GB2560679B

GB2560679B - Method of controlling a tessellated array of electrodes

Info

Publication number: GB2560679B
Application number: GB1810375.4A
Authority: GB
Inventors: Ma Hanbin; Nathan Arokia
Original assignee: Acxel Tech Ltd
Current assignee: Acxel Tech Ltd
Priority date: 2017-07-17
Filing date: 2018-06-25
Publication date: 2019-09-18
Anticipated expiration: 2038-06-25
Also published as: CN109475871B; KR102224545B1; GB2559216B; CN109475871A; GB2560679A; KR20200018704A; GB201711420D0; GB201810375D0; GB2559216A; WO2019016506A1

Description

Method of controlling a tessellated array of electrodes

Field of the Invention

The present invention relates to a method of controlling a tessellated array of electrodes for use in electrowetting-on-dielectric droplet manipulation.

Background

Electrowetting-on-dielectric droplet manipulation can be used to control droplets in microfluidic applications.

An introduction to electrowetting is given in F. Mugele and J. C. Baret: “Electrowetting: from basics to applications”, Journal of Physics: Condensed Matter, volume 17, page R705 (2005) and an overview of electrowetting-on-dielectric devices is given in W. Nelson & C-J Kim: “Droplet Actuation by Electrowetting-on-Dielectric (EWOD): A Review”, Journal of Adhesion Science and Technology, volume 26, pages 1747-1771 (2012), which are incorporated herein by reference.

Reference is also made to US 2015/158028 Al and US 2017/113224 Al, which are incorporated herein by reference. US 2015/158028 Ai ibid, describes an active matrix electrowetting-on-dielectric device which includes a plurality of array elements configured to manipulate one or more droplets of fluid on an array. US 2017/113224 Ai ibid, describes a liquid droplet manipulation instrument.

Summary

According to a first aspect of the present invention there is provided a method of controlling a tessellated array of electrodes which includes at least some non-rectangular polygonal electrodes, an array of control devices, and sets of first and second address lines, wherein each control device is individually addressable by a given pair of first and second address lines. The method comprises retrieving a set of routedefining parameters stored in a computer-readable data structure for defining a set of electrodes in the tessellated array of electrodes that are to be active in a given time window (or “frame”) and causing first and second address control units to apply control signals to corresponding pairs of first and second address lines so as to activate the set of electrodes in the given time window.

An electrode may be made active by applying a voltage of suitable magnitude, for example, in a range between 1V to 200 V, with suitable polarity for a given liquid.

The set of route-defining parameters maybe a first set of route-defining parameters, the set of electrodes maybe a first set of electrodes and the given time window maybe a first time window. The method may further comprise retrieving a second set of routedefining parameters stored in the computer-readable data structure for defining a second set of electrodes in the tessellated array of electrodes that are to be active in a second time window which follows the first time window, and causing first and second address control units to apply control signals to corresponding pairs of first and second address lines so as to activate the second set of electrodes in the second time window.

The method may comprise causing first and second address control units to control or manipulate droplets independently in different regions of the tessellated array of electrodes. Thus, same tessellated array of electrodes can have different regions in which operate separately.

The method may comprise causing first and second address control units and a third address control unit to activate a first electrode at a first activate level (e.g. Vi) and a second electrode at a second activate level (e.g. V2, where |V2| > |Vi|. This can allow a droplet to be split into two droplets of different sizes by applying different voltages to adjacent electrodes.

According to a second aspect of the present invention there is provided a computer program which, when executed by at least one processor, causes the at least one processor to perform the method of the first aspect of the invention.

According to a third aspect of the present invention there is provided a computer program product comprising a computer-readable medium (which maybe non-transitory) which stores the computer program according to the second aspect of the present invention.

Brief Description of the Drawings

Certain embodiments of the present invention will now be described, by way of example, with reference to the accompanying drawings, in which:

Figure 1 is schematic block diagram of a microfluidic system which includes an electrowetting-on-dielectric droplet manipulation device;

Figure 2 is a cross-sectional view of a pixel comprising a bottom-gate thin-film transistor used in the droplet manipulation device shown in Figure 1;

Figure 3 is a cross-sectional view of a pixel comprising a top-gate thin-film transistor; Figure 4 schematically illustrates an array of address lines for addressing electrodes; Figure 5 schematically illustrates circuit cells for controlling electrodes;

Figure 6 is a plan view of layout of a circuit cell;

Figure 7 illustrates droplet splitting in a droplet actuation device;

Figure 8A to 8C illustrates droplet creation in a droplet actuation device;

Figure 9 illustrates a tessellated array of electrodes using irregular pentagonal electrodes; and

Figure 10 illustrates a tessellated array of electrodes using triangular electrodes and square electrodes.

Detailed Description of Certain Embodiments

Microfluidic system 1

Referring to Figure 1, a microfluidic system 1 is shown.

Referring also to Figures 2, 3, 4 and 5, the microfluidic system 1 includes an electrowetting-on-dielectric (EWOD) droplet manipulation device 2 in or on which droplets 3 can be freely manipulated in two-dimensions across a surface 4 using a tessellated array of electrodes 5. As will be explained in more detail later, the surface 4 is provided by a hydrophobic layer 6 supported on a dielectric layer 7 which is used to help isolate droplets 3 from underlying electrodes 5. The device can be used a variety of different liquids such as, for example, a saline buffer, biosamples (such as DNA or proteins) or bodily fluids (such as blood or urine). Droplet size can vary from, for example, 10 pl to, for example, 1 ml.

Droplet manipulation 3 can take different forms. A droplet 3 can be moved (or “actuated”) along a routable path, in other words, along a path whose course can be selectably set and changed. As will be explained in more detail later, a route can be defined as sequence of coordinates, such as Cartesian coordinates (x, y) or three-axis coordinates (a, b, c), vectors, or other route-defining parameters stored in a table, script or other suitable computer-readable data structure. Manipulation of droplets 3 can also take the form of two or more droplets 3 being fused into a single droplet 3 or, conversely, a single droplet 3 being split into two or more droplets 3. A sequence of droplet manipulations can be performed.

The tessellated array of electrodes 5 takes the form of an array of hexagonal electrodes 5. A hexagonal shape is closer to the shape of a liquid droplet than a square shape. Also, for a given pitch, a hexagonal array can allow a tighter packing of electrodes, than square electrodes. A hexagonal array can make it easier to split a droplet. Furthermore, a hexagonal array can provide a better inlet design.

The droplet manipulation device 2 comprises a first, main portion 9 (or “base”) which provides the surface 4 on which droplets 3 are manipulated and an optional second, overlying portion (or “cover”) 10.

The base 9 comprises a first substrate 11, for example a generally planar substrate, having first and second opposite faces 12,13 (herein referred to as lower and upper faces or surfaces) and which supports the electrodes 5 either directly or indirectly on the upper face 13.

The substrate 11 supports an array of control devices 17 for controlling a bias applied to each electrode 5, each of which, in this case, comprise a thin-film transistor 18 having a channel C, a source S, a drain D and a gate G, and a capacitor 19. The substrate 11 also supports respective sets of first and second address lines 20, 21 (herein referred to as “rows” and “columns” respectively and which may also be referred to as “first and second control lines” or simply “control lines”) which are arranged in such a way that each control device 17 is individually addressable by a given pair of first and second (or “crossing”) address lines 20, 21. A set of third address lines 22 may be optionally provided. A set of third address lines 22 can be used to provide multilevel voltages, which can be used define more than one activate voltage for additional functionality with respect to droplet manipulation. The substrate 11 also supports dielectric layers 23, 24.

The thin-film transistor 18 can take the form of a bottom-gate thin-film transistor, for example, as shown in Figure 2, a top-gate thin-film transistor, for example, as shown in Figure 3. The electrode 5 and corresponding control device 18 is herein also referred to a “pixel”.

The cover 10 includes a second substrate 25 having first and second opposite faces 26, 27 (herein referred to as lower and upper faces or surfaces). The lower face 26 may support (in order going away from the second substrate 25) an electrode 28, a dielectric layer (not shown) and a hydrophobic layer 30 which provides a base-facing surface 31 (or “lower cover face”). The base 9 and cover 10 define a shallow space 32 between the upper base surface 4 and the lower cover face 31, through which droplets 3 may move.

Referring in particular to Figure 1, the droplet manipulation device 2 may include reservoir electrodes 33 (which are generally larger than the tessellated electrodes 5) which can be used to supply droplets 3 into (or receive droplets 3 from) the tessellated array of electrodes 5.

The droplet manipulation device 2 may include wells 34 to hold respective charges 35 of liquid and which are arranged to supply liquid to (or receive liquid from) the reservoir electrodes 33. Supply of liquid to or from the wells 34 may be assisted by gravity. Supply of liquid may, however, be controlled electrostatically.

The system 1 may include a fluid handling system 36, e.g. comprising tubes (not shown), valves (not shown) and pumps (not shown), for controlling supply and removal of liquid from the droplet manipulation device 2. The fluid handling system 36 may be provided with an interface 37 to other instruments, such as, for example, flow cytometry instrument, a next-generation sequencing machine, a mass spectrometer, an electrochemical workstation or the like.

Referring also to Figure 2, the system 1 includes first and second address control units 38, 39 (herein also referred to as “control line drivers”) for applying control signals to respective sets of first and second address lines 20, 21. The system 1 may optionally include a third address control unit 40 for applying control signals to the set of third address lines 22.

The system 1 includes a controller 41 for example in the form of a microcontroller or single-board computer for controlling the fluid handling system 36 and the address control units, 38, 39, 40. The controller 41 may be provided with a display 44.

The system 1 includes a computer system 45 which can be used to control the controller 41. As will be explained in more detail later the computer system 42 includes at least one processor 46 and memory 47 which stores control program 48 and droplet manipulation instructions 49 which may take the form of a script or a series of tables, one table for each frame, each storing a list of active electrodes. In some cases, the controller 41 may store the control program 48 and droplet manipulation instructions 49. Thus, the computer system 42 may, therefore, be omitted, at least during operation.

Referring to Figure 6, the thin-film transistor 18 is disposed at the centre of the electrode 5.

The arrangement can help to provide symmetric droplet movement in all directions.

Programmable control

The address control units 38,39, under the control the controller 41, activate and deactivate electrodes 5 in a series of frames (herein referred to as “time windows”) ti, t2, ..., ti,...tN. As explained earlier, a computer-readable data structure such a table or script store a sequence of sets of route-defining parameters, each set of route-defining parameters specifying which electrodes in a given frame are active. The table or script can be seen as a video or movie of active (and inactive) pixels. By changing the routedefining parameters, different routes can be selected. Thus, using the same droplet manipulation device 2, different microfluidic operations can be performed.

Droplet splitting

Referring to Figure 7, splitting of a single droplet 31 into two droplets 33, 33 will now be described.

The address control units 38,39activate a first electrode 51 (for example, by causing the control device 17 to apply a positive bias to the electrode 51) which causes the droplet 31 to be held at a first position 5I1 (step S7.1).

The address control units 38,39 then additionally activate a first neighbouring pair of adjacent electrodes 52,53 and a second neighbouring pair of adjacent electrodes 54,55 which lie on opposite sides of (or “at opposite ends of’) the first electrode 51 (step S7.2). The first neighbouring pair of adjacent electrodes 52, 53 comprises second and third electrodes 52, 53 which are adjacent to the first electrode 51 (i.e. they are neighbouring) and to each other (i.e. they are an adjacent pair). Likewise, the second neighbouring pair of adjacent electrodes comprise fourth and fifth electrodes 54, s5 which are adjacent to the first electrode 51 and to each other. Activating opposite, neighbouring pairs of adjacent electrodes 52, 53,54, 55 causes the droplet 31 to be stretched not only in opposite directions, but also to be spread out in a direction which is generally orthogonal to the direction of splitting thereby giving the droplet 31 a “bone-shaped”- or “bow-tie”-like appearance.

The address control units 38,39 then de-activate the first electrode 51 (step S7.3). This results in first and second elliptical droplets 32,33 which are spread over the first pair of adjacent electrodes 52,53 and the second pair of adjacent electrodes 52, 53 respectively.

The address control units 38,39 then de-activate one electrode in each electrode pair 52, 53,54,55 which causes the droplet 31 to be held at a second and third position 512, 5i3 (step S7.4).

Using neighbouring, adjacent pixels, especially using hexagonally-shaped pixels, can help to split a droplet more evenly compared with square electrodes.

Droplet creation

Referring to Figures 8Ato 8C, creation of droplets 31 will now be described. A well 34 holds a charge 35 of liquid (step S8A.1).

The address control units 38,39 activate a reservoir electrode 33 and a neighbouring pair of adjacent bridging electrodes 5a, 5b which draws a pool 52 of liquid which sits on the reservoir electrode 33 and the first adjacent electrodes 5a, 5b (step S8A.2). The neighbouring pair of first adjacent electrodes 5a, 5b lie between reservoir electrode 33 and a bridging electrode 5c. The bridging electrodes 5a, 5b, 5c form a bridge (or “connection”) between the reservoir electrode 33 and the rest of the tessellated array of electrodes 5. Thus, to reach the tessellated array of electrodes 5, liquid flows through one or both of the first and second bridging electrodes 5a, 5b and through the third bridging electrode 5c.

The address control units 38,39) then de-activate the reservoir electrode 33 (step S8A.3). This results in an elliptical droplet 3a which is spread over the first and second bridging electrodes 5a, 5b.

Droplets of different sizes can be injected into the array.

Referring in particular to Figure 8B, creation of a smaller droplet, which covers an area roughly that of an electrode 5, will first be described.

The address control units 38,39 activate (in addition to the already-activated first and second bridging electrodes 5a, 5b), the third bridging electrodes 5c and a neighbouring pair of adjacent electrodes 5d, 5e which lie next to the third bridging electrode 5c (step S8B.1). This causes the droplet 3a to be pull and stretched into a “bone-shaped” droplet.

The address control units 38,39 (under the control the controller 41) then de-activate the third bridging electrode 5c (step S8B.2). This results in first and second elliptical droplets 3b, 3c which are spread over the first and second bridging electrodes 5a, 5b and the neighbouring pair of adjacent electrodes 5d, 5e respectively.

The address control units 38,39 (under the control the controller 41) then activate a sixth electrode 5f which is adjacent to both the neighbouring pair of electrodes 5d, 5e and then deactivate the neighbouring pair of electrodes 5d, 5e (step S8B.3). This results in a droplet 3c sitting over the sixth electrode 5f. In some cases, the neighbouring pair of electrodes 5d, 5e may be de-activated at the same as the sixth electrode 5f is activated.

Referring to Figure 8C, creation of a larger droplet, which covers an area roughly double the area of an electrode 5, will now be described.

The address control units 38, 39 (under the control the controller 41) activate (in addition to the already-activated first and second bridging electrodes 5a, 5b) a third, bridging electrode 5c which is adjacent to both the first and second bridging electrodes 5a, 5c and then deactivate the first and second bridging electrodes 5a, 5b (step S8C.31). This results in a droplet 3d sitting over the third electrode 5c.

The address control units 38, 39 (under the control the controller 41) activate (in addition to the already-activated third bridging electrode 5c) a neighbouring pair of adjacent electrodes 5d, 5e which lie next to the third bridging electrode 5c (step S8C.2). This results in an elliptical droplet 3e spread over the neighbouring pair of adjacent electrodes 5d, 5e-

The address control units 38, 39 (under the control the controller 41) then activate a sixth electrode 5f which is adjacent to both the neighbouring pair of electrodes 5d, 5e and then deactivate the neighbouring pair of electrodes 5d, 5e (step S8C.3). This results in a droplet 3f sitting over the sixth electrode 5f. In some cases, the neighbouring pair of electrodes 5d, 5e may be de-activated at the same as the sixth electrode 5f is activated

Other shapes of electrodes and other arrangements of tiled arrays

As explained earlier, the tessellated array of electrodes 5 can be provided by hexagonally-shaped electrodes. The array of electrodes, however, can be provided by electrodes of other shapes.

Referring to Figure 9, the array of electrodes can be provided by monohedral tiling of irregular pentagonal electrodes 5. Shapes with greater number of sides, such as irregular octagonal electrodes may be used.

Monohedral tiling, however, need not be used.

Referring to Figure 10, the array of electrodes can be provided by tiling of electrodes of two (or more) shapes, such as regular (i.e. equilateral) triangular- and square-shaped electrodes 5. 52. Other shapes can be used, such as regular octagons.

Addressing of the electrodes can be carried out in the same way as that described earlier. If necessary, however, there may be redundancy, in other words, there is no control device at certain pairings of row and columns.

Claims

1. A method of controlling a tessellated array of electrodes which includes at least some non-rectangular polygonal electrodes, an array of control devices, and sets of first and second address lines, wherein each control device is individually addressable by a given pair of first and second address lines, the method comprising: retrieving a set of route-defining parameters stored in a computer-readable data structure for defining a set of electrodes in the tessellated array of electrodes that are to be active in a given time window; and causing first and second address control units to apply control signals to corresponding pairs of first and second address lines so as to activate the set of electrodes in the given time window.

2. The method of claim 1, wherein the set of route-defining parameters are a first set of route-defining parameters, the set of electrodes is a first set of electrodes and the given time window is a first time window, the method comprising: retrieving a second set of route-defining parameters stored in the computer-readable data structure for defining a second set of electrodes in the tessellated array of electrodes that are to be active in a second time window which follows the first time window; and causing first and second address control units to apply control signals to corresponding pairs of first and second address lines so as to activate the second set of electrodes in the second time window.

3. The method of claim 1 or 2, comprising: causing first and second address control units to control or manipulate droplets independently in different regions of the tessellated array of electrodes.

4. The method of any one of claims 1 to 3, comprising: causing first and second address control units and a third address control unit to activate a first electrode at a first activate level and a second electrode at a second activate level.

5. A computer program which, when executed by at least one processor, causes the at least one processor to perform the method of any one of claims 1 to 4.

6. A computer program product comprising a computer-readable medium, which stores the computer program according to claim 5.