This application relates to the field of microscale heating technologies, and in particular, to a microfluidic chip, apparatus and system, and a control and preparation method therefor.
The microfluidic chip technology integrates basic operation units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes into a micron-sized chip to automatically complete the entire analysis process. Due to its features of controllable liquid flow, very little sample and reagent consumption, and analysis speed improvement by dozens or hundreds of times, this technology has great potential in the fields of biology, chemistry, medicine, etc., and has received extensive attention from scientific research institutions in and out of China.
In recent years, as microfluidic technologies develop, the research on microscale heating technologies has attracted the attention of academia. A microscale heating method has the advantages of low heating power, fast response, small heat loss, easy integration with other microelectronic devices, etc. It has been used, to varying extents, in fields including nucleic acid amplification, thermophoresis, particle manipulation, cell culture, etc.
At present, most of the existing microscale heating technologies integrate metal blocks or films as heating electrodes into a chip. By heating the metal blocks or films, different positions in the chip are heated. Common heating solutions mainly include the following: (1) metal block heating method; (2) indium tin oxide film heating method; (3) infrared heat source heating method.
Metal block heating method: Metal heaters are usually located in opaque channels to quickly and accurately control temperatures of liquid samples. However, because this method is optically opaque and easy to electrolyze in liquid samples, it is usually necessary to use relatively expensive metals such as platinum and gold and other precious metals. Consequently, the heating status is not easily observed and costs are high. Indium tin oxide film heating method: In this technology, microfluidic channels are usually etched on the glass, and the transparent indium tin oxide film is integrated as an electrode into a microfluidic chip, so as to improve the visibility of internal channels for easy observation. However, the heating region in this method is fixed and cannot be changed. Infrared heat source heating method: In this technology, tungsten and other materials are used as the infrared radiation source, and the far-infrared source is used for heating. The energy efficiency of this radiation heating is not high, and optical devices such as lens filters are required. In addition, infrared rays affect experimental observation.
In conclusion, the heating efficiency of the existing microscale heating chip is not high, costs are high, the heating source region is fixed, and the heating process is not easily observed.
In view of the above, an objective of this application is to provide a microfluidic chip, apparatus and system, and a control and preparation method therefor, so as to provide a microfluidic chip that features high energy conversion efficiency, fast heating, and implementation of heating in a specific region.
According to a first aspect, an embodiment of this application provides a microfluidic chip, including: a substrate, and an electrode layer and a functional layer sequentially formed on the substrate, where the electrode layer includes multiple electrode groups arranged in an array;
The electrode group is configured to: When being activated, convert an electrical signal into an acoustic signal, and transmit the acoustic signal to the functional layer; and
the functional layer is configured to: carry a sample to be tested; absorb the acoustic signal emitted by the activated electrode group and convert the acoustic signal into thermal energy; and heat the sample to be tested that is carried at a position corresponding to the activated electrode group.
With reference to the first aspect, in a first possible implementation of the first aspect according to the embodiment of this application, the electrode group includes two interdigital electrodes arranged in interdigital fingers, interdigital widths of the two interdigital electrodes of the same electrode group are equal, gaps between adjacent interdigital fingers are equal, and the interdigital width is equal to the gap.
With reference to the first possible implementation of the first aspect, in a second possible implementation of the first aspect according to the embodiment of this application, interdigital electrodes of each of the multiple electrode groups arranged in an array have equal interdigital widths.
With reference to the first possible implementation of the first aspect, in a third possible implementation of the first aspect according to the embodiment of this application, among the multiple electrode groups arranged in an array, interdigital widths of interdigital electrodes in the same column of electrode groups change progressively in a column direction, and interdigital widths of interdigital electrodes in the same row of electrode groups change progressively in a row direction.
With reference to the first aspect, in a fourth possible implementation of the first aspect according to the embodiment of this application, the functional layer includes a first functional layer and a second functional layer, the first functional layer is located above the electrode layer and is bonded to the substrate, the second functional layer is located above the first functional layer, and a channel for carrying the sample to be tested is disposed between the first functional layer and the second functional layer.
With reference to the first aspect, in a fifth possible implementation of the first aspect according to the embodiment of this application, the functional layer is made from polydimethylsiloxane.
With reference to the first aspect, in a sixth possible implementation of the first aspect according to the embodiment of this application, the substrate is made from any material from lithium niobate, zinc oxide, or aluminum oxide.
With reference to the sixth possible implementation of the first aspect, in a seventh possible implementation of the first aspect according to the embodiment of this application, the substrate is made from 128°YX double-sided polished lithium niobate.
According to a second aspect, an embodiment of this application provides a microfluidic apparatus, where the apparatus is configured to control the microfluidic chip according to any one of the first aspect to the seventh possible implementation of the first aspect, and includes a controller and a signal generator, where the controller is connected to the signal generator;
The controller is configured to control the signal generator to generate an electrical signal based on a set frequency; and
The signal generator is configured to transmit the generated electrical signal to an electrode group for activation when connected to the electrode group, so that the activated electrode group generates an acoustic signal.
With reference to the second aspect, in a first possible implementation of the second aspect according to the embodiment of this application, the apparatus further includes a frequency divider, where the frequency divider includes a signal input interface and multiple signal output interfaces, the frequency divider is connected to the signal generator through the signal input interface, and the multiple signal output interfaces are configured to connect to different electrode groups respectively; and
The frequency divider is configured to divide the electrical signal generated by the signal generator into electrical signals of different frequencies, and when connected to different electrode groups, transmit the electrical signals of different frequencies through the signal output interfaces to the electrode groups for activation.
According to a third aspect, an embodiment of this application provides a microfluidic system, where system includes the microfluidic chip according to any one of the first aspect to the seventh possible implementation of the first aspect, and the microfluidic apparatus according to the second aspect or the first possible implementation of the second aspect.
According to a fourth aspect, an embodiment of this application provides a microfluidic chip control method, where the method is used to control the microfluidic apparatus according to the second aspect or the first possible implementation of the second aspect, and includes:
Controlling, by the controller, the signal generator to generate an electrical signal based on a set frequency; and
Controlling, by the controller, the signal generator to transmit the generated electrical signal to the electrode group for activation when the signal generator is connected to the electrode group, so that the activated electrode group generates an acoustic signal.
With reference to the fourth aspect, in a first possible implementation of the fourth aspect according to the embodiment of this application, the method further includes:
Transmitting, by the controller, the electrical signal to the frequency divider by using the signal generator; and
Dividing, by the controller, the electrical signal into electrical signals of different frequencies by using the frequency divider, and transmitting the electrical signals to the electrode groups for activation.
According to a fifth aspect, an embodiment of this application provides a microfluidic chip preparation method, Where the method is used to prepare the microfluidic chip according to any one of the first aspect to the seventh possible implementation of the first aspect, and includes:
Forming a photoresist layer on the substrate;
Performing photoetching on the photoresist layer to form a set pattern arranged in an array on the substrate;
Performing sputtering on the substrate corresponding to the pattern to form an electrode layer, where the formed electrode layer includes multiple electrode groups arranged in an array, so that the electrode group converts an electrical signal into an acoustic signal when activated, and transmits the acoustic signal to the functional layer; and
Forming the functional layer on the electrode layer, so that the functional layer carries a sample to be tested, absorbs the acoustic signal emitted by the activated electrode group and converts the acoustic signal into thermal energy, and heats the sample to be tested that is carried at a position corresponding to the activated electrode group.
With reference to the fifth aspect, in a first possible implementation of the fifth aspect according to the embodiment of this application, the performing photoetching on the photoresist layer to form a set pattern arranged in an array on the substrate includes:
Laying a mask on the photoresist layer for exposure, where the mask is the set pattern arranged in an array; and
Developing and dissolving a non-transparent region in the photoresist layer when the photoresist layer is exposed, to form the set pattern arranged in an array on the substrate.
Different from the prior art, in this application, an external device transmits an electrical signal to the electrode layer, and the electrode layer converts the electrical signal into an acoustic signal. The acoustic signal can be absorbed by the functional layer to generate thermal energy, and the electrode layer includes multiple electrode groups arranged in an array. As long as some of the multiple electrode groups are activated through separate control, the corresponding functional layer at the position of the activated electrode group can genera thermal energy, thereby heating the sample to be tested. This application provides a microfluidic chip that features high energy conversion efficiency, fast heating, and implementation of heating in a specific region.
To make the foregoing objectives, features, and advantages of this application clearer and more comprehensible, the following provides a detailed description by using preferred embodiments with reference to the accompanying drawings.
To describe the technical solutions in the embodiments of this application more clearly, the following briefly describes the accompanying drawings required for the embodiments. It should be understood that, the accompanying drawings show merely some embodiments of this application; and therefore should not be considered a limitation on the scope. A person of ordinary skill in the art may derive other drawings from these accompanying drawings without creative efforts.
Reference numerals: 100—microfluidic chip; 101—substrate; 102—electrode layer; 103—functional layer; 1021—electrode group; 1021A—interdigital electrode; 400—microfluidic apparatus; 401—controller; 402—signal generator; 403—frequency divider; 4031—signal input interface; 4032—signal output interface; 104—photoresist layer.
To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the following clearly and comprehensively describes the technical solutions in the embodiments of this application with reference to the accompanying drawings in the embodiments of this application. Clearly, the described embodiments are merely some but not all of the embodiments of this application. Generally, the components of the embodiments of this application that are described and illustrated in the accompanying drawings herein can be arranged and designed in various configurations. Therefore, the following detailed description of the embodiments of this application provided in the accompanying drawings is not intended to limit the claimed scope of this application, but merely represents selected embodiments of this application. All other embodiments obtained by a person skilled in the art based on the embodiments of this application without creative efforts shall fall within the protection scope of this application.
Embodiment 1 of this application provides a microfluidic chip 100.
The electrode group 1021 is configured to: when being activated, convert an electrical signal into an acoustic signal, and transmit the acoustic signal to the functional layer 103.
As shown in
A resonant frequency of each electrode group is related to an acoustic velocity and an interdigital width. A formula of the resonant frequency ƒ s as follows:
ƒ=Vm/M, where Vm represents the acoustic velocity, and M=4a=4b.
Here, an interdigital period P=2(a+b).
Changing the interdigital period indirectly changes the resonant frequency of the electrode group. For a specific input signal frequency, only an electrode group whose resonant frequency corresponds to the input signal frequency can be activated, thereby generating an acoustic signal of the corresponding frequency.
In a preferred embodiment, in the technical solution provided in Embodiment 1 of this application, interdigital electrodes of each of the multiple electrode groups arranged in an array have equal interdigital widths.
If the interdigital electrodes of each electrode group have equal interdigital widths, resonant frequencies of the electrode groups are equal. If electrical signals of the same frequency are used to activate the electrode groups, frequencies of acoustic signals generated by the electrode groups are equal, and electrical signals can be selectively input into some electrode groups. In this way, only the selected electrode groups can generate acoustic signals, the frequencies of the input electrical signals are equal, and therefore the frequencies of the acoustic signals generated by these electrode groups are equal.
In a preferred embodiment, in the technical solution provided in Embodiment this application, among the multiple electrode groups arranged in an array, interdigital widths of interdigital electrodes in the same column of electrode groups change progressively in a column direction, and interdigital widths of interdigital electrodes in the same row of electrode groups change progressively in a row direction.
It can be seen from the resonant frequency formula that, the resonant frequency of the electrode group is related to the interdigital width of the interdigital electrode, and therefore the resonant frequency of the electrode group can be adjusted by controlling the interdigital width of the interdigital electrode. For example, among the multiple electrode groups arranged in an array, the interdigital widths of the interdigital electrodes in the same column of electrode groups are adjusted to change progressively in a column direction, so that the resonant frequencies of the same column of electrode groups change progressively in the column direction. In this way, when electrical signals of the same frequency are input into the same column of electrode groups, because the resonant frequencies of the column of electrode groups change progressively, amplitudes of the generated acoustic signals also change progressively, and temperatures corresponding to thermal energy generated at the functional layer also change progressively, forming a temperature gradient field. Similarly, the interdigital widths of the interdigital electrodes in the same row of electrode groups are adjusted to change progressively in a row direction, so that the resonant frequencies of the same row of electrode groups change progressively in the row direction.
In this way, for the electrode groups arranged in an array at the electrode layer, the resonant frequencies of electrode groups in the same row are different, and the operating frequencies of electrode groups in the same column are also different. When electrical signals that have different frequencies and that can enable an electrode group to resonate are input into the electrode group, a hotspot array can be formed at the electrode layer. For example, the electrode group of the set pattern is selected to generate resonance, so that the functional layer corresponding to the electrode group forming the set pattern generates thermal energy, and therefore the set pattern can be formed in a thermal imaging device.
The functional layer 103 is configured to: carry a sample to be tested; absorb the acoustic signal emitted by the activated electrode group 1021 and convert the acoustic signal into thermal energy; and heat the sample to be tested that is carried at a position corresponding to the activated electrode group 1021.
The functional layer is made from a viscoelastic material. When an acoustic wave is absorbed by the viscoelastic material, heat can be generated, causing the temperature of the material to rise. Polydimethylsiloxane is a high-molecular organosilicon compound. Research shows that polydimethylsiloxane can absorb more acoustic energy than liquid samples and other materials such as glass or silicon, thereby significantly increasing the temperature, and thus heating the sample placed on polydimethylsilane.
In a preferred embodiment, in the technical solution provided in Embodiment 1 of this application, the functional layer includes a first functional layer and a second functional layer, the first functional layer is located above the electrode layer and is bonded to the substrate, the second functional layer is located above the first functional layer, and a channel for carrying the sample to be tested is disposed between the first functional layer and the second functional layer.
In this application, the acoustic signal generated by the electrode group propagates along the substrate, and is refracted at an interface between the polydimethylsiloxane and the substrate and enters the polydimethylsiloxane sheet. This part of acoustic wave is absorbed by the polydimethylsiloxane to generate heat, causing the temperature of the polydimethylsiloxane material to rise.
In a preferred embodiment, in the technical solution provided in Embodiment 1 of this application, the substrate is made from any material from lithium niobate, zinc oxide, or aluminum oxide. These materials are semi-elastic dielectric materials, and the acoustic waves generated by the electrode group are surface acoustic waves. Surface acoustic waves are elastic waves propagating on a semi-elastic dielectric surface, and their energy is less absorbed by the substrate material. Therefore, the acoustic wave in the microfluidic chip provided in this application features small transmission loss, effectively ensuring the energy conversion efficiency.
In a preferred embodiment, in the technical solution provided in Embodiment 1 of this application, to obtain high electromechanical conversion efficiency between the electrode group and the substrate, the substrate is generally made from 128° YX double-sided polished lithium niobate.
Embodiment 2 of this application provides a microfluidic apparatus 400. The microfluidic apparatus 400 is configured to control the microfluidic chip 100 provided in Embodiment E As shown in
The controller 401 is configured to control the signal generator 402 to generate an electrical signal based on a set frequency.
The signal generator 402 is configured to transmit the generated electrical signal to an electrode group for activation when connected to the electrode group, so that the activated electrode group generates an acoustic signal.
In a preferred embodiment, in the technical solution provided in Embodiment 2 of this application, as shown in
The frequency divider 403 is configured to divide the electrical signal generated by the signal generator into electrical signals of different frequencies, and when connected to different electrode groups, transmit the electrical signals of different frequencies through the signal output interfaces 4032 to the electrode groups for activation.
The frequency divider can transform, by using a specific circuit structure, the same electrical signal into electrical signals of different frequencies for outputting, so as to concurrently control multiple electrode groups with different resonant frequencies.
Preferably, each signal output interface of the frequency divider 403 is provided with a control switch, and each control switch is connected to the controller 401.
For example, the frequency divider 403 has five signal output interfaces 4032, and the five signal output interfaces 4032 are all provided with control switches, which are respectively denoted as A, B, C, D, and E. These five control switches are all connected to the controller.
The controller 401 is further configured to control on-off of a set control switch, so as to control connection or disconnection of an electrical signal that is output by the signal output interface 4032 corresponding to the set control switch in the frequency divider.
For example, a signal output interface of the frequency divider is connected to an electrode group A in the first row and the first column. A control switch A is disposed on a connecting wire of the signal output interface and the electrode group, and the control switch is connected to the controller. The controller can control the control switch A to be closed or open, so as to control whether to input an electrical signal into the electrode group A.
Embodiment 3 of this application provides a microfluidic system, as shown in
Embodiment 4 of this application provides a microfluidic chip control method, which is used for the microfluidic apparatus in Embodiment 2. A flowchart of this method is shown in
S700: A controller controls a signal generator to generate an electrical signal based on a set frequency.
S710: When connected to an electrode group, the signal generator transmits the generated electrical signal to the electrode group for activation, so that the activated electrode group generates an acoustic signal.
In a preferred embodiment, in the technical solution provided in Embodiment 4 of this application, as shown in
S800: The signal generator transmits the electrical signal to a frequency divider.
S810: When connected to an electrode group, the frequency divider divides the electrical signal into electrical signals of different frequencies, and transmits the electrical signals to the electrode group for activation.
Embodiment 5 of this application provides a microfluidic chip preparation method, which is used to prepare the microfluidic chip in Embodiment 1. A flowchart of this method is shown in
S900: Form a photoresist layer on a substrate.
On a completely clear and clean surface of the substrate, apply the photoresist AZ4620 through spin-coating at 5000 rpm for 30 s, place a product on a 120° C. heating plate for baking for three minutes, and then test the thickness of the photoresist by using a step profiler. The thickness of the photoresist is about 5 μm. The obtained cross-sectional view is shown in
S910: Perform photoetching on the photoresist layer to form a set pattern arranged in an array on the substrate.
In a preferred embodiment, in the technical solution provided in Embodiment 5 of this application, S910 specifically includes the following steps, and a flowchart is shown in
S9101: Lay a mask on the photoresist layer for exposure, where the mask is the set pattern arranged in an array.
The mask here may be a film, and the film with the set pattern is overlaid on the photoresist layer formed in
S9102: Develop and dissolve a non-transparent region in the photoresist layer when the photoresist layer is exposed, to form the set pattern arranged in an array on the substrate.
Use AZ400 to develop and dissolve a non-cured part in the non-transparent region, and then bake the non-cured part on a 150° C. heating plate for 10 minutes. The formed cross-sectional view is shown in
S920: Perform sputtering on the substrate corresponding to the pattern to form an electrode layer, where the formed electrode layer includes multiple electrode groups arranged in an array, so that the electrode group converts an electrical signal into an acoustic signal when activated, and transmits the acoustic signal to a functional layer.
Perform magnetron sputtering on the substrate after S9102 to form a metal layer with a thickness of about 200 nm. The metal layer is the electrode layer 102, as shown in
Place the previously obtained chip in an acetone solution, and peel off the non-photoetched photoresist through ultrasonic vibration of an ultrasonic cleaning machine. The formed cross-sectional view is shown in
S930: Form the functional layer on the electrode layer, so that the functional layer carries a sample to be tested, absorbs the acoustic signal emitted by the activated electrode group and converts the acoustic signal into thermal energy, and heats the sample to be tested that is carried at a position corresponding to the activated electrode group.
After the functional layer is formed on the electrode layer, the obtained cross-sectional view is shown in
In addition, during the rapid temperature rise and temperature control of the microfluidic chip using surface acoustic waves, the applicant obtained the experimental result shown in
The experimental result shows that, by adjusting an input pulse length and frequency, the fluid temperature in the channel of polydimethylsiloxane can be accurately increased and maintained at the desired temperature, which are 37° C., 42° C., and 50° C. respectively, as shown in
Different from the prior art, in this application, an external device transmits an electrical signal to the electrode layer, and the electrode layer converts the electrical signal into an acoustic signal. The acoustic signal can be absorbed by the functional layer to generate thermal energy, and the electrode layer includes multiple electrode groups arranged in an array. As long as some of the multiple electrode groups are activated through separate control, the corresponding functional layer at the position of the activated electrode group can generate thermal energy, thereby heating the sample to be tested. This application provides a microfluidic chip that features high energy conversion efficiency, fast heating, and implementation of heating in a specific region.
In addition, the temperature gradient field designed in this application can enable the droplets in the channel of the functional layer to move a low temperature region under action of thermal capillary force, so as to implement precise control of droplets, organisms, polystyrene microspheres, etc.
It should be noted that similar reference numerals and letters indicate similar items in the following drawings. Therefore, once an item is defined in one drawing; the item does not need to be further defined and explained in subsequent drawings.
In descriptions of this application, it should be noted that a direction or a position relationship indicated by terms such as “center”, “upper”, “lower”, “left”, “right”, “vertical”, “horizontal”, “inside”, or “outside” is a direction or a position relationship shown based on the accompanying drawings, or a direction or a position relationship usually placed when the invented product is used, is merely intended to describe this application and simplify the descriptions, but is not intended to specify or imply that an indicated apparatus or element needs to have a particular direction, needs to be constructed and operated in a particular direction, and therefore shall not be construed as a limitation on this application. In addition, the terms “first”, “second”, “third” etc. are merely intended to distinguish between descriptions, and shall not be understood as an indication or implication of relative importance.
In the descriptions of this application, it should be further noted that unless otherwise specified or limited, terms “dispose”, “installation”, “link”, and “connection” shall be understood in a broad sense, for example, may be a fixed connection, or may be a detachable connection or an all-in-one connection; may be a mechanical connection or an electrical connection; or may be a direct connection, an indirect connection through an intermediate medium, or an internal connection of two components. A person of ordinary skill in the art may understand specific meanings of the above-mentioned terms in this application depending on specific situations.
Finally, it should be noted that the foregoing embodiments are merely specific implementations of this application, and are intended for describing the technical solutions in this application but not for limiting this application. The protection scope of this application is not limited thereto. Although this application is described in detail with reference to the foregoing embodiments, persons of ordinary skill in the art should understand that they may still make modifications to the technical solutions described in the foregoing embodiments, or readily figure out variations, or make equivalent replacements to some technical features thereof, within the technical scope disclosed in this application. However, these modifications, variations, or replacements do not make the essence of the corresponding technical solutions depart from the spirit and scope of the technical solutions in the embodiments of this application, and therefore shall fall within the protection scope of this application. Therefore, the protection scope of this application shall be subject to the protection scope of the appended claims.
Number | Date | Country | Kind |
---|---|---|---|
201711480468.5 | Dec 2017 | CN | national |
The present application is a continuation-application of International (PCT) Patent Application No. PCT/CN2018/070070, filed on Jan. 2, 2018, which claims foreign priorities of Chinese Patent Application No, 201711480468.5, filed on Dec. 29, 2017, the entire contents of which are hereby incorporated by reference.
Number | Date | Country | |
---|---|---|---|
Parent | PCT/CN2018/070070 | Jan 2018 | US |
Child | 16903415 | US |