TWI794603B - Microfluidic devices and methods of making the same - Google Patents

Abstract

A microfluidic device including: (a) top plate, including: a top substrate; a first layer of hydrophobic material coupled to a surface of the top substrate; a continuous electrode between the first layer of hydrophobic material and the top substrate; (b) a bottom plate, comprising: a bottom substrate; a plurality of electrodes coupled to the bottom substrate; a second layer of hydrophobic material coupled to the second substrate and atop the plurality of electrodes. The top plate and the bottom plate are placed in a spaced relationship, thereby defining a gap between the first and second layers of hydrophobic material to permit droplet motion within the gap under application of propulsion voltages. At least one of the top substrate, the first layer of hydrophobic material, the second layer of hydrophobic material, the bottom substrate, and the plurality of electrodes have a non-uniform thickness, and the gap has a plurality of heights.

Description

Microfluidic device and method of manufacturing the same

This application claims priority to US Patent Application Serial No. 62/840,443, filed April 30, 2019, which is hereby incorporated by reference in its entirety.

Digital microfluidic devices use independent electrodes to move droplets in a confined environment, thereby providing a "lab-on-a-chip." Digital microfluidic devices may be referred to as dielectric wetting, or "EWoD," to further differentiate the approach from competing microfluidic systems, which rely on electrophoretic flow and/or micropumps. Wheeler, in "Digital Microfluidics," Annu. Rev. Anal. Chem. 2012, 5:413-40, which is hereby incorporated by reference in its entirety, provides a 2012 review of electrowetting technology. This technology can implement sample separation, detection, and synthetic chemistry with trace samples and reagents. Controlled droplet manipulation using electrowetting in microfluidic cells has become commercially viable in recent years; and products are now available from large life science companies such as Oxford Nanopore.

Most literature reports on EWoD involve so-called "passive matrix" devices (also known as "segmented" devices), in which 10 to 20 electrodes are directly driven by a controller. While segmented devices are easy to fabricate, the number of electrodes is limited by space and actuation constraints. Therefore, large-scale parallel detection, reaction, etc. cannot be implemented in passive matrix devices. In contrast, "active matrix" devices (also known as active matrix EWoD, also known as AM-EWoD) can have thousands, hundreds of thousands, or even millions of addressable electrodes. The electrodes are generally switched by thin-film transistors (TFTs) and the droplet motion can be programmed, so that the AM-EWoD array can be used as a general-purpose device with a large degree of freedom to control multiple droplets and perform simultaneous analysis methods.

The basic operation of a conventional EWoD device is described in the cutaway view of FIG. 5 . EWoD 200 includes a cell filled with oil 202 and at least one water droplet 204 . As shown in FIG. 5 , in a basic configuration, a plurality of propelling electrodes 205 are disposed on a substrate, and a single upper electrode 206 is disposed on the opposite surface. The cell additionally includes a hydrophobic coating 207 on the surface in contact with the oil layer, and a dielectric layer 208 between the propulsion electrode 205 and the hydrophobic coating 207 (the upper substrate may also include a dielectric layer, but not shown in FIG. Show). The hydrophobic layer prevents droplets from wetting the surface. When no voltage difference is applied between adjacent electrodes, the droplet maintains a spherical shape while minimizing contact with the hydrophobic surface (oil and hydrophobic layer). Because the droplets do not wet the surface, they are less likely to contaminate the surface or interact with other droplets, except when that behavior is desired. When a voltage difference is applied between adjacent electrodes, the voltage on one electrode attracts an opposite charge in the droplet at the dielectric-to-droplet interface, and the droplet moves toward that electrode.

As depicted in Figure 5, an EWoD device typically includes two parallel substrates. The operation of moving a droplet in the gap between two substrates is usually one of four main operations: transport (i.e. moving the droplet laterally through the gap), splitting (i.e. splitting a droplet into two or more smaller ones). droplet), dispensing (ie, drawing a droplet from a large fluid reservoir), and mixing/merging (ie, combining two droplets into one larger droplet). The efficiency of each operation depends on many factors. For example, the voltage required for acceptable droplet propulsion depends on the properties of the dielectric and hydrophobic layers. However, another important factor is the aspect ratio (h/L) of the droplet. The drop height ("h") will be equal to the gap height between the two parallel substrates since the drop will span this full dimension. The length ("L") is equal to the width or dimension of the vertical height of the droplet. Droplets have an optimal aspect ratio depending on the operation to be performed. For example, if the droplet aspect ratio is too low (i.e., the droplet length is too large) in the transport-dedicated region of the device, higher drive voltages may be required to move the droplet due to the large contact area between the droplet and the hydrophobic layer . Droplets with too high an aspect ratio (ie, too small a droplet length) may not be able to perform the splitting operation. Due to manufacturing constraints, EWoD device designs typically have uniform gap heights and include uniformly sized electrodes; thereby limiting the available aspect ratios for each region of the device. Accordingly, there is a need for improved EWoD devices with more efficient droplet propulsion operations and cost-effective fabrication methods.

In a first aspect, the present invention provides a microfluidic device, which includes: (a) an upper plate, which includes an upper substrate, a first layer of hydrophobic material connected to the surface of the upper substrate, and a layer between the first layer of hydrophobic material and the upper A continuous electrode between the substrates; (b) a lower plate comprising a lower substrate, a plurality of electrodes connected to the lower substrate, a second layer of hydrophobic material connected to the second substrate and over the plurality of electrodes. The upper plate and the lower plate are disposed in a spaced relationship thereby defining a gap between the first and second layers of hydrophobic material such that droplets can maneuver within the gap upon application of a propulsion voltage. At least one of the following has non-uniform thickness: the upper substrate, the first layer of hydrophobic material, the second layer of hydrophobic material, the lower substrate, and a plurality of electrodes, and the gap has a plurality of heights.

In a second aspect, the present invention provides a method of manufacturing a microfluidic device, which includes: providing a first substrate and a second substrate, at least one of the first and second substrates has a plurality of thicknesses; A first layer of hydrophobic material is used to form an upper plate; a plurality of electrodes are applied to the surface of the second substrate, and a second layer of hydrophobic material is applied on the plurality of electrodes to form a lower plate; and the lower plate is arranged in a spaced relationship A gap is defined between the first and second layers of hydrophobic material, so that the droplet can move in the gap under the application of a driving voltage.

In a third aspect, the present invention provides a method for manufacturing a microfluidic device, which includes: providing a first substrate and a second substrate; applying a first layer of hydrophobic material to the surface of the first substrate to form an upper plate; A plurality of electrodes are applied on the surface of the substrate, and a second layer of hydrophobic material is applied on the plurality of electrodes to form a lower plate; There are gaps of multiple heights, so that the droplet can move in the gaps under the application of a driving voltage.

These and other aspects of the present invention will be apparent from the following description.

In the following detailed description, numerous specific details are set forth by way of example in order to provide a thorough understanding of the relevant teachings. However, it will be apparent to those skilled in the art that the present teachings can be practiced without such details.

Various embodiments of the present invention provide EWoD devices that include dual substrates. The "lower" substrate described herein includes a plurality of electrodes to propel individual droplets through the microfluidic region. The "top" substrate includes a layer of conductive material that acts as a common conductor. The use of "upper" and "lower" is for convenience only, as the positions of the two substrates are interchangeable, and the device can be oriented in many ways, for example the upper and lower substrates can be roughly parallel, and the overall device is oriented so that the substrates are normal to the work surface (as opposed to parallel working surfaces shown in the drawings). The upper or lower substrate may include additional functionality, such as resistive heating and/or temperature sensing. Various materials that can be used to form the upper and/or lower substrates include, but are not limited to, glass and other oxides, semiconductor materials such as silicon, plastics such as acrylics, and combinations thereof.

The term "bonding" means any direct or indirect structural link or connection between two or more parts of a device, where the parts may be in direct physical contact or connected via intermediate parts (such as intermediate layers, members or adhesives) . For example, a layer "bonded" to a substrate may, in certain instances, refer to a configuration in which the layer is directly adjacent and in physical contact with the substrate. However, one or more additional layers or other components may be interposed between the layers and the substrate, depending on the context.

Referring now to FIG. 1 , a microfluidic device 10 includes an upper plate and a lower plate. The upper plate includes an upper base plate 12 , and the lower plate includes a lower base plate 14 . The two boards are usually parallel to each other and fixed relative to each other. As used herein, "fixed" means that the device 10 does not include any mechanical or electromechanical components that can variably adjust the distance between the upper and lower plates. In one embodiment, the upper and lower plates are pressed together to form a reversible attachment. Alternatively the attachment may be secured via removable or permanent fasteners.

The upper substrate 12 includes an inner surface to which a continuous layer 16 of conductive material may be applied to all or most of the inner surface. A layer 22a of hydrophobic material may then be applied on the continuous electrode 16 . The entire area of the continuous electrode 16 is preferably coated with a layer 22a of hydrophobic material. The conductive material of the continuous electrode includes but not limited to metal oxides (such as indium tin oxide) and conductive polymers (PEDOT:PSS). The hydrophobic layer 22a may be fabricated from a hydrophobic material which is deposited on the surface via a suitable technique to form a coating. Depending on the hydrophobic material to be applied, examples of deposition techniques include spin coating, molecular vapor deposition, and chemical vapor deposition. A hydrophobic layer may be more or less wettable, which is generally defined by the respective contact angle. Unless otherwise indicated, angles are measured herein in degrees (°) or diameters (rad) as the context dictates. For the purpose of measuring the hydrophobicity of a surface, it is understood that the term "contact angle" means the contact angle of a surface with respect to deionized (DI) water. If the contact angle of water is between 0°<θ<90°, the surface is classified as hydrophilic, while the surface with a contact angle of 90°<θ<180° is regarded as hydrophobic. Medium contact angles are generally considered to be in the range of about 90° to about 120°, and high contact angles are generally considered to be in the range of about 120° to about 150°. When the contact angle is 150°<θ, the surface is recognized as superhydrophobic or superhydrophobic. Surface wetting forces can be measured by analytical methods known in the art, such as dispensing liquid droplets onto the surface and performing contact angle measurements using a contact angle goniometer. Anisotropic hydrophobicity can be tested by tilting a substrate with a gradient surface wetting force along the horizontal axis of the pattern, and examining the minimum tilt angle for a mobile droplet.

The hydrophobic layer of medium contact angle generally includes a fluoropolymer or a blend of fluoropolymers, such as PTFE (polytetrafluoroethylene), FEP (fluorinated ethylene propylene), PVF (polyvinyl fluoride), PVDF (polyylidene Difluoroethylene), PCTFE (polychlorotrifluoroethylene), PFA (perfluoroalkoxy polymer), FEP (fluorinated ethylene propylene), ETFE (polyethylene tetrafluoroethylene), and ECTFE (polyethylene chlorotrifluoroethylene) vinyl). Commercially available fluoropolymers include ^Cytop® (AGC Chemicals, Exton, PA) and ^Teflon® AF (Chemours, Wilmington, DE). An advantage of fluoropolymer membranes is that they can be highly inert and remain hydrophobic even after exposure to oxidative treatments such as corona treatment and plasma oxidation.

The lower substrate 14 has an inner surface to which a plurality of electrodes 18a, 18b can be applied. The electrodes can be passive matrix or active matrix, such as a TFT array. A layer of dielectric material 20 is coated on the plurality of electrodes, preferably over the entire electrode area, and a hydrophobic material layer 22b, which may be of the same or similar composition as hydrophobic material layer 22a, is applied to the upper substrate. The dielectric layer may comprise a layer of approximately 20-40 nm _SiO2 overlying 200-400 nm plasma deposited silicon nitride. Alternatively, the dielectric layer may comprise ALD Al ₂ O ₃ between 2 and 100 nm thick, preferably between 20 and 60 nm thick. Although single layers can be used for both dielectric and hydrophobic functions, these layers generally have to be thick inorganic layers (to prevent pinholes) resulting in low dielectric constants, thus requiring over 100 volts for droplet movement. For low voltage actuation, it is preferably high capacitance and pinhole-free with a thin dielectric inorganic layer overlaid with a thin organic hydrophobic layer. This combination enables electrowetting operation at voltages in the range of +/-10 to +/-50 volts, which is available for conventional TFT arrays. It uses AC drive through various electrochemistries to reduce degradation of droplets, dielectrics and electrodes. The operating frequency of EWoD can be in the range of 100 Hz to 1 MHz, but it is preferably a low frequency of 1 kHz or below for using TFTs with limited operating speed. Examples of various architectures for electrodes and driving methods are disclosed in US Patent Application Serial No. 16/161,548, the entire contents of which are incorporated herein by reference.

As before, the upper and lower plates may be fixed relative to each other, for example by pressing together until a reversible attachment is established. To provide a gap 25 between the substrates 12, 14, the distance and separation between the upper and lower plates may be maintained by one or more spacers 24a, 24b. The gap 25 is preferably filled with interstitial fluid. Droplet samples propelled within the device should be immiscible in the interstitial fluid. For example, if the microfluidic device is used to analyze aqueous droplet samples, it is generally preferred that the interstitial fluid is a hydrophobic fluid, such as silicone oil, dodecane, or other long-chain, non-polar hydrocarbon oils.

As depicted in FIG. 1 , the upper substrate 12 does not have a uniform thickness. Instead, the thickness of the upper substrate 12 in one cross-sectional region 26b may be smaller than the thickness of the upper substrate 12 in an adjacent cross-sectional region 26a. As a result, the height of the gap 25 in region 26a is smaller than the height of the gap in region 26b. Each area 26a, 26b may be a designated operating area. For example, the area 26a with a small gap height can be a designated operation area dedicated to splitting operations, and the area 26b with a large gap height can be a transport area. The clearance height of each designated operating area (eg, transport area, distribution area, split area, and mixing area) can be different from the clearance height of at least one other designated operating area. The height of each gap typically ranges from 50 to 200 microns, but the gaps can be larger.

In order to provide the upper substrate 12 with non-uniform thickness, the upper substrate 12 may be made of an etchable material, such as glass. Etching methods, such as wet etching methods, can be performed by first applying a photoresist to the surface of the glass substrate in a desired pattern. The patterned surface can then be exposed to a chemical etchant for a specified amount of time to remove a portion of the exposed glass. After a sufficient amount of material has been chemically etched away, the patterned surface can be cleaned to remove photoresist and any residual etchant. Dry etching methods such as plasma or light-induced etching can also be used to provide a non-uniform thickness of the upper substrate.

In another method according to an embodiment of the present invention, one or both substrates of the microfluidic device may be molded or shaped to provide a non-uniform surface. For example, a stamp bearing the inverse of the desired pattern of the substrate surface may be applied to one or both substrates, preferably before any additional layers are applied. Another method of providing a substrate with non-uniform thickness is by embossing. For example, the substrate can be made of an imprintable material, such as a plastic film, and an inverse roller with the desired pattern can be applied to the surface of the substrate material. The embossing method can be a roll-to-roll method, as disclosed in US Patent No. 6,930,818, the entire contents of which are incorporated herein by reference. The embossing step may be used after the substrate surface has been coated, eg after coating the upper substrate with a layer of conductive material or the layer of hydrophobic material, to provide a substrate surface with a desired surface topography. However, it is preferred that embossing is carried out before applying the layers.

In some embodiments, both the upper and lower substrates may have a non-uniform thickness; however, it is less favorable for the lower substrate to have a non-uniform surface topography because applying an array of electrodes to a non-uniform surface is less effective than coating a non-uniform surface on the top substrate. Applying a continuous layer of conductive material is more difficult and therefore more expensive. Therefore, it is preferred that only the one of the two substrates carrying the continuous conductor has a surface topography. In another aspect of the present invention, the upper substrate can be changed to another upper substrate with a different surface topography. Accordingly, various embodiments of the present invention may be in the form of a kit comprising a lower substrate, and a plurality of topographically varied upper substrates designed to be releasably attached to the lower substrate (eg, using fasteners). In this way, the user can select various upper substrate options according to the operations to be performed in the microfluidic device.

As depicted in FIG. 1 , the side lengths of the electrodes on the lower substrate 14 in one cross-sectional area 26 a may be shorter than those of the electrodes on the lower substrate 14 in the other cross-sectional area 26 b. Thus, a device fabricated in accordance with an embodiment of the present invention may have a given electrode width depending on the gap height 25 of the cross-sectional area where the electrode is located. This allows for greater control over how droplets within a particular area of device 10 achieve a desired aspect ratio. Due to the difficulty of forming an array of electrodes of different sizes, it is preferred to provide the lower substrate 14 with an array of substantially uniform side lengths. For microfluidic devices having arrays of actuated electrodes of similar size, by bonding a set of electrodes together such that the set of electrodes operate in unison, a desired cross-sectional area of larger electrode side length can be obtained. In order to carry out each propulsion operation efficiently, an aspect ratio of about 1:2, more preferably about 1:3 should generally be maintained. Therefore, the width of the drop formed by the electrode or electrode group should be about 3 times larger than the height.

As an alternative to removing or etching material, according to various embodiments of the present invention, microfluidic devices with gaps of multiple heights can be fabricated by applying a pattern of additional material to the inner surfaces of one or both substrates. Referring to FIG. 2, for example, a microfluidic device 30 having the same features as the previous embodiments is depicted. The upper plate of the device 30 may comprise an upper substrate 32 having a layer of conductive material forming a continuous electrode 38, and a layer of hydrophobic material 42a applied to the inner surface of the upper substrate 32, and the lower plate comprises a lower substrate 34, a plurality of electrodes 40, A dielectric layer 41, and a layer of hydrophobic material 42b are also applied to the inner surface. One or more spacers 44a, 44b maintain the upper and lower substrates 32, 34 apart to provide a gap 45 between the layers of hydrophobic material 42a, 42b. The embodiment depicted in FIG. 2 differs from the previously described embodiments in that the upper and lower substrates 32, 34 have substantially uniform thicknesses, but additional material 36 has been applied at designated locations on the inner surface of the upper substrate 32 such that the adjacent additional material 36 is reduced. The clearance is 45 heights.

In some embodiments, the additional material can be the same material as the conductive material or the hydrophobic material. However, with respect to upper substrate 32 , it is less preferable for additional material 36 to be the same conductive material as continuous electrode 38 because a non-uniform thickness layer of conductive material would cause electrical properties to vary across device 30 . The additional material 36 may be applied to the substrate before or after the layer of conductive material 38 is applied, preferably before. If the additional material 36 is not hydrophobic, it is also preferred to apply the additional material 36 before the layer of hydrophobic material 42a. Additional material 36 may also be patterned on the inner surface of lower substrate 34 or across electrodes 40 . However, using a pattern of dielectric material 41 provides surface topography as a less favorable option because it may cause electrical properties to be non-uniform across the inner surface of lower substrate 34 . Additional types of materials that may be used to form the surface topography of the substrate include, but are not limited to, photoresist materials (such as SU-8), polymeric materials (such as PMMA), and dielectric materials (such as inorganic oxides).

It may be desirable in some applications for microfluidic devices fabricated in accordance with various embodiments of the present invention to have optically transmissive upper and/or lower substrates and layers applied thereto to perform specific tests on droplet samples within the device gap. analysis steps. Fluorescent markers can be observed, for example, by illuminating the droplet with a light source through the upper substrate and then observing the resulting fluorescent light through the upper substrate using a detector, optionally and a color filter. In other embodiments, the light can be passed through the upper and lower substrates to allow for absorbance measurements at IR, UV or visible wavelengths. Alternatively attenuated (frustrated) total internal reflection spectroscopy may be used to detect droplet content and/or position in the system.

There is no limitation as to how the additional material may be patterned on the surface of one of the substrates of the microfluidic device. For example, if the additional material comprises a hydrophobic material, an initial uniform coating of hydrophobic material followed by a pattern of added hydrophobic material, or vice versa, may be applied to the conductive layer. In another approach, one or more stencils or masks with the desired pattern may be applied to the substrate prior to coating the surface of the substrate with the additional material. The mask can then be raised to reveal the desired pattern. If multiple masks are used, it is preferred to allow the additional coat of material to dry between applications. Once patterned, layers of conductive material and hydrophobic material can be applied over the patterned add-on material. In another approach, it is possible to apply a uniform layer of additional material over the entire surface of the substrate. It uses lasers to etch additional material to create surface topography. Alternatively, one or more masks or photoresists may be applied in a pattern to the uniform coating of additional material before using a chemical etchant to remove any exposed material. Again after etching and cleaning the surface pattern, a layer of conductive material and hydrophobic material can be applied on top of the additional material.

As previously indicated, it is possible to modify the upper and/or lower substrates to include additional materials to provide devices with multiple gap heights. Figure 3, for example, depicts a less preferred embodiment of the present invention. The microfluidic device 31 includes an array of short electrodes 40 a and high electrodes 40 b on a lower substrate 34 . The high electrode 40b is formed using additional conductive material, thereby reducing the height of the gap 45 adjacent to the high electrode 40b relative to the gap height of the adjacent short electrode 40a.

Referring now to FIG. 4, after application of the dielectric material 60 and hydrophobic layer 62b, the microfluidic device 50 may be formed by applying a plurality of spacers 64a, 64b, 64c of various heights to the lower substrate 54. Then, the substrate 52 with the common electrode layer 56 and the hydrophobic layer 62a can be pressed and bonded to a plurality of spacers 64a, 64b, 64c, so that the spacers 64a, 64b, 64c maintain gaps 66 with different heights, and The height of the gap at any location within the device 50 depends on the size of the spacers 64a, 64b, 64c in the vicinity of the gap 66. Heat and/or pressure can be used in each deformation method to provide a more compliant and deformable substrate and facilitate bonding of the upper substrate to the spacer.

From the above, it can be seen that in order to more effectively control the propulsion operation of the same droplet in the microfluidic device, the present invention provides an improved method of manufacturing the device, which allows greater design options for the gap height to match the electrode size in a designated area of the device. For example, a customized gap height at the location of the reagent input reservoir changes the frictional and capillary forces that dispense the droplets into the device. A larger gap height produces a more favorable capillary action. Smaller gap heights in conjunction with smaller electrodes improve droplet volume control. Some operations are also improved, such as mixing, where droplets can move from areas with large gap heights to areas with small gap heights. A smaller effective gap height also allows for the use of less reagent volume. Reagents for some assays are very expensive, so the ability to efficiently perform reactions and manipulations with reduced reagent volumes offers a potential cost advantage.

Having shown and described herein a preferred embodiment of the invention, it should be understood that this embodiment is provided by way of example only. Those skilled in the art can make many changes, changes and substitutions without departing from the spirit of the present invention. It is therefore intended that the appended claims cover all such variations as fall within the spirit and scope of the invention.

The contents of all of the above patents and applications are incorporated herein by reference in their entirety. In the event of any inconsistency between the contents of this application and any patents and applications incorporated herein by reference, the contents of this application shall control to the extent necessary to resolve such inconsistency.

10: Microfluidic devices 12: Upper substrate 14: Lower substrate 16: Continuous electrode 18a: electrode 18b: electrode 20: Dielectric material 22a: Hydrophobic material layer 22b: Hydrophobic material layer 24a: spacer 24b: spacer 25: Clearance 26a: Cross section area 26b: Cross section area 30: Microfluidic Devices 31: Continuous electrode 32: upper substrate 34: Lower substrate 36: Additional material 38: Continuous electrode 40: electrode 40a: short electrode 40b: high electrode 41: Dielectric layer 42a: Hydrophobic material layer 42b: Hydrophobic material layer 44a: spacer 44b: spacer 45: Gap 50: Microfluidic Devices 52: upper substrate 54: Lower substrate 56: Common electrode layer 60: Dielectric material 62a: Hydrophobic layer 62b: Hydrophobic layer 64a: spacer 64b: spacer 64c: spacer 66: Clearance

200: Dielectric Wetting (EWoD)

202: oil

204: water drop

205:Propulsion electrode

206: Upper electrode

207: Hydrophobic coating

208: dielectric layer

210: Negative charge induced in a liquid at the liquid/dielectric interface above an electrode receiving an AC signal

212: This pixel always has the opposite charge of the charge induced at the droplet interface

214: Apply AC voltage to the electrode, this figure shows an example of positive charge on the electrode

216: Positive charge induced when a negative voltage is applied to the electrode

218: Droplets move in this direction

The drawings illustrate one or more implementations in accordance with the concepts of the present invention, which are presented by way of example only and not by way of limitation. Drawings are not to scale. In the drawings, the same reference numerals refer to the same or similar elements.

FIG. 1 is a schematic cross-sectional side view of an EWoD device according to a first embodiment of the present invention.

2 is a schematic cross-sectional side view of an EWoD device according to a second embodiment of the present invention.

3 is a schematic cross-sectional side view of an EWoD device according to a third embodiment of the present invention.

4 is a schematic cross-sectional side view of an EWoD device according to a fourth embodiment of the present invention.

Fig. 5 is a schematic cross-sectional side view of a conventional EWoD device.

10: Microfluidic devices

12: Upper substrate

14: Lower substrate

16: Continuous electrode

18a: electrode

18b: electrode

20: Dielectric material

22a: Hydrophobic material layer

22b: Hydrophobic material layer

24a: spacer

24b: spacer

25: Clearance

26a: Cross section area

26b: Cross section area

Claims (9)

A microfluidic device comprising: (a) an upper plate, which includes: an upper substrate; a first layer of hydrophobic material, which is connected to the surface of the upper substrate; a continuous electrode, which is located between the first layer of hydrophobic material and the between an upper substrate, wherein the upper substrate has a uniform thickness, and an additional material of non-uniform thickness positioned between the upper substrate and the continuous electrode and the first layer of hydrophobic material; (b) a lower substrate comprising : a lower substrate; a plurality of electrodes, which are connected to the lower substrate; a second layer of hydrophobic material, which is connected to the lower substrate and is positioned above the plurality of electrodes; wherein the upper plate and the lower plate are arranged in a spaced relationship, thus A gap having a plurality of heights is defined between the first and the second layers of hydrophobic material to allow droplet motion within the plurality of heights of the gap upon application of a propulsion voltage, wherein the gap has the plurality of heights heights to form a plurality of designated operating areas, and wherein the first height of the plurality of heights of the gap in one of the designated operating areas is different from the gap in at least one of the other designated operating areas The second height of the plurality of heights. The microfluidic device of claim 1, wherein the upper plate is attached to the lower plate such that the upper plate is fixed relative to the lower plate. The microfluidic device as claimed in claim 1, further in the plurality of electrodes A dielectric material layer is included between the second layer of hydrophobic material. The microfluidic device of claim 1, wherein the first and second layers of hydrophobic material are located on opposite sides of the gap. The microfluidic device according to claim 1, further comprising one or more spacers between the upper substrate and the lower substrate. The microfluidic device as claimed in claim 1, wherein the plurality of electrodes comprises two or more sets of electrodes, and the side lengths of the electrodes of the first set of the two or more sets of electrodes are different from the lengths of the sides of the electrodes of the second set of the two or more sets of electrodes The side length of the electrode. The microfluidic device according to claim 1, wherein the plurality of designated operation areas include a transport area, a split area, a distribution area, and a mixing area. A method of manufacturing a microfluidic device, which includes: providing a first substrate and a second substrate; applying an additional material with a non-uniform thickness, a continuous electrode, and a first layer of hydrophobic material to the surface of the first substrate to form a plurality of A plate with an upper thickness; applying a plurality of electrodes to the surface of the second substrate, and applying a second layer of hydrophobic material on the plurality of electrodes to form a lower plate; and placing the lower plate in a spaced relationship, defined in A gap having a plurality of heights between the first and second layers of hydrophobic material to allow droplet motion within the plurality of heights of the gap under an applied push voltage, wherein the gap has the plurality of heights heights to form a plurality of designated operating areas, and wherein the first height of the plurality of heights of the gap in one of the designated operating areas is different from that of the gap in at least one of the other designated operating areas The second height of the plurality of heights. The method according to claim 8, wherein the plurality of electrodes comprises two or more sets of electrodes, and the side lengths of the electrodes in the first set are different from the lengths of the sides of the electrodes in the second set.

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