Conductive spacers for microfluidic devices

Abstract

To provide a microfluidic device such as an active matrix electrowetting on dielectric (AMEWOD) device that allows a complex circuit configuration.SOLUTION: A microfluidic device of the present invention comprises: a first substrate and a second substrate; a gasket 10 spacing the first substrate from the second substrate to define a fluid chamber between the first substrate and the second substrate; and one or more ports 18, 28 for introducing a fluid sample into the fluid chamber. An inner edge face of the gasket defines a lateral boundary of the fluid chamber. A plurality of independently addressable array elements are provided on a surface of the first substrate facing the fluid chamber, and at least one circuit element is disposed on a surface of the second substrate facing the fluid chamber. The gasket is configured to provide a conductive path between the circuit element disposed on the surface of the second substrate facing the fluid chamber and an associated terminal.SELECTED DRAWING: Figure 2a

Description

[Technical Field]

[0001] The present invention relates to microfluidic devices and methods of using microfluidic devices. Aspects of the invention relate to precharging droplets of fluid as they are transferred into the microfluidic device or at some point after they have been transferred into the microfluidic device. Further aspects of the invention relate to conductive circuits for characterizing one or more droplets in a microfluidic device. [Background technology]

[0002] Applicant's co-pending European Patent Applications No. 18182737.9, No. 18182772.6, No. 18194096.6 and No. 18194098.2 disclose aspects of microfluidic systems including side-fill structures and molded housings for microfluidic devices, the contents of which are incorporated herein by reference.

[0003] Patent Document 1 discloses a method for driving an electrowetting display panel and an electrowetting display device for implementing the method.

[0004] Non-Patent Document 1 describes "Droplet Transport Using a Precharging Method for Digital Microfluidics." The authors state that a droplet is first charged by applying a "precharge" voltage between the droplet and an electrode embedded under a dielectric layer. Then, the droplet is driven to the next electrode by applying a "drive" voltage between two adjacent embedded electrodes. The concept of precharging is demonstrated by the polarity of the charge accumulated on the droplet. If a droplet is precharged with a positive voltage, it is driven with a negative voltage, and vice versa. Choi et al. also state, "In this paper, we propose a new droplet driving scheme for single-plate digital microfluidic devices through the use of a 'droplet precharge' method." Choi et al. do not disclose an enclosed microfluidic device in which a gasket (which may be a conductive gasket) exists to define the gap distance between plate elements having conductive circuits thereon.

[0005] FIG. 1 is a schematic perspective view illustrating the details of an exemplary active matrix electrowetting-on-dielectric (AM-EWOD) device 10. The AM-EWOD device 10 includes a lower substrate 12 having thin-film electronics 14 disposed thereon, and a reference electrode (not shown) integrated into an upper substrate 16. The lower and upper substrates 12 and 16 define a channel or gap (also called a "fluid chamber") between them. The electrode configuration may be reversed, with the thin-film electronics integrated into the upper substrate and the reference electrode integrated into the lower substrate. The thin-film electronics 14 are arranged to drive array element electrodes 18. A plurality of array element electrodes 118 are arranged in an electrode or element array 120 having X by Y array elements, where X and Y can be any integer. The term "plate element" may be used to refer to the combination of a substrate with various components, such as any electrode(s) and / or any thin-film electronics, disposed on the substrate.

[0006] The droplet 122 may comprise any polar liquid, typically aqueous, and is enclosed between the lower substrate 14 and the upper substrate 16 separated by a spacer 124, although it will be understood that there may be multiple droplets 122. The droplet 122 may typically reside within a layer of a non-polar liquid, which may be an oil (not shown) that generally fills the channel between the lower substrate 12 and the upper substrate 16.

[0007] Droplets 122 containing polar materials, i.e., droplets manipulated by operation of the AM-EWOD device, must be input into the AM-EWOD channels from an external "reservoir" of fluid. The external reservoir may be, for example, a pipette or a structure built into the device housing. As fluid from the reservoir enters the AM-EWOD, oil may generally be displaced and removed from the AM-EWOD channels.

[0008] The droplets (122) may be manipulated in an automated manner to perform certain protocols or tests. For testing, it may be possible to perform tests on the droplets while they remain inside the device. The droplets may be interrogated in several ways, including electrical and optical methods. For electrical interrogation, more complex device configurations may be required than when electrical interrogation is not performed.

[0009] Microfluidic devices, such as electrowetting-on-dielectric (EWOD) devices, function most effectively when the droplet is in full or intimate electrical contact with a reference electrode. In many devices, the reference electrode is provided by a simple conductive substrate that faces another (more complex) substrate containing the EWOD electrode, which physically contains the device's fluid and is also used to define the device's cell gap.

[0010] This reference electrode would most ideally be connected to the same drive electronics board that supplies the signal to the main EWOD substrate, so that if an AC voltage is used (as is typically the case), the frequency of the signal applied to the reference electrode matches the frequency of the signal applied to the EWOD element. This halves the maximum voltage signal required from the EWOD substrate, making it possible to use TFT electronics as the drive electronics on the substrate of the EWOD device.

[0011] The connection from the main driving electronics to the reference electrode can be achieved externally (e.g., by using overlapping substrates and cables as shown schematically in Figure 12(a)), but is better achieved by including a pad for the desired reference voltage on the bottom substrate and making an internal connection, e.g., using a blob of solder paste or other conductive material, to the reference electrode on the opposing (top) substrate separated by the device's cell gap. A similar technique is used to provide electrical connections in liquid crystal displays (LCDs). Such an internal connection is shown in Figure 12(b). Such a connection structure may be referred to as a "top-plate via."

[0012] In some devices, it is desirable for the top substrate electrode to be more complex than a single reference electrode, resulting in the need to make multiple independent electrical connections to the top substrate. This requires either reverting to the inelegant overhang technique of Figure 12(a) or facing the technical challenge of creating several top plate vias. Creating multiple top plate vias with a simple solder paste blob may be possible for a small number of electrodes, but quickly becomes more difficult as the number of required electrical connections to the top plate increases. In extreme cases, the top plate may require as many or perhaps more separate electrical connections as the EWOD substrate—e.g., tens or hundreds—and the required connection pitch may be too small to use multiple solder paste blobs. [Prior art documents] [Patent documents]

[0013] [Patent Document 1] U.S. Patent No. 9,019,200 [Non-patent literature]

[0014] [Non-Patent Document 1] Choi, K., Im, M., Choi, JM et al., MicrofluidNanofluid (2012) 12:821(https: / / link.springer.com / article / 10.1007 / s10404-011-0921-3) Summary of the Invention

[0015] The present invention provides microfluidic devices, such as electrowetting on dielectric (EWOD) devices or active-matrix electrowetting on dielectric (AMEWOD) devices, which allow for more complex circuit configurations. The spacers or gaskets used to hold the top and bottom plate elements at a fixed gap distance also provide conductive paths between circuit elements and associated terminals located on the surface of the second substrate facing the fluid chamber. In one aspect, a gasket that forms a conductive bridge between the bottom and top plate elements is used as a spacer to hold the top and bottom plate elements at a fixed gap distance. In a further embodiment, a spacer including multiple conductive circuit elements is provided, which facilitates performing more complex electrical measurements of droplets present in the fluid chamber of the AMEWOD device.

[0016] A first aspect of the present invention provides a microfluidic device comprising: a first substrate and a second substrate; a gasket separating the first substrate from the second substrate to define a fluid chamber between the first and second substrates, the inner edge surface of the gasket defining a lateral boundary of the fluid chamber; a plurality of independently addressable array elements provided on a surface of the first substrate facing the fluid chamber; at least one circuit element disposed on a surface of the second substrate facing the fluid chamber; and at least one port for introducing a fluid sample into the fluid chamber, wherein the gasket is configured to provide a conductive path between the circuit element disposed on the surface of the second substrate facing the fluid chamber and an associated terminal.

[0017] In one embodiment, the terminals are provided on the first substrate and the gasket provides a conductive path that extends through at least the thickness of the gasket.

[0018] In one embodiment, the gasket provides a conductive path that extends further within the plane of the gasket.

[0019] In one embodiment, the terminals are provided on the gasket at locations spaced from the inner edge surface of the gasket, and the gasket provides a conductive path that extends at least within the plane of the gasket.

[0020] In one embodiment, the gasket is electrically conductive in bulk.

[0021] In one embodiment, a plurality of circuit elements are provided on a surface of the second substrate facing the fluid chamber, and the gasket is configured to provide a plurality of independent conductive paths, each conductive path between a respective one of the circuit elements and a respective associated terminal.

[0022] In some embodiments, the gasket includes a protruding portion that protrudes beyond the first and second substrates, and the conductive pathway extends through the protruding portion of the gasket.

[0023] In one embodiment, an electrically conductive layer is provided on a surface of the second substrate facing the fluid chamber layer, and circuit elements are defined in the electrically conductive layer.

[0024] In one embodiment, the gasket further provides a conductive path between a conductive member disposed on a portion of the inner edge surface of the gasket and an associated terminal.

[0025] In one embodiment, the gasket comprises a material having an anisotropic electrical conductivity, and optionally the gasket comprises a material that is electrically conductive in a thickness direction of the gasket and substantially non-conductive in a direction perpendicular to the thickness direction ("thickness direction" means a thickness "h" that defines the separation between the first and second substrates, as referred to below).

[0026] In one embodiment, the inner edge surface of the gasket is shaped to define at least one port.

[0027] Another aspect of the present invention provides a method comprising introducing a fluid sample into a fluid chamber of a device according to any one of claims 1-11, controlling array elements provided on a first substrate of the device to move the fluid sample adjacent to a circuit element or a selected one of the circuit elements arranged on a second substrate, and applying a voltage to a terminal associated with the circuit element or the selected circuit element.

[0028] In one embodiment, the method comprises applying a voltage to thereby charge the fluid sample.

[0029] In one embodiment, the method comprises performing one or more further fluidic operations on the charged fluid sample. Performing one or more further fluidic operations on the charged fluid sample may comprise, for example, separating at least one fluidic droplet from the fluid sample.

[0030] In one embodiment, the method comprises applying a voltage, thereby passing a measurement signal, through the fluid sample.

[0031] As will be described in more detail in the description of the embodiments, aspects of the present invention can provide many advantages. In some embodiments, the gasket (which also functions as a spacer) may be an isotropic gasket / spacer, in that at a certain point within the gasket, the conductivity of the gasket has the same value in all directions. This embodiment allows the spacer to be used to precharge droplets immediately after loading into the microfluidic device, thus obtaining better dispensing of the droplets. It also allows the position of the spacer relative to the array elements of the device to be detected, thus checking that the device is correctly manufactured.

[0032] In other embodiments, the gasket / spacer is an anisotropic spacer. In one example, the spacer may be a spacer that is conductive in only one direction, or at least preferentially in one direction, such as a z-conducting spacer (potentially achieved using a thick ACF film), or it may be a more complex circuit, such as a gasket made using FPC manufacturing methods. The advantages described for isotropic gaskets / spacers also apply to anisotropic spacers, but the anisotropy offers additional advantages. For example, multipoint electrical connections to the spacer can be provided, enabling top-plate resistance checks (which cannot be done with a completely isotropic spacer because a current path through the spacer would exist, making such measurements impossible. However, such measurements may be possible using a spacer with two or more portions that are individually isotropically conductive but insulated from each other). A further advantage is the ability to transmit multiple pairs of sensing signals to / from the droplet through the top-plate substrate.

[0033] In a further embodiment, the gasket / spacer is an anisotropic spacer and is used for sensing purposes (i.e., to detect the position and / or properties of droplets within a microfluidic device). Signals to / from the droplets can be carried directly through the spacer rather than through the top plate electrodes, thereby eliminating the need for appropriate circuitry or tracks on the top plate.

[0034] In a further embodiment, the gasket / spacer is a shielding spacer. The spacer does not have patterning in the xy plane, but provides a conductive shield around the edges of the microfluidic device to shield droplets within the device. This can be done, for example, using a multi-layer spacer formed from tape, conductive layers, tape, etc. [Brief explanation of the drawings]

[0035] [Figure 1] FIG. 1 shows a prior art dielectric electrowetting device. [Figures 2a-2g] 2a-2g show top plan views of one embodiment of the present invention illustrating the loading and subsequent dispensing of a droplet from a fluid reservoir, with the sample being loaded along the edge of the top substrate. [Figures 3a-3e] 3a-3e show top plan views of one embodiment of the present invention illustrating the loading and subsequent dispensing of a droplet from a fluid reservoir, where the sample is loaded through an opening in the surface of the top substrate. [Figures 4a-4f] 4a-4f show top plan views of one embodiment of the present invention in which additional conductive circuitry is provided on the upper substrate and tracked through the upper substrate to corresponding electrode pads on the lower substrate. [Figures 5a-5e] Figures 5a-5e show top plan views of an embodiment of the invention similar to that shown in Figure 4, except that the tracks are within the gasket of the device instead of passing through the top substrate. [Figure 6a-6b] 6a and 6b show a top plan view of a further embodiment of the invention in which the conductive paths within the gasket lead directly out of the device to an external connector rather than being routed to electrode pads on the underlying substrate. [Figure 7a-7b] 7a-7b show a top plan view of a further embodiment of the present invention in which an anisotropic gasket provides electrical contact to both the bottom and top substrates. [Figures 8a-8d] 8a-8d show a top plan view of a further embodiment of the invention, in which a patterned top substrate overhangs the edge of the device, and electrical contact is made between the top substrate and the device via a flexible printed circuit element. [Figure 9a-9b] 9a-9b show a top plan view of a further embodiment of the invention in which there is no electrode pattern on the top substrate as electrical signals to / from the droplet are transmitted directly through the gasket rather than via the top substrate electrodes. [Figure 10a] FIG. 10a shows a top plan view of a further embodiment of the invention, in which the gasket is multi-layered and allows for either pre-charging of droplets within the device or electrical shielding of the upper substrate electrode from circuitry on the lower substrate, or both. [Figures 10b-10c] Figures 10b and 10c show partial cross-sectional views through the EWOD of Figure 10a. [Figure 10d] FIG. 10d shows a top plan view of a further embodiment of the invention, in which the gasket is multi-layered and allows for either pre-charging of droplets within the device or electrical shielding of the upper substrate electrode from circuitry on the lower substrate, or both. [Figure 11a-11b] 11a and 11b are schematic cross-sectional views of an EWOD device according to a further embodiment of the present invention. [Figure 12a-12b] 12a and 12b are schematic diagrams of two known techniques for making electrical connections to the top substrate of a microfluidic device. [Figure 13] FIG. 13 shows another application of the EWOD device according to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0036] 2a-2g show top plan views of one embodiment of the present invention in which an isotropic gasket is used to form a gap between the top and bottom plates of an AMEWOD device. Figure 2a shows a top plan view of an exemplary AMEWOD device (10) according to one embodiment of the present invention, in which a liquid sample is introduced into the device along the edge of the top substrate. The AMEWOD device (10) comprises a bottom substrate (12), a gasket (14), a top substrate (16), ports (18, 28), an edge connector (20), and contact pads (22). For clarity, Figure 2b shows only the gasket (14) and top substrate (16), and Figure 2c shows only the bottom substrate. Line 23 in Figure 2c indicates the boundary of the active area of ​​the device.

[0037] The fluid chamber of the EWOD device corresponds to an opening or bore inside the gasket, and the boundaries of the fluid chamber are defined by the lower substrate, the upper substrate, and the inner edge surfaces of the gasket.

[0038] The edge connector (20) includes multiple contacts (24). Typically, the AMEWOD device (10) includes multiple ports (18) for applying a liquid sample (typically a polar liquid sample) and a single port (28) for applying a fill fluid (not shown). The fill fluid is typically a non-polar fluid, non-limiting examples of which include silicone oil, fluorosilicone oil, pentane, hexane, octane, decane, dodecane, pentadecane, and hexadecane, which may generally be referred to as oil. According to the embodiment of FIG. 2, the ports (18, 28) are defined by the edge profile configuration of the gasket (14) and the edge (16a) of the upper substrate (16). The ports (18, 28) thus allow a liquid sample to be loaded into a cavity (26) defined between the lower substrate (12) and the upper substrate (16), the height of which is determined by the thickness of the gasket (14). The opening through which the liquid sample is introduced is therefore defined by the inner edge surface 14a of the gasket and the outer edge 16a of the upper substrate (16).

[0039] In the embodiment of FIGS. 2a-2c, as shown in FIG. 2b, the inner edge surface 14a of the gasket 14 includes an edge profile configuration including inwardly oriented protrusions 14b (i.e., toward the interior of the fluid chamber). When the AM-EWOD device is assembled, the protrusions 14b overlap the upper substrate 16, while an area of ​​the gasket between two adjacent protrusions does not overlap the upper substrate 16, thereby forming a fluid input port 18, 28. (Alternatively, the gasket can be understood as having a recess 14c defined in the inner edge 14a.) The inner edge 14a of the gasket and the edge 16a of the upper substrate are not limited to the specific arrangement shown in FIG. 2a or 2b. Other arrangements may be used, provided that at least one of the inner edge 14a of the gasket and the edge of the substrate is not straight, resulting in at least one area of ​​the gasket not overlapping the upper substrate 16, thereby forming a port 18. Although Figure 2b shows the fluid chamber as generally rectangular with the inner edge surface 14a of the gasket defining the generally rectangular perimeter of the fluid chamber, the invention is not limited in principle to rectangular fluid chambers.

[0040] The lower substrate (12), the inner edge surface 14a of the gasket (14), and the upper substrate (16) define a cavity (26) therebetween, the cavity having a height h determined by the thickness of the gasket (14), and a width w and length l defined by the inner edge length dimension. Here, the height h is preferably at least about 25 μm, at least about 50 μm, at least about 75 μm, at least about 100 μm, at least about 150 μm, at least about 200 μm, at least about 250 μm, at least about 300 μm, at least about 400 μm, at least about 500 μm, at least about 600 μm, at least about 700 μm, at least about 800 μm, at least about 900 μm, or at least about 1000 μm, and the width w is preferably at least about 5 mm, at least about 7.5 mm, at least about 10 mm, at least about 12.5 mm, at least about 15 mm, at least about 17.5 mm, or at least about at least about 20 mm, at least about 22.5 mm, at least about 25 mm, at least about 27.5 mm, at least about 30 mm, at least about 32.5 mm, at least about 35 mm, at least about 37.5 mm, at least about 40 mm, at least about 50 mm, at least about 55 mm, at least about 60 mm, at least about 65 mm, at least about 70 mm, at least about 75 mm, at least about 80 mm, at least about 85 mm, at least about 90 mm, at least about 95 mm, at least about 100 mm, at least about 125 mm, at least about 150 mm, at least about 175 mm, at least about 200 mm. The length 1 is preferably at least about 10 mm, at least about 15 mm, at least about 20 μm, at least about 25 mm, at least about 30 mm, at least about 35 mm, at least about 40 mm, at least about 45 mm, at least about 50 mm, at least about 55 mm, at least about 60 mm, at least about 65 mm, at least about 70 mm, at least about 75 mm, at least about 80 mm, at least about 85 mm, at least about 90 mm, at least about 95 mm, at least about 100 mm, at least about 125 mm, at least about 150 mm, at least about 175 mm, or at least about 200 mm.In use, the cavity (26) is typically filled with oil before a polar liquid sample is applied to the device.

[0041] In this embodiment, the gasket 14 is an isotropic, electrically conductive gasket (14). The gasket is formed from a conductive material, examples of which include metal, carbon, or a material containing metal or carbon particles. Generally, some medium must be present to connect the bulk of the gasket material to its surface to establish electrical contact between the upper and lower substrates. For example, the gasket may be a double-sided carbon tape containing a conductive adhesive on both sides of the tape, such as that used to mount samples for SEM measurements. Alternatively, the gasket may be composed of a non-adhesive metal layer that electrically contacts the upper and lower substrates via a conductive adhesive or paste, such as a silver-containing paint or glue. The gasket is generally uniform in its structural composition, particularly in the distribution of its conductive components, so that electrical current can flow freely throughout its thickness. The isotropic gasket (14) forms a conductive path between the contact pads (22) and at least one conductive element (not shown) on the upper substrate (16).

[0042] The lower substrate (12) has a first major surface covered by a dielectric insulating layer and having at least one conductive element disposed thereon, and a hydrophobic layer (not shown). The at least one conductive element is connected to at least one contact (24) of the edge connector (20). (In an AM-EWOD device, multiple array elements, each with an associated element electrode, are typically provided on the lower substrate. Each array element is connected to one or more contacts of the edge connector (20).) Contact pads (22) not covered by the dielectric layer and hydrophobic layer are conductively connected to the contacts (24) of the edge connector (20), such as a PCB (printed circuit board) connector. The upper substrate (16) has a major surface on which at least one conductive element is disposed, and is covered by a layer of hydrophobic material (not shown). The at least one conductive element on the upper substrate (16) does not have a hydrophobic layer at a location that contacts the isotropic gasket (14). Thus, the isotropic gasket 14 forms a conductive path between the contacts 24 of the edge connector 20 on the lower substrate and at least one conductive element on the upper substrate 16 via the contact pads 22 (as shown in FIG. 2a, the gasket 14 does not overlap any of the other connectors 20 of the edge connector 24). The respective surfaces of the lower substrate 12 and the upper substrate 16 bearing conductive elements are held in a facing arrangement, with a gap distance defined by the isotropic gasket 14. This is shown in FIG. 2d, a partial cross-sectional view of the device of FIG. 2a (the dielectric layer, insulating layer, and contacts 24 and edge connector 20 are omitted from FIG. 2d for ease of illustration).

[0043] When a droplet of liquid, e.g., a polar liquid such as saline, is present in the cavity (26), a capacitively coupled circuit is formed when the droplet forms a bridge between the respective conductive elements on the lower substrate (12) and the upper substrate (16). Such droplets can therefore be controlled by electrowetting, as described, for example, in U.S. Patent Application Publication No. 2018 / 0284423, the contents of which are incorporated herein by reference. Figures 2e-2g show the AM-EWOD device of Figure 2a after introducing a liquid sample (30) through port (18 or similar) of the AM-EWOD device (10) into fluid chamber 26, which was previously at least partially filled with oil via port (28). The liquid sample (30) can be introduced through port (18), for example, using a pipette or syringe (not shown). After initially (Figure 2e) applying the liquid sample (30) through port (18), the liquid sample (30) can be transported into cavity (26) by electrowetting. A microprocessor (not shown) can be configured to run a script to execute a protocol designed to control the movement of polar liquid samples by electrowetting.

[0044] When the liquid sample 30 enters the cavity 26, it can move by electrowetting and come into contact with the edge elements 32 of the isotropic gasket 14 that are exposed within the cavity 26 (FIG. 2f). When the liquid sample 30 comes into contact with the edge elements 32 of the isotropic gasket 14, a charging voltage can be applied to the liquid sample 30. The charging voltage can be applied between the conductive elements (e.g., array element electrodes) of the lower substrate 12 and the edge elements 32 of the isotropic gasket 14. When the liquid sample 30 is charged after coming into contact with the edge elements 32, it can move to another location within the cavity 26 by electrowetting. Applicant's co-pending application, U.S. Patent Application No. 15 / 661,609, filed July 27, 2017, which is incorporated herein by reference, describes an electrowetting on dielectric (EWOD) device having a pre-charge structure for pre-charging a fluid reservoir.

[0045] FIG. 2g illustrates dispensing individual droplets 34 from the liquid sample 30 after charging the liquid sample 30 through contact with the edge elements 32. Charging the liquid sample 30 through contact with the edge elements 32 can alter the surface tension characteristics at the interface between the liquid sample 30 and the oil used to fill the cavity 26. When a scripted microprocessor (not shown) applies an electrowetting "dispense" sequence to the AMEWOD device 10, the efficiency with which the droplets 34 separate from the liquid sample 30 is improved compared to a liquid sample that is not charged upon contact with the edge elements 32. The beneficial effects of charging the liquid sample may vary based on the composition of the liquid sample.

[0046] 2b is not electrically continuous around the perimeter of the device, but rather consists of two conductive sections insulated from each other (e.g., using a non-conductive adhesive), each section attached to one of the top plate via structures 22 on the lower substrate. In this embodiment, it is also possible to perform a continuity test remotely from the edge connector, through one via, through the common electrode, and back through the other via 22 to another terminal on the edge connector, thereby testing the electrical connection to the top plate.

[0047] Figures 3a-3e illustrate a further embodiment of the invention in which a liquid sample is applied to an AMEWOD device (10) through one or more openings in the surface of an upper substrate. In such an embodiment, one or more openings 18 are provided in the upper substrate (16) and align with the edge profile configuration along the inner periphery of the isotropic gasket (14). Figure 3a is a top view of the device according to this embodiment, while Figure 3b shows the upper substrate separately for ease of illustration. The gasket 14 and lower substrate of this embodiment generally correspond to the gasket 14 and lower substrate of Figures 2b and 2c, respectively.

[0048] Thus, the liquid sample can enter the AMEWOD device 10 through openings in the top substrate 16 (compared to ports 18, 28 in the embodiment shown in FIG. 2). In FIGS. 2a-2c, the top substrate 16 has a length and width that are smaller than the length and width of the isotropic gasket 14, and the edges of the top substrate 16 are configured to bisect the edge profile configuration of the isotropic gasket 14 near the inner edge of the gasket that defines the cavity 26. According to the embodiment of the invention shown in FIG. 3, the top substrate 16 has a length and width that are equal to or substantially equal to the length and width of the isotropic gasket 14.

[0049] Figure 3a shows a top plan view of an AMEWOD device (10) according to a further embodiment of the present invention, prior to the introduction of a liquid sample. Ports (18, 28) are located along the periphery of the upper substrate (16), coinciding with the regions between adjacent edge profile configurations of the isotropic gasket (14). The ports (18, 28) are typically provided by drilling holes in the substrate. A hydrophobic coating (not shown) applied to the upper substrate (16) is removed in at least one region corresponding to the gasket (14) in the assembled device, thereby forming a conductive path from contacts (22) on the lower substrate (connected to respective terminals of the edge connector) to at least one conductive element on the surface of the upper substrate (16) in contact with the isotropic gasket (14).

[0050] Figures 3c-3e show the progression of a droplet 30 being introduced into the EWOD device 10 through an opening 18 or similar in the surface of the upper substrate 16. When the droplet 30 is applied through the port 18, it is first moved by the EWOD into the cavity 26 (Figure 3c). The droplet 30 is then moved to contact an edge element 32 of the isotropic gasket 14 (Figure 3d). While in contact with the edge element 32, a voltage is applied to the droplet 30 to charge it. Following contact with the edge element 32, once the droplet 30 is charged, it is again moved by the EWOD to a further location within the cavity 26 (Figure 3e). A microprocessor configured to run a script (not shown) causes the droplet 34 to be dispensed from the liquid sample 30. The droplets (34) can then be used for further reaction processes or schemes within the AMEX device (10) according to their intended use.

[0051] In the embodiment of FIGS. 2 and 3, gasket 14 is “isotropic” in that it is made from a bulk conductive material, so that the electrical conductivity at a point within the gasket has the same or substantially the same value in all directions (which may typically be uniform or generally uniform throughout the gasket). (A “bulk” property of a material, also known as an “intensive property,” is a local physical property of the material whose value does not depend on the amount of material being measured.) In other embodiments, the gasket is not isotropic, but rather its conductivity is anisotropic in some sense; for example, the conductivity may vary throughout the volume of the gasket to define independent conductive paths separated by insulating regions, or the gasket may be made from a material that conducts electricity in only one direction, or at least preferentially in one direction.

[0052] Figure 11a shows a cross-sectional view of a microfluidic device with a gasket made of a material that conducts electricity in the z-direction (the vertical direction in Figure 11a) but not along the x- and y-directions, known as a "z-conducting spacer." Multiple electrodes are located on the upper substrate, which are addressed by a corresponding set of electrodes on the lower substrate (labeled "EWOD substrate" in Figure 11a) and connected to respective terminals of a connector (e.g., an edge connector similar to those in Figures 2 and 3) on the lower substrate. The gasket has minimal conductivity perpendicular to the z-direction, shorting the multiple electrodes in the z-direction. Thus, the gasket provides via regions that electrically connect the electrodes on the upper substrate to corresponding electrodes on the lower substrate while ensuring that the electrodes on the upper substrate are isolated from other electrodes on the lower substrate. Such an anisotropic gasket can be achieved by using an anisotropic conductive film (ACF) or paste (ACP) by itself (so that the gasket is formed of a bulk of anisotropic conductive material), or by using an anisotropic conductive film (ACF) or paste (ACP) in conjunction with structural features of the gasket that allow electrical conduction in only one direction. Another method of making an anisotropic gasket is by the traditional method used to make FPCs (flat printed circuits), where the vias are made from copper and the insulating portions between them are made from Kapton™.

[0053] FIG. 11b shows an embodiment in which the "xy" locations of the electrodes on the two opposing substrates are mismatched, and therefore the gasket requires a more complex design to provide "xy" connection routing of conductive paths that extend in the z-direction (through the thickness of the gasket) and also extend within the plane of the gasket (the xy plane) to provide electrical connection between the electrodes on one substrate and the electrodes on the other substrate. This can be achieved, for example, by providing a patterned conductive layer, such as an FPC, that provides electrical connection from the electrodes on the lower substrate to points on the lower substrate that are below the corresponding electrodes on the upper substrate. Electrical connection to the electrodes on the upper substrate is completed by vias in the gasket, for example, by using a gasket formed of a material that is electrically conductive in the z-direction but not in the x- and y-directions, or by other techniques described herein.

[0054] In yet another embodiment of the present invention, an AMEWOD device (10) is shown in top plan view in Figures 4a-4f. Figure 4a schematically illustrates an AMEWOD device (10) similar to the embodiment shown in Figure 3, but with some modifications. Figure 4b is a cross-sectional view of the device of Figure 4a taken along the dashed line shown in Figure 4a. As shown in Figure 4a, the top substrate (16) extends to the outer dimensions of the isotropic gasket (14).

[0055] In Figure 4c, the upper substrate (16) is separately illustrated. As shown in Figures 4a and 4c, the upper substrate includes an array of electrode pairs (36, 38), which may be located near the edge of the upper substrate. As shown in Figure 4b, a conductive layer 41 may be deposited on the surface of the upper substrate 16, and this conductive layer may be patterned to define the electrode pairs. The remaining portion of the conductive layer may be used to provide a continuous conductive element, such as a common electrode. As shown in Figures 4a and 4c, the electrodes of the electrode pair protrude beyond the gasket into the fluid chamber. Although Figures 4a and 4c show the electrodes of the electrode pair extending approximately perpendicular to the boundary of the fluid chamber, this embodiment is not limited thereto. The electrodes of the electrode pair may include (or be connected to) respective conductive tracks that extend to the edge of the upper substrate. For simplicity, two electrode pairs (36, 38) are shown in the diagram of FIG. 4a, but it will be understood that fewer or more electrode pairs (36, 38) may be provided. For example, a pair of electrodes may be provided corresponding to each edge profile element (32) of the gasket (14). It will be further understood that multiple electrode pairs (36, 38) may be provided on a single edge profile element (32) or in permutations, e.g., one edge profile element may include a single electrode pair, one edge profile element may include two or more electrode pairs, and yet another edge profile element may not have an electrode pair. In yet another embodiment, a common terminal, such as a negative terminal, may be implemented that serves as a pair for multiple individual positive terminals.

[0056] As shown in FIG. 4d, the gasket is provided with conductive portions 22′ that, when the device is assembled, contact each of the conductive tracks on the upper substrate and also contact corresponding conductive tracks on the lower substrate (shown separately in FIG. 4e). Thus, the electrodes of the electrode pairs 36, 38 can be electrically coupled through their respective conductive bridges 22′ to contacts of the extended edge connector 20′ on the edge of the lower substrate 12 for connection to a control device (not shown). The upper substrate 16 adjacent the cavity 26 may comprise a continuous conductive element as described hereinabove, but the area surrounding the electrode pairs 36, 38 may comprise an insulating region 40 such that the electrodes of the electrode pairs are electrically isolated from each other and from the continuous conductive element. Each respective electrode pair (36, 38) can be used for a variety of purposes, including, but not limited to, i) performing electrochemical measurements, such as amperometric or potentiometric measurements, of the droplets, ii) applying a charging voltage to the droplets, and iii) determining the impedance characteristics of the droplets. Figure 4f shows the presence of a droplet (42) at each electrode of each respective electrode pair (36, 38). The characteristics of each droplet (42) may be determined as appropriate by a suitable measurement process, or a charging voltage may be applied to such droplets.

[0057] Schlicht et al. describe "Droplet-interface-bilayer assays in microfluidic passive networks" (Scientific Reports, (2015) v5 pp9951). In a further aspect of the present invention, pairs of droplets (42) may be manipulated by EWOD to contact and subsequently form stable droplet interface bilayers (DIBs). Such droplet pairs can then be moved by EWOD to contact their respective electrode pairs (36, 38). When each droplet contacts a respective electrode and the pair of droplets (42) that formed the DIBs are held in contact with the electrode pair (42), a circuit is formed across the DIB interface. An electrode pair (36, 38) is then used to monitor the transport of solutes from one droplet to another across the DIB interface, detected as a change in the current that flows when a fixed voltage is applied between the electrode pair (36, 38).

[0058] In an alternative embodiment, the necessary conductive electrode paths between the measurement pads (contacting the droplet) on the upper substrate and the corresponding pads on the lower substrate are created via conductive tracks in the gasket, as opposed to tracks in the upper substrate to pads aligned vertically between the upper and lower substrates (as in FIG. 4). This embodiment is illustrated in FIGS. 5a-5e. FIG. 5a is a top plan view of an EWOD device according to this embodiment, showing the upper substrate (16) having smaller length and width dimensions than the isotropic gasket (14), as described with respect to FIG. 2, such that the edge of the upper substrate (16) bisects the edge profile configuration of the isotropic gasket (14) along the inner edge of the gasket that defines the cavity (26). Thus, the port (18) is defined by the edge of the upper substrate (16) and the edge structure of the isotropic gasket (14).

[0059] The electrode pairs (36, 38) shown in Figure 5a are configured differently from the embodiment shown in Figure 4. As shown in Figure 5c, a top view of the upper substrate, the portions of each electrode pair (36, 38) exposed on the upper substrate (16) and extending into the cavity (26) are fabricated similarly to those in Figure 4 insofar as they are defined in a conductive layer disposed on the surface of the upper substrate (16) facing the lower substrate (12), as shown in Figure 5c, a top view of the upper substrate. However, as shown in Figure 5d, a top view of the gasket, the electrode pair tracks (36', 38') are provided in / on the gasket (14). When the device is assembled, the electrode tracks in / on the gasket make electrical contact with the electrode pairs (36, 38) on the upper substrate (16) and, via conductive bridges (22′), with the terminals of the extended edge connector (20′) on the lower substrate (12). (If desired, the respective parts may be directly coupled to each other, but they do not need to be physically coupled to each other as long as a conductive path exists between them.) The lower substrate is shown in plan view in Figure 5e (the inner rectangle in Figure 5e indicates the boundary of the fluid chamber). Figure 5b is a partial cross-sectional view of the EWOD device along the dashed line shown in Figure 5a, and also shows the electrical connections between the electrode tracks in / on the gasket, the electrode pairs (36, 38) on the upper substrate (16), and the terminals of the extended edge connector (20′) on the lower substrate.

[0060] In the structures described so far, the goal is to connect one or more electrodes on the upper substrate to corresponding terminals on the lower substrate, which has been achieved through different types of gaskets. One reason for doing this is that a single electrical connection is made between the lower substrate and the electronics board in the equipment driving the device. The electrical connection to the components on the upper substrate is made from the terminals on the lower substrate through the gasket, eliminating the need for terminals on the upper substrate for connection to the equipment. This electrical connection can be made in a variety of ways, including through a flexible printed circuit (FPC) connector or a printed circuit board (PCB) connector. If the number of contacts 24 in the edge connector 20 is so large that the width of each contact 24 and the spacing between them become too narrow, good electrical contact between each contact 24 and the receiving connector (not shown) in the equipment may be compromised. In such cases, one or more additional edge connectors (not shown) may be provided on another edge (e.g., on a long edge) of the lower substrate 12.

[0061] Alternatively, electrical connections to components on the upper substrate may be made directly through conductive paths within the anisotropic gasket 14'. Rather than routing a circuit from the upper substrate 16 through conductive pads 22', 40 onto the lower substrate 12 and then to an edge connector 20 on the lower substrate, an edge connector (not shown) may instead be provided along the outer edge of the gasket 14'. A potential advantage of forming electrical connections directly from the gasket 14' to the upper substrate 16 is that it minimizes the overall size of the lower substrate 12. Furthermore, it reduces the risk of conductive path damage between substrate layers. In this case, a fairly simple gasket may be used, as shown, for example, in FIG. 6a, a plan view of an EWOD device according to this embodiment, and in FIG. 6b, a plan view of the gasket of the EWOD device of FIG. 6a. The upper substrate of the EWOD device corresponds to the upper substrate of FIG. 5c and is provided with a common electrode and one or more electrode pairs 36, 38. The gasket is provided with conductive paths 25, and when the device is assembled, the common electrode and one or more electrode pairs 36, 38 are in electrical contact with the respective conductive paths in / on the gasket. The gasket shown here may be non-conductive for the majority of its length, but may, for example, have printed circuitry on only one surface and no "via" structures that create local electrical conductivity in the "z" direction.

[0062] The device of Figure 6a requires two separate edge connectors, or an edge connector having two portions, to provide the electrical interface between the device and the appliance: one connector (or portion) for connection to components provided on the upper substrate, and the other connector (or portion) for electrical connection to any components provided on the lower substrate. This is indicated by line 20a in Figure 6a, which shows that edge connector 20 has two portions: one portion for connection to components only on the lower substrate, and the other portion for connection only to the upper substrate, including connections to conductive tracks 36' and 38' (in this embodiment, the lower substrate may be generally conventional, e.g., a TFT lower substrate).

[0063] An alternative arrangement has a single FPC connector providing electrical connection to both the lower and upper substrates, as shown in Figures 7a and 7b. Figure 7a is a plan view of an EWOD device according to this embodiment, and Figure 7b is a plan view of a gasket 14'. (Only tracks from the upper substrate are shown; conductive tracks on the lower substrate are not shown, except for the edge connector 20.) Here, the anisotropic gasket 14' extends beyond the boundary of the lower substrate (12). Such an anisotropic gasket (14') may consist of an insulating layer with printed circuits on both sides (one side provides signals to / from the lower substrate, and the other side provides signals to / from the upper substrate, respectively). The thickness of the anisotropic gasket (14') determines the height of the cavity (26) in the electrowetting device. Alternatively, external electrical connections may be made directly to the top plate electrodes 36, 38 via conductive tracks 36', 38' rather than back to the edge connector 20.

[0064] FIG. 8a shows an EWOD device according to a further embodiment of the present invention, in which the upper substrate (16′) (shown in FIG. 8b) includes an extended long edge profile that covers the long edge of the lower substrate (12). Electrode pairs (36, 38) are etched into a conductive layer (such as an ITO layer) on the major surface of the upper substrate (16) facing the cavity (26). In the case of FIG. 8a, the gasket used to separate the upper substrate (16′) from the lower substrate (12) does not form an electrical bridge between the respective substrates. Rather, FPC or PCB connectors can be directly bonded to conductive tracks on the respective substrates for connection to equipment. FIG. 8c shows the EWOD device after the connector (shown in FIG. 8d), in this example an FPC (60), defines conductive paths (36′, 38′, 40′) that are electrically coupled to the respective elements of the upper substrate (16′). That is, the conductive paths 36', 38' on the connector are bonded to the electrodes of the electrode pairs 36, 38 defined in the ITO layer on the top substrate, and the remaining conductive paths (40') form an electrical path to the main portion of the ITO layer on the top substrate (16') which acts as a counter or ground electrode to the circuitry of the TFT layer on the bottom substrate (12). In the embodiment of Figure 7a, external electrical connections may be made directly to the top plate electrodes 36, 38 via conductive tracks rather than back to the edge connector 20.

[0065] In a further embodiment of the invention, as illustrated in Figures 9a-9b, discrete conductive circuits are provided within the anisotropic gasket (14'), but not on the inner surface of the upper substrate (16) facing the cavity (26). In such an embodiment, a single conductive layer is provided across the entire surface of the upper substrate (16) facing the cavity (26), for example to form a common electrode. The gasket 14' includes conductive paths / pads 40 that, when the device is assembled, contact pads 22 on the lower substrate and also contact a conductive layer on the inner surface of the upper substrate. The anisotropic gasket (14') also includes one or more electrode pairs (36", 38"), the ends of which may be contacted by pairs of liquid droplets (42). The gasket of the EWOD according to this embodiment may generally correspond to the gasket of Figure 5d when viewed in plan view, but the conductive paths 36', 38' may not contact the conductive layer on the inner surface of the upper substrate when the device is assembled, but instead may contact the fluid droplet 42 in the fluid chamber (e.g., the conductive paths 36', 38' may be formed as shown in Figure 10c below).

[0066] In some embodiments, the anisotropic gasket (14') may include one or more electrode pairs (36", 38") in a laminated structure, such as multiple conductive layers positioned one above the other with an insulating layer sandwiched between them. For example, the gasket may be multi-lamellar, a common structure used in flexible printed circuits (see, for example, https: / / kenvins.wordpress.com / 2014 / 07 / 25 / next-up-flexible-stackup-type-pcb / ). Thus, each electrode pair may operate in either the x- or z-plane of the cavity (26). As shown in FIG. 9a, conductive paths are connected through the gasket to the underlying substrate in the manner described with respect to FIGS. 4 and 5. However, it will be understood that the conductive paths may be connected directly to an external connector, for example, in the manner described with respect to FIG. 6.

[0067] As shown in Figures 10a-10d, when an anisotropic gasket (14') is utilized, a conductive edge (50) may be provided around the inner edge of the gasket that defines the gap between the lower substrate (12) and the upper substrate (16). The conductive edge (50) may be used to achieve voltage setting of a liquid sample in contact therewith, in a manner similar to that described in Figures 2e and 2f. An extended edge connector (20') may be provided on either side of the edge connector (20) to provide electrode pair tracks (36', 38') at the end of the AMEWOD device (10) for connection to an instrument (not shown). It should be noted that the conductive edge (50) must not contact the upper substrate to ensure that it does not contact the electrodes (36, 38) and form a short circuit between them. For similar reasons, it may also be disadvantageous for the conductive edge (50) to contact the lower substrate. A suitable structure may therefore be a layered gasket comprising at least three layers, the outer layers of which are non-conductive, as shown in Figure 10b, which is a cross-sectional view of the EWOD of Figure 10a taken along the dashed line in Figure 10a (the gasket of an EWOD according to this embodiment may generally correspond to the gasket of Figure 5d when viewed in plan, with the difference being that the edge profile configuration where the electrode pairs 36, 38 are present protrudes further towards the inside of the gasket).

[0068] In a further aspect of the invention, the conductive layer within the gasket of the previous embodiment can extend beyond the area shown in Figures 10a-10b to cover all or most of the area surrounding the active region on the lower substrate, as shown in another second cross-section in Figure 10c. This structure can have the advantage of reducing the likelihood that electrostatic discharge, either from a user of the AMEWOD device (10) or from the environment, will damage the sensitive thin-film transistor (TFT) circuitry present on the surface of the lower substrate (12) facing the cavity (26). The gasket effectively provides a conductive ring around the TFT circuitry that interfaces with contacts (24) on the edge connector (20). The conductive edge 50 connects to additional tracks (not shown) within the gasket that contact the lower substrate, so any electrostatic discharge onto the device can be conducted around the gasket rather than through the TFT layer.

[0069] In a further variation of Figures 10a-10d, the gasket may simply provide electrical shielding to limit the influence of the drive electronics surrounding the TFT electronics on the EWOD substrate, which could adversely affect device performance. In this case, the gasket may have a cross-section as shown in Figures 10b or 10c, i.e., a conductive layer or conductive edge 50 is present within the gasket, so that the gasket is not conductive throughout its thickness. In the "sandwich structure" of Figure 10c, for example, the two outer layers 51 may be layers of non-conductive adhesive, and only the inner conductive layer or conductive edge 50 is conductive. The inner conductive layer or conductive edge 50 may be grounded, connected to another reference electrode, or left floating.

[0070] FIG. 13 is a schematic diagram of another application of the device of the present invention. In this example, an electrode of an electrode pair is used as a sensing electrode that can pass electrical signals to and from adjacent droplets. The method of FIG. 13 can be performed, for example, using a device generally as shown in FIG. 4a, but with the spacing between the electrodes of the electrode pair being such that when two droplets contact the two electrodes of the pair, the two droplets touch each other, as shown in FIG. 13 (rather than being separated as shown in FIG. 4f). The electrodes of the electrode pair can be connected to appropriate drive / measurement electronics to monitor droplet properties such as resistivity.

[0071] In some embodiments, when an anisotropic gasket (14') is utilized, such a gasket can be realized using an anisotropic conductive film (ACF) (e.g., 3M ACF 7303 manufactured by Minnesota Mining and Manufacturing Company, Minnesota, USA, or Hitachi AC-7106U-25 manufactured by Hitachi, etc.). Such anisotropic materials comprise conductive particles dispersed in a non-conductive carrier. When such an ACF film is compressed, it becomes conductive through the thickness of the layer but remains insulating along its length and width.

[0072] Due to the limited conductive pathways that can be achieved when using ACF materials, multi-layer flexible circuits may be used to achieve anisotropic gaskets (14') that allow for the definition of more complex circuits within the AMEWOD device (10). (See, for example, https: / / www.flexiblecircuit.com / products / multi-layer-flex / ) Such circuits are typically made from layers of insulator (such as a polyimide, such as Kapton™) and layers of conductors, such as copper or gold. The inventions described in the claims of the original application are set forth below. [1] A microfluidic device, a first substrate and a second substrate; a gasket separating the first substrate from the second substrate to define a fluid chamber between the first and second substrates, the inner edge surface of the gasket defining a lateral boundary of the fluid chamber; a plurality of independently addressable array elements disposed on a surface of the first substrate facing the fluid chamber; at least one circuit element disposed on a surface of the second substrate facing the fluid chamber; at least one port for introducing a fluid sample into the fluid chamber; the gasket is configured to provide a conductive path between a circuit element disposed on a surface of the second substrate facing the fluid chamber and an associated terminal. Microfluidic devices. [2] The device described in [1], wherein the terminal is provided on the first substrate and the gasket provides the conductive path extending at least in the thickness direction of the gasket. [3] The device of [2], wherein the gasket provides the conductive path further extending within the plane of the gasket. [4] The device described in [1], wherein the terminal is provided on the gasket at a position away from the inner edge surface of the gasket, and the gasket provides a conductive path extending at least within the plane of the gasket. [5] The device according to any one of [1] to [4], wherein the gasket is electrically conductive in bulk. [6] A device described in any one of [1] to [4], wherein a plurality of circuit elements are provided on the surface of the second substrate facing the fluid chamber, and the gasket is configured to provide a plurality of independent conductive paths, each conductive path being between a respective one of the circuit elements and a respective associated terminal. [7] The device described in [6], wherein the gasket has a protruding portion that protrudes beyond the first substrate and the second substrate, and the conductive path extends to the protruding portion of the gasket. [8] The device described in [6] or [7], wherein an electrically conductive layer is provided on the surface of the second substrate facing the fluid chamber layer, and the circuit elements are defined within the electrically conductive layer. [9] The device of any one of [6], [7], or [8], wherein the gasket further provides a conductive path between a conductive member disposed on a portion of the inner edge surface of the gasket and an associated terminal.

[10] The device of any one of [6], [7], or [8], wherein the gasket comprises a material having anisotropic electrical conductivity, and optionally wherein the gasket comprises a material that is electrically conductive in a thickness direction of the gasket and substantially non-conductive in a direction perpendicular to the thickness direction.

[11] The device described in any one of [1] to

[10] , wherein the inner edge surface of the gasket is shaped to define the at least one port.

[12] Introducing a fluid sample into the fluid chamber of the device according to any one of [1] to

[11] . controlling the array elements disposed on the first substrate of the device to move the fluid sample adjacent to the circuit elements or a selected one of the circuit elements disposed on the second substrate; applying a voltage to the terminal associated with the circuit element or the selected circuit element; A method comprising:

[13] The method of

[12] , comprising applying the voltage to charge the fluid sample.

[14] The method of

[13] , further comprising performing one or more further fluidic operations on the charged fluid sample, and optionally, performing the one or more further fluidic operations on the charged fluid sample comprises separating at least one fluidic droplet from the fluid sample.

[15] The method of

[12] , comprising applying the voltage to pass a measurement signal through the fluid sample.

Claims

1. 1. A microfluidic device comprising: a first substrate and a second substrate; a gasket separating the first substrate from the second substrate to define a fluid chamber between the first and second substrates, the inner edge surface of the gasket defining a lateral boundary of the fluid chamber; a plurality of independently addressable array elements disposed on a surface of the first substrate facing the fluid chamber; at least one circuit element disposed on a surface of the second substrate facing the fluid chamber; at least one port for introducing a fluid sample into the fluid chamber; the gasket is configured to provide a conductive path between a circuit element disposed on a surface of the second substrate facing the fluid chamber and an associated terminal; the terminal is provided on the first substrate, and the gasket provides the conductive path extending at least in a thickness direction of the gasket; the gasket providing the conductive path further extending within the plane of the gasket; Microfluidic devices.

2. 10. The device of claim 1, wherein the terminals are disposed on the gasket at a location spaced from the inner edge surface of the gasket, the gasket providing a conductive path that extends at least within the plane of the gasket.

3. The device of any one of claims 1 to 2, wherein the gasket is electrically conductive in bulk.

4. 3. The device of claim 1, wherein a plurality of circuit elements are provided on the surface of the second substrate facing the fluid chamber, and the gasket is configured to provide a plurality of independent conductive paths, each conductive path between a respective one of the circuit elements and a respective associated terminal.

5. The device of claim 4 , wherein the gasket includes a protruding portion that protrudes beyond the first and second substrates, and the conductive pathway extends to the protruding portion of the gasket.

6. 6. The device of claim 4 or 5, wherein an electrically conductive layer is provided on the surface of the second substrate facing the fluid chamber layer, and the circuit elements are defined in the electrically conductive layer.

7. 7. The device of claim 4, 5, or 6, wherein the gasket further provides a conductive path between a conductive member disposed on a portion of the inner edge surface of the gasket and an associated terminal.

8. 7. The device of claim 4, 5, or 6, wherein the gasket comprises a material having anisotropic electrical conductivity, and optionally wherein the gasket comprises a material that is electrically conductive in a thickness direction of the gasket and substantially non-conductive in a direction perpendicular to the thickness direction.

9. The device of any one of claims 1 to 8, wherein the inner edge surface of the gasket is shaped to define the at least one port.

10. Introducing a fluid sample into the fluid chamber of the device according to any one of claims 1 to 9. controlling the array elements disposed on the first substrate of the device to move the fluid sample adjacent to the or selected one of the circuit elements disposed on the second substrate; applying a voltage to the terminal associated with the circuit element or the selected circuit element; A method comprising:

11. The method of claim 10, comprising applying the voltage to charge the fluid sample.

12. 12. The method of claim 11, comprising performing one or more further fluidic operations on the charged fluid sample, and optionally, performing the one or more further fluidic operations on the charged fluid sample comprises separating at least one fluidic droplet from the fluid sample.

13. The method of claim 10, comprising applying the voltage to pass a measurement signal through the fluid sample.

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