 can be used depending on the circumstances and placed in different positions along the conduit. In a non-limiting manner, any electronically sensitive part of the circuit arranged within the sensor body shall be adequately protected against external agents, in accordance with an appropriate IP standard, so that, if necessary, the sensor can be washed, cleaned, sterilized or disinfected in a convenient manner without significant risks of damaging it and without contaminating blood lines when it is reinstalled for subsequent treatments.

In general terms, and according to the schematic representation of Figure 2, the sensor 100 comprises at least one optical source 55 that emits optical radiation through the conduit segment 101 that is filled with a fluid comprising blood. The optical radiation thus passes through the walls of the conduit segment 101 and the fluid contained therein, then reaches an optical sensor 57 that is capable of detecting at least one amplitude variation of the received optical radiation. The sensor transmits an output signal 200R that is then suitably processed to extract the heart rate. In a particular embodiment disclosed in Figure 3, the sensor 100 comprises a plastic housing 51, represented only schematically in the attached drawings. The housing 51 is designed to be firmly coupled to the blood line segment 61 of the extracorporeal blood circuit 60, where it is necessary to measure the blood or plasma parameters. The housing 51 may be an independent body or may be attached to or be part of a support structure 70a of the apparatus. For example, the housing 51 may be secured to the front panel of the support structure (see Figure 12) and configured to receive at least one (in the drawing examples only one) segment 61 of the extracorporeal blood circuit. For this purpose, the housing 51 may have a shape directly opposite to a portion of a blood line tubing, namely a circular cross-sectional segment of a flexible transparent plastic tubing of a blood collection line 6 or a blood return line 7. The housing may be an openable and closable housing defining a through interior passage 52 for receiving the blood circuit tubing.

Notably, the housing 51 may be made of two or more parts 51a, 51b either separated or joined together, e.g. with hinges, to define an uncoupled configuration (see Fig. 3a) and a coupled configuration (see Fig. 3). In the coupled configuration, the through passage 52 is shaped contrary to the tube it is to receive so as to perfectly couple it and receive the tube. It should be noted that the first part 51a defines a first portion of the portion formed contrary to the through passage 52, while the second part 51b defines a second portion of the portion formed contrary to the through passage 52: in more detail, in the attached figures those parts are half circles of identical shape. The schematic drawings illustrate a situation where the flexible blood tube is coupled to the sensor 100. However, the housing 51 may have an alternative shape to couple with a rigid cuvette (such as the cuvette for the Hemoscan® sensor from Baxter). In such a case, the flexible tube of the blood circuit has the rigid cuvette correctly applied so that the blood flowing in the extracorporeal blood circuit 60 passes through the cuvette itself; in this latter case, the through passage has a shape contrary to the outer surface of the cuvette, which is not necessarily rounded but may alternatively have flat outer surfaces (polygonal section).

It is clear that in case the housing is to be applied to the flexible circular tube of the extracorporeal blood circuit 60, any position of the sensor along the blood collection line 6 or the blood return line 7 is suitable. In case the sensor 100 has a direct passage in the opposite way to a specific cuvette, the sensor must be applied in correspondence with the cuvette itself for its correct operation.

The housing 51 may be made of a highly absorbing material which prevents external ambient light from reaching the receivers. This helps to reduce the risk of external optical radiation sources adversely influencing the heartbeat reading by providing spurious peaks or dips in the amplitude of the light, particularly when such peaks or dips are close in frequency to that of a physiological heartbeat.

The sensor 100 comprises at least one signal source 53 for directing a signal towards the blood along an emission axis 54. The signal source 53 may include any suitable signal emitter, such as an optical (or acoustic) emitter that directs a suitable emitted signal towards the interior of the tube through which the blood flows. In embodiments of the present invention, the signal source 53 includes a source of electromagnetic radiation, particularly a light source such as an LED source, a SLED or a laser source. In the following description, we refer to an optical emitter and in detail to an LED emitter 55; however, this should not be construed as limiting. It has been observed that the non-limiting wavelength peak of the optical radiation transmitted by the signal source 53 is set at 800-810 nm, corresponding to the point of the Hgb absorption spectrum where absorption is not dependent on oxygenation. Again, this should not be considered a limiting aspect; In fact, in principle, any optical radiation in the infrared or red light field can be used for the present application. In a simple embodiment as described in Figure 2, the signal source 53 may comprise a simple, non-coherent multimode LED transmitting an optical radiation with a first wavelength peak Á<1> within the infrared or red region, or within a predetermined emission window of wavelengths (or frequencies) where said first wavelength peak Ai falls. The specific implementation of the signal source 53 further includes a multi-wavelength LED emitter (specifically MTMD6788594SMT6, Marktech Optoelectronics, NY, USA) used for the light emission. The emitter 55 in particular includes 5 LEDs on the same chip, with wavelength peaks A<1>, A<2>, A<3>, A<4>, A<5>, in the red/infrared bands. These five LEDs emit optical radiation with wavelength peaks that are different from each other. In this way, a diversity of wavelengths (or equivalently of frequency) can be obtained in order to increase the accuracy of heartbeat detection and to reduce any external influence on the heartbeat reading.

The source 53 further comprises an optical fiber 56 having one end 56a coupled with the signal emitter 55 and the other end 56b fixed to the housing 51 and positioned to direct the optical radiation toward the blood along the emission axis 54 of the source 53. As shown in Figure 3, the second end 56b of the optical fiber 56 is positioned in the counter-shaped portion and faces the tube in a condition of coupling the housing with the tube segment 61.

The sensor 100 comprises a plurality of detectors 57 for receiving the signal emitted by said source after passing at least partially through the blood; in particular the detectors 57 collect the reflected signal, the scattered signal and/or the transmitted signal depending on their respective position. Since the emitter 55 is an LED emitter, the detectors 57 may comprise photodiode receivers 58. In one embodiment, the detectors 57 are positioned at different angular degrees with respect to the emission axis 54. In more detail, the sensor 50 of Figure 3 includes four different detectors 57 for receiving electromagnetic radiation from the source 53, a first photodiode receiver PD1 being positioned at approximately 180° with respect to the emission axis 54 of the signal source, a second photodiode receiver PD2 being positioned at approximately 90° with respect to the emission axis of the signal source, a third photodiode receiver PD3 being positioned at approximately 45° with respect to the emission axis of the signal source, a fourth photodiode receiver PD4 being positioned at approximately 0° with respect to the emission axis of the signal source. Of course, more (or less) than 4 receivers may be used depending on the specific need and also more than one receiver may be positioned at the same angular degree with respect to the emission axis 54 of the optical fiber. More specifically all detectors 57 are arranged in a single plane, which in turn coincides with the plane in which the source 53 is arranged. This allows for spatial diversity of detection which, when present, cooperates with the emission of multiple wavelengths of optical radiation to further increase the quality of the heartbeat reading and makes the sensor 100 more resistant to external radiation influences. Each detector 57 is configured to receive the signal emitted by the signal source (and appropriately reflected, scattered or transmitted) radially along the normal section of blood flow in the tubing of the extracorporeal blood treatment apparatus. The new measurement system extends the architecture of the traditional design to collect light at different geometric angles with respect to the emitter, allowing discrimination between reflected, scattered and transmitted light. A loss of transmitted light due to increased scattering is not erroneously detected as an increase in absorbance if, at the same time, the scattered light is picked up by a different receiver. To achieve the above configuration, each detector 57 includes a respective optical fiber 59, one end of which is positioned in correspondence with the segment 61 and the other end is coupled to a receiver, in detail a photodiode receiver. In more detail, the end of the optical fiber 59 in correspondence with the segment 101 is fixed to the housing 51 and is positioned in the portion formed opposite and facing the segment 101 in a coupling condition of the housing with the segment 101. As mentioned, all the channels for receiving the signals are positioned radially along the normal section of the blood flow, except the reflection channel (0°) which is slightly offset along the flow direction to allow the positioning of the emission fiber 56. Both the emitted and collected optical radiation are coupled to and from the segment 101 using, for example, plastic optical fiber (ESKA GH4001, Mitsubishi Rayon). The photodiode receivers 58 may have specific fiber coupling mechanics (e.g., IFD91, Industrial Fiber Optics, Tempe, USA) for the light collection channels corresponding to PD1-4 in Fig. 3.

The photodiode receivers 58 are housed on a printed circuit board 60a together with an analog transimpedance amplification circuit 62; the transimpedance amplification circuit 62 includes a current to voltage converter (for example implemented using an operational amplifier). The circuit 62 can be used to amplify the current output of the photodiode receivers 58. Current to voltage converters are used with photodiodes that have a current response that is more linear than the voltage response (it is common for the current response to have better than 1% linearity over a wide range of light input). The transimpedance amplifier presents a low impedance to the photodiode and isolates it from the operational amplifier output voltage. There are several different configurations of transimpedance amplifiers, the one factor they all have in common being the requirement to convert the low level current of a sensor to voltage. The printed circuit board 60a further includes a low pass filter stage 63 and a gain amplification stage. The cut-off frequency of the low pass filter 63 is set to, for example, 30 Hz. This helps to reduce unwanted noise that may affect the signal processing performed on the output signal 200R produced by the detector. The low pass filter 63 may further be set to a lower frequency, e.g., less than 10 Hz, particularly at or below 5 Hz or 4 Hz, to further limit the upper bandwidth of the output signal 200R. The gain is set to channel specific values based on preliminary testing and calibration. The analog signals are then converted to digital signals by a suitable converter 64. In more detail, the analog outputs are sampled at a rate of 100 Hz with a 12-bit resolution using an NI USB-6008 DAQ card (National Instruments Italy Sri, Milan, Italy) and recorded using a custom LabView Virtual Instrument. The multi-LED emitter, the signal conditioning board and the DAQ card were assembled together in a 3D printed housing and placed inside a grounded metal box (see Figure 3), as electromagnetic shielding, provided with openings 56, 59 for optical fiber, data connection and power supply. In a particular embodiment, each of the detectors 57 is configured to receive optical radiation at a predetermined wavelength or in a predetermined frequency window. In more detail, the first detector 57 (PD1) is configured to receive optical radiation at the first wavelength Á<1>, or in a first frequency window comprising said first wavelength, the second detector 57 (PD2) is configured to receive optical radiation at the second wavelength Á<2>, or in a second frequency window comprising said second wavelength, the third detector 57 (PD3) is configured to receive optical radiation at the third wavelength Á3, or in a third frequency window comprising said third wavelength and the fourth detector 57 (PD4) is configured to receive optical radiation at the fourth wavelength Á4, or in a fourth frequency window comprising said fourth wavelength. The various radiation wavelengths described above can be used to detect flow variations by more or less specific analysis of hematocrit flow and osmolarity; since the effects of osmolarity can be detected and decoupled, a better estimate of blood volume variation can also be obtained. The use of several channels to detect radiation at different wavelengths allows undesired effects to be determined and eliminated and, even better, allows heartbeat detection because the influence on the overall transmission of radiation is given by two different properties of the blood. It may turn out that variations at least in the amplitude of the received optical radiation in some channels may be more sensitive to specific parameters, while the behavior of other channels is rather a mixture of properties (hematocrit and osmolarity). The digital signals are input to a controller 65 for use in detecting the heartbeat and heart rhythm through the tube segment 61 of the extracorporeal blood treatment apparatus, as will become clear from the following detailed description.

Signal processing and method for detecting heartbeats

The Applicant has understood that a measured response signal (e.g., an optical signal) from a detector (e.g., an optical signal) in a method for detecting heartbeats is affected at least by the concentration of red blood cells resulting from the pulses provided by the heart. Furthermore, said concentration of red blood cells is also affected by the pulses provided by the cyclic operation of the peristaltic pump. The Applicant has further discovered that the information signal received by the one or more detectors 57 is not substantially altered and/or is not substantially related to or is not substantially a function of variations in size and/or geometry of at least a portion of the segment 101 in which said information signal is received, said variations in size and/or geometry being the result of said disturbance of the flow of blood flowing through the segment 101. This means that even if the segment 101 may be enlarged and/or deformed as a result of flow peaks induced by the heart or, above all, by the operation of any of the pumps of the apparatus, ultimately, the reliability and accuracy of the detection of the appropriate heartbeat frequency are not substantially affected. In this regard, it is noted that detecting the heartbeat frequency in accordance with the present disclosure makes it possible to reduce the requirements on the materials and/or design of the segment 101, which may be very hard or, on the contrary, soft; Conversely, reading the heartbeat rate through any heartbeat measurement by assessing the deformation of segment 101 may require significant consideration of the materials and sizes used to size segment 101.

Figure 4 shows a block diagram of the main signal processing operations performed through the sensor 100 according to the present disclosure; it should be noted that said processing is described below as being performed by the controller 65. At least part, or any part, of the signal processing may be performed by a data processing unit that is different from the controller 65 and may be arranged outside the body of the sensor 100. It should further be noted that while current technology allows at least part of the signal processing described herein to be performed through software, e.g. through software loaded into electronically accessible memory, e.g. the controller 65, at least part of the processes and steps of the following description may be performed or carried out through physical, i.e. hardware, steps shown in Figure 4. As shown in Figure 4, after the photodiode receiver 58, a transimpedance amplifier 62 is arranged to transform the current signal generated by said detector 57 into a voltage output signal. The output of the transimpedance amplifier 62 feeds the input of the low-pass filter 63 whose output in turn feeds the inputs of the analog-to-digital converter 64, which samples the signal, transforming it so that the output signal that will be further processed electronically is in the numerical domain.

As schematically shown in Figure 5, and as reported in the brief flow chart of Figure 7, an output signal 200R, produced as an output after receipt of the optical signal passed through the blood and the segment 101 (these steps correspond to block 1000 of Figure 5), is first sampled in a sampling reference window 200W of a predetermined length. Figure 5 shows an example where said window has a length of 30 s, but this example is not intended to be limiting since the sampling reference window 200W may have, for example, a duration equal to or less than 1 minute, or equal to or less than 45 s, or equal to or less than 30 s, or equal to or less than 20 seconds, or equal to or less than 15 seconds, or equal to or less than 10 seconds. The portion of the output signal 200R contained within such a window will hereinafter be referred to as the reference portion of the output signal 200R. It should be noted that the longer the window, the greater the averaging of the processing results. Although lengthening the window may have a positive effect by averaging out occasional noise spikes in the output signal 200R, excessive window length should be discouraged in order to reduce the risk of significant heartbeat frequency variation within the window, which could compromise the quality of the heart rate reading and the subsequent processing to which the signal is subjected.

In case the controller 65 is implemented via hardware processing stages, the windowing of the output signal 200R into a sampling reference window 200W of a predetermined length may be implemented by a time-domain window stage 67, operating with digital signals, the input of which is fed, in particular directly fed, by the output of the analog-to-digital converter 64.

The output signal 200R of Figure 5 contains not only the heartbeat information carried by the flow pulses induced by the patient's heart, but also unwanted noise, including unwanted noise that is produced by the peristaltic blood pump 11 operating to force the flow of fluid into the blood circuit, in particular into segment 101. In more detail, Figure 5 is the result of a raw (unfiltered) signal at the detector output under the following test conditions:

- fluid flow in segment 101 with the peristaltic blood pump 11 set to 200 ml/min, which for the reference apparatus 1 used for the test results in an unwanted pump noise whose frequency is approximately 1.0 Hz;

- fluid flow in segment 101 with a cardiac simulator set to 70 bpm, whose nominal frequency corresponds substantially to 1.16 Hz.

Subsequently, via the controller 65, further electronic processing of the signal is performed. In particular, the output signal 200R, and in particular its relevant portion within the aforementioned window, is subjected to a frequency domain transformation, for example by applying a Fourier transform, in particular a fast Fourier transform (this step corresponds to block 1001 of FIG. 7). It should be noted that the fast Fourier transform may not be the only way of calculating the frequency domain transformation, but it is the one selected by the Applicant since one of the illustrative embodiments described herein operates with an output signal in the numerical domain, as it was converted thereto via the analog-to-digital converters disclosed above.

6 shows an example diagram of the spectrum of the signal of FIG. 5 after it has been converted from the time domain to the frequency domain. If the controller 65 were formed by hardware signal processor stages, the step of transforming the windowed reference part of the output signal 200R from the time domain to the frequency domain is performed via a Fourier transform stage 68, particularly a stage performing processing according to FFT algorithms, the inputs of which are fed directly by the output of the time domain window stage 67. The maximum frequency of the examined spectrum is set to 4 Hz; this is done e.g. via the time domain low pass filter stage 63, or it can be performed otherwise by a hard cut-off of the Fourier transform at the above-mentioned frequency; the choice of a low maximum frequency for the electronic spectrum processing is made since the search for the heartbeat is performed considering the fundamental harmonic and the 2nd harmonic of the same, which physiologically and/or typically in the normal resting condition in which the patient is during the treatment, does not exceed 4 Hz. In any case, as a precautionary measure, higher frequencies can be chosen, e.g. up to 30 Hz as described above when analyzing the operation of the low-pass filter 63. It is observed that below 0.3 Hz, the amplitude of the spectrum increases rapidly. Once again, the Applicant has considered that the fundamental frequency of a physiologically beating heart, at least under the resting conditions in which the patient remains during treatment, is not below 0.6 Hz, 0.5 Hz, 0.4 Hz or even 0.3 Hz. The Applicant has therefore chosen to electronically select a first lower frequency window 200L containing portions of the spectrum which are not relevant to the present detection, and an upper frequency window 200U starting with a lower frequency just above the highest frequency of the lower frequency window 200L. The latter, in the diagram of Figure 6, is 0.6 Hz. The lower frequency window 200L is excluded from further signal processing; This helps to analyze a portion of the spectrum free of highly relevant unwanted noise, which has been shown to be in the lower part of the spectrum and may be due to, for example, blood flow within segment 101, respiration, and/or other physiological or external "disturbances." Any relevant data regarding the boundaries of the lower frequency window 200L, e.g. the upper frequency of the lower frequency window 200L and/or any relevant data regarding the upper frequency window 200U, e.g. its lowest and highest frequencies, may be conveniently stored in a memory 65m, disposed within the body of the sensor 100 or otherwise operatively accessible at least by the Fourier transform stage 68. The window of interest is then the upper frequency window 200U, which in the example diagram in Figure 6 starts at the lowest frequency of 0.6 Hz and ends with an upper frequency of 4 Hz. In these regions there are substantially any fundamental physiological heart rate, its 2nd harmonic and - where applicable, as shown - the fundamental harmonic and at least the 2nd harmonic of the peristaltic pump 11. Actually, the diagram in Figure 6 shows relevant peaks which are marked with the reference numbers "1", "2", "3", "4" and "5" enclosed in a circle. Among them, the fundamental frequency of the pump 11 is marked with the reference frequency "fp", and its 2nd harmonic is marked with the reference frequency "fph<2>"; As can be seen, the fast Fourier transform of Figure 6 shows the fundamental frequency fp of pump 11 just below 1 Hz and its 2nd harmonic just below 2 Hz. The selection of the upper frequency window 200U, or otherwise the filtering of the lower frequency window 200L, may be performed by an upper frequency window selection stage 69, should the controller 65 comprise hardware signal processing stages. It can be seen that the upper frequency window selection stage 69 actually behaves as a high pass filter, or a band pass filter whose lowest frequency substantially coincides with the highest frequency of the lower frequency window 200L. The inputs of the upper frequency window selection stage 69 are fed by the output of the Fourier transform stage 68; The outputs of the upper frequency window selection stage 69 feed a peak detection stage 70 whose operation will be clarified in the next part of the description.

The fundamental frequency of the heartbeat, as will become clearer when reading the next part of the description, corresponds to peak "3" of the spectrum, and the frequency is marked with the reference name "fHR". It is noted here that the diagram also shows a 2nd harmonic of this heartbeat frequency, the peak of which is designated with the reference number 200P. It should be noted that up to this step, the heartbeat frequency is not yet known and is retrieved after performing some further processing steps. In fact, the fundamental frequency of pump 11 and therefore its 2nd harmonic which, like any 2nd harmonic, is nominally twice the fundamental, is known to the controller 65. In fact, any apparatus 1 is provided with a specific pump 11, in particular a specific set of pumps in case there are many of them, which for any preset flow rate [l/min] rotate at a predetermined angular speed, i.e. their rollers cyclically compress and allow to expand a portion of pipe at a predetermined frequency. Thus, one of the following cases may occur:

- if a pre-established finite table of flow rates can be established for the operation of the pump 11, the biunique flow rate/frequency relationship is presented in a table stored in advance in a memory operatively accessible to the controller 65;

- in case the user can set at will an undefined flow rate, a sensor, e.g. a Hall sensor, may be arranged in the apparatus, in particular in substantial correspondence with the pump, to directly detect the operating frequency of the pump itself. Recapitulating, and as schematically marked in block 1006 of the flow diagram of Figure 7, this part of the signal processing generally comprises recovering the operating frequency of the pump 11 forcing the fluid flow towards the relevant segment 101 to which the sensor 100 is coupled, and this recovery may be performed electronically by direct detection or by loading a value from a table. It is therefore evident that the peaks referred to in Figure 6 by the references "2" and "5" can be clearly identified and then discarded by further electronic processing. In other words, the electronic processing performed by the controller 65 comprises (block 1007 in the flow diagram of Figure 7) a search and exclusion of the fundamental frequency fp of the pump 11 and any of its harmonics fph<2>, fph3, ... fphn. In case the controller 65 is manufactured using hardware processing stages, this last operation may be performed by a pump peak exclusion stage 71, the inputs of which are fed by the output of the peak detection stage 70.

A particular embodiment of the processing disclosed herein involves setting a spectral amplitude threshold 200T before searching for any amplitude peaks. Such a threshold value 200T may be fixed in time, or in some way adaptive. In Figure 4, this operation is schematically represented by the input 200T of the peak detection stage 70, which is fed by the output of the upper frequency window selection stage 69. Although careful selection of appropriate threshold values may be performed, Applicant shows that applying a threshold allows to reduce the computational load of the controller 65 and reduces the risks of false readings, provided that only peaks whose amplitude lies beyond the threshold 200T are considered as possible useful signal frequencies; this helps to reduce the risk of interpreting a noise peak as a real heartbeat.

Depending on the application of the threshold, which according to Figure 5 is set at a reference value of 1 of the spectrum, only the peaks identified by the marks "1", "3", "4" could be of potential interest.

The controller 65 then performs further electronic processing on the spectrum taking into consideration any peak beyond (i.e., above) the 200T threshold (which is called the peak under test) and considering the presence of another peak at exactly twice the frequency at which the peak under test is located. Then, for each peak under test whose amplitude is beyond the 200T threshold (particularly moving from lower to higher frequencies):

- if a 200P peak is found at a frequency that corresponds exactly to twice the frequency of the peak under test, this means that the peak under test corresponds to the sought beat signal, so the frequency of said peak is assigned the reference fHR;

- if no peak is found at a frequency that corresponds exactly to twice the frequency of the peak under test, this means that the peak under test does not correspond to the heartbeat signal sought and therefore does not correspond to the heartbeat; in this case, the algorithm proceeds to take into account another peak whose amplitude exceeds the 200T threshold (if present).

These operations are performed by the harmonic search stage 72, in case the controller 65 is designed to perform such operations with a hardware processor; as shown in Figure 4, the input of the harmonic search stage 72 is fed by the output of the pump peak exclusion stage 71. The harmonic search stage 72 is provided with an output that is configured to produce a signal representing the value of the reference frequency fHR of the heartbeat. This reference frequency may be provided on a display that is schematically represented by the fHR display stage 73 in Figure 4.

In a particular but non-limiting embodiment, the electronic search for peaks in the signal spectrum at twice the frequency at which the peak under test is located can be performed taking into account also the peaks that are below the threshold level 200T. This helps to reduce the risk of discarding a real peak corresponding to the 2nd harmonic of the heartbeat. This step corresponds to block 1008 of the flow diagram of Figure 7. The frequency fHR of the heartbeat obtained in this way is then stored, at least temporarily, in a memory electronically accessible to the controller 65 and, in particular, is provided as, or in, an electronic signal to be transmitted to a monitor or display of the apparatus 1, so that the user knows the heart rate (block 1009, flow diagram of Figure 7). The heart rate can be transmitted by the controller 65, or by any other electronic device operatively connected thereto, to a remote device, e.g. a smartphone or laptop, particularly using a wireless channel whose electromagnetic behavior is compatible (and does not interfere) with medical applications.

In the case of Figure 6, only the peak with reference "3" is the peak to which another peak exactly twice its frequency actually corresponds. Peaks "1" and "4" are peaks due to noise captured by detector 57 and do not actually correspond to a heartbeat. Through the algorithm carried out by controller 65, the system is able to discriminate very well between noises and real heartbeat frequencies, even if they are very close to each other and even if the noise peaks exceed the magnitude of the peak that actually corresponds to the heartbeat. In the case of Figure 6, in fact, peak "4" is less than 0.1 Hz from the real heartbeat frequency, and even if its amplitude is almost twice as large as the amplitude of the peak corresponding to the real heartbeat, the latter can actually be detected and peak "4" is discarded.

The detection of peaks in the pump spectrum is performed by a step of processing the output spectrum with a peak detection algorithm; in a non-limiting embodiment, the peak detection comprises, moving from lower frequencies to higher frequencies, calculating the derivative of the spectral signal to detect, and at least temporarily storing, the frequencies at which the derivative changes from positive to negative sign (which is indicative of a peak); Said temporary storage, which is performed in a memory electronically accessible by the controller 65, e.g. an internal memory, is performed by virtue of an electronic table where a first column represents the values of the frequency peaks searched for through the peak detection algorithm and where the second column represents the corresponding amplitude values. In this way, a table similar to the following example can be stored in said memory.

In another solution, the search for peaks in the output spectrum may be performed by a moving window algorithm. In the moving window algorithm, a frequency examination window of predefined width is considered and is made to move, e.g., from lower to higher frequencies of the reference spectrum, e.g., from lower to higher frequencies of the higher frequency window 200U. It should be noted that the controller 65 may be configured to electronically make the window move in a stepwise manner. For each step of window movement, the local maximum amplitude of the spectrum is considered and its corresponding frequency is entered into a table in a similar manner as above. It should be noted that it is desirable that at each step the frequencies of the moving window do not overlap with the frequencies of the moving window of the previous step. When the controller 65 goes through hardware processing steps, those operations are conveniently performed by the peak detection step 70 and/or by the harmonic search step 72. It is noteworthy that the algorithm disclosed herein, even with a low computing power processing unit, allows to obtain substantially the heart rate in real time and in a substantially reliable manner, without any relevant delay, especially if done after a setup period, e.g. to obtain the first signal window in the time domain.

Induced modulation algorithm

The Applicant has further considered that the reliability of reading the correct heartbeat frequency fHR could be achieved by applying the following electronic signal processing to the signal at the output of the detector 57. The following signal processing steps, which may be conveniently carried out by the controller 65, should be performed prior to the step of transforming the output signal of said 200 W sampling reference window into the frequency domain. That is, considering the flow chart of Figure 7, the steps to be described below will be located between block 1000 and block 1001. The Applicant has discovered that the reliability of the reading of the correct frequency fHR of the heartbeat, even in the presence of strong noise signals, for example induced by the operation of the pump 11, can be further increased by processing the output signal 200R so that when the spectrum analysis is performed, the frequency peaks corresponding to the heartbeat are provided with an amplitude greater than the amplitude of the noise peaks (the latter remaining unchanged) or, correspondingly, so that when the spectrum analysis is performed, the frequency peaks corresponding to the noise have an amplitude that has been attenuated with respect to the amplitude of the frequency peaks corresponding to the heartbeat. At first, this algorithm involves electronically multiplying, in the time domain, the output signal 200R emitted by the detector 57 (block 1010, figure 11) with a signal 300P associated with the pump whose shape is cyclic and/or repeated in time, and is correlated with the point of the pump cycle; figure 8 shows an example of a pair of diagrams where the output signal 200R (upper diagram) is multiplied by said signal 300P associated with the pump (lower diagram). The multiplication step corresponds to block 1011 of Figure 11. Generally speaking, the signal 300P associated with the pump is periodically set to zero in correspondence with time portions where the pump provides flow pulses at least in the segment 101 in which the sensor 100 is arranged. Conveniently, in an embodiment shown in the lower diagram of Figure 8, the signal 300P associated with the pump is a square wave, with a predetermined duty cycle, which for each cycle is provided with a first portion of unitary amplitude and a second portion which is set to zero. The first part clearly corresponds to the time portions in which the pump does not provide flow pulses. The multiplication of the output signal 200R by the signal 300P associated with the pump results in the production of a resulting signal 301 whose shape is represented in the upper diagram of Figure 9. Clearly also the resulting signal 301 is characterized by portions which are set to zero in correspondence with the same time portions in which the signal 300P associated with the pump is zero. It is noted that the use of a square wave makes it possible not to alter the shape of the output signal 200R in the portion not set to zero, and this contributes to keeping its spectrum unchanged. Subsequently, as schematically represented by block 1012 of the flow diagram of Figure 11, an electronic calculation of the average magnitude Vm of the resulting signal 301 is carried out for the portions not set to zero, or more generally across a window of a predetermined time duration. The value Vm of the average magnitude is then subtracted from the resulting signal 301, in particular only in correspondence of the portions that are not set to zero, so as to produce an averaged signal 301A whose shape is shown in the lower diagram of Figure 9.

Therefore, a frequency domain transformation is performed on the averaged signal 301A, e.g. as disclosed above. Further processing performed on the spectrum of the output signal is finally performed on the spectrum of the averaged signal 301A. Figure 10 clearly shows the effect of the induced modulation in terms of the frequency spectrum. Although prior to induced modulation the amplitude peaks of the noise induced by the action of the pump 11 (peaks P1, P2, P3, P4, P5, corresponding respectively to the fundamental, 2nd, 3rd, 4th and 5th harmonics) are much higher, up to 4 times higher, than the peaks of the heartbeat (peaks H1, H2, H3, corresponding respectively to the fundamental, 2nd, and 3rd harmonics), after applying the aforementioned induced modulation processing, the amplitude peaks of the heartbeat in the corresponding averaged signal 301A are enhanced. This therefore reduces the requirements for appropriate threshold settings and/or allows for a clearer identification of the correct heartbeat and allows for a more accurate and reliable reading. It should be noted that also the implementation of the induced modulation algorithm, described above, still allows for producing the indication of the heartbeat frequency fHR in substantially real time.

It is noted herein that the windowing process by applying the predetermined length time domain reference window 200W is cyclically repeated by either moving the window for a predetermined amount of time or by providing buffering of a new sample of the reference portion output signal 200R for processing as described above. If the buffering stage allows, the time difference between two consecutive reference windows could be reduced at will, down to a single sample delay. Figure 4 also shows this induced modulation solution within the dashed line box. Since induced modulation is not necessarily part of the disclosed signal processing algorithm, two dummy switches 77' are depicted between the time domain window stage 67 and the Fourier transform stage 68 to identify the optionality. In one embodiment, the controller 65 may comprise a square wave generating stage 74 which receives a first input from a pump cycle sensor 100s, in particular the Hall sensor coupled to the blood pump 11, and outputs the signal 300P associated with the aforementioned pump. Next, a hardware multiplier 75 arranged downstream of the square wave generating stage 74 multiplies the windowed reference part of the output signal 200R by the signal 300P associated with the aforementioned pump, to obtain as output the aforementioned resulting signal 301 whose shape is represented in the upper diagram of Figure 8. The aforementioned averaging operations may be performed by virtue of an averaging stage 76 of the controller 65, which is arranged downstream of the multiplier 75 so that its output directly feeds the input of the averaging stage 76; the output of the averaging stage then feeds the input of the Fourier transform stage 68. The applicant has finally envisaged conceiving a subroutine for validating and applying the heartbeat reading, which comprises repeating at least part of the above steps for a predetermined number of times, e.g. three times. With a sufficiently short reference window, and thanks to the real-time processing allowed by the algorithm disclosed herein, we are substantially in the conditions where the following hypotheses are formulated: 1) the flow rate of the pump 11 does not change during the previous repetition, 2) the heartbeat frequency remains substantially stable. Through the aforementioned repetition, a series of n heartbeat frequency values fHRn are electronically calculated: fHR<1>, fHR<2>, fHR3, in case of three repetitions. These n values (e.g. 3) can be averaged together; the controller 65 could be configured to discard at least one of the n frequency values, this coinciding, e.g., with the one that is furthest from the average values of the remaining ones. Further statistical processing could be performed for the set of n heartbeat frequency fHRn values.

The Applicant has further noted that during blood treatment, which is usually quite long, the heartbeat frequency of the patient under treatment, even under resting conditions, tends to drift (positive or negative), due at least partially to the continuous change in his fluid dynamic conditions. This drift may result in an overlap of the heartbeat frequency with the fundamental frequency of the pump. The controller 65 may be further configured to allow a warning signal to be triggered if the heartbeat rate fHR is too close to the operating rate fP<1> of the pump 11. If during blood treatment it is observed that, progressively over time, the heartbeat rate fHR is getting too close to the operating rate fP1 of the pump 11, a warning signal (e.g., a visible and/or audible alarm) is triggered for the user and optionally all recent peak amplitudes of the pump 11 are started to be recorded in a dedicated buffer. This is a warning condition, because if the heart rate fHR substantially overlaps the operating rate fP<1> of the pump 11, the current algorithm is no longer able to distinguish it. The Applicant has also considered this event and has planned to design and configure the controller 65 so that, in this case, in addition to the activation of the alarm signal, the controller 65 sends an appropriate signal to the electric actuator of the pump 11 so that its speed (therefore, flow rate and operating frequency) changes so that the resulting new operating frequency becomes further away from the heartbeat frequency. In one embodiment, the change in speed and therefore the flow rate and rotation frequency of the pump 11 is carried out automatically in an iterative control cycle carried out by the controller 65; in order not to vary the total volume of blood being treated during the entire session, the control unit can provide alternative changes in the blood flow rate of the pump (e.g., ± 30 ml/min) during the treatment session. In other circumstances, the controller 65 may be configured to provide through the monitor of the apparatus 1 an indication to the operator to set a new speed of the pump 11, so that the change is made manually.

Operationally, a difference (or its absolute value) between the operating frequency fP<1> of the pump 11 and the heartbeat frequency fHR is electronically calculated; the result of the difference is then compared with a reference value, and the control of the pump 11 is performed so that the resulting new operating frequency of the pump 11 becomes further away from the heartbeat frequency. Another relevant advantage of the detection provided by applying the algorithm for heartbeat detection described herein is that any sudden disappearance of the heartbeat can be easily detected. The Applicant has noted that the disappearance of the heartbeat, i.e. a sudden condition where the sensor 100 no longer detects any heartbeat frequency fHR may be the result of an unwanted disconnection of the venous port of the blood circuit 6, 7, which may result in a large blood leak that could result in a hypovolemic condition that may even affect the life of a patient. To this end, an alarm signal may be produced in case the sensor 100 detects a sudden lack of any beating frequency, i.e. in case the sensor loses and/or is not able to detect any beating frequency according to the process described above, in particular in the presence of the informative signal, i.e. while in reality the optical source 53 is operative and/or while the detector 57 actually receives the informative signal with the pump signal but without any other useful signal with a 2nd harmonic within the conditions disclosed in the previous part of the description. Said alarm signal may be an electrical signal transmitted to a user interface (e.g. monitor and/or speaker) of the blood treatment apparatus 1 or may be directly an acoustic or visible signal produced directly by the sensor 100 itself. Any part of the controller 65 may be realized through a hardware data processing unit, in case it comprises an arithmetic logic unit, suitable for carrying out at least part of the steps of the signal processing algorithms described herein. In particular, the controller may execute an appropriate program, comprising portions of software code which, when executed by the controller 65, cause the execution of one or more of the steps described in the present disclosure. The program may be called software or firmware and may be stored in a memory, in particular an operatively, in particular electrically, non-transitory memory accessible by the controller 65; said memory may be physically arranged inside or outside the body of the sensor 100, and in particular may be part of the blood treatment apparatus. The data processing unit of the controller 65 may be in the form of a general-purpose processor or in the form of a dedicated processor; portions of the controller 65 and/or such data processing unit may be realized by an application-specific integrated circuit or by an FPGA. In one or more embodiments, the apparatus 1, the sensor 100, the controller 65, or the method may be implemented using one or more computer programs executed on programmable computers, such as computers that include, for example, processing capabilities, data storage (e.g., volatile or nonvolatile memory and/or storage elements), input devices, and output devices. Program code and/or logic described herein may be applied to input data to perform the functionality described herein and generate desired output information. The output information may be applied as input to one or more devices and/or methods as described herein or as would be applied in a known manner. The program used to implement the methods and/or processes described herein may be provided using any programmable language or code, for example, a high-level procedural and/or object-oriented programming language that is suitable for communicating with a computer system. Any such program, for example, may be stored on any suitable device, for example, a storage medium, that is readable by a general-purpose or special-purpose program running on a computer system (e.g., including a processor apparatus) to configure and operate the computer system when read by the suitable device to perform the procedures described herein. In other words, in at least one embodiment, the apparatus 1, sensor 100, controller 65, or method may be implemented using a computer-readable storage medium configured with a computer program, wherein the so-configured storage medium causes the computer to operate in a specific, predefined manner to perform the functions described herein. Furthermore, in at least one embodiment, the apparatus 1, sensor 100, controller 65, or method may be described as being implemented by logic (e.g., object code) encoded in one or more non-transitory media that includes execution code and that, when executed by a processor, serves to effect operations such as the methods, processes, and/or functionality described herein. The controller 65 may be, for example, any fixed or portable computing system (e.g., a controller, microcontroller, personal computer, minicomputer, etc.). The exact configuration of the controller 65 is not limiting, and essentially any device capable of providing suitable computing capabilities and control capabilities may be used (e.g., graphics processing, extracorporeal blood treatment control apparatus, etc.). As described herein, a digital file may be any medium (e.g., volatile or non-volatile memory, a CD-ROM, a punched card, magnetic recordable tape, etc.) containing digital bits (e.g., binary encoded, trinary, etc.) that can be readable and/or writable by the controller 65 described herein. Also, as described herein, a file in user-readable format may be any representation of data (e.g., ASCII text, binary numbers, hexadecimal numbers, decimal numbers, graphics, etc.) presentable on any medium (e.g., paper, a monitor, etc.) readable and/or understandable by an operator. In view of the foregoing, it will be apparent that the functionality described in one or more embodiments according to the present disclosure may be implemented in any manner known to one of skill in the art. In this regard, the computer language, computer system, or any other software/hardware used to implement the processes described herein shall not limit the scope of the apparatus, sensor, processes, or programs (e.g., the functionality provided by such apparatus, sensor, processes, or programs) described herein. The methods and/or logic described in this disclosure, including those attributed to the sensor and/or apparatus and/or controller, or to the various constituent components, may be implemented at least in part, in hardware, software, firmware, or any combination thereof. For example, various aspects of the techniques may be implemented within one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or other equivalent discrete or integrated logic circuits, as well as any combination of such components or other devices. The term "processor" or "processing circuit" may generally refer to any of the foregoing logic circuits, alone or in combination with other logic circuits or any other equivalent circuits. Such hardware, software, and/or firmware may be implemented within the same device or in separate devices to support the various operations and functions described herein. Also, any of the components described may be implemented together or separately as discrete but interoperable logic devices. The depiction of different features, e.g., using block diagrams, etc., is intended to highlight different functional aspects and does not necessarily imply that such features must be realized by separate hardware or software components. Rather, the functionality may be realized by separate hardware or software components or integrated within common or separate hardware or software components. When implemented in software, the functionality attributed to the controller, sensor, apparatus, and methods described herein may be embodied as instructions and/or logic in a computer-readable medium such as RAM, ROM, NVRAM, EEPROM, flash memory, magnetic data storage media, optical data storage media, or the like. The instructions and/or logic may be executed by one or more processors to support one or more aspects of the functionality described herein.

Claims (16)

1. An apparatus for extracorporeal blood treatment, comprising: a) a blood pump (11) configured at least to control the flow of blood in a blood circuit (6, 7), b) a circuit for extracorporeal blood treatment, comprising: - a filtration unit (2) having a primary chamber (3) and a secondary chamber (4) separated by a semipermeable membrane (5); - the blood circuit (6, 7), comprising a blood collection line (6) having a first end connected to an inlet of the primary chamber (3), and a blood return line (7) having a first end connected to an outlet of the primary chamber (3), said blood collection line (6) and said blood return line (7) being designed to be connected to a cardiovascular system of a patient, wherein the blood collection line (6) has a second end provided with an arterial connector (40) and the blood return line (7) has a second end provided with a venous connector (41), said arterial connector (40) and said venous connector (41) being designed to be connected to a vascular access of a patient, wherein said blood circuit is configured to be interconnected with the blood pump (11) to control the flow in the blood circuit (6, 7), and wherein the blood circuit comprises an extracorporeal segment (101); and - an effluent fluid line (13) in fluid communication with an outlet of the secondary chamber (4) and optionally a dialysis fluid line (19) in fluid communication with an inlet of the secondary chamber (4); and c) a non-invasive heartbeat sensor (100) for determining a heartbeat and/or a heart rhythm in the extracorporeal segment (101), characterized in that said sensor (100) comprises: - at least one source (53) for directing an optical signal towards the blood flowing through the segment (101), the optical signal being directed along at least one emission axis (54); - detectors (57) positioned in different radial directions or arranged at different angular degrees with respect to the emission axis (54) of the source (53) for collecting the reflected signal, the scattered signal and/or the transmitted signal, depending on their respective position and each receiving an optical information signal comprising the signal emitted by said source (53) after at least partially passing through the blood flowing through the segment (101), each of said detectors (57) emitting a respective output signal (200R) related to the received optical information signal, - a controller (65) configured to receive the respective output signals (200R) from the detectors (57) and to recover a heart beat frequency (fHR) and/or detect a heart rate value, based on a predetermined number of output signals (200R), wherein said controller is particularly configured to process the output signals (200R) based on the information signal altered, in particular, at least in its amplitude, by a flow disturbance of the blood flowing through the segment (101), said flow disturbance being generated at least partially by the flow pulses originating from a beating heart. 2. An apparatus according to the preceding claim 1, wherein said controller (65) is configured to: - electronically calculating a transformation of at least a reference part (200W) of one or more output signals (200R) from the time domain to the frequency domain, obtaining an informative signal spectrum or an output signal spectrum corresponding to the informative signal spectrum, - determining whether at least one pump (11) is forcing fluid through said segment (101), - in case at least one pump (11) is forcing fluid through said segment (101), identifying and, optionally, discarding, a first amplitude peak in said information signal spectrum or output signal spectrum, said first amplitude peak optionally corresponding to a first noise amplitude peak corresponding to a spurious disturbance of the flow through said segment (101) caused by at least one pump (11) forcing fluid through said segment (101), - carrying out an electronic identification and subsequent selection of a first amplitude peak sought in said information signal spectrum or output signal spectrum, in particular after said discarding has occurred, said selection being calculated by means of an identification of a second amplitude peak sought in the information signal spectrum or in the output signal spectrum, the second peak corresponding to a subsequent harmonic, in particular a 2nd harmonic of said first amplitude peak sought, - electronically assign to at least one provisional heartbeat and/or to the heart rate (fHR) the frequency corresponding to the first amplitude peak sought. 3. An apparatus according to the preceding claim 2, wherein said controller (65) is further configured to electronically load frequency values corresponding to a first lower frequency region (200L) and to at least one second upper frequency region (200U), the second upper frequency region (200U) being located above said first lower frequency region (200L); wherein the controller (65) is configured to store and set an upper frequency value of said lower frequency region (200L) below a frequency threshold for non-physiological heart beats, in particular below 0.7 Hz or below 0.4 Hz, comprising processing the output signal by performing the following processing on the information signal spectrum or output signal spectrum: - filtering the portion of said information signal spectrum or output signal spectrum corresponding to the first lower frequency region (200L), or - discard any amplitude peaks found in said first lower frequency region (200L), so that the identification, and optionally the discarding of the first noise amplitude peak and the electronic selection of the first sought amplitude peak are carried out in said at least one second higher frequency region (200U). 4. An apparatus according to one or more of the preceding claims as dependent on claim 2, wherein a processing of said output signal comprises a low-pass filtering of the output signal, through a filter stage (63), at a predetermined frequency, optionally below 10 Hz, below 7 Hz, below 5 Hz or below 4 Hz, wherein the low-pass filtering is performed before electronically calculating the transformation of at least the reference part of the output signal from the time domain to the frequency domain. 5. An apparatus according to one or more of the preceding claims as dependent on claim 2, wherein the identification of a second sought amplitude peak (200P) is performed by searching for an amplitude peak in the information signal spectrum or in the output signal spectrum corresponding to a frequency (fHR<2>) corresponding to twice the frequency (fHR) of the first sought amplitude peak. 6. An apparatus according to one or more of the preceding claims as dependent on claim 2, wherein said controller (65), when electronically processing the output signals of said optical detectors (57), is configured to effect electronic selection of an output signal sampling reference window, said reference window having a predetermined duration, optionally less than 1 minute in duration, or less than 30 seconds in duration, or less than 20 seconds in duration, or less than 10 seconds in duration, wherein the portion of the output signal constitutes the reference part of the output signal, and wherein the electronic calculation of the transformation of at least part of the output signal is performed on said reference part of the output signal and is performed after said window. 7. An apparatus according to one or more of the preceding claims as dependent on claim 2, wherein said identification of the first noise amplitude peak and/or the identification of the first sought amplitude peak and/or of said second sought amplitude peak are effected by applying a peak detection algorithm to at least part of said informative signal spectrum or output signal spectrum, wherein the peak detection algorithm comprises considering a part of the informative signal spectrum or output signal spectrum, said part optionally corresponding to the second upper frequency region (200U), and electronically calculating the derivative of said spectrum obtaining a derivative spectrum, and then comprising a subsequent electronic search and selection of at least one frequency where said derivative spectrum changes sign, optionally where said derivative spectrum changes sign from a positive value to a negative value, proceeding to increase the analysis frequency, to identify positive peaks, said peak corresponding to the frequency at which said derivative spectrum changes sign, from a positive value to a negative value. 8. An apparatus according to claim 7, wherein the peak detection algorithm, for which the controller (65) is configured, comprises searching for points of local relative maximum amplitude in said information signal spectrum or output signal spectrum, said part optionally corresponding to the second upper frequency region (200U), by using a moving window signal processing in said spectrum, and a further selection of frequencies corresponding to said points of maximum amplitude as a frequency at which a peak occurs. 9. An apparatus according to any one of the preceding claims 7 or 8, wherein the peak detection algorithm comprises defining a moving window of a predetermined amplitude within at least a part of the informative signal spectrum or output signal spectrum, said part optionally corresponding to the second upper frequency region (200U), and electronically defining at least one position, particularly a plurality of positions for said moving window within said at least a part of the informative signal spectrum or output signal spectrum and, for said position(s), optionally for each of said positions, electronically calculating the maximum amplitude of the spectrum within said window, and electronically extracting and storing the frequency corresponding to said maximum amplitude. 10. An apparatus according to one or more of the preceding claims, wherein the controller (65) is configured to process the output signals of said detectors (57) with a signal (300P) associated with the pump whose shape is cyclic and/or repeated in time, and is correlated with a point of the pump cycle, in order to obtain a corresponding resulting signal (301) whose spectrum contemplates an enhancement of the components or peaks, related to the heartbeat or to the heart rate, with respect to the components or peaks associated with the operation of a pump (11) of said apparatus, wherein the controller (65) is configured to process, for example, multiply, the output signals of said optical detectors (57) with said signal (300P) associated with the pump to zero a resulting signal (301) produced as output of said processing, in particular, to zero it periodically or cyclically, in correspondence with the time portions in which said pump provides pulses in at least said segment (101). 11. An apparatus according to claim 10, wherein the controller (65) is further configured to calculate an average magnitude (Vm) of said resulting signal (301) over a predetermined time duration analysis window, and further to subsequently subtract said average magnitude (Vm) from at least a portion of said resulting signal (301), in particular, a portion where said resulting signal (301) was not set to zero by said processing, for example, multiplication, thereby producing an averaged signal (301A) constituting a reference part of said output signal to which at least one transformation from the time domain to the frequency domain is performed. 12. An apparatus according to any one of claims 10 or 11, wherein said controller (65) is configured to select a plurality of reference parts (200W) of at least one of the one or more output signals (200R) by electronically selecting, through a sampling window, a plurality of portions of said output signal (200R) that are at least partially, optionally completely, non-overlapping in time, - performing a transformation from the time domain to the frequency domain, obtaining a plurality of informative signal spectra or a plurality of output signal spectra corresponding to, or related to, the corresponding plurality of informative signal spectra, for each of said plurality of reference parts (200W) of the output signal (200R); - for each load spectrum or output signal spectrum of said plurality: • identifying and discarding a first noise amplitude peak in said information signal spectrum or output signal spectrum, said first predetermined amplitude peak corresponding or being associated, at least partially, with a spurious flow disturbance in said segment (101) that has been caused by at least one pump (11) forcing fluid flow through at least said segment (101), • performing an electronic identification and subsequent selection of a first amplitude peak sought in said information signal spectrum or output signal spectrum after said discarding has occurred, said selection being calculated electronically by means of an identification of a second amplitude peak sought in the information signal spectrum or in the output signal spectrum, the second peak corresponding to a 2nd harmonic of said first amplitude peak sought, • electronically assign to a provisional heartbeat and/or heart rate (fHR<1>, fHR<2>, fHR3) the frequency corresponding to the first amplitude peak sought; • calculating a definitive heartbeat and/or heart rate (fHR) according to the plurality of provisional heartbeat and/or heart rate values (fHR<1>, fHR<2>, fHR3) obtained for each of said spectra, in particular, wherein the definitive heartbeat and/or heart rate (fHR) is calculated according to an average calculation between the plurality of provisional heartbeat and/or heart rate values (fHR<1>, fHR<2>, fHR3) obtained for each of said spectra. 13. An apparatus according to any one of the preceding claims, wherein the source (53) comprises an optical emitter of electromagnetic radiation, in particular in the form of: - a single wavelength LED (light emitting diode), optionally multimode and non-coherent; or - a single wavelength LASER or SLED; or - a multi-wavelength emitter, wherein the multi-wavelength emitter has a plurality of optical radiation sources with wavelength peaks in the red and infrared bands, wherein at least one illumination wavelength peak of the source (53) is comprised between 0.7 pm and 1000 pm and more particularly between 1 pm and 350 pm or between 790 nm and 820 nm, for example between 800 nm and 810 nm and/or, in the red region, between 620 nm and 750 nm, wherein the source (53) is configured to transmit a composite optical radiation comprising at least a first optical radiation component centered on a first wavelength A<1>, or on a first frequency window comprising said first wavelength, and a second optical radiation component centered on a second wavelength A<2>, or on a second frequency window comprising said second wavelength, optionally with a third optical radiation component centered on a third wavelength A3, or on a third frequency window comprising said third wavelength, and with a fourth optical radiation component centered on a fourth wavelength A4, or on a fourth frequency window comprising said fourth wavelength, optionally wherein said first, second, third and fourth wavelengths differ from each other and/or wherein said first, second, third and fourth frequency windows are not, at least partially, overlapping in frequency, and wherein the detectors (57) comprise at least a first detector (57; PD1) configured to receive optical radiation at the first wavelength Á<1>, or in a first frequency window comprising said first wavelength and a second detector (57; PD2) configured to receive optical radiation at the second wavelength Á<2>, or in a second frequency window comprising said second wavelength, optionally further comprising a third detector (57; PD3) configured to receive optical radiation at the third wavelength Á3, or in a third frequency window comprising said third wavelength and a fourth detector (57, PD4) configured to receive optical radiation at the fourth wavelength Á4, or in a fourth frequency window comprising said fourth wavelength. 14. An apparatus according to any one of the preceding claims, wherein the sensor further comprises: - an optical fiber having one end coupled to the source (53) and the other end positioned to direct the emitted signal towards the blood along at least said predetermined emission axis; - a first detector positioned at approximately 180° with respect to the emission axis of the source, and a second detector positioned at approximately 90° with respect to the emission axis of the source, and a third detector positioned at approximately 45° with respect to the emission axis of the source, and a fourth detector positioned at approximately 0° with respect to the emission axis of the source; and - a housing (51) having a portion having a shape substantially opposite to said tube segment (101), the housing (51) being made of two or more pieces and defining a through passage (52) having a shape opposite to the outer shape of the tube segment for receiving the tube segment (101) within the through passage (52), each detector (57) including a respective end positioned on the portion of opposite shape facing the tube segment (101) in a coupling condition of the housing (51) with the tube segment (101), the source (53) including, in particular, an end positioned on the portion of opposite shape facing the tube in a coupling condition of the housing with the tube segment (101), wherein each detector (57) includes an optical fiber, one end of the optical fiber being arranged in correspondence with the tube segment (101) and being fixed to the housing, the end of the optical fiber being placed in the portion opposite and facing the tube segment (101) in a condition of coupling the housing with the tube segment (101). 15. An apparatus according to any one of the preceding claims, wherein the segment (101) of the extracorporeal blood treatment circuit is a tube portion, said detectors and said source being arranged around said tube portion at different angular degrees around the same cross section, in particular said tube having a substantially circular cross section, the sensor being directly restricted to an external portion of the segment (101) having circular inner and outer sections, wherein said segment (101) is made of a flexible material with a predetermined degree of transparency to optical radiation, in particular the tube not including any rigid cuvette in correspondence of the sensor. 16. A non-invasive heartbeat sensor (100) for determining a heartbeat and/or a heart rhythm in an extracorporeal segment (101) of a conduit for connection to an extracorporeal blood treatment apparatus, said sensor (100) comprising: - at least one source (53) for directing an optical signal towards the blood flowing through the segment (101), the optical signal being directed along at least one emission axis (54); - detectors (57) positioned in different radial directions or arranged at different angular degrees with respect to the emission axis (54) of the source (53) for collecting the reflected signal, the scattered signal and/or the transmitted signal, depending on their respective position and each receiving an optical information signal comprising the signal emitted by said source (53) after at least partially passing through the blood flowing through the segment (101), said detectors (57) emitting respective output signals (200R) related to the received information signal, - a controller (65) configured to receive respective output signals (200R) from each of the detectors (57) and to recover a heartbeat frequency (fHR) and/or detect a heart rate value, based on a predetermined number of the output signal (200R), wherein said controller is particularly configured to process the output signal (200R) based on the information signal altered, in particular, at least in its amplitude, by a flow disturbance of the blood flowing through the segment (101), said flow disturbance being generated at least partially by the flow pulses originating from a beating heart.