Not Applicable
This application is a continuation-in-part of application Ser. No. 10/307,907, filed 02 Dec. 2002.
1. Field of the Invention
The invention is a self-regulated Electrothermal Flow (ETF) micropump for infusion of fluids into the body of a patient. The self-regulated ETF micropump can also be used other application requiring miniaturized, self-regulating pumps. The micropump monitors flow rates using Laser-Induced Fluorescence Photobleaching Anemometry (LIFPA), impedance anemometry, or other flow measuring device. Data from fluid monitoring is transferred to a control system that controls the flow rate generated by the pump. The operation of the micropump can be set to maintain a constant flow rate or to deliver a pre-programmed flow rate pattern, for example.
2. Description of Related Art
Infusion pumps have a wide range of applications such as the controlled delivery of antibiotics, antiviral agents, anesthesia, chemotherapy, total parenteral nutrition (TPN), and patient-controlled analgesia. Control of infusion rates is particularly important for delivering small volumes of high concentration drugs and high flow rate infusions of large volumes.
Miniaturized, self-regulated flow pumps for drug infusion allow, for example, the controlled delivery of concentrated drug over extended periods to ambulatory patients (low flow rate) and the controlled infusion of high volumes of fluids (high flow rate).
Miniaturized electrokinetic pumps to move fluids through microfluidic devices are known and employ a variety of elecrtokinetic phenomena including electroosmotic flow, and electrohydrodynamic flow. Electokinetic pumps and their advantages are described in Fuhr G et al. (1994) J. Micromech. Microeng. 4:217-226; Laser D J and Santiago J G (2004) J. Micromech. Microeng. 14:R35-R64; Wang, GR et al. (2004) J. Micromech. Microeng. 14:1037-1046; Yao S et al. (2001) Proc. 2001 ASME Int. Mechanical Engineering Congress and Exposition; Yao S H et al. (2003) J. Colloid Interface Sci. 268:143-53; and Corbin et al. US 2005/0084385 A1, which are incorporated by reference in their entirety.
The use of time varying waveform ETF, such as traveling-wave ETF in applications such as micropumps is disclosed in U.S. Pat. No. 10/307,907, filed 02 Dec. 2002, which is incorporated by reference in its entirety. Unlike other electrokinetic phenomena, the ETF generated by the present invention provides mean pumping velocities that increase with the 4th power of the applied voltage. This enables ETF pumps to generate higher flow rates and hence, head pressures than existing electrokinetic pumps. A theoretical description of ETF is described in Ivan R et al. (2004) J. Phys. D: Appl. Phys. 37:2323-2330, which is incorporated by reference in its entirety.
In addition to providing high flow rates and/or head pressures through the use of ETF, the present invention provides for a self-regulating micropump that monitors the pump's flow rate. This is accomplished by coupling a flow rate monitor or sensor with a pump power supply controller. The flow rate produced by the pump is measured using, for example, Laser-Induced Fluorescence Photobleaching Anemometry (LIFPA) or Flow Induced Differential Electrochemical Impedance Spectroscopy (FI-DEIS). These methods are described in Wang GR and Fiedler HE (2000) Experiments in Fluids 265-274; Wang G R (2005) Lab on a Chip. 5:450-456; Fiedler, H. E.; Wang, G. R. (1998) Deutsches Patent. No. 19838344.4; and Collins J and Lee A P (2004) Lab. Chip. 4:7-10, which are incorporated by reference in their entirety.
The present invention involves drug infusion apparatus and methods comprising an ETF micropump, an anemometer, and a micropump controller in communication with both the micropump and anemometer. Self-regulation of flow rates is exemplified using LIFPA and FI-DEIS for flow rate sensing. The applications of the present invention include drug delivery by infusion and auto-controlled pumping in microfluidic systems and biochips.
In one aspect, the present invention is a method for automatically controlling the flow of an ETF pump using an inline flow sensor and power supply controller. In another aspect, the invention is an apparatus for delivering drugs by infusion comprising a self-regulated EFT flow pump. In yet another aspect, the invention is a method for delivering drugs by infusion using a self-regulated EFT flow pump.
The ETF micropump minimally comprises a pumping chamber containing a fluid to be pumped, an inlet into and an outlet from the pumping chamber, at least one set of four elongated electrodes arranged in parallel in one wall of the pumping chamber in contact with the fluid, and a power supply electrically coupled to each of the electrodes in such a way as to produce tw-ETF of fluid within the volume of the pumping chamber in a direction perpendicular to the elongated electrodes. The pumping chamber may have multiple sets of 3 or, preferably, 4 or more parallel electrodes located in one or opposing walls of the chamber. These electrodes are activated in a phase-shifted manner to produce ETF of the fluid to be pumped with a phase shift of 2π/n for n electrodes per set.
The efficiency increases with the number of phase-shifted electrodes in a set. There is practical limit to the number of phase-shifted electrodes in a set, however, because the number of electrical leads required is equal to the number of electrodes in a set. Phase-shifted electrode sets may optimally be located on opposing walls directly across from one another (eclipsed), or offset in the direction normal to the electrodes by an offset distance (staggered). Additionally, electrodes within a set may be located on opposing walls in a staggered configuration. Each of the preceding configurations is described in more detail in the examples. The numbers and locations of electrodes in a set, sets of electrodes, inlets and outlets, and channel dimensions are variable and may be changed to suit particular applications needs.
The flow channel is optimally made of a material that is electrically insulating such as glass, silicon, PDMS, or other plastic. Electrodes are optimally made of gold or other electrically conducting material that does not react chemically with the fluid being pumped.
Computational simulations validated using experimental results conducted by the inventors indicate that the head pressure generated by the ETF pump increases linearly with the length of the pumping chamber and that reducing the gap between electrodes and increasing the number of electrodes improves the performance of the pump. Further improvements in flow rate can be achieved by stacking pumping chambers within a single micropump.
Guidance for Micropump Design:
Optimal performance can be achieved by a simulation-based design approach based on the following description. When an electric current is passed through a conducting fluid, it induces Joule heating and creates a temperature gradient. The electrical properties such as permittivity and conductivity vary with temperature and thereby with the spatial location. Under the action of externally imposed electric field, this non-uniformity in the dielectric property of the liquid induces dielectric forces leading to bulk fluid flow known as electrothermal induced flow. The flow rate and the associated maximum pressure head depend on electrode dimension, form, electrode distance and configuration, channel dimensions, applied voltages, fluid properties and phase shifts in the electric field.
The steady state free charge density is described by
where D is the electric displacement, σ and ε are conductivity and dielectric constant. The intrinsic electric relaxation time τ represents the time needed by a free charge to relax from the fluid to its external boundary and thus determines different responses to AC electric signal. The electrostatic force applied to dielectric material is given by
Here ρm is the fluid density and {right arrow over (E)} is electric field. For most experimental conditions of practical interest in which harmonically oscillating AC field is applied to produce non-uniform electric field, the averaged force density is approximately given by
ω is the angular frequency of the AC signal, i=√{square root over (−1)}, and T is the temperature. The superscript star represents for complex conjugate. Joule heating due to electric current is the primary heat resource and is related to the current by
j=σE2 (5)
When this intrinsic time scale is comparable to period of AC signal, the force density exhibits traveling wave features that respond to phase shift in the applied field. At small amplitudes, the flow and thermal fields can be linearized and the scaling analysis indicates that the velocity and temperature vary as V4 and V2, respectively, where V is externally applied voltage. Detailed scaling analysis of linearized governing equations indicate that the average velocity induced can be expressed as:
The scaling of flow rate is σV4L0/(μk). In general, the flow rate increases with increasing applied potential, increasing solution conductivity, and/or increasing channel size.
A first exemplary embodiment of an ETF micropump having opposed sets of parallel electrodes on the top and bottom surfaces of a flow chamber is shown in
A portion of a ETF micropump manufactured according to the design in Example 2 and having transparent top and bottom walls is shown in
The flow generated by the pump in
Experimental data showing the relationship between flow velocity and AC frequency for an aqueous inositol solution in the micropump shown in
The magnitude of the electric field is controlled by the applied AC voltage. Theoretically, ETF velocity increases with the fourth power in voltage, as opposed to second power variation in electroosmotic flow. Experimental data demonstrating ETF in a fabricated micropump of the present invention is shown in
The effects of changing the width of electrodes on flow rate and head pressure of an eclipsed electrode design are shown in
The effects of changing the width of gaps between electrodes on flow rate and head pressure of a staggered electrode design are shown
An impedance based flow sensor applies an alternating electric field to a target solution flowing through a microchannel, and changes in the impedance of the solution are measured and correlated with the flow rate. In its simplest form this methodology requires two electrodes at the bottom wall of a channel, applying an AC electric field, and monitoring impedance.
Flow rate dependent impedance in a microfluidic channel was measured using a simple impedance flow sensor and the results are shown in
An ETF pump, sensor, and controller may be combined, for example, as shown in
Pump 10 is connected to a conduit 22 that delivers fluid from the pump to a conduit outlet 23 that is located at a delivery target site in a patient. The micropumps may be arranged in series and/or parallel to produce the desired maximum flow rate and head pressure. Combining 100 micropumps shown in
The sensor may be any sensor capable of measuring the rate of fluid flow from the pump to the patient and is preferably a LIFPA or impedance anemometer. The fluid reservoir may contain a drug in fluid form such as an aqueous solution containing an active ingredient or saline solution. The reservoir may comprise compartments containing different drugs for programmed release into a patient. The microprocessor may use flow rate information from the slow sensor to maintain minimum and/or maximum flow rates, provide preprogrammed flow rates, preprogrammed delivery of different drugs or drug combinations from a multi-drug reservoir, and/or provide an emergency cut off in response to abnormal or undesired flow rates.
The patient may be human or other mammal. The term “patients” may also include pets, livestock, and other animals as well as reptiles, amphibians, insects, and plants.
Although particular embodiments of the present invention have been described, it is not intended that such references be construed as limitations upon the scope of this invention except as set forth in the following claims.
This Application is a Continuation In Part of application Ser. No. 10/307,907, filed 02 Dec. 2002.
The U.S. Government may have certain rights in this invention pursuant to SBIR Contract Number: W81XWH06C0067 awarded by the United States Army
Number | Date | Country | |
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Parent | 10307907 | Dec 2002 | US |
Child | 11516269 | Sep 2006 | US |