Measuring and testing – Liquid analysis or analysis of the suspension of solids in a... – Viscosity
Reexamination Certificate
2001-11-09
2004-01-27
Williams, Hezron (Department: 2856)
Measuring and testing
Liquid analysis or analysis of the suspension of solids in a...
Viscosity
Reexamination Certificate
active
06681616
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention is generally related to analytical tools for the biological and chemical sciences, and in a particular embodiment, provides microfluidic devices, systems, and methods for determining the viscosity of fluids within microfluidic channels of a microfluidic network, optionally without adding dye (or other agents) which can alter the properties of the fluids.
Microfluidic systems are now in use for the acquisition of chemical and biological information. These microfluidic systems are often fabricated using techniques commonly associated with the semiconductor electronics industry, such as photolithography, wet chemical etching, and the like. As used herein, “microfluidic” means a system or device having channels and chambers which are at the micron or submicron scale, e.g., having at least one cross-sectional dimension in a range from about 0.1 &mgr;m to about 500 &mgr;m.
Applications for microfluidic systems are myriad. Microfluidic systems have been proposed for capillary electrophoresis, liquid chromatography, flow injection analysis, and chemical reaction and synthesis. Microfluidic systems also have wide ranging applications in rapidly assaying compounds for their effects on various chemical, and preferably, biochemical systems. These interactions include the full range of catabolic and anabolic reactions which occur in living systems, including enzymatic, binding, signaling, and other reactions.
A variety of methods have been described to effect the transport of fluids between a pair of reservoirs within a microfluidic system or device. Incorporation of mechanical micro pumps and valves within a microfluidic device has been described to move the fluids within a microfluidic channel. The use of acoustic energy to move fluid samples within a device by the effects of acoustic streaming has been proposed, along with the use of external pumps to directly force liquids through microfluidic channels.
The capabilities and use of microfluidic systems advanced significantly with the advent of electrokinetics: the use of electrical fields (and the resulting electrokinetic forces) to move fluid materials through the channels of a microfluidic system. Electrokinetic forces have the advantages of direct control, fast response, and simplicity, and allow fluid materials to be selectively moved through a complex network of channels so as to provide a wide variety of chemical and biochemical analyses. An exemplary electrokinetic system providing variable control of electro-osmotic and/or electrophoretic forces within a fluid-containing structure is described in U.S. Pat. No. 5,965,001, the full disclosure of which is incorporated herein by reference.
Despite the above-described advancements in the field of microfluidics, as with all successes, still further improvements are desirable. For example, while electrokinetic material transport systems provide many benefits in the micro-scale movement, mixing, and aliquoting of fluids, the application of electrical fields can have detrimental effects in some instances. In the case of charged reagents, electrical fields can cause electrophoretic biasing of material volumes, e.g., highly charged materials moving to the front or back of a fluid volume. Where transporting cellular material is desired, elevated electrical fields can, in some cases, result in a perforation or electroporation of the cells, which may effect their ultimate use in the system.
To mitigate the difficulties of electrokinetic systems, simplified transport systems for time domain multiplexing of reagents has been described in WO 00/45172 (assigned to the assignee of the present invention), the full disclosure of which is incorporated herein by reference. Still further alternative fluid transport mechanisms and control methodologies to enhance the flexibility and capabilities of known microfluidic systems, including multiple modulated pressure-driven techniques, have been described in International Application No. PCT/US01/05960, the full disclosure of which is also incorporated herein by reference.
Regardless of the mechanism used to effect movement of fluid and other materials within a microfluidic channel network, accuracy and repeatability of microfluidic flows can be problematic. Quality control can be challenging in light of variability of the fluids making up these flows, and accurate control over microfluidic flows in applications such as high throughput screening would benefit significantly from stable and reliable assays. It would also be beneficial to determine additional characteristics of the fluids flowing within the microfluidic channels of a microfluidic network.
In light of the above, it would be advantageous to provide improved microfluidic devices, systems, and methods. It would be desirable if these improved techniques allowed better control over the flows within a microfluidic network, and/or increased the information provided by the microfluidic systems regarding one or more of the characteristics of the fluids flowing within a microfluidic channel of the network. It would be particularly beneficial if these enhanced techniques provided real-time and/or quality control feedback on the actual flows, ideally without relying on significantly increased system complexity or cost.
SUMMARY OF THE INVENTION
The present invention generally provides improved microfluidic devices, systems, and methods. The devices and systems of the invention generally allow the characteristics of a fluid within in a microfluidic system to be determined, often using high-throughput techniques. In many embodiments, the invention will determine the viscosity of one or more sample fluids within a microfluidic channel network of a microfluidic body. The microfluidic networks will generally include at least one flow-resisting channel segment, and viscosity may be determined by flowing the sample fluid through the channel segment, often without altering the sample viscosity by adding any detectable marker (such as fluorescent dyes or the like) to the fluid before it flows through the channel segment. These techniques can also allow the use of dyes which are not normally compatible with a particular sample fluid, for example, dyes which are not soluble or the like. The viscosity may be determined by mixing the sample fluid with a detectable marker at an intersection downstream of the flow-resisting channel segment, with the mixing characteristics at the intersection indicating the pressure drop along the channel segment (and hence the viscosity of the sample fluid). Viscosities may be determined by comparing the flow characteristics of the sample fluid with a reference fluid having a known viscosity. The sensing range may be enhanced using a plurality of flow-resisting channel segments and/or detectable fluid channel intersections.
In a first aspect, the invention provides a microfluidic viscometer system comprising a microfluidic channel network including a first flow-resisting channel segment. A sensor coupled to the first segment of the network determines a viscosity of a sample fluid therein.
In many embodiments, a body having channel walls will define the network. The network will often include a plurality of channels with one or more intersections therebetween. A flow generator coupled to the network can induce a flow of the sample fluid within the first segment. A first intersection may be in communication with the first segment, with the sensor coupled to the network at a sensor location disposed downstream of the first segment. This allows the sensor to sense a change in the flow which propagates from the first intersection to the sensor location so as to determine the viscosity of the sample fluid.
In some embodiments, the change in flow may comprise a pulse of a detectable fluid introduced at the first intersection, which may be upstream of the first segment. The system can then determine the viscosity of the sample fluid using a steady state propagation of the flow (which includes the detectable fluid pulse) from the intersection thro
Chien Ring-Ling
Chow Andrea W.
Kopf-Sill Anne R.
Parce J. Wallace
Spaid Michael
Caliper Technologies Corp.
McKenna Donald R.
Politzer Jay L
Quine Intellectual Property Law Group
Williams Hezron
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