This application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/CN2018/093584, filed Jun. 29, 2018, the contents of which are incorporated by reference in the entirety.
The present invention relates to microfluidic technology, more particularly, to a digital microfluidic device, a microfluidic device, a lab-on-a-chip device, a digital microfluidic method, and a method of fabricating a digital microfluidic device.
Microfluidics enables precise control and manipulation of fluids that are geometrically constrained to small volumes (e.g., microliter-scale). Microfluidics can transform routine bioassays into rapid and reliable tests due to its rapid kinetics and the potential for automation. Digital microfluidics has been developed for miniaturized bioassays. The technique enables manipulation of discrete droplets of fluids across a surface of patterned electrodes. Using digital microfluidics, array-based bioassays can be easily performed to conduct various biochemical reactions by merging and mixing those droplets. Moreover, large, parallel scaled, multiplexed analyses can be performed using digital microfluidics. Digital microfluidics has found a wide variety of applications including cell-based assays, enzyme assays, protein profiling, and the polymerase chain reaction.
In one aspect, the present invention provides a digital microfluidic device, comprising a base substrate; and an electrode array including a plurality of discrete electrodes continuously arranged on the base substrate; wherein the plurality of discrete electrodes can be grouped into a plurality of first electrode groups, each of which comprising a plurality of directly adjacent discrete electrodes; a cross-section of each individual group of the plurality of first electrode groups along a plane substantially parallel to a main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a first direction; the plurality of discrete electrodes can be alternatively grouped into a plurality of second electrode groups, each of which comprising a plurality of directly adjacent discrete electrodes; a cross-section of each individual group of the plurality of second electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a second direction; the first direction and the second direction are different from each other.
Optionally, the cross-section of each individual group of the plurality of first electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape of a first convex-concave shape, a convex side of the first convex-concave shape protruding toward the first direction; and the cross-section of each individual group of the plurality of second electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape of a second convex-concave shape, a convex side of the second convex-concave shape protruding toward the second direction.
Optionally, the plurality of discrete electrodes can be alternatively grouped into a plurality of biconcave electrode groups and a plurality of biconvex electrode groups alternately arranged; a cross-section of each individual one group of the plurality of biconcave electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape of a biconcave shape; and a cross-section of each individual one group of the plurality of biconvex electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape of a biconvex shape.
Optionally, each individual one group of the plurality of biconcave electrode groups is directly adjacent to one or more groups of the plurality of biconvex electrode groups; and each individual one group of the plurality of biconvex electrode groups is directly adjacent to one or more groups of the plurality of biconcave electrode groups.
Optionally, each individual one group of the plurality of biconcave electrode groups has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of biconvex electrode groups; and each individual one group of the plurality of biconvex electrode groups has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of biconcave electrode groups.
Optionally, each individual one group of the plurality of biconcave electrode groups consists of a single biconcave electrode; and each individual one group of the plurality of biconvex electrode groups consists of a single biconvex electrode.
Optionally, each individual one group of the plurality of biconcave electrode groups has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of biconvex electrode groups; and each individual one group of the plurality of biconvex electrode groups has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of biconcave electrode groups.
Optionally, the digital microfluidic device further comprises a plurality of first signal lines and a plurality of second signal lines; wherein the plurality of first signal lines are respectively connected to the plurality of first electrode groups, each individual one of the plurality of first signal lines being connected to all of directly adjacent discrete electrodes in a respective one of the plurality of first electrode groups; and the plurality of second signal lines are respectively connected to the plurality of second electrode groups, each individual one of the plurality of second signal lines being connected to all of directly adjacent discrete electrodes in a respective one of the plurality of second electrode groups.
Optionally, the digital microfluidic device further comprises a plurality of first signal lines and a plurality of second signal lines; wherein a first directly adjacent pair of one of the plurality of biconcave electrode groups and one of the plurality of biconvex electrode groups are connected to a same one of the plurality of first signal lines but two different ones of the plurality of second signal lines; a second directly adjacent pair of one of the plurality of biconcave electrode groups and one of the plurality of biconvex electrode groups are connected to a same one of the plurality of second signal lines but two different ones of the plurality of first signal lines; and the first directly adjacent pair and the second directly adjacent pair have at least one electrode in common.
Optionally, each individual one of the plurality of first signal lines is connected to a respective one of the plurality of biconcave electrode groups and a respective one of the plurality of biconvex electrode groups directly adjacent to each other; each individual one of the plurality of second signal lines is connected to a respective one of the plurality of biconcave electrode groups and a respective one of the plurality of biconvex electrode groups directly adjacent to each other; each individual one of the plurality of biconcave electrode groups is connected to a respective one of the plurality of first signal lines and a respective one of the plurality of second signal lines; and each individual one of the plurality of biconvex electrode groups is connected to a respective one of the plurality of first signal lines and a respective one of the plurality of second signal lines.
Optionally, the plurality of biconcave electrode groups have a substantially uniform overall shape; and the plurality of biconvex electrode groups have a substantially uniform overall shape.
Optionally, each individual one of the plurality of discrete electrodes has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more of the plurality of the plurality of discrete electrodes.
Optionally, each individual group of the plurality of first electrode groups has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of second electrode groups; and each individual group of the plurality of second electrode groups has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of first electrode groups.
Optionally, numbers of discrete electrodes in each individual group of the plurality of first electrode groups is equal to or greater than 2; and numbers of discrete electrodes in each individual group of the plurality of second electrode groups is equal to or greater than 2.
Optionally, the digital microfluidic device further comprises a dielectric insulating layer on a side of the electrode array distal to the base substrate, and configured to insulate the plurality of discrete electrodes from each other; and a hydrophobic layer on a side of the dielectric insulating layer distal to the base substrate.
In another aspect, the present invention provides a microfluidic device comprising the digital microfluidic device described herein or fabricated by a method described herein.
In another aspect, the present invention provides a lab-on-a-chip device comprising the digital microfluidic device described herein or fabricated by a method described herein.
In another aspect, the present invention provides a digital microfluidic method, comprising selectively transporting a liquid droplet using the digital microfluidic device described herein or fabricated by a method described herein; wherein the digital microfluidic device comprises a base substrate; and an electrode array including a plurality of discrete electrodes on the base substrate; wherein the plurality of discrete electrodes can be grouped into a plurality of first electrode groups, each of which comprising a plurality of directly adjacent discrete electrodes; a cross-section of each individual group of the plurality of first electrode groups along a plane substantially parallel to a main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a first direction; the plurality of discrete electrodes can be alternatively grouped into a plurality of second electrode groups, each of which comprising a plurality of directly adjacent discrete electrodes; a cross-section of each individual group of the plurality of second electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a second direction; the first direction and the second direction are different from each other; the method comprises in a forward mode, sequentially actuating and de-actuating the plurality of first electrode groups one group after another, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along a forward direction; and in a backward mode, sequentially actuating and de-actuating the plurality of second electrode groups one group after another, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along a backward direction, the backward direction being different from the forward direction.
Optionally, the digital microfluidic device further comprises a plurality of first signal lines and a plurality of second signal lines; wherein the plurality of first signal lines are respectively connected to the plurality of first electrode groups, each individual one of the plurality of first signal lines being connected to all of directly adjacent discrete electrodes in a respective one of the plurality of first electrode groups; and the plurality of second signal lines are respectively connected to the plurality of second electrode groups, each individual one of the plurality of second signal lines being connected to all of directly adjacent discrete electrodes in a respective one of the plurality of second electrode groups; the method comprises in the forward mode, sequentially providing an actuating voltage to the plurality of first signal lines, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along the forward direction; and in the backward mode, sequentially providing an actuating voltage to the plurality of second signal lines, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along the backward direction.
Optionally, the plurality of discrete electrodes comprise a plurality of biconcave electrode groups and a plurality of biconvex electrode groups alternately arranged; a cross-section of each individual one of the plurality of biconcave electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape of a biconcave shape; and a cross-section of each individual one of the plurality of biconvex electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape of a biconvex shape; the method comprises selectively actuating and de-actuating directly adjacent pairs of one of the plurality of biconcave electrode groups and one of the plurality of biconvex electrode groups one pair after another, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate.
Optionally, the digital microfluidic device further comprises a plurality of first signal lines and a plurality of second signal lines; wherein a first directly adjacent pair of one of the plurality of biconcave electrode groups and one of the plurality of biconvex electrode groups are connected to a same one of the plurality of first signal lines but two different ones of the plurality of second signal lines; a second directly adjacent pair of one of the plurality of biconcave electrode groups and one of the plurality of biconvex electrode groups are connected to a same one of the plurality of second signal lines but two different ones of the plurality of first signal lines; and the first directly adjacent pair and the second directly adjacent pair have at least one electrode in common; the method comprises in the forward mode, sequentially providing an actuating voltage to the plurality of first signal lines, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along the forward direction; and in the backward mode, sequentially providing an actuating voltage to the plurality of second signal lines, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along the backward direction.
In another aspect, the present invention provides a method of fabricating a digital microfluidic device, comprising forming an electrode array including a plurality of discrete electrodes on a base substrate; wherein the plurality of discrete electrodes can be grouped into a plurality of first electrode groups, each of which comprising a plurality of directly adjacent discrete electrodes; a cross-section of each individual group of the plurality of first electrode groups along a plane substantially parallel to a main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a first direction; the plurality of discrete electrodes can be alternatively grouped into a plurality of second electrode groups, each of which comprising a plurality of directly adjacent discrete electrodes; a cross-section of each individual group of the plurality of second electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a second direction; the first direction and the second direction are different from each other.
The following drawings are merely examples for illustrative purposes according to various disclosed embodiments and are not intended to limit the scope of the present invention.
The disclosure will now be described more specifically with reference to the following embodiments. It is to be noted that the following descriptions of some embodiments are presented herein for purpose of illustration and description only. It is not intended to be exhaustive or to be limited to the precise form disclosed.
To manipulate droplets of fluids using digital microfluidics, a driving voltage is required on the electrodes. Typically, a voltage having a level greater than 100 V is needed to effectively manipulate the droplets. As a high voltage may trigger certain side reactions between reagents in the droplets, this presents a limitation to the application of digital microfluidics in certain fields.
In conventional digital microfluidics, the electrodes for driving the droplets are typically made of a square shape. A droplet partially overlaps with a square electrode thereby forming a contact line. Due to the square shape of the electrode, a chord length of the contact line is relatively small, particularly when a volume of the droplet is relative small. When the chord length is relatively small, the driving force for moving the droplet forward is correspondingly relatively small. As a result, a relatively higher driving voltage is required to move the droplet forward. However, a high driving voltage often is associated with a risk of short through a dielectric insulating layer between the droplet and the electrode. Also, as discussed above, a higher driving voltage may trigger undesired side reactions in the droplet.
Accordingly, the present disclosure provides, inter alia, a digital microfluidic device, microfluidic device, a lab-on-a-chip device, a digital microfluidic method, and a method of fabricating a digital microfluidic device that substantially obviate one or more of the problems due to limitations and disadvantages of the related art. In one aspect, the present disclosure provides a digital microfluidic device. In some embodiments, the digital microfluidic device includes a base substrate and an electrode array including a plurality of discrete electrodes continuously arranged on the base substrate. Optionally, the plurality of discrete electrodes can be grouped into a plurality of first electrode groups, each of which including a plurality of directly adjacent discrete electrodes. Optionally, a cross-section of each individual group of the plurality of first electrode groups along a plane substantially parallel to a main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a first direction. Optionally, the plurality of discrete electrodes can be alternatively grouped into a plurality of second electrode groups, each of which including a plurality of directly adjacent discrete electrodes. Optionally, a cross-section of each individual group of the plurality of second electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a second direction. Optionally, the first direction and the second direction are different from each other.
The overall shape of the cross-section of each individual group of the plurality of first electrode groups G1 along a plane substantially parallel to a main surface of the base substrate BS may be of any appropriate shape, as long as the overall shape has a recess on one side, and a protrusion on an opposite side protruding toward the first direction. The overall shape of the cross-section of each individual group of the plurality of second electrode groups G2 along the plane substantially parallel to the main surface of the base substrate BS may be of any appropriate shape, as long as the overall shape has a recess on one side, and a protrusion on an opposite side protruding toward the second direction.
Each individual group of the plurality of first electrode groups G1 can include any appropriate numbers of discrete electrodes, but the numbers of discrete electrodes in each individual group of the plurality of first electrode groups G1 is equal to or greater than 2. Each individual group of the plurality of second electrode groups G2 can include any appropriate numbers of discrete electrodes, but the numbers of discrete electrodes in each individual group of the plurality of second electrode groups G2 is equal to or greater than 2.
In some embodiments, each individual one of the plurality of discrete electrodes has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more of the plurality of the plurality of discrete electrodes. Optionally, each individual group of the plurality of first electrode groups G1 has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of second electrode groups G2. Optionally, each individual group of the plurality of second electrode groups G2 has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of first electrode groups G1.
The plurality of discrete electrodes can be further grouped in another alternative manner. In some embodiments, the plurality of discrete electrodes can be grouped into a plurality of biconcave electrode groups and a plurality of biconvex electrode groups alternately arranged.
A cross-section of each individual one of the plurality of biconcave electrode groups G3 along the plane substantially parallel to the main surface of the base substrate BS has an overall shape of a biconcave shape S3 (depicted using thick dotted lines). A cross-section of each individual one of the plurality of biconvex electrode groups G4 along the plane substantially parallel to the main surface of the base substrate BS has an overall shape of a biconvex shape S4 (depicted using thick dotted lines). As used herein, the term “biconcave” refers to a shape having two concave sides, e.g., substantially opposite to each other. As used herein, the term “biconvex” refers to a shape having two convex sides, e.g., substantially opposite to each other. Optionally, the biconcave shape S3 has a smooth edge (
Each individual group of the plurality of biconcave electrode groups G3 can include any appropriate numbers of discrete electrodes, but the numbers of discrete electrodes in each individual group of the plurality of biconcave electrode groups G3 is equal to or greater than 1. Each individual group of the plurality of biconvex electrode groups G4 can include any appropriate numbers of discrete electrodes, but the numbers of discrete electrodes in each individual group of the plurality of biconvex electrode groups G4 is equal to or greater than 1. As shown in
Optionally, each individual one group of the plurality of biconcave electrode groups has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of biconvex electrode groups. Optionally, each individual one group of the plurality of biconvex electrode groups has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more groups of the plurality of biconcave electrode groups.
In some embodiments, the digital microfluidic device further includes a plurality of first signal lines and a plurality of second signal lines providing actuating voltages to the electrode array in the digital microfluidic device.
In some embodiments, the droplet on the digital microfluidic device can be transported by sequentially actuating and de-actuating the plurality of first electrode groups G1 one group after another along a forward direction (e.g., the second direction in
In some embodiments, the droplet on the digital microfluidic device can be transported by sequentially actuating and de-actuating the plurality of second electrode groups G2 one group after another along a backward direction (e.g., the first direction in
Similarly, the droplet driving mechanism can also be illustrated when the plurality of discrete electrodes are grouped into a plurality of biconcave electrode groups and a plurality of biconvex electrode groups.
Referring to
In some embodiments, the droplet on the digital microfluidic device can be transported by sequentially actuating and de-actuating adjacent pairs of one of the plurality of biconcave electrode groups and one of the plurality of biconvex electrode groups one pair after another along a forward direction (e.g., the second direction in
In some embodiments, the droplet on the digital microfluidic device can be transported by sequentially actuating and de-actuating adjacent pairs of one of the plurality of biconvex electrode groups and one of the plurality of biconcave electrode groups one pair after another along a backward direction (e.g., the first direction in
In some embodiments, and referring to
Optionally, the plurality of biconvex electrode groups do not have a substantially uniform overall shape.
Optionally, the plurality of biconcave electrode groups do not have a substantially uniform overall shape.
In some embodiments, each individual one of the plurality of discrete electrodes has a boundary substantially complementary to, and insulated from, corresponding portions of directly adjacent one or more of the plurality of the plurality of discrete electrodes (see, e.g.,
In some embodiments, each of the plurality of discrete electrodes has a dimension (e.g., width or length) in a range of approximately 1 mm to approximately 3 mm, e.g., approximately 2 mm.
In some embodiments, a ratio of a chord length of the contact line of the droplet to a width of electrode (e.g., a width along a direction perpendicular to an extension direction of the plurality of discrete electrodes) is greater than 1.5:2, e.g., greater than 1.6:2, greater than 1.7:2, greater than 1.8:2, greater than 1.9:2, greater than 1.95:2, greater than 1.99:2, and approximately 2:2.
In another aspect, the present disclosure provides a microfluidic device including a digital microfluidic device described herein or fabricated by a method described herein.
In another aspect, the present disclosure provides a lab-on-a-chip device including a digital microfluidic device described herein or fabricated by a method described herein.
In another aspect, the present disclosure provides a digital microfluidic method. In some embodiments, the digital microfluidic method includes selectively transporting a liquid droplet using the digital microfluidic device described herein or fabricated by a method described herein. In some embodiments, the method includes, in a forward mode, sequentially actuating and de-actuating the plurality of first electrode groups one group after another, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along a forward direction. In some embodiments, the method includes, in a backward mode, sequentially actuating and de-actuating the plurality of second electrode groups one group after another, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along a backward direction. The backward direction is different from the forward direction. Optionally, the forward direction and the backward direction are reversed directions, the forward direction and the backward direction are reverse to each other. Optionally, the forward direction and the backward direction are substantially opposite to each other. Optionally, the method includes, in the forward mode, sequentially providing an actuating voltage to the plurality of first signal lines, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along the forward direction. Optionally, the method includes, in the backward mode, sequentially providing an actuating voltage to the plurality of second signal lines, thereby transporting the liquid droplet on a side of the electrode army distal to the base substrate along the backward direction.
In some embodiments, the method includes, selectively actuating and de-actuating directly adjacent pairs of one of the plurality of biconcave electrode groups and one of the plurality of biconvex electrode groups one pair after another, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate. Optionally, the method includes, in the forward mode, sequentially providing an actuating voltage to the plurality of first signal lines, thereby transporting the liquid droplet on aside of the electrode array distal to the base substrate along the forward direction. Optionally, the method includes, in the backward mode, sequentially providing an actuating voltage to the plurality of second signal lines, thereby transporting the liquid droplet on a side of the electrode array distal to the base substrate along the backward direction.
In another aspect, the present disclosure provides a method of fabricating a digital microfluidic device. In some embodiments, the method includes forming an electrode array including a plurality of discrete electrodes on a base substrate. Optionally, the electrode array is formed so that the plurality of discrete electrodes can be grouped into a plurality of first electrode groups, each of which including a plurality of directly adjacent discrete electrodes; and the plurality of discrete electrodes can be alternatively grouped into a plurality of second electrode groups, each of which including a plurality of directly adjacent discrete electrodes. A cross-section of each individual group of the plurality of first electrode groups along a plane substantially parallel to a main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a first direction. A cross-section of each individual group of the plurality of second electrode groups along the plane substantially parallel to the main surface of the base substrate has an overall shape having a recess on one side, and a protrusion on an opposite side protruding toward a second direction. The first direction and the second direction are different from each other.
In some embodiments, the method further includes forming a dielectric insulating layer on a side of the electrode array distal to the base substrate, and configured to insulate the plurality of discrete electrodes from each other; and forming a hydrophobic layer on a side of the dielectric insulating layer distal to the base substrate. Optionally, the method further includes forming a common electrode on a side of the hydrophobic layer distal to the dielectric insulating layer, the common electrode being formed to be spaced apart from the hydrophobic layer.
In some embodiments, the electrode array is formed using a substantially transparent conductive material such as indium tin oxide. Optionally, the step of forming the electrode array including providing a base substrate having an indium tin oxide layer formed thereon (e.g., an “ITO glass”), followed by patterning the indium tin oxide layer to form the electrode array.
The foregoing description of the embodiments of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form or to exemplary embodiments disclosed. Accordingly, the foregoing description should be regarded as illustrative rather than restrictive. Obviously, many modifications and variations will be apparent to practitioners skilled in this art. The embodiments are chosen and described in order to explain the principles of the invention and its best mode practical application, thereby to enable persons skilled in the art to understand the invention for various embodiments and with various modifications as are suited to the particular use or implementation contemplated. It is intended that the scope of the invention be defined by the claims appended hereto and their equivalents in which all terms are meant in their broadest reasonable sense unless otherwise indicated. Therefore, the term “the invention”, “the present invention” or the like does not necessarily limit the claim scope to a specific embodiment, and the reference to exemplary embodiments of the invention does not imply a limitation on the invention, and no such limitation is to be inferred. The invention is limited only by the spirit and scope of the appended claims. Moreover, these claims may refer to use “first”, “second”, etc. following with noun or element. Such terms should be understood as a nomenclature and should not be construed as giving the limitation on the number of the elements modified by such nomenclature unless specific number has been given. Any advantages and benefits described may not apply to all embodiments of the invention. It should be appreciated that variations may be made in the embodiments described by persons skilled in the art without departing from the scope of the present invention as defined by the following claims. Moreover, no element and component in the present disclosure is intended to be dedicated to the public regardless of whether the element or component is explicitly recited in the following claims.
Filing Document | Filing Date | Country | Kind |
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PCT/CN2018/093584 | 6/29/2018 | WO | 00 |
Publishing Document | Publishing Date | Country | Kind |
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WO2020/000352 | 1/2/2020 | WO | A |
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20200330995 A1 | Oct 2020 | US |