Pumps – Processes
Reexamination Certificate
1999-06-30
2001-02-27
Walberg, Teresa (Department: 3742)
Pumps
Processes
C417S118000, C417S121000
Reexamination Certificate
active
06193471
ABSTRACT:
BACKGROUND OF THE INVENTION
(a) Field of the Invention
This invention relates to a process, and system, and to system elements for controlling formation and movement of small volumes of liquid by means of controlled gas pressures. More particularly, this invention relates to a process and system and to system elements for gating, transporting, and mixing small volumes of liquid samples wherein the liquid samples are treated or analyzed.
(b) Description of Prior Art
Fluid circuits require gates to control fluid movement. However, at the present time, there is no accepted mechanism or process for valving fluid volumes smaller than about a hundred nanoliters. At dimensions smaller than the microliter dimension, mechanical seals are both ineffective and impractical to manufacture.
Prior to the present invention, attempts have been made to process small volumes of liquids in the nanoliter range in order to effect a chemical reaction, analysis or the like. For example, capillary microfluidic circuits have been utilized to control movement of small volumes of liquid samples by applying large voltages to the samples. The voltages induce electroosmotic flow that allows control of direction and flow rate of the liquid samples. However, there exist environmental conditions that compete with the voltage force for effecting hydrodynamic fluid flow, including those induced by small pressure gradients. Electroosmotic flow is also sensitive to variations in the ionic composition of the fluid, and on factors such as the temperature, so the control of flow rates by this method is inaccurate at best. In addition, the electroosmotic flow is sometimes detrimental to the circuit function and suppression of electroosmotic control leaves little external control. As microfluidic circuits become more complicated, electroosmotic control does not effectively provide for isolation of different parts of the circuit. As a result, the design of microfluidic circuits controlled by electroosmotic forces is limited to only simple circuit designs.
It has also been proposed to provide mechanical valves in very small fluid circuits. However, as the surface finish of most materials at micron dimensions is not uniform, devices such as mechanical valves are unreliable. In addition, the problem of aligning a mechanical valve with one or more fluid conduits is extremely difficult at micron dimensions. In another embodiment of micromachined valves, silicon diaphragms are fabricated at small dimensions to be used as valve closures, but the actuation mechanisms for these diaphragms have not been suitable for liquid transport at nanoliter scales. Thus, from a practical standpoint, mechanical valves made from these materials are not useful in systems for transporting small liquid in volumes such as that at the nanoliter level.
It has also been proposed to use nonmechanical means to control fluid movements in capillaries. The concept of utilizing menisci to control fluid movements in capillaries has been utilized extensively in devices such as in the Lang-Levy micropipette. However, prior to the present invention the use of the menisci has not been used in a capillary microfluidic system for several reasons. The most important reason has been the absence of a controllable method for creating menisci in a liquid capillary and for removing menisci from a liquid capillary. At the present time, menisci in capillaries are widely regarded as undesirable and stringent efforts are made to prevent any sources of bubbles (the most common form of menisci) including cavitation or degassing. In present liquid transport systems, bubbles become trapped at particular locations within the systems and undesirably function to obstruct liquid flow or otherwise compromise performance.
Accordingly, it would be highly desirable to provide a process and system for transporting small volumes of liquid samples such as at the nanoliter level. In addition, it would be desirable to provide such a process and system which permits the inclusion and/or the removal of menisci from a liquid sample. Furthermore, it would be desirable to provide such a process and system which permits the transport of exact small volumes of liquid sample from a storage means to a point of use in order to permit precise treatment of the sample such as for analysis or reaction. In addition, it would be desirable to provide such a process and system which permits mixture of two or more liquids. Such a process and system would permit the user to provide small samples to a point of use while providing reliable results at the point of use such as by analysis or reaction of the sample.
BRIEF DESCRIPTION OF THE INVENTION
The present invention provides a process and system for forming and transporting small volumes of liquid samples including samples having nanoliter volumes. In addition, the present invention provides a process and system for introducing menisci, arresting the movement of menisci at defined locations in the system, and for removing menisci from capillary volumes of a liquid sample. Furthermore, the present invention provides a process and system for delivering precise small volumes of liquid samples to a point of use.
The present invention is based upon the discovery that menisci can be formed, moved, arrested and removed in small capillary volumes of a liquid sample. The formation of menisci on a liquid sample permits the application of an externally controlled hydrostatic pressure on the sample without causing the sample to move within a capillary. This permits the formation of precise volumes of capillary liquid samples. The removal of menisci between two or more liquid samples permits the samples to be mixed. More generally, removal of unwanted bubbles or menisci from a capillary stream is an important part of chemical hygiene in fluid circuits, and especially in very small fluid circuits.
The active control of menisci in a capillary fluid circuit depends on the device geometry of the capillary circuit. The relationship between the device geometry and the forces in the system is an interesting problem in thermodynamics. The general capillarity equation of Young and Laplace describes the pressure difference across a meniscus necessary to keep the system in mechanical equilibrium. This equation demonstrates that the pressure difference &Dgr;P depends on only the surface tension &ggr; (i.e., the surface free energy per unit area of the meniscus, with units of ergs/cm
2
) and the shape of the meniscus.
&Dgr;
P
=&ggr;(1
/R
1
+1
/R
2
) (1)
The meniscus is a three-dimensional surface, the shape of which is described by its radii of curvature (R
1
and R
2
) in two orthogonal planes. Calculation of the meniscus shape generally requires the sophisticated mathematical tools of differential geometry. However, a wetted capillary in the shape of a simple circular cylinder has a meniscus with a very simple shape as shown in FIG.
1
A.
The meniscus of
FIG. 1A
is constrained to lie parallel to the wall of the capillary, forcing the meniscus into a hemisphere, with R
1
=R
2
=radius of the capillary. The total surface free energy of the meniscus is 2&pgr;r
2
&ggr;. If the capillary radius is decreased incrementally by a distance dr, the surface free energy of the meniscus will decrease by 4&pgr;r&ggr;dr. At mechanical equilibrium, this will be balanced by a change in the pressure difference &Dgr;P across the meniscus, where the work against the pressure difference is &Dgr;P2&pgr;r
2
dr. The result is &Dgr;P=2&ggr;/r, the Young-Laplace equation. If the capillary is held in a vertical orientation and dipped in a reservoir of liquid, the meniscus will rise in the capillary until mechanical equilibrium is reached where the liquid head pressure balances &Dgr;P. In this case, the capillary forces can be calculated directly from the capillary device geometry (i.e., the capillary diameter).
If the capillary channel ends abruptly, normal to a plane surface as shown in
FIG. 1B
, the shape of the meniscus flattens out as the meniscus approaches
Karnakis Andrew T.
Patel Vinod D.
PerSeptive Biosystems Inc.
Walberg Teresa
LandOfFree
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