Description of the Related Art The ability to manipulate different species (e. g. , chemical reagents, environmental toxins, cellular material, polymers, proteins, DNA, and the like) is important in many applications, for example, in the fields of biotechnology, analysis, purification, detection, and synthesis, amongst others. Depending on the application, the manipulations may involve accumulating, separating, transporting, positioning, and/or storing the species.

In connection with at least some of these types of manipulations, fluidic systems have been used that are formed from a substrate. The substrate may have a network of channels formed therein in which fluid is contained. The species can be caused to flow through the fluid to different locations on the substrate as desired for a particular application.

In conventional fluidics systems, particularly microfluidics systems, a number of species may be located proximate to the channel walls as they flow through the fluid. This can be the result of normal flow distribution across width of the channel, diffusion within the fluid, and gravitational settling. Such species may adhere to channel walls as a result of non- specific binding. This adherence can prevent the species from reaching their desired location and, thus, can affect the performance of the fluidics system. Furthermore, the buildup of species adhered to the channels walls can restrict flow through the channels. The restriction of flow can especially be problematic at small channel widths. Even in cases in which species do not adhere to the channel walls, species proximate the channel walls may lag behind other species because the wall functioning as a boundary condition for flow.

Summary of the Invention This invention relates to fluidic systems, as well as methods of manufacturing and using the same.

In one aspect, a fluidics system is provided. The system includes a substrate having a surface defining a channel. The surface includes a first region having a first affinity for a fluid and a second region having a second affinity different from the first affinity. The system further includes an a source of an electric or magnetic field. The source is capable of applying the electric or magnetic field to the substrate.

In another aspect, a fluidics system is provided. The system includes a substrate having a surface that defines a channel. The surface that defines the channel includes a first region having a first affinity and a second region having a second affinity different from the first affinity. The surface is able to produce a pinned meniscus in a fluid within the channel.

In another aspect, a fluidics system is provided. The system includes a substrate having a surface that defines a channel. The fluidics system is designed to produce a static potential minimum located within the channel in an electric or magnetic field when the channel contains a fluid and is exposed to a respective electric or magnetic field.

In another aspect, a fluidics system is provided. The system includes a substrate having a surface including a portion that defines a fluid channel and a non-channel portion.

The non-channel portion being coated with an agent able to substantially alter an electric or magnetic field applied to the substrate. The portion that defines the channel being substantially free of the agent.

In another aspect, a method is provided. The method includes adding a fluid to a channel. The fluid carrying a plurality of species. The method further includes applying an electric or a magnetic field to the species to move the species away from the surface that defines the channel.

In another aspect, a method is provided. The method includes passing a fluid laminar through a channel. The fluid carries a species that defines a longitudinal flow distribution width within the fluid in the channel. The method further includes substantially controlling the longitudinal flow distribution width of the species in the fluid.

In another aspect, a method is provided. The method includes applying an electric or magnetic force to a fluid containing a species to produce a concentrated portion of the fluid carrying a majority of the species and a dilute portion of the fluid carrying a minority of the species. The method further includes removing some of the dilute portion of the fluid.

Other advantages, novel features, and aspects of the invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings, which are schematic and which are not intended to be drawn to scale. In the figures, each identical, or substantially similar component that is illustrated in various figures is represented by a single numeral or notation. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention.

Brief Description of the Drawings Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying drawings in which: Figs. 1 and 1B respectively illustrates embodiment of fluidics systems of the invention ; Figs. 2A-2C respectively illustrate different cross-sections of channels formed in substrates used in fluidics systems; Fig. 3 illustrates a substrate that includes a plurality of intersecting channels; Figs. 4A-4F illustrate the localization of a species within a fluid using methods of the present invention; Figs. 5A-5D respectively illustrate various meniscus types formed using methods of the present invention; Figs. 6A-6C respectively illustrate a method that employs a mask in connection with an embodiment of the present invention; Figs. 7A-7C respectively illustrate masks used in different embodiments of the invention; Figs. 8A and 8B respectively illustrate masks used in other embodiments of the invention; Figs. 9A-9E illustrate a method of manufacturing an embodiment of the invention ; Figs. 10A-10C illustrate the flow of a species in an embodiment of the invention ; Fig. 11 is a photocopy of a photomicrograph of a fluid profile created in one embodiment of the invention ; Figs. 12, sections A and B, show methods of the invention used to accumulate (A) or separate (B) a species; Fig. 13 is a graph illustrating an embodiment of the invention used to accumulate or separate a species ; Figs. 14A and 14B show a system used to accumulate or trap species; and Fig. 15, sections a-d, is an illustration of an embodiment of the invention, as compared to a mathematical model.

Detailed Description This invention relates to fluidic systems, as well as methods of manufacturing and using the same. In general, the invention involves manipulating species within a fluid, for example causing species within a fluid to preferentially reside in or migrate to a particular section of the fluid by application of a magnetic and/or electric field to the fluid.

Generally, systems of the invention include a substrate having a surface that defines one or more channels. The channels contain a fluid (e. g. , water) into which different species<BR> (e. g. , biological or chemical materials) are introduced. The species are generally caused to flow through the channels to a desired location within the system. As described further below, the species can be attracted away from the channel walls using magnetic or electric fields while they flow through the channels. This attraction can enhance the flow of species through the system and can limit problems associated with the species adhering to channel walls such as increased drag or clogging channels. The systems can be used to perform various functions, for example, the separation or accumulation of different species. The systems are particularly well-suited for use in microfluidic applications which include channels with relatively small widths, and detection/purification of minute quantities of species in large volumes of fluids.

A static electric or magnetic field potential minimum can be produced at an interface between two fluids using various embodiments of this invention, to which an electrically or magnetically susceptible species is attracted. By creating the static potential minimum at the interface, the potential minimum can be located inside the channel, rather than along a wall or surface of the channel. Thus, the invention is able to move the species away from the walls of the channel, for example, as shown in Fig. 11. By drawing the species away from the walls, the species may be, for example, concentrated within a particular region of the fluid.

The species may then be collected, for example, for detection purposes or for purification of the species or the fluid. Drawing the species away from the walls may also reduce nonspecific binding of the species within the channel, which may, for example, reduce adsorption of the species within the fluidics system, or result in improved flow properties of the fluid, for example, due to lower surface drag.

Preferably, the field potential minimum can be created in any channel where the surface tension is dominant over the gravitational force, for example, a channel of less than about a few centimeters in width for air and water. However, it should be understood that in certain embodiments of the invention, wider channel widths are possible.

The potential minimum can be created by producing a curved interface between at least two incompatible fluids at an interface, and applying a substantially homogeneous field at least to the area of the interface, where the potential minimum is created at the peak (or minimum, depending on the perspective) of the curved interface. In one aspect, the invention involves application of an electric field that is substantially homogeneous in a plane tangent to the peak (or minimum) of the curved meniscus, with the field in the third axis (the axis perpendicular to the plane being irrelevant. A substantially homogeneous magnetic field is applied in the plane tangent to the peak (or minimum) of the curved meniscus and increases monotonically in the third axes perpendicular to the peak (or minimum) of the curved meniscus'. Application of fields to practice the invention as described herein, including fields as described specifically above, is routine to those of ordinary skill in the art.

The curved interface can be produced, for example, using a pinned meniscus, where differences in affinities between regions of channel walls cause a pinned meniscus to form within a channel.

A potential minimum can also be created by producing a field that attracts species to a specific region of a fluid/fluid interface, regardless of any shape of the interface, thus, a minimum in energy can be created in connection with a fluid/fluid interface that is not necessarily curved, or is not curved to the extent that a substantially homogeneous field (as described above) creates a minimum energy position for any species within either fluid. For example, an applied homogeneous field can be partially masked to create a potential minimum within the interface.

As used herein,"static,"in referring to electric or magnetic fields, refers to electric or magnetic fields that are not periodically variable with respect to time, at least on the timescale of concentration, separation, etc. of species in accordance with the invention. Physically, a static electric or magnetic field potential minimum may be created when there is a difference in curvature between the static field and the fluid. This difference in curvature between may be created by a variety of methods. As mentioned above, for example, in one set of embodiments, a uniform electric or magnetic field may be applied to a system where the surface of the fluid is substantially curved. In another set of embodiments, a non-uniform or "curved"electric or magnetic field may be applied such that the applied field creates a local potential minimum region within the surface of the fluid. In still other embodiments, a combination of a curved fluid and a curved field may be used, for example, by a combination of techniques described herein.

Referring now to Fig. 1A, a fluidics system 10 uses an electric field to manipulate a species carried by a fluid according to one embodiment of the invention. In this figure, fluidics system 10 includes substrate 11 having channels 12 formed thereon and/or therein. It is to be understood that wherever channels are described in connection with any embodiment of the invention, channels can take the form of any channels as broadly defined below. The substrate 11 is placed between plates of a capacitor 13 which generates the electric field, in the embodiment illustrated.

Fig. 1B illustrates an embodiment similar to Fig. 1A except that a magnetic field is used to manipulate a species carried by a fluid. In this embodiment, magnet 14 is used to apply the magnetic field to substrate 11.

Fig. 3 further illustrates substrate 11 according to one embodiment of the present invention. As shown, substrate 11 illustrates a plurality of intersecting channels 12, which may contain fluid 41 carrying species 42. The channels are designed to carry species 42 to different locations as desired for a particular application. Other fluids or species may also be present within channels 12 as well. It should be understood that, in other embodiments, the substrate may include only a single channel, and in other embodiments any number of channels, any of which may intersect other channels (allowing fluid flow between channels) or be separated from other channels (isolating fluid flow within that channel).

A"fluidics"system is any system that contains at least one channel for fluid flow.

The system may use flowing gases or liquids to perform various functions or manipulations, in some cases without the use of moving or other mechanical parts. As used herein, "microfluidics"generally refers to fluidics systems that have a characteristic dimension that is on the border of micrometers, i. e. , < 1 cm. For example, any one of the length, width, or height of a channel of the microfluidics system is less than 1 cm (or other dimensions, described below).

In one set of embodiments, a static field potential minimum can be created by producing a curved interface between two fluids (e. g. , water and air) and applying a substantially homogeneous electric or magnetic field. In Figs. 5A-5D, a curved interface is formed between two fluids 51,52. Either fluid may carry species 41. The curved interface, also referred to herein as the"meniscus, "may be produced by any technique. The meniscus may have any shape, for example, flat, concave up (e. g., Fig. 5A), or concave down (e. g., Fig.

5B) (of course, "up"and"down"depends upon perspective; it is to be understood that, e. g. in a two-fluid system, a curved interface can have a maximum, or minimum, from the perspective of either fluid). The shape of the meniscus is related to the difference in affinity between the two fluids and the wall of the channel containing the fluids, as well as the relative volumes of the two fluids within the channel. As used herein, the"affinity"of a fluid refers to the hydrophobic/hydrophilic properties of the fluid, i. e. , a measure of attraction of the fluid to water or other charged solutions (a polar or a"hydrophilic"fluid), or to organic or uncharged solutions (a non-polar or a"hydrophobic"fluid). One technique for determining the affinity of a fluid is to measure the partitioning of the fluid between an organic solvent and an aqueous solvent, for example, between n-octanol and water. Other techniques such as contact angle measurements on various surfaces can be useful, and are known to those skilled in the art.

Examples of embodiments having curved meniscuses are illustrated in Figs. 4A-4F.

The meniscus may have any curvature, for example, concave up (e. g., Fig. 4A) or concave down (e. g., Fig. 4D). In Fig. 4A, fluid 41 within channel 40 contains species 42 homogeneously dispersed therein. Species 42 may be any electrically or magnetically susceptible species. In Fig. 4B, a uniform electric or magnetic field 43 is applied. Field 43, in this embodiment, causes the species to be attracted towards static potential minimum 44 created in the peak of the meniscus. In Fig. 4C, species 42 have been concentrated near static potential minimum 44, creating a non-homogeneous fluid, where a portion of the fluid has been enriched with species 42.

In some embodiments, the curved meniscus may be a pinned meniscus, as illustrated in Figs. 5C and 5D. A"pinned meniscus"is a meniscus that has generally fixed endpoints, such that a change in volume of fluid 52 alters the curvature of meniscus, for example, from a negative curvature to a positive curvature, rather than moves the endpoints of the meniscus.

As illustrated in Figs. 5C and 5D, a pinned meniscus formed in channel 40 can range between a concave up profile, as shown in Fig. 5C, and a concave down profile, as shown in Fig. SD, for example, by altering the volume of fluid within channel 40. The endpoints of the meniscus do not change between the concave up and concave down profiles. The volume of fluid 52 within channel 40 may be altered by any suitable means, for example, by changing the volume of fluid directly, or by changing the flow rate of fluid within channel 40, or the pressure drop across channel 40. In the embodiment illustrated in Figs. 5C and 5D, fluid 51 is a gas that can leave channel 40 upon a change in the volume of fluid 51. However, other embodiments having pinned meniscuses are also possible. For example, channel 40 may be a covered channel (e. g. , as is shown in Figs. 2C and 2D), or fluid 51 may be a gas or a liquid.

In covered channel embodiments, the volume of gas can be compressed to increase the volume of liquid therein.

Any pinned meniscus may be used in accordance with this invention. For example, the pinned meniscus may be caused by the physical geometry of the channel, or, in certain embodiments, by the construction of channels having a first region having one affinity, and a second region having an affinity different from the first region, as shown in Fig. 5C. In some embodiments, a pinned meniscus may be formed at the uppermost portion of an open channel, for example, a channel as is shown in Fig. 2A. The pinned meniscus forms when the endpoints of the meniscus reach the rim of the channel. The pinned meniscus may also be created using a change in affinity along the channel wall to"pin"the meniscus at a certain location, for example at a junction between two regions having different affinities. For example, the lower region may be a hydrophilic region, while the upper region may be a hydrophobic region. Note that these terms are used in a relative sense; the lower region may be more hydrophobic or hydrophilic compared to the upper region, but both regions may have a high affinity for water and be considered to be hydrophilic surfaces.

An illustrative example of a pinned meniscus formed at a junction is as follows. In a channel having a lower relatively hydrophilic region and an upper relatively hydrophobic region, if a hydrophilic fluid in the channel, the meniscus of the hydrophilic fluid normally assumes a concave up shape when in contact with the lower hydrophilic region, as is shown in Fig. 5C. However, as more fluid is added to the channel, the edge of the meniscus eventually reaches the junction between the hydrophilic surface and the hydrophobic surface.

The meniscus is unable to rise past the junction, as the hydrophilic fluid is repelled by the hydrophobic surface. Thus, the meniscus is said to be"pinned"at the junction. As the edge of the meniscus cannot rise beyond the junction, the addition of more fluid causes the meniscus to flatten and eventually form a concave down profile, as is shown in Fig. 5D.

The junction between the two regions having different affinities may be created in any suitable fashion. For example, two substrates having different affinities may be placed, or adhered, together to form a single substrate. Channels may be formed in one or both of the substrates, for example, as shown in Figs. 2B and 2C. As another example, a channel may be formed in a single substrate, but a portion of the channel may be coated with an agent that has a different affinity than the substrate. Any agent able to coat the channel and alter the affinity of the channel may be used, for example, a silicon coating, a fluorocarbon polymer such as polytetrafluoroethylene, a surfactant, an ionic layer, or the like.

In one set of embodiments, a static field potential minimum can be created by producing an inhomogeneous or"curved"electric or magnetic field. This field may have a region of maximum field strength. The inhomogeneous electric or magnetic field may be created by any suitable technique, for example, by the application of a non-uniform field source, or by the application of a homogenous source that is altered or"masked"to create the curved field. For example, when a mask 60 is able to substantially block an applied field, a curved field will be created near holes or other defects within the mask as shown in the electric or magnetic contours of Figs. 6B and 6C. The curvature of the field around the hole may be affected by the thickness or material of the mask, or by the size of the hole.

Magnetically or electrically susceptible species in a fluid near the hole will be drawn towards the static field potential minimum, as is indicated by arrows 61 in Fig. 6A.

The mask may be designed to conform with the arrangement of the channels. For example, mask 60 may be positioned at the top of the channels in an open arrangement, as shown in Fig. 7A. In other embodiments, the mask may be an integral part of the substrate.

For example, mask 60 may be positioned at the top of the channels or positioned to intersect with at least a portion of channels 40 within the substrate, as illustrated in Figs. 7B and 7C, respectively. A field produced using a mask having this configuration will substantially conform to the shapes and positions of the channels. Thus, in a complex series of channels, for example, straight channels, curved channels, or channels with different sizes, the resulting field produced by the mask will conform to these channels.

The mask may be created out of any suitable material able to substantially block or alter an applied electric or magnetic field. For example, if the applied field is an electric field, then any material that alters the electric field can be used, such as copper or silver. If the applied field is a magnetic field, then any material that alters the magnetic field can be used, for example, a ferromagnetic substance such as iron or nickel. Combinations or alloys of these materials can be used as well, for example, to achieve a certain field intensity. The mask may have any dimension and be formed by any technique, for example, by sputtering the mask on the substrate, or by"painting"a thin coating of the material on the substrate to form the mask.

One example of a method able to create a mask that substantially conforms to the channels is illustrated in Fig. 9. In Fig. 9A, a substrate 11 having channels formed therein is fashioned out of a mold 90. The mold is then removed in Fig. 9B. In Fig. 9C, the channels are filled with a discardable material 91, for example, a plastic. A layer of a field-altering material 92 is then placed on top, for example, by sputtering, spraying, or painting, depending on the nature of the material. This is illustrated in Fig. 9D. The discardable material is then removed, for example, physically or by burning or decomposing the material, as shown in Fig. 9E. Field-altering material 92 that was attached to discardable material 91 is removed during this process, leaving behind a mask 93 having holes 94 that substantially conforms to the shape of the channels formed within substrate 11. Additional processing steps may occur afterwards, for instance, covering the substrate with other layers of material (e. g. , to produce closed channels as is shown in Figs. 7B and 7C).

In another set of embodiments, a mask may be used to create an inhomogeneous electric or magnetic field, but the substrate may not have channels formed therein. For example, in Fig. 8A, mask 60 is placed near substrate 11, and the presence of the masked field on species 42 within fluid 41 defines specific channels of fluid located on top of substrate 11. In another set of embodiments, as shown in Fig. 8B, mask 60 may be placed near fluid 41 positioned on a substrate, which may be, for example, a thin film. The masked field causes regions of localized field maxima to be formed near holes 94 within mask 60.

Species 42 that are electrically or magnetically susceptible are then attracted to the maxima.

In any of the embodiments described herein, fluidics channels 12 may be used to transport a fluid carrying a species through fluidics system 10. Channels 12 may include any region within the system through which fluid flows or may be contained within, such as a reaction chamber or"cell. "As used herein, "channel"refers to any region within system 10 through which a fluid can flow, including, but not limited to, channels and other passageways, reaction chambers or cells, or the like, for example, as illustrated in Fig. 3.

Channels may be sealed at one end, be open at both ends, or may have a plurality of inlets and outlets. Multiple inlets and outlets within channels 12 may be able to handle one fluid or several fluids simultaneously. Channels 12 may further be connected to other components within fluidics system 10 having other functions. Channels 12 may also have different shapes or configurations, which include tapered channels or channels with enlarged regions.

In some cases, channels 12 may include a closed end that defines, for example, an enlarged region that may have a width greater than that of the length of the channel. Such enlarged regions may be used, for example, storing or temporary holding of various species.

As used herein, the term"substrate"refers to any article usable in fluidics applications in and/or on which a channel may be formed. The substrate may be a substantially planar component (e. g. , a chip), a tube, a network of tubes, and the like. In one set of embodiments,<BR> the substrate is a chip. Suitable substrate materials include semiconductor (e. g. , silicon) materials, glass materials, or polymeric materials (e. g, polydimethylsiloxane). Substrate 11 may have a number of layers formed thereupon including oxide layers, metallic layers (which may be able to alter electric or magnetic fields applied to the substrate), and the like. The dimensions of substrate 11 may be determined, in part, by the application. In some cases, the surface area of substrate is less than about 10 cm2 ; in others less than about 1 cm2 ; and in <BR> <BR> others less than about 1 mm2. The maximum dimension (e. g. , length or width) of substrate 14 may be less than about 10 cm, 5 cm, in other cases less than 5 mm; and, in other cases, less than 1 mm.

In some embodiments, substrate 11 is free of patterned wires or other conductive pathways. Such substrates may be easier to produce and may avoid problems of heat generation as compared to substrates that include such wires.

Fluidic channels 12 may have a variety of different dimensions, as required for a particular application of system 10. Certain systems and methods of the invention may be particularly useful when used in connection with channels that have relatively small cross- <BR> <BR> sectional dimensions (i. e. , channel width). For example, in some cases, channel widths are less than about 5 cm, in some cases less than about 1 mm. In other cases, shorter channel widths are desired, such as widths of less than about 500 um, in some cases less than about 100 um, in some cases less than about 50 um, and in some cases less than about 10 u. m.

"Width", in this context, means the smallest cross-sectional dimension of the channel at least one location along its length, in some cases along its entire length. Shorter channel widths may be desired, for example, when a pattern requires a large number of channels. Generally, channel lengths are less than about 5-10 cm, but need not be. Shorter channel lengths may be utilized in some cases, such as channels with lengths of less than about 5 mm, or less than about 0.5 mm. In some embodiments, system 10 may include a number of channels 12 which have different lengths or widths. Channels 12 may be open and exposed to the atmosphere (see, for example, Fig. 2A), or the channels may be covered, for example, with a flat upper layer of material (e. g. , as shown in Fig. 2B). The channels may have any cross-sectional shape, for example, a square, a rectangle, a circle, a triangle, a trapezoid, a polygon, or the lilce, and different channels in a substrate may not all have the same cross-sectional shape (e. g. , as is shown in Fig. 2C). The channels may be free of features extending from the channel surface into the channel (for example, magnetic posts), which can facilitate construction and use.

The fluids in channel 12 may be any two fluids able to form a meniscus, preferably two immiscible fluids. For example, the fluids may include a liquid-gas system, such as air and water, or a liquid-liquid system, such as water and carbon tetrachloride. Any two-phase system may be used, preferably where the two fluids have different affinities. Suitable fluids include water, non-aqueous fluids, or biological fluids, as well as mixtures and solutions thereof. Additives may be added to the fluid to promote dispersion or for other reasons.

In some cases, fluids are pumped through fluidics channels 12. For example, in some embodiments, capillary action is used to draw fluid through fluidics channels 12. In other embodiments, the fluid is drawn through fluidics channels 12 using gravitational flow or siphoning techniques. Alternatively, pressure-induced methods to cause fluid flow are used in some embodiments of the invention. For example, a syringe pump or a peristaltic pump may be used to drive fluid through fluidics channels 12. In still other embodiments, fluid flow is electrically induced. For example, fluids containing charged particles or species move preferentially in a direction under the influence of an applied electric field.

Alternatively, fluid flow may be generated using electroosmotic techniques.

It should be understood that, however, fluid flow is not required in all embodiments of the present invention. In some cases, the fluid remains relatively stagnant within the fluidics system. In these cases, the species may be caused to flow through the fluid.

In some embodiments, when a curved meniscus is generated, the maximum width of channel 12 may be about several times the width at which gravitational forces on the fluid begins to dominate over the surface tension. At channel widths below this length, the surface tension dominates over gravity, allowing a curved meniscus to be maintained throughout the width of the channel. The maximum width of the channel in some of these embodiments may be estimated by using the following relation: where y is the surface tension, Ap is the density difference between the two fluids within the channel, g is the gravitational acceleration constant, and x is the capillary length scale. For a water-air interface, x is approximately 3-4 mm, so that the width of the channel can be any width which is less than or equal to several times this value, for example, a channel of about 100 urn or 1 um in width. For other fluid compositions, the maximum width may have other values, which can be determined using the above equation. For example, if the two fluids have a small density difference, then x may be on the order of centimeters or tens of centimeters; conversely, if the density difference between the two fluids is large, x may have small values, for example, on the order of micrometers or nanometers. At smaller length scales, the surface tension may be very large relative to the gravitational forces, such that gravity may be ignored at these scales, and the channels and the fluids contained therein may have any orientation.

Species 42 can be any species susceptible to an electric field or a magnetic field. As used herein, a species that is"susceptible"to an applied field, such as an electric or magnetic field, is a species that experiences a substantial force able to alter the movement of the species, when the species is placed in an electric or a magnetic field. In many cases, the species is a chemical or biological material or molecule. Typical examples include chemical reagents, cellular material, nucleic acids, proteins, polypeptides, lipids, carbohydrates, and polymers including synthetic polymers. Any charged molecule, including charged biological molecules such as proteins or DNA, may be susceptible to external electric fields. Examples of species susceptible to magnetic fields include paramagnetically, superparamagnetically, or ferromagnetically species, such as copper, silver, iron, nickel or neodymium. In some applications, more than one type of species may be manipulated at the same time using system 10, or the susceptible species may further be attached to a nonsusceptible species, for example, as a molecular"tag." In some cases, particles can be used as species 42, or species 42 may be attached to particles. The particles may have a variety of shapes and sizes depending on the application.

In some embodiments, a substantially spherical particle (i. e. , a bead) may be preferred, for example, a bead having a diameter of less than 100 um. However, larger size particles may also be used if desired. In some embodiments, the particle size is less than about 10 um ; in others, the particle size is less than about 1 um ; in others less than about 100 nm. In some embodiments the particle size is between about 1 um and about 10 um. Smaller particle sizes may be desired, for example, in systems that have small channel widths.

Any electrical or magnetic field may be used in accordance with this invention. For example, the electrical field can be created by placing the channels between two plates of a parallel-plate capacitor, as is shown in Fig. 1A, or by placing the channels near a charged object. Magnetic fields can be created, for example, by placing the channels near an external permanent magnet is shown in Fig. 1B, or an electromagnet, which may allow the field to be activated, deactivated, or altered as desired. In a few embodiments, it is preferable to have an external field source. The application of an external field, such as a magnetic or an electric field, thus does not require energy input to the channels or the substrate. In these embodiments, heating caused by the production of the electric or magnetic field would not occur within or near the channels. The lack of heating may be advantageous in certain applications such as when the species may be temperature sensitive. In these embodiments, other effects, for example, side chemical reactions, also would not affect the channels.

In certain embodiments, the electric or magnetic field may be maintained with minimal or negligible power requirements. For example, an external permanent magnet creates a magnetic field without requiring an additional energy source. Similarly, in a parallel-plate capacitor, the electric field within the capacitor may be maintained without substantial power requirements, although minimal power may be needed to maintain the charge across the parallel-plate capacitor to control for leakage of charge.

A substantially homogenous or uniform electric field may be created by any suitable technique. For example, a substantially homogeneous electric field may be created in a parallel-plate capacitor (although some edge effects may be present). Other arrangements able to create a substantially uniform electric field may also be used with the present invention. Similarly, a substantially homogeneous or uniform magnetic field may be produced using any suitable technique. For example, a substantially homogeneous magnetic field may be created next to a permanent magnet or an electromagnetic coil.

System 10 may be used in any system where manipulation of a species may be desired. Such manipulations may include, but are not limited to, directing, transporting, storing, positioning, confining, separating, mixing, sorting, immobilization, trapping, segregating, filtration, assaying, purifying, concentrating, accumulating or detection. Other manipulations may include reducing fluid drag, controlling the flow distribution of the species, or trapping or releasing the species.

For example, an embodiment of the invention may be used to control or maintain the flow distribution of a species 42 within fluid 41. In certain embodiments of the invention, the channels may be filled with fluids moving in laminar flow with a parabolic profile, as illustrated in Fig. 10A. Under these conditions, fluids near the edges of the channel move slower and the fluids in the center of the channel move more quickly. The flow distribution of species 42 in this fluid thus increases due to the distribution in fluid velocities across the channel. For example, in Fig. 1 OB, a pulse of a species that initially starts out with a narrow distribution becomes broader and more diluted over time, as the particles are separated due to the effects of laminar flow within the channel.

However, if an electric or a magnetic field is applied to attract species 42 to the center of the channel, for example, as shown in Fig. l OC, as the flow velocity near the center of the channel is approximately constant, the fluid does not separate quickly during flow. By varying the field, the distribution of species along the longitudinal or transverse directions may be controlled, for example, so that an increase in width of greater than a certain value does not occur, e. g. , a spreading of the species to twice the starting width. For example, in Fig. 10C, the flow distribution width is maintained at a substantially constant width, even for longer distances of flow. As used herein, "longer distances"generally refers to distances that<BR> are greater than the characteristic size of the channel, i. e. , a distance that is greater than the width or height of the channel.

In another example, an embodiment of the invention may be used as an accumulator.

An accumulator is a device that is able to concentrate a species in a fluid without physically trapping or immobilizing the species. An example of an accumulator having a closed-loop path is shown in Figs. 14A and 14B. Fig. 14B is a cross-sectional illustration taken along line B-B of Fig. 14A.. In this embodiment, a fluid 41 carrying species 42 enters accumulator 141 through inlet 140. The accumulator is constructed such that the application of an electric or magnetic field (not shown) produces a static potential minimum 44 at the meniscus of the fluid within the accumulator. Species 42 is attracted to potential minimum 44, separating fluid 41 into a region 142 concentrated with species 42 and a diluted region 143. In the embodiment illustrated in Figs. 14A and 14B, a portion of diluted fluid 143 may be withdrawn, leaving the concentrated fluid 142 carrying species 42 within the accumulator.

By this technique, the concentration of species 42 within fluid 41 may be increased as desired. Other configurations able to accumulate a species are also contemplated, for example, having multiple fluids or species contained therein.

In another set of embodiments, the invention may be used to alternately trap or release a species within a fluid. For example, as illustrated in Fig. 12A, species 42 within fluid 41 are attracted to a static potential minimum 44 created by an applied field (not shown), located at the peak of the meniscus of fluid 41. However, upon a change in the curvature of the meniscus, for example, by altering the flowrate or the pressure of fluid 41, the curvature may be reversed, such that the particles are now drawn to the sides of the channel, where the static potential minimum now occurs. This process may also be reversed. For example, species 41 may initially be nonspecifically bound to the edges of the channel, then transported away from the walls upon a change in fluid volume, for example, for concentration or detection purposes.

The function and advantages of these and other embodiments of the present invention will be more fully understood from the following examples. These examples are intended to be illustrative in nature and are not considered to be limiting the scope of the invention.

Example 1 This example illustrates theoretical calculations corresponding to an embodiment of the invention. In this example, a uniformly applied magnetic field, together with a curved fluid interface, was shown to be able to control movement of a species within a fluid within a channel.

A curved fluid interface was achieved by assuming an interface curvature between two immiscible fluids, as defined by the Young-Laplace equation: AP =r (X/R, +l/R2), where AP, y, and R are respectively the pressure difference across the fluid surface, the surface tension, and the surface radii of curvature for fluid 1 and fluid 2, respectively. The interface was assumed to be pinned at a channel wall boundary, for example between a hydrophobic surface and a hydrophilic surface, as shown in Figs. 5C and 5D. The pressure difference within the channel set the liquid-wall contact angle 0. The surface curvature of the interface could be readily controlled through, for example, controlling the fluid flow velocity, the pressure within the channel, the channel width, or the like. For example, in a typical system such as an air-water interface (pater 72 dyn/cm), a microfluidic channel width on the order of approximately 10-100 llm would require a pressure difference of approximately 1- 10% of atmospheric pressure, allowing the liquid-wall contact angle to be controlled as desired. For 9 > 90°, the interface bulges upward in the center, creating a local electromagnetic potential minimum where the magnetic species would be attracted to, such as illustrated in Fig. 12A. Conversely, for 0 < 90°, as is shown in Fig. 12B, the interface would be lower along the center than at the edge, and particles would be attracted towards the channel walls, where the electromagnetic potential minimum would be located.

In the case of an infinitely long channel, or equivalently, of a channel gently curved into an annular ring of large radius such as shown in Fig. 15, implicitly solving the following differential equation yields the surface profile z (x) within the channel: Apgz (x) + const =y z" (x)/ (1 + z' (x) 2)" where Ap is the density difference of the two fluids within the channel, g is the gravitational acceleration constant, and the primes indicate derivatives with respect to the horizontal coordinate x.

Figs. 15A and 15B illustrate results based on these calculations. Fig. 15A corresponds to a situation in which 0 > 90° (i. e. , where the interface is bulges upward in the<BR> center); Fig. 15B corresponds to a situation in which 6 < 90° (i. e. , where the interface bends down in the center). As shown in these figures, for an annular ring channel of approximately 25 mm in diameter, a 50 mm-diameter uniformly magnetized disk magnet (or, equivalently, a current-curing coil) gave negligible field curvature over the ring and the area enclosed by it; thus, the magnetic field, as applied to the substrate, was substantially uniform.

The field of such a magnet interacting with the curved interface was numerically calculated over the interface, as defined by a solution of the surface tension equation given above. The magnitude of the magnetic field is shown in Figs. 15A and 15B as a density plot overlaid on the fluid interface surface. In these figures, darker regions indicate magnetic fields of higher field strength, to which magnetic particles or other species would be attracted.

In Fig. 15A, the region of maximum field strength corresponds to a annular region located between the surface of the channel. Conversely, in Fig. l 5B, the regions of maximum field strength are created immediately next to the surface of the channel.

Thus, this example illustrates theoretical calculations corresponding to an embodiment of the invention.

Example 2 This example illustrates an embodiment of the invention used to concentrate particles in a fluid. This apparatus mimics the theoretical calculations described in Example 1.

A ring channel was fabricated out of polydimethylsiloxane (PDMS). A recirculating flow of water was set up in the ring channel with flow velocities ranging from 1 mm/s to several cm/s. Superparamagnetic 4.5 um diameter beads were dispersed within the recirculating flow. These bead sizes readily allowed optical detection of their location within the fluid. By restricting the position of the beads to the fluid interface within the ring, imaging was possible with minimal requirements on the optical depth of the field, as shown in Figs. 15C and 15D. Fig. 13A is a figure showing the number of magnetic beads detected within the ring as a function of time. Over this time (about 1000 s), the observed bead counts showed no measurable decay, with no loss due to outward diffusion, adhesion to the side walls, or gravitational settling. The beads were confined about the channel center, within a defined width, allowing accurate control over longitudinal spreading due to Poiseuille flow as is shown in Fig. 15C. The application of higher magnetic fields gave tighter confinement of the beads within the channel, which focused the particles more tightly and created a particle accumulator able to concentrate the particles within the channel.

In Fig. 13B, a similar experiment was performed, but the flow rate was altered at a time of approximately 700 s, altering the curvature of the fluid within the channel from a positive curvature (A > 90°) to a negative one (0 < 90°). As can be seen in Fig. 13B, the number of particles flowing within the channel rapidly decreased to negligible levels upon a change in curvature. Thus, this embodiment illustrates that this invention can also be used to filter or separate a species in a fluid.

This example therefore illustrates that an embodiment of the invention can be used to concentrate or separate particles in a fluid. Furthermore, the data in this example are consistent with the theoretical calculations described in Example 1.

While several embodiments of the invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and structures for performing the functions and/or obtaining the results or advantages described herein, and each of such variations or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art would readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that actual parameters, dimensions, materials, and configurations will depend upon specific applications for which the teachings of the present invention are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described. The present invention is directed to each individual feature, system, material and/or method described herein. In addition, any combination of two or more such features, systems, materials and/or methods, if such features, systems, materials and/or methods are not mutually inconsistent, is included within the scope of the present invention. In the claims, all transitional phrases or phrases of inclusion, such as"comprising,""including,""having,""containing,"and the like are to be understood to be open-ended, i. e. to mean"including but not limited to. "Only the transitional phrases or phrases of inclusion"consisting of'and"consisting essentially of'are to be interpreted as closed or semi-closed phrases, respectively.

What is claimed is: