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.
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.
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.
In one example, the base layer 110 can be molded over the die to form a coplanar surface (see e.g.,
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 110 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
In some examples, at least one other die can be positioned in line with the die in the base layer 110 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
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.
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.
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.,
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
In view of the foregoing structural and functional features described above, an example method will be better appreciated with reference to
Proceeding to
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.
Filing Document | Filing Date | Country | Kind |
---|---|---|---|
PCT/US2017/028808 | 4/21/2017 | WO | 00 |
Publishing Document | Publishing Date | Country | Kind |
---|---|---|---|
WO2018/194648 | 10/25/2018 | WO | A |
Number | Name | Date | Kind |
---|---|---|---|
6548895 | Benavides et al. | Apr 2003 | B1 |
6790011 | Le Pesant et al. | Sep 2004 | B1 |
7524464 | Ahn et al. | Apr 2009 | B2 |
7547380 | Velev | Jun 2009 | B2 |
7658829 | Kanagasaba et al. | Feb 2010 | B2 |
7682817 | Cohen et al. | Mar 2010 | B2 |
7754150 | Wada et al. | Jul 2010 | B2 |
8021961 | Sparks | Sep 2011 | B2 |
8403557 | Li et al. | Mar 2013 | B2 |
9481945 | Juncket et al. | Jan 2016 | B2 |
9421544 | Wang | Aug 2016 | B2 |
20030153119 | Nathan | Aug 2003 | A1 |
20030183525 | Elrod et al. | Oct 2003 | A1 |
20030215335 | Criveiii | Nov 2003 | A1 |
20040028566 | Ko et al. | Feb 2004 | A1 |
20040163958 | Kao et al. | Aug 2004 | A1 |
20050196321 | Huang | Sep 2005 | A1 |
20080169197 | McRuer et al. | Jul 2008 | A1 |
20080199362 | Chong et al. | Aug 2008 | A1 |
20080210306 | Xie et al. | Sep 2008 | A1 |
20090326279 | Tonkovich et al. | Dec 2009 | A1 |
20100018584 | Bransky et al. | Jan 2010 | A1 |
20100181195 | Garcia Tello | Jul 2010 | A1 |
20110020141 | Van Zon et al. | Jan 2011 | A1 |
20110220505 | Wang et al. | Sep 2011 | A1 |
20120298233 | Rothacher | Nov 2012 | A1 |
20130118901 | Pollack et al. | May 2013 | A1 |
20130121892 | Fuhrmann et al. | May 2013 | A1 |
20130206597 | Wang | Aug 2013 | A1 |
20140051159 | Bergstedt et al. | Feb 2014 | A1 |
20140083858 | Teh et al. | Mar 2014 | A1 |
20150001083 | Martin et al. | Jan 2015 | A1 |
20150306598 | Khandros et al. | Oct 2015 | A1 |
20160296929 | Chen et al. | Oct 2016 | A1 |
20170141278 | Hamaguchi | May 2017 | A1 |
20180015460 | Sells et al. | Jan 2018 | A1 |
Number | Date | Country |
---|---|---|
1499949 | May 2004 | CN |
103170383 | Jun 2013 | CN |
104603595 | May 2015 | CN |
105916689 | Aug 2016 | CN |
102004011667 | Nov 2005 | DE |
1643288 | Apr 2006 | EP |
2003294770 | Oct 2003 | JP |
2004000935 | Jan 2004 | JP |
2005292092 | Oct 2005 | JP |
2010539503 | Dec 2010 | JP |
2012112724 | Jun 2012 | JP |
2016153725 | Aug 2016 | JP |
200534916 | Nov 2005 | TW |
200911375 | Mar 2009 | TW |
201525464 | Jul 2015 | TW |
2005075081 | Aug 2005 | WO |
2006044966 | Apr 2006 | WO |
2009004533 | Jan 2009 | WO |
2012085728 | Jun 2012 | WO |
2014165373 | Oct 2014 | WO |
2015019520 | Feb 2015 | WO |
2016111251 | Jul 2016 | WO |
2016122554 | Aug 2016 | WO |
2016122572 | Aug 2016 | WO |
Entry |
---|
Brown et al., An Experimental Validation of the Pressure Capacity of a Modular Gasketless Microfluidic Interconnect, 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, 14CBMS-0001, Oct. 26-30, 2014, pp. 1665-1667. |
Le et al., Fabrication of 25 um-filter microfluidic chip on silicon substrate, Advances in Natural Sciences: Nanoscience and Nanotechnology 8/1/015003, 2017, 11 pages. |
Jung et al., A novel actuation method of transporting droplets by using electrical charging of droplet in a dielectric fluid, AIP Biomicrofluidics Fundamentals, Perspectives & Applications, 3(2): 022402, 2009, 7 pages. |
Zhou et al., One-Step Injection Molding of Oste+Microfluidic Devices With Screw Threaded Ports, 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, 14CBMS-0001 , Oct. 26-30, 2014, pp. 1671-1673. |
Wood et al., Microfabricated high-throughput electronic particle detector, Review of Scientific Instruments 78, 104301, 2007, 6 pages. |
Xu et al, A Droplet-Manipulation Method for Achieving High-Throughput in Cross-Referencing-Based Digital Microfluidic Biochips, IEEE Transaction on Computer-Aided Design of Integrated Circuits and Systems, vol. 27, No. 11, Nov. 2008, pp. 1905-1917. |
International Search Report dated Jan. 31, 2018 for PCT/US2017/028808, Applicant Hewlett-Packard Development Company, L.P. |
Fan et al., Droplet-on-a-wristband: Chip-to-chip digital microfluidic interfaces between replaceable and flexible electrowetting modules, the Royal Society of Chemistry, Lab on a Chip, vol. 11, 2011, pp. 343-347. |
Number | Date | Country | |
---|---|---|---|
20200038872 A1 | Feb 2020 | US |