BACKGROUND

[0001] Fluid processing systems can be constructed in very small packages and are sometimes referred to as lab-on-a-chip. These systems can be based upon

micromanipulation of discrete fluid droplets on micro-liter or smaller scales. Thus, micro-fluidic processing can be performed on unit-sized packets of fluid that are then transported, stored, mixed, reacted, and/or analyzed in a discrete manner using a standard set of basic fluid control instructions. These basic fluid control instructions can be combined and reused within hierarchical design structures such that more complex fluid processing procedures (e.g., chemical synthesis or biological assays) can be constructed.

BRIEF DESCRIPTION OF THE DRAWINGS

[0002] FIG. 1 illustrates a top view of an example apparatus for fluid manipulation.

[0003] FIG. 2 illustrates a view of layers of to fabricate an example apparatus for fluid manipulation.

[0004] FIG. 3 illustrates a side view of an example apparatus for fluid manipulation.

[0005] FIG. 4 illustrates a top view of an example apparatus for fluid manipulation.

[0006] FIG. 5A illustrates a top view of an example fluidic transport layer for fluid manipulation.

[0007] FIG. 5B illustrates a magnified view of a wire bonding area between a die and a printed circuit assembly depicted in FIG. 5A.

[0008] FIG. 6 illustrates a bottom view of a reagent packs that are coupled to a base layer for fluid manipulation.

[0009] FIG. 7 illustrates an example fabrication method for a fluid manipulation assembly. [00010] FIGS. 8 through 12 illustrate an example fabrication process to form an apparatus containing multiple die that can be installed as a coplanar assembly with a base player.

[00011] FIG. 13 illustrates an alternative coplanar assembly process between a die and a base layer.

DETAILED DESCRIPTION

[00012] A digital microfluidic (DMF) apparatus is provided to enable fluid manipulation of larger droplets that can be exchanged via user-accessible input/output (I/O) ports. Small volumes of the fluid (e.g., droplets) can be routed via channels from the I/O ports to designated manipulation and/or mixing areas of the apparatus. Fluid

routing/manipulation can be digitally controlled via integrated dies (e.g., silicon dies with electrode control elements) for more precise pico-liter, nano-liter, and/or micro-liter processing of the fluids. A hybrid construction of the DMF apparatus, which includes electrode-carrying dies disposed in surface of a base layer, allows a less expensive material (compared to all silicon implementations) to provide a base layer for supporting the I/O ports, channels and other microfluidic structures while also providing supporting a number of die in the base layer. Since less silicon can be used in the DMF apparatus, the overall cost can be reduced accordingly.

[00013] As a further example, a coplanar construction is provided where the base layer and the die layer are integrated to provide a substantially smooth, coplanar fluid manipulation surface to mitigate impediments to fluid flow across the die. Instead of constructing the base out of silicon as in previous implementations, the base can be constructed of a more inexpensive material (e.g., polymer or copolymer) while providing DMF control via a number of smaller integrated die residing in the base layer. In one example, the base layer supports a die that includes a fluid droplet manipulation surface which is co-planar with a surface of the base layer. The integrated DMF apparatus can be constructed to ensure that the die surface is substantially coplanar with a surface of the base layer. The die includes a control electrode (or electrodes) to generate an electric field to perform manipulation (e.g., mixing/routing) of fluids across the fluid manipulation surface of the die. For instance, the die can also include control circuitry to implement the fluid manipulation via the electrodes.

[00014] FIG. 1 illustrates a top view of an example apparatus 100 for fluid droplet manipulation. The apparatus 100 includes a base layer 1 10 that provides a substrate to support a fluid manipulation assembly (e.g., integrated assembly for routing and/or mixing fluids). The base layer 1 10 can provide a substrate composed of a single material (e.g., polymer resin) or can provide a substrate assembly of more than one material (e.g., layered materials forming the base layer). In one example, the base layer 1 10 can be formed as an epoxy molding compound (EMC), such as a

thermosetting epoxy polymer resin material (e.g., catalog no. CEL400ZHF40WG from Hitachi, Inc.). An example amount of epoxy molding material to fabricate a base layer to support a 30mm x 30mm substrate size is about two grams. A die 130 includes side edges that extend longitudinally (Along Y axis) between spaced ends of the die. Each side edge of the die 130 forms a coplanar surface with the polymer base layer 1 10 that contact each adjacent edge of the polymer base layer.

[00015] In one example, the base layer 1 10 can be molded over the die to form a coplanar surface (see e.g., FIGS. 8-12). In another example, the die 130 can be inserted into a recessed portion of the base layer to form a coplanar surface (see e.g., FIG. 13). The die 130 can include a control electrode 140 which can be electrically connected to receive electrical energy (e.g., from a power supply) and generate an electrical field to perform manipulation of fluid across the fluid manipulation surface of the die. Example fluids that can be manipulated on the fluid manipulation surface of the die can include biological fluids, reagents, chemicals, aqueous solutions, oils, and sample preparation fluids, for example.

[00016] As used herein, the term "substantially coplanar" refers to aligning the top surface of the die 130 with the top surface of the base layer 1 10 such that substantially no impediment to fluid flow occurs at the juncture between the two surfaces and from an interconnect formed between an input/output port and the die. Fabrication processes are described herein with respect to FIGS. 8-13 to provide the coplanar construction. Such coplanar fabrication allows the base layer 1 10 to be fabricated out of a less expensive material (as opposed to being the same material as the die) while the die 130 which includes fluidic flow controls described herein can have its area minimized to reduce overall assembly costs. As shown, the die 130 includes the control electrode (or electrodes) 140 to control fluid flow across the surface of the die. The control electrode can be used to generate an electric field to perform fluid manipulation across the surface of the die. In addition to control electrodes 140, the die 130 can include other logic such as switches of control devices to control the electrodes. Control devices in some examples can also be implemented in external processing circuits where control signals form such devices are routed via printed circuit board connections which are described below with respect to FIGS. 2-5.

[00017] In some examples, at least one other die can be positioned in line with the die in the base layer 1 10 or positioned at a different angle from the die in the base layer to enable routing of fluids in more than one dimension (e.g., dies are fabricated at right angles to allow fluidic control in multiple dimensions). The die 130 can be formed of silicon but other semiconductor types are possible. Example fabrication processes for achieving coplanar fabrication between dissimilar base layer and die materials are disclosed herein with respect to FIGS. 8-13.

[00018] The control electrode 140 supports mixing and routing of fluid droplets across the surface of the die 130. Fluid droplets can be formed using the surface tension properties of liquid. For example, water placed on a hydrophobic surface will lower its contact with the surface by creating drops whose contact angle with the substrate can increase as the hydrophobicity increases. However, in some cases it is possible to control the hydrophobicity of the substrate by using electrical fields which are provided by the electrodes 140. This is sometimes referred to as "Electro-wetting On Dielectric" or EWOD (e.g., a hydrophobic layer disposed over a dielectric layer, which is disposed over the co-planar surface of the die and base layer). Such electrode implementations can be referred to as digital micro-fluidic (DMF) applications. FIGS. 2 though 6 below illustrate an example fabrication process to provide a DMF assembly where fluid can be manipulated (e.g., mixed and routed).

[00019] FIG. 2 illustrates a view of layers of to fabricate an example apparatus 200 for fluid droplet manipulation. A polymer base layer 210 includes a die (single or multiple) 230. The die 230 includes a fluid manipulation surface that is substantially coplanar with a surface of the base layer 210. The die 230 includes a control electrode (or electrodes) to perform manipulation of fluid across the fluid droplet manipulation surface of the die.

[00020] A fluidic transport layer 240 includes a fluidic channel (or channels) fluidly coupled with an input/output (I/O) port 250 and supported by the base layer 210. The I/O port 250 can be spaced apart from the fluid manipulation surface of the die 230. The fluidic channel (not visible but fabricated within transport layer) extends

longitudinally across the fluidic transport layer 240 from the die 230 to the I/O port 250. Fluid can be injected (e.g., via pipette dispenser) into the port 250 and travel to the channel for mixing/routing and/or extracted according to interaction with the one or more electrodes of the die 230. As shown, the fluidic transport layer 240 can be mounted on top of the base layer 210 and can provide one or more fluidic channels to couple fluids from one or more I/O ports such as shown at 250 to the fluid droplet manipulation surface of the die 230.

[00021] In an example, the fluidic transport layer 240 can be coated with a conductive layer (not shown) to provide a return path for the control electrode to perform

manipulation of fluids across the fluid droplet manipulation surface of the die 230. In another example, the fluid transport layer is not coated and all control current paths are routed to the die 230 (e.g., both power and return path electrode for manipulating fluids routed to die). The fluidic transport layer 240 can include a mixing area (see e.g., FIG. 5) to enable premixing of fluids before the fluids are injected into the I/O port 250. The fluidic transport layer 240 can also include a reagent port (see e.g., FIGS. 4 and 5) to receive a reagent fluid to be mixed with the fluids in the mixing area or to be mixed with fluids in the fluidic channel of the fluidic transport layer 240.

[00022] A reagent storage package 270 (e.g., blister pack) can be coupled to the base layer 210 to provide the reagent fluid to the reagent port of the fluidic transport layer 240. In another example, the reagent storage package 270 can be coupled to a separate reagent layer before coupling the reagent layer to the base layer 210. The reagent storage package 270 can be pressed by a user to release the reagent fluid for mixing at the fluid transport layer 240 via the reagent port. A printed circuit assembly (PCA) 280 having a connector 290 can be mounted on top of the fluidic transport layer via adhesive 294. The PCA 280 couples the control electrode from the connector 290 to the die 230 via a wire bonding area depicted in FIG. 5B. The fluidic transport layer 240 can be formed in one or more layers of a Cyclic Olefin Polymer (COP) or Cyclic Olefin Copolymer (COC), for example. Other materials can be used in other examples.

[00023] FIG. 3 illustrates a side view of the example apparatus depicted in FIG. 2 for fluid droplet manipulation. This view shows the layers depicted in FIG. 2 after they have been fabricated into a single fluid manipulation assembly. As shown, the reagent storage package 270 is coupled to a surface of the base layer 210 that is opposite the fluid manipulation surface thereof. The fluidic transport layer 240 is mounted on the base layer 210. The printed circuit assembly (PCA) 280 having a connector 290 is mounted on top of the fluidic transport layer 240. Input/output (I/O) port 250 of the fluidic transport layer 240 is shown appearing through an opening of the PCA 280 (shown as reference numeral 244 in FIG. 4).

[00024] FIG. 4 illustrates a top view of an example apparatus for fluid droplet manipulation. This view shows the top view of the apparatus depicted in FIGS. 2 and 3. In this view, the connector 290 is mounted on PCA 280. An opening 244 in the PCA 280 allows access to I/O port 250 of the fluidic transport layer 240. In this example, ten I/O ports are shown but more or less than ten ports can be provided. The base layer 210 provides support for the overall assembly. A die (or dies) 230 can be mounted in the base layer 210 and connected through the PCA 280 to the connector 290. A reagent portal 294 in the fluidic transport layer 240 is provided to allow reagent fluid to be injected from the reagent storage package (not visible in this view) through the base layer 210 to the mixing area and/or fluidic channels of the fluidic transport layer that are described below with respect to FIG. 5A.

[00025] FIG. 5A illustrates a top view of an example fluidic transport layer 500 and printed circuit assembly (PCA) 504 for fluid droplet manipulation. One or more I/O ports 510 can be provided to allow users to insert or extract fluids to a fluidic channel 520 providing access to a die 530. A wire bonding area 534 for connecting the PCA 504 to the die 530 can provided, where a magnified view of the wire bonding area is depicted in FIG. 5B. An opening 540 at the bottom of the I/O port 510 provides access to the fluidic channel 520. Connections 550 in the PCA 504 can be provided for mounting a connector as described herein (not shown in this view). The fluidic transport layer 500 can include a mixing area 560 to enable premixing of fluids before the fluids are injected into the I/O port 540 (e.g., provide a macro mixing area for fluid before it is injected into the I/O port). The fluidic transport layer 500 can also include a reagent port 570 (or ports) to receive a reagent fluid to be mixed with the fluids in the mixing area 560 or to be mixed with fluids in the fluidic channel 520 of the fluidic transport layer 500. The I/O port 520 can be spaced apart from the fluid droplet manipulation surface of the die 530. The fluidic channel 520 extends longitudinally across the fluidic transport layer from the die 530 to the I/O port 520. As shown, other ports (or port pairs and channels) can be spaced in parallel to the port 510 along the surface of the fluidic transport layer 500.

[00026] FIG. 5B illustrates a magnified view of the wire bonding area 534 of FIG. 5A where connections can be made between the die 530 and the printed circuit assembly 504 depicted in FIG. 5A. An example wire 536 is shown connecting the PCA 504 to the die 530. The wire bonding assembly can occur after the various layers described herein have been constructed to form a microfluidic assembly. A polymer cap (not shown) can be placed over the wire bonding area 534 to seal the area after the wires have been bonded.

[00027] FIG. 6 illustrates a bottom view of reagent storage package (or packages) 610 that are coupled to a base layer 620 for fluid droplet manipulation. The storage packages can be ruptured by user pressure to inject reagent fluids to the channels and/or mixing areas of the fluidic transport area such as via the reagent port 570 described above with respect to FIG. 5A.

[00028] In view of the foregoing structural and functional features described above, an example method will be better appreciated with reference to FIG. 7. While, for purposes of simplicity of explanation, the method is shown and described as executing serially, it is to be understood and appreciated that the method is not limited by the illustrated order, as parts of the method could occur in different order and/or concurrently from that shown and described herein. Such method can be executed by various components configured as machine readable instructions stored in memory and executable in an IC or a processor, for example.

[00029] FIG. 7 illustrates an example fabrication method 700 for a fluid droplet manipulation assembly. At 710, the method 700 includes joining a die to a polymer base layer. The die includes a control electrode at a fluid manipulation surface of the die to generate an electric field to perform microfluidic manipulation of fluid across the fluid manipulation surface of the die. A distal portion of the die extends from the fluid manipulation surface of the die into the polymer base layer such that the fluid

manipulation surface of the die remains exposed and substantially coplanar with an exposed adjacent surface of the base layer (see e.g., FIGS. 8-1 1 ). At 720, the method 700 includes forming a fluidic transport layer on the exposed surfaces of the base layer and the die. The fluidic transport layer includes a fluidic channel and an input/output (I/O) port (see e.g., FIG. 12). The channel fluidly couples the I/O port and the fluid manipulation surface of the die. Although not shown, with respect to joining the die, the method can include placing the die on a carrier layer and molding an Epoxy Molding Compound (EMC) on top of the die and the carrier layer to form the coplanar surface with the polymer base layer. In an alternative method such as depicted in FIG. 13, the die can be inserted into a recessed portion of the base layer to form a coplanar surface for fluid manipulation.

[00030] FIGS. 8 through 12 illustrate assembly fabrication process to form a die that can be molded to a base layer to provide a DMF apparatus as disclosed herein. In this example, the die and base layer can be formed of different material and the die and the base layer be integrated into a common package where their surfaces that are substantially coplanar. In this example, the die can be formed of a semiconductor material and base layer is formed of a relatively less expensive material (e.g., a polymer, such as EMC). To begin the coplanar fabrication process at FIG. 8, a temporary carrier 810 (e.g., ceramic) is provided having a tape lamination layer 820. At FIG. 9 of the coplanar process, one or more dies 91 0 are attached to the tape lamination layer 820. The dies 910 can be placed via a pick and place integrated circuit placement process, for example.

[00031] Proceeding to FIG. 10 of the coplanar fabrication process, a base layer at 1010 can be molded over the dies. The base layer 1 010 can include a liquid molding compound, such as an EMC, for example. Proceeding to FIG. 1 1 of the coplanar fabrication process, carrier 810 and tape layer 820, are removed (e.g., de-bonded via heat treatment) after the base layer 1010 has been formed and cured. Proceeding to FIG. 12, a fluidic transport layer 1220 can be attached to the base layer and die assembly of FIG. 1 1 . Although a molding processes is shown FIGS. 8-12 where co- planarity is provided between the die and base layer, an alternative coplanar fabrication process is depicted in FIG. 13 where the die is fitted into a preexisting recessed portion of the base layer.

[00032] FIG. 13 illustrates an alternative coplanar assembly process between a die 1300 and a base layer 1310. As shown, the base layer includes a recessed portion 1320 where the die 1300 can be installed. The die 1300 can be assembled into a preformed pocket or recessed portion 1320 in the base layer 1310, where the die should be sufficiently planar, and no appreciable gap should exist between the die edge and the base layer edge. To achieve this in one example, a small amount of adhesive can be stamped into the recessed portion 1320 (or needle dispensed around the perimeter of the recessed portion). The amount of adhesive can be tuned to ensure a slightly proud adhesive, or nearly flush. After the die 1300 is placed into the recessed portion 1320, a film that is designed to not stick to the adhesive during cure such as Teflon coated films can be used to "planarize" the perimeter where the die edge meets the base layer 1310 during cure. Subsequently this films can be peeled off, leaving a sufficiently co-planar and no appreciable gap between the die 1300 and the base layer 1310. Another example approach can be to use the channel layer itself as a planarizing film to mitigate this gap. In this case, if there is a small step at the edge of the die 1300, a thick film (e.g., 2-4 urn) of polymer material may be used to fill in this small gap (e.g., <10um), and attempt to planarize between the die and base layer.

[00033] What have been described above are examples. One of ordinary skill in the art will recognize that many further combinations and permutations are possible.

Accordingly, this disclosure is intended to embrace all such alterations, modifications, and variations that fall within the scope of this application, including the appended claims. Additionally, where the disclosure or claims recite "a," "an," "a first," or "another" element, or the equivalent thereof, it should be interpreted to include one or more than one such element, neither requiring nor excluding two or more such elements. As used herein, the term "includes" means includes but not limited to, and the term "including" means including but not limited to. The term "based on" means based at least in part on.