Much research is currently put into developing electroosmotic and other micropumps for microfluidic systems (which is a sort of micro electromechanical systems (MEMS) or microsystem technology (MST)).
Microfluidics is an emerging technology which is expected to get vast implications in a number of technical fields. A microfluidic device typically consists of a number of microsensors or microanalyzers, connected to each other and the environment by microchannels. The liquid to be analyzed or delivered as well as reagents should preferably be pumped by means of microfabricated pumps. While the other components have already been commercially available for some time, the development of microactuators/-pumps is still at an early stage and several problems remains to be solved. Thus, the real breakthrough and commercialization of this technology is expected to come when improved actuators have been developed. It is an object of the present invention to provide actuators for microfluidic systems which are suited as micropumps or mixers with an improved flow through of fluid.
One class of known micropumps is the reciprocating pumps, which involves mechanical actuations. Usually, a membrane is actuated by piezoelectric, electrostatic or other forces. Common to them is the involvement of moving parts, which complicates fabrication and may reduce their useful life.
Field-induced flow pumps include electrohydrodynamic (EHD), magnetohydrodynamic (MHD) and electroosmotic (EO) pumps. One obvious advantage is the lack of movable parts. However, these pumps have a requirement for high voltages, with EO pumps being the most versatile.
Further, the EHD pumps are restricted to non-conducting liquids, ruling out all applications where a solution of significant ion concentration should be transported (e.g. body fluids). Also, high voltages are needed. PCT WO 02/07292 A2 describes an EHD micropump operating at 25 kV.
MHD pumps on the other hand are restricted to conducting solutions, omitting applications with very dilute solutions.
Electroosmotic (EO) micropumps is considered an especially promising technology for many applications, as it is relatively simple to fabricate, and good performance can be obtained for a wide range of concentrations. However, several technological challenges still remain to be solved. The main problems are i) electrode gas evolution, ii) electrochemical reactions, iii) stability and iv) need for large electric potentials. These challenges will be detailed below:
Electrode gas evolution: Relatively strong electric fields must be applied, and a direct current component is necessary. This results in gas evolution on the electrodes.
Electrochemical reactions: These reactions are responsible for the gas evolution and may also occur in other part of the system. In cooling applications, de-ionized water cold be used as liquid medium, resulting in the formation of H2 and O2 gas only. However, for “lab-on-a-chip”—applications, fluids could be altered due to reactions, which could influence or ruin the analysis or system operation. Also, substances harmful to the system could be produced, e.g. corrosive gases like Cl2 resulting from electrolysis of NaCl solutions. In addition, reaction products and concominant pH changes can also influence the pump surface potential, resulting in altered electro osmotic characteristics, e.g. reverse flow.
Stability: In addition to the influence of electrochemical reactions, establishment of pore concentration profiles along pore axis in a direct electric field may hamper the EO transport over time. Also, various phenomena like diffusiophoresis and osmosis might reduce the flow. Thus, DC electroosmosis usually degrades over time, ultimately zero flow is obtained, due to the side-effects described. These effects can be reduced by using a pulsating field, but as classical EO is linear in the field, the DC component must always be present, and thus the side effects also to some degree.
Large electric potentials (kV range) are usually required, demanding expensive and bulky (reducing portability) power-supplies. Also, this leads to danger in the case of leakage currents, especially for devices to be used close to the body.
PCT WO 02/070118 A2 discloses a microfabricated pump, where the problem of electrode gas evolution is met by separating the channel from the electrodes by a non-porous ion-conducting membrane. The gas bubbles are allowed to escape from the electrode chamber to the environment. Drawbacks include the need for an open structure, possible production of harmful reaction products and relatively complicated structure.
US 2003/0085024 A1 describes a cooling device with an EO micropump with separate chambers for catalytic gas recombination (platinum catalyst). This device is limited to pure or buffered water as the working fluid. As it is not guaranteed that the gas recombination is complete, gas is also allowed to escape the system through a membrane. Good pump performance was obtained, but without obtaining complete gas recombination. Obvious disadvantages of this system are the cost of catalyst, and size of recombiner. Also, the combiner was only designed to deal with the dissociation products of pure water, not e.g. Cl2 formed from NaCl solutions. A 2 kV electric potential difference was applied.
In U.S. Pat. No. 6,568,910 B1 an EO pump is described, for which the liquid is pumped from a first channel containing electrodes into and through a second channel where no electric field is present. Again, this solution is aimed at avoiding the electrode gas evolution to take place in the microchannel of primary interest.
In [J. G. Santiago, “electroosmotic flows in microchannels with finite inertial and pressure forces”, Anal. Chem., 73: 2356-2365, 2001] is described a pump using a capillary containing a porous frit of 3.5 μm silica particle for reducing pore-size (and thus increasing pressure). A flow of 3.6 μl/min was achieved using 2 kV potential difference. Deionized water was used as the working fluid, but still gas evolution was observed at the electrodes. Pumps with channel diameter 0.5 and 0.7 mm were used, while the length of the porous frit was 5.4 cm.
Using an open glass channel of dimensions 1 mm (length), 0.9 mm (height) and 38 mm (width), an electroosmotic velocity degrading from 15 to 0.2 μl/min in two months was obtained [Chen, C. H., Zeng, S., Mikkelsen J. C. and Santiago, J. G. “Development of a Planar Electrokinetic Micropump”, Department of Mechanical Engineering, Stanford University]. The potential difference was 1 kV. Again, deionized water was used as working fluid, but electrode reactions (gas evolution) were present.
Because of small channel size, the Reynolds number is low and the flow normally laminar. As a consequence, mixing mainly takes place by diffusion, which is in many cases efficient in micrometer dimensions. However, for large molecules (e.g. DNA), bacteria and cells, convection is the only way to achieve rapid mixing. Different methods have been tested for introducing chaotic flows in microchannels, but this is still considered a challenge.
The paper [Shishi, Q. and Haim H. Bau. “A Chaotic Electroosmotic Stirrer”, Anal. Chem., 74(15):3616-3625, 2002] describes a solution where mixing was possible by varying the wall surface potential in time and along the channel length coordinate, which could be done by introducing field effect control in short adjacent channel sections, by means of several electrodes and a control unit. This system has the drawback of having a relatively complicated structure.
An electrokinetic instability micromixer was also produced by using a sinusoidally electric field above 100 V/mm [Oddy, M. H., Santiago, J. G. and Mikkelsen, J. C. Anal. Chem. 73, 5822-5832 (2001)].
An EO driven micropump for insulin delivery is described in [E. L. P. Uhlig, W. F. Graydon, and W. Zingg. “The Electro-Osmotic Actuation of implantable Insulin Micropumps”, Journal of Biomedical Materials Research, 17:931-943, 1983]. The electrochemical cell (Ag|AgCl|NaCl| cation exchange membrane |NaCl|AgCl|Ag) was used for actuation, where the current was reversed every 10 minutes. The reversing was necessary in order not to run the reactions in one direction until termination, after which little or no current would flow. An electro-magnetically controlled valve was used to obtain uni-directional flow in a secondary channel despite the current reversals. This channel was in contact with a metal bellows containing the insulin, which could then be pumped into the body. This system has the drawback of being complicated, and involving moving parts.
Further prior art is described in US2003164296A1, U.S. Pat. No. 5,985,119, and in the following publications:
Dukhin S. S.: “Electrokinetic phenomena of the second kind and their applications” ADVANCES IN COLLOID AND INTERFACE SCIENCES vol. 35, 1991, Elsevier Science Publishers B. V. Amsterdam, pages 173-196, XP002976010.
Dukhin S. S.: et al: “Intensification of electrodialysis based on electroosmosis of the second kind” JOURNAL OF MEMBRANE SCIENCE vol. 79, 1993, Elsevier Science Publishers B. V. Amsterdam, pages 199-210, XP002974593.
Mishchuk N. A.: “Electro-osmosis of the second kind near the heterogeneous ion-exchange membrane” COLLOIDS AND SURFACES A: PHYSICOCHEMICAL AND ENGINEERING ASPECTS vol. 140, 1998, pages 75-89, XP002974594.
Mishchuk N. A. et al: “Electroosmosis of the second kind” COLLOIDS AND SURFACE A: PHYSICOCHEMICAL AND ENGINEERING ASPECTS vol. 95, 1995, Ukraine, pages 119-131, XP002976009.
It is clear that even if EO micropumps have several advantages, important problems are not satisfactory solved by the current state of the art. Generally, the electrode gas evolution problem is met by i) using special liquids (deionized water and possibly a buffer) which limits the field of applications greatly, or ii) by moving the electrodes away from the area of EO pumping, to some device where gas bubbles can escape. The latter requires even larger potentials as the potential difference is proportional to the electrode distance. It also makes the design more complicated, especially if the structure involves several pumps with respective electrode pairs.
It is an object of the present invention to develop new actuators for which the technological challenges are solved. Specifically, it is an object of the present invention to provide an actuator which can be driven with no DC signal using much lower potentials, and being less influenced by the system chemistry. In many cases, it will be possible to arrange the electrodes close to the pump, which brings the minimum voltage further significantly down, and is excellent for producing multi-pump systems. Further, it is an object to provide a solution with much higher flow velocities than can be obtained by prior art solutions. Further, it is an object to provide actuators which can be used for mixing liquids in microchannels, which is also a challenge in microfluidics. For most designs, the actuator in accordance with the present invention can operate reversibly, showing identical pumping characteristics in either direction.
It is an object of the invention to provide microchannels which are capable of transporting a fluid from the inlet of the channel to the outlet Compared to known prior art solutions based on traditional electroosmosis the microchannels according to the present invention provides an increased fluid flow, i.e. that the liquid is forced to flow through the microchannel with an increased flow rate. The net flow, i.e. the amount of liquid forced through the microchannel is increased. This improved flow is obtained by arranging conducting means with specific geometrical shapes in the microchannel. More precisely, a surface portion of said conducting means is curved, or inclined with respect to the electrical field applied to the microchannels.
The underlying theoretical concept for the invention is so called “electroosmosis of the second kind” (EO2) or “superfast electroosmosis”. A number of conditions have to be fulfilled in order to obtain EO2, especially if directed transport shall be achieved.
Liquid transport by EO2 is 10-100 times faster than for classical electroosmosis (EO1) applying the same electric field strength E. Lowering the electrical field strength E reduces the problem with electrochemical reactions, and also reduces the dangers of possible leakage current, which is especially important for implantable devices, and devices to be used close to the body. In addition, the needs for high voltage generators are eliminated, reducing the system cost and size, while enhancing portablility.
Being non-linear in the electric field strength, EO2 also makes it possible to achieve directed liquid transport using an alternating electric field, with little or no direct field component. Thus, the stability problems mentioned above can be reduced or eliminated. In addition, electrode reactions (including electrode gas evolution) will also be reduced or eliminated in an alternating field, as the polarization current will be larger, and the faradayic current smaller for alternating fields.