Liquid pumping system

Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition

Reexamination Certificate

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C422S050000, C422S105000, C422S105000, C422S063000, C422S068100, C422S081000, C422S091000, C436S043000, C436S174000, C436S180000

Reexamination Certificate

active

06805841

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to liquid flows and, in particular, liquid flows at relatively slow speeds within relatively small bores such as those of microchannel structures or microcapillaries. The invention further relates to a liquid outlet link assembly for such liquid flows and to a microchannel structure assembly for microfluidic systems.
2. Background of the Invention
In recent years, microminiaturized fluidic systems are used extensively in analytical chemistry, drug discovery and life sciences. Microchannel structures of 20-100 &mgr;m in cross section are used in chemistry to achieve fast speed electrophoretic separation for chromatography. These structures, often referred to as bioelectronic chips or bio chips, could offer a convenient method of isolating, lysing, and detecting of micro-organisms in complex samples and could have applications in drug discovery, genetic testing and separation sciences (e.g. capillary electrophoresis).
For chemistry and drug discovery microfluidic reactors, microchannel structures and microcomponents present the possibility of decreasing the time of technological processes by integrating several units in relatively small areas. This could facilitate the execution of a number of reactions in parallel and increase efficiency in high throughput screening and combinatorial analysis. Overall, sample volumes within microcomponents are in the microliters range, which can save considerably on the amounts of reagents per reaction. For successful control of microreactors, efficient detection and separation of chemical specimens, it is absolutely necessary to provide fluid delivery at the low flow rates.
In the area of life sciences, the study and manipulation of single biological cells on microfluidic structures could potentially enable considerable experimental progress Manipulation of cells is becoming important for clinical diagnostics and genetic measurements. Lysing of cells, cell-cell interaction, interaction and manipulation of a single cells is now possible and it is more efficient using microchannel structures. It is expected that integrated analytical systems will allow genetic measurements and drug screening at the single cell level.
In these wide areas of application of microstructures, pumping systems play a significant role. Delivering required solutions to the sites of reaction, mixing different fluids, creating gradients of concentration of the reagents, controlling the positions of biological samples, transporting and manipulating them are all tasks, which require a highly accurate pumping system. Despite a major effort in developing pumping systems for a microchannel structure, the problem still remains. Many conventionally used pumping systems are operating with significantly bigger volumes of fluids, therefore they cannot provide pumping accuracy or in some cases adequate pumping speed when it comes to establishing flows inside the microstructures with a microchannel diameter from 5 to 100 &mgr;m.
DESCRIPTION OF PRIOR ART
Various constructions of positive displacement pumps, including syringe pumps, positive pressure infusion pumps and peristaltic pumps have been used with capillaries. These are, for example, described in U.S. Pat. No. 4,715,786 (Wolff et al. Syringe pumps with microflow rate capabilities to provide precise and reproducible volumetric flow ranges of the order of 0.1 &mgr;l to 1 ml per minute have been described, for example, in U.S. Pat. No. 5,630,706 (Yang) and U.S. Pat. No. 5,656,034 (Kochersperger et al). One of the main objects of these inventions has been to deliver pulse free flow, the problem being that the pressure of the fluid inside the syringe pump changes during the stroke of the syringe pump, which stroke is usually controlled by a stepper motor. Unfortunately, such an operation results in a large pressure surge which alters the volumetric flow rate. For example, Japanese Patent Specification No. 4058074A (Nagataka et al) describes a method to reduce fluctuations of the flow in a syringe pump to provide a more stable flow rate by setting the syringe vertically and forming a gas layer between the front surface of the piston forming the syringe pump and the liquid being pumped. This invention, however, is directed towards relatively large flow rates of the order of microliters per minute and would be useful for drug infusion but would not be particularly suitable for microchannel structures and the like, where the flow rates are, as mentioned already, substantially less.
U.S. Pat. No. 4,137,913 (Georgi) describes a method of controlling the flow rate by changing the stroke periods. U.S. Pat. No. 5,242,408 (Jhuboo et al) describes a method of controlling pressure inside a syringe pump by measuring the force acting on the plunger and detecting an occlusion. Unfortunately, heretofore, such syringe and positive displacement pumps are relatively inefficient at delivering fluid flow at rates of the order of nanoliters per minute, which flow rate is required to transport liquids in microchannel structures. Generally, the limitation on the flow rate is the movement accuracy of the various mechanical parts of the syringe pump such as the stepper motor, plunger, valves, and so on. However, syringe pumps used in high pressure liquid chromatography (HPLC) have achieved volumetric flow rates as low as 0.1 &mgr;l/min. A typical example of this is described in U.S. Pat. No. 5,630,706 (Yang). However, for commercially available syringe pumps, the linear displacement of the piston or plunger would be several micrometers per step of the motor controlling the pump. Thus, general sealing surface wear makes it impossible to achieve accuracy for shorter displacements.
A further disadvantage of the syringe pump when used for pumping fluids in microchannel structures, is that it cannot deliver a sufficiently low pumping speed for many applications of the structures.
Typically, a syringe pump would dispense 0.6 &mgr;l/min for one step of the motor which then has to be delivered into a microchannel structure possibly having a cross sectional diameter of the order of 40 &mgr;m which translates into 1.9 mm/sec. through the microchannel structure which is much too fast for the observation of biological specimens, detection of proteins, single cells and the creation of low gradients of reagents, which is required in many microfluidic applications. Indeed, one can readily appreciate that at this speed, visual observation is difficult and further would not allow for the manipulation or sensing of biological samples. Thus, heretofore, positive displacements pumps and in particular, syringe pumps, while very attractive for their simplicity, have not as of yet been useful for these applications.
Electrokinetic pumps have been proposed for such pumping operations. Pumps based on electroosmotic phenomena have been described in U.S. Pat. No. 3,923,426 (Theeuwes et al) and U.S. Pat. No. 5,779,868 (Wallace Parce et al). When a buffer is placed inside a capillary, the inner surface of the capillary acquires a charge. This is due to the ionisation of the wall or adsorption of ions from the buffer. In the case of silicate glass, the surface silanol groups (Si—OH) are ionised to silanoate groups (Si—O

). These negatively charged groups attract positively charged cations from the buffer, which form an inner layer of cations at the capillary wall. These cations are not in sufficient density to neutralize all the negative charges, therefore a second layer of cations forms. The inner layer of cations, strongly held by the silanoate groups, forms a fixed layer. The second layer of cations is less strongly held because it is further away from the negative charges, threfore it forms a mobile layer. When an electric field is applied, the mobile layer is pulled toward the cathode. Since ions are in solution, they drag the whole buffer solution with them and cause electroosmotic flow. The distribution of charges due to the formation of charged layers create a potential termed the zeta po

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