CN209043694U - A kind of micro drop acceleration agitating device - Google Patents

Abstract

The utility model belongs to the field of micro-fluid detection, in particular to a micro-droplet acceleration stirring device. The accelerated stirring device includes: an interdigital transducer for generating surface acoustic waves and acting on micro-droplets; a nano-layer for enhancing the sensitivity of electrochemical detection; a co-acting for anchoring and enrichment The super-hydrophobic layer and super-hydrophilic site of a small amount of droplets to be tested; a substrate; the interdigital transducers are arranged at both ends of one side of the substrate, and the nanometers are arranged in sequence from bottom to top at the remaining positions on the side layer and the super-hydrophobic layer; the super-hydrophilic site is arranged in the center of the super-hydrophobic layer. The micro-droplet acceleration stirring device can generate specific surface acoustic waves and stir the fixed droplets, thereby accelerating the self-diffusion of the micro-droplets to be tested fixed on the hydrophilic point, and realizing the rapid detection of micro-samples. In addition, by increasing the hydrophilic site of the device, simultaneous rapid stirring and detection of multiple micro droplets can be realized, which further improves the detection efficiency.

Description

A micro-droplet accelerated stirring device

technical field

The utility model belongs to the field of micro-fluid detection, in particular to a micro-droplet acceleration stirring device.

Background technique

With the continuous progress in the field of life science, liquid detection is gradually developing towards the trend of miniaturization and trace amount. For example, the volume of droplets used in protein crystallization tests, gene recombination, DNA analysis and other fields are all ultra-trace, while the content of effective target detection substances in liquids used in fields such as body fluid detection is often extremely low, so the amount of droplets used in micro-droplets is very low. Effective enrichment and rapid detection have put forward higher requirements.

The existing detection technology often requires a long pretreatment process for the sample, so that the effective detection substance in the sample is combined with the label, thereby increasing the detection time. For some samples with short activity time, long detection time will lead to the decrease of their activity and affect the detection result. Therefore, it is necessary to develop tools to accelerate stirring, shorten sample preparation time, and conduct fast and effective detection of samples with integrated multimodality.

SUMMARY OF THE INVENTION

In view of this, the present utility model proposes a micro droplet acceleration stirring device, which can fix the micro droplet to be measured at the hydrophilic point and generate specific surface acoustic waves to stir the droplet to be measured. , so that the self-diffusion of the micro droplets to be tested fixed on the hydrophilic point is accelerated, and the rapid detection of micro samples is realized; in addition, by increasing the hydrophilic point of the device, the simultaneous rapid stirring and detection, and further improve the detection efficiency.

The utility model is achieved through the following technical solutions:

A micro-droplet accelerated stirring device, the accelerated stirring device comprising:

an interdigital transducer for generating surface acoustic waves and acting on droplets;

a nanolayer for enhancing the sensitivity of electrochemical detection;

A co-acting superhydrophobic layer and superhydrophilic sites for anchoring and enriching microscopic droplets;

a substrate;

The interdigital transducers are arranged at both ends of one side of the substrate, and the nano-layer and the super-hydrophobic layer are arranged in sequence from bottom to top at the remaining positions of the side; the super-hydrophilic sites are arranged on the super-hydrophobic site. the center of the hydrophobic layer.

The above-mentioned aspects and any possible implementations further provide an implementation, wherein the substrate is a silicon/zinc oxide substrate, an ITO glass/zinc oxide substrate or an FTO glass/zinc oxide substrate, but not only Limited to these three substrates, any other achievable material can be used as a substrate.

The above aspects and any possible implementations further provide an implementation, wherein the accelerated stirring device can fix the droplet to be tested on the hydrophilic site by modifying the hydrophilic and hydrophobic properties on the surface of the nanolayer , it is difficult to move due to external force. The accelerated stirring device can adjust the size of the hydrophilic sites according to the size of the droplets, or form an array of the hydrophilic points to realize the simultaneous accelerated stirring of multiple droplets.

According to the above-mentioned aspect and any possible implementation manner, an implementation manner is further provided, wherein the distal end of the interdigital transducer is connected with an exciter for generating an acoustic wave signal.

The interdigital transducer is formed by wiring on the four sides of the aluminum film by conventional photolithography and lift-off techniques.

According to the above-mentioned aspect and any possible implementation, an implementation is further provided, wherein the exciter includes:

a waveform generator for generating acoustic signals;

a power amplifier for amplifying the acoustic wave signal generated by the waveform generator;

The waveform generator is connected to the power amplifier.

The above-mentioned aspects and any possible implementation manners further provide an implementation manner, wherein the superhydrophobic layer and the superhydrophilic sites work together to anchor the microdroplets on the hydrophilic sites, and will not move to the superhydrophobic layer.

The above aspects and any possible implementation manners further provide an implementation manner, wherein the nano-layer is a nano-dendritic gold layer or a titanium dioxide nano-layer, the nano-layer can enhance the electrochemical detection sensitivity of the device, and can make the The microdroplets undergo electrochemical detection directly after accelerated stirring.

The above-mentioned aspects and any possible implementation manners further provide an implementation manner, in which the nanolayers can be replaced with other alternative nanostructures, which are set according to the needs of different detection methods.

In the above aspect and any possible implementation, an implementation is further provided, wherein the surface of the nano-branched gold layer is modified by dodecyl mercaptan or fluorosilane to form the superhydrophobic layer; using a mask The superhydrophilic sites are arranged on the surface of the superhydrophobic layer by photo-etching or Plasma etching.

According to the above aspects and any possible implementations, an implementation is further provided, wherein the superhydrophilic sites are one or more than two.

The above aspect and any possible implementation manner further provide an implementation manner, the accelerated stirring device can also be applied to the accelerated stirring of arrayed droplets, by arranging a plurality of superhydrophilic sites on the hydrophobic layer ( That is, when there are more than two super-hydrophilic sites), accelerated stirring of multiple droplets at the same time can be achieved.

According to the above aspect and any possible implementation manner, an implementation manner is further provided, wherein the accelerated stirring device can simultaneously realize the direct subsequent detection of the liquid droplets after the accelerated stirring.

When in use, the accelerated stirring device transmits the acoustic wave signal generated by the signal generator and the power amplifier to the IDT, and the surface acoustic wave generated by the direct excitation of the IDT acts on the droplets at the hydrophilic site, and the surface acoustic wave acts on the liquid. By providing a stable driving force on the surface of the droplet, the droplet accelerates the stirring of the solute in the droplet to be tested.

Compared with the prior art, the utility model can obtain the following technical effects:

(1) A micro droplet acceleration stirring device of the present invention utilizes super-hydrophilic sites to enrich and anchor droplets to be measured, and generates surface acoustic waves through an interdigital transducer (IDT) to act on the droplets Accelerates the diffusion rate of solutes in droplets, and finally realizes the enrichment and trace detection of droplets to be tested. It has the advantages of large detection range and short detection time. It is of great value in realizing rapid and accurate detection. It has broad application prospects in clinical rapid detection, rapid detection of trace markers, and integrated analysis of microdroplets.

(2) A micro liquid droplet acceleration stirring device of the present invention can generate specific surface acoustic waves and stir the enriched anchor liquid droplets, thereby accelerating the self-diffusion of the micro liquid droplets to be detected or accelerating the markers. Combined with the substance to be tested, the detection time of the droplet to be tested is greatly shortened.

(3) The micro-droplet acceleration stirring device of the present invention can array a plurality of hydrophilic sites on the surface of the hydrophobic layer as required, and simultaneously accelerate the stirring of a plurality of droplets, reduce the workload, and ensure a The accelerated stirring time of the series of droplets is highly consistent, which is convenient for subsequent analysis.

(4) The micro-droplet acceleration stirring device of the present invention can also be directly used for the subsequent chemical detection after the accelerated stirring of the liquid droplets, avoiding the loss in the process of moving the micro-droplets after the accelerated stirring, and one step In place to improve the efficiency of detection.

Of course, any product implementing the present invention does not necessarily need to achieve all the above-mentioned technical effects at the same time.

Description of drawings

FIG. 1 is a schematic structural diagram of a micro-droplet acceleration stirring device based on surface acoustic wave technology according to an embodiment of the present invention.

2 is a schematic top view of the stirring direction of the liquid droplets in the micro-droplet acceleration stirring device based on the surface acoustic wave technology according to the embodiment of the present invention when the liquid droplets are stirred with the acceleration of the surface acoustic wave.

3 is a schematic side view of the stirring direction of the liquid droplets in the micro-droplet acceleration stirring device based on the surface acoustic wave technology according to the embodiment of the present invention when the liquid droplets are accelerated and stirred with the surface acoustic wave.

FIG. 4 is a schematic structural view of the structure of a micro-droplet acceleration stirring device based on surface acoustic wave technology according to an embodiment of the present invention.

FIG. 5 is a schematic diagram of a hydrophilic site array of a micro-droplet accelerated stirring device based on surface acoustic wave technology according to an embodiment of the present invention.

FIG. 6 is a schematic diagram showing the comparison of the redox peak value with time of the micro-droplet accelerated stirring device based on the surface acoustic wave technology according to the embodiment of the present invention.

Description of reference numerals: 11-nanodendritic gold layer, 12-superhydrophobic layer, 13-superhydrophilic site; 21-interdigital transducer; 3-silicon/zinc oxide substrate.

Detailed ways

In order to better understand the technical solutions of the present invention, the embodiments of the present invention are described in detail below with reference to the accompanying drawings.

It should be clear that the described embodiments are only a part of the embodiments of the present invention, but not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the protection scope of the present invention.

The terms used in the embodiments of the present invention are only for the purpose of describing specific embodiments, and are not intended to limit the present invention. As used in the embodiments of the present invention and the appended claims, the singular forms "a," "the," and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise.

It should be understood that although the terms first and second may be used to describe XXX in the embodiments of the present invention, these documents should not be limited to these terms. These terms are only used to distinguish files from one another. For example, without departing from the scope of the embodiments of the present invention, the first XXX may also be referred to as the second XXX, and similarly, the second XXX may also be referred to as the first XXX.

Depending on the context, the word "if" as used herein can be interpreted as "at" or "when" or "in response to determining" or "in response to detecting." Similarly, the phrases "if determined" or "if detected (the stated condition or event)" can be interpreted as "when determined" or "in response to determining" or "when detected (the stated condition or event)," depending on the context )" or "in response to detection (a stated condition or event)".

It should be understood that the term "and/or" used in this document is only an association relationship to describe the associated objects, indicating that there may be three kinds of relationships, for example, A and/or B, which may indicate that A exists alone, and A and B exist at the same time. B, there are three cases of B alone. In addition, the character "/" in this document generally indicates that the related objects are an "or" relationship.

The utility model provides a micro-droplet acceleration stirring device, which can fix a micro-droplet to be measured at a hydrophilic point and generate a specific surface acoustic wave to stir the droplet, so that the microdroplet can be stirred. The self-diffusion of droplets is accelerated, thereby realizing rapid detection of trace samples. It is suitable for the rapid clinical detection of body fluids and the rapid detection of trace markers.

Several embodiments of the present invention are listed below.

Example 1

This embodiment proposes a micro liquid droplet acceleration stirring device, as shown in Figures 1 to 6, including:

an interdigital transducer 21 (IDT) for generating surface acoustic waves and acting on microdroplets;

a nanolayer 11 for enhancing the sensitivity of electrochemical detection;

a superhydrophobic layer 12 and superhydrophilic sites 13 acting together for anchoring and enriching microscopic droplets to be tested;

a substrate 3;

The interdigital transducers are arranged at both ends of one side of the substrate, and the nano-layer and the super-hydrophobic layer are arranged in sequence from bottom to top at the remaining positions of the side; the super-hydrophilic sites are arranged on the super-hydrophobic site. the center of the hydrophobic layer.

The substrate is a silicon/zinc oxide substrate 3 .

The nano-layer is the nano-dendritic gold layer 11 .

As shown in Figure 1 and Figure 4, when preparing the interdigital transducer, first, a layer of zinc oxide is deposited on the silicon substrate by electromagnetic sputtering, and then a layer of aluminum film is deposited on the zinc oxide layer by chemical vapor deposition. When depositing the aluminum film layer, it is necessary to cover the central part of the zinc oxide layer with a square Kapton tape. The interdigital transducer 21 (IDT) is fabricated by wiring on the four sides of the aluminum film by traditional photolithography and lift-off techniques, and the IDT and the exciter are connected by wires.

The exciter includes a waveform generator and a power amplifier, the waveform generator inputs the acoustic wave signal into the power amplifier by two wires, and then the positive and negative electrodes of the power amplifier are respectively connected to the interdigital transducer. device 21; the power amplifier is used to amplify the sound wave signal generated by the signal generator, and amplify the sound wave signal to the voltage amplitude required by the IDT.

Let the IDT and the exciter be used as the acoustic wave device unit of the accelerated stirring device.

After the preparation of the surface acoustic wave device unit is completed, the Kapton tape in the central part of the zinc oxide layer is removed, and then the entire IDT is covered with the Kapton tape. At this time, a nano-dendritic gold layer 11 is deposited in the center of the zinc oxide layer by an electrochemical deposition process. A superhydrophobic layer 12 is formed on the surface of the nano-dendritic gold layer 11 by modification with dodecyl mercaptan or fluorosilane. Then, superhydrophilic sites 13 are formed on the surface of the superhydrophobic layer 12 by a mask photo-etching method or a Plasma etching method. It should be noted that the electrochemical deposition process, the photo-etching method using the dodecyl mercaptan modification process and the Plasma etching method are all existing processes, and the layers of the stirring device of the present invention can be completed by using the general parameters of the existing process. structure, which will not be repeated here.

The accelerated stirring device transmits the acoustic wave signal generated by the signal generator and the power amplifier to the IDT, the surface acoustic wave generated by the direct excitation of the IDT acts on the droplet at the hydrophilic site, and the surface acoustic wave acts on the droplet and passes through. Provide a stable driving force to the surface of the droplet to accelerate the stirring of the solute in the droplet to be tested. As shown in Figure 2 and Figure 3, the micro droplet is stirred in the direction of the arrow shown in the surface acoustic wave action diagram.

Example 2

This embodiment is basically the same as the micro-droplet accelerating and stirring device in Embodiment 1, the only difference is that the nano-layer is a titanium dioxide nano-layer.

The preparation method of the titanium dioxide nano-layer and the corresponding super-hydrophobic layer 12 and the super-hydrophilic site 13 is as follows:

1. Take the surface acoustic wave device units covered with Kapton tape for IDT and ultrasonically treat them in acetone, ethanol and ultrapure water for 10~15min, and simultaneously take 10~15mL concentrated hydrochloric acid (37%wt), 10~20mL ultrapure water and 250-350 μL of tetrabutyl titanate were mixed together and stirred for 15-20 minutes, then the mixed solution and the surface acoustic wave device unit were transferred to a 50-mL sealed Teflon reactor and hydrothermally synthesized in an oven at 150 °C for 10-15 hours to obtain the titanium dioxide nanolayer;

2. Immerse the titanium dioxide nanolayer prepared above in anhydrous toluene solution containing 2% to 3% octadecyltrichlorosilane for 1 to 2 hours, then rinse the nanolayer with absolute ethanol and dry, and finally Micropores are formed on the nanolayer by a photomask etching method under ultraviolet irradiation; the unirradiated part still maintains superhydrophobicity, which is the superhydrophobic layer 12, and the irradiated area has superhydrophilicity, which is the superhydrophobicity layer 12. Superhydrophilic site 13.

Example 3

This embodiment is basically the same as the micro-droplet acceleration stirring device in Embodiment 1, the difference is that the superhydrophobic surface is arranged by mask photo-etching or Plasma etching method to form an array of superhydrophilic sites such as: shown in Figure 5.

The superhydrophilic site 13 array includes at least two or more than two array sites.

By dropping different droplets to be tested on different hydrophilic spots on the same microchip, rapid stirring of the arrayed droplets can be achieved.

Further, in combination with the aforementioned stirring device, in order to prove that the stirring device has an accelerated stirring effect on micro droplets, the embodiment of the present utility model also provides the following experimental verification:

The superhydrophilic site-superhydrophobic surface of the uppermost layer of the accelerated stirring device prepared in Example 1 or Example 2 was wiped with ultrapure water and air-dried naturally to ensure that the hydrophilic site was clean. Drop 1-10 μL of ultrapure water on the hydrophilic spot, and then add 0.5-2 μL of 10 ^-2 M fluorescein on the surface of the droplet. At this time, turn on the waveform generator and act on the IDT to generate surface acoustic waves. The droplet acceleration stirring device acts on the droplet, and the surface acoustic wave accelerates the diffusion rate of fluorescein on the droplet, and the observation is performed after 5-10s stirring by the surface acoustic wave. At the same time, take another micro-droplet accelerated stirring device and add the same 1-10 μL of ultrapure water and 0.5-2 μL of 10 ^-2 M fluorescein. After standing for 5-10 s, it is accelerated in comparison with the diffusion phenomenon of surface acoustic wave accelerated stirring. The stirring effect is obvious. The fluorescein accelerated by the surface acoustic wave has been completely mixed with the liquid, and the boundary between the fluorescein and the liquid is clear in the case of standing.

The accelerated stirring device of the utility model has a wide range of applications, and can be widely used in the fields of life science, medical testing, environmental monitoring, chemical analysis, etc. The device can be used to obtain better results, among which the detection of base complementary pairing in droplets belongs to a typical application in these fields. The specific process of the application of the accelerated stirring device in the detection of base complementary pairing in droplets will now be described in detail:

First, take the micro-droplet accelerated stirring device built in the above Example 1, wipe with ultrapure water and air dry the superhydrophilic site-superhydrophobic surface to ensure that the hydrophilic site is clean; Needle DNA (5-20 μM) was added dropwise to the superhydrophilic site 13, placed at room temperature for 10-30 minutes, and the sulfhydryl group on the DNA formed a gold-sulfur bond with the superhydrophilic site 13 to self-assemble to the hydrophilic site 13. Spot the surface with water, and then wash off excess unbound DNA probes with ultrapure water. At this time, 2-7 μL of buffer solution containing 100-200 mM NaCl and 50-150 mM NaClO ₄ was added dropwise to the hydrophilic site, using a two-electrode system (microchip as working electrode, Ag/AgCl as counter electrode and reference electrode) and differential Electrochemical detection was performed by pulse voltammetry at voltages ranging from -0.2V to 0.2V, with no redox peaks at this time. Here, the unit mM is the abbreviation for millimoles per liter, μM is the abbreviation for micromoles per liter, and M is the abbreviation for moles per liter.

Take the same microdroplet acceleration stirring device, wipe with ultrapure water and air dry the superhydrophilic site-superhydrophobic surface, and treat as above to make the probe DNA modified with sulfhydryl group and the superhydrophilic site 13 to form a gold-sulfur bond self-assembly to the surface of the hydrophilic site, and then dropwise add 2-7 μL of the detection solution containing 100-200 mM NaCl, 50-150 mM NaClO ₄ and DNA single-strand (5-20 μM) to the constructed microdroplet acceleration stirring device for super-hydrophilic At position 13, the waveform generator is turned on to act on the IDT to generate surface acoustic waves, and the micro-droplet acceleration stirring device acts on the DNA droplets to be tested. The DNA and the probe DNA were base-complementary paired, and after the surface acoustic wave was stirred for 90s to 180s, the device detected a strong redox signal by differential pulse voltammetry.

At the same time, a stirring device without surface acoustic wave was used to compare the detection conditions under the same conditions as the above-mentioned base complementary pairing stirring conditions. The stirring efficiency of the micro-droplet accelerated stirring device based on the surface acoustic wave technology provided by the present invention is much higher than that without the device, which further proves the accelerated stirring effect of the stirring device provided by the present invention.

It should be noted that the sequence of the probe DNA in this base pairing detection experiment is 5'-ATCTTGACTATGTGGGTGCT-SH-3', and the sequence of the DNA to be tested is 5'-AGCACCCACATAGTCAAGAT-Fc-3'. Other DNA or RNA sequences can also be used according to actual needs.

Those skilled in the art can clearly understand that, for the convenience and brevity of description, for more specific working processes of the above-described systems, devices or units, reference may be made to corresponding processes commonly used in the art, which will not be repeated here.

In the several embodiments provided by the present invention, it should be understood that the disclosed systems, devices and methods may be implemented in other manners. For example, the device embodiments described above are only illustrative; for example, the division of the droplet anchoring device and the surface acoustic wave device device is only a logical function division, and other division methods may be used in actual implementation; For example, multiple units or components may be combined or integrated into another system, or some features may be omitted, or not implemented.

The units described as separate components may or may not be physically separated, and components displayed as units may or may not be physical units, that is, may be located in one place, or may be distributed to multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution in this embodiment.

In addition, the waveform generator and the power amplifier in the various embodiments of the present invention may be integrated into one processing unit, or two units may exist physically alone, or may include other units or only use one unit, as long as the satisfaction of the The generation of surface acoustic waves under conditions is sufficient. The above-mentioned integrated unit may be implemented in the form of hardware, or may be implemented in the form of hardware plus software functional units.

The above are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall include within the scope of protection of the present invention.

Claims (6)

1. a micro droplet accelerated stirring device, is characterized in that, described accelerated stirring device comprises: an interdigital transducer for generating surface acoustic waves and acting on droplets; a nanolayer for enhancing the sensitivity of electrochemical detection; A co-acting superhydrophobic layer and superhydrophilic sites for anchoring and enriching microscopic droplets; a substrate; The interdigital transducers are arranged at both ends of one side of the substrate, and the nano-layer and the super-hydrophobic layer are arranged in sequence from bottom to top in the remaining positions of the side; the super-hydrophilic sites are arranged on the super-hydrophobic site. the center of the hydrophobic layer. 2 . The device for accelerating and stirring a micro droplet according to claim 1 , wherein the distal end of the interdigital transducer is connected with an exciter for generating a sound wave signal. 3 . 3. The device for accelerating and stirring a micro droplet according to claim 2, wherein the exciter comprises: a waveform generator for generating acoustic signals; a power amplifier for amplifying the acoustic wave signal generated by the waveform generator; The waveform generator is connected to the power amplifier. 4 . The device for accelerating and stirring a micro droplet according to claim 1 , wherein the nano-layer is a nano-dendritic gold layer or a titanium dioxide nano-layer. 5 . 5 . The device of claim 1 , wherein the substrate is a silicon/zinc oxide substrate, an ITO glass/zinc oxide substrate or an FTO glass/zinc oxide substrate. 6 . 6 . The device for accelerating and stirring micro droplets according to claim 1 , wherein the superhydrophilic sites are one or more than two. 7 .