The present application is a U.S. National Stage Application under 35 U.S.C. § 371 of International Patent Application No. PCT/CN2018/109781, filed on Oct. 11, 2018, which claims priority to Chinese Patent Application No. 201810198840.1 filed on Mar. 12, 2018, the disclosure of both of which are incorporated by reference herein in entirety.
The present disclosure relates to a microfluidic chip, a biological detection device and a method.
The microfluidic chip technology may integrate basic operation units such as sample preparation, reaction, separation and detection in biological, chemical and medical analysis processes onto a micrometer-scale chip, to automatically complete the entire analysis process. Since the cost may be reduced by using the microfluidic chip and the microfluidic chip has such advantages as short detection time and high sensitivity, the microfluidic chip has showed great prospect in biological, chemical, and medical fields and the like.
In recent years, the numerical microfluidic technology based on the dielectric wetting technology by which discrete droplets may be controlled with such advantages as low reagent consumption, low cost, no cross-contamination, being able to controlling droplets individually, and easy implementation of an integrated portable system, has become a research hotspot in the scientific research community.
According to one aspect of embodiments of the present disclosure, a microfluidic chip is provided. The microfluidic chip comprises: a first substrate and a second substrate that are oppositely disposed; a first electrode and a second electrode that are oppositely disposed between the first substrate and the second substrate, the first electrode comprising a plurality of spaced first electrode units, and the second electrode comprising a plurality of spaced second electrode units, wherein the first electrode units are disposed oppositely to the second electrode units in one-to-one correspondence; a first dielectric layer and a second dielectric layer that are between the first electrode and the second electrode; and a first hydrophobic layer and a second hydrophobic layer that are between the first dielectric layer and the second dielectric layer, wherein a gap is between the first hydrophobic layer and the second hydrophobic layer.
In some embodiments, a plurality of spaced first pins connected to the first electrode are provided on the first substrate, wherein the first pins are connected to the first electrode units in one-to-one correspondence; and a plurality of spaced second pins connected to the second electrode are provided on the second substrate, wherein the second pins are connected to the second electrode units in one-to-one correspondence, the first pins are disposed oppositely to the second pins in one-to-one correspondence; wherein each first pin is adhered and electrically connected to a corresponding second pin by a conductive adhesive.
In some embodiments, the conductive adhesive comprises metal particles, at least one of the metal particles being between one of the first pins and the corresponding one of the second pins, such that one of the first electrode units corresponding to the one of the first pins is electrically connected to one of the second electrode units corresponding to the one of the second pins.
According to another aspect of embodiments of the present disclosure, a biological detection device is provided. The device comprises the microfluidic chip as described above.
According to another aspect of embodiments of the present disclosure, a method for manufacturing a microfluidic chip is provided. The method comprises: forming a patterned first electrode on a first substrate, and forming a patterned second electrode on a second substrate, wherein the first electrode comprises a plurality of spaced first electrode units, and the second electrode comprises a plurality of spaced second electrode units; forming a first dielectric layer on the first electrode, and forming a second dielectric layer on the second electrode; forming a first hydrophobic layer on the first dielectric layer, and forming a second hydrophobic layer on the second dielectric layer; and disposing oppositely the first substrate and the second substrate, such that the first electrode, the second electrode, the first dielectric layer, the second dielectric layer, the first hydrophobic layer, and the second hydrophobic layer are all between the first substrate and the second substrate, wherein a gap is formed between the first hydrophobic layer and the second hydrophobic layer.
In some embodiments, before forming the first dielectric layer and the second dielectric layer, the method further comprises: forming a plurality of spaced first pins connected to the first electrode on the first substrate, wherein the first pins are connected to the first electrode units in one-to-one correspondence; and forming a plurality of spaced second pins connected to the second electrode on the second substrate, wherein the second pins are connected to the second electrode units in one-to-one correspondence; wherein in the step of disposing oppositely the first substrate and the second substrate, the first pins are disposed oppositely to the second pins in one-to-one correspondence.
In some embodiments, the step of disposing oppositely the first substrate and the second substrate comprises: adhering and electrically connecting each first pin to a corresponding second pin by a conductive adhesive.
According to another aspect of embodiments of the present disclosure, a method for moving a sample droplet using the microfluidic chip as described above is provided. The method comprises: introducing a sample droplet into the gap of the microfluidic chip; and applying sequentially a plurality of groups of driving signals to the first electrode and the second electrode that are oppositely disposed to move the sample droplet, wherein applying each group of driving signals comprises: applying a driving voltage to one of the first electrode units and a driving voltage to one of the second electrode units, wherein the one of the first electrode units and the one of the second electrode units are closest to the sample droplet on a moving direction side of the sample droplet, and the driving voltage applied to the one of the first electrode units has the same polarity as the driving voltage applied to the one of the second electrode units, and applying a ground voltage to remaining first electrode units and remaining second electrode units.
In some embodiments, the driving voltage applied to the one of the first electrode units is equal to the driving voltage applied to the one of the second electrode units.
According to another aspect of embodiments of the present disclosure, a method for separating a sample droplet using the microfluidic chip as described above is provided. The method comprises: introducing a sample droplet into the gap of the microfluidic chip; and applying a first group of driving voltages to at least one group of electrode units on one side of the sample droplet, and applying a second group of driving voltages having the same polarity as the first group of driving voltages to at least one group of electrode units on another side of the sample droplet, to separate the sample droplet, wherein each group of electrode units comprises one of the first electrode units and a second electrode unit disposed oppositely to the one of the first electrode units, and each group of driving voltages comprises a driving voltage applied to the one of the first electrode units and a driving voltage applied to the second electrode unit.
In some embodiments, the step of applying the first group of driving voltages and the second group of driving voltages comprises: applying the first group of driving voltages to one group of electrode units on the one side of the sample droplet and closest to the sample droplet, and applying the second group of driving voltages to another group of electrode units on the other side of the sample droplet and closest to the sample droplet.
In some embodiments, the driving voltage applied to the one of the first electrode units is equal to the driving voltage applied to the second electrode unit.
Other features and advantages of the present disclosure will become apparent from the following detailed description of exemplary embodiments of the present disclosure with reference to the accompanying drawings.
The accompanying drawings, which constitute part of this specification, illustrate embodiments of the present disclosure and, together with this specification, serve to explain the principles of the present disclosure.
The present disclosure may be more clearly understood from the following detailed description with reference to the accompanying drawings, in which:
It should be understood that the dimensions of the various parts shown in the drawings are not drawn to the actual scale. In addition, the same or similar reference signs are used to denote the same or similar components.
Various exemplary embodiments of the present disclosure will now be described in detail with reference to the accompanying drawings. The following description of the exemplary embodiments is merely illustrative and is in no way intended as a limitation to the present disclosure, its application or use. The present disclosure may be implemented in many different forms, which are not limited to the embodiments described herein. These embodiments are provided to make the present disclosure thorough and complete, and fully convey the scope of the present disclosure to those skilled in the art. It should be noticed that: relative arrangement of components and steps, material composition, numerical expressions, and numerical values set forth in these embodiments, unless specifically stated otherwise, should be explained as merely illustrative, and not as a limitation.
The use of the terms “first”, “second” and similar words in the present disclosure do not denote any order, quantity or importance, but are merely used to distinguish between different parts. A word such as “comprise”, “includes” or variants thereof means that the element before the word covers the element(s) listed after the word without excluding the possibility of also covering other elements. The terms “up”, “down”, “left”, “right”, or the like are used only to represent a relative positional relationship, and the relative positional relationship may be changed correspondingly if the absolute position of the described object changes.
In the present disclosure, when it is described that a particular device is located between the first device and the second device, there may be an intermediate device between the particular device and the first device or the second device, and alternatively, there may be no intermediate device. When it is described that a particular device is connected to other devices, the particular device may be directly connected to said other devices without an intermediate device, and alternatively, may not be directly connected to said other devices but with an intermediate device.
Unless otherwise defined, all terms (comprising technical and scientific terms) used herein have the same meanings as the meanings commonly understood by one of ordinary skill in the art to which the present disclosure belongs. It should also be understood that terms as defined in general dictionaries, unless explicitly defined herein, should be interpreted as having meanings that are consistent with their meanings in the context of the relevant art, and not to be interpreted in an idealized or extremely formalized sense.
Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail, but where appropriate, these techniques, methods, and apparatuses should be considered as part of this specification.
At present, numerical microfluidic chips may be divided into two categories: single-substrate structure and dual-substrate structure. The single-substrate structure which is relatively simple and easy to integrate into a circuit, has such disadvantages as the droplets being easily evaporated and contaminated, and it being difficult to implement droplet separation. The dual-substrate structure which may implement droplet separation is relatively complicated and difficultly fabricated with a great upper substrate resistance and a great lower substrate resistance. Currently, the numerical microfluidic chip based on the dual-substrate structure typically requires a driving voltage to be applied to an electrode on one side of the gap. For example, the driving voltage may be tens to hundreds of volts.
The inventor of the present disclosure has found that, since the numerical microfluidic chip based on the dual-substrate structure in the related art typically requires a driving voltage to be applied to an electrode on one side of the gap, the applied driving voltage is relatively high, so that it is easy to result in breakdown of the chip.
In view of this, embodiments of the present disclosure provide a microfluidic chip structure, by which a driving voltage applied to the microfluidic chip is reduced and the breakdown of the chip may be prevented. The structure of the microfluidic chip according to some embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings.
As shown in
In some embodiments, materials of the first substrate 41 and the second substrate 42 comprise glass, quartz, or plastic and the like.
As shown in
It should be noted that the term “disposed oppositely” as described in the embodiments of the present disclosure means that, for two structural layers disposed on both sides of the gap, the positions at which they are situated cause that when such two structural layers respectively project to a plane in which one of such two structural layers is situated, such two projections at least partially overlap (e.g., completely overlap). For example, the first electrode unit 111 and the second electrode unit 121 are oppositely disposed, that is, the projection of the first electrode unit 111 on the upper side of the gap on the plane in which the second electrode unit 121 is situated completely overlaps with the projection of the second electrode unit 121 on the lower side of the gap on the plane in which the second electrode unit 121 is situated.
In some embodiments, as shown in
As shown in
As shown in
In the microfluidic chip of the above-described embodiment, the first electrode are provided on the upper side of the gap and the second electrode are provided on the lower side of the gap. Here, the first electrode comprises a plurality of spaced first electrode units, and the second electrode comprises a plurality of spaced second electrode units. That is, the first electrode and the second electrode are both array electrodes. By this, in the process of moving a sample droplet or separating a sample droplet using the microfluidic chip, a driving voltage may be applied to the first electrode unit on the upper side of the gap and another driving voltage may be applied to the second electrode unit on the lower side of the gap, wherein the first electrode unit corresponds to the second electrode unit. Compared to the case in the known related art that a driving voltage can only be applied to an electrode on one side of the gap, the driving voltages applied to the microfluidic chip of embodiments of the present disclosure are lower. Therefore, the risk of the breakdown of the chip may be reduced.
For example, as shown in
In some embodiments, each of the first electrode units 111 and the corresponding second electrode unit 121 are symmetrically disposed with respect to the gap 50. For example, each of the first electrode units has the same area or shape as the corresponding second electrode unit, and the position of each of the first electrode units and the position of the corresponding second electrode unit are symmetrical with respect to the gap. In this way, it is favorable that the induced charge distribution on the surface of the droplet is as symmetrical as possible when the same driving voltage is applied to the first electrode unit and the second electrode unit that are oppositely disposed. Thereby, the movement of the droplet may be better controlled, and the driving voltage may be reduced as much as possible to prevent breakdown of the chip.
The structure of the microfluidic chip according to some embodiments of the present disclosure is described in further detail below with reference to
In some embodiments, as shown in
In some embodiments, as shown in
Here, the first pins 61 are disposed oppositely to the second pins 62 in one-to-one correspondence. In some embodiments, as shown in
In the above-described embodiment, the pins of the first electrode are electrically connected to the pins of the second electrode at the periphery of the chip using the conductive adhesive. By controlling the distribution density of the metal particles and the spacing of the pins, there is no overlap between the metal particles so that it is only possible to electrically connect the first electrode unit to the corresponding second electrode unit without causing short-circuit to adjacent pins. This reduces the difficulty in manufacturing the chip, and facilitates the fabrication of large-scale integrated circuits without a requirement for a complicated process. Therefore, the microfluidic chip of embodiments of the present disclosure is not only simple in structure but also relatively easy in its manufacturing process.
In the above-described embodiment, the first electrode unit is electrically connected to the second electrode unit by the conductive adhesive, wherein the first electrode unit and the second electrode unit are oppositely disposed, so that the same driving voltage may be applied to the first electrode unit and the corresponding second electrode unit to control the movement of the droplet. However, the scope of embodiments of the present disclosure is not limited thereto. Those skilled in the art can understand that a driving voltage may be applied to the first electrode unit and another driving voltage may be applied to the corresponding second electrode unit. For example, the driving voltage applied to the first electrode unit is equal or unequal to the other driving voltage applied to the corresponding second electrode unit.
In embodiments of the present disclosure, a biological detection device is also provided. The biological detection device comprises the microfluidic chip as described above, such as the microfluidic chip as shown in
As shown in
Returning to
Returning to
Returning to
In a method of the above-described embodiment, the patterned first electrode is formed on the first substrate, and the patterned second electrode is formed on the second substrate, wherein the first electrode and the second electrode are both array electrodes. The first dielectric layer is formed on the first electrode, and the second dielectric layer is formed on the second electrode. The first hydrophobic layer is formed on the first dielectric layer, and the second hydrophobic layer is formed on the second dielectric layer. The first substrate and the second substrate are oppositely disposed. By this, a microfluidic chip according to embodiments of the present disclosure is formed. The procedure of the manufacturing process is relatively simple and easy to implement.
In some embodiments, before forming the first dielectric layer 21 and the second dielectric layer 22, the manufacturing method may further comprise: for example, referring to
In some embodiments, the step of disposing oppositely the first substrate 41 and the second substrate 42 comprises: adhering and electrically connecting each first pin to a corresponding second pin by a conductive adhesive. The each first pin and the corresponding second pin are oppositely disposed. For example, the first dielectric layer, the second dielectric layer, the first hydrophobic layer, and the second hydrophobic layer are patterned in the process of forming the first dielectric layer, the second dielectric layer, the first hydrophobic layer, and the second hydrophobic layer, so that the first pins and the second pins are exposed. Then, each first pin is adhered and electrically connected to the corresponding second pin by a conductive adhesive.
In some embodiments, in the process of adhering and electrically connecting each first pin to the corresponding second pin by a conductive adhesive, the distribution density of the metal particles within the conductive adhesive and the spacing of the pins may be controlled by controlling the process conditions (e.g., amount of adhesive application, speed of adhesive application, etc.), so that there is no overlap between the metal particles and the first pin corresponding to the first electrode unit is electrically connected to the second pin corresponding to the corresponding second electrode unit without causing short-circuit to adjacent pins.
In step S902, a sample droplet is introduced into a gap of the microfluidic chip.
In step S904, a plurality of groups of driving signals are sequentially applied to the first electrode and the second electrode that are oppositely disposed to move the sample droplet, wherein applying each group of driving signals comprises: applying a driving voltage to one of the first electrode units and a driving voltage to one of the second electrode units, wherein the one of the first electrode units and the one of the second electrode units are closest to the sample droplet on a moving direction side of the sample droplet, and the driving voltage applied to the one of the first electrode units has the same polarity as the driving voltage applied to the one of the second electrode units, and a ground voltage is applied to remaining first electrode units and remaining second electrode units.
For example, as shown in
In the above-described method for moving a sample droplet, the polarity of the driving voltage applied to the first electrode unit is the same as the polarity of the driving voltage applied to the second electrode unit. This may make the applied driving voltage reduced as much as possible, so that it is possible to prevent breakdown of the chip as much as possible, and there is a relatively favorable effect in driving the movement of a sample droplet.
In the method for moving a sample droplet by the microfluidic chip in the above-described embodiment, since a driving voltage is applied to the first electrode unit on the upper side of the gap and another driving voltage is applied to the second electrode unit disposed oppositely to the first electrode unit on the lower sides of the gap to drive the movement of the sample droplet, these driving voltages applied may be respectively lower than the driving voltage of the related art, so that it is possible to prevent breakdown of the chip as much as possible.
In some embodiments, the driving voltage applied to the one of the first electrode units is equal to the driving voltage applied to the one of the second electrode units. This makes the driving voltages applied to the two electrode units both relatively low.
In step S1002, a sample droplet is introduced into a gap of the microfluidic chip.
In step S1004, a first group of driving voltages is applied to at least one group of electrode units on one side of the sample droplet, and a second group of driving voltages having the same polarity as the first group of driving voltages is applied to at least one group of electrode units on another side of the sample droplet, to separate the sample droplet. Each group of electrode units comprises one of the first electrode units and a second electrode unit disposed oppositely to the one of the first electrode units. Each group of driving voltages comprises a driving voltage applied to the one of the first electrode units and a driving voltage applied to the second electrode unit. The one side of the sample droplet is opposite to the other side of the sample droplet.
In some embodiments, the step S1004 may comprise: applying the first group of driving voltages to one group of electrode units on the one side of the sample droplet and closest to the sample droplet, and applying the second group of driving voltages to another group of electrode units on the other side of the sample droplet and closest to the sample droplet.
For example,
In the method for separating a sample droplet by the microfluidic chip of the above-described embodiment, since driving voltages having the same polarity are applied to both the first electrode unit on the upper side of the gap and the second electrode unit on the lower side of the gap that are oppositely disposed, the driving voltages may be reduced. Thereby, breakdown of the chip is prevented as much as possible.
In some embodiments, the driving voltage applied to the one of the first electrode units is equal to the driving voltage applied to the second electrode unit disposed oppositely to the one of the first electrode units. This makes the driving voltages relatively low.
Hereto, various embodiments of the present disclosure have been described in detail. Some details well known in the art are not described to avoid obscuring the concept of the present disclosure. According to the above description, those skilled in the art would fully know how to implement the technical solutions disclosed herein.
Although some specific embodiments of the present disclosure have been described in detail by way of examples, those skilled in the art should understand that the above examples are only for the purpose of illustration and are not intended to limit the scope of the present disclosure. It should be understood by those skilled in the art that modifications to the above embodiments and equivalently substitution of part of the technical features can be made without departing from the scope and spirit of the present disclosure. The scope of the disclosure is defined by the following claims.
Number | Date | Country | Kind |
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201810198840.1 | Mar 2018 | CN | national |
Filing Document | Filing Date | Country | Kind |
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PCT/CN2018/109781 | 10/11/2018 | WO | 00 |
Publishing Document | Publishing Date | Country | Kind |
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WO2019/174222 | 9/19/2019 | WO | A |
Number | Name | Date | Kind |
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20160059230 | Hsu | Mar 2016 | A1 |
20190126279 | Gach | May 2019 | A1 |
Number | Date | Country |
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105572398 | May 2016 | CN |
107649223 | Feb 2018 | CN |
108465491 | Aug 2018 | CN |
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Number | Date | Country | |
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20200391207 A1 | Dec 2020 | US |