SELF-FILLING STRUCTURE FOR SEALING MICROFLUIDIC ARCHITECTURES, MICROFLUIDIC DEVICE, METHOD AND ASSOCIATED USES THEREOF

FIELD OF THE INVENTION

The present invention lies within the technical field of microfluidics. More specifically, the invention relates to a self-filling structure for an effective and faster sealing of microfluidic architectures patterned over a substrate, the resulting microfluidic device, the method of sealing using said structure, and the associated uses thereof.

BACKGROUND OF THE INVENTION

In the field of microfluidics, sealing a patterned substrate without damaging the encapsulated microstructures (i.e., microchannels and chambers) remains a technical challenge and an obstacle for the commercialization and mass-scale manufacturing of polymer-based microfluidic devices. These low-cost and disposable devices are fabricated by several techniques, based on using or not an intermediate material to assist in the bonding between a patterned substrate and a sealing element (normally, a cover plate). However, none of these techniques provides sufficient bonding strength to get a functional and leak-tight device without sealing or mechanical stability problems.

Thermal bonding allows simple and uniform surface bonding by applying high temperature and pressure over the whole substrate and cover plate but leads to microstructures deformation [Zhu et al. Microsyst. Technol., 2007, 13 (3), 403-407], On the contrary, adhesive bonding and chemical bonding approaches require low pressure and low temperature [Song et al. Micromachines, 2017, 8 (9), 284; Nguyen et al. Lab Chip, 2019, 19 (21), 3706-3713], However, adhesives are vulnerable to solvent degradation and can cause microchannel clogging, while chemical surface modifications are time consuming by involving multi-step processes. Solvent bonding strategies are relatively simple joining methods with short process times that results in high bonding strength, but also, in microchannel clogging and distortion due to solvent uptake by the substrates to be bonded [Shah et al. Anal. Chem., 2006, 78 (10), 3348-3353; Lin et al. Sens. Actuators B Chem., 2007, 121 (2), 698-705], Although this drawback can be controlled by adjusting the solvent exposure time, it needs to be balanced by the required bonding strength. Solvent toxicity, flammability and disposal effects on the environment also need to be considered.

Recently, a solvent bonding method to fuse poly(methyl methacrylate) microfluidic chips using isopropanol with minimal distortion of microchannels has been demonstrated [Ng et al. Procedia Eng., 2016, 141 , 130-137], However, it involves a pre-processing step of pressure and thermal annealing of the PMMA substrates, and a post-processing step of solvent removal by subjecting the chip to vacuum.

The present invention proposes a solution to the technical problems mentioned above, by means of a microfluidic structure that allows an effective and faster sealing of microfluidic architectures patterned over a substrate without damaging their integrity.

BRIEF DESCRIPTION OF THE INVENTION

A first object of the present invention relates to a microfluidic structure for sealing a microfluidic architecture, wherein said microfluidic structure comprises: a substrate comprising: at least a patterned microfluidic architecture; at least a main sealing region; and, at least an inlet port, patterned over the substrate and arranged at the main sealing region; and, a cover plate, comprising a material suitable for transporting a sealing agent by capillarity.

Advantageously in the invention, the cover plate is arranged over the main sealing region, covering a part of the inlet port and leaving a part thereof open. Preferably, the cover plate covers between 25% and 85% of the inlet port surface. In this way, the sealing agent can be deposited in the inlet port through the open part thereof and, when said sealing agent fills the inlet port, it contacts the cover plate and flows through the main sealing region by capillary action, sealing the patterned microfluidic architecture with the cover plate.

Optionally, the cover plate can also be patterned with microfluidic or other topological, structural and/or functional elements, such as electrodes or magnetic stripes. In a preferred embodiment of the invention, the inlet port is connected to one or more blind channels patterned over the substrate to facilitate the entry of the sealing agent into the main sealing region.

In another preferred embodiment of the invention, the substrate further comprises a plurality of inlet ports arranged at the main sealing region, so as to speed up and homogenize (void free) the movement of the sealing agent by capillarity along said sealing region. Preferably, the blind channels connected to these inlet ports are arranged with double mirror symmetry to guarantee a homogeneous and controlled sealing between the substrate and the cover plate. More preferably, said blind channels comprise a short-finger-shaped tail, a long- finger-shaped tail, or a comb-shaped tail.

In yet another preferred embodiment of the invention, the substrate further comprises a plurality of overflow channels arranged at each of the larger sides of the main sealing region. In case that the amount of sealing agent deposited in the inlet port is larger than what the surface of the main sealing region can hold, said overflow channels would receive the excess of fluid avoiding the clogging, collapse, or damage of nearby microfluidic architectures.

In yet another preferred embodiment of the invention, the substrate further comprises a plurality of secondary sealing regions adjacent to the overflow channels. Then, if the amount of sealing agent deposited in the inlet port is larger than the volume the overflow channel can hold, the excess of fluid will flow by capillarity to the adjacent secondary sealing region. This aspect assures not only the confinement of the sealing agent avoiding the clogging, collapse, or damage of nearby microfluidic architectures, but also multiple sealing regions between the substrate and the cover plate, this increasing the bonding strength. Overflow channels act, then, as sealing agent reservoirs for the self-filling of new sealing regions between the substrate and the cover plate.

In yet another preferred embodiment of the invention, the surface/s of the main sealing region, the overflow channels and/or the secondary sealing regions comprise/s a hydrophilic and/or a hydrophobic treatment. Hereby, the speed of the sealing agent in said surfaces can be controlled based on the treatment done.

In yet another preferred embodiment of the invention, the patterned microfluidic architecture comprises a microchannel, a chamber, or any combination thereof. In yet another preferred embodiment of the invention, the substrate and/or the cover plate comprise/s glass or non-polymeric materials which are transparent in the LIV-NIR wavelength range.

In yet another preferred embodiment of the invention, the substrate and/or the cover plate comprise/s a polymer. Preferably, polycarbonate (PC), polymethylmethacrylate (PMMA), polystyrene (PS), cyclic olefin copolymer (COC), cyclic olefin polymer (COP), or any combination thereof.

In yet another preferred embodiment of the invention, the depth of the inlet port/s, the blind channel/s and/or the overflow channels is comprised between 2 pm and 5 mm.

In yet another preferred embodiment of the invention, the height of the main sealing region and/or the secondary sealing regions is comprised between 1 nm and 500 pm.

In yet another preferred embodiment of the invention, the diameter of the inlet port is comprised between 5 pm and 10 mm.

In yet another preferred embodiment of the invention, the sealing agent used to fill the inlet port comprises a solvent, a polymer, an adhesive, a surfactant, a curing agent, an initiator, or any combination thereof.

A second object of the invention relates to a microfluidic device that comprises a microfluidic structure according to any of the embodiments herein described. In the context of the present invention, the term “microfluidic device” is interpreted as an instrument that contains, manipulates, controls, and/or conducts fluids within the microfluidic architecture/s comprised in any of the microfluidic structures herein described. Examples of these microfluidic devices can be cell culture chambers, reaction chambers, hybridization chambers, multi-channel microfluidic chips, micro-valves, micro-pumps, and micro-mixers.

A third object of the invention relates to a method of sealing a microfluidic architecture comprised in a microfluidic structure according to any of the embodiments herein described. Advantageously, the method comprises performing the following steps: a) providing a substrate with a first bonding surface that comprises: a patterned microfluidic architecture; at least a main sealing region; and, at least an inlet port, patterned over the substrate and arranged at the main sealing region; b) providing a cover plate with a second bonding surface; c) arranging the second bonding surface of the cover plate on top of the first bonding surface of the substrate in such a way that the inlet port is partially covered by the cover plate (preferably, between 25% and 85%); and, d) bonding the substrate with the cover plate by injecting a sealing agent into the inlet port.

Alternatively, said method can be used for sealing a plurality of microfluidic architectures over a substrate at the same time. In that case, the substrate comprises a plurality of main sealing regions interspersed with said patterned microfluidic architectures.

A fourth object of the invention relates to the use of any of the microfluidic structures herein described as sealing means of microfluidic architectures patterned over a substrate for making a microfluidic device.

DESCRIPTION OF THE FIGURES

Figures 1a and 1b show, respectively, the top view and perspective view of the microfluidic structure of the invention in one of its preferred embodiments. Said microfluidic structure is comprised by a patterned substrate and a cover plate. The substrate further comprises a plurality of chambers interspersed with a plurality of main sealing regions. Over said main sealing regions, a plurality of inlet ports connected to blind channels are patterned, and at each of the larger sides of these main sealing regions, a plurality of overflow channels is arranged.

Figure 2 shows how the microfluidic structure of the invention self-fills with a sealing agent in one of its preferred embodiments. Specifically, from left to right: injection of the sealing agent into the inlet port; self-filling of the main sealing region through the blind channels by capillary action; and partially filling of the overflow channels, as the injected amount of sealing agent is larger than what the surface of the main sealing region can hold.

Figure 3 shows different configurations of the blind channel of the microfluidic structure of the invention. From left to right: short-finger-shaped tail, long-finger-shaped tail, and combshaped tail. Figures 4a and 4b show, respectively, the top view and perspective view of the microfluidic structure of the invention in one of its preferred embodiments, wherein said microfluidic structure comprises a plurality of overflow channels and a plurality of secondary sealing regions.

Figure 5 shows the self-filling process of the microfluidic structure of the invention in another of its preferred embodiments. Specifically, from left to right: injection of the sealing agent into the inlet port; self-filling of the main sealing region through the blind channels by capillary action; and self-filling of the secondary sealing regions through the overflow channels by capillarity, as the injected amount of sealing agent is larger than the volume the overflow channels can hold.

NUMERICAL REFERENCES USED IN THE DRAWINGS

In order to provide a better understanding of the technical features of the invention, the referred Figures 1-5 are accompanied of a series of numerical references which, with an illustrative and non-limiting character, are hereby represented:

DETAILED DESCRIPTION OF THE INVENTION

While aspects of the subject matter of the present disclosure may be embodied in a variety of forms, the following description and accompanying drawings are merely intended to disclose some of these forms as specific examples of the subject matter. Accordingly, the subject matter of this disclosure is not intended to be limited to the forms or embodiments so described and illustrated.

Unless defined otherwise, all terms of art, notations and other technical terms or terminology used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this disclosure belongs.

As described in preceding paragraphs, one object of the present invention relates to a microfluidic structure for sealing microfluidics architectures (i.e. , microchannels, chambers, or any combination thereof) patterned over a substrate, without damaging their integrity or clogging them. To do so, the microfluidic structure comprises a substrate (1) and a cover plate (2). In the example of microfluidic structure chosen to illustrate the present invention (Figures 1a and 1 b), the substrate (1) further comprises a plurality of patterned microfluidic architectures (3) interspersed with a plurality of main sealing regions (4), and a plurality of inlet ports (5) patterned over the substrate (1) and arranged at the main sealing regions (4). The cover plate (2) comprises a material suitable for transporting the sealing agent by capillarity and can also be patterned with microfluidic or other topological, structural and/or functional elements, such as electrodes or magnetic stripes.

Advantageously, the cover plate (2) is arranged over the main sealing regions (4) of the substrate (1), covering between 25% and 85% of the inlet ports (5) and leaving a part thereof open (Figures 1a and 1b). In this way, the sealing agent can be dispensed in the inlet ports

(5) through the open part thereof and, when said sealing agent fills the inlet ports (5), it contacts the cover plate (2) and flows along the main sealing region (4) by capillary action, sealing the patterned microfluidic architecture (3) with the cover plate (2) (Figure 2).

The inlet ports (5) are arranged at each end of the main sealing regions (4), to speed up the movement of the sealing agent by capillarity along said sealing region (4). Furthermore, each of said inlet ports (5) are connected to a blind channel (6), also patterned over the substrate (1), to facilitate the entry of the sealing agent into the main sealing region (4). Said effect is enhanced by the arrangement of these blind channels (6) with double mirror symmetry, as it contributes to a homogeneous and controlled self-filling of the corresponding main sealing region (4) (Figures 1a and 1 b). Preferably, said blind channels

(6) comprise a short-finger-shaped tail, a long-finger-shaped tail, or a comb-shaped tail (Figure 3).

The substrate (1) also comprises a plurality of overflow channels (7) arranged at each of the larger sides of the main sealing region (4) (Figures 1a and 1 b). In case that the injected amount of sealing agent is larger than what the surface of the main sealing region (4) can hold, said overflow channels (7) would receive the excess of fluid avoiding the clogging, collapse, or damage of nearby microfluidic architectures (3) (Figure 2).

The substrate (1) can additionally comprise a plurality of secondary sealing regions (8) adjacent to the overflow channels (7) to ensure a greater bonding strength and sealing (Figures 4a and 4b). When the injected amount of sealing agent is larger than the volume the overflow channel (7) can hold, the excess of fluid flows by capillarity to the adjacent secondary sealing region (8). This aspect assures not only the confinement of the sealing agent avoiding the clogging, collapse, or damage of nearby microfluidic architectures (3), but also multiple sealing regions between the substrate (1) and the cover plate (2) (see elements (4) and (8) in Figure 5). In this embodiment, the overflow channels (7) act, then, as sealing agent reservoirs for the self-filling of new sealing regions (8) between the substrate (1) and the cover plate (2).

Optionally, the surfaces of the main sealing regions (4), the overflow channels (7) and/or the secondary sealing regions (8) can be exposed to a hydrophilic treatment to improve its/their wettability and, therefore, its/their self-filling capability by capillary action.

The depth of the inlet ports (5), the blind channel/s (6) and/or the overflow channels (7) is typically comprised between 2 pm and 5 mm.

The height of the main sealing regions (4) and/or the secondary sealing regions (8) is comprised between 1 nm and 500 pm.

The diameter of the inlet ports (5) is typically comprised between 5 pm and 10 mm.

The substrate (1) and the cover plate (2) are typically glass- or polymer-based. Preferably, said mating substrates (1 , 2) can comprise polycarbonate (PC), polymethylmethacrylate (PMMA), polystyrene (PS), cyclic olefin copolymer (COC), cyclic olefin polymer (COP), or any combination thereof. Alternatively, they (1 , 2) can also comprise a non-polymeric material which is transparent in the LIV-NIR wavelength range.

With regards to the sealing agent, it comprises a wide range of low viscosity fluids: from thermally curable materials that become solid after irradiation or temperature, to those that locally dissolve the area comprised by the main sealing region (4), either only the substrate (1) or the substrate (1) and the cover plate (2). The only requirement that all of them should fulfil is propagating easily through the surface of the main (4) and secondary (8) sealing regions. Clearly, the higher the hydrophilicity, the faster the capillarity and, straightforwardly, the bonding process between the substrate (1) and the cover plate (2). Preferably, the sealing agent used in the invention comprises a solvent, a polymer, an adhesive, a surfactant, a curing agent, an initiator, or any combination thereof.

The amount of sealing agent introduced at the inlet ports (5) is defined according to the length and width of the corresponding main sealing region (4). However, note that the bonding quality is improved if multiple drops of smaller volumes are dispensed, rather than a single drop of larger volume.

A second object of the invention relates to a microfluidic device that comprises a microfluidic structure according to any of the embodiments herein described. Said microfluidic device can be, for example, a cell culture chamber, a reaction chamber, a hybridization chamber, a multi-channel microfluidic chip, a micro-valve, a micro-pump, or a micro-mixer.

A third object of the invention relates to a method of sealing a microfluidic architecture (3) comprised in a microfluidic structure according to any of the embodiments herein described. Advantageously, the method comprises performing the following steps: a) providing a substrate (1) with a first bonding surface that comprises at least: a patterned microfluidic architecture (3); a main sealing region (4); and, an inlet port (5), patterned over the substrate and arranged at the main sealing region (4); b) providing a cover plate (2) with a second bonding surface; c) arranging the second bonding surface of the cover plate (2) on top of the first bonding surface of the substrate (1) in such a way that the inlet port (5) is covered by the cover plate (2) between 25 and 85%; and, d) bonding the substate (1) with the cover plate (2) by injecting a sealing agent into the inlet port (5), which flows along the main sealing region (4) by capillary action sealing the patterned microfluidic architecture (3) with the cover plate (2) (Figure 2).

A fourth object of the invention relates to the use of any of the microfluidic structures described above as sealing means of microfluidic architectures (3) patterned over a substrate (1) for making a microfluidic device. Therefore, the invention proposes an effective and faster solution to overcome the known techniques for sealing microfluidic architectures. It not only prevents the clogging, collapse, or damage of said microfluidic architectures (3) during the sealing process, but also allows aligning the mating substrates (1 , 2) before bonding, which increases the manufacturing yield as misalignment errors are potentially reduced.