Multi-channel microfluidic system design with balanced fluid...

Fluid handling – Flow affected by fluid contact – energy field or coanda effect

Reexamination Certificate

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C137S806000, C137S841000, C204S451000, C204S601000

Reexamination Certificate

active

06637463

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to methods and apparatus for controlling fluid flow through flow paths. More specifically, the present invention relates to microfluidic methods and circuit devices in which flow path configurations are designed to control pressure drops on selected flow path segments to balance fluid flow among multiple flow paths, leading to efficient operation of the wetted microfluidic circuit.
2. Description of Related Art
Controlling the movement of fluids through channels on a micro-scale has important applications in a number of technologies. For example, in the field of molecular biology and diagnostic testing and detection, polymerase chain reactions (PCR) have been performed in a chip containing microfabricated flow channels (U.S. Pat. Nos. 5,498,392, 5,587,128, and 5,726,026). In the electronics field, thermal ink jet printers use print heads with flow paths through which ink must flow in a well-controlled manner (U.S. Pat. No. 5,119,116). Proper control of fluids through flow paths has been a challenge, because microdimensions impart characteristics and behaviors that are not found in larger scale systems, which are due primarily to the greater influence of surface effects.
The term “surface effects” is used to describe specific characteristics of a surface on a micro-scale. Materials often have unbound electrons, exposed polar molecules, or other molecular level features that generate a surface charge or reactivity characteristic. Due to scaling, these surface effects or surface forces are substantially more pronounced in microstructures than they are in traditionally sized devices. This is particularly true in micro-scale fluid handling systems where the dynamics of fluid movement are governed by external pressures and by attractions and repulsions between liquids and the materials of the microfluidic systems through which they flow.
It is frequently the case that micro-scale fluid handling systems are designed to perform multiple fluid handling steps in parallel, and it is often considered desirable to process fluids in multiple parallel flow paths simultaneously. However, such systems frequently suffer from uneven and irregular fluid flow. Many such problems are due to surface effects such as those mentioned above. Some micro-scale fluid systems fill unevenly. In others, channels fill at different rates. Additionally, some fluid circuits that split samples into multiple reaction chambers may do so unevenly. Those combining samples from multiple reaction chambers may do so incompletely or unevenly.
Such problems may result in incomplete assays or assays conducted with insufficient amounts of reagent or sample. Some of these problems may result in differences in the reaction times for the different assays, thus changing the results. These and other problems may affect the accuracy of assays and the usability of the micro-scale fluid handling systems themselves. Furthermore, uneven filling tends to result in the waste of valuable reagent or sample material, because larger volumes of fluid may be required to insure that all portions of the system are filled completely.
Yet further, many known chip designs have several wells. In order to provide the most compact arrangement of wells and flow paths, the flow paths must often be asymmetrical in design. The flow paths may thus provide different resistances to the flow of fluids filling the wells or draining from the wells. The presence of differential resistance to flow contributes to the unevenness with which the wells are filled and emptied, and therefore further reduces the accuracy of the assay.
Still further, many microfluidic circuits have well designs in which, due to the configuration of the well, fluids tend to stagnate within the well rather than exiting upon entry of a different fluid. Hence, samples or reagents within the well may not be washed or flushed properly at lower pressures. Additionally, gas bubbles, which may skew the results of the assay, may not be effectively removed from the wells. The use of higher volumes may improve washing but results in waste or inefficient use of limited sample and increased reagent costs.
Accordingly, a need becomes apparent for microfluidic circuits in which fluid flow may be regulated. Fluid flow should preferably be well-controlled during both the initial filling of the unwetted circuit and during subsequent introduction of additional reagents or wash solutions to the wetted circuit, so that gas removal and liquid exchange or flushing can be effectively carried out. Preferably, such regulation can be performed with flow paths and wells that are laid out in a compact, and possibly asymmetrical, fashion. Furthermore, a need exists for fluid circuits, and associated well structures, that can be reliably flushed to remove a liquid or gas at a low pressure and with a low volume of fluid. Such fluid circuits and methods for their use are disclosed herein.
SUMMARY OF THE INVENTION
The apparatus of the present invention has been developed in response to the present state of the art, and in particular, in response to the problems and needs in the art that have not yet been fully solved by currently available micro-scale fluid handling systems, also called microfluidics systems.
Thus, the present invention discloses a system and method for controlling the flow of fluids through microchannels in multiple parallel flow paths in such a manner that fluid can be evenly distributed among several parallel channels for multiprocessing. The parallel flow paths are configured to have uniform resistances to fluid flow so that fluid is induced to flow through all of the flow paths at substantially the same flow rate. One or more segments of each flow path may be specially configured to provide a desired relative pressure drop to, so that the pressure gradients can be equalized even though the flow paths may not be symmetrical or coextensive to each other.
According to certain embodiments, the flow of the fluid front through the flow paths is initially controlled by structures that act as passive fluid flow barriers, which in the present invention are abrupt changes in the geometry or surface properties of certain portions of the flow paths. These passive fluid flow barriers act to stop fluid flow by creating a passive pressure barrier that may be overcome by sufficient pressure, or by wetting both sides of the barrier.
Unlike flow barriers that require moving parts, the passive fluid flow barriers or abrupt flow path widenings can be static and their operation does not depend upon the use of moving parts. They are thus cheaper and simpler to construct than the various types of microelectromechanical active valves, and they do not require external controls.
According to certain embodiments, a microfluidic circuit within the scope of the invention may have a plurality of flow paths branching from a common inlet. Each flow path may have a filling portion that supplies fluid to an associated well or structure, and a draining portion that receives fluid from the well or structure for collection, further processing, or disposal. Throughout the specification, any such structures, which serve as sites at which chemical reactions and/or read-outs take place, will simply be referred to as wells. However, it should be understood that a well is just an example of a fluid handling structure that may be included in the flow path, and the flow path could include other fluid handling structures, e.g., a combination of several wells in series or parallel, channels or chambers of various dimensions, or chambers containing a matrix material, such as a filter, separation, or binding medium, including fibers, resins, beads or other materials. Any such structures may be used in the practice of the present invention, providing it is possible to identify the contribution of the fluid processing structure to the resistance to fluid flow and pressure drop over that portion of the flow path.
The common inlet may feed a main distribution channel.

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