WO2015095590A1

WO2015095590A1 - System and method of control of a reciprocating electrokinetic pump

Info

Publication number: WO2015095590A1
Application number: PCT/US2014/071270
Authority: WO
Inventors: Kenneth Kei-ho NIP; Robert B. LEWIS; Doris Sun-Chia SHIEH
Original assignee: Eksigent Technologies Llc
Priority date: 2013-12-18
Filing date: 2014-12-18
Publication date: 2015-06-25

Abstract

A method of controlling the output of an electrokinetic pump includes: (1) measuring an initial pressure in an electrokinetic pump system; (2) applying a pump drive signal to the electrokinetic pump to begin a pump stroke; (3) measuring the pressure after a predetermined time of applying the pump drive signal; (4) identifying when the pressure has returned to the initial pressure plus a constant; and (5) stopping the pump drive signal to complete the stroke.

Description

SYSTEM AND METHOD OF CONTROL OF A RECIPROCATING

ELECTROKINETIC PUMP CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No.

61/917,896, filed December 18, 2013, entitled "SYSTEM AND METHOD OF CONTROL OF A RECIPROCATING ELECTROKINETIC PUMP". INCORPORATION BY REFERENCE

[0002] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. FIELD

[0003] This application relates to electrokinetic pump control schemes.

BACKGROUND

[0004] Precise pumping systems are important for chemical analysis, drug delivery, and analyte sampling. However, traditional pumping systems can be inefficient due to a loss of power and accuracy incurred by movement of a mechanical piston. Still further, conventional systems may not be configured to compensate for errors or backpressure during delivery.

[0005] Accordingly, there remains a need for a pumping system with improved flow control schemes.

SUMMARY OF THE DISCLOSURE

[0006] In some embodiments, described herein is a method of controlling the output of an electrokinetic pump including: (1) measuring an initial pressure in an electrokinetic pump system; (2) applying a pump drive signal to the electrokinetic pump to begin a pump stroke; (3) measuring the pressure after a predetermined time of applying the pump drive signal; (4) identifying when the pressure has returned to the initial pressure plus a constant; and (5) stopping the pump drive signal to complete the stroke.

[0007] The method can further comprise applying the pump drive signal for a set time after identifying that the pressure has returned to the initial pressure plus a constant. In some embodiments, the method further comprises detecting that the pressure has peaked. The predetermined time can be based upon pressure readings from a previous stroke of the electrokinetic pump. The method can further comprise calculating a total time duration for applying voltage based upon the identifying step, and then applying a pump drive signal to run the electrokinetic pump for another stroke.

[0008] In some embodiments, a method of controlling the output of an electrokinetic pump is provided. The method comprises applying a pump drive signal to the electrokinetic pump for an initial duration to begin a pump stroke; measuring the completion pressure upon completion of the pump drive signal; increasing the duration by a set value if the measured completion pressure is not below a cutoff pressure and applying a subsequent pump drive signal with the increased duration; and repeating the measuring and increasing steps until the completion pressure is measured to be below the cutoff pressure.

[0009] The set value can be about 1-7 ms. The method can further comprise decreasing the duration of the pump drive signal; measuring the pressure after completion of a stroke; and decreasing the duration of the subsequent drive signal if the measured pressure is less than the cutoff pressure.

[00010] In some embodiments, a system for delivery of fluid is provided. The system comprises an electrokinetic pump configured to deflect a diaphragm in an outlet chamber, the outlet chamber having an inlet and an outlet; a first check valve in communication with the inlet; a second check valve in communication with the outlet; a pressure sensor positioned to indicate a pressure within the system between the first check valve and the second check valve; and a computer controller in communication with the electrokinetic pump and the pressure sensor containing computer readable instructions to determine duration of application of a pump drive signal of the electrokinetic pump based at least in part on a comparison of a pressure signal from the pressure sensor taken after completion of a stroke with an other set pressure value.

[00011] The system can further comprise a flow restrictor between the pressure sensor and the second check valve. The system can comprise a reservoir containing a delivery fluid and having an outlet in communication with the outlet chamber inlet. In some embodiments, the system comprises a delivery conduit in communication with the outlet chamber outlet. Each stroke can deliver about 25-50 μΐ. In some embodiments, the other set pressure value is an initial pressure as measured before application of the pump drive signal. In some embodiments, the computer readable instructions include instructions to increase a duration of a subsequent pump drive signal if the pressure signal is greater than the set value. The system can be configured to deliver a total volume of about 200-1000 ml. BRIEF DESCRIPTION OF THE DRAWINGS

[00012] The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative

embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which.

[00013] In the drawings:

[00014] FIGS. 1A-1B show embodiments of existing pressure control systems.

[00015] FIG. 2 is a graph showing pressure vs. time during a stroke of an electrokinetic engine.

[00016] FIG. 3 is a schematic view of an embodiment of a pressure control system.

[00017] FIG. 4 is a section view of an embodiment of an electrokinetic pump block that incorporates the pressure control system components described in FIG. 3.

[00018] FIG. 5 is a graph of pressure versus time for a single full stroke of an electrokinetic engine.

[00019] FIG. 6 shows an exemplary voltage application configured to power a single full stroke of an electrokinetic engine.

[00020] FIGS. 7, 8, 9 and 10 are flow charts showing exemplary pressure control methods in an electrokinetic pump system.

[00021] FIGS. 1 1 A-B are graphs showing a voltage pulse and pressure vs. time for pulses of varying durations.

DETAILED DESCRIPTION

[00022] In one aspect of the present invention, pressure control techniques are used to monitor and control the output and performance of an electrokinetic pump (EK pump). The methods and systems described herein are designed to take advantage of the unique operating characteristics of the electrokinetic pump. Chief among these characteristics is the ability of the EK pump to deliver fluid as long as a voltage is applied, even against significant back pressures.

[00023] Existing control systems use a calculation of volume delivered to control voltage applied to deliver fluid. Such systems utilize a pressure differential to calculate volumetric flow rate. Two pressure sensors PS1, PS2 can be positioned on either side of a flow restrictor, as shown in FIG. 1 A. The flow through a flow restrictor can be described by the Hagen-Poiseuille equation: n_r4 , where: APis the pressure loss (PS 1 -PS2)

Lis the length of pipe

Ws the dynamic viscosity

Qis the volumetric flow rate

ris the radius

dis the diameter

uris the mathematical constant Pi

[00024] As shown in the equation, the difference between the sensed pressure at PS 1, PS2 is the ΔΡ, and this value can be used to calculate Q, the volumetric flow rate. The integral of the ΔΡ with respect to time will yield a total flow volume, as shown in FIG. IB.

[00025] A drawback of a method based on a calculated delivered volume is that it is temperature sensitive. A temperature change will change the viscosity and so the pressure integral also changes. As such, to produce an accurate calculation, such systems must monitor temperature as well. Furthermore, such systems require high processing capability to constantly perform the calculations necessary to determine volume delivered.

[00026] An alternative control method is to use a pressure change (ΔΡ), instead of volume delivered to control voltage application. A ΔΡ of zero indicates no flow or stopped flow. The system can monitor one pressure trace, for example, the pressure before a flow restrictor. If the pressure of the trace returns to the pressure level before the voltage pulse, flow has stopped.

FIG. 2 shows an example of a pressure trace, increasing during a stroke and dropping again (e.g., to 0) when flow stops. By basing the control system on pressure change rather than calculated volume delivered, the system is independent of any temperature changes.

[00027] In general, the control system described herein includes running an EK system through a full stroke or pulse (i.e., until the movable member has been extended all the way to the edge of the delivery chamber). A pressure sensor can detect an increase in pressure as fluid is transferred and then a decrease in pressure as the stroke is completed. Upon sensing that the pressure has returned to the initial pressure reading, the controller can determine that the stroke has been completed and thereby reverse the stroke.

[00028] As noted above, the control system described herein can be used to full stroke volume pumps. As such, the control system can advantageously be suited for use in reciprocating EK pump systems for delivering fluids in a large volume or at a high rate. For example, the control system can be used in pumps for delivering pain medication or wound rinsing. Such systems can deliver, for example, about 25-50 μΐ per stroke and can deliver total volumes of about 200-1000 ml, for example about 200 ml, 500ml, or 1000 ml. [00029] FIG. 3 is a schematic view of an embodiment of an EK pump system 1000 used to deliver fluid using an exemplary pressure control system. The electrokinetic pump system 1000 includes a delivery chamber 122 connected to an electrokinetic engine 103. The delivery chamber 122 is positioned between an inlet check valve 142 and an outlet check valve 144. A pressure sensor 154 is placed after the outlet check valve 144, but before a flow restrictor 160, which leads to an outlet of the pump system 1000. The system 1000 also includes a reservoir

141 containing a fluid to be delivered by action of the electrokinetic engine 103.

[00030] FIG. 3 also illustrates a power source 180 and a controller 175 used to operate the EK pump. The controller 175 functions based on the pump control scheme selected, input from the pressure sensor 1 4, and target delivery volume. The controller 175 includes memory with computer readable instructions to implement the pump control scheme, including, for example receiving and interpreting signals from system components such as the pressure sensor, performing calculations according to the control scheme, and providing control signals to the EK pump. One commercially available microcontroller suited to the configurations described herein is the C8501 F310, available from Silicon Laboratories Inc., Austin, Texas.

[00031] The system of FIG. 3 is set up so as to accurately detect, through the pressure sensor 154 and the restrictor 160, the completion of the stroke of the engine 103. The pressure sensor 154 may be any pressure sensor suited to the range of pressures and flows used in the system. Further, the flow restrictor 160 may be any suitable flow restrictor according to the type of measurement scheme being used. For example, the flow restrictor may be configured as a venturi, an orifice, or a flow nozzle.

[00032] FIG. 4 is a section view of an embodiment of an electrokinetic pump block that incorporates the pressure control system components described in FIG. 3. The electrokinetic ("EK") pump assembly 100 includes an EK pump 101 connected to an EK engine 103. The EK engine 103 includes a first chamber 102 and a second chamber 104 separated by a porous dielectric material 106, which provides a fluidic path between the first chamber 102 and the second chamber 104. Capacitive electrodes 108a and 108b are disposed within the first and second chambers 102, 104, respectively, and are situated adjacent to or near each side of the porous dielectric material 106. The EK engine 103 includes a movable member 1 10 in the first chamber 102, opposite the electrode 108a. The moveable member 1 10 can be, for example, a flexible impermeable diaphragm. A pump fluid (or "engine fluid"), such as an electrolyte, can fill the EK engine, such as be present in the first and/or second chambers 102 and 104, including the space between the porous dielectric material 106 and the capacitive electrodes 108a and 108b. The capacitive electrodes 108a and 108b are in communication with an external voltage source, such as through lead wires or other conductive media. [00033] The EK pump 101 includes a delivery chamber 122 and a movable member 1 13 having a first edge 1 12 contacting the delivery chamber 122 and a second edge 1 1 1 contacting the second chamber 104. In some embodiments, the first and second edges 1 12, 11 1 are flexible diaphragms having a mechanical piston therebetween. In other embodiments, the first and second edges 1 12, 1 1 1 are flexible diaphragms having a gel material therebetween. Gel couplings are described further in U.S. Patent Application No. 13/465,939, filed May 7, 2012, and entitled "GEL COUPLING FOR ELECTROKINETIC DELIVERY SYSTEMS," the contents of which are incorporated herein by reference. In other embodiments, the first and second edges 1 12, 1 1 1 are edges of a single flexible member or diaphragm.

[00034] The delivery chamber 122 can include a delivery fluid, such as a drug or medication, e.g., insulin or pain management medications, or a cleansing fluid, such as a wound cleansing fluid, supplied to the delivery chamber 122 from a fluid reservoir 141. An inlet check valve 142 between the fluid reservoir 142 and delivery chamber 122 can control the supply of delivery fluid to the delivery chamber 122, while an outlet check valve 144 can control the delivery of delivery fluid from the delivery chamber 122, such as to a patient. A pressure sensor 154 can monitor the flow of fluid from the system. Further, a flow restrictor 160 can be placed after the pressure sensor 154 and before the outlet to increase the pressure signal, thereby allowing for better detection of changes in the pressure signal.

[00035] In use, the electrokinetic assembly 100 works by producing electrokinetic or electroostmostic flow. A voltage, such as a positive voltage, is applied to the electrodes 108a, 108b, which causes the engine fluid to move from the second chamber 104 to the first chamber 102. The engine fluid may flow through or around the electrodes 108a and 108b when moving between the chambers 104, 102. The flow of fluid causes the movable member 1 10 to be pushed out of the chamber 102 and the movable member 1 13 to be pulled into chamber 104. As a result of the movement of the movable member 1 13, delivery fluid is pulled from the reservoir 141 into the delivery chamber 122. The movement of delivery fluid from the reservoir into the delivery chamber 122 is called the "intake stroke" of the pump cycle. When the opposite voltage is applied, such as a negative voltage, fluid moves from the first chamber 102 to the second chamber 104. The movement of engine fluid between chambers causes the movable member 1 10 to be pulled into the first chamber 102 and the movable member 113 to expand to compensate for the additional volume of engine fluid in the second chamber 104. As a result, delivery fluid in the chamber 122 is pushed out of the chamber 122 and delivered, such as to a patient, through the outlet check valve 144. The delivery of fluid is called the "outtake stroke" of the pump cycle. Although the exemplary assemblies and systems described below are configured such that a positive voltage corresponds to the intake stroke and a negative voltage corresponds to an outtake stroke, it is to be understood that the opposite configuration is also possible - i.e., that a negative voltage corresponds to an intake stroke and a positive voltage corresponds to an outtake stroke.

[00036] Figure 5 shows an exemplary graph of pressure versus time for a full stroke of an electrokinetic system as described above with respect to Figures 3 and 4. As voltage is applied to the electrokinetic system, the pump delivers fluid from the delivery chamber. As the fluid is delivered, the generated flow will cause the pressure sensor (just before the flow restrictor) to detect an increase in pressure. The pressure trace will hit a peak as the pulse continues and will then drop off again. After a time, the amount of fluid flowing through the system goes essentially to zero (as the delivery chamber empties), and the pressure reading returns back to the initial pressure. This pressure curve can be used to control when to turn on and off voltage as well as to determine how much fluid has been delivered.

[00037] Referring to Figure 6, a voltage can be applied to the electrokinetic system until the pressure has gone through the peak and has returned back to the initial pressure plus a constant. (i.e., the voltage can be stopped just before the pressure returns back to the initial pressure). At this point, the stroke has completed, and thus a known volume (equivalent to the stroke volume) has been delivered for the system. In some embodiments, a set time (Tc) can be added on to the voltage to provide a safety factor to compensate for the constant (i.e. stopping just before the pressure reaches the final), to compensate for a delay between the sensor and the pump, and/or to compensate for compliance in the housing.

[00038] Figures 7 and 8 describe an exemplary method of controlling the operation of an electrokinetic pump system using a pressure control system as described herein. Referring to Figure 7, at step 601 , the initial pressure (Pj) is measured with the pressure sensor (such as pressure sensor 154, described above). A voltage is applied for an initial duration (Vt), such as a duration expected to reach at least past the peak in the curve shown in Figure 6. At step 603, the pressure sensor can then be checked. At step 605, if the pressure is less than the initial pressure plus a constant, then the voltage can be stopped OR a set additional time can be added as a safety feature as shown at step 607. The process can then be continued for additional pulses as desired. By following the steps shown in Figure 7, a known amount of fluid can be delivered (i.e., the amount of fluid will be equivalent to the total sweep volume of the diaphragm and/or approximately twice the volume of the delivery chamber).

[00039] Figure 8 shows a similar exemplary method of Figure 7 for controlling the operation of an electrokinetic pump. However, the method of Figure 8 includes error detection - i.e., it can be used to identify that the fluid is flowing as expected and thus goes through a pressure peak. At step 501, the initial pressure (Pj) is measured with the pressure sensor (such as pressure sensor 154, described above). The voltage can continue to be applied. At step 503, a voltage can be applied to the electrokinetic pump system to begin the stroke. At step 505, it can be determined whether there has been a pressure increase. If so, this indicates that fluid flow has started. At step 507, it can be determined that there has been a subsequent pressure decrease, indicating that the pressure peak has been reached. At step 509, it can be determined whether the pressure has returned to the initial pressure (or the initial pressure plus a constant, as described above). If the pressure has been returned the initial pressure or the initial pressure plus a constant, then the voltage can be stopped (at step 503) OR a set additional time can be added as a safety feature (as described above) at step 51 1. Once the voltage has been stopped, a known amount of fluid will have been delivered (i.e., the amount of fluid will be equivalent to the total sweep volume of the diaphragm and/or approximately twice the volume of the delivery chamber).

[00040] The steps shown in Figures 7 and 8 can be repeated to deliver additional fluid, i.e., the pump can reciprocate and deliver more fluid. In some embodiments, fluid can be delivered only on the outtake strokes. In other embodiments, the pump can be configured as a dual action reciprocating pump where fluid is delivered on both the intake and outtake strokes. In such dual action system, the pressure control system described herein can be used during both the intake and the outtake strokes.

[00041] The steps shown in Figures 7 and 8 do not need to all be actively performed. For example, referring to Figure 8, the system need not detect whether there has been a pressure increase and subsequent pressure decrease. Rather, the system can be set to run for a set period of time estimated to be the approximate time for a full stroke to complete. Once that time has passed, the pressure sensor can be tested. If the pressure is above Pt, voltage can continue to be applied. However, if the pressure has returned to Pi, then the voltage can be stopped.

[00042] Further, referring to Figure 9, in some embodiments, a voltage can be applied for an estimated duration (Vt) can be applied at step 701, the pressure can be checked at step 703, and at step 705, it can be determined whether the pressure is less than the initial pressure plus a constant. If not, the pressure can continue to be checked. Once the pressure has reached the initial pressure plus a constant, the total time that voltage was applied can be determined at step 707. At step 709, it can then be determined whether the estimated time duration was appropriate. That is, if the total time is greater than the estimated duration (Vt), then Vt can be increased at step 713 for the next stroke. If the total time is less than the estimated duration (Vt), then Vt can be decreased at step 71 1 for the next stroke. The process can be repeated, as shown in Figure 9 OR the corrected time duration can be used for future pulsing with no or only intermediate pressure checking. [00043] Another example for determining duration of voltage application is shown in FIG. 10.

The pump can initially be run with an estimated voltage duration (Vt), as shown at step 801. In some embodiments, the pulse can be about 1500-2000 mS. For example, the initial duration can be set to about 1750 mS. The pressure can be measured after the pulse has ended, as shown at step 803. If the measured pressure is not below a cutoff pressure, then the duration of voltage application can be increased by a certain amount, as shown at step 807. In some embodiments, the time is increased by about 1 -7 mS. For example, the duration can be increased by about 4 mS to 1754 mS. The pressure at the end of the pulse is measured again. If the pressure is still not below a cutoff pressure, the duration can be increased again until the measured pressure is below the cutoff pressure. At that point, the system can stop increasing the pulse.

[00044] FIGS. 1 1A and 1 IB are graphs showing the pressure trace and pulse for an initial estimated duration (FIG. 1 1A) and subsequent longer duration (FIG. 1 IB). As shown in FIG. 1 1 A, at the end of the pulse, the pressure has not dropped below the cutoff pressure to indicate stopped flow. Thus, the pulse duration is increased in FIG. 1 IB. The pressure at the end of the pulse is lower, but still has not returned to below the cutoff pressure. As the pulse duration is increase, the pressure measured at the end of the pulse will eventually be within the cutoff threshold, and the system can stop increasing the pulse duration.

[00045] To ensure that energy is not being wasted by applying too long a pulse, the duration can be occasionally decreased to determine whether the pressure returns to zero before the end of the pulse. If it does, the pulse can be decreased.

[00046] As noted above, in some embodiments, the cutoff pressure point is not set to zero. Instead a value above zero can be used. This adjustment can compensate for the delay in flow rate and any error in measurement. Additionally, electronic measurements and any residual pressure inside the pump can affect the 'zero' pressure within the pump. In some embodiments, the pressure cutoff is set to about 0.1 - 0.4 PSI (e.g., 0.4 PSI) above the 'zero' pressure. In some embodiments, the pressure cutoff or 'zero' value is determined by measuring the pressure prior to the start of the pulse and using that initial pressure as a reference or 'zero' point.

[00047] In some embodiments, the system can be continuously performing the algorithms described herein as the flow rate may change over time. For example, a temperature change can affect flow rate. As long as the system checks that the pressure returns to an initial or cutoff pressure after a pulse, these flow variations will not affect system functionality.

[00048] In some embodiments, because the slope of the pressure curve returns substantially to zero after fluid has been delivered (see Figure 3), the voltage can also only be stopped when the slope has hit zero (or close to zero). This can provide an extra check to ensure that all of the fluid has been delivered. That is, when the slope is at zero, there is no flow. Using this as an extra check thereby ensures that there is no backpressure slowing the flow.

[00049] The pressure control system described herein can further be used to detect a blockage in the electrokinetic system. For example, when there is a blockage, the pressure peak will be much higher than usual, as there is fluid build-up in the system. Accordingly, the pressure peak can be monitored. If the pressure goes above a certain value, such as 1.5 to 2 times the previous peak, then the system can detect a blockage error and respond accordingly (e.g., sound an alarm, turn on a warning light, turn off automatically, etc.).

[00050] Advantageously, as noted above, the pressure control system described herein can be used to accurately deliver fluids for high volume delivery. For example, the pressure control system can be used for flow applications of over about 0.5ml/hr, such as between about 0.5ml/hr and 120ml/hr. The pressure control system described herein is also advantageously temperature insensitive (as opposed to differential pressure systems), thereby providing for increased accuracy.

[00051] The control system described herein uses a volumetric system for determining duration of voltage application during each stroke. As described above, the known systems can utilize more intensive systems requiring a calculation of volume delivered during each stroke to determine voltage application. Such systems can use a pressure differential to calculate volume delivered. A drawback of such systems can be the processing requirements to carry out the calculation. In contrast, the control systems described herein do not have such high processing requirements.

[00052] Moreover, because the pressure control system described herein is used with an electrokinetic pump, it can accurately control the amount of fluid delivered, even under increased backpressure. That is, traditional mechanical systems, when encountering increased

backpressure in the system, may never reach the initial pressure and may plateau at a higher pressure than the starting pressure because the mechanical system may not be set to overcome the increased force. In contrast, the electrokinetic system is set up such that, in general, as long as voltage is flowing, fluid will move. Because the pressure control system described herein applies voltage until the initial pressure is reached, the system ensures that all of the fluid is delivered in the stroke.

[00053] Those of ordinary skill will appreciate that the various processing steps, comparisons, methods, techniques, signal processing and component specific operations performed by a controller are provided to the controller or contained within electronic memory accessible to the controller in the form of appropriate computer readable code. Similarly, the various diagnostic routines, abnormal condition detectors, functional indicators and pump control schemes and other operational considerations described in this patent application are also stored in an appropriate computer readable code within the memory of or accessible to the controller.

[00054] As for additional details pertinent to the present invention, materials and

manufacturing techniques may be employed as within the level of those with skill in the relevant art. The same may hold true with respect to method-based aspects of the invention in terms of additional acts commonly or logically employed. Also, it is contemplated that any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein. Likewise, reference to a singular item, includes the possibility that there are plural of the same items present. More specifically, as used herein and in the appended claims, the singular forms "a," "and," "said," and "the" include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only" and the like in connection with the recitation of claim elements, or use of a "negative" limitation. Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The breadth of the present invention is not to be limited by the subject specification, but rather only by the plain meaning of the claim terms employed.

[00055] It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMS What is claimed is:

1. A method of controlling the output of an electrokinetic pump, comprising:

measuring an initial pressure in an electrokinetic pump system;

applying a pump drive signal to the electrokinetic pump to begin a pump stroke;

measuring the initial pressure after a predetermined time of applying the pump drive signal;

identifying when the pressure has returned to the initial pressure plus a constant; and stopping the pump drive signal to complete the pump stroke.

2. The method of claim 1, further comprising applying the pump drive signal for a set time after identifying that the pressure has returned to the initial pressure plus a constant.

The method of claim 1, further comprising detecting that the pressure has peaked.

The method of claim 1, wherein the predetermined time is based upon pressure reading from a previous stroke of the electrokinetic pump.

The method of claim 1, further comprising calculating a total time duration for applying voltage based upon the identifying step, and then applying a pump drive signal to run the electrokinetic pump for another stroke.

A method of controlling the output of an electrokinetic pump, comprising:

applying a pump drive signal to the electrokinetic pump for an initial duration to begin a pump stroke;

measuring the completion pressure upon completion of the pump drive signal;

increasing the duration by a set value if the measured completion pressure is not below a cutoff pressure and applying a subsequent pump drive signal with the increased duration; and

repeating the measuring and increasing steps until the completion pressure is measured to be below the cutoff pressure.

7. The method of claim 6, wherein the set value is about 1-7 mS.

8. The method of claim 6, further comprising

decreasing the duration of the pump drive signal;

measuring the pressure after completion of a stroke; and

decreasing the duration of the subsequent drive signal if the measured pressure is less than the cutoff pressure.

9. A system for delivery of fluid, comprising:

an electrokinetic pump configured to deflect a diaphragm in an outlet chamber, the outlet chamber having an inlet and an outlet;

a first check valve in communication with the inlet;

a second check valve in communication with the outlet;

a pressure sensor positioned to indicate a pressure within the system between the first check valve and the second check valve; and

a computer controller in communication with the electrokinetic pump and the pressure sensor containing computer readable instructions to determine duration of application of a pump drive signal of the electrokinetic pump based at least in part on a comparison of a pressure signal from the pressure sensor taken after completion of a stroke with an other set pressure value.

10. The system of claim 9, further comprising a flow restrictor between the pressure sensor and the second check valve.

1 1. The system of claim 9, further comprising: a reservoir containing a delivery fluid and having an outlet in communication with the outlet chamber inlet.

12. The system of claim 9, further comprising: a delivery conduit in communication with the outlet chamber outlet.

13. The system of claim 9, wherein each stroke delivers about 25-50 μΐ.

14. The system of claim 9, wherein the other set pressure value is an initial pressure as

measured before application of the pump drive signal.

1 . The system of claim 9, wherein the computer readable instructions include instructions to increase a duration of a subsequent pump drive signal if the pressure signal is greater than the set value.

16. The system of claim 9, wherein the system is configured to deliver a total volume of about 200-1000 ml.

17. The system of claim 9, wherein the system is used for flow applications of between about 0.5ml/hr and 120ml/hr.