This application claims priority to Chinese Patent Application No. 202110081632.5, filed on Jan. 21, 2021, the disclosure of which is incorporated by reference herein in its entirety.
The disclosure belongs to the field of microfluidic technology, and more particularly, to a microfluidic chip.
Microfluidics technology is an emerging interdisciplinary subject related to chemistry, fluid physics, microelectronics, new materials, biology and biomedical engineering, and can realize precise control and manipulation of micro droplets. Devices employing microfluidic technology are often referred to as microfluidic chips, and microfluidic chips generally have multiple operation regions, each having different functions (e.g., functions of driving liquid flow, generating sample droplets, mixing liquid, heating liquid, etc.) to realize cultivation, movement, detection, analysis, etc. of the sample liquid. When different reactions are carried out, the microfluidic chip is required to carry out different operations on the sample liquid, so that each reaction requires revising or designing different operation regions and combination modes of the operation regions, and various different reactions cannot be flexibly adapted. In addition, it is difficult to realize local repair and damage repair for the micro-fluidic chip as a whole, so waste is easily caused.
The present disclosure provides a microfluidic chip including a plurality of microfluidic units, each microfluidic unit has an operation region, and different microfluidic units can be freely combined to form a microfluidic chip, which can adapt to various biological detections, and can be repaired or replaced locally, thereby avoiding waste.
The present disclosure provides a microfluidic chip including a plurality of microfluidic units, each of the plurality of microfluidic units including an operation region and a transition region located at least one side of the operation region, the transition regions located at adjacent sides of two adjacent microfluidic units of the plurality of microfluidic units being disposed opposite to each other. Each of the plurality of microfluidic units includes: a first substrate; a first electrode layer disposed on the first substrate, the first electrode layer including a plurality of first sub-electrodes located in the operation region and at least one second sub-electrode located in the transition region, and the at least one second sub-electrode being configured to drive a droplet to move from one of the plurality of microfluidic units to an adjacent microfluidic unit.
In some embodiments, each of the plurality of microfluidic units further includes a first dielectric layer disposed on the first electrode layer, and the first dielectric layer is made of a material having hydrophobicity.
In some embodiments, each of the plurality of microfluidic units further includes: a first dielectric layer disposed on the first electrode layer; and a first hydrophobic layer disposed on the first dielectric layer, and the first dielectric layer is made of a material having no hydrophobicity.
In some embodiments, an area of an orthographic projection of the at least one second sub-electrode on the first substrate is smaller than an area of an orthographic projection of each of the plurality of first sub-electrodes on the first substrate.
In some embodiments, a ratio of the area of the orthographic projection of the at least one second sub-electrode on the first substrate to the area of the orthographic projection of each of the plurality of first sub-electrodes on the first substrate is 1:9 to 1:2.
In some embodiments, each of the plurality of microfluidic units further includes: a second substrate disposed opposite to the first substrate; and a reference electrode disposed on a side of the second substrate close to the first substrate, an orthographic projection of the reference electrode on the first substrate covering an orthographic projection of the plurality of first sub-electrodes on the first substrate and at least partially overlapping an orthographic projection of the at least one second sub-electrode on the first substrate.
In some embodiments, the reference electrode includes a plurality of sub-reference electrodes in one-to-one correspondence with the plurality of first sub-electrodes and the at least one second sub-electrode.
In some embodiments, an orthographic projection of the second substrate on the first substrate partially overlaps an orthographic projection of the at least one second sub-electrode on the first substrate in the same microfluidic unit.
In some embodiments, an orthographic projection of the second substrate on the first substrate partially overlaps the orthographic projection of the at least one second sub-electrode on the first substrate in the same microfluidic unit.
In some embodiments, the orthographic projection of the second substrate on the first substrate overlaps half of the orthographic projection of the at least one second sub-electrode on the first substrate in the same microfluidic unit.
In some embodiments, each of the plurality of microfluidic units further includes a bonding layer disposed between the first substrate and the second substrate and surrounding an edge region of each microfluidic unit; the bonding layer has a first opening at the transition region, and the first openings of two adjacent microfluidic units are arranged opposite to each other.
In some embodiments, the microfluidic chip further includes a fixation assembly for fixing the plurality of microfluidic units to form the microfluidic chip.
In some embodiments, the fixation assembly includes an outer frame, a plurality of stoppers and a plurality of springs arranged within the outer frame, the outer frame is configured to define the plurality of microfluidic units therein, and has a rectangular shape, one ends of the plurality of springs are connected to at least two inner sidewalls of the outer frame, and the other ends of the plurality of springs are connected to the plurality of stoppers, and the plurality of stoppers are in contact with some of the plurality of microfluidic units at an outer edge, respectively, others of the microfluidic units at the outer edge are in contact with other inner sidewalls of the outer frame other than the at least two inner sidewalls, and the plurality of springs are in a compressed state such that restoring forces of the plurality of springs are applied to the plurality of microfluidic units.
In some embodiments, the microfluidic chip further includes a flat support layer, the plurality of microfluidic units being disposed on the flat support layer.
In some embodiments, the microfluidic chip further includes an adhesive structure disposed on the first substrate in the transition regions of two adjacent microfluidic units to connect the two adjacent microfluidic units to each other.
In some embodiments, at least one microfluidic unit in the microfluidic chip further includes a temperature measuring circuit coupled to at least two adjacent first sub-electrodes of the at least one microfluidic unit to detect a temperature of the droplet flowing through the two adjacent first sub-electrodes.
In some embodiments, the temperature measuring circuit includes an operational amplifier, a signal processing circuit and a feedback capacitor; the operational amplifier has a first input port, a second input port and an output port, and the first input port is coupled to the two adjacent first sub-electrodes that are coupled to the temperature measuring circuit; the feedback capacitor is coupled between the first input port and the output port; the signal processing circuit is coupled to the output port.
In some embodiments, the at least one microfluidic unit coupled to the thermometric circuit further includes two feedback electrodes disposed on the first substrate of the at least one microfluidic unit and on one side of the first electrode layer in a direction perpendicular to an arrangement direction of the plurality of first sub-electrodes so as to correspond to the two adjacent first sub-electrodes; the two feedback electrodes are two electrode plates of the feedback capacitor, and the two feedback electrodes are respectively coupled to the first input port and the output port.
In some embodiments, the at least one microfluidic unit coupled to the temperature measuring circuit further includes a dummy electrode disposed between the two feedback electrodes and the two adjacent first sub-electrodes and configured to isolate a signal between the two feedback electrodes and the two adjacent first sub-electrodes.
In some embodiments, the at least one microfluidic unit further includes a temperature adjusting circuit and a control circuit, the temperature measuring circuit and the temperature adjusting circuit are both coupled to the control circuit; the control circuit is configured to control the temperature adjusting circuit to adjust the temperature of the droplet according to the temperature measured by the temperature measuring circuit.
In some embodiments, the temperature adjusting circuit includes a thermoelectric temperature adjusting sheet disposed on a side of the first substrate of the at least one microfluidic unit coupled to the temperature measuring circuit facing away from the plurality of first sub-electrodes; and an orthographic projection of the thermoelectric temperature adjusting sheet on the first substrate covers an orthographic projection of each of the plurality of first sub-electrodes of the at least one micro-fluidic unit coupled to the temperature measuring circuit on the first substrate.
The technical solutions of the present disclosure will be better understood by those skilled in the art by the following detailed description with reference to the accompanying drawings.
The shapes and sizes of the components in the drawings do not reflect true scale, but are merely for the purpose of facilitating understanding of the contents of the embodiments of the present disclosure.
The technical or scientific terms used herein should have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs, unless defined otherwise. The terms “first,” “second,” and the like used in this disclosure are not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another. Likewise, the terms “a,” “an,” or “the” and the like do not denote a limitation of quantity, but rather denote the presence of at least one. The word “include” or “comprise”, and the like, means that the element or item preceding the word includes the element or item listed after the word and its equivalent, but does not exclude other elements or items. The terms “connected” or “coupled” and the like are not restricted to physical or mechanical connections, but may include electrical connections, whether direct or indirect. The terms “upper”, “lower”, “left”, “right”, and the like are used only to indicate relative positional relationships, and when the absolute position of the object being described is changed, the relative positional relationships may also be changed accordingly.
In a first aspect, as shown in
Specifically, as shown in
The microfluidic chip provided by the embodiment of the disclosure is provided with a plurality of microfluidic units, each microfluidic unit has one operation region, and the plurality of microfluidic units can be freely combined according to a flow path required by biological detection to form the microfluidic chip, so that the microfluidic chip can adapt to various biological detections. In addition, when the microfluidic unit with a certain function is damaged, the microfluidic unit can be independently removed for local repair or replacement, thereby avoiding a case where the whole microfluidic chip needs to be discarded due to local damage, and avoiding waste. Furthermore, by providing the second sub-electrode in the transition region A1 of each microfluidic unit, it is possible to drive the droplet from one microfluidic unit to another microfluidic unit adjacent thereto.
In some embodiments, as shown in
In some embodiments, as shown in
In some embodiments, the microfluidic chip provided by embodiments of the present disclosure can manipulate various types of droplets. For example, the droplet may be water (H2O), blood, or the like. In addition, a fluid (e.g., silicone oil) with a lubricating effect may be added to a fluid layer where the droplet is located to reduce damping of the liquid during movement, and the added fluid may also be another fluid, which is not limited herein.
It should be noted that
In some embodiments, the reference electrode 6 may have various shapes. For example, the reference electrode 6 may be a plate electrode covering the plurality of first sub-electrodes 11 and the at least one second sub-electrode 12. For another example, the reference electrode 6 includes a plurality of sub-reference electrodes (e.g., a plurality of strip-shaped electrodes). In the operation region, one sub-reference electrode corresponds to one first sub-electrode 11, and the orthographic projection of each sub-reference electrode on the first substrate 2 covers the orthographic projection of the first sub-electrode 11 corresponding to the sub-reference electrode on the first substrate 2. In the transition region A1, one sub-reference electrode corresponds to one second sub-electrode 12, and the orthographic projection of each sub-reference electrode on the first substrate 2 covers the orthographic projection of the second sub-electrode 12 corresponding to the sub-reference electrode on the first substrate 2. In the microfluidic chip provided in the embodiments of the present disclosure, the microfluidic unit may include only the first substrate 2, or may include both the first substrate 2 and the second substrate 5, and for convenience of explanation, the following embodiments of the microfluidic unit are described as including the first substrate 2 and the second substrate 5, but are not limited to this application.
In some embodiments, referring to
In some embodiments, referring to
In the microfluidic chip provided by the embodiment of the disclosure, the droplet 001 is controlled based on the voltages applied to the first sub-electrode 11 and the second sub-electrode 12, and the hydrophobicity and the dielectric wetting effect between the hydrophobic layers and the droplet 001, so that the first sub-electrode 11 of the first electrode layer 1 in the operation region can have different arrangement modes according to different functions of different microfluidic units.
Referring back to
For another example, in the microfluidic unit 100b having a function of controlling the turning of the droplet, the first electrode layer 1 has two groups of first sub-electrodes 11 (e.g., square electrodes), the first group of first sub-electrodes 11 are arranged along the first direction, and the second group of first sub-electrodes 11 are arranged along the second direction, that is, the two groups of first sub-electrodes 11 are arranged in a cross shape. The two ends of the first group of first sub-electrodes 11 in the first direction are respectively provided with two second sub-electrodes 12, and the two ends of the second group of first sub-electrodes 12 in the second direction are respectively provided with two second sub-electrodes 12, so that the droplet can enter the microfluidic unit 100b in the first direction or the second direction under the driving of the second sub-electrodes 12, be transferred to the opposite side in the first direction or the second direction, and be moved to another adjacent microfluidic unit (e.g., 100c) under the driving of the second sub-electrodes 12.
For another example, in the microfluidic unit 100c having a function of mixing different kinds of droplets, the first electrode layer 1 includes a plurality of first sub-electrodes 11 (e.g., square electrodes). Some of the plurality of first sub-electrodes 11 are arranged in a closed loop pattern (e.g., a rectangular pattern) to form a closed moving path, and the remaining first sub-electrodes 11 of the plurality of first sub-electrodes 11 are respectively disposed between the closed loop pattern and the second sub-electrodes 12 in the transition region A1. In this case, different droplets may enter the microfluidic unit 100c from the second sub-electrode 12 in the transition region A1 on one side, pass through the first sub-electrode 11 between the second sub-electrodes 12 in the transition region A1 and the closed loop pattern and be mixed by turning around the closed loop pattern. Subsequently, the mixed droplets may flow to the transition region A1 on the other side, and be driven by the second sub-electrode 12 in the transition area A1 on the other side to be moved to another adjacent microfluidic unit (e.g., 100d).
For another example, in the microfluidic unit 100d having a function of moving the droplet, the first electrode layer 1 includes a plurality of first sub-electrodes 11 (e.g., square electrodes). The plurality of first sub-electrodes 11 are arranged in the first direction, and a plurality of second sub-electrodes 12 are respectively disposed at both ends of the plurality of first sub-electrodes 11 in the first direction. In this case, the droplet entering the microfluidic unit 100d may move in the first direction and move to another adjacent microfluidic unit via the second sub-electrode 12.
For another example, in the microfluidic unit 100e having the function of splitting the droplet into sub-droplets, the first electrode layer 1 includes a plurality of first sub-electrodes 11, the plurality of first sub-electrodes 11 may include a plurality of sheet-shaped sub-electrodes 11e and a hollow sub-electrode 11f, and the hollow sub-electrode 11f has a hollow portion. When the droplets move to the hollow sub-electrode 11f, the droplets may be broken at the hollow portion under the condition of the same voltage because the stress at the non-hollow portion is different from that at the hollow portion. As a result, the position of the hollow portion of the hollow sub-electrode 11f is a breaking point of the droplet. The hollow portion may include various types of shapes, such as a circular hole shape, a straight shape, a cross shape, and the like. For example, in
For another example, in the microfluidic unit 100f having the function of sampling the droplet, the first electrode layer 1 includes a plurality of first sub-electrodes 11, the plurality of first sub-electrodes 11 may include first rectangular electrodes 11a and second rectangular electrodes 11b, and an area of one second rectangular electrode 11b is larger than an area of one first rectangular electrode 11a. The microfluidic unit 100f may be disposed at a position corresponding to the last step of the microfluidic chip, and when the droplet for which the biological detection is completed is driven into the microfluidic unit 100f, the droplet first flows through the first rectangular electrode 11a with a smaller area and then flows through the second rectangular electrode 11b with a larger area, so as to increase the area of the droplet, thereby meeting the requirements of the sampling operation on the droplet.
For another example, in the microfluidic unit 100g having a function of regulating the temperature of the droplet, the first electrode layer 1 may include a plurality of first sub-electrodes 11 arranged in an array pattern, and the first sub-electrodes 11 are not disposed in a central region of the array pattern. The microfluidic unit 100g may also include a heating element R1, and the heating element R1 may include various types of structures. For example, the heating element R1 may be a resistance wire, the heating end of the resistance wire may be located in a central region of the array pattern where the first sub-electrode 11 is not disposed, and the plurality of first sub-electrodes 11 are arranged around the heating end of the resistance wire. The resistance wire may have multiple functions, for example, the resistance wire may heat the droplet flowing into the microfluidic unit 100g, and/or the resistance wire may measure the temperature of the droplet flowing into the microfluidic unit 100g. In a case where the resistance wire heats the droplet flowing into the microfluidic unit 100g, a large driving voltage may be applied to two ends of the resistance wire, and the resistance wire heats up to generate joule heat to heat the droplet; in a case where the resistance wire measures the temperature of droplet flowing into the microfluidic unit 100g, since the resistance value of the resistance wire varies with the temperature, and the temperature of the resistance wire may be changed when the droplet flows around the resistance wire, a small operation voltage may be applied to the two ends of the resistance wire to measure the resistance value of the resistance wire, and then the temperature value is obtained according to the resistance-temperature relationship of the resistance wire, thereby realizing the temperature measurement. By combining the two modes, the temperature of the droplet can be detected through the resistance wire, and if the temperature is lower, the droplet can be heated to the preset temperature through the resistance wire. In addition, the microfluidic unit 100g may also include various temperature measuring or temperature regulating methods, and the heating element R1 may also have other structures, which are not limited herein.
It should be noted that, since the microfluidic chip formed by combining the plurality of microfluidic units may have an irregular shape, in order to keep the microfluidic chip in a regular shape such as a rectangular shape, the microfluidic chip may further include at least one blank unit 100i. The blank unit 100i does not have a function of manipulating droplet, and may be configured to supplement the microfluidic chip by being placed at a position related to the irregular shape, so that the microfluidic chip becomes a regular shape as a whole, so as to be stored or clamped conveniently.
The operation process of the microfluidic units of the microfluidic chip provided by the embodiments of the present disclosure for manipulating droplets are described in detail below by taking the manipulation of droplet movement and the manipulation of droplet splitting as examples.
As shown in
Specifically, the relationship of the voltage of any one of the first sub-electrode 11a, the first sub-electrode 11b, and the second sub-electrode 12 and the contact angle between the droplet 001 and the first hydrophobic layer 4 may be expressed by the following equation:
where ε0 is a vacuum dielectric constant, εr is a relative dielectric constant of the first hydrophobic layer 4, γlg is a surface tension coefficient of a liquid-air interface, ΔV is a potential difference between a lower surface of the first hydrophobic layer 4 close to the first substrate 2 and an upper surface of the first hydrophobic layer 4 close to the droplet 001, and D is a thickness of the first hydrophobic layer 4.
In some embodiments, as can be seen from the above equation, if the relative dielectric constant εr of the first hydrophobic layer 4 is increased, in the case where the same voltage V is applied to any one of the first sub-electrode 11a, the first sub-electrode 11b, and the second sub-electrode 12, the dielectric contact angle θV of the droplet 001 is increased so that it is easier to manipulate the droplet 001. However, if the relative dielectric constant εr of the first hydrophobic layer 4 is too large, the droplet is easily polarized during the movement, therefore, the manipulation of the droplet 001 by the microfluidic chip is disabled. Accordingly, the first hydrophobic layer 4 in the embodiments of the present disclosure may be made of a material having a relative dielectric constant within a predetermined range, for example, the predetermined range of the relative dielectric constant εr of the first hydrophobic layer 4 is [2.9, 3.1]. The second hydrophobic layer 8 is similar to the first hydrophobic layer 4, for example, the predetermined range of the relative dielectric constant of the second hydrophobic layer 8 is [2.9, 3.1].
As shown in
As can be seen from the above process of manipulating the droplet movement, in order to generate a sufficient difference in pressure inside the droplet 001 to drive the droplet 001 to move, the droplet 001 needs to cover at least two adjacent electrodes (two first sub-electrodes 11, or a first sub-electrode 11 and a second sub-electrode 12).
For example, referring to
No voltage is applied to the second sub-electrode 12 of the microfluidic unit 100a and a voltage is applied to the second sub-electrode 12 of the microfluidic unit 100d to drive the droplet 001 to move towards the second sub-electrode 12 of the microfluidic unit 100d. However, due to inevitable factors such as low alignment accuracy, a gap S1 exists at the interface between the microfluidic unit 100a and the microfluidic unit 100d, which will cause a part of the droplet 001 flowing through the gap S1 to be pressed into the gap S1, while the total volume of the droplet 001 is constant, resulting in that the coverage area of the droplet 001 is greatly reduced. As a result, the droplet 001 may not cover the second sub-electrode 12 of the microfluidic unit 100a and the second sub-electrode 12 of the microfluidic unit 100d at the same time, and the droplet 001 cannot move to the microfluidic unit 100d.
In order to avoid the above situation, in the embodiment of the present disclosure, an area of an orthographic projection of one second sub-electrode 12 of the microfluidic unit on the first substrate 2 may be smaller than an area of an orthographic projection of one first sub-electrode 11 on the first substrate 2. In this way, it is ensured that the second sub-electrode 12 of each of the adjacent microfluidic units can be covered by the droplet 001 during the movement between the transition regions A1 of the adjacent microfluidic units, thereby achieving the movement of the droplet 001. In addition, the area ratio of the orthographic projection of the first sub-electrode 11 to the orthographic projection of the second sub-electrode 12 may be set as needed, and is not limited herein.
However, if the area of the second sub-electrode 12 is too small, the second sub-electrode 12 may not have enough driving ability. Therefore, in some embodiments, the ratio of the area of the orthographic projection of one second sub-electrode 12 on the first substrate 2 to the area of the orthographic projection of one first sub-electrode 11 on the first substrate 2 is 1:9 to 1:2. In the present embodiment, an example in which the ratio of the area of the orthographic projection of one second sub-electrode 12 on the first substrate 2 to the area of the orthographic projection of one first sub-electrode 11 on the first substrate 2 is 1:4 is described, but the present disclosure is not limited thereto.
It should be noted that in order to ensure that the droplet can move from one microfluidic unit to another, the second sub-electrode 12 in each microfluidic unit should be as close as possible to the edge of the adjacent microfluidic unit, and the edges of the first substrates 2 of the adjacent two microfluidic units should be aligned with each other. Such an arrangement enables adjacent microfluidic units to be as close as possible and the gap S1 between the second sub-electrodes 12 of two adjacent microfluidic units to be as small as possible.
In some embodiments, for example, referring to
The orthographic projection of the second substrate 5 on the first substrate 2 may at least partially overlap the orthographic projection of the second sub-electrode 12 on the first substrate 2 to ensure that the gap S1 between the second substrates 5 of two adjacent microfluidic units is not too large, thereby avoiding the droplet 001 from being squeezed into the gap S1 and ensuring that the movement of the droplet is smoothly completed. In addition, when the orthographic projection of the second substrate 5 of each microfluidic unit on the first substrate 2 covers the orthographic projection of the edge of the transition region A1 of the microfluidic unit adjacent to another microfluidic unit on the first substrate 2, the edge of the second substrate 5 of each microfluidic unit adjacent to another microfluidic unit and the edge of the transition region A1 of the microfluidic unit adjacent to another microfluidic unit coincide with the dotted line as in
In some embodiments, referring to
In some embodiments, referring to
The fixation assembly may include various types of structures, for example, the fixation assembly 01 may include an outer frame 011 and a plurality of springs 012 and a plurality of stoppers 013 disposed within the outer frame. The outer frame 011 encloses the plurality of microfluidic units 100 combined with each other therein, and has a rectangular shape. One end of each of the plurality of springs 012 is connected to at least two side walls (i.e., inner side walls) (e.g., right and upper sides) of the outer frame 011 near the plurality of microfluidic units 100, and the other end of each of the plurality of springs 012 is connected to one stopper 013.
One stopper 013 corresponds to one microfluidic unit 100, for example, the microfluidic units 100 located on the outermost sides (e.g., upper and right sides) among the microfluidic units 100 combined with each other may be respectively in contact with one stopper 013. When the plurality of stoppers 013 are respectively in contact with some of the plurality of microfluidic units located at the outer edge, the other microfluidic units located at the outer edge of the plurality of microfluidic units are in contact with the other inner side walls (e.g., left and lower sides) of the outer frame 011, and the springs 012 are in a compressed state (i.e., their natural length (length without force) is smaller than the distance between the inner side wall of the outer frame 011 connected thereto and the stoppers 013), the restoring force of the plurality of springs 012 is applied to the plurality of microfluidic units. Specifically, since the springs 012 are in a compressed state, under the restoring force of the compressed springs 012, the plurality of stoppers 013 may apply a force to the inside of the microfluidic unit 100 in contact therewith (for example, as shown in
In addition, the shape of the inner wall of the outer frame 011 can be fitted to the shape of the microfluidic unit 100 of the microfluidic chip formed by combining a plurality of microfluidic units 100. The length of the spring 012 may be adjusted according to the number and size of the microfluidic units 100.
Because the compression length of the spring 012 has a certain range when the springs 012 are used to fix a plurality of microfluidic units 100, the fixation assembly 01 can be compatible with microfluidic chips formed by combining microfluidic units 100 with various sizes in a certain range. For example, referring to
In some embodiments, in order to accommodate the shapes of the microfluidic chips formed by combining the plurality of microfluidic units 100, the springs 012 and the stoppers 013 may be fixed in a detachable connection manner, and the springs 012 and the inner wall of the outer frame 011 may also be fixed in a detachable connection manner, so as to replace springs of different specifications according to the number and size of the microfluidic chips, which is not limited herein.
In some embodiments, in order to apply the restoring force generated by the compressed springs 012 to the microfluidic units 100 by the stoppers 013, the thickness of the stoppers 013 may be greater than the thickness of each microfluidic unit 100 in a third direction perpendicular to the first direction and the second direction.
In some embodiments, referring to
In some embodiments, referring to
In summary, each microfluidic unit of the plurality of microfluidic units may have different functions according to the arrangement of the first sub-electrodes 11, and the microfluidic chip formed by combining different microfluidic units can perform different biological detections. An example of a microfluidic chip formed by combining the microfluidic chip shown in
As shown in
Specifically, the microfluidic chip includes two microfluidic units 100a having a function of generating droplets, two microfluidic units 100b having a function of controlling the turning of the droplet, one microfluidic unit 100c having a function of mixing different kinds of droplets, one microfluidic unit 100d having a function of moving the droplet, one microfluidic unit 100e having a function of splitting the droplet into sub-droplets, and one microfluidic unit 100f having a function of sampling the droplet, which are arranged in the form of a 4×2 array, where a first row of the array includes the microfluidic units 100a, 100b, 100c, and 100d in an order from left to right, and a second row of the array includes the microfluidic units 100a, 100b, 100e, and 100f in an order from left to right. The biological reaction process of the microfluidic chip is as follows.
In S1, a reagent of the first droplet and a reagent of the second droplet are respectively introduced through the two microfluidic units 100a for droplet generating in the first and second rows of the array, and two droplets are generated.
In S2, the first droplet enters the microfluidic unit 100b for controlling the turning of the droplet in the first row from the microfluidic unit 100a in the first row and then enters the microfluidic unit 100c for mixing. The second droplet enters the microfluidic unit 100b for controlling the turning of the droplet in the second row from the microfluidic unit 100a in the second row, and then turns to enter the microfluidic unit 100b for controlling the turning of the droplet in the first row, and turns again to enter the microfluidic unit 100c for mixing in the first row. In this case, the two kinds of droplets are uniformly mixed after several turns in the microfluidic unit 100c for mixing different kinds of droplets in the first row.
In S3, the droplet after uniform mixing returns to the microfluidic unit 100b in the first row again, then turns to enter the microfluidic unit 100b in the second row, and turns again to enter the microfluidic unit 100e for splitting, and the droplet is split into two sub-droplets uniformly.
In S4, the two sub-droplets sequentially enter the microfluidic unit 100f for sampling, and are sampled separately, thereby completing the reaction flow.
As shown in
Specifically, the microfluidic chip includes, in the form of a 2×5 array, two microfluidic units 100a having a function of generating the droplet, two microfluidic units 100b having a function of controlling the turning of the droplet, one microfluidic unit 100c having a function of mixing different kinds of droplets, one microfluidic unit 100g having a function of regulating a temperature of the droplet, one microfluidic unit 100f having a function of sampling the droplets, and three blank units 100i, where the three blank units 100i are disposed to combine the above microfluidic units 100 into a regular array, and the three blank units 100i may also be omitted. The first row of the array includes, from left to right, the microfluidic units 100a, 100b, 100c, 100g and 100f; the second row of the array includes, from left to right, the microfluidic units 100a, 100b and three 100i. The biological reaction process of the microfluidic chip is as follows.
In S1, the reagent of the first droplet and the reagent of the second droplet are respectively introduced through the two microfluidic units 100a for droplet generation in the first and second rows of the array, and two droplets are generated.
In S2, the first droplet enters the microfluidic unit 100b for controlling the turning of the droplet in the first row from the microfluidic unit 100a in the first row, and then enters the microfluidic unit for mixing 100c. The second droplet enters the microfluidic units 100b for controlling the turning of the droplet in the second row from the microfluidic units 100a in the second row, then turns to enter the microfluidic units 100b for controlling the turning of the droplet in the first row, and turns again to enter the microfluidic units 100c for mixing in the first row. In this case, the two kinds of droplets are uniformly mixed after several turns in the microfluidic unit 100c for mixing different kinds of droplets in the first row.
In S3, the uniformly mixed droplets are moved from the microfluidic units 100c for mixing different kinds of droplets in the first row to the microfluidic unit 100g for regulating a temperature of the droplet, and the droplet turns along the first sub-electrode 11 for a desired reaction time.
In S4, the droplet after the completion of the reaction enters the microfluidic unit 100f for sampling from the microfluidic unit 100g for regulating a temperature of the droplet, and is sampled, thereby completing the reaction flow.
Of course, the foregoing are only two exemplary combinations of the microfluidic chip provided in the embodiments of the present disclosure, and different microfluidic units can also be combined in different ways according to different reaction requirements to adapt to multiple reactions, which is not limited herein.
Referring to
For most biochemical reactions, the reaction temperature is critical to the reaction result, and therefore, it is necessary to detect and control the temperature of the reaction process in the microfluidic chip. Thus, referring to
Referring to
Referring to
where ε0 is the vacuum dielectric constant, εr(T) is the relative dielectric constant of the droplet 001 that changes with temperature, A is an area of the first sub-electrode 11c or the first sub-electrode 11d (the first sub-electrode 11d has the same area as the first sub-electrode 11c), and d is the thickness of the droplet 001.
Further, the moving position of the droplet 001 can be monitored by detecting the capacitance of C(T). For example, when there is no droplet 001 between the first sub-electrode 11c, the first sub-electrode 11d, and the reference electrode 6, εr(T) in equation (2) is the relative dielectric constant of the medium around the droplet 001. The medium around the droplet may include air, silicone oil, etc., where the air has a relative dielectric constant of 1, and the silicone oil has a relative dielectric constant of 2.6. In this case, there is a difference of several tens of times between the empty capacitance that can be measured and the capacitance of the capacitor C(T) (hereinafter referred to as the detection capacitor) when the droplet is present, and it is thereby possible to determine whether or not there is a droplet 001 on the first sub-electrode 11c and the first sub-electrode 11d.
In some embodiments, the temperature measuring unit M2 may include a variety of configurations. For example, as shown in
When the changes in the temperature is ΔT, an amount of change in output voltage is:
The relative dielectric constant of the droplet 001 changes 0.3066 per 1° C. change in temperature, while the relative dielectric constant of the medium of the feedback capacitor C′ (e.g., a medium (e.g., air) around the droplet) does not change with the change in temperature, so that the relative dielectric constant of the air medium (εr′=1) can be obtained, and thus the amount of change in the output voltage is 30.66% Vin. Assuming that the capacitance medium of the feedback capacitor C′ is silicone oil, the relative dielectric constant εr′=2.6 of the silicone oil medium, and the variation of the output voltage is 11.79% Vin, which enables the proportional amplifying circuit included in the temperature measuring unit M2 to reduce the difficulty of detection and improve the sensitivity of temperature detection.
In some embodiments, since the capacitance of the feedback capacitor C′ is the reference capacitance, the relative dielectric constant of the capacitance medium of the feedback capacitor C′ does not change with temperature, and the capacitance of the feedback capacitor C′ should be the same as the capacitance between the first sub-electrode 11c, the first sub-electrode 11d, and the reference electrode 6 without the droplet 001, two adjacent first sub-electrodes 11 may be directly used as the lower plate of the feedback capacitor C′. Specifically, referring to
In some embodiments, in order to ensure the accuracy of detection, at least one first sub-electrode may be included between the first sub-electrodes 11 forming the feedback capacitor C′ and a detection capacitor C(T), so that it is possible to prevent the occurrence of signal crosstalk due to the droplet 001 simultaneously covering the first sub-electrodes 1 forming the feedback capacitor C′ and the detection capacitor C(T).
In some embodiments, referring to
In some embodiments, as shown in
In some embodiments, the temperature adjusting unit 003 can include various types of structures, such as a resistance wire, a thermoelectric temperature adjusting pad (e.g., peltier thermoelectric semiconductor device), and the like. An example in which the temperature adjusting unit 003 is a thermoelectric temperature adjusting sheet will be described below, and the temperature adjusting unit 003 may be disposed on a side of the first substrate 2 of the microfluidic unit coupled to the temperature measuring unit M2 facing away from the first sub-electrode 11.
In some embodiments, referring to
In some embodiments, referring to
Referring to
In addition, referring to
In some embodiments, referring to
The microfluidic chip provided in the disclosure has a plurality of microfluidic units, each microfluidic unit has one operation region, and the microfluidic units can be freely combined to form the microfluidic chip, so that the microfluidic chip can adapt to various biological detection and can be locally repaired or replaced, thereby avoiding waste. Furthermore, a second sub-electrode is provided at the transition region of adjacent microfluidic units, which is capable of driving a droplet to move from one microfluidic unit to another microfluidic unit adjacent thereto.
It will be understood that the above embodiments are merely exemplary embodiments employed to illustrate the principles of the present disclosure, and the present disclosure is not limited thereto. It will be apparent to those skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope of the disclosure, and these changes and modifications are to be considered within the scope of the disclosure.
Number | Date | Country | Kind |
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202110081632.5 | Jan 2021 | CN | national |