This invention relates to digital microfluidic (DMF) devices and, in particular, to methods of dispensing and splitting droplets in DMF devices having a parallel plate structure.
In an electrowetting-on-dielectric (EWOD) DMF device, the formation and motion of individual droplets can be controlled by applying an external electric field to designated electrodes within the device. Intricate pump and/or valve systems are thus not needed in such devices to drive and regulate the flow of liquids. In addition, droplets can be individually created and controlled in an EWOD DMF device, thus permitting the multiplexing of many droplets on a two-dimensional surface. Due to these advantages, EWOD DMF devices have been used in a variety of applications. For some applications, droplet volume precision, droplet volume consistency, droplet dispensing or splitting frequency, and/or droplet motion speed can be important.
Unfortunately, many existing DMF devices suffer from low droplet volume precision, poor droplet volume consistency, and/or slow droplet dispensing or splitting speeds. Some existing DMF devices also include complicated components for controlling droplet formation and/or movement, leading to an increase in fabrication cost and/or the number of failure modes. Therefore, there exists a need for improved DMF devices and methods of dispensing and splitting droplets in such devices.
In one aspect, DMF devices are described herein which, in some embodiments, can provide one or more advantages compared to some prior devices. For example, in some embodiments, a device described herein can dispense individual nanodroplets with a high precision and/or high consistency in droplet volume. Volume precision can be defined as the difference between dispensed volume and volume subtended by the drop-dispensing electrode of a device, where smaller differences correspond to higher volume precision. Volume consistency can be defined as the standard deviation of the volumes of a population of dispensed droplets. In some cases, a device described herein can provide a volume precision and/or a volume consistency of ±5% or less. A device described herein, in some cases, can also dispense and/or split droplets rapidly. For instance, in some embodiments, a device described herein can dispense and/or split a droplet in less than 15 ms. Moreover, a device described herein can provide one or more of the foregoing advantages without the need to use additional device components or additional process steps, such as those used in some prior capacitive feedback devices. Additionally, in some embodiments, a device described herein can be used to couple droplets having precise and consistent volumes to an additional apparatus, such as a polymerase chain reaction (PCR) apparatus. Thus, devices described herein, in some instances, can be used for various drug delivery, bioassay, in vitro, ecology, and/or pharmaceutical applications.
A DMF device described herein, in some embodiments, comprises an EWOD device. Further, DMF devices described herein can be “closed,” “parallel plate,” or “two-sided” devices, as opposed to “open” or “single-sided” devices. Thus, in some cases, a DMF device described herein can comprise a first parallel plate, a second parallel plate in facing opposition to the first parallel plate, and a gap between the first and second parallel plates. Fluid droplets can be formed and/or manipulated in the gap while in contact with the first and/or second parallel plate. Moreover, the first and/or second parallel plate can comprise a substrate, electrical contacts or electrodes positioned on or over the substrate, a dielectric layer positioned over the electrodes and substrate, and, in some cases, a hydrophobic coating positioned on the dielectric layer. A droplet disposed between the plates can be in contact with the topmost layer, such as the dielectric layer or hydrophobic coating, of each plate. Further, the spatial position of the electrodes in a parallel plate EWOD device described herein can define, form, or determine functional components of the device. For example, the placement of electrodes in a parallel plate device can form droplet-dispensing components, droplet-splitting components, bioassay components, reaction components, and other components, as described further herein.
In some embodiments, a DMF device described herein comprises a droplet-dispensing component. In some cases, the droplet-dispensing component comprises a droplet-generating electrode and a T-shaped electrode adjacent to the droplet-generating electrode. Additionally, in some embodiments, such a droplet-dispensing component further comprises an additional electrode adjacent to the T-shaped electrode. As described further hereinbelow, this additional electrode can contact or be immediately adjacent to the T-shaped electrode on three sides, four sides, or five sides of the T-shape of the T-shaped electrode. For example, in some instances, the additional electrode is a first C-shaped electrode adjacent to the T-shaped electrode. Further, in some cases, the droplet-dispensing component of a device described herein also comprises a second additional electrode, such as a second C-shaped electrode, adjacent to the first additional electrode. The T-shaped electrode, the first additional electrode, and the second additional electrode can be immediately adjacent to one another, including in embodiments wherein the first additional electrode is a first C-shaped electrode and the second additional electrode is a second C-shaped electrode. Moreover, in some such instances, the second C-shaped electrode is larger than the first C-shaped electrode, and the first C-shaped electrode and the second C-shaped electrode are nested. Further, the droplet-generating electrode, the T-shaped electrode, the first additional (e.g., C-shaped) electrode, and the second additional (e.g., C-shaped) electrode may be symmetric about a common axis, such as an axis corresponding to the direction of movement of a droplet dispensed by the droplet-dispensing component. Additionally, in some cases, about one-third to two-thirds of the droplet-generating electrode overlaps with the T-shape of the T-shaped electrode. Further, in some embodiments, the droplet-generating electrode of a device described herein has a rounded shape, such as a circular shape or a tear-drop shape.
In other cases, a droplet-dispensing component of a device described herein comprises a first linear electrode segment, a second linear electrode segment, and a curved electrode segment connecting the first linear electrode segment and the second linear electrode segment, wherein the curved electrode segment subtends an angle of about 90 degrees. Thus, in some embodiments, the droplet-dispensing component formed by the first linear electrode segment, the second linear electrode segment, and the curved electrode segment can be L-shaped or define an L-junction. Further, in some instances, the first and/or second linear electrode segment is formed from a plurality of contiguous electrodes. Additionally, the contiguous electrodes may be rectangular. The curved electrode segment of the droplet-dispensing component may also be formed from a plurality of electrodes, such as angled or sector-shaped electrodes.
Digital microfluidic devices described herein, in some embodiments, can also comprise a droplet-splitting component. The droplet-splitting component, in some cases, comprises a first linear electrode segment, a second linear electrode segment, a third linear electrode segment, and a Y-junction electrode segment connecting the first linear electrode segment to the second and third linear electrode segments. Further, in some embodiments, the first linear electrode segment, the second linear electrode segment, the third linear electrode segment, and the Y-junction electrode segment can form a Y-shape and/or define an acute angle. Additionally, in some instances, the Y-shape and the first linear electrode segment are symmetric about a common axis. Such an axis may correspond to a direction of movement of a droplet split by the droplet-splitting component. Moreover, in some embodiments, the first, second, and/or third linear electrode segment is formed from a plurality of contiguous electrodes. Additionally, the contiguous electrodes of the first, second, and/or third linear electrode segment may be rectangular. Further, in some cases, the second and third linear electrode segments form the arms of the Y-shape. In addition, in some embodiments, the Y-junction electrode segment of the droplet-splitting component is formed from a plurality of contiguous electrodes, which may be angled electrodes. In some such instances, the angles formed by the angled electrodes decrease from the first linear segment toward the second and third linear segments.
In another aspect, methods of dispensing and/or splitting a droplet in a DMF device are described herein. Methods described herein, in some instances, can be carried out using a DMF device described hereinabove, including a parallel plate DMF device.
A method of dispensing a droplet described herein, in some embodiments, comprises dispensing the droplet from a reservoir fluid in a DMF device. Such a method can comprise covering a droplet-generating electrode of the device with a portion or “finger” of the reservoir fluid, the portion having a larger area than the droplet-generating electrode. Additionally, the method further comprises withdrawing the portion of the reservoir from the droplet-generating electrode while the droplet-generating electrode is in an on state to form a droplet on the droplet-generating electrode. The area of the droplet formed in this manner can be substantially the same as the area of the droplet-generating electrode. Moreover, in some cases, the droplet-generating electrode has a rounded shape, such as a circular, elliptical, or “rounded square” shape. Further, in some embodiments, the droplet-generating electrode is symmetric about an axis corresponding to the direction of droplet dispensing. Dispensing a droplet in this manner can improve the precision and consistency of droplet volumes.
In other cases, a method of dispensing a droplet from a reservoir fluid of a DMF device comprises providing a droplet-generating electrode having a rounded shape, such as a circular shape, and switching the droplet-generating electrode to an on state to form the droplet on the droplet-generating electrode. Moreover, in some embodiments, the area of the droplet is substantially the same as the area of the droplet-generating electrode. It is further to be understood that the droplet-generating electrode can be adjacent to the reservoir fluid. Further, in some instances, forming the droplet on the droplet-containing electrode comprises covering the droplet-generating electrode with a portion of the reservoir fluid having a larger area than the droplet-generating electrode. In addition, in some such embodiments, forming the droplet on the droplet-containing electrode further comprises withdrawing the portion of the reservoir fluid from the droplet-generating electrode while the droplet-generating electrode is in the on state. Dispensing a droplet in this manner can further improve the precision and consistency of dispensed droplet volumes, including by reducing or eliminating the unwetted area of the drop-generating electrode during drop formation.
Additionally, in still other embodiments, a method of dispensing a droplet from a reservoir fluid described herein comprises removing a portion of the reservoir fluid to form a droplet and a tail extending between the droplet and the reservoir fluid. Such a method further comprises forming at least one fixed meniscus of the reservoir fluid adjacent to the tail and also forming a fixed meniscus of the droplet adjacent to the tail. In some instances, the fixed meniscus of the reservoir fluid is substantially parallel to the fixed meniscus of the droplet. Alternatively, in other embodiments, the fixed meniscus of the reservoir fluid is substantially orthogonal to the fixed meniscus of the droplet. Additionally, in some cases, the curvature of the reservoir fluid adjacent to the tail and the curvature of the droplet adjacent to the tail are each infinite. Moreover, in some instances, two fixed menisci of the reservoir fluid are formed adjacent to the tail, the two fixed menisci being substantially parallel to one another. In addition, in some embodiments, a method described herein further comprises splitting the tail to divide the droplet from the reservoir fluid. Dispensing a droplet in a manner described herein can completely eliminate or reduce the length of the tail portion of the droplet, thereby improving the volume precision and consistency of dispensed droplets.
Further, in yet other embodiments, a method of dispensing a droplet from a reservoir fluid described herein comprises withdrawing a portion of the reservoir fluid and forcing the portion to form or subtend an acute angle during de-wetting and movement of the portion over a curved electrode segment. In some cases, such a method further comprises “pinching off” or separating the portion from the remainder of the reservoir fluid, thereby forming the dispensed droplet. In some such embodiments, dispensing the droplet also comprises forming a tail extending between the droplet and the reservoir fluid, forming at least one fixed meniscus of the reservoir fluid adjacent to the tail, and forming a fixed meniscus of the droplet adjacent to the tail, wherein the fixed meniscus of the reservoir fluid is substantially orthogonal or perpendicular to the fixed meniscus of the droplet. Dispensing a droplet in a manner described herein can improve the speed of droplet dispensing and/or the volume precision and consistency of dispensed droplets.
Methods of dispensing a droplet described herein, in some embodiments, can also comprise coupling or providing the dispensed droplet to an external apparatus, including an apparatus that is not a DMF device. For example, in some cases, a droplet dispensed in a manner described herein can be coupled or provided to a PCR apparatus. Droplets dispensed in a manner described herein can also be combined with one another and/or with other materials, including to react with chemical species present in the droplets. Thus, in some cases, methods described herein can be used to improve the precision, consistency, and/or throughout of another process, such as a bioassay process.
In still another aspect, methods of splitting a droplet in a DMF device are described herein. Methods of splitting a droplet described herein, in some cases, can provide divided or split droplets having high volume precision and/or high volume consistency. Methods of splitting a droplet described herein can also provide split or divided droplets at a high speed, thus facilitating improved throughput.
A method of splitting a droplet described herein, in some embodiments, comprises providing a droplet-splitting component described hereinabove, such as a droplet-splitting component comprising a first linear electrode segment, a second linear electrode segment, a third linear electrode segment, and a Y-junction electrode segment connecting the first linear electrode segment to the second and third linear electrode segments, wherein the first linear electrode segment, the second linear electrode segment, the third linear electrode segment, and the Y-junction electrode segment form a Y-shape or define an acute angle. Such a method can further comprise moving the droplet from the first linear component to the Y-junction electrode segment to split the droplet into a first droplet portion and a second droplet portion. Additionally, in some cases, the first droplet portion is disposed on the second linear electrode segment and the second droplet portion is disposed on the third linear electrode segment of the droplet-splitting component. More generally, in some instances, a method of splitting a droplet described herein comprises forcing a leading meniscus of the droplet to split at a junction defining an acute angle.
These and other embodiments are described in more detail in the detailed description which follows.
Embodiments described herein can be understood more readily by reference to the following detailed description, examples, and figures. Elements, apparatus, and methods described herein, however, are not limited to the specific embodiments presented in the detailed description, examples, and figures. It should be recognized that these embodiments are merely illustrative of the principles of the present invention. Numerous modifications and adaptations will be readily apparent to those of skill in the art without departing from the spirit and scope of the invention.
In addition, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a stated range of “1.0 to 10.0” should be considered to include any and all subranges beginning with a minimum value of 1.0 or more and ending with a maximum value of 10.0 or less, e.g., 1.0 to 5.3, or 4.7 to 10.0, or 3.6 to 7.9.
All ranges disclosed herein are also to be considered to include the end points of the range, unless expressly stated otherwise. For example, a range of “between 5 and 10” should generally be considered to include the end points 5 and 10.
Moreover, when the term “about” is used in connection with an amount or quantity, it is to be understood that the amount can vary by 5% or less, 3% or less, or 1% or less, where the percentage is based on the stated amount. For example, an amount of “about 100” can refer to an amount of 95-105, 97-103, or 99-101.
In one aspect, DMF devices are described herein. In some embodiments, a DMF device described herein comprises a droplet-dispensing component. A droplet-dispensing component of a device described herein can provide one or more improvements compared to some prior DMF devices. For example, a droplet-dispensing component described herein can dispense individual nanodroplets with a high speed and/or a high precision and/or high consistency in droplet volume.
In contrast to the process of dispensing a droplet illustrated in
A “C-shaped” electrode, for reference purposes herein, can be formed from or defined by a first segment, a second segment, and a third segment, wherein the segments are contiguous and the second and third segments are orthogonal or substantially orthogonal to the first segment and are spaced apart from one another in a direction corresponding to the long axis of the first segment. “Substantially” orthogonal segments or objects, for reference purposes herein, can define or be separated by an angle of about 80-100 degrees or about 85-95 degrees. In addition, in some embodiments, the second C-shaped electrode of a droplet-dispensing component described herein is larger than the first C-shaped electrode. Moreover, in some instances, the first C-shaped electrode and the second C-shaped electrode are nested.
A “T-shaped” electrode, for reference purposes herein, can be formed from two non-bisecting orthogonal segments having the same or differing lengths. Further, the first orthogonal segment can be of equal length and width on each side of the second orthogonal segment, as in the letter “T.” Moreover, in some cases, the second orthogonal segment of a T-shaped electrode has a long axis parallel to a droplet-dispensing direction of the droplet-dispensing component. In addition, it is to be understood that a T-shaped electrode may include a vacancy or “carve out,” as illustrated in
In some cases, the overlap of a droplet-generating electrode with the T-shape of a T-shaped electrode can affect the distance between the droplet-generating electrode and another electrode of the droplet-dispensing component, such as a reservoir electrode of the component. A “reservoir electrode,” as understood by one of ordinary skill in the art, refers to an electrode on which a reservoir fluid is disposed. Similarly, a “reservoir fluid” refers to a fluid that is used as the source of droplets formed or dispensed by the droplet-generating component. For example, in the embodiment of
In addition, in some cases, the size and/or shape of a droplet-generating electrode can be selected to provide a desired distance between the droplet-generating electrode and a reservoir electrode. For example, in some instances, a sector shaped or “tear drop” shaped droplet-generating electrode is used to provide a separation distance of 0 mm, as illustrated in
In general, a droplet-dispensing electrode of a droplet-dispensing component described herein can have any size and shape not inconsistent with the objectives of the present disclosure. In some embodiments, a droplet-generating electrode has a rounded shape. An electrode having a “rounded” shape, for reference purposes herein, does not include an acute interior angle or does not include more than one acute interior angle or more than one 90° interior angle. For example, in some cases, a droplet-generating electrode is circular or elliptical. A droplet-generating electrode can also be rectangular or square or have a rounded rectangular or rounded square shape, wherein one or more corners of the rectangle or square have been rounded. In addition, in some embodiments, a droplet-generating electrode described herein is sector shaped. Other shapes are also possible.
Additionally, in some cases, one or more of the droplet-generating electrode, the T-shaped electrode, the first additional (e.g., C-shaped) electrode, and the second additional (e.g., C-shaped) electrode of a droplet-dispensing component described herein is symmetric about an axis, such as an axis corresponding to the direction of movement of a droplet dispensed by the droplet-dispensing component. In some instances, the droplet-generating electrode, the T-shaped electrode, the first additional (e.g., C-shaped) electrode, and the second additional (e.g., C-shaped) electrode are all symmetric about a common axis, such as an axis corresponding to the droplet-dispensing direction or to the direction of tail formation, as illustrated by common axis X in
Again with reference to
Not intending to be bound by theory, it is believed that the structure of the droplet-dispensing component (200) illustrated in
Another portion of an exemplary droplet-dispensing component described herein is illustrated in
As illustrated in
In contrast to the linear electrode segments (510, 520), the curved electrode segment (530) of
A droplet-dispensing component (500) having a structure described above can be used to dispense droplets more rapidly and/or with improved volume precision and/or consistency, as compared to some other droplet-dispensing components. Not intending to be bound by theory, it is believed that improved volume precision and/or consistency, and/or increased speed of dispensing a droplet can be achieved by forcing a portion of a fluid reservoir to form an acute angle or substantially acute angle during de-wetting and movement of the portion over the curved electrode segment. This process is illustrated in
The droplet-dispensing process of
Not intending to be bound by theory, it is believed that a droplet-dispensing component such as that illustrated in
wherein ΔPL is the Laplace pressure drop at the point A, γ is the surface tension, rA is the radius of curvature at the point A, and Rt is as defined above. With reference to
Again not intending to be bound by theory, it is further believed that the use of contiguous electrodes as described herein in a droplet-dispensing component, including but not limited to a droplet-dispensing component having a L-junction, can minimize the deformation of the fluid moving across the electrodes and thereby maximize the speed of the head/front meniscus of the liquid and the speed of de-wetting.
Various portions and features of droplet-dispensing components have been described herein. It is to be understood that a droplet-dispensing component described herein can include any combination of features not inconsistent with the objectives of the present disclosure. In some cases, for instance, the droplet-generating electrode (210) of the droplet-dispensing component (200) of
As described above, droplet-dispensing components of a DMF device described herein, in some cases, can provide reduced variation in unit droplet and/or reduced time to dispense a droplet. In some instances, for example, a device described herein can provide a volume precision and/or consistency of ±10% or less, ±5% or less, ±1% or less, ±0.5% or less, or ±0.1% or less, where the percentage is based on the volume subtended by a droplet-generating electrode described herein (in the case of volume precision) or on the standard deviation of the volumes of a population of 10 to 100, 100 to 1000, or 1000 to 10,000 sequentially dispensed droplets (in the case of volume consistency). In some embodiments, the volume precision of a device described herein is about 1-20%, about 1-10%, about 1-5%, or about 1-3%. The volume consistency of a device described herein can be about 0.05-10%, about 0.05-5%, about 0.05-1%, about 0.1-10%, about 0.1-1%, about 0.5-10%, about 0.5-5%, about 0.5-1%, about 1-5%, or about 1-3%. Additionally, in some cases, a device described herein has a droplet-dispensing speed of less than about 100 ms, less than about 50 ms, less than about 30 ms, less than about 20 ms, or less than about 15 ms per droplet. In some instances, the droplet-dispensing speed is about 5-100 ms, 5-50 ms, 10-100 ms, 10-50 ms, 10-30 ms, or 10-20 ms per droplet. Moreover, such a dispensing speed, in some cases, can be obtained in an air environment at an applied voltage of 80-150 V, such as an applied voltage of 125 V. In some embodiments, an applied voltage of less than about 80 V, less than about 60 V, less than about 50 V, or less than about 20 V may also be used. In general, the applied voltage is sufficient to provide wetting of the device surface with fluid for a given device architecture. Similarly, it is to be understood that devices described herein can be used with an oil medium or other medium rather than an air medium. In such instances, rapid, precise, and consistent droplet-dispensing can still be obtained.
In addition to droplet-dispensing components, droplet-splitting components of a DMF device are also described herein. One non-limiting example of a droplet-splitting component described herein is illustrated in
In addition, the speed and/or efficiency of droplet splitting can be further improved by forming the first, second, and/or third linear electrode segments (710, 720, 730) from a plurality of contiguous electrodes, such as a plurality of contiguous rectangular electrodes (E16-E24, E29-L through E38-L, and E29-R through E38-R in the exemplary embodiment of
Similarly, the Y-junction electrode segment (740) may also be formed from a plurality of contiguous electrodes (E25-E28 in the exemplary embodiment of
Similarly, it is to be understood that the present invention is not limited to the precise structures depicted in the figures and examples, such as the “TCC,” “L-junction,” or “Y-junction” structures described above. Other specific structures may also be used consistent with the objectives of the present disclosure, as described further hereinbelow in Section II and Section III.
In addition, it is to be understood that droplet-splitting and droplet-dispensing components described herein may be used in conjunction with one another. For example, in some cases, a droplet-dispensing component such as that illustrated in
Further, in addition to a droplet-dispensing component and/or a droplet-splitting component described above, a DMF device described herein can also comprise other components. For example, in some cases, a DMF device described herein comprises a first parallel plate, a second parallel plate in facing opposition to the first parallel plate, and a gap between the first and second parallel plates. Fluid droplets can be formed and/or manipulated in the gap while in contact with the first and/or second parallel plate. Moreover, the first and/or second parallel plate can comprise a substrate, electrical contacts or electrodes positioned on or over the substrate, a dielectric layer positioned over the electrodes and substrate, and a hydrophobic coating positioned on the dielectric layer. A droplet disposed between the plates can be in contact with the topmost layer, such as the dielectric layer or hydrophobic coating, of each plate. A first parallel plate, second parallel plate, substrate, electrode, dielectric layer, and/or hydrophobic coating of a DMF device described herein can be formed from any material not inconsistent with the objectives of the present disclosure. For example, in some instances, a substrate of a DMF device is formed of a glass such as a glass made of soda-lime, a borosilicate, an aluminosilicate, a titanium silicate, pure silica, or quartz. Further, in some embodiments, electrodes are formed from a highly conductive material such as a metal or metal alloy or mixture of metals. For example, in some instances, electrodes are formed from chromium, gold, silver, copper, aluminum, indium, or a combination or mixture thereof. Electrodes may also be formed from a conductive oxide such as a transparent conductive oxide (TCO). Non-limiting examples of transparent conductive oxides suitable for use in some embodiments described herein include indium tin oxide (ITO), gallium indium tin oxide (GITO), and zinc indium tin oxide (ZITO). A dielectric layer, in some instances, is formed from an inorganic material such as a ceramic, which may include a silicon nitride (SiN). A dielectric layer may also be formed of an organic dielectric material such as a poly(p-xylylene) or parylene (including Parylene C). A dielectric photoresist such as SU-8 may also be used as a dielectric layer in some embodiments described herein. Similarly, any hydrophobic coating not inconsistent with the objectives of the present disclosure may be used in a DMF device described herein. In some cases, for instance, a poly(tetrafluoroethylene) or Teflon material is used. Substrates, electrodes, dielectric layers, and hydrophobic coatings formed from other materials are also possible.
Moreover, in some embodiments, a DMF device described herein does not include or comprise a capacitive feedback component, such as a capacitive feedback component comprising a thin film capacitor, an electrode for measuring capacitance, a processor, and/or a signal I/O capacity structure to perform feedback control.
Further, a device described herein can be made in any manner not inconsistent with the objectives of the present disclosure. In some instances, for example, a DMF device described herein is fabricated in a cleanroom using layer-by-layer microfabrication. As understood by one of ordinary skill in the art, such a process, in some embodiments, can comprise one or more blanket depositing steps (e.g., to deposit ITO on a glass substrate), one or more evaporating steps (e.g., to deposit a metal electrode), one or more chemical or physical vapor deposition steps (e.g., to deposit a ceramic dielectric material), and one or more patterning, masking, and/or etching steps, including one or more photolithographic steps (e.g., to define one or more electrodes or functional structures of the device). One or more spin-coating or casting steps may also be used (e.g., to deposit a hydrophobic coating on a dielectric layer).
In another aspect, methods of dispensing a droplet in a DMF device are described herein. In some embodiments, a method of dispensing a droplet in a DMF device comprises dispensing the droplet from a reservoir fluid of the DMF device. Accordingly, some features of methods described herein can be understood with reference to
In some instances, a method described herein comprises covering a droplet-generating electrode of a DMF device with a portion or “finger” of a reservoir fluid, wherein the portion has a larger area than the droplet-generating electrode. The method further comprises withdrawing the portion of the reservoir from the droplet-generating electrode while the droplet-generating electrode is in an on state to form a droplet on the droplet-generating electrode, wherein the area of the droplet is substantially the same as the area of the droplet-generating electrode. The “area” of a droplet, portion of reservoir fluid, or electrode, for reference purposes herein, refers to the planar area, as opposed to a total surface area. Further, the planar area corresponds to the plane of the surface on which the fluid is disposed. In addition, areas that are “substantially” the same have areas that differ by no more than about 10 percent, no more than about 5 percent, no more than about 3 percent, no more than about 1 percent, or no more than about 0.5 percent, the percent being based on the larger area. Moreover, in some embodiments of a method described herein, the volume of the droplet is less than half of the total volume of the portion of the reservoir fluid used to cover the droplet-generating electrode.
The steps of covering a droplet-generating electrode with a portion of a reservoir fluid and subsequently withdrawing the portion are illustrated in
In the embodiment of
Additionally, the steps of a method described herein can be carried out in any manner not inconsistent with the objectives of the present disclosure. In some embodiments, for instance, the droplet-generating electrode is covered with the portion of the reservoir fluid by switching the droplet-generating electrode and one or more additional electrodes immediately adjacent to the droplet-generating electrode to an on state, as illustrated in
In other embodiments, a method of dispensing a droplet from a reservoir fluid of a DMF device is described herein, wherein the method comprises providing a droplet-generating electrode having a rounded shape and switching the droplet-generating electrode to an on state to form the droplet on the droplet-generating electrode, wherein the droplet-generating electrode being adjacent to the reservoir fluid. Moreover, the reservoir fluid, in some cases, can be disposed on a reservoir electrode, and the method can further comprise switching the reservoir electrode to an off state, including at the same time or substantially the same time as the droplet-generating electrode is switched to the on state. Additionally, in some embodiments, the area of the droplet is substantially the same as the area of the droplet-generating electrode. Any droplet-generating electrode having a round shape described hereinabove in Section I may be used in a method described herein. In some cases, for instance, the droplet-generating electrode has a circular shape. Dispensing a droplet in a manner described herein, in some cases, can reduce the amount of “empty” or “unused” area of a droplet-generating electrode, thus permitting more efficient droplet formation and the formation of droplets having more precise and consistent volumes corresponding to the volume subtended by the known area of the droplet-generating electrode.
In still other embodiments, a method of dispensing a droplet from a reservoir fluid of a DMF device is described herein, wherein the method comprises removing a portion of the reservoir fluid to form a droplet and a tail extending between the droplet and the reservoir fluid, forming at least one fixed meniscus of the reservoir fluid adjacent to the tail, and forming a fixed meniscus of the droplet adjacent to the tail, wherein the fixed meniscus of the reservoir fluid is substantially parallel to the fixed meniscus of the droplet. Alternatively, in other embodiments, the fixed meniscus of the reservoir fluid is substantially orthogonal to the fixed meniscus of the droplet. Additionally, in some cases, a method described herein further comprises splitting the tail to divide the droplet from the reservoir fluid. Moreover, in some instances, the curvature of the reservoir fluid adjacent to the tail and the curvature of the droplet adjacent to the tail are each infinite. Further, in some embodiments, two fixed menisci of the reservoir fluid are formed adjacent to the tail, and the two fixed menisci are substantially parallel to one another. “Substantially” parallel menisci, for reference purposes herein, are within about 10 degrees, within about 5 degrees, or within about 1 degree of a parallel configuration.
The alignment of menisci according to one embodiment of a method described herein is illustrated in
Various methods of dispensing a droplet have been described herein. However, it is to be understood that steps of methods of dispensing a droplet described herein can be combined in any manner not inconsistent with the objectives of the present disclosure. For example, in some instances, a droplet is formed by providing a droplet-generating electrode having a rounded shape and switching the droplet-generating electrode to an on state to form the droplet on the droplet-generating electrode, wherein forming the droplet on the droplet-containing electrode comprises covering the droplet-generating electrode with a portion of the reservoir fluid having a larger area than the droplet-generating electrode. Moreover, in some such embodiments, forming the droplet on the droplet-generating electrode can further comprise withdrawing the portion of the reservoir fluid from the droplet-generating electrode while the droplet-generating electrode is in the on state. Further, in some cases, the distance between the droplet-generating electrode and the reservoir electrode has a value described hereinabove in Section I.
Moreover, it is to be understood that a method of dispensing a droplet described herein, in some cases, can be carried out using any device structure described hereinabove in Section I, not only the device structure of
Additionally, methods of dispensing a droplet described herein, in some cases, can further comprise providing the dispensed droplet to an apparatus that is not a digital microfluidic device. For example, in some instances, the apparatus comprises a PCR apparatus.
In another aspect, methods of splitting a droplet in a DMF device are described herein. In some embodiments, a method of splitting a droplet described herein comprises moving a droplet over a droplet-splitting component described herein. Any droplet-splitting component described hereinabove in Section I may be used. For example, in some cases, a method of splitting a droplet comprises providing a droplet-splitting component comprising a first linear electrode segment, a second linear electrode segment, a third linear electrode segment, and a Y-junction electrode segment connecting the first linear electrode segment to the second and third linear electrode segments, wherein the first linear electrode segment, the second linear electrode segment, the third linear electrode segment, and the Y-junction electrode segment form a Y-shape and wherein the second and third linear electrode segments define an acute angle. Additionally, in some instances, the first linear electrode segment, the second linear electrode segment, the third linear electrode segment, and/or the Y-junction electrode is formed from a plurality of contiguous rectangular electrodes having an aspect ratio of about 4 to 10. The method further comprises moving the droplet from the first linear component to the Y-junction electrode segment to split the droplet into a first droplet portion and a second droplet portion. A method splitting a droplet according to one such embodiment is illustrated in
Various embodiments of the present invention have been described in fulfillment of the various objectives of the invention. It should be recognized that these embodiments are merely illustrative of the principles of the present invention. Numerous modifications and adaptations thereof will be readily apparent to those skilled in the art without departing from the spirit and scope of the invention.
This application claims priority pursuant to 35 U.S.C. §119(e) to U.S. Provisional Patent Application Ser. No. 62/094,744, filed on Dec. 19, 2014, which is hereby incorporated by reference in its entirety.
This invention was made with government support under contract W31P4Q-11-1-0012 awarded by the Defense Advanced Research Projects Agency/Microsystems Technology Office (DARPA/MTO). The government has certain rights in the invention.
Number | Date | Country | |
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62094744 | Dec 2014 | US |