Method of using an ultrasonic flow sensor to monitor the fill weight accuracy of clinical, commercial and process development filling / finishing operations

Description

1 / 38 METHOD OF USING AN ULTRASONIC FLOW SENSOR TO MONITOR THE FILLING WEIGHT ACCURACY OF CLINICAL AND COMMERCIAL DEVELOPMENT FILLING / FINISHING OPERATIONS AND OF THE PROCESS CROSS-REFERENCE TO RELATED REQUESTS

[0001] Priority is claimed to Provisional Patent Application No. US 63 / 455,847, filed March 30, 2023, the contents of which are incorporated herein by reference in their entirety. FIELD OF REVELATION

[0002] The present disclosure relates generally to the monitoring of a process of filling containers with liquid and, more specifically, to the use of one or more flow sensors to detect the amount of filling. BACKGROUND

[0003] Pharmaceutical product filling is a complex unit operation, essential to ensuring that high-quality products are administered to patients. Among other considerations, a good filling process needs to consistently deliver, within a tight tolerance, a consistent amount of drug to each container, so that all units can be considered safe and effective according to scientifically determined action limits. Such consistency could potentially be ensured with 100% in-process control (IPC) of filling weight. One IPC approach is to weigh each dose on a balance of sufficient precision to confirm that the dose quantity is within the action limits. However, the mechanics of this process (in which an empty container is placed on a gravimetric balance of Petition 870250088098, dated 09 / 29 / 2025, page 20 / 70 (2 / 38 weighing, taring, removing from the scale, filling, then returning to the scale and weighing again) tends to be very time-consuming. Therefore, there is a need for an alternative IPC that can guarantee accurate and consistent dose quantities. SUMMARY OF REVELATION

[0004] In one example, a system for filling containers with liquid comprises a flow control device configured to transfer liquid from a storage reservoir to a container via piping and at least one sensor disposed in the piping. The system further comprises one or more processors configured to cause the flow control device to transfer liquid from the storage reservoir to the container via piping. The one or more processors of the system are further configured to receive from at least one sensor a plurality of values ​​indicative of a plurality of respective flow rates at a plurality of respective times within a filling time interval and to compute, based at least in part on the plurality of values ​​received, an indication of the filling quantity.Furthermore, one or more processors in the system are configured to compare the fill quantity indication with a target fill quantity and to generate a fill quantity compliance indication.

[0005] In another example, a method for verifying container fill quantity compliance comprises having one or more processors transfer a flow control device from a container. Petition 870250088098, dated 09 / 29 / 2025, page 21 / 70 3 / 38 storage reservoir for a container via piping. The method further comprises receiving, by one or more processors and from at least one sensor located in the piping, a plurality of values ​​indicative of a plurality of respective flow rates at a plurality of respective times within a filling time interval. Further, the method comprises: i) computing, by one or more processors, based at least in part on the plurality of values ​​received, an indication of the filling quantity; ii) comparing, by one or more processors, the indication of the filling quantity with a target filling quantity; and generating, by one or more processors, an indication of filling quantity conformity. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Figure 1 schematically illustrates an example system for filling containers with liquid.

[0007] Figure 2 schematically illustrates another example system for filling containers with liquid.

[0008] Figure 3 schematically illustrates an example system for detecting compliance with the filling quantity.

[0009] Figure 4 schematically illustrates another exemplary system for detecting fill quantity compliance.

[0010] Figure 5 schematically illustrates an exemplary non-contact flow sensor arranged in a pipe section.

[0011] Figures 6A and 6B schematically illustrate an operating principle of an ultrasonic flow sensor. Petition 870250088098, dated 09 / 29 / 2025, page 22 / 70 4 / 38

[0012] Figures 7A and 7B schematically illustrate exemplary flow profiles.

[0013] Figure 8 is a block diagram of an exemplary method for verifying the conformity of container filling quantity. DETAILED DESCRIPTION

[0014] The present disclosure relates to the operation of a system for filling dispensing containers (e.g., ampoules, vials, cartridges, syringes, etc.) with liquids (e.g., therapeutic liquids such as chemical drugs, biopharmaceuticals, etc.) in clinical or commercial settings. The examples described herein may complement or replace gravimetric process control in filling operations with process control based, at least in part, on the use of flow sensors (e.g., ultrasonic, electromagnetic, etc.). Measuring dispensed quantities based on flow rates has a significant speed advantage compared to gravimetric systems that measure each individual filling. Gravimetric process control systems that sample only a portion of filled containers can increase productivity.Improved yield may come at the cost of potential product waste if a sample is non-conforming and an entire batch needs to be discarded. Thus, flow rate-based process control systems as presented herein can reduce product waste and improve efficiency compared to gravimetric sampling systems. Furthermore, flow rate-based process control systems as presented herein can be... Petition 870250088098, dated 09 / 29 / 2025, page 23 / 70 5 / 38 used to quickly and effectively identify filling process problems and thus offer a diagnostic advantage over gravimetric systems. The systems and methods of this disclosure are most broadly applicable to many container filling operations where filling accuracy and / or filling speed are of high importance. Additionally, the systems and methods described in this disclosure can include flow rate measurement in the filling operation during development work, ensure robust process characterization, and allow operators to more easily detect and resolve filling weight deviations.

[0015] The systems and methods described in this disclosure overcome several challenges in converting flow rate measurements into indications of fill quantities. Some of these challenges are specific to fill processes involving doses of therapeutic liquids. For example, the absolute accuracy required to fill a volume from a fraction of a milliliter to several milliliters with high relative accuracy is considerably more challenging to achieve than the equivalent relative accuracy for larger volumes. Rapid fill processes with small fill quantities may depend on frequent start and stop of pumping or valve operations. The rapid cycle of pumping or valve operation, in turn, leads to requirements for flow rate sampling as well as detection of start and stop times for each fill time interval.Furthermore, sensitivity to potential contamination from therapeutic fluids requires minimal contact with the equipment. Thus, Petition 870250088098, dated 09 / 29 / 2025, page 24 / 70 6 / 38 The pumps, valves, and sensors used in the systems described in this disclosure may be contactless pumps, valves, and sensors. Peristaltic pumps, for example, used in filling operations, can cause ripples in flow rates. Thus, the systems and methods of this disclosure may use suitable flow rate integration algorithms and / or other techniques to overcome filling quantity errors resulting from flow rate variations.

[0016] The techniques described can achieve results comparable to or better than techniques using gravimetric weighing scales, which allow for 100% non-invasive, non-destructive, and in-line product-free evaluation of fill weights, without negatively impacting line speed or productivity.

[0017] Figure 1 schematically illustrates an exemplary system 110 for filling containers with liquid. The system 110 includes a flow control device 120, one or more sensors 130a, and a processing unit 140. Sensor 130b is represented with a dashed line to illustrate that sensor 130b is optional, and the exemplary system 110 can be configured with only sensor 130a. Sensors 130a, b are in communicative connection with processing unit 140 and in fluidic connection with flow control device 120. Flow control device 120 may also be in fluidic connection with processing unit 140. In addition, flow control device 120 may be in fluidic connection with piping 150 and, via piping 150, with a storage reservoir 160 and a container 170. Petition 870250088098, dated 09 / 29 / 2025, page 25 / 70 7 / 38

[0018] The flow control device 120 may include one or more pumps (e.g., peristaltic pump, gear pump, diaphragm pump, etc.), one or more valves, and / or any other suitable flow control elements. The flow control device 120 may be distributed along the fluid portion of the system 110. For example, a pump may be arranged in the reservoir 160 or at a point along the piping 150, while one or more valves may be arranged at different points along the piping 150.

[0019] Sensors 130a, b may be ultrasonic, electromagnetic, or any other suitable flow sensors. Additionally or alternatively, at least one of the sensors 130a, b may be an imaging sensor, a particle velocimetry sensor, or any other suitable type of sensor capable of measuring the flow rate within the pipe 150. The system 110 may additionally include sensors for measuring fluid or ambient temperature, fluid or ambient pressure, fluid density, opacity, viscosity, and / or uniformity.

[0020] The processing unit 140 may include one or more processors. The one or more processors may be included in a single computing device or, in some examples, may be distributed among several devices. For example, the processing unit 140 may have some components integrated into the sensors 130a, b, other components integrated into the flow control device 120, and still other components integrated into a general process control and / or notification system. At least one of the one or more processors included in the unit of Petition 870250088098, dated 09 / 29 / 2025, page 26 / 70 8 / 38 Processing 140 can be implemented in the cloud. At least one of the one or more processors included in Processing Unit 140 can be included in a laptop-type computer or a mobile computing device. The one or more processors of Processing Unit 140 can include one or more microcontrollers (μCs), single-core or multi-core central processing units (CPUs), graphics processing units (GPUs), field-programmable gate arrays (FPGAs), or any other suitable processor architecture.

[0021] The processing unit 140 may include memory elements communicatively connected to one or more processors. The memory elements may include a read-only memory (ROM) component and a random-access memory (RAM) component, removable memory devices, etc. The memory elements may be communicatively connected to one or more processors via bus structures including a memory bus or memory controller, a peripheral bus or a local bus, etc., and may use any suitable bus architecture. By way of example, and without limitation, such architectures include the Industry Standard Architecture (ISA) bus, Micro Channel Architecture (MCA) bus, Enhanced ISA bus (EISA), and Peripheral Component Interconnect (PCI) bus (also known as Mezzanine bus).

[0022] The processing unit 140 can be communicatively connected to the flow control device 120 and to the sensors 130a, by any suitable combination of wired and / or wireless connections. Petition 870250088098, dated 09 / 29 / 2025, page 27 / 70 9 / 38

[0023] The 150 tubing may be uniform or include multiple fluidly connected portions. The 150 tubing may be rigid, flexible, or include a combination of rigid and / or flexible portions. The 150 tubing may be composed of glass, metal, plastic (e.g., silicone, Teflon, etc.) or any other suitable material. The 150 tubing may include different portions with different internal and / or external diameters. The tubing may be terminated by a nozzle configured to direct the liquid to the 170 container. The 150 tubing may have a diameter of 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15 mm or any other suitable diameter.

[0024] Reservoir 160 may be a compensation vessel, a tank, a vat, or any other suitable reservoir composed of glass, metal, plastic, or any other suitable material or combination of materials. Reservoir 160 may include an outlet for connection to piping 150. Reservoir 160 may include one or more inlets through which reservoir 160 may receive liquid and / or gas to pressurize reservoir 160. One or more sensors may be disposed within reservoir 160 to monitor, for example, environmental conditions within reservoir 160. One or more pumps and / or heating elements may be disposed in reservoir 160 to control environmental conditions within reservoir 160. In some examples, reservoir 160 may include an agitator or a mixing element to assist in mixing, homogenizing, or degassing the liquid in reservoir 160. Petition 870250088098, dated 09 / 29 / 2025, page 28 / 70 10 / 38

[0025] The liquid in reservoir 160 may be a therapeutic agent, a drug, a biopharmaceutical, or any other liquid to fill container 170. In some examples, the liquid in reservoir 160 is a suspension. The challenge of transferring the suspension from reservoir 160 to container 170 includes maintaining the appropriate composition of the suspension.

[0026] Container 170 may be a syringe, an ampoule, a cartridge, or any other container suitable for receiving the liquid from reservoir 160. Container 170 may be made from glass, metal, plastic, or any other suitable material. The liquid may be an injectable therapeutic, and container 170 may be configured to hold one or more doses of the therapeutic.

[0027] In some embodiments, the system 110 may include multiple reservoirs with different liquids and multiple flow control devices configured to transfer liquids from the multiple reservoirs to the container 170 at appropriate relative ratios. A person skilled in the art may apply the techniques of this disclosure to implement measurements and / or controls to add liquids from multiple reservoirs to the container with precise quantities of the different liquids from the corresponding reservoirs.

[0028] In operation, the flow control device 120 of the system 110 can transfer at least a portion of the liquid from the storage reservoir 160 to the container 170. A peak flow rate in the pipe 150 during the transfer of liquid to the container 170 can be 0.1, 0.2, 0.5, 1, 2, 5, 10 ml / s or any other Petition 870250088098, dated 09 / 29 / 2025, page 29 / 70 11 / 38 appropriate peak flow rate. In some examples, the flow control device 120 may initiate and / or terminate the transfer based on a signal from the processing unit 140. That is, the processing unit 140 may cause the flow control device 120 to transfer, through the piping 150, a portion of the liquid from the storage reservoir 160 to the container 170. In other examples, the flow control device 120 may operate independently of the processing unit 140. Furthermore, in some implementations, the flow control device 120 may be placed outside a system to determine the conformity of a container filling process.In Figure 1, to indicate that the flow control device 120 and the processing unit 140 do not need to communicate with each other, the arrow symbolizing a communicative connection between the processing unit 140 and the flow control device 120 is shown with a dashed line.

[0029] Sensors 130a, b arranged in pipe 150 are configured to measure, directly or indirectly, as described in more detail below, the flow rate of liquid flowing through pipe 150. In some example, the flow rate is between 0.1 and 1 ml / s. Sensors 130a, b do not need to measure the flow rate directly. Instead, sensors 130a, b can, for example, measure the velocity of the liquid flowing through pipe 150. Even if the velocity in pipe 150 is not uniform, i.e., varies within the cross-section of pipe 150, sensors 130a, b can effectively measure an average velocity or, for that matter, any suitable indication of velocity. In Petition 870250088098, dated 09 / 29 / 2025, page 30 / 70 12 / 38 In some examples, the average velocity is between 1 and 100 cm / s. More generally, sensors 130a, b can measure any flow rate indication. The processing unit 140 can convert any flow rate indication into an accurate flow rate measurement using calibration data obtained as described in more detail below with reference to Figures 2, 7 and 8. It should be noted that the sensor output may have a different relationship with the flow depending, for example, on flow properties such as flow laminarity and / or liquid properties.

[0030] In some examples, sensors 130a, b can transduce a physical property of flow, such as velocity, into an analog voltage or current. In other examples, sensors 130a, b can be integrated with analog-to-digital (A / D) converters and configured to generate a digital signal indicating the flow rate. Such sensors can transfer the digital data indicating flow rate measurements to the processing unit 140 using any suitable wired or wireless interface. Sensors 130a, b can have multiple outputs, which generate a plurality of signals, whether analog or digital. In addition to flow rate indication signals, sensors 130a, b can generate signals indicating internal transduction amplitude and / or diagnostic signals, as described in more detail with reference to Figures 6A, B.

[0031] Sensors 130a, b can be configured to sample indicative flow rate values ​​at regular time intervals indicated by sampling frequency or sampling. In other examples, sensors 130a, b can be configured to generate indicative flow rate signals. Petition 870250088098, dated 09 / 29 / 2025, page 31 / 70 13 / 38 flow based on received trigger signals. For example, processing unit 140 can generate trigger signals to request samples from sensors 130a, b.

[0032] Processing unit 140 can read or receive, in real time or with some delay, some or all of the values ​​encoded in the signals generated by sensors 130a, B. As described above, the values ​​can be analog or digital values. The processing unit can digitize analog values ​​received from sensors 130a, b using an A / D converter. Along with the flow rate indicators received from sensors 130a, b, processing unit 140 can receive or generate time indicators associated with the flow rate values. At least some of the time indicators associated with the flow rate values ​​may correspond to a filling time interval, that is, the time interval during which the liquid flowing through the pipe 150 is transferred to the container 170.

[0033] In some examples, the filling time interval may correspond to a time interval or a sequence of time intervals during which the flow control device 120 is continuously transferring liquid to the container 170. That is, the flow control device 120 may cause the liquid flow to be intermittent, with one or more filling time intervals interrupted by substantially zero flow. Additionally or alternatively, the filling time interval may correspond to a time interval during which there is a fluidic connection between the tubing 150 and the Petition 870250088098, dated 09 / 29 / 2025, page 32 / 70 14 / 38 container 170. For example, during a period of substantially uninterrupted liquid flow through pipe 150, a robotic system (or any other suitable method) may exchange container 174 for another container. The processing unit 140 may receive or generate indicative values ​​of time intervals during which a fluidic connection exists between pipe 150 and container 170 and during which the flow control device 120 transfers liquid to container 170. In some examples, the processing unit 140 may generate trigger signals causing changes in the liquid flow through pipe 150 and / or trigger signals causing the replacement of container 170 with another container. In other examples, the processing unit 140 may receive time indications when the liquid flow started and / or stopped, and / or when container 170 was in fluidic connection with pipe 150.

[0034] Processing unit 140 can compute, based at least in part on the plurality of received values ​​indicative of flow rates, and fill quantity indication corresponding to the amount of liquid transferred to container 170 during the filling time interval or, equivalently, a sequence of filling time intervals comprising a total filling time interval or filling time. The computation can also be based on time indications corresponding to the filling time interval received and / or generated by processing unit 140. To compute the fill quantity indication, which for simplicity can be referred to as Petition 870250088098, dated 09 / 29 / 2025, page 33 / 70 15 / 38 filling quantity, processing unit 140 can numerically integrate the liquid flow rate into container 170 during the total filling time. For simplicity, the total filling time can be referred to as the filling time interval, with the understanding that the filling time interval may comprise a sequence of filling time intervals. That is, the discussion below will assume that the total duration during which container 170 receives the liquid is represented by a single filling time interval. The total filling time for container 170 may be between 0.1, 0.2, 0.5, 2, 5, 10 s or another suitable time.

[0035] After computing the filling quantity, processing unit 140 can compare the filling quantity with a target filling quantity. In some examples, the filling quantity and the target filling quantity are between 0.2 ml and 40 ml and / or between 0.2 mg and 40 mg. The comparison may include computing the absolute difference between the filling quantity and the target filling quantity, as well as the possibility of the filling quantity being greater than or less than the target filling quantity. In some examples, processing unit 140 can perform an analog signal comparison. For this purpose, processing unit 140 can use one or more comparators to generate one or more respective binary outputs by comparing an integrated analog output of a sensor (e.g., sensor 130a or b) with a reference voltage.Alternatively, processing unit 140 may include an A / D converter following a... Petition 870250088098, dated 09 / 29 / 2025, page 34 / 70 16 / 38 differential amplifier to digitize a difference between the integrated sensor voltage output and a reference voltage. In other examples, the 140 processing unit can perform comparison in the digital domain. For this purpose, the 140 processing unit can receive or generate a binary value with a suitable resolution (e.g., 8 bits, 12 bits, 16 bits, 24 bits, etc.) indicative of the amount of fill and compare the binary value with the target fill quantity value stored in the 140 processing unit's memory.

[0036] Based on a comparison of the fill quantity computed from sensor measurements with the target fill quantity, it can generate a fill quantity compliance indication. For example, the measured fill quantity can be indicated as compliant when it falls within a range of the target fill quantity. Processing unit 140 can receive the target quantity and the compliance range to generate compliance indications. Processing unit 140 can store a record of computed fill quantities and / or generated compliance indications. Furthermore, processing unit 140 can display the compliance indication on a display unit, as described in more detail below with reference to Figure 2.

[0037] Figure 2 schematically illustrates another exemplary system 210 for filling containers with liquid. The exemplary system 10 includes a flow control device 220 (which may be the flow control device 120), one or more sensors 230a, b (which may be sensors 130a, b) and a processing unit 240 (which Petition 870250088098, dated 09 / 29 / 2025, p. 35 / 70 17 / 38 may be processing unit 140). The system may additionally include piping 250 (which may be piping 150) and a reservoir 260 (which may be reservoir 160) that serves as the source of liquid to be transferred to container 270 (which may be container 170).

[0038] System 210 additionally includes a display unit 280 communicatively connected to the processing unit 240. The display unit 280 may include a liquid crystal display (LCD), an organic light-emitting diode (OLED) display, or any other suitable matrix display. Additionally or alternatively, the display unit 280 may include one or more luminous indicators, such as lamps and / or light-emitting diodes (LEDs). Furthermore, the display unit 280 may include one or more sound generators (e.g., buzzer, speakers, etc.) configured to generate audible alerts (e.g., to indicate compliance). In some examples, a display belonging to the display unit 280 may be integrated into a user device (e.g., laptop computer, tablet computer, smartphone, etc.).In any case, a graphical user interface can be rendered on a display of the display unit 280, and the processing unit 240 can display the fill quantity compliance indication through the graphical user interface with, for example, a virtual button or a bar graph configured to change color as the bar passes a threshold and / or a text alert. Additionally, the display unit 280 can generate a... Petition 870250088098, dated 09 / 29 / 2025, page 36 / 70 18 / 38 audible alert as a buzzer pattern, a beep pattern and / or a pre-recorded or synthesized speech message.

[0039] The processing unit 240 of the system 10 may be in communicative connection with a gravimetric balance 290 or simply balance 290. In some examples, the balance 290 may be included in the system 210. Using the balance 290, the processing unit 240 may perform one or more calibrations, as described in more detail below, with reference to Figures 7A and 7B. In general terms, the processing unit 240 may record one or more weights associated with the respective fill quantities computed based on measurements from the sensors 230a, and create a lookup table and / or a formula that relates fill quantities to the weights measured by gravimetric sheets. In other examples, the system 210 may include a device (e.g., a camera, a level sensor, etc.) to measure the liquid volume or liquid level within the container 270. The processing unit 240 can use the measured liquid volume or liquid level to calibrate fill quantities computed by the processing unit 240 based on measurements from sensors 230a, b.

[0040] In some examples, processing unit 240 can control flow control device 220 to perform a variety of calibrations, such as those described above. For example, processing unit 240 can cause flow control device 220 to induce liquid flow in the piping for one or more periods of time of any suitable duration. The processing unit can use, for each of the periods of Petition 870250088098, dated 09 / 29 / 2025, page 37 / 70 19 / 38 time, respective weights or weight increments measured by the calibration flow rates of the balance 292 measured by sensors 230a, b. Additionally or alternatively, the processing unit 240 may cause the flow control device to interrupt the liquid flow in the pipe 250 and receive baseline measurements from sensors 230a, b.

[0041] Figure 3 schematically illustrates an exemplary system 315 for detecting fill quantity conformance, which may be a portion of a system for filling containers with liquid (e.g., system 110 or 210). System 315 includes a processing unit 340 (which may be processing unit 140 or 240) and two flow sensors 330a, b (which may be sensors 130a, b or sensors 230a, b). Note that system 315 need not include a flow control device. Generally, a flow control device does not need to be included in a system for detecting fill quantity conformance, but a flow control device (e.g., flow control device 120 or 220) may be included in a larger system for filling a container with liquid that may include system 315.

[0042] The sensors 330a, b of the system 315 can be arranged, respectively, in two pipe sections 350a, b which can be pipe sections 150 or 250. The pipe sections 350a, b communicate fluidically with each other and are connected in series to transfer liquid to a container 370 (which can be container 170 or 270). The pipe section 350a can have a thinner internal diameter than the pipe section 350b. Consequently, Petition 870250088098, dated 09 / 29 / 2025, page 38 / 70 20 / 38 for liquid transfer with a constant flow velocity in section 350a may be faster than the flow velocity in section 350b. In some examples, pipe sections 350a and b may be connected by means of an adapter or an adapter section with an internal diameter that changes gradually, for example, to avoid the possibility of creating turbulence.

[0043] The inner diameter of section 350b may be larger than the inner diameter of section 350a by 10%, 20%, 40%, 50%, 100% or any other suitable ratio. For example, the inner diameter of section 350b may be 2 mm, while the diameter of section 350b may be 3 mm, that is, 50% larger than the diameter of section 350a.

[0044] System 315 can use the two sensors 330a, b arranged in the two pipe sections 350a, b in a variety of ways. First, as with two sensors (e.g., sensors 130a, b or 230a, b) arranged in sections of the same pipe diameter (e.g., pipe 150 or 250), the processing unit 340 can receive values ​​from the two sensors 350a, b and average them to reduce noise. Alternatively, processing unit 340 can correlate time sequences of flow rate values ​​from the two sensors 350a, b to identify changes in intermittent flow, for example, forward or backward boundaries of a liquid section, as discussed with reference to Figure 5. Furthermore, also as discussed with reference to Figure 5, processing unit 340 can identify flow anomalies (e.g., unexpected discontinuities or bubbles) by correlating time sequences of flow values. Petition 870250088098, dated 09 / 29 / 2025, p. 39 / 70 21 / 38 By using sensors 330a, b, arranged in different pipe sections of diameter 350a, b, system 315 can allow for additional insight into flow properties or sensor performance. Because liquid flow is substantially incompressible, the average flow velocities in pipe sections of different sizes 350a, b are inversely proportional to the areas of the respective pipe cross-sections. For example, if the cross-sectional diameter of pipe section 350b is 20% larger than the cross-sectional diameter of pipe section 350a, the average flow velocity in section 350a should be 44% faster than in section 350b (because the area varies as the square of the diameter).Although the indicative values ​​of the flow rates received from sensors 330a, b may not have the same ratio as the respective average flow velocities (due to the particularities of flow velocity measurements), the relationship between the two values ​​can be deduced from the calibration. Deviations from the relationship deduced from the calibration may indicate changes or anomalies in the flow. Furthermore, system 315 can use velocity measurements in pipe sections of different sizes 350a, b to improve the accuracy of the flow velocity measurements, at least because the faster or slower velocity may be closer to the ideal range of a flow rate sensor 330a or b.

[0045] Figure 4 schematically illustrates another exemplary system 415 for detecting fill quantity conformity. System 415 includes a processing unit 440 (which may be processing unit 140, 240 or 340) and three flow sensors 430a-c. The sensors Petition 870250088098, dated 09 / 29 / 2025, pp. 40 / 70 22 / 38 Sensors 430a-c are arranged in piping 450 configured to transfer liquid to a container 470 (which may be container 170, 270, or 370). The sensors 430a-c do not need to be arranged with equal spacing. System 415 can use the three sensors 430a-c in a variety of ways. First, averaging and averaging values ​​from multiple sensors can increase measurement accuracy. Second, processing unit 440 can correlate time sequences of values ​​from the three sensors 430a-c to identify changes in intermittent flow, for example, forward or backward boundaries of a liquid section, as discussed with reference to Figure 5. Furthermore, also as discussed with reference to Figure 5, processing unit 440 can identify flow anomalies (e.g., discontinuities or unexpected bubbles) by correlating time sequences of flow values. Additionally, system 415 can use the three sensors for diagnostic purposes.For example, when the values ​​generated by one of the sensors are inconsistent with the values ​​generated by the other two, the outlier value can be ignored and the matching sensor can be flagged as malfunctioning.

[0046] Figure 5 schematically illustrates an example of a 530 non-contact flow sensor (which may be one of the 130a, b, 230a, b, 330a, b or 430a-c flow sensors) arranged in a pipe section. Having a non-contact sensor can be particularly important in medical applications. The 530 sensor may be an ultrasonic sensor, an electromagnetic sensor, an optical sensor or another suitable non-contact sensor. The sensor may include a 532 configured channel. Petition 870250088098, dated 09 / 29 / 2025, page 41 / 70 23 / 38 to match the pipe diameter. In some examples, a sleeve may be placed over the pipe to provide better contact with the flow sensor 530. As discussed above, the sensor 530 can assist in identifying discontinuities in intermittent flow. For example, a system (e.g., system 110, 210, 315, or 415) may use the sensor 530 to identify a forward boundary 555a or a backward boundary 555b that separates a liquid portion 555c from an empty (i.e., gas-filled) portion of the intermittent flow. Additionally, the system may use the sensor 530 to identify an air pocket or bubble 555e or other anomaly within the liquid portion 555c. The system may further include vibration isolation, thermal insulation, and electrical shielding to reduce measurement noise.

[0047] Figures 6a, B schematically illustrate an operating principle of an ultrasonic flow sensor 630 (which may be one of flow sensors 130a, b, 230, a, b, 330 a, b, 430a-c or 530). The sensor may include one channel 632 and four ultrasonic transducers 635a-d. Channel 632 is configured to clamp tightly around a section of pipe, creating a sonically conductive path, particularly when the pipe is filled with liquid. Of the transducers 635a-d, two 635a, b may be used as ultrasonic transmitters and two 635c-d may be used as ultrasonic receivers. Three arrows within channel 632 schematically illustrate a flow velocity profile within channel 632. Near the center, a liquid may move faster than the liquid near the edge (e.g., during laminar flow). In some instances, the flow may be turbulent (e.g., at high flow rates). Petition 870250088098, dated 09 / 29 / 2025, page 42 / 7024 / 38 higher) or transitional between laminar and turbulent flow. Curved dashed lines between transducer 635a and transducer 635d in Figure 6a and, in Figure 6B, between transducer 635b and transducer 635c schematically illustrate sonic wavefronts. Leaving ultrasonic transmitters 635a, b, the wavefronts are equally spaced in Figures 6a and 6B. However, in Figure 6a, the wavefronts arrive at ultrasonic receiver 635d with greater spacing than the wavefronts arriving at ultrasonic receiver 635c in Figure 6B, because the ultrasonic waves move with the flow in Figure 6a and against the flow in Figure 6B. The change in wavefront spacing can be considered an example of the Doppler effect, and the ultrasound frequency received in Figure 6A is lower than the ultrasound frequency in Figure 6B.The 630 sensor may include electronic components to generate an analog or digital output indicative of flow velocity based on the difference in received ultrasound frequencies. In some examples, instead of transmitting continuous ultrasound waves, the 630 sensor may transmit ultrasound pulses. When using ultrasound pulses, the 630 sensor may generate an output indicative of flow velocity based on the difference in transit times (transit time difference or TTD) of ultrasonic pulses with and against the flow. Additionally or alternatively, the 630 sensor may be configured to use phase differences in ultrasound signals received with and against the flow. The phase difference method may be particularly advantageous when the time and frequency differences of the TTD and Doppler methods are small. Furthermore, the sensor... Petition 870250088098, dated 09 / 29 / 2025, page 43 / 70 25 / 38 630 can output values ​​for received signal strengths. A system (e.g., system 110, 210, 315, or 415) can use output values ​​indicative of signal strengths to identify intermittent flow liquid limits, sound transduction problems, and / or changes in one or more liquid flow properties within the tube disposed in channel 632. Furthermore, the system can use the various outputs above to generate fault mode alerts indicative of fill quality fault modes (e.g., dripping, splashing, bubble formation, etc.) and / or alerts indicative of system malfunction (e.g., blockage, etc.) as described in more detail with reference to Figure 8. During a test or calibration process, the system can be configured to generate a set of faults of different types during which sensor outputs (e.g., flow rates, signal strengths, etc.) can be sampled.Based on the generated set of failures and corresponding data, a classifier to identify failure rates can be generated. During operation, the system can then use classifiers to estimate the probabilities of different types of failures and generate alerts when the respective probabilities exceed the corresponding threshold.

[0048] Figures 7A and B illustrate exemplary flow profiles during the operation of a system (e.g., system 110 or 210). The graphs in Figures 7A and B illustrate sample flow rates as a function of time. The system may cause a flow control device to maintain a constant flow rate for an interval of 100 ms or more (as in Figure 7A), for example, to Petition 870250088098, dated 09 / 29 / 2025, page 44 / 70 26 / 38 generate a fill of 10 ml or more for use in flow rate calibration, as discussed in more detail below with reference to Figure 8. The flow rate during a normal container filling operation, on the other hand, may include short bursts of flow rate, to generate, with each burst, a smaller fill volume (e.g., 2 ml). It should be noted that during calibration, a larger calibration volume (e.g., > 10 ml) may be filled in multiple bursts instead of using a constant flow rate during a single time interval, as in Figure 7A. Although not visible in Figures 7A and B, flow rate profiles may include start and stop ramps. The start and stop ramps may be substantially linear, each with a substantially constant slope, or may have any other suitable shape.

[0049] Figure 8 illustrates an example method 800 for verifying the conformity of the container filling quantity. Method 800 can be executed, at least in part, by one or more processors of processing units 140, 240, 340, or 440 of systems 110, 210, 315, or 415 discussed above with reference to Figures 1-4. In some examples, method 800 can be executed, at least in part, by processors external to systems 110, 210, 315, or 415.

[0050] In block 810, method 800 includes causing one or more processors to cause a flow control device (for example, flow control device 120 or 220) to transfer a liquid from a storage reservoir (for example, storage reservoir 160 or 260) to a container (for example, container 170, 270, 370 or 470) Petition 870250088098, dated 09 / 29 / 2025, page 45 / 70 27 / 38 via piping (e.g., 150, 250, 450 piping or 350a, b piping segments). The piping may be terminated by a nozzle configured to direct the flow to the vessel.

[0051] In block 820, method 800 involves receiving, by one or more processors and at least one sensor located in the pipeline, a plurality of values ​​indicative of a plurality of respective flow rates at a plurality of respective times within a filling time interval. The plurality of times for which the received flow rate values ​​may include regularly spaced times based on a sampling rate (equivalently, sampling frequency or sampling period). The sampling rate may be between 10 Hz and 1 kHz (10 to 1000 samples / s), for example. The filling time interval may be between 0.1 and 10 seconds. It may be advantageous to have more sample points during a filling time interval. There is, however, a trade-off between the sampling rate and the noise per sample.Thus, for continuous flow, having a higher sampling rate may not necessarily decrease noise in the estimation of the average flow rate. On the other hand, a higher sampling rate can help identify flow start and stop points, particularly when the flow increase and decrease profiles are not well known. Furthermore, in addition to random variations due to thermal noise, systemic noise can affect the samples. In particular, a peristaltic pump can cause flow pulsations. The coupling of alternating current (AC) power frequencies (e.g., 50 Hz, 60 Hz, etc.) in a sensor signal can also affect the samples. Petition 870250088098, dated 09 / 29 / 2025, pp. 46 / 70 28 / 38 can cause systemic periodic fluctuations. To alleviate systemic noise problems, method 800 may include receiving, by one or more processors, one or more indications of at least one of i) a measurement noise indication, ii) a periodic flow rate disturbance indication, and / or iii) a line voltage variation indication. Method 800 may additionally include altering the sampling rate based on one or more received indications. One approach may include increasing the sampling rate beyond the Nyquist rate of signal fluctuations. Another approach may include adjusting the sampling rate to avoid aliasing effects. For example, method 800 may include adjusting the sampling rate to match or be a fraction of a flow fluctuation frequency caused by the peristaltic pump.Furthermore, to avoid the effect of inconsistent sampling with respect to the phase fluctuations caused by the peristaltic pump, the method may include adjusting the sampling phase. Method 800 may additionally include generating, by one or more processors, a trigger signal for synchronization operation of the flow control device and the sampling rate.

[0052] In block 830, method 800 includes computing, by one or more processors, based at least in part on the plurality of received values, an indication of the filling quantity; the indication of the filling quantity may be referred to as the filling quantity to which the indication may be converted using appropriate calibration and / or other multipliers. Generally, computing the filling quantity includes numerical integration of flow rate samples by summing sample values ​​or. Petition 870250088098, dated 09 / 29 / 2025, page 47 / 70 29 / 38 using any other suitable numerical integration method.

[0053] Calculating the fill quantity using numerical integration may involve determining, by one or more processors, a start time and an end time of the fill time interval based, at least in part, on the plurality of received values ​​indicative of the plurality of respective flow rates at the plurality of respective times within the fill time interval. For example, the 800 method may include determining a start time and / or a stop time by comparing the measured flow rate with a threshold. In other examples, the 800 method may include determining a slope corresponding to an increase or decrease in the flow rate and finding a zero intercept to identify a start time and / or a stop time.

[0054] Calculating the fill quantity may include calculating a fill weight. To this end, method 800 may include obtaining, by one or more processors, an estimate of the liquid density. Calculating the fill weight may then be based on the density estimate. Obtaining the density estimate may include receiving information about the liquid (e.g., fluid composition), measuring environmental parameters such as temperature, pressure, and / or humidity. Additionally or alternatively, obtaining the density estimate may include performing a calibration. Calibration may include weighing (e.g., using balance 290) any suitable filled container and subtracting the container's tare weight. Calibration is Petition 870250088098, dated 09 / 29 / 2025, pp. 48 / 70 30 / 38 described in more detail below with reference to block 860.

[0055] In block 840, method 800 involves comparing, by one or more processors, the fill quantity indication to a target fill quantity. Method 800 can perform the comparison in the analog or digital domain as described in more detail above with reference to Figure 1.

[0056] In block 850, method 800 includes generating, by one or more processors, an indication of conformity with the filling quantity. For this purpose, method 800 may include comparing the difference between the measured filling quantity and the target filling quantity with an indicative threshold of assigned tolerance. The tolerances for a positive excursion from the target value and the negative excursion from the target value need not be the same. The tolerances may be defined for a specific filling process and may depend on the liquid, the desired filling quantity and / or the type of container to be filled.

[0057] Method 800 may additionally include generating an alert based on the indication of compliance with the filling quantity. The alert may be a visual alert or an audible alert generated on a display unit (e.g., display unit 280). Additionally or alternatively, method 800 may include generating one or more alerts indicating one or more failure modes and / or other malfunctions. The alerts may include: Indication of sensor malfunction (e.g., as described with reference to Figure 4), indication of an air pocket in Petition 870250088098, dated 09 / 29 / 2025, pp. 49 / 70 31 / 38 liquid (e.g., as described with reference to Figure 5), drip indication, blockage indication (e.g., at a nozzle), and / or other suitable indications. The drip indication may be generated based on the measurement or detection of a non-zero flow rate when the flow rate should nominally be zero. The blockage indication may be generated based on the measurement or detection of a line flow rate value with the expected flow rate value. More generally, sensor data may be correlated to independently detected problems or faults to extract indicative data features of the respective problems and faults. The system may use digital signal processing methods (e.g., correlation filters) and / or machine learning models to detect fault modes and / or other problems.The system can compare the output of a suitable digital filter and / or a suitable machine learning model to a threshold for a specific alert and issue the alert if the threshold is exceeded. Method 800 may include generating an interface to allow a user to select thresholds for different alerts.

[0058] In an optional block 860, method 800 may include receiving, by one or more processors and at least one sensor, a calibration flow value and computing the fill quantity indication based, at least in part, on the received calibration flow value. In one example, the calibration flow value may be a baseline or a zero flow value generated by a sensor. To obtain the baseline value, method 800 may include having, by one or more processors, the device Petition 870250088098, dated 09 / 29 / 2025, pages 50 / 70 32 / 38 flow control prevents liquid transfer during a reference calibration time interval. Computing the fill quantity indication can be based, at least in part, on the received baseline value.

[0059] Alternatively, calibration may include determining one or more conversion multipliers to convert a numerical integration of flow rate indicators into a fill quantity. To obtain the conversion factors, method 800 may include having one or more processors transfer the flow control device at a constant flow rate during a flow rate calibration time interval, as discussed with reference to Figures 7A, B. Method 800 may additionally include receiving, from one or more processors and at least one sensor, a calibration flow value or a set of calibration flow values ​​during the flow rate calibration time interval. Method 800 may additionally include numerically integrating the flow rate values ​​during the flow rate calibration time interval.Furthermore, method 800 may include an independent measurement of a quantity of liquid accumulated in a container during the flow rate calibration time interval. The independent measurement may be a volume measurement and / or a weighing measurement, for example, using balance 290 in Figure 2. As discussed with reference to Figures 7A, B, the calibration quantity need not be the same as the target quantity. In some examples, the calibration quantity may be greater than the target quantity. Petition 870250088098, dated 09 / 29 / 2025, pp. 51 / 70 33 / 38 target by a factor of 2, 5, 10, 20, 50, 100 or any other suitable factor. Calibrations can be performed for different liquids, different flow rates, different environmental conditions, etc., and can compensate for variations in liquid density and sensor measurement accuracy.

[0060] The calibration process described above may include a series of calculations. For example, the calibration process may include liquid accumulation in a container during a calibration time interval (e.g., as illustrated in Figure 7A). The system may compute an estimate of the mass flow rate and volume flow rate corresponding to a sensor output during calibration as: _ cal „ _ ^cal ^cal = ~7 deal = ~ cal P where μcal is the flow rate during calibration, mcal is the mass accumulated in a container during calibration (e.g., measured by balance 290), Qcal is the volume flow rate, and ρ is the density of the liquid. In some examples, ρ may be an external input to the calculation based on the predetermined density of the liquid. In other examples, it may be computed based on the measurement of the volume of liquid accumulated in the container during calibration (e.g., by measuring the liquid level inside the container of known cross-section). The system can compute the mass and volume flow rates during filling operations as _ ^cal „ „ _ Qcal „ ^med t7 med mmed 77 med 'calvcal where pmede Qmed are, respectively, mass and volume flow rates during a single filling Fmede 7cal are integrated voltages (or other integrated output values). Petition 870250088098, dated 09 / 29 / 2025, pp. 52 / 70 34 / 38 as described above), respectively, during measurement and during calibration.

[0061] Method 800 may include performing calibrations at different flow velocities, for different internal pipe diameters, under different environmental conditions, etc. In some examples, calibration may include generating a calibration profile equivalent to multiple filling operation profiles (e.g., as in Figure 7B vs. Figure 7A). Additionally, during the calibration process, Method 800 may include statistically analyzing the sample sequence (e.g., as illustrated in Figures 7A and B) to generate a sensor noise estimate. In some examples, the system may vary the sampling rate to find the ideal sampling rate to reduce total noise during integration. Alternatively, Method 800 may include generating an alert if the noise during calibration exceeds a threshold.

[0062] Further considerations relating to this disclosure will now be addressed.

[0063] Some of the Figures described in this document illustrate exemplary block diagrams that have one or more functional components. It will be understood that these block diagrams are for illustrative purposes and the devices described and shown may have additional components, fewer components, or alternative components to those illustrated. Additionally, in various embodiments, the components (as well as the functionality provided by the respective components) may be associated with, or otherwise integrated as part of, any suitable components. Petition 870250088098, dated 09 / 29 / 2025, pp. 53 / 70 35 / 38

[0064] The disclosure modalities refer to a non-transient, computer-readable storage medium including computer code for performing various computer-implemented operations. The term “computer-readable storage medium” is used herein to include any medium capable of storing or encoding a sequence of instructions or computer code to perform the operations, methodologies, and techniques described herein. The media and computer code may be those specially designed and constructed for the purposes of the disclosure modalities, or they may be of a type well known and available to those skilled in the art of computer software.Examples of computer-readable storage media include, but are not limited to: magnetic media, such as hard disks, floppy disks, and magnetic tape; optical media, such as CD-ROMs and holographic devices; magneto-optical media, such as optical discs; and hardware devices that are specially configured to store and execute program code, such as ASICs, programmable logic devices (PLDs), and ROM and RAM devices.

[0065] Examples of computer code include machine code, such as that produced by a compiler, and files containing higher-level code that are executed by a computer using an interpreter or a compiler. For example, a manifestation of disclosure can be implemented using Java, C++, or another object-oriented programming language and development tools. Additional examples of computer code include encrypted code and compressed code. Furthermore, a Petition 870250088098, dated 09 / 29 / 2025, pp. 54 / 70 36 / 38 The disclosure modality can be transferred by download as a computer program product, which can be transferred from a remote computer (e.g., a server computer) to a requesting computer (e.g., a client computer or a different server computer) via a transmission channel. Another disclosure modality can be implemented in wired circuit assemblies in place of, or in combination with, machine-executable software instructions.

[0066] As used in this document, the singular terms “a”, “an” and “the” may include the referring plural forms, unless the context clearly indicates otherwise.

[0067] As used in this document, the terms “approximately,” “substantially,” “substantial,” and “about” are used to describe and represent small variations. When used in conjunction with an event or circumstance, the terms may refer to instances where the event or circumstance occurs precisely, as well as instances where the event or circumstance occurs approximately. For example, when used in conjunction with a numerical value, the terms may refer to a range of variation less than or equal to ±10% of that numerical value, such as less than or equal to ±5%, less than or equal to ±4%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1%, less than or equal to ±0.5%, less than or equal to ±0.1%, or less than or equal to ±0.05%. For example, two numerical values ​​can be considered to be "substantially" the same if the difference between the values ​​is less than or equal to ±10% of the average of the values, such as less than or equal to ±5%, less than or equal to ±4%. Petition 870250088098, dated 09 / 29 / 2025, pp. 55 / 70 37 / 38%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1%, less than or equal to ±0.5%, less than or equal to ±0.1%, or less than or equal to ±0.05%.

[0068] Additionally, quantities, ratios, and other numerical values ​​are sometimes presented in this document in a range format. It should be understood that this range format is used for convenience and brevity and should be understood flexibly as including numerical values ​​explicitly specified as limits of a range, but equally as including all individual numerical values ​​or sub-ranges encompassed within that range as if each numerical value and sub-range were explicitly specified.

[0069] Although the present disclosure has been described and illustrated with reference to specific embodiments thereof, these descriptions and illustrations do not limit the present disclosure. It should be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the present disclosure as defined by the appended claims. The illustrations are not necessarily drawn to scale. There may be distinctions between the artistic interpretations in the present disclosure and the actual apparatus due to manufacturing processes, tolerances, and / or other reasons. There may be other embodiments of the present disclosure that are not specifically illustrated. The descriptive report (beyond the claims) and the drawings should be considered illustrative rather than restrictive. Modifications may be made to adapt a situation, material, composition Petition 870250088098, dated 09 / 29 / 2025, pp. 56 / 70 38 / 38 of the particular matter, technique, or process to the objective, spirit, and scope of this disclosure. All such modifications are intended to be encompassed within the scope of the appended claims. Although the techniques disclosed herein have been described with reference to particular operations performed in a particular order, it will be understood that these operations may be combined, subdivided, or rearranged to form an equivalent technique without departing from the teachings of this disclosure. Consequently, unless specifically indicated herein, the order and grouping of operations are not limitations of this disclosure. Petition 870250088098, dated 09 / 29 / 2025, pp. 57 / 70

Claims

1 / 7 CLAIMS 1.A system for filling containers with liquid, wherein the system is characterized by comprising: a flow control device configured to transfer a liquid from a storage reservoir to a container via piping; at least one sensor disposed in the piping; and one or more processors configured to: cause the flow control device to transfer at least a portion of the liquid from the storage reservoir to the container via piping; receive from at least one sensor a plurality of values ​​indicative of a plurality of respective flow rates at a plurality of respective times within a filling time interval; compute, based at least in part on the plurality of values ​​received, an indication of filling quantity; compare the indicated filling value with a target filling value; and generate an indication of filling quantity compliance.

2. System according to claim 1, characterized by further comprising: a scale, configured to measure the weight of one or more filled containers.

3. System, according to any one of claims 1 or 2, characterized by one or more processors being configured to generate a trigger signal for the flow control device.

4. System, according to any one of claims 1, 2 or 3, characterized in that the target filling quantity is between 0.2 ml and 40 ml or between 0.2 mg and 40 mg.

5. System according to any one of claims 1, 2, 3 or 4, characterized in that at least one sensor includes an ultrasonic sensor.

6. System, according to any one of claims 1, 2, 3, 4 or 5, characterized in that at least one sensor includes a first sensor and a second sensor configured to measure a first flow rate and a second flow rate in a first pipe section and a second pipe section, respectively.

7. System according to claim 6, characterized in that the internal diameter of the first pipe section is at least 10% larger than the internal diameter of the second pipe section.

8. System, according to any one of claims 1, 2, 3, 4, 5, 6 or 7, characterized in that at least one sensor includes at least three sensors.

9. System according to any one of claims 1, 2, 3, 4, 5, 6, 7 or 8, characterized by further comprising: a display device configured to generate a visual and / or auditory representation of the indication of conformity of the filling quantity.

10. System according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8 or 9, characterized in that the flow control device includes a peristaltic pump. Petition 870250088098, dated 09 / 29 / 2025, p. 59 / 70 3 / 7 11. Method for verifying the conformity of the container filling quantity, the method being characterized by comprising: causing, by one or more processors, a flow control device to transfer a liquid from a storage reservoir to a container by means of piping; receiving, by one or more processors and at least one sensor located in the piping, a plurality of values ​​indicative of a plurality of respective flow rates at a plurality of respective times within a filling time interval; computing, by one or more processors, based at least in part on the plurality of values ​​received, an indication of the filling quantity; comparing, by one or more processors, the indication of the filling quantity with a target filling quantity; and generating, by one or more processors, an indication of the conformity of the filling quantity.

12. Method according to claim 11, characterized by further comprising: obtaining, by one or more processors, an estimate of the liquid density; wherein: computing the fill quantity indication includes computing a fill weight indication based, at least in part, on the liquid density estimate; and Petition 870250088098, dated 09 / 29 / 2025, pp. 60 / 70 4 / 7 the target fill quantity is a target fill weight.

13. Method, according to claim 12, characterized by obtaining the density estimate, includes measuring the weight of one or more filled containers.

14. Method, according to any one of claims 12 or 13, characterized in that obtaining the density estimate includes an estimate of the liquid composition.

15. A method according to any one of claims 11, 12, 13 or 14, characterized in that at least part of the plurality of respective times within the filling time interval are arranged at regular intervals determined by a sampling rate, and wherein the method further comprises controlling the sampling rate.

16. Method according to claim 15, characterized by further comprising: receiving, by one or more processors, one or more indications of at least one of i) an indication of measurement noise, ii) an indication of periodic disturbances of the flow rate, and / or iii) an indication of line voltage variations; and altering the sampling rate based on one or more indications received.

17. Method, according to any one of claims 15 or 16, characterized by further comprising: generating, by one or more processors, a trigger signal for the synchronization operation of the flow control device and the sampling rate. Petition 870250088098, dated 09 / 29 / 2025, p. 61 / 70 5 / 7 18. Method, according to any one of claims 11, 12, 13, 14, 15, 16 or 17, characterized in that the sampling rate is between 10 Hz and 300 Hz.

19. A method according to any one of claims 11, 12, 13, 14, 15, 16, 17 or 18, characterized by further comprising: causing, by one or more processors, the flow control device to prevent the transfer of liquid during a baseline calibration time interval; and receiving, by one or more processors and at least one sensor, a baseline value; wherein computing the fill quantity indication is based, at least in part, on the received baseline value.

20. A method according to any one of claims 11, 12, 13, 14, 15, 16, 17, 18 or 19, characterized by further comprising: causing, by one or more processors, the flow control device to transfer the liquid at a constant flow rate during a flow rate calibration time interval; and receiving, by one or more processors and at least one sensor, a calibration flow value; wherein computing the filling quantity indication is based, at least in part, on the received calibration flow value.

21. Method, according to any one of claims 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, characterized by further comprising: Petition 870250088098, dated 09 / 29 / 2025, pp. 62 / 70 6 / 7 determining, by one or more processors, a start time and an end time of the filling time interval based, at least in part, on the plurality of received values ​​indicative of the plurality of respective flow rates at the plurality of respective times within the filling time interval.

22. Method according to claim 21, characterized by further comprising: determining, by one or more processors, and indicating the slope in a plurality of values ​​indicative of a plurality of respective flow rates; wherein determining the start time or the end time is based, at least in part, on the slope indication.

23. A method according to any one of claims 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22, characterized in that the liquid is an injectable therapeutic and the container is configured to hold one or more doses of the injectable therapeutic.

24. Method according to any one of claims 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23, characterized in that the target filler quantity is between 0.2 ml and 40 ml or between 0.2 mg and 40 mg.

25. Method according to claim 11, characterized in that at least one sensor includes an ultrasonic sensor.

26. Method, according to any one of claims 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23, wherein the method is characterized by further comprising measuring, using a first sensor to measure a first flow rate in a first section of piping and using a second sensor to measure a second flow rate in a second section of piping.

27. Method according to claim 26, characterized in that the internal diameter of the first pipe section is at least 10% larger than the internal diameter of the second pipe section.

28. A method according to any one of claims 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 or 27, characterized in that at least one sensor includes at least three sensors, and the method further comprises: determining, by one or more processors, that one of the at least three sensors has generated an outlier measurement; and generating, by one or more processors, an alert based on the outlier measurement; wherein computing the indication of the filling quantity is based, at least in part, on the omission of the outlier measurement.

29. A method according to any one of claims 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or 28, characterized by further comprising generating an alert indicating a failure mode or other malfunction.

30. Method, according to claim 29, characterized by the warning indicating dripping, splashing, blockage and / or air pocket. Petition 870250088098, dated 09 / 29 / 2025, pp. 64 / 70

Images