Patent Description:
Illustrative embodiments generally relate to a fluid pump and, more particularly, the illustrative embodiments relate to a tightly load-coupled pneumatic driver for the same.

A variety of known pumps are used for fluid dispensing in laboratory and medical settings. In the laboratory, pumps and pipettes are commonly used for both aspiration and dispensing of samples, reagents, chemicals, solutions, and other liquids. In medical applications, pumps are useful for providing medicaments to patients, especially for the delivery of medical therapies requiring an extended period of time and through various routes of delivery, including intravenously, intra-arterially, subcutaneously, intradermally, intraperitoneally, in close proximity to nerves, and into an intraoperative site, epidural space or subarachnoid space. In addition to medication delivery, pumps are also commonly found in hospital pharmacies drug compounding applications, especially with highly complex parenteral nutrition compounded solutions. In laboratory applications, fluid pumps are general purpose tools often in the form of syringe pushers or tube based peristaltic pumps.

<CIT> discloses a fluid control system for delivery of a liquid including a pneumatic drive that incorporates a linear actuator to effect known volume changes in a gas reservoir. The gas reservoir is in fluid communication with a gas-side reservoir that is separated from a fluid-side reservoir by a flexible membrane. Movement of the linear actuator effects positive or negative volume differences on the gas in the gas-side reservoir, resulting in a decrease or increase in pressure of the gas that is transmitted to the fluid-side reservoir to draw fluid, primarily liquid, in from a source or deliver liquid out to a sink. In another aspect, a mechanism is provided for the detection and elimination of air bubbles in the fluid path.

<CIT> discloses a micro dosing system having a liquid reservoir with a storage space for the liquid to be dosed and a gas displacement system with a micropump, coupled to a dosing control for providing a reduced or raised pressure for the liquid reservoir upon operation of the micropump, for drawing liquid into the storage space or ejecting it from the storage space.

<CIT> discloses methods and systems for pumping fluids at desired average flow rates by applying a predetermined force to a pump chamber and pulsing an outlet valve of the pump chamber to deliver a fluid therefrom. In some embodiments, pump chambers are provided within removable pumping cartridges that are constructed and configured to be coupled to a reusable pump drive component. In other embodiments, the pumping cartridges include multiple pump chambers, which pump chambers are operated so that a pump flow rate of one pump chamber is a predetermined fraction of the pump flow rate of another pump chamber within the pumping cartridge.

In accordance with one aspect of the disclosure, there is provided a system for precision liquid delivery according to claim <NUM>.

In accordance with one aspect of the disclosure, there is provided a method of determining fluid flow characteristics in a liquid delivery system according to claim <NUM>.

In accordance with one aspect of the disclosure, there is provided a computer program product for use on a computer system for precision liquid delivery according to claim <NUM>.

Those skilled in the art should more fully appreciate advantages of various embodiments of the invention from the following "Description of Illustrative Embodiments," discussed with reference to the drawings summarized immediately below.

In illustrative embodiments, a tightly load-coupled pneumatic driver (a "TLCP driver"), such as one implemented as a microblower, produces a gas drive pressure that pumps fluid in accordance with a desired pressure and/or flow rate. The system enables rapid and precise changes in the gas drive pressure, and thus, in the pressure and/or flow rate of the pumped fluid. The TLCP driver generates differential pressure and flow of gas based on an electrical power input that is highly coupled to the work output (i.e., the mathematical product of pressure and flow). When the TLCP driver is used to maintain a constant pressure via a feedback control system, changes in flow rate compel a change in input power of comparable magnitude that is detectable by the system. Among other benefits, the TLCP driver provides highly sensitive fluid flow because it does not rely on mechanical linkages (e.g., gear box of a motor or leadscrews or tube-crushing fingers of peristaltic pump) for pumping the fluid.

Some conventional pumps (e.g., a syringe pump) require a backpressure of more than about <NUM> psi before an occlusion is detected. When the built-up pressure hits a predetermined threshold, the conventional pumps stop pumping. As another example, a peristaltic pump has an occlusion threshold of about <NUM> psi. Illustrative embodiments detect an occlusion from resultant pressure increases of less than about <NUM> psi.

In addition to providing high sensitivity, illustrative embodiments provide very precise pressure adjustments, as will be described further below. Conventional prior art pumps, such as a syringe pump, are not able to provide fine pressure adjustments (e.g., the syringe pump requires a significant application of force to overcome the stiction from the contact between the stopper and the inner wall of the syringe cylinder). Accordingly, conventional pumps may overcorrect when attempting to make fine pressure adjustments. In contrast, illustrative embodiments allow for fine pressure adjustments of about <NUM>% to about <NUM>% of drive pressure. Further advantages of illustrative embodiments include significant reduction in the size and weight of the pump relative to conventional syringe and peristaltic pumps. Details of illustrative embodiments are discussed below.

<FIG> schematically shows a system <NUM> for fluid delivery configured in accordance with illustrative embodiments of the invention. The system <NUM> has a TLCP driver <NUM>, implemented as a microblower <NUM>, that is configured to output gas <NUM> at a given drive pressure. The TLCP driver <NUM> is a pneumatic driver that is configured to generate differential pressure and flow of gas. Furthermore, the work output (i.e., the mathematical product of pressure and flow) is highly coupled to the electrical input power <NUM> provided to the TLCP driver <NUM>. Thus, when the TLCP driver <NUM> is used in a feedback control system to maintain a constant pressure, changes in flow rate cause a change in input power <NUM> of comparable magnitude. In a similar manner, when the TLCP driver <NUM> is set to maintain a constant flow rate, changes in pressure cause a change in input power <NUM> of comparable magnitude.

While illustrative embodiments generally apply to any type of TLCP driver <NUM>, some embodiments use a TLCP driver <NUM> known as a microblower <NUM>. The microblower <NUM> functions as a TLCP driver <NUM> by using the vibration of piezoelectric material (e.g., ceramics) and preferably operates at its resonant frequency (most commonly in the ultrasonic range). The microblower <NUM> is a small device, generally weighing less than <NUM> grams and is suitable for pressures below <NUM> bar and flow rates below <NUM> per minute. For discussion purposes, illustrative embodiments below refer to the microblower <NUM>. However, it should be understood that any discussion of the microblower <NUM> may also apply more generally to the TLCP driver <NUM>, and that reference to the microblower <NUM> is not intended to limit various embodiments. Accordingly, any discussion of the microblower <NUM> also refers to the TLCP driver <NUM>, unless the context of the discussion otherwise requires.

To produce the gas drive pressure, the microblower <NUM> receives a gas input <NUM> (e.g., from filtered ambient air). The microblower <NUM> also receives the power input <NUM> from a power controller <NUM>. As described previously, the work output of the TLCP driver <NUM> is highly coupled to the electrical input received. Thus, an increasing power input <NUM> produces a correspondingly larger work output by the microblower <NUM>. This relationship may be approximately linear or have another relationship.

In illustrative embodiments, the gas output <NUM> of the microblower <NUM> is directed into a gas reservoir <NUM> having a known volume. Other embodiments can support the orientation of the TLCP driver <NUM> in the opposite direction to direct flow out from the gas reservoir <NUM> to the atmosphere. Further embodiments include a plurality of the TLCP drivers <NUM> and the valves to support bi-directional flow. The microblower <NUM> outputs the gas <NUM> at a given pressure and flow rate, as dictated by the input power <NUM>. The gas reservoir <NUM> serves as the repository for the output gas <NUM> of the microblower <NUM>. In some embodiments, the gas reservoir <NUM> may be a container having a known volume. However, in some other embodiments, the gas reservoir <NUM> may be and/or include the known volume of the tubing and/or other gas passageways downstream of the output of the microblower <NUM>. In some embodiments, the gas reservoir <NUM> is coupled to a pressure sensor 116A that feeds a pressure signal <NUM> to the power controller <NUM>.

The gas reservoir <NUM> is pneumatically coupled to a fluid reservoir <NUM>. The fluid reservoir <NUM> may be, for example, within a bottle or vial, a syringe housing or a pipette tip. Accordingly, in illustrative embodiments, the volume of the fluid reservoir <NUM> may be the sum total of the volume of the interface <NUM>, as well as the gas and the fluid separated by the interface <NUM>. In illustrative embodiments, a pneumatic valve <NUM> selectively couples or isolates the gas reservoir <NUM> and the fluid reservoir <NUM>. When the gas reservoir <NUM> and the fluid reservoir <NUM> are pneumatically coupled, their pressures become substantially the same. The drive pressure from the output gas <NUM> directly acts upon the fluid-gas interface <NUM> without any substantial interface components that might otherwise attenuate pressure.

In various embodiments, the pneumatic valve <NUM> may be a manually controlled valve, a passively activated checkvalve, an electromagnetic solenoid valve, a memory-metal activated valve, or other valve that serves to selectively isolate or connect pneumatic spaces.

In various embodiments, the fluid reservoir <NUM> is a rigid container of a fixed size and may be full of liquid or may be partially filled with liquid and gas. Regardless of the ratio of the contents in the fluid reservoir <NUM>, when the valve <NUM> is open, a fluid-gas interface <NUM> is formed. The fluid-gas interface <NUM> may be formed by direct contact of the gas with the fluid. However, in some other embodiments, the interface <NUM> may be formed from a flexible membrane (e.g., formed from polyurethane or polyisoprene) that imposes no stretching forces. The membrane may be elastic but does not stretch. In that way, the system <NUM> allows the gas pressure to be substantially identical to the fluid.

In illustrative embodiments, the fluid path <NUM> is separated from the gas in the fluid reservoir <NUM> using a flexible membrane as the gas-fluid interface <NUM>. For example, the flexible membrane gas-fluid interface <NUM> may be used in applications where the system <NUM> is subject to changes in orientation, such as inverting the system <NUM>, so that the gas and the liquid would otherwise become interchanged. Other use examples for the flexible membrane gas-fluid interface <NUM> also include applications where the fluid path <NUM> cannot be exposed to gas in the fluid reservoir <NUM> because of concerns about sterility or contamination of the fluid.

As described previously, substantially all of the drive pressure from the gas reservoir <NUM> acts on the fluid in the fluid reservoir <NUM>. This is in contrast to prior art methods known to the inventors that attenuate pressure (e.g., because of mechanical connections in a motor or from stretching of an elastic interface material). Thus, when the gas reservoir <NUM> and the fluid reservoir <NUM> are pneumatically coupled, the pressure generated by the microblower <NUM> is substantially the same as the pressure in the fluid reservoir <NUM>, and the fluid in the fluid reservoir <NUM> therefore is driven at a known pressure. Accordingly, a pressure sensor 116B coupled to the fluid reservoir <NUM> may be used to monitor the pressure of the system <NUM> in addition to, or alternatively, to the pressure sensor 116A.

Furthermore, because the pump system <NUM> is pneumatically driven, it is more energy efficient and sensitive to small pressure adjustments than prior art pumps known to the inventors (e.g., using a stepper motor, or a syringe pump). For example, a stepper motor uses mechanical linkages that are not able to provide small adjustments in pressure. As another example, syringe pumps similarly are not able to produce small adjustments in pressure because of friction caused by the interface between the syringe walls and the stopper sliding therein. Furthermore, because both of these described prior art pumps have a large activation energy requirement, they cannot be considered to operate substantially instantaneously (e.g., at an ultrasonic frequency) as with the TLCP driver <NUM>. In contrast, the output of the TLCP driver <NUM> is fluidly coupled to the input of the fluid path <NUM>. Furthermore, the gas drive pressure does not have to overcome the forces of friction associated with traditional motors.

While the drive pressure created by the flow of gas may be substantially effectively frictionless (i.e., extremely low friction), resistance is encountered as the drive pressure moves the fluid in the fluid path <NUM> towards a fluid destination <NUM> (e.g., a patient receiving a medication). The resistance may be caused by, for example, viscous losses in the fluid path <NUM> line and/or an obstruction in the fluid path <NUM>. In illustrative embodiments, increased resistance in the line causes an increase in pressure that is detected by the pressure sensor(s) 116A and/or 116B. The increase in pressure is instantaneously detected and fed back to the fluid system controller <NUM>. The fluid system controller then controls the operation of the power controller <NUM> in a desired manner. Specifically, as noted above, in illustrative embodiments, the power controller <NUM> adjusts the electrical power input <NUM> as a function of the pressure signal(s) <NUM> so that the pressure may remain constant. In some other embodiments, the power controller <NUM> may adjust the electrical power input <NUM> so that flow rate in the fluid path <NUM> remains constant. In illustrative embodiments, the power controller <NUM> adjusts the input power on the same time scale as the pressure sensor, which is on the order of <NUM> samples per second. In some embodiments, the pressure sensor(s) may have a sampling rate of <NUM> to <NUM> samples per second. The power controller <NUM> may operate on the same or a similar timescale.

<FIG> schematically shows a chart of pressure over time in the system <NUM> of <FIG>. <FIG> schematically shows a chart of drive voltage input for the system <NUM> of <FIG> over a period of seconds. At point <NUM>, a constant work output is maintained by a constant drive pressure produced by the microblower <NUM>. At point some, the fluid path <NUM> may become occluded or encounter increased resistance. The increased resistance results in a build-up in the path <NUM>, and thus, an increased pressure (shown at point <NUM>). It should be noted that in the example illustrated in the chart, the change is pressure is approximately <NUM> PSI, a change that is considered to be effectively invisible to conventional prior art pumping systems.

In illustrative embodiments, the power controller <NUM> is configured to keep pressure constant, and thus, the system <NUM> may compensate by approximately simultaneously decreasing the drive voltage input (starting at point <NUM>). The power controller <NUM> adjusts the input power on the same time scale of the pressure sensor, which is on the order of <NUM> samples per second. The drive voltage decreases (e.g., at point <NUM>), until it is sufficiently low (at point <NUM>) for pressure to normalize at point <NUM>. While the changes between input voltage <NUM> and pressure may not be <NUM>:<NUM>, they generally are on the same order of magnitude and maintain proportionality.

In some embodiments, the power controller <NUM> may increase drive voltage, which increases drive pressure to maintain a constant work output of the microblower <NUM>. When the occlusion/resistance is removed, the drive pressure has a rapid decrease (e.g., at point <NUM>). The power controller <NUM> may be configured to increase the drive voltage (e.g., beginning at point <NUM>) to cause pressure to return to the set value (e.g., at point <NUM>), at which point the drive voltage remains steady (e.g., at point <NUM>).

Most conventional prior art pump systems known to the inventors operate at a constant speed with a geared mechanical system. If the flow resistance increases, the back pressure increases. However, the power input to the system does not change significantly. In contrast, illustrative embodiments of the system <NUM> are configured to maintain a substantially constant pressure. Because of the sensitivity of the TLCP driver <NUM>, changes to the power input required to maintain the pressure may be substantially instantaneously observed and adjusted.

In illustrative embodiments, the TLCP driver <NUM> detects occlusions or other resistance changes in the fluid path <NUM>. In a conventional pump, the pump continues at its constant speed, and pressure against the occluded path builds up until it reaches a detectable alarm condition. When the occlusion releases, a large pressure induced bolus in undesirably released. It should be understood based on the previous discussion, that illustrative embodiments do not build up non-negligible pressures. Instead, the system <NUM> is configured to maintain pressure constant to virtually eliminate the potential risk and dangers of a pressure induced bolus. To that end, the TLCP driver <NUM> has substantially greater pressure sensitivity, allowing for substantially faster occlusion detection.

While the discussion of <FIG> refers to maintaining pressure constant within the system <NUM> as load changes, it should be understood that this is merely an example of how the system <NUM> may operate. In some other embodiments, the system <NUM> may be configured to maintain flow rate constant as load (e.g., resistance) increases. In a similar manner to the pressure example described previously, when resistance in the fluid path <NUM> increases, pressure in the fluid path <NUM> increases. The drive voltage may thus be increased (instead of decreased as in the previous example) to further increase flow rate.

<FIG> schematically shows details of the fluid system controller <NUM> of <FIG> configured in accordance with illustrative embodiments of the invention. Each of these components is operatively connected by any conventional interconnect mechanism. <FIG> simply shows a bus communicating each the components. Those skilled in the art should understand that this generalized representation can be modified to include other conventional direct or indirect connections. Accordingly, discussion of a bus is not intended to limit various embodiments.

Indeed, it should be noted that <FIG> only schematically shows each of these components. Those skilled in the art should understand that each of these components can be implemented in a variety of conventional manners, such as by using hardware, software, or a combination of hardware and software, across one or more other functional components. For example, the power controller <NUM> (discussed in detail below) may be implemented using a plurality of microprocessors executing firmware. As another example, the power controller <NUM> may be implemented using one or more application specific integrated circuits (i.e., "ASICs") and related software, or a combination of ASICs, discrete electronic components (e.g., integrated circuits), and microprocessors. Accordingly, the representation of the power controller <NUM> and other components in a single box of <FIG> is for simplicity purposes only. In fact, in some embodiments, the power controller of <FIG> is distributed across a plurality of different components - not necessarily within the same housing or chassis.

It should be reiterated that the representation of <FIG> is a significantly simplified representation of an actual fluid system controller <NUM>. Those skilled in the art should understand that such a device has other physical and/or functional components, such as central processing units, other packet processing modules, and short-term memory. Accordingly, this discussion is not intended to suggest that <FIG> represents all of the elements of the fluid system controller <NUM>. In fact, much of what was said here with regard to <FIG> can also be applied to components of the system <NUM> of <FIG>.

As described previously, the power controller <NUM> controls the power input <NUM> provided to the microblower <NUM>. The fluid system controller <NUM> thus instructs the power controller <NUM> to provide the power input <NUM> to the microblower <NUM>. Accordingly, the power controller <NUM> controls the pressure of the output gas <NUM>. To that end, the fluid system controller <NUM> has a user interface <NUM> configured to receive an input from a user. For example, the user interface <NUM> may receive a setting of a constant pressure or a constant flow rate that the microblower <NUM> should output. In various embodiments, the user interface <NUM> may be provided as a touchscreen display, a mechanical interface, and/or as a smartphone connected application.

The fluid system controller <NUM> also has a pressure sensor interface <NUM> configured to receive pressure signals <NUM> from the noted pressure sensors 116A and 116B (or other pressure sensors). As described further below with reference to <FIG>, the pressure signals <NUM> provide a feedback loop to the fluid system controller <NUM> that allows the power controller <NUM> to adjust the power input <NUM> provided to the microblower <NUM> as a function of the amount of pressure in one or both the gas reservoir <NUM> and the fluid reservoir <NUM>. Those skilled in the art will recognize that the feedback control loop can be substantially modified by, for example, adjusting coefficients for errors that are proportional, integrative, and derivative (PID). Such PID coefficients can even be modified during operation of the system <NUM>, providing a wide dynamic range of behaviors.

The fluid system controller <NUM> also has a TLCP power input engine <NUM> configured to receive the settings from the user interface <NUM> (e.g., a constant pressure setting), receive pressure data from the pressure sensor interface <NUM>, and to instruct the power controller <NUM> to increase or decrease pressure and/or flow rate. The power input engine <NUM> performs calculations relating to what power input <NUM> should be provided to the microblower in accordance with the desired pressure setting in the gas reservoir and/or the fluid reservoir <NUM>. The power input engine <NUM> then provides that information to the power controller <NUM>, that provides the power input <NUM> to the microblower. The fluid system controller <NUM> has a volume calculation engine <NUM> configured to calculate the unknown fluid volume in the fluid reservoir <NUM>, based on the known volume in the gas reservoir, and the known pressures in the fluid reservoir <NUM> and the gas reservoir <NUM>. In some embodiments, the fluid volume calculation engine <NUM> may also be configured to calculate the flow rate of fluid out of the fluid reservoir <NUM>. Additionally, or alternatively, the volume calculation engine <NUM> may also be configured to measure fluid going into the fluid reservoir <NUM>. Fluid flow directional references of gas or fluids should be considered to represent flow in either direction. The fluid system controller <NUM> also has a valve controller <NUM> that controls the opening and closing of the valve <NUM>.

<FIG> shows a process of modulating the drive pressure inside a fluid system <NUM> in accordance with illustrative embodiments of the invention. It should be noted that this method is substantially simplified from a longer process that may normally be used. Accordingly, the method shown in <FIG> may have many other steps that those skilled in the art likely would use. In addition, some of the steps may be performed in a different order than that shown, or at the same time. Furthermore, some of these steps may be optional in some embodiments. Accordingly, the process <NUM> is merely exemplary of one process in accordance with illustrative embodiments of the invention. Those skilled in the art therefore can modify the process as appropriate.

The process begins at step <NUM>, which provides input power <NUM> to the TLCP driver <NUM>. As described previously, the power input <NUM> is provided to the TLCP driver <NUM>, and the TLCP driver <NUM> begins to pump gas in accordance therewith. Of course, as noted above, the pressure and flow of gas is a function of the input power <NUM>. Thus, the input power <NUM> may be initially set, for example, by a user through the user interface <NUM>. The microblower <NUM> then begins to pump the output gas <NUM> into the gas reservoir <NUM>.

At step <NUM>, the valve controller <NUM> optionally opens the pneumatic valve <NUM> between the fluid reservoir <NUM> and the gas reservoir <NUM>. The fluid path <NUM> and the gas reservoir <NUM> thus become pneumatically coupled, and their pressures become substantially the same (e.g., because of the interface <NUM>, which does not substantially attenuate the pressure). The gas drive pressure presses against the fluid at the interface <NUM>, either directly, or via the flexible, inelastic membrane.

At step <NUM>, the pressure in the fluid path <NUM> moves the fluid towards its destination <NUM>. For example, the destination <NUM> may be a patient in a hospital setting who is receiving an IV infusion of a particular drug. In many instances, it is desirable to pump a fluid into the patient at, or less than, a specific flow rate and/or specific pressure. In prior art systems known to the inventors, fluid line occlusion undesirably goes largely undetected, resulting in large bolus administrations of drug after the occlusion is removed. Illustrative embodiments mitigate this problem by providing a self-regulating system that controls pressure and ensures that the patient receives the prescribed drug dosage in a safe manner.

To that end, the process moves to step <NUM>, in which the pressure sensor 116B measures the pressure in the gas reservoir and/or the fluid path to determine whether pressure is constant at the set amount. As described previously, the system <NUM> is highly sensitive to even small changes in pressure (e.g., because of the lack of friction and/or mechanical gear components in the TLCP driver <NUM>). The pressure readings (e.g., from pressure sensor 116A and/or 116B) are fed back to the fluid system controller <NUM> via the pressure sensor interface <NUM>. The process then moves to step <NUM>, which determines whether the pressure is constant at the specified level.

The fluid system controller <NUM> determines whether there is an occlusion or resistance in the line by looking at the pressure. As described with reference to <FIG>, the fluid system controller <NUM> may determine whether there is occlusion/resistance in the line by noticing a change in the pressure in the system (e.g., gas reservoir, fluid reservoir, and/or fluid line). However, in some embodiments, pressure is kept constant by the system <NUM>. Accordingly, when the line is occluded, to maintain pressure constant, input power goes down. The change in input power <NUM> allows the system <NUM> to determine changes in flow/resistance while maintaining pressure constant. Thus, the system <NUM> may detect an occlusion while keeping pressure constant.

If the pressure measurement shows that the pressure is not at the specified amount, the process proceeds to step <NUM>, in which the power controller <NUM> modulates the input power <NUM> toward an appropriate level. As such, the fluid system controller <NUM> determines that the pressure is not with at the correct setting and its power controller <NUM> sends a signal to the power controller <NUM> to make a corresponding adjustment to the output power <NUM>. The process <NUM> then returns to step <NUM>, which again measures the pressure. If the pressure is still incorrect, the process repeats. This may occur many times, and steps <NUM>-<NUM> may occur substantially simultaneously (e.g., pressure readings may be taken continuously). If the pressure reading is at the appropriate setting in step <NUM>, then the system <NUM> continues to step <NUM> and pumps the fluid to the patient at the set pressure.

The operation of valve <NUM> may vary, but some embodiments open the valve <NUM> for a period on the order of <NUM> second to allow substantial equilibration between the pressure in the gas reservoir <NUM> and the pressure in the fluid reservoir <NUM>. In some applications, the valve controller <NUM> may open the valve <NUM> for a small fraction of a second, allowing partial equilibrium of pressures.

In some embodiments, the process may optionally move to step <NUM>, in which the volume calculation engine <NUM> calculates the unknown volume of fluid in the fluid reservoir <NUM>. Although shown here at the end of the process, step <NUM> may additionally, or alternatively, be performed earlier in the process and multiple times throughout the process (e.g., in the feedback loop of steps <NUM>-<NUM>). The volume calculation engine <NUM> may calculate the unknown volume by using, for example, the methodologies described below with reference to <FIG>.

<FIG> shows a process <NUM> of calculating the unknown volume of fluid in the fluid reservoir <NUM> and measuring flow rate from the fluid reservoir <NUM> in accordance with illustrative embodiments of the invention. It should be noted that this method is substantially simplified from a longer process that may normally be used. Accordingly, the method shown in <FIG> may have many other steps that those skilled in the art likely would use. In addition, some of the steps may be performed in a different order than that shown, or at the same time. Furthermore, some of these steps may be optional in some embodiments. Accordingly, the process <NUM> is merely exemplary of one process in accordance with illustrative embodiments of the invention. Those skilled in the art therefore can modify the process as appropriate.

In a manner similar to the process <NUM> of <FIG>, the process <NUM> begins at step <NUM> by providing the power input <NUM> to the TLCP driver <NUM>. As described previously, this target pressure may be set by the user using the user interface <NUM>. At step <NUM> the process measures the pressure in the gas reservoir <NUM> using the pressure sensor 116A. The pressure sensor 116A passes the pressure data to the pressure sensor interface <NUM>, and the fluid system controller <NUM> uses this data at step <NUM> to determine whether the pressure is at the target level.

If the pressure is not at the target level at step <NUM>, then the process proceeds to step <NUM>, where the input power <NUM> is modulated. This adjustment either increases or decreases the gas pressure output by the TLCP driver <NUM>. This process may be repeated until the pressure in the gas reservoir <NUM> is at the target level. After the pressure in the gas reservoir <NUM> reaches the target level, the process proceeds to step <NUM>, where the pressure in the fluid reservoir <NUM> is measured by the pressure sensor 116B. At this point in the process, the gas reservoir <NUM> and the fluid reservoir <NUM> are pneumatically isolated. The pressure data is fed to the fluid system controller <NUM> through the pressure sensor interface <NUM>.

The process then proceeds to step <NUM>, where the valve controller <NUM> opens the pneumatic valve <NUM> between the fluid reservoir <NUM> and the gas reservoir <NUM> to pneumatically couples the reservoirs. In some embodiments, the valve controller <NUM> may receive an indication of when to open and close the valve <NUM> from the volume calculation engine <NUM>. As is shown later with reference to <FIG>, pneumatically coupling the reservoirs <NUM> and <NUM> causes them to have substantially the same internal pressure. The process then measures the pressure (or the pressure changes) in each of the reservoirs <NUM> and <NUM>, and the volume calculation engine <NUM> uses this data to compute the unknown gas volume in the fluid reservoir <NUM> based on the change in pressure. The volume calculation engine <NUM> may then subtract the calculated gas volume from the total known volume of the fluid reservoir <NUM> (e.g., <NUM> syringe housing) to calculate the previously unknown volume of fluid within the fluid reservoir <NUM>.

The process then proceeds to step <NUM>, where the valve controller <NUM> closes the pneumatic valve <NUM> between the fluid reservoir <NUM> and the gas reservoir <NUM>. At this point, the reservoirs <NUM> and <NUM> are no longer pneumatically coupled, and thus, pressure changes within one reservoir does not affect the pressure in the other reservoir. As fluid flows out of the fluid reservoir <NUM> through the fluid path <NUM>, the pressure sensor 116B detects a pressure drop. At step <NUM>, the volume calculation engine <NUM> may use this change in pressure along with the previously calculated volume from step <NUM> to determine the flow rate of the fluid from the fluid reservoir <NUM> (i.e., by watching the pressure "leak").

Additionally, or alternatively, to step <NUM>, the process <NUM> may measure fluid flow by periodically calculating (e.g., every minute) the volume of liquid in the liquid reservoir <NUM> using the feedback loop <NUM>. In a manner similar to the process described previously, the valve <NUM> may be reopened to combine the pressures of the two reservoirs <NUM> and <NUM>, the volume calculation engine <NUM> may use the pressure change to calculate the volume of liquid in the liquid reservoir <NUM>, and the change in volume may be used to determine flow rate at discrete sampling intervals. This process may be repeated for a plurality of cycles (e.g., by reopening the valve <NUM>, taking a pressure measurement to calculate volume loss, and reclosing the valve <NUM>).

<FIG> provides an example of the volume calculations made by the volume calculation engine <NUM> in accordance with illustrative embodiments of the invention. The following examples are provided as an exemplary embodiment of the gas volume-based calculations that can be made by the system <NUM>. The system <NUM> has a known volume (e.g., the gas reservoir <NUM>) or a known volume change and an unknown volume. Illustrative embodiments also measure the pressures of the known volume(s) (or known volume changes) and the unknown volume(s), individually and after they are pneumatically combined according to the forgoing methods and modes of operation of the system <NUM>.

Three examples are provided in the table of <FIG> with a known volume (e.g., the gas reservoir <NUM>) of <NUM> microliters (mcL), and three respective (and different), unknown volumes-<NUM> mcL, 300mcL, and <NUM> mcL. The figure shows the pressure signals <NUM> taken from the first pressure sensor 116A for the gas reservoir <NUM> and the second pressure sensor 116B for the resulting combined known (gas reservoir <NUM>) and unknown (fluid reservoir <NUM>) volumes, sitting respectfully at knowable and measurable pressures, and occurring at roughly time "<NUM>" on the x-axis timeline of the figure.

In the first example, labeled "<NUM>" (mcL) in the table and "VOL <NUM>" in the figure shows an initial gauge pressure of <NUM> PSIg for the known volume (reference volume <NUM>). The unknown volume(s) have a gauge pressure of <NUM> PSIg (as measured by second pressure sensor 116B. The value of the actual pressures of the two respective volumes is unimportant, as long as they are measurable and different. When the two volumes, known <NUM> and unknown <NUM> and <NUM>, are combined at t = <NUM>, by opening the pneumatic valve <NUM>, the pressure of the combined volumes is measured by one or both pressure sensors 116A and 116B, and are the same at that point in time, t. In this example (with the <NUM> mcL unknown volume), the resulting final combined pressure falls to exactly the midpoint (<NUM> PSIg), between the two initial pressures of <NUM> PSIg (for the gas reservoir <NUM>) and <NUM> PSIg (for the unknown volumes).

The known volume experienced a pressure change down from <NUM> PSIg to <NUM> PSIg = <NUM> PSIg, and the unknown volume experienced a pressure change up from <NUM> PSIg to <NUM> PSIg = <NUM> PSIg. The resulting ratiometric difference between the two is calculated by dividing the net pressure difference each respective volume experienced, <NUM>/<NUM> = <NUM>. Accordingly, the unknown volume(s) can be calculated by multiplying the known volume (reference volume <NUM> = <NUM> mcL) by this ratio, <NUM>, resulting in a calculated unknown volume of <NUM> mcL (i.e. <NUM> mcL * <NUM> = <NUM> mcL). When two identical volumes with different known pressures are combined, the resulting combined pressure is expected to be the average of the two.

The second example, labeled "<NUM>" (mcL) in the table and "VOL <NUM>" in <FIG> also shows an initial gauge pressure of <NUM> PSIg for the known volume (reference volume <NUM>). Like in the previous example, the unknown volume has a measured (by the second pressure sensor 116B) gauge pressure of <NUM> PSIg. When combined according to the same mechanism as described in the previous example, the resulting final pressure of the combined volumes, as measure by one or both of the pressure sensors 116A and 116B, is measured to be <NUM> PSIg. Therefore, the known volume experienced a pressure change down from <NUM> PSIg to <NUM> PSIg = <NUM> PSIg, and the unknown volume experienced a pressure change up from <NUM> PSIg to <NUM> PSIg = <NUM> PSIg. The resulting ratiometric difference between the two is calculated by dividing the net pressure difference each respective volume experience, <NUM>/<NUM> = <NUM>. Accordingly, the unknown volume(s) can be calculated by multiplying the known volume (gas reservoir <NUM> = <NUM> mcL) by this ratio, <NUM>, resulting in a calculated unknown volume of <NUM> mcL (i.e., <NUM> mcL * <NUM> = <NUM> mcL). This is because a larger volume at a high pressure is combined with a smaller volume at a lower pressure, and the resultant combined pressure is closer to the higher pressure of the larger volume.

Referring still to <FIG>, the third example, labeled "<NUM>" (mcL) in the table and "VOL <NUM>" in the figure also shows an initial gauge pressure of <NUM> PSIg for the known volume (reference volume <NUM>). Like in the previous two examples, the unknown volume has a measured (by second sensor 116B) gauge pressure of <NUM> PSIg. And, when combined according to the same mechanism as described in two previous examples, the resulting final pressure of the combined volumes, as measure by one or both of the pressure sensors 116A and 116B, is measured to be <NUM> PSIg. Therefore, the known volume experienced a pressure change down from <NUM> PSIg to <NUM> PSIg = <NUM> PSIg, and the unknown volume experienced a pressure change up from <NUM> PSIg to <NUM> PSIg = <NUM> PSIg. The resulting ratiometric difference between the two is calculated by dividing the net pressure difference each respective volume experience, <NUM>/<NUM> = <NUM>. Accordingly, the unknown volume(s) can be calculated by multiplying the known volume (reference volume <NUM> = <NUM> mcL) by this ratio, <NUM>, resulting in a calculated unknown volume of <NUM> mcL (i.e., <NUM> mcL * <NUM> = <NUM> mcL). This makes intuitive sense, since when a larger volume at a low pressure is combined with a smaller volume at a higher pressure, one would expect the resultant combined pressure to be closer to the lower pressure of the larger volume.

As a verification for the use of this ratiometric calculation and methodology, reference is made to the Ideal Gas Law (PV = nRT), where the mathematical product of the absolute pressure (P) multiplied by the volume (V) should remain constant if the amount of gas is unchanged. Here, it is assumed in the instant example the absolute temperature (T) remains constant. With two volumes, one can take the sum of the PV values and compare it to the PV of the final combined volumes. In this formula, the pressures must be absolute pressures, yet for the ratiometric calculation gauge pressure measurements are sufficient since one is only comparing the ratios of pressure changes. Therefore, to verify the ratiometric calculation and methodology, referring to the first example, and the corresponding first column of the table in <FIG>, the measured atmospheric pressure is <NUM> PSIa; the known volume is <NUM> mcL (although the unit of measure is not relevant in this verification); the unknown volume is <NUM> mcL. Initially, the pressure in the known volume is measured as <NUM> PSIg. Therefore, the PV calculation for the combined volumes is ((<NUM> + <NUM>) * <NUM> + (<NUM> + <NUM>) * <NUM>) = <NUM>,<NUM>. Knowing that the combined volume is <NUM>,<NUM>, the expected pressure ("Final Pressure PSIa") in the combined volume is <NUM>,<NUM>/<NUM>,<NUM> = <NUM> PSIa. Subtracting the atmospheric pressure of <NUM> PSIa, one is left with a gauge pressure of <NUM> PSIg. Accordingly, a similar verification in kind is found for the second and third examples in the second and third columns of the table in <FIG>, for unknown volumes of <NUM> mcL and <NUM> mcL, respectively.

Due to the modularity of the system <NUM> and in particular of the pneumatic drive components (e.g., microblower(s) <NUM>, pneumatic valve <NUM>, first pressure sensor 116A, and second pressure sensor 116B), illustrative embodiments may be applied to a broad and complex set of use cases by adding additional pneumatic drive components. For example, to deliver liquid to multiple channels in a parenteral nutrition pharmacy compounder, a discrete set of pneumatic drive components may be added to each channel.

<FIG> show examples of pressure measurements in the gas reservoir <NUM> and the fluid reservoir <NUM> before and after they are pneumatically coupled in accordance with illustrative embodiments of the invention. In these figures, the gas reservoir <NUM> has a know volume and a measured pressure <NUM>. The fluid reservoir <NUM> has an unknown volume and a measure pressure <NUM>. In <FIG> and <FIG>, pressures <NUM> and <NUM> are at <NUM> PSIg merely because they had been opened to atmosphere prior to the process. In illustrative embodiments, the analysis of pressure changes do not require any restriction on the initial conditions, except that the pressures in the gas and fluid reservoirs <NUM> and <NUM> are different than each other prior to the opening of valve <NUM>. At point <NUM>, the valve <NUM> is activated to pneumatically join the two reservoirs <NUM> and <NUM>, and the two pressures combine to have a measured pressure <NUM>. The relationship between the measured pressures of both reservoirs <NUM> and <NUM> and the known volume of one reservoir <NUM> can be used to calculate the volume of the other reservoir <NUM>.

<FIG> shows a different example of the fluid reservoir <NUM> being joined with the gas reservoir <NUM>. Again, the volume of the gas reservoir <NUM> may be known. Joining the two reservoirs <NUM> and <NUM> results in a joined pressure <NUM>. As can be seen from <FIG>, the reservoir with the larger volume has a greater overall effect on joined pressure. For example, in <FIG> the larger volume is the fluid reservoir <NUM>, whereas in <FIG>, the two volumes are about the same.

In <FIG>, the gas reservoir <NUM> has a known volume and a measured pressure <NUM>. The fluid reservoir <NUM> has an unknown liquid volume and a measured pressure <NUM>. At a point of time <NUM>, the valve <NUM> is activated to pneumatically join the two reservoirs <NUM> and <NUM>. The resultant pressure <NUM> can be measured, and the unknown liquid volume can be calculated by the volume calculation engine <NUM>. After point <NUM>, the pneumatic valve <NUM> may be closed by the valve controller <NUM>. Thus, each reservoir remains pressurized at substantially the same pressure as when the reservoirs <NUM> and <NUM> were coupled. However, as fluid flows from the fluid reservoir <NUM>, the pressure in the fluid reservoir <NUM> decreases. This change in pressure is shown in line <NUM>, whereas the pressure in the gas reservoir <NUM> remains constant (shown by line <NUM>). The change in absolute pressure represents the proportional change in volume over time, or flow. Accordingly, in illustrative embodiments the volume calculation engine <NUM> may be used to calculate flow out of the system <NUM> over the time (i.e., fluid flow rate).

A person of skill in the art understands that illustrative embodiments provide a number of advantages. For example, illustrative embodiments include a much more rapid and precise response to pressure changes over prior art pumps known to the inventors. This is, for example, because some conventional pumps have a small motor and a gear box. Illustrative embodiments provide a high-frequency, self-resonating driver where a change in the load is seen directly by the system <NUM>. Because there is no substantial interference with the coupling between the drive pressure and the liquid in the fluid reservoir (including the interface <NUM> which is flexible and negligible) when the valve <NUM> is open, the gas pressure is substantially the same as the liquid pressure. This intimate connection allows the system <NUM> to be delicately balanced. A further advantage of the system <NUM> is that line occlusion and/or changes in resistance may be detected while keeping pressure constant (e.g., by detecting a change in input power <NUM>).

It should be understood that the term fluid encompasses liquids. The term "liquid" may be applied throughout the previous description to replace the term "fluid," for example, to refer to the fluid reservoir <NUM> and the gas-fluid interface <NUM>.

Various embodiments of the invention may be implemented at least in part in any conventional computer programming language. For example, some embodiments may be implemented in a procedural programming language (e.g., "C"), or in an object oriented programming language (e.g., "C++"). Other embodiments of the invention may be implemented as preprogrammed hardware elements (e.g., application specific integrated circuits, FPGAs, programmable analog circuitry, and digital signal processors), or other related components.

In an alternative embodiment, the disclosed apparatus and methods (e.g., see the various flow charts described above) may be implemented as a computer program product for use with a computer system. Such implementation may include a series of computer instructions fixed either on a tangible, non-transitory medium, such as a computer readable medium (e.g., a diskette, CD-ROM, ROM, or fixed disk). The series of computer instructions can embody all or part of the functionality previously described herein with respect to the system.

Those skilled in the art should appreciate that such computer instructions can be written in a number of programming languages for use with many computer architectures or operating systems. Furthermore, such instructions may be stored in any memory device, such as semiconductor, magnetic, optical or other memory devices, and may be transmitted using any communications technology, such as optical, infrared, microwave, or other transmission technologies.

Among other ways, such a computer program product may be distributed as a removable medium with accompanying printed or electronic documentation (e.g., shrink wrapped software), preloaded with a computer system (e.g., on system ROM or fixed disk), or distributed from a server or electronic bulletin board over the network (e.g., the Internet or World Wide Web). In fact, some embodiments may be implemented in a software-as-a-service model ("SAAS") or cloud computing model. Of course, some embodiments of the invention may be implemented as a combination of both software (e.g., a computer program product) and hardware. Still other embodiments of the invention are implemented as entirely hardware, or entirely software.

Disclosed embodiments, or portions thereof, may be combined in ways not listed above and/or not explicitly claimed. In addition, embodiments disclosed herein may be suitably practiced, absent any element that is not specifically disclosed herein. Accordingly, the invention should not be viewed as being limited to the disclosed embodiments.

Claim 1:
A system (<NUM>) for precision liquid delivery, the system comprising:
a gas reservoir (<NUM>) having a known volume;
a tightly load-coupled pneumatic, TLCP, driver (<NUM>) configured to receive input power causing the TLCP driver to move gas into the gas reservoir to produce a gas drive pressure;
a valve (<NUM>) configured to couple the gas reservoir with a fluid reservoir (<NUM>) having an unknown volume of a liquid, the valve further configured to selectively pneumatically isolate and pneumatically couple pressures in the gas reservoir and the fluid reservoir;
a gas-fluid interface (<NUM>) configured to couple pressure in the fluid reservoir to pressure in a fluid path (<NUM>), the gas-fluid interface configured so that the fluid drive pressure driving liquid in the fluid path is substantially the same as the fluid reservoir pressure; and
a pressure sensor (116A, 116B) configured to detect pressure in the gas reservoir and/or the fluid reservoir.