Patent Application
20110301049
The exemplary embodiment relates to fluidic devices. It finds particular application in connection with a device and method for controlling fluid pulse shape, flow contour and flow direction in a high aspect ratio flow channel.
A fluidic device includes a channel which permits the flow of fluid therethough. High aspect ratio fluid devices, in which the channel height is substantially less than its width, find application in a variety of fields, including sensing. For example, DNA analysis chips include an array of sensor cells in contact with a fluid in a high aspect ratio channel having a small inlet port. One problem with such devices is that, proximate the small inlet, the reagent added to the device does not flow evenly over the array, with the result that some of the cells see more of the reagent than others. The flow contour that arises has a nearly circular shape, and flow at the edges of the channel is limited. The portions of the chip near the sides receive very little treatment of the reagents due to the low-flow condition. The distributed sensing elements receive different flow rates, yielding uneven sensor response.
To address this problem, the DNA analysis chips are manually placed on a shaker prior to analysis. This adds an additional step to the procedure and makes automation difficult.
Many applications are targeted toward mixing of fluids. One uses obstructions to force fluid flowing in a channel to break up and recombine the flow, yielding a mixed flow. See A. A. S. Bhagat, E. T. K. Peterson, and I. Papautsky, “A passive planar micromixer with obstructions for mixing at low Reynolds numbers,” Journal of Micromechanics and Microengineering, vol. 17, pp. 1017-1024, 2007. Another uses bifurcations where the Coanda effect splits and recombines the flow. See C. C. Hong, J. W. Choi, and C. H. Ahn, “A novel in-plane passive microfluidic mixer with modified Tesla structures,” Lab on a Chip, vol. 4, pp. 109-113, 2004. Grooves in top and bottom surfaces of a device have also been used to redirect the flow. D. R. Mott, P. B. Howell, J. P. Golden, C. R. Kaplan, F. S. Ligler, and E. S. Oran, “Toolbox for the design of optimized microfluidic components,” Lab on a Chip, vol. 6, pp. 540-549, 2006; T. M. Floyd-Smith, J. P. Golden, P. B. Howell, and F. S. Ligler, “Characterization of passive microfluidic mixers fabricated using soft lithography,” Microfluidics and Nanofluidics, vol. 2, pp. 180-183, 2006. P. B. Howell, D. R. Mott, S. Fertig, C. R. Kaplan, J. P. Golden, E. S. Oran, and F. S. Ligler, “A microfluidic mixer with grooves placed on the top and bottom of the channel,” Lab on a Chip, vol. 5, pp. 524-530, 2005; F. G. Bessoth, A. J. deMello, and A. Manz, “Microstructure for efficient continuous flow mixing,” Analytical Communications, vol. 36, pp. 213-215, 1999; A. D. Stroock, S. K. W. Dertinger, A. Ajdari, I. Mezic, H. A. Stone, and G. M. Whitesides, “Chaotic mixer for microchannels,” Science, vol. 295, pp. 647-651, 2002. Grooves formed in the top or bottom surfaces of a channel influence fluid flow characteristics, which can lead to improvements in mixing. See, for example, US 2008/0221844.
Fluid entering or flowing in a fluidics channel can have varying velocities for a variety of reasons. Also, if plug flow is desirable, channel geometries can prevent plug flow, or a flat flow contour, from occurring.
In accordance with one aspect of the exemplary embodiment, a micro-fluidic device includes a micro-channel with an inlet port at a first end and an outlet port at a second end. A first fluid is in the micro-channel. A focusing structure extends into the micro-channel, e.g., from a roof of the micro-channel, whereby when a pulse of a second fluid is introduced to the channel, the pulse advances adjacent to the sides of the micro-channel at a faster rate than would occur without the focusing structure.
In accordance with another aspect of the exemplary embodiment, a method of sensing includes providing a micro-channel with an inlet port at a first end and an outlet port at a second end, a sensor array defining, at least in part, a floor or roof of the micro-channel, and a first fluid disposed in the micro-channel. A pulse of a second fluid is introduced to the micro-channel through the inlet port. Flow of the pulse along a longitudinal axis of the micro-channel is restricted, whereby edges of the sensor array are exposed to the pulse without shaking of the micro-channel.
In accordance with another aspect of the exemplary embodiment, a micro-fluidic sensing device includes a micro-channel with an inlet port at a first end and an outlet port at a second end. The micro-channel is defined between a floor and a roof. The roof of the micro-channel is spaced from the floor. A first fluid, such as a gas or liquid, is disposed in the micro-channel. A sensor array defines, at least in part, at least one of the floor and roof of the micro-channel A focusing structure extends into the micro-channel from the other of the floor and the roof by a maximum distance which is less than a spacing between the roof and the floor, whereby a pulse of a second fluid flows between the focusing structure and the sensor array along a longitudinal axis of the micro-channel and at sides of the focusing structure to more closely approximate plug flow over the sensor array than would occur without the focusing structure.
In accordance with another aspect of the exemplary embodiment, a fluidic device includes a channel with an inlet port at a first end and an outlet port at a second end. The channel has a width and a maximum height, perpendicular to the width, the maximum height being defined between a floor and a roof of the channel. A ratio of the width to the maximum height is at least 10:1. A focusing structure extends from the roof or floor into the channel by a maximum distance which is less than the maximum height, the focusing structure having a height which is greater adjacent a longitudinal axis of the channel than adjacent sides of the channel for focusing a pulse of a fluid between the inlet and outlet ports whereby fluid flow adjacent to the sides of the channel is increased.
a-f show flow patterns of a plug of dye in simulated micro-fluidic devices in accordance with aspects of the exemplary embodiments.
a and 12b show flow patterns simulated using the incompressible Navier-Stokes steady state COMSOL® multiphysics solver.
Aspects of the exemplary embodiment relate to a fluidic device and to a method of use. The fluidic device is described herein in terms of a micro-fluidic device with a micro-channel, although it is to be appreciated that larger devices are also contemplated.
With reference to
The micro-channel 12 includes a fluid inlet port 14 and a fluid outlet port 16 defined in end walls 18, 20 of the micro-channel, respectively. Inlet 14 and outlet 16 may be axially aligned, as shown. Fluid 22, such as a liquid (or gaseous) biological sample or other liquid sample to be tested, enters the inlet port 14 via an inlet tube 24 and exits the outlet 16 of the micro-channel through an exit tube 26. Inlet and outlet 14, 16 can have a width w which is substantially less than the width W of the micro-channel, e.g., W≧10 w. However, in other embodiments, the inlet 14 can have a width which is up to the width of the channel, i.e., w≦W. The inlet 14 and outlet 16 can have a height which is ≦H. The fluid is constrained to travel along the micro-channel by generally parallel opposed side walls 30, 32, a roof 34, and an opposed floor 36, positioned below the roof 34. In the exemplary embodiment, the walls 30, 32, 34, 36 and those in which the inlet and outlet are formed, are all formed from a rigid material, such as plastic, glass, metal, or the like.
As shown in
The roof 34 has a planar lower surface 40 with the exception of a focusing structure 42, which depends from the roof 34 into the micro-channel by a maximum distance h. h and H are measured in a direction perpendicular to the plane of the roof, i.e., perpendicular to the longitudinal axis x of the channel. h is less than H to provide a gap 44 through which the fluid can flow between the focusing structure and the floor 36 of the micro-channel channel. h can be, for example, at least 0.25H, and can be up to 0.9H, such as up to 0.75H. In one specific embodiment, h is up to about 0.5H. For example, in a micro-channel of about 2 mm in height H, the focusing structure can have a maximum height h which ranges from 0.5-1.5 mm, and in one embodiment, h is less than 1.25 mm. The minimum height of the gap 44 is thus H-h, which in the exemplary embodiment, is at least 0.25H. In some embodiments, the height of the focusing structure 42 varies in height in at least one direction between a minimum height (e.g., about 0 mm) and the maximum height h. In other embodiments, the height of the focusing structure is substantially uniform, e.g., has a height h over at least ⅔ of its area.
The exemplary focusing structure 42 is axially aligned with the length axis x of the micro-channel and is a rigid, stationary structure which may be entirely solid or at least have an exterior surface which is resistant to flexing in response to liquid flow thereover. The focusing structure may be contoured to increase the plug flow character of a pulse of fluid as it passes through the micro-channel, as illustrated by the flow contours in
As will be appreciated, the area of the focusing structure is not limited to such a size and in one embodiment, could occupy the entire roof. In other embodiments, the focusing structure 42 may extend upward from the floor 36, i.e., from a lower surface of the channel, and have similar dimensions.
In the embodiment shown in
In particular, by changing the height of the roof of the channel in one or more strategic locations with one or more focusing structures 42, the profile of the flow contour can be adjusted as needed. The exemplary focusing structure 42 shown in
Since flow resistance is inversely proportional to channel dimension, the regions with lowered roof height, as in the region of focusing structure 42 produce a flow path with more resistance. Similar to an electrical current, the fluid follows the path of least resistance. Although in the lowered regions the fluid still flows, the flow rate is reduced in proportion to the channel height. The higher the resistance, the slower the flow. The crescent-shaped focusing structure 42 has the slowest flow straight up the middle of the micro-channel, along the x-axis, and fastest around the sides, thus changing the shape of the plug as it flows over the focusing structure 42.
While a contoured crescent shape with its concave surface facing the inlet port and which reaches its maximum height away from the edges of the crescent at about point 54 is one example of a focusing structure, other contoured structures are contemplated. For example the focusing structure can have an approximately Gaussian shape in x and y directions, as illustrated in the micro-fluidic device of
In other embodiments, a focusing structure 66 can have the shape of an arc, as shown in
The focusing structures 42, 60, 66 shown herein are symmetrical about the x axis such that the flow rate of the sample pulse along the edges of the array 50 is approximately equal. In other embodiments, the focusing structure may have an asymmetric configuration for increasing the flow in one region while decreasing it in another. In yet other devices, for example, where sensors are on the roof, the focusing structure may alternatively or additionally extend from the floor of the channel.
In the case of a sensing device, the roof 34 of the channel can be optically transparent, or transparent to other electromagnetic radiation used in analyzing the cells of the array 50. For example, the roof of the channel, and optionally also the focusing structure and walls, can be formed of glass, plastic, or the like. The focusing structure 42, 60, 66 may be integrally formed with the roof and made of the same material, e.g., by molding the roof and focusing structure from plastic. Or, lithographic techniques or the like may be used for forming a focusing structure on a planar surface which is to form the roof. In this case, the focusing structure may be formed from a different material than the rest of the roof. Techniques for forming micro-liter volume devices are described, for example, in U.S. Pub No. 2002/0060156 and 2006/0292628, the disclosures of which are incorporated herein by reference in their entireties.
While the exemplary micro-channel is rectangular in top plan view, other structures for the micro-channel are also contemplated. For example, the micro-channel may be U-shaped in top plan view (like a racetrack), rather than rectangular, with the focusing structure 42 located proximate the inlet end of the U. In this embodiment, the focusing structure may be positioned closer to one side of the micro-channel (the inner side) than the other, to compensate for the differences in the flowpath length along the outer and inner sides.
A method of using the microfluidic device 10 shown in any of the disclosed embodiments includes introducing an aliquot of a sample to be tested to the micro-channel 12, allowing the sample to flow over the array 50, and for excess liquid to be discharged through the outlet port. The sample may be left in contact with the array for a prescribed time, followed by washing the array, e.g., by introducing another fluid through the inlet port. Finally, detection includes examining the array for evidence of reaction of target species in the sample with one or more of the probes of the array. The exemplary method excludes a shaking step—the micro-fluidic device including the array can remain fixed in position throughout the procedure. However, in other embodiments, shaking may be performed.
While in the exemplary embodiment, the focusing structures are configured for enhancing plug flow, i.e., achieving a flow which is closer to that of
The exemplary micro-channel with a focusing structure has a variety of applications including use in a Genechip™ chamber or other biosensor chamber to produce even flow across width of chamber. However, other devices are also contemplated where a change in flow characteristics is desired.
As will be appreciated, the exemplary micro-fluidic device 10 is not limited to sensor applications. It may also be used to minimize or eliminate effects of Poiseuille flow, to minimize or eliminate the effects of dispersion on plug flow so that plug flow will maintain integrity longer. Other applications include fluid focusing and eliminating the racetrack effect. This latter is due to the longer path around the outside of a curved channel. The flow thus normally deviates from plug flow around the curve. The present focusing structure can be used to provide resistance to flow along the shorter inner edge of the curved channel, evening out the flow across the channel. As another example, where the channel inlet w≧½W, the focusing structure may be used to prevent parabolic flow and maintain plug flow for the length of the channel.
Another application is to adjust roof shape “on-the-fly” to direct fluid flow in real time (e.g., for sorting).
Without intending to limit the scope of the exemplary embodiment, the following examples demonstrate a method for identifying suitable focusing structures for achieving different flow characteristics.
Microfluidic devices without sensors were prepared to simulate fluid flow in actual micro-fluidic devices. Clear poly(methyl methacrylate) (PMMA) sheet material was used to fabricate a roof and floor of a micro-channel. The two layers were separated by rubber about 1 mm in thickness with a cut out to define the micro-channel (approximately 31×34×1 mm) and inlet and outlet tubes. A red rubber was used for clarity. The micro-channel was filled with a clear liquid.
A 100 μl plug of dyed water was injected into the channel via the inlet port.
a shows the flow pattern around the inlet (LHS) for a conventional micro-channel with a planar roof. The plug should appear circular. However, the nearness of the outlet port likely distorts the shape to be slightly thinner.
b shows a similar plug of dye, except the top plate of the micro-channel has a smooth layer of clay built up in the middle to simulate an elongate focusing structure (the inner dashed ring indicates the deepest part of the focusing structure). The micro-channel height was lowest in the center and highest towards the sides, increasing the path resistance down the middle of the chamber, forcing fluid to flow more slowly down the middle and providing more flow down the sides. Rather than a rounded pulse, the focusing structure creates two lobes and there is flow closer to the edges of the channel. As will be appreciated, if the height of the focusing structure had been somewhat less, a more uniform plug flow could have been generated.
c-f show results with alternative focusing structure configurations (with their approximate shapes shown in dashed lines) made from several layers of tape (totaling ˜0.5 mm thick) cut out and attached to the top of the channel.
A flow channel with a portion of the roof lowered, as in the examples using shapes cut out from tape, was simulated using the incompressible Navier-Stokes steady state COMSOL® multiphysics solver.
The exemplary embodiment(s) described herein have been described with reference to the preferred embodiments. Obviously, modifications and alterations will occur to others upon reading and understanding the preceding detailed description. It is intended that the exemplary embodiment be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.
