Patent Grant
11498073
The present application is a 35 U.S.C. 371 national stage application of PCT International Application No. PCT/CN2019/093240, filed on Jun. 27, 2019, which claims the benefit of Chinese Patent Application No. 201810690544.3, filed on Jun. 28, 2018, the entire disclosures of which are incorporated herein by reference.
The present disclosure relates to the field of microfluidic technologies, and particularly to a digital microfluidic chip, a method for driving the same, and a digital microfluidic device.
With the development of micro electro mechanical techniques, the digital microfluidic technique has made a breakthrough in driving and controlling of a micro-droplet, and has been widely applied in biological, chemical and medical fields due to its own advantages. The digital microfluidic technique is an emerging inter-discipline in which chemistry, fluid physics, microelectronics, novel materials, biology, and biomedical engineering are involved. Due to features of miniaturization and integration, a device which adopts the microfluidic techniques is usually referred to as a digital microfluidic chip. Various samples like cells can be cultured, moved, detected, and analyzed in the digital microfluidic chip. From the wide applications in various fields, it can be seen that the digital microfluidic chip has advantages of small volume, small reagent dosage, fast reaction, portability, parallel processing, and automation. Besides, the digital microfluidic chip has great development potential and wide application prospects.
Embodiments of the present disclosure provide a digital microfluidic chip, comprising a state transition layer configured to bear a droplet; and a light driving layer configured to provide light for controlling a lyophobicity-lyophobicity transition of the state transition layer so as to drive the droplet to move
In one or more embodiments, the state transition layer comprises a photosensitive material in which a lyophobic cis-structure is transitioned into a lyophilic trans-structure upon irradiation by light.
In one or more embodiments, the photosensitive material comprises a copolymer of isopropylacrylamide and acryloxysuccinimide.
In one or more embodiments, the digital microfluidic chip further comprises a base plate, wherein the light driving layer is arranged on the base plate, and the state transition layer is stacked on the light driving layer.
In one or more embodiments, the droplet is beared on a surface of the state transition layer away from the base plate.
In one or more embodiments, the light driving layer is spaced apart from the state transition layer, and a space for bearing the droplet is formed between the light driving layer and the state transition layer.
In one or more embodiments, the state transition layer comprises a first state transition layer and a second state transition layer which are spaced apart from each other, and a space for bearing the droplet is formed between the first state transition layer and the second state transition layer.
In one or more embodiments, the digital microfluidic chip further comprises a detect circuit configured to detect a position of the droplet; and a control circuit configured to generate a control signal according to the position of the droplet and a preset movement direction and/or speed of the droplet, and send the control signal to the light driving layer, wherein the control signal comprises a position to which light is required to be provided and an intensity of the provided light.
In one or more embodiments, the light driving layer comprises a plurality of light emitting units which are arranged in an array.
In one or more embodiments, the control circuit is configured to determine first light emitting units from the plurality of light emitting units according to the position of the droplet, determine second light emitting units from the plurality of light emitting units which are required to provide light according to the preset movement direction of the droplet, and determine the intensity of light provided by the second light emitting units according to the preset movement speed of the droplet.
In one or more embodiments, the photosensitive material has a lyophilic degree in direct proportion to the intensity of light provided by the light driving layer.
In one or more embodiments, the digital microfluidic chip further comprises a thermal control layer configured to control the temperature of the state transition layer.
In one or more embodiments, the thermal control layer is arranged between the light driving layer and the state transition layer.
In one or more embodiments, the state transition layer is transitioned from lyophobicity to lyophilicity during the lyophobicity-lyophobicity transition.
In one or more embodiments, each of the plurality of light emitting units is a micro-LED.
Embodiments of the present disclosure further provide a digital microfluidic device, comprising the digital microfluidic chip as described above.
Embodiment of the present disclosure further provide a driving method for a digital microfluidic chip, wherein the digital microfluidic chip comprises a light driving layer and a state transition layer configured to bear the droplet, the driving method comprising:
as a response to a control signal, providing light for controlling a lyophobicity-lyophobicity transition of the state transition layer so as to drive the droplet to move by using the light driving layer.
In one or more embodiments, the driving method further comprises: detecting a position of the droplet; and generating the control signal according to the position of the droplet and the preset movement direction and speed of the droplet.
In one or more embodiments, the control signal comprises a position to which light is required to be provided and an intensity of the provided light.
In one or more embodiments, the light driving layer comprises a plurality of light emitting units which are arranged in an array, and generating the control signal comprises: determining first light emitting units from the plurality of light emitting units according to the position of the droplet, determining second light emitting units from the plurality of light emitting units to which light is required to be provided according to the preset movement direction of the droplet, determining the intensity of light provided by the second light emitting units according to the preset movement speed of the droplet, and generating the control signal comprising information about a position of the second light emitting units and information about the intensity of light provided by the second light emitting units.
The accompanying drawings are used for providing further understanding of the present disclosure, and constitute a part of the specification. The accompanying drawings are used for explaining technical solutions of the present disclosure together with the following embodiments, but are not intended to limit the present disclosure. The shapes and sizes of components in the drawings are not drawn in a true scale, and only intend to illustrate the content of the present disclosure.
The technical solutions of the embodiments in this disclosure are clearly and completely described in combination with the drawings. The following embodiments are used for explaining the present disclosure, but are not intended to limit the present disclosure. It is noted that without conflict, the embodiments and features of the embodiments in the present disclosure can be combined with one another.
Currently, a mainstream driving mode for the digital microfluidic chip is electrode driving, and the digital microfluidic chip is also referred to as a voltage-type digital microfluidic chip. The operation principle follows. A droplet is provided on a surface comprising a hydrophobic layer. A voltage is applied to the droplet, and the wettability between the droplet and the hydrophobic layer is increased by means of electrowetting effect. As a result, the droplet is subject to asymmetric deformation and an internal pressure difference is produced, so that the droplet is moved in a specified direction and mixed. In addition, the digital microfluidic chip can further be drove by dielectrophoresis, surface acoustic wave, electrostatic force, or the like. However, these driving manners suffer from various problems.
An existing digital microfluidic chip comprises a first substrate and a second substrate which are arranged oppositely. The first substrate comprises a first electrode, a dielectric layer and a hydrophobic layer which are formed on a base plate in this order. The second substrate comprises a second electrode, a dielectric layer and a hydrophobic layer which are formed on a base plate in this order. The structure is relatively complex. The fabricating process is also relatively complex. Usually electrode layers are formed by deposition, dielectric layers are formed by evaporation, and hydrophobic layers are formed by spin-coating and baking. Two or three masks are required. The fabricating cost is relatively high. Furthermore, the digital microfluidic chip of this construction is drove by electrode driving. A voltage is applied between the first electrode and the second electrode, and an electric field is generated between the first substrate and the second substrate, to change the hydrophobic or hydrophilic state of the droplet. Due to the relatively high operation voltage, active substance in the droplet, such as cells, DNA or proteins, may suffer from irreversible damage. Meanwhile, the digital microfluidic chip of an electrode driving has a complex structure and a relatively high fabricating cost.
It is the fact these technical issues have not been effectively solved that hinders the development of microfluidic technique.
In order to overcome the defects of the existing digital microfluidic chip, such as irreversible damage to the active substance, complex structure, high fabricating cost, embodiments of the present disclosure there provide a digital microfluidic chip.
In particular, the light driving layer 20 comprises a plurality of light emitting units which are arranged in an array on a base plate 10. Each of the light emitting units can be addressed and controlled, and emits light of a given intensity by driving separately. In an embodiment, the light emitting unit can adopt a micro light-emitting diode (Micro LED), and a plurality of micro-LEDs form a micro-LED array. Currently, the micro-LED has been developed greatly, and can become thinner, miniaturized, and arranged in an array. The micro-LED has a dimension only of the order of 1˜10 μm, and is very applicable to the digital microfluidic chip of the order of millimeters. As an embodiment, thee micro-LED comprises a first electrode and a second electrode which are arranged oppositely, and a light emitting functional layer between the first electrode and the second electrode. The light emitting functional layer comprises a P type semiconductor layer, an active layer, and an N type semiconductor layer. The operation principle follows. A forward bias is applied between the first electrode and the second electrode, so that when a current pass through the active layer, electron-hole pairs recombine in the active layer and emit monochromatic light. By controlling the voltage difference between the first electrode and the second electrode, the intensity of the emitted light can be controlled. The intensity of the emitted light by the micro-LED can be controlled in a range of 0-20000 nit. Each micro-LED can act as one light emitting unit. The plurality of light emitting units are arranged in a matrix to form a micro-LED array. In an embodiment of the present disclosure, the micro-LED array can adopt the existing construction and can be formed by a mature process, which is not repeated here for simplicity. The intensity of light emitted by each micro-LED can be controlled by active matrix driving, so that different light emitting units in the micro-LED array emits different intensities of light.
In an embodiment of the present disclosure, upon irradiation by light, the state transition layer 30 changes from a lyophobic cis-structure into a lyophilic trans-structure. By means of the transition from lyophobicity to lyophilic, the movement of the droplet on the state transition layer 30 can be controlled by the driving principle based on the wetting effect. The light of different intensities emitted by the plurality of light emitting units irradiates the state transition layer 30, so that a plurality of regions are formed in the state transition layer 30, and each of the regions has different lyophilic degree. As a result, the droplet on the state transition layer 30 may exhibit different wetting degrees, i.e., different solid-liquid contact angles, so that the droplet is provided with a drive force to move. Finally, it is realized that movement speed and movement direction of the droplet is controlled by the micro-LED array.
A surface wettability is one of the major properties of a solid surface. If a liquid is uniformly is dispersed on a surface without forming a droplet, it is believed that this surface essentially tends to be hydrophilic and allows water to disperse. In contrast, if water forms a droplet on a lyophobic surface, it is believed that this surface essentially tends to be hydrophobic. The wettability the solid surface is usually measured and determined by a contact angle.
cos θ=(γsol-gasγsol-liq)/γgas-liq,
wherein, γsol-gas, γsol-liq and γgas-liq are the surface tension coefficient of a solid gas interface, the surface tension coefficient of a solid liquid interface and the surface tension coefficient of a gas liquid interface, respectively. Based on Young's equation, lyophilicity indicates the contact angle of the droplet on the solid surface is smaller than 90°, while lyophobicity indicates the contact angle of the droplet on the solid surface is larger than 90°.
In an embodiment of the present disclosure, the state transition layer comprises a photosensitive material. In case the photosensitive material is irradiated by light at a temperature below a critical temperature, a lyophobic cis-structure in the photosensitive material is transitioned into a lyophilic trans-structure, so that the surface with which the droplet contacts changes from lyophobic into lyophilic. The photosensitive material is a type of a photo responsive hydrogel. A common photo-sensitive compound comprises chlorophyllin, dichromates, aromatic azide-compounds, aromatic diazo-compounds, aromatic nitro-compounds, organohalogen compounds. The photo-sensitive compound is decomposable by light, and is added to a polymer gel. Upon stimulation by light, a great number of ions are formed in the gel, and this introduces an abrupt change of the osmotic pressure inside the gel. As a result, the solvent is diffused from outside towards inside, and this prompts the volume phase transition of the gel to produce a photo-sensitive effect. When the intensity of light is absorbed to a critical point, a transition from cis-isomer to trans-isomer occurs in the molecular structure, realize lyophobicity-lyophobicity transition. In an embodiment, the photosensitive material layer comprises a copolymer of isopropylacrylamide and acryloxysuccinimide, and acryloxysuccinimide is boned at the side group to form aminopropoxy azobenzene. The structure imparts the copolymer with photosensitive property. When the azo group at the side chain is present as a stable hydrophobic cis-structure, upon irradiation with visible or UV light at a temperature below the critical temperature, the azo group changes into a hydrophilic trans-structure. When the temperature reaches the critical temperature (or higher than the critical temperature), upon irradiation with light for a second time, the azo group recovers into a hydrophobic cis-structure, so that the surface with which the droplet contacts changes from lyophilic to lyophobic. The lyophilic degree of the photosensitive material layer corresponds with the irradiation intensity. The higher the irradiation intensity is, the higher lyophilic degree the photosensitive material layer will have. The lower the irradiation intensity is, the lower lyophilic degree the photosensitive material layer will have. Thus, by controlling the irradiation intensity of the light emitting units in the micro-LED array, the lyophilic degree of a region of the photosensitive material layer corresponding with the respective light emitting unit can be changed. The light emitted by the light emitting units with different intensities irradiates the state transition layer, so that the state transition layer forms a plurality of regions, and these regions have different lyophilic degrees. Since different regions of the photosensitive material layer have different lyophilic degrees, when a droplet is dripped onto the photosensitive material layer, the droplet may exhibit different wetting degrees, i.e., different solid-liquid contact angles. According to the driving principle based on wetting effect, the droplet obtains the drive force to move, and finally it is realized to control the movement speed and movement direction of the droplet by light irradiation. In case the photosensitive material is a copolymer of isopropylacrylamide and acryloxysuccinimide, the critical temperature is about 40° C. The temperature below the critical temperature indicates a room temperature, e.g., 15° C.-30° C. In case the temperature is higher than about 40° C., the reverse reaction may occur. As for other photosensitive materials, the critical temperature may vary. Since the photosensitive material layer comprising a copolymer of isopropylacrylamide and acryloxysuccinimide is a commercially available product, the composition, characteristics, and fabricating process of the photosensitive material layer is well known for a person with ordinary skill in the art, which is not repeated herein for simplicity.
The state transition layer 30 comprises state transition regions which correspond in position with these three light emitting regions, i.e., a first state transition region 301, a second state transition region 302 and a third state transition region 303. It is assumed that the irradiation intensity of the first light emitting region 201 to which the first state transition region 301 corresponds<the irradiation intensity of the second light emitting region 202 to which the second state transition region 302 corresponds<the irradiation intensity of the third light emitting region 203 to which the third state transition region 303 corresponds. As a result, the droplet may exhibit different wetting degrees, i.e., different solid-liquid contact angles. The lyophilic degree of the first state transition region 301<the lyophilic degree of the second state transition region 302<the lyophilic degree of the third state transition region 303. Namely, the lyophobic degree of the first state transition region 301>the lyophobic degree of the second state transition region 302>the lyophobic degree of the third state transition region 303. Thus, a contact angle θ1 of the first state transition region 301>a contact angle θ2 of the second state transition region 302>a contact angle θ3 of the third state transition region 303. Based on the physical property of the droplet, under drive by the internal pressure difference, the droplet may move in a direction from a region of a high lyophobic degree to a region of a low lyophobic degree. Namely, under drive by the internal pressure difference, the droplet in a poorly wetted region may move in a direction towards a well wetted region. Thus, when the droplet lies in the first state transition region 301, different portions of a same droplet have different solid-liquid contact angles, so that the surface tension is distributed asymmetrically, and there is a pressure difference inside the droplet. As a result, the droplet moves towards the second state transition region 302 under the drive of this internal pressure difference. In addition, when the droplet lies in the second state transition region 302, the droplet may be drove to move toward the third state transition region 303. By controlling an irradiation intensity difference between two neighboring light emitting regions, the variation gradient of contact angle between two neighboring state transition regions of the state transition layer can be controlled, and the movement speed of the droplet can thus be controlled. By controlling an irradiation intensity difference between two neighboring light emitting regions in a certain direction, the variation gradient of contact angle between two neighboring state transition regions of the state transition layer in a corresponding direction can be controlled, and the movement direction of the droplet can thus be controlled, as shown in
Usually, the droplet 100 has a dimension about a millimeter (mm), the micro-LEDs 210, 220, 230 have a dimension about a micrometer (μm), and one droplet may cover a plurality of micro-LEDs. Thus the light emitting region as described above can be understood as a region covered by the droplet.
In an embodiment of the present disclosure, a digital microfluidic chip further can comprise a detect circuit 40 and a control circuit 50, as shown in
In another embodiment, a digital microfluidic chip of the present disclosure for example further comprises a thermal control layer 60, as shown in
As an embodiment, a digital microfluidic chip in an embodiment of the present disclosure can be designed to have the structure shown in
As an embodiment, in the construction shown in
As another embodiment, in the construction shown in
In addition, the light driving layer and state transition layer in the stacked structure can directly contact with each other, can be spaced apart by a predefined distance, or can comprise other films therebetween. The present disclosure is not limited in this regard. It is noted that in
During implementations, a digital microfluidic chip in an embodiment of the present disclosure further can change the morphology of the droplet. In case the droplet stays static at a certain region, the irradiation intensity of light provided by light emitting units corresponding to this region is by controlled to vary at a predefined rate. The lyophilic degree of this region can be changed, and the droplet may exhibit different solid-liquid contact angles and thus change its morphology. In this case, the state transition layer can comprise a photosensitive material in which a lyophilic trans-structure is capable of transitioning to a lyophobic cis-structure. Upon irradiation, the lyophilic trans-structure in the material is transitioned to the lyophobic cis-structure, so that the surface of the material changes from lyophilic to lyophobic.
According to embodiments of the present disclosure, the novel digital microfluidic chip comprises the light driving layer configured to provide light and the state transition layer which can realize a lyophobicity-lyophobicity transition. The light driving layer provides light to the state transition layer, so as to control the lyophobicity-lyophobicity transition of the state transition layer, which in turn drives the droplet to move. In the existing digital microfluidic chip, the driving voltage is higher than 100V. However, in the light control manner of the present disclosure, there is no need for such a high voltage. A voltage for drive the micro-LED is required, and this voltage is low, so that the power consumption is reduced significantly. In the existing digital microfluidic chip, active substances are subject to irreversible damage. However, in the light control manner of the present disclosure, no current is applied to the droplet, and a strong electric field is not formed. As a result, active substances in the droplet, such as cells, DNA, proteins will not be damaged. Since there no special requirement for the droplet, the light control manner of the present disclosure is applicable to more fields with less limitations. The existing digital microfluidic chip has a multiple-layer structure comprising two substrates which are arranged oppositely. However, in the present embodiment, only one substrate is needed to drive the droplet to move in a certain direction. Besides, the substrate body has a two-layer structure. Thus, the structure is simple, the fabricating process is simple, and the fabricating cost is low. This makes the digital microfluidic chip suitable for mass production with a large area. In addition, by virtue of the fast-growing micro-LED array, it is possible to realize miniaturization and integration to a maximum extent, and it is more easy to realize mass production.
Based on the technical solution as mentioned above, an embodiment of the present disclosure further provides a digital microfluidic device, which comprises the digital microfluidic chip as described above.
Based on the same technical concept, an embodiment of the present disclosure further provides a driving method for a digital microfluidic chip. The digital microfluidic chip comprises a light driving layer, a state transition layer, a detect circuit and a control circuit. The state transition layer is configured to bear the droplet, and comprises a photosensitive material in which a lyophobic cis-structure is transitioned into a lyophilic trans-structure upon irradiation by light. The lyophilic degree of the photosensitive material layer corresponds with the intensity of light provided by the light emitting units. The light driving layer comprises a plurality of light emitting units which are arranged in an array. The light emitting units comprise light-emitting diode.
The driving method for a digital microfluidic chip comprises:
S1, detecting a position of the droplet by using a detect circuit, and sending a position of the droplet to the control circuit;
S2, generating a control signal according to the position of the droplet and a preset movement direction and/or speed of the droplet by using the control circuit, and sending the control signal to the light driving layer, wherein the control signal comprises a position to which light is required to be provided and an intensity of the provided light; and
S3, as a response to a control signal, providing light for controlling a lyophobicity-lyophobicity transition of the state transition layer so as to drive the droplet to move by using the light driving layer.
For example, step S2 comprises:
determining first light emitting units from the plurality of light emitting units according to the position of the droplet, determining second light emitting units from the plurality of light emitting units to which light is required to be provided according to the preset movement direction of the droplet, determining the intensity of light provided by the second light emitting units according to the preset movement speed of the droplet, and generating the control signal comprising information about a position of the second light emitting units and information about the intensity of light provided by the second light emitting units.
For example, the digital microfluidic chip further comprises a thermal control layer, and the driving method further comprises: controlling the temperature of the state transition layer by using the thermal control layer.
It is noted that, in the description of embodiments of the present disclosure, orientational or positional relations indicated by “middle”, “up”, “down”, “front”, “back”, “vertical”, “horizontal”, “top”, “bottom”, “inside”, “outside” or the like are the orientational or positional relations shown in the figures, and are only for purpose of simplified descriptions for facilitating the description of embodiments of the present disclosure, not for indicating or implying that the described apparatus or elements must have specific orientations. Therefore, they should be construed to limit the present disclosure.
In embodiments of the present disclosure, a digital microfluidic chip, a method for driving the same, and a digital microfluidic device are provided. The digital microfluidic chip includes a state transition layer configured to bear a droplet, and a light driving layer configured to provide light for controlling a lyophobicity-lyophobicity transition of the state transition layer to drive the droplet to move. The light driving layer includes light emitting units arranged in an array and provides light. The state transition layer realizes a lyophobicity-lyophobicity transition. The light driving layer controls the lyophobicity-lyophobicity transition by providing light to drive the droplet to move. An existing digital microfluidic chip has a complex structure and a high fabricating cost, while the digital microfluidic chip of the present disclosure has a simple structure, a simple fabricating process and a low fabricating cost, and can realize miniaturization and integration to a maximum extent.
It is noted that in the description of embodiments of the present disclosure, unless otherwise defined, the terms “installed”, “interconnected”, or “connected” shall be understood broadly. For example, these terms may mean “connected in a fixed manner”, “connected in a detachable manner”, or “connected in an integrated manner”. These terms may mean “mechanically connected”, or “electrically connected”. These terms may mean “directly interconnected”, “interconnected through a medium”, or “communicated inside two elements”. As for the person with ordinary skill in the art, the specific meaning of these terms in the present disclosure can be understood in the context.
It will be appreciated that the present invention is not limited to the exact construction that has been described above and illustrated in the accompanying drawings, and that various modifications and changes can be made without departing from the scope thereof. It is intended that the scope of the present invention only be limited by the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 201810690544.3 | Jun 2018 | CN | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/CN2019/093240 | 6/27/2019 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2020/001528 | 1/2/2020 | WO | A |
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| Number | Date | Country | |
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| 20200391213 A1 | Dec 2020 | US |
