STOP STRUCTURE FOR MICROFLUIDIC DEVICE

This invention relates to stop structures for microfluidic devices. In particular it relates to three dimensional stop structures.

BACKGROUND TO THE INVENTION

A novel microfluidic device is described in our co-pending international patent application number PCT/AU2005/001341. This device and other known microfluidic devices move fluids through microchannels. The forces acting upon the moving fluids are complex and include capillary forces (i.e. wall/fluid interaction) as well as pressure, electrohydrodynamical and magnetic forces. The driving force is provided by some form of pump such as a peristaltic pump, a ferrofluidic pump, electroosmotic pump, thermopneumatic pump or a diaphragm pump. In some applications the driving force is generated locally, for example by a capillary driving force. In most cases, structures are required to help control the flow of fluid through the microchannels in addition to the control provided by the pump, if useful devices are to be constructed.

One form of device for flow control is a mechanical valve which commonly is in the form of a membrane, pin or ball. These type of moving part structures can be problematic in microchannel devices as they typically have leak problems and introduce significant dead volumes. They also tend to fatigue with repeated use which leads to failure.

Another approach to flow control includes using chemical and/or other materials to physically block flow. Typical physical flow control solutions include wax plugs, hydrogels, magneto-rheological fluids and electro-rheological fluids. This approach is problematic for microassay applications as the chemicals can cause contamination of the microassay. Furthermore, the performance of these solutions is usually microassay dependent, leading to non-robust solutions.

Flow control may also be affected by using chemical and/or physical modifications to change the local surface energy of a capillary. These solutions

are commonly referred to as passive valves. A typical example is described in United States published patent application number 2002/0003001. This patent application describes the use of a hydrophobic coating to increase surface tension. Chemical modifications can lead to unwanted binding of reagents which changes the assay. This is a very unwanted effect since handled volumes are small and unspecific binding is one of the largest challenges within the field of microfluidics. Similarly, physical changes generally lead to increased surface energy which leads to the same effects as occurs for the chemical modifications.

A second shortcoming of the surface energy solution is that the free surface energy density of the wall-fluid contact has a lower limit. For fluids with a low free surface energy density, no large contact angle will be formed. (The contact angles can be calculated via the Young-Laplace equation using the free surface energy densities of the solid-gas, gas-liquid and liquid-solid interaction. The gas can in principle be a second liquid.) Since no large contact angle can be formed, no passive chemical valve can be generated. United States published patent application number 2004/0028566 includes a description of the effect of hydrophobic and hydrophilic materials on contact angle, which description is incorporated herein by reference.

In our co-pending application mentioned above, we describe passive stop structures to control movement of fluids. We describe the passive stop structures in the following terms, "The bioassay chip incorporates a number of passive stop structures allowing the containment of reagents in individual chambers. In general terms, a minimum cross-sectional dimension of the stop structure is sufficiently smaller than a minimum cross-sectional dimension of the second channel so that differential capillary forces prevent wicking of fluid from the first channel, through the stop structure, and into the second channel when there is no fluid in the second channel".

As the range of applications of microchannel devices expands the demands on control of movement of fluid in the microchannels become more

severe. The inventors have found that the known structures and approaches are not adequate.

We have recently filed Australian provisional patent application number 2007901390 that describes a novel stop structure. It has been found that the novel stop structure provides particular advantage when combined in a series of stop structures. Although this concept was disclosed in the earlier specification it is described in greater detail below.

OBJECT OF THE INVENTION It is an object of the present invention to provide a structure for control of movement of fluid in a microchannel.

Further objects will be evident from the following description.

DISCLOSURE OF THE INVENTION In one form, although it need not be the only or indeed the broadest form, the invention resides in a stop structure for a microfluidic device comprising: a passage in fluid connection with a microchannel wherein at an intersection of the passage and the microchannel the passage widens in all directions orthogonal to the direction of the passage. Suitably the change in dimension at the intersection between the passage and the microchannel is sufficient to promote formation of a meniscus of a fluid in the passage.

Preferably an angle between a wall of the passage and an adjoining wall of the microchannel is nominally at least 225 degrees. Suitably there are two microchannels joined by the passage.

The passage is suitably a hole. In another form the passage is a tube that extends beyond the surface of the microchannel.

The preferred shape of the passage is round but other shapes would also be suitable.

In a further form the invention resides in a method of manufacturing a stop structure in a microfluidic device including the steps of: forming a microchannel in a substrate; and forming a passage intersecting the microchannel wherein at an intersection of the passage and the microchannel the passage widens in all directions orthogonal to the direction of the passage.

In another form the invention resides in a structure for control of movement of fluid in a microfluidic device comprising: a series of stop structures in fluid connection wherein each stop structure in the series comprises a passage providing fluid connection between a pair of microchannels, wherein at an intersection of the passage and at least one microchannel of the pair of microchannels the passage widens in all directions orthogonal to the direction of the passage, and wherein adjacent stop structures share a common microchannel.

Suitably the passages of the stop structures in the series are parallel to each other.

In one form the passage may suitably be a hole formed between adjacent microchannels. In another form the passage may be a tube that extends beyond the surface at least one of the microchannels.

In a further form the invention resides in a method of manufacturing a structure for control of movement of fluid in a microfluidic device including the steps of: forming at least a first microchannel in one part of a substrate; forming at least a second microchannel in another part of the substrate; and forming a series of stop structures connecting the first and second microchannels, each stop structure comprising a passage intersecting an end of the first microchannel and an end of the second microchannel wherein at an

intersection of the passage and the microchannel the passage widens in all directions orthogonal to the direction of the passage.

BRIEF DETAILS OF THE DRAWINGS To assist in understanding the invention preferred embodiments will now be described with reference to the attached figures in which:

Fig 1 is a schematic of a first stop structure in a series of stop structures according to a first embodiment of the invention showing a cross-sectional side view (1a), a cross-sectional end view (1b) and a plan view (1c); Fig 2 shows the stop structure of Fig 1 with a fluid;

Fig 3 is a schematic of a stop structure according to a second embodiment of the invention;

Fig 4 is a schematic of a stop structure according to a third embodiment of the invention; Fig 5 shows the stop structure of Fig 4 with a fluid;

Fig 6 is a schematic of a stop structure according to a fourth embodiment of the invention;

Fig 7 shows the stop structure of Fig 6 with a fluid;

Fig 8 is a perspective view of a structure for control of movement of fluid in a microfluidic device comprising a series of three stop structures according to a fifth embodiment of the invention; and

Fig 9 shows a side view of the stop structure of Fig 8.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In describing different embodiments of the present invention common reference numerals are used to describe like features.

Referring to Fig 1 there is shown a structure for control of movement of fluid in a microfluidic device. The structure comprises a single stop structure in a microfluidic device 10 having a first microchannel 11 in fluid connection with a second microchannel 12 via a passage 13. The microchannels 11, 12 are connected by the passage 13 that extends from the first microchannel 11 to the second microchannel 12. Fig 1a shows a side elevation that indicates that the microchannels 11 , 12 continue to complete the microfluidic device. The passage 13 and the second microchannel 12 form a stop structure when fluid flows from the first microchannel 11 to the second microchannel 12. When the fluid flows in the opposite direction a stop structure is formed by the passage 13 and the first microchannel 11. The structure therefore provides for bi-directional control of movement of fluid in the microfluidic device.

As is evident in Fig 1 , the first microchannel 11 is formed on one side of the microfluidic device 10 and the second microchannel 12 is formed on the other side. The passage 13 therefore is constructed to pass through the microfluidic device 10.

The microchannels 11 , 12 extend beyond the intersection with, and are wider than, the passage 13 so that a nominally 270 degree corner is formed all around the passage 13. These structures constitute sharp edges that promote surface tension within fluid 20 that flows through continuing microchannel 11 and into the passage 13. The large angle between all walls of the passage 13 and walls of the microchannel 12 means that creep of the fluid along the wall is virtually eliminated. This is contrasted with prior art structures which are essentially two dimensional and allow fluid creep along the "floor" and "ce ^' ling" of the passive stop structure.

Although a sharp 270 degree corner is depicted in the figures it will be appreciated that manufacturing techniques may not produce such a sharp edge. In reality the corner may nominally be 225 degree or greater but may vary from this value by several degrees. For example, the angle between the wall of the microchannel 12 and the wall of the passage 13 at the intersection (i.e., at the

corner) is nominally 270 degree if the passage 12 is created by drilling through the microchannel with an angle that is normal to the wall surface of the microchannel 12.

As is most clearly seen in the plan view of Fig 1 c there is a corner completely around the intersection of the passage 13 with the microchannels 11 , 12. The microchannels 11, 12 and passage 13 are depicted as having a circular cross-section but the invention is not limited to this configuration. It will be appreciated that any shaped channel (oval, rectangular, irregular) can be constructed to form the stop structure. As is clear from FIG 1 the passage 13 widens in all directions orthogonal to the direction of the passage 13 at microchannel 12 (or in the reverse direction, microchannel 11). It will be appreciated by persons skilled in the art that a problem with the 2D structures of the prior art is that there is always at least one continuous wall between the microchannel and the passage so that fluid creeps along the wall and the stop structure fails. In contrast the adjoining walls between the passage 13 and the microchannels 11, 12 are discontinuous and therefore wall creep is virtually eliminated or at least significantly reduced.

As seen in Fig 2, fluid 20 flowing from microchannel 11 to microchannel 12 flows through passage 13 and a meniscus 21 is formed at the intersection of the passage 13 and the microchannel 12. A small increase in pressure is needed to overcome the surface tension of the meniscus 21 and continue flow of the fluid 20. The intersection of the passage 13 and the microchannel 12 therefore operates as a stop structure that allows control of fluid movement from microchannel 11 to microchannel 12. Fig 3 shows a second embodiment incorporating two adjacent stop structures in a series. The embodiment of Fig 3 adds effective stop structures to conventional microfluidic device designs. A portion of a microfluidic device 30 has a first microchannel 31 that extends to other parts of the device 30. A first passage 32 is formed to extend from the continuing microchannel 31 to a connecting microchannel 33 and a second passage 34 reconnects the

connecting microchannel 33 with the continuing microchannel 31. There is a stop structure 35 formed at the intersection of the first passage 32 and the connecting microchannel 33 and another stop structure 36 formed at the intersection of the second passage 34 and the continuing microchannel 31. The incorporation of an even number of stop structures (for example, a pair of the stop structures 35, 36) provides a high degree of control of the movement of fluid through microfluidic device 30. This is because even if one stop structure in a pair of stop structures fails to control the movement of fluid, another subsequent stop structure in the pair can control the movement of fluid. For example, even if the first stop structure 35 fails to control the movement of fluid, the second stop structure 36 can control the movement of fluid.

Microfluidic devices, such as those depicted in our co-pending application, are typically produced by forming open microchannels in a surface of a substrate and bonding a cover to the substrate to close the microchannels. In this technique microchannels of odd numbered stop structures in the series are all conveniently formed in the same side of the microfluidic device and microchannels of even numbered stop structures in the series are conveniently formed in the other side of the microfluidic device. For example, a first stop structure and a third stop structure in a series are on the same side of the microfluidic device, whereas a second stop structure in the series and a fourth stop structure in the series are on the same other side of the microfluidic device.

The microfluidic device 30 can be constructed by forming microchannels in both sides of a substrate. As discussed above, microchannels 33 are all formed in the same one side of the microfluidic device and microchannels 31 are all formed in the same another side of the microfluidic device. The connecting passages 32, 34 may be, for example, drilled between microchannels 31, 33. Covers 37, 38 are bonded to the top and bottom surfaces of the substrate to complete the microfluidic device.

Therefore, according to some embodiments of the invention, a designer of a microfluidic device suitably is able to construct a fluid pattern of continuing

microchannels in the same plane and introduce a pair of stop structures at any point of the continuing microchannels to provide a robust control of the movement of fluid. As discussed above, a pair of stop structures is more robust than one stop structure because of a fail safe feature of a control structure comprising a series of stop structures.

Furthermore, it can be more advantageous to design and manufacture a microfluidic device having all continuing microchannels in the same one side of a substrate of the microfluidic device and having connecting microchannels in the same other side of the substrate. For example, the design of mould inserts for injection moulding can be rationalized and simplified. In many cases an even number of stop structures in the series will be preferable from a manufacturing perspective but there is no inherent limitation on the number of stop structures in the series.

Suitably all connecting microchannels are similar in length. For example, all connecting microchannels 33 in the microfluidic device 30 can have the same length, whereas the continuing microchannels can have different arbitrary lengths. As discussed above, this can simplify both design and manufacturing processes. It also assists manufacturing if passages in the series are parallel.

It is known that many fluids exhibit wall creep and do not easily form a meniscus. The embodiment shown in Fig 4 is particularly useful for such situations. The stop structure of Fig 4 is similar to the stop structures described above except that the passage extends beyond the microchannel.

In Fig 4 a first microchannel 41 is in fluid connection with a second microchannel 42. The microchannels 41 , 42 are connected by a passage 43 that extends from the first microchannel 41 to the second microchannel 42. The passage 43 extends beyond the surface of the second microchannel 42 and forms an apron 44. The angle between the surface of the apron 44 and the wall of the passage 43 at the intersection is greater than 270 degrees and therefore promotes the formation of a meniscus 51 in fluid 50, as shown in Fig 5.

An even greater contact angle is achieved by the embodiment shown in Fig 6. A first microchannel 61 is in fluid connection with a second microchannel 62. The microchannels 61, 62 are connected by a tube 63 that extends from the first microchannel 61 to the second microchannel 62. The passage 63 extends beyond the surface of the second microchannel 62 and forms a stub 64 that extends into the second microchannel 62. The angle between the top of the stub 64 and the wall of the second microchannel 62 is much greater than 270 degrees and therefore promotes the formation of a meniscus 71 in fluid 70, as shown in Fig 7. The structures depicted above can be constructed in a variety of ways.

The key feature is that there is no continuous wall between the microchannel and the passage that allows fluid creep. As mentioned above, conventional construction of microfluidic devices involves the etching of channels in a substrate followed by sealing of the channels by bonding a cover slip to the substrate. Each of the embodiments can be constructed by injection moulding with the passages formed by pins placed through the mould. Other manufacturing techniques can be applied. For example, a step of through-hole drilling or laser ablation during manufacture is the only additional step required for construction of the first and second embodiments. The third embodiment can involve a modified etching process to form the apron 44. The fourth embodiment can involve a bonding step to bond a tube 63 into a hole formed in the manner used for the first and second embodiments.

The passage may also be formed in the same plane as the microchannels as shown in FIG 8. FIG 8 shows an example of a structure for control of movement of fluid that incorporates three stop structures. This embodiment demonstrates that the invention is not limited to an even number of stop structures.

The microchannels 82 are formed in a conventional manner with passages

81 formed between the microchannels 82. One approach is to injection mould the substrate 80 with pins positioned to form the passages 81. The pins are removed

and the apertures 83 are sealed with epoxy plug 84 (shown in FIG 9). The microchannels 82 may then be etched into the substrate 80 in conventional manner and a cover slip 85 used to seal the microchannels. As can be seen in the cross-section view of FIG 9, a stop structure is formed at each intersection of the microchannel 82 and the passage 81.

Although the stop structures have been described in terms of a passage between a pair of microchannels, it will be appreciated that this is not essential. The primary requirement is an intersection of a passage and one microchannel. The other end of the passage may be in fluid connection with a buffer chamber or other microfluidic structure. For example, in Fig 10 a stop structure is used to control movement of fluid 100 from buffer chamber 101 to microchannel 103 through passage 103, forming a meniscus 104.

The stop structures are used in the microfluidic device to control the movement of fluids through the device. The fluids may be reagents, detergents, buffers or any of many fluids that are used in microfluidic assay devices.

Throughout the specification the aim has been to describe the preferred embodiments of the invention without limiting the invention to any one embodiment or specific collection of features.