WO2004058333A1

WO2004058333A1 - Fluid dispensing system

Info

Publication number: WO2004058333A1
Application number: PCT/IB2003/005585
Authority: WO
Inventors: Menno W. J. Prins
Original assignee: Koninklijke Philips Electronics N.V.
Priority date: 2002-12-30
Filing date: 2003-11-28
Publication date: 2004-07-15
Also published as: JP2006512127A; US20060131343A1; CN1732026A; AU2003283673A1; EP1581283A1

Abstract

A fluid dispensing system comprises an inlet to receive an input fluid and an outlet to dispense an amount of output fluid. A pump is placed between the inlet and the outlet to pump the amount of output fluid to the outlet. The pump includes one or several channels, which are provided with an electrode. A barrier is provided, preferably within the channels to separate the input fluid from the output fluid. The barrier being impermeable for the input and/or output fluids. Preferably, the barrier is formed as a fluid plug that can move along the channels.

Description

Fluid dispensing system

The invention relates to a fluid dispensing system comprising

- an inlet to receive an input fluid,

- an outlet to dispense an amount of output fluid,

- a pump placed between the inlet and the outlet to pump the amount of output fluid to the outlet .

Such a fluid dispensing system is known from the paper 'Fluid control in multichannel structures by electrocapiUary pressure' in Science 291(2001)277 by M.W.J. Prins et al.

The known fluid dispensing system comprises a microchannel with electrodes inside the walls. The microchannel is filled with two fluids that are immiscible and have different electrical conductivities. In the known fluid dispensing system the fluid flow is controlled on the basis of the phenomenon of electrocapillarity, i.e. the apparent dependence of the interfacial tension on the electric charge density accumulated a the interface between the fluid and the wall of the microchannel. The microchannel with the electrode performs the function of the pump. The known fluid dispensing system involves micropumping by electrocapiUary effects. In particular, micropumping action is generated by the electrocapiUary pressure, which originates from electrostatic control of the interfacial tension in the microchannel. The flow into or out of the microchannels is mediated by communication channels that function as the inlet and outlet respectively. The cited article mentions that about 4000 microchannels are employed in the known fluid dispensing system.

An object of the invention is to provide a fluid dispensing system, which is able to operate with a wide variety of input and output fluids.

This object is achieved by a fluid dispensing system according to the invention in which the pump includes one or several channels and

- the one or several channels are provided with an electrode, - the fluid dispensing system being provided with a barrier to separate the input fluid from the output fluid and

- the barrier is impermeable for the input and/or output fluids.

The barrier separates the input fluid from the output fluid. Hence, incompatible or even mutually aggressive fluids may be employed as input and output fluids. In particular the barrier is formed as a fluid membrane, i.e. a meniscus. Such a fluid membrane is formed when a fluid plug, that can be a gas or a liquid, is inserted in the channel or channels between the input fluid and the output fluid. In particular, the channel or channels are formed as capillary tubes. Fluid membranes are formed as the meniscus between the input fluid and the fluid plug and between the output fluid and the fluid plug, respectively. These fluid membranes move very smoothly and without hysteresis along the longitudinal axis of the channel. Accordingly, the amount of output fluid that is dispensed is very precisely controlled. Further, the fluid dispensing system based on the electrocapiUary effect has low leakage and a high-energy efficiency. This makes the fluid dispensing system of the invention particularly suitable to be employed as an implantable drug delivery system. These and other aspects of the invention will be further elaborated with reference to the embodiments defined in the dependent Claims.

Preferably, in the one or several channels at their side facing the inlet an inlet obstacle is provided. Preferably, also in the one or several channels at their side facing the outlet an outlet obstacle is provided. This inlet and outlet obstacles function to keep the fluid plug inside its channel. Because the fluid plug is kept inside the channel(s) at issue, accurate control of the amount of the output fluid is ensured. Notably, uncontrolled dispensing of the output fluid due to the fluid plug exiting the channel is avoided. There are various ways how such an inlet obstacle and/or outlet obstacle are formed. For example, a fluidophilic coating is applied locally at the inside of the wall of the channel. Such a fluidophilic coating has a high adhesion for the fluid of the fluid plug. For example when the fluid plug is made of an aqueous solution, the inlet obstacle and/or outlet obstacle are made as a hydrophilic coating. When the input fluid is a non-polar oil, an oliophilic coating is applied locally at the inside of the wall of the channel to form the inlet obstacle and/or outlet obstacle. Another example of the inlet obstacle and or outlet obstacle is a porous structure provided at the outlet side of the channel. Such a porous structure acts as a barrier for the fluid plug. For example a honeycomb structure may be employed as the porous structure. This porous structure more strongly withholds the meniscus between the input fluid and the fluid plug from leaving the multichannel than that it increases the flow resistance of the input fluid into the channel. With electrocapiUary forces, flows between 0 and 0.1 m/s have been demonstrated. However, for dispensing applications low velocities can be used, e.g. of the order of microliters per minute or lower, so the increased flow resistance does not negatively affect the operation of the fluid dispensing system. In another preferred embodiment, the fluid dispensing system is provided with a pressure system to apply a controllable offset pressure to the fluid(s) in the channels. This offset pressure is exerted as a hydrostatic pressure. Accordingly, the voltages required to generate the electrocapiUary effect, which achieves the pumping action, are in a relatively low region compared to the voltage a which a saturation of the electrocapiUary effect occurs. The offset pressure is adjustable to control the fluid dispensing system so as to avoid that input fluid enters the channel and consequently the output fluid is unintentionally dispensed at the outlet without a voltage being applied.

Preferably, the function of the pressure system is performed by the fluid plug. The fluid of the fluid plug is then chosen such that the fluid of the fluid plug forms mirrored menisci with the input fluid and output fluid, respectively. Examples are aqueous solution / non-polar oil / aqueous solution, and aqueous solution / gas / aqueous solution. Such a configuration gives rise to a capillary pressure in the channel that acts as the offset pressure.

In a further preferred embodiment of the fluid dispensing system, the fluid plug is much shorter than the length of the channel. For example a plug with a length of a few micrometers in a microchannel with a length of a centimetre. The ratio of plug/channel can be between 10^"4 to 0.2. In this embodiment the pump function is entirely integrated in the channel so that the fluid dispensing system is compact and small in size, e.g. a few cubic centimeters. Such a compact fluid dispensing system is very suitable to implant in the human body without any discomfort for the user. This implanted fluid dispensing system is advantageously employed to administer doses of drags from the outlet to the user. The fluid dispensing system enables dispensing drugs continuously or very regularly without intervention such as injecting the drug or oral administration of the drug.

These and other aspects of the invention will be elucidated with reference to the embodiments described hereinafter and with reference to the accompanying drawing wherein

Figure 1 shows a schematic representation of a fluid dispensing system according to the invention, Figure 2 shows another embodiment of the fluid dispensing system of the invention,

Figure 3 shows another version of the embodiment shown in Figure 2 of the fluid dispensing system of the invention and Figure 4 shows a frontal view of one of the channels 5 of the fluid dispensing system shown in Figure 3.

Figure 1 shows a schematic representation of a fluid dispensing system according to the invention. The pump 3 is placed between the inlet 1 and the outlet 2. The pump includes several channels 5. Here only two channels are shown by way of example, but in practice larger number of channels may be employed. It is advantageous to employ more channels, because that allows more fluid to be displaced. Also, it is advantageous to use channels with a small diameter, because the pressure scales with the inverse of the channel diameter. These channels may be formed as capillary microchannels having a capillary radius between 1 mm and 3 μm, for example about 40μm. The microchannels are filled with immiscible fluids; meniscus 11 between these fluids are shown. On the walls of the microchannels partially cylindrical electrodes 12 are provided. For example, the electrodes are metal layers that are applied in or on a part of the cylindrical surface of the microchannels. The cylindrical electrodes are formed from several segments. These segments can be individually activated in that respective voltages are applied to the separate segments. The potential difference between the fluid in the microchannel and the wall depends on the voltage applied to the electrode 12 and this potential difference gives rise to the electrocapiUary pressure in the microchannel that drives the pumping action of the pump 3. A voltage supply 51 provides the electrical voltage to the electrode segments. A selection circuit 52 arranges to supply the electrical voltage to the respective electrode segments of respective microchannels 5. A control unit 53, for example a microprocessor, is coupled to a control input of the selection circuit the control the setting of the selection circuit 52 so as to apply the voltage to the respective electrode segments. For example when adjacent electrode segments are activated successively, the meniscus 11 between both fluids in the microchannels is driven along the microchannels so as to achieve the pumping action.

In the embodiment of the fluid dispensing system shown in Figure 1, the inlet is connected to an inlet reservoir 21 and the outlet 2 is connected to an outlet reservoir 22. The outlet reservoir is filled with the output fluid. In the outlet reservoir for example a drug to be released into the outlet is stored and the inlet reservoir is filled with the input fluid. In the inlet reservoir there is placed an inlet barrier 61 and in the outlet reservoir there is placed an outlet barrier 62. The inlet barrier separates the input fluid from the fluid in the microchannels. The outlet barrier separates the output fluid from the fluid in the microchannels. These inlet barrier and the outlet barrier are flexible membranes that are moveable along the longitudinal axis of the inlet reservoir and outlet reservoir, respectively. The longitudinal axes extend through the inlet reservoir and outlet reservoir along the direction from the inlet to the outlet in which the pumping action of the pump displaces the fluids that are pumped. These flexible membranes also cause the fluid pressure to remain even at either side of the membranes when an amount of output fluid is dispensed from the outlet 2. Thus, small amounts of fluids, e.g. pharmaceuticals, maybe dispensed in an accurately controlled way.

Figure 2 shows another embodiment of the fluid dispensing system of the invention. In the embodiment of Figure 2 the barrier 6 is formed as a fluid plug 8 in the individual microchannels 5. The fluid plug 8 is formed from a fluid that is immiscible with the input and output fluids and forms respective meniscus with the input and output fluids. The fluid plug 8 is moved by the electrocapiUary pressure that is generated by activating the electrodes 12. The fluid plug 8 is moveable in the microchannels and the fluid plug 8 with its meniscus formed with the input fluid and output fluid separates the input fluid from the output fluid. Moreover, the fluid plug 8 is moved along the microchannels with very low resistance and almost no hysteresis. In the embodiment of the fluid dispensing system shown in Figure 2 the inlet obstacle and/or outlet obstacle structure 7 is employed in the form of a local fluidophilic coating 7 that is applied on the inner wall of the microchannels at the end of the microchannel towards the inlet and outlet, respectively. This fluidophilic coating has a high affinity for the fluid of the fluid plug. The high affinity prevents the fluid plug 6 to exit from its microchannel. For example, the barrier is a porous material coated with a fluidophilic layer, e.g. porous alumina or a porous plastic that is coated with aluminium oxide, and the fluid an aqueous solution.

Figure 3 shows another version of the embodiment shown in Figure 2 of the fluid dispensing system of the invention. Notably, in the fluid dispensing system shown in Figure 3 the inlet obstacle and/or outlet obstacle is formed as a porous structure in the microchannels at the end of the microchannels towards the inlet. Owing to the high surface area in the porous structure 8 prevents the meniscus between the input fluid and the fluid plug 8 to pass through the porous structure 8 and exit from the microchannel. Figure 4 shows a frontal view of one of the channels 5 of the fluid dispensing system shown in Figure 3. In Figure 4 the porous structure having a honeycomb-like stracture 8 is shown.

Claims

CLA S:

1. A fluid dispensing system comprising

- an inlet to receive an input fluid

- an outlet to dispense an amount of output fluid

- a pump placed between the inlet and the outlet to pump the amount of output fluid to the outlet, and wherein

- the pump includes one or several channels and

- the one or several channels are provided with an electrode,

- the fluid dispensing system being provided with a barrier to separate the input fluid from the output fluid - the barrier being impermeable for the input and/or output fluids.

2. A fluid dispensing system as claimed in Claim 1, wherein the barrier is provided in at least one of the channels.

3. A fluid dispensing system as claimed in Claim 2, the channels being directed along respective longitudinal axes, wherein the barrier includes a separating flexible membrane that is moveable along the relevant longitudinal axis(es).

4. A fluid dispensing system as claimed in Claim 2, wherein the channels being directed along respective longitudinal axes, wherein the barrier includes a separating fluid plug that is moveable along the relevant longitudinal axis(es).

5. A fluid dispensing system as claimed in Claim 2, including an inlet obstacle stracture at the side of the one or several channels facing the inlet and/or an outlet obstacle at the side of the one or several channels facing the outlet.

6. A fluid dispensing system as claimed in Claim 5 wherein the inlet obstacle stracture and/or outlet obstacle structure includes a fluidophilic coating.

7. A fluid dispensing system as claimed in Claim 5, wherein the inlet obstacle and/or outlet obstacle stracture includes a porous stracture, in particular a honeycomb shaped structure.

8. A fluid dispensing system as claim in Claim 5, wherein the inlet obstacle and/or outlet obstacle structure includes a pressure system to apply an controllable offset pressure to the fluid in the channels.

9. A fluid dispensing system as claimed in Claim 4, wherein the fluid plug is much shorter than the length of the channel, in particular the ratio of the size of the fluid plug to the length of the channel is in the range of 10^" to 0.2.