News Column

Patent Application Titled "Devices and Methods for Programming Fluid Flow Using Sequenced Microstructures" Published Online

September 11, 2014



By a News Reporter-Staff News Editor at Politics & Government Week -- According to news reporting originating from Washington, D.C., by VerticalNews journalists, a patent application by the inventors Di Carlo, Dino (Los Angeles, CA); Amini, Hamed (Beverly Hills, CA); Sollier, Elodie (Gagny, FR), filed on September 27, 2012, was made available online on August 28, 2014.

No assignee for this patent application has been made.

Reporters obtained the following quote from the background information supplied by the inventors: "Flow control and fluid interface manipulation in microfluidic platforms is of great importance in a variety of applications. For example, fluid control can be employed to focus fluids or entrain particles at certain lateral positions within a microfluidic channel. Flow control can also be used to mix and even separate fluid components. Control of fluid streams is also useful in biological processing and chemical reaction control. Current approaches to manipulate fluids generally rely on complex designs or difficult to fabricate three-dimensional (3D) platforms. Still other microfluidic platforms require the incorporation of active elements. In addition, existing state-of-the art devices operate with the mind set of inducing chaos to enhance mixing at the microscale level. Consequently, these approaches essentially operate to induce disorder into the flow system which can lead to unpredictable flow control."

In addition to obtaining background information on this patent application, VerticalNews editors also obtained the inventors' summary information for this patent application: "In one aspect of the invention, a microfluidic platform or device is disclosed that uses obstacles placed at particular location(s) within the channel cross-section to turn and stretch fluid in a manner that, unlike under Stokes flow conditions, does not precisely reverse after passing the obstacle(s). The asymmetric flow behavior upstream and downstream of the obstacle due to fluid inertia manifests itself as a total deformation of the topology of streamlines that effectively creates a tunable net secondary flow which in some ways resembles the recirculating Dean flow in curving channels. The system and methods passively creates strong secondary flows at moderate to high flow rates in microchannels. These flows can be accurately controlled by the number and particular geometric placement of the obstacle(s) within the channel. The fluid motions within the channels can be predicted and numerically simulated to characterize secondary fluid flow and predict net inertial flow deformations so that particular fluid patterns can be engineered in the channel cross-section.

"Sequences of these obstacles can be assembled in series or in parallel within a channel to conduct additional fluidic operation on flowing fluid streams. Importantly, the secondary transport shape and magnitude remains relatively constant after passing an obstacle for over an order of magnitude of Reynolds numbers (or flow rates) enabling the prediction of the programmed flow field based on one mapping of transport after passing an obstacle without having to simulate each new configuration. In this regard, because of their deterministic nature, different sequences of obstacles can be used to 'program' specific microfluidic flow stream patterns or shapes.

"This system and method creates the possibility of exceptional control of the three-dimensional structure of the fluid within a microfluidic platform which can significantly advance applications requiring fluid interface control (e.g., optofluidics) or generation of gradients of molecules. Specific tailoring of fluid flow within a microfluidic channel can also be used to manufacture filaments or particles having specific cross-sectional dimensions. The microfluidic platform can also be used to provide for ultra-fast mixing or heat transfer. Microfluidic flows can be tailored for fluid exchange applications (i.e., exchanging fluid around cells or the like). Additional, selective separation of particles can be conducted due to the secondary flow interacting with the underlying inertial lift forces acting on the particles.

"Rather than apply flow transformations that prevent or disrupt order, the flow control method and platform described herein is needed to program fluid flow based on the deterministic behavior of fluids interacting with objects contained with a microfluidic environment. A hierarchical approach is taken to engineer fluid streams into a broad class of complex configurations. The inertial flow deformations associated with the flow around a library of single fundamental operations (e.g., flow around a sequence of pillars) can act as the basic programming operators. Since these transformations provide a deterministic mapping of fluid elements from upstream to downstream of an obstacle, one can sequentially arrange obstacles to apply the associated nested maps and therefore program complex fluid structures without additional numerical simulation. Consequently, functions composed of multiple operators (e.g., posts, pillars, or other protuberances) such as 'rotate stream to centerline', or 'move stream right', can be hierarchically assembled to execute practical programs.

"The cross-sectional shape of a stream can be sculpted into complex geometries (such as various concavity polygons, closed rings, and inclined lines), moved and split, rapidly mixed, shaped to form complex gradients, or tuned to transfer particles from a stream, and separate particles by size. The introduction of a general strategy to program fluid streams in which the complexity of the nonlinear equations of fluid motion are abstracted from the user can impact biological, chemical and materials automation in a similar way that abstraction of semiconductor physics from computer programmers enabled a revolution in computation.

"In one embodiment of the invention, a method of programming flow within a channel includes selecting a plurality of operators from a library, each of the plurality of operators from the library having a known net secondary fluid affect; creating a program from the plurality of selected operators; and manufacturing a channel having formed therein the program of selected operators.

"In another embodiment, a device includes a channel having at least one intersecting sheath fluid channel at an upstream location; and a plurality of different operators disposed within the channel at a downstream location, each operator comprising one or more protuberances having a known net secondary fluid affect, each of the plurality of operators being separated from one another along a length of the channel.

"In another embodiment, a method of exchanging fluids around particles within a channel includes initiating sheath flow within a channel, wherein the particles are contained in a carrier fluid and absent from a sheathing fluid. The particles are passed through a program comprising a plurality of operators disposed within the channel configured to alter the flow around the particles such that the particles are contained within the sheathing fluid and not contained in the carrier fluid.

"In another embodiment, a method of forming a filament using a channel includes: initiating sheath flow within a channel of a precursor material; passing the precursor material through a program comprising a plurality of pillar operators disposed within the channel configured to alter the cross-sectional profile of the flow in a pre-determined manner; and polymerizing the precursor material into a filament within the fluidic channel.

"In another embodiment, a method of forming three-dimensional particles using a channel includes initiating sheath flow within a channel of a precursor material; passing the precursor material through a program comprising a plurality of pillar operators disposed within the channel configured to alter the cross-sectional profile of the flow in a pre-determined manner; and polymerizing the precursor material into particles within the channel by exposing a portion of the precursor material to light through a mask interposed between the channel and a light source.

"In yet another embodiment, a method of heat transfer using a channel having one or more hot regions adjacent to a surface thereof includes initiating flow within a channel, wherein the flow includes one or more streams therein having a lower temperature; and passing the flow through a program comprising a plurality of operators disposed within the channel configured to alter the cross-sectional profile of the flow so as to move the one or more streams having the lower temperature adjacent to the one or more hot regions.

"In still another embodiment a method of exposing target species to a reaction surface located on a surface of a channel includes initiating flow within a channel, the flow containing targets therein; and passing the flow through a program comprising a plurality of operators disposed within the channel configured to alter the cross-sectional profile of the flow so as to move the targets adjacent to the reaction surface.

"In another embodiment, a method of generating or altering the gradient of one or more species in a fluid within a channel includes maintaining flow within a channel, the flow containing a fluid having an initial concentration profile of the one or more species in a cross sectional direction; and passing the flow through a program comprising a plurality of operators disposed within the channel configured to alter the cross-sectional profile of the flow so as to alter the concentration profile of the one or more species in the cross sectional direction.

BRIEF DESCRIPTION OF THE DRAWINGS

"FIG. 1A schematically illustrates four different microchannels having different operator configurations.

"FIG. 1B graphically illustrates a library containing multiple operator configurations.

"FIG. 1C illustrates an exemplary program that includes multiple operators. The combination of operators 1 and 2 rotate fluid while the combination of operators 3 and 1 move the stream to the right.

"FIG. 2A illustrates a method of generating a library as well as selecting operators from the library to create a program sequence that can then be made into a microfluidic device.

"FIG. 2B schematically represents how a final flow state F(s) is achieved by selecting different operator functions based on an initial condition S. In this example, a program is illustrated that uses three operator functions (f.sub.1, f.sub.2, f.sub.3) in four, serially processed, logical steps.

"FIG. 3A illustrates the flow in a microfluidic channel that passes a plurality of microstructures in the form of posts or pillars. The arrow plot shows the average lateral velocity field as fluid parcels travel from input cross-section (upstream) to output cross-section (downstream). FIG. 3A also illustrates a cross-sectional image of fluid flowing through the microfluidic channel at the inlet, after ten (10) pillars, after twenty (20) pillars, and after thirty (30) pillars.

"FIG. 3B illustrates five different pillar configurations whereby the position of the net circulation is controlled by pillar location. Above each pillar configuration is shown the respective net deformation arrow plots as predicted by numerical simulations. Below are confocal cross-sectional images of the microfluidic channel at different downstream locations for each pillar configuration.

"FIG. 4A illustrates a comparison of Stokes and inertial flow development along the channel near the pillar (shown in the top-right quarter of the channel).

"FIG. 4B is a graph of .sigma.--the maximum fluid transfer normalized by the downstream flow velocity--as a function of Reynolds number (Re).

"FIG. 4C illustrate simulation results of a vertical set of inlet streamlines and their deformations in a quarter of the channel at four different Reynolds numbers. The top-view of streamlines at z=0 reveals the creation of post-pillar eddies with increasing Re which corresponds to the shift from increasing to decreasing .sigma. with Re. The front view illustrates the outline of an initially vertical line of fluid parcels at the inlet (labeled dashed line, x/D=-4), traced at x=0 (labeled dashed line, x/D=4) and the outlet (labeled solid line). Solid lines show channel walls and the dash-dot lines indicate channel symmetry. The grey area shows the outline of a quarter of the pillar in the respective channel quarter.

"FIG. 4D illustrates a phase diagram for inertial flow deformation for a simplified case when the deformation-inducing obstacle is a cylindrical pillar at the center of a straight channel showing four dominant modes of operation. Non-dimensional analysis proves that a set of three independent non-dimensional groups are needed to define a specific condition (shown on the axes). The phase diagram shows which mode is in effect at any given set of non-dimensional groups, or equivalently a given set of flow conditions and geometric parameters.

"FIG. 4E illustrates confocal cross-sectional images taken of the four modes that were achieved experimentally. The images, showing the flow pattern in a quarter of the channel, are overlaid with arrows indicating the direction of motion for that mode of operation.

"FIG. 5A illustrates a top view of the lateral position of pillar centers at various positions within a microfluidic channel.

"FIG. 5B illustrates four different programs (i.e., sequence of pillars and the inlet condition of the stream of interest) based on selected pillar positions using the scheme of FIG. 5A. Illustrated below each program is the respective cross-sectional flows based on the numerical prediction of flow as well as experimental observations. Note that numerical predictions are not based on full finite element simulations of the flow around the sequence of pillars but the sequential mapping of the basic operators from the library.

"FIG. 5C illustrates eight different programs as well as the respective cross-sectional flows showing the variety of geometric shapes that can be produced by different programs.

"FIG. 5D illustrates inlet and outlet images, respectively, of a microfluidic channel whereby particles contained within a carrier fluid are separated from the carrier fluid after passing a sequence of obstacles. The last obstacle in the sequence can be seen in the 'outlet' image.

"FIG. 5E illustrates 10 .mu.m sized particles that remain focused near the centerline while 1 .mu.m sized particles follow laterally displaced fluid streams, resulting in the separation of the two populations.

"FIG. 6A illustrates a microfluidic channel that is used to exchange fluid around particles according to one embodiment.

"FIG. 6B illustrates a cross sectional view of showing the particles and fluid being inertially focused within the microfluidic channel, before reaching the pillars.

"FIG. 6C illustrates a cross sectional view of showing the particles and fluid after being passed through a first program.

"FIG. 6D illustrates a cross sectional view of showing the particles and fluid after being passed through a second program.

"FIG. 6E illustrates a view of the outlets coupled to the microfluidic device of FIG. 6A.

"FIG. 7 illustrates fluorescent images taken of the inlet and outlet of a microfluidic channel that uses sheath flow in combination with a program to cause a single, fluorescently labeled stream to split into three (3) streams at the outlet.

"FIG. 8 illustrates cross-sectional confocal views of microfluidic mixing of a stream.

"FIG. 9A illustrate a microfluidic channel based device that uses sheath flow in conjunction with programmed fluid flow to manufacture a polymerized fiber having custom made cross-sectional shape.

"FIG. 9B illustrates the cross-sectional view of the polymer precursor aligned within the sheath fluid.

"FIG. 9C illustrates the cross-sectional shape of the polymer precursor after passing through the programmed area of the microfluidic channel.

"FIG. 9D illustrates a fiber created from the polymer precursor, after being shaped into the desired shape and undergoing polymerization.

"FIG. 10A illustrate a microfluidic channel based device that uses sheath flow in conjunction with programmed fluid flow to manufacture three dimensional particles.

"FIG. 10B illustrates the cross-sectional view of precursor material aligned within the sheath fluid.

"FIG. 10C illustrates three different types of programmed fluid geometries that can be created by passing the fluid by one or more operators as part of one or more program(s).

"FIG. 10D illustrates the formation of an individual particle by exposure of light through a mask onto the shaped flow within the microfluidic channel.

"FIG. 10E illustrates outlets of the microfluidic channel device of FIG. 10A.

"FIG. 11A illustrates a microfluidic channel that is used to create focused fluid stream for subsequent optical interrogation such as flow cytometry, or for reducing dispersion of the fluid stream.

"FIG. 11B illustrates the initially established sheath flow cross section.

"FIG. 11C illustrates a cross-sectional view of the focused stream after being subject to the program.

"FIG. 12 illustrates a microfluidic device that uses flow splitting to generate two cold streams adjacent to two hot spots or regions.

"FIG. 13A illustrates a cross-sectional view of a microfluidic channel having binding entities on an upper and lower surface with target species located in about one half of the channel volume.

"FIG. 13B illustrates a cross-sectional view of a microfluidic channel having binding entities on an upper and lower surface with target species being focused adjacent to the upper and lower surfaces.

"FIG. 13C illustrates a cross-sectional view of a microfluidic channel having binding entities on an upper and lower surface with non-specific binding molecules being focused away from the upper and lower surfaces.

"FIG. 14 illustrates a cross sectional image (top) of a plug of fluid having a uniform gradient. FIG. 14 further illustrates two different programs (A and B) that create, respectively, different gradients of the plug of fluid within the microfluidic channel."

For more information, see this patent application: Di Carlo, Dino; Amini, Hamed; Sollier, Elodie. Devices and Methods for Programming Fluid Flow Using Sequenced Microstructures. Filed September 27, 2012 and posted August 28, 2014. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=6786&p=136&f=G&l=50&d=PG01&S1=20140821.PD.&OS=PD/20140821&RS=PD/20140821

Keywords for this news article include: Patents.

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