CN106370598A - Microsphere control device based on surface acoustic waves and manufacturing method thereof, and imaging system - Google Patents

Abstract

The invention discloses a microsphere control device based on surface acoustic waves and a manufacturing method thereof, and an imaging system. The microsphere control device comprises a substrate and a plurality of electrode parts, wherein the substrate is made from a piezoelectric material; and the electrode parts are positioned in the plane of the substrate, the electrode parts at least comprise two electrode parts, along a first direction, which are arranged symmetrically about a target area, and the target area is used for placing microsphere samples. An alternating current signal is introduced into the electrode parts, the surface acoustic waves can be stimulated and generated on the surface of the substrate, the surface acoustic waves propagating in opposite directions are laminated in the target area to form a surface acoustic wave stationary field, and microspheres are driven to move under the effect of the stationary field. According to the microsphere control device based on surface acoustic waves and the imaging system disclosed by the invention, the microspheres are controlled to move by using the surface acoustic waves, the formation of an imaging blind area can be avoided during scanning imaging, and overall area imaging of the samples can be obtained.

Description

Surface acoustic wave-based microsphere manipulation device, manufacturing method, and imaging system

technical field

The invention relates to the technical field of microscopic imaging, in particular to a surface acoustic wave-based microsphere manipulation device and a manufacturing method thereof. The invention also relates to an imaging system.

Background technique

With the development of modern biology and material science, higher and higher imaging resolution is required in the study of microstructure. Scientists hope to reveal the physical essence of life processes and material properties from the molecular level.

For ordinary optical microscopes, due to the limitation of the optical diffraction limit, its lateral resolution is limited to more than 200nm, which is far from meeting the requirements for studying deep subwavelength structures or cell structures. In order to break through the limitation of the diffraction limit, researchers from all over the world have carried out in-depth research on this. Among them, the most typical methods include stimulated emission loss microscopy, structured illumination microscopy, and random light field reconstruction microscopy. However, most of these methods are based on the subsequent processing of complex data, and there are problems such as complex systems, high prices, and low efficiency, and cannot be widely applied.

The super-resolution imaging technology based on the microsphere nanocone effect was first proposed by the research team of the University of Manchester in 2011. This technology uses a white light illumination source to excite the sample to generate evanescent waves, and uses micron-scale microspheres to couple the evanescent waves. Space amplification is performed to generate an enlarged virtual image, and then secondary imaging is performed on the virtual image to obtain a super-resolution microscopic image of the sample surface, realizing far-field super-resolution microscopic imaging based on white light wide-field illumination. Based on its simple system structure, high efficiency, low cost and other advantages, this technology has attracted widespread attention.

At present, in the super-resolution microscopy imaging technology using microspheres, since the microspheres cannot move during the scanning imaging process, only the area around the position of the microspheres can be imaged, and an imaging blind area will be formed at the position of the microspheres, resulting in The full area of the sample cannot be imaged.

Contents of the invention

In view of this, the present invention provides a microsphere manipulator based on surface acoustic waves, which can use surface acoustic waves to manipulate the movement of microspheres, thereby avoiding the formation of imaging blind spots during scanning and imaging, so as to ensure imaging of the entire area of the sample. The invention also provides a manufacturing method and an imaging system of a surface acoustic wave-based microsphere manipulation device.

To achieve the above object, the present invention provides the following technical solutions:

A microsphere manipulation device based on surface acoustic waves, including a substrate and a plurality of electrode parts;

The substrate is made of piezoelectric material;

The plurality of electrode parts are located in the plane of the substrate, and the plurality of electrode parts include at least two electrode parts arranged oppositely along the first direction and centered on the target area, and the target area is used to place micro Ball samples.

Optionally, the plurality of electrode portions further include at least two electrode portions disposed opposite to each other along the second direction and centered on the target area.

Optionally, the first direction is perpendicular to the second direction.

Optionally, the plurality of electrode parts further include two electrode parts disposed opposite to each other along a third direction and centered on the target area, and the third direction is the same as the first direction and the second direction. directions are crossed.

Optionally, the electrode part includes bus lines on both sides parallel to each other, and periodically arranged electrodes located in the middle area of the bus lines on both sides. Two sets of electrodes connected alternately, the midline axis of the electrode part points to the target area.

Optionally, among the electrodes of each period, a group of electrodes includes one electrode or two electrodes connected to the bus on the same side.

Optionally, the piezoelectric material includes quartz, lithium niobate, lithium tantalate or gallium lanthanum silicate.

An imaging system comprising:

Optical microscopes including eyepieces and objectives;

A microsphere manipulator as described above disposed on the stage of the optical microscope.

A method for manufacturing a surface acoustic wave-based microsphere manipulation device, comprising:

A piezoelectric material is used to make a substrate, and a metal layer is deposited on one side of the substrate;

forming a mask plate with electrode patterns on the metal layer of the substrate;

An electrode pattern is formed on the metal layer by dry etching, the photoresist is removed, and an electrode portion is formed on the substrate.

Optionally, the method further includes: using cured silver paste to bond the metal wires to the bus lines of the electrode part, and curing the bonding points through drying treatment.

It can be seen from the above technical solutions that the surface acoustic wave-based microsphere manipulation device provided by the present invention includes a substrate and a plurality of electrode parts, wherein the substrate is made of piezoelectric material, and the plurality of electrode parts are located in the plane of the substrate. It includes at least two electrode parts arranged opposite to each other along the first direction and centered on the target area, where the target area is used to place microsphere samples. When an alternating current signal is applied to the electrode part, due to the piezoelectric effect, the substrate made of piezoelectric material will generate mechanical strain, which will generate surface acoustic waves on the surface excitation; Similarly, standing waves are formed after superimposition in the target area, and the microspheres are subjected to force in the formed surface acoustic wave standing wave field, thereby driving the microspheres to move.

Therefore, the surface acoustic wave-based microsphere manipulator and imaging system of the present invention realizes the use of surface acoustic waves to manipulate the movement of microspheres, avoids the formation of imaging blind spots during scanning and imaging, and can obtain imaging of the entire area of the sample.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only These are some embodiments of the present invention. Those skilled in the art can also obtain other drawings based on these drawings without creative work.

Fig. 1 is a schematic diagram of the principle of manipulating microspheres by a surface acoustic wave-based microsphere manipulation device provided by an embodiment of the present invention;

2 is a schematic diagram of a surface acoustic wave-based microsphere manipulation device provided by an embodiment of the present invention;

3 is a schematic diagram of the electrode portion of the microsphere manipulation device shown in FIG. 2;

Fig. 4 is a flowchart of a manufacturing method of a surface acoustic wave-based microsphere manipulation device provided by an embodiment of the present invention;

Fig. 5 is a schematic diagram of a fabrication method of a surface acoustic wave-based microsphere manipulation device provided by an embodiment of the present invention.

detailed description

In order to enable those skilled in the art to better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described The embodiments are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts shall fall within the protection scope of the present invention.

An embodiment of the present invention provides a surface acoustic wave-based microsphere manipulation device, including a substrate and a plurality of electrode parts;

The substrate is made of piezoelectric material;

The plurality of electrode parts are located in the plane of the substrate, and the plurality of electrode parts include at least two electrode parts arranged oppositely along the first direction and centered on the target area, and the target area is used to place micro Ball samples.

It can be seen that the surface acoustic wave-based microsphere manipulation device provided in this embodiment includes a substrate and a plurality of electrode parts, wherein the substrate is made of piezoelectric material, and the plurality of electrode parts are located in the plane of the substrate, at least including Two electrode parts arranged opposite to each other in one direction and centered on a target area for placing microsphere samples. When an alternating current signal is applied to the electrode part, due to the piezoelectric effect, the substrate made of piezoelectric material will generate mechanical strain, which will generate surface acoustic waves on the surface excitation; Similarly, a standing wave is formed after the target area is superimposed, and the microsphere is subjected to a force in the formed surface acoustic wave standing wave field, thereby driving the microsphere to move, as shown in Fig. 1, which is a schematic view of the device in this embodiment to manipulate the microsphere Schematic diagram of the principle.

Therefore, the surface acoustic wave-based microsphere manipulator of the present invention realizes the use of surface acoustic waves to control the movement of the microspheres, which can avoid the formation of imaging blind areas during scanning and imaging, and can obtain imaging of the entire area of the sample.

In the surface acoustic standing wave field formed by the microspheres, the acoustic force suffered by the microspheres includes the primary radiation force and the secondary radiation force. The main radiation force is the force of the standing wave field itself on the microsphere, and the secondary radiation force is the force generated by the scattered sound wave of the microsphere. Among them, the main radiation force plays a leading role, and the main radiation force can be decomposed into axial component force and transverse component force. To the standing wave node, the microspheres move under the action of the standing wave field. The axial component F _r of the microsphere is expressed as follows:

${\mathrm{<span\; class="notranslate">\; f</span>}}_{\mathrm{<span\; class="notranslate">\; r</span>}}<span\; class="notranslate">\; =</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\frac{{\mathrm{<span\; class="notranslate">\; \&pi;p</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}{\mathrm{<span\; class="notranslate">\; V</span>}}_{\mathrm{<span\; class="notranslate">\; c</span>}}{\mathrm{<span\; class="notranslate">\; \&beta;</span>}}_{\mathrm{<span\; class="notranslate">\; w</span>}}}{\mathrm{<span\; class="notranslate">\; 2</span>}\mathrm{<span\; class="notranslate">\; \&lambda;</span>}}<span\; class="notranslate">\; )</span>\mathrm{<span\; class="notranslate">\; \&phi;</span>}<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; \&phi;</span>}<span\; class="notranslate">\; ,</span>\mathrm{<span\; class="notranslate">\; \&rho;</span>}<span\; class="notranslate">\; )</span>\mathrm{<span\; class="notranslate">\; the\; s</span>}\mathrm{<span\; class="notranslate">\; i</span>}\mathrm{<span\; class="notranslate">\; no</span>}<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 2</span>}\mathrm{<span\; class="notranslate">\; k</span>}\mathrm{<span\; class="notranslate">\; x</span>}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; ;</span>$

$\mathrm{<span\; class="notranslate">\; \&phi;</span>}<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; \&beta;</span>}<span\; class="notranslate">\; ,</span>\mathrm{<span\; class="notranslate">\; \&rho;</span>}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; =</span>\frac{\mathrm{<span\; class="notranslate">\; 5</span>}{\mathrm{<span\; class="notranslate">\; \&rho;</span>}}_{\mathrm{<span\; class="notranslate">\; c</span>}}<span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; 2</span>}{\mathrm{<span\; class="notranslate">\; \&rho;</span>}}_{\mathrm{<span\; class="notranslate">\; w</span>}}}{\mathrm{<span\; class="notranslate">\; 2</span>}{\mathrm{<span\; class="notranslate">\; \&rho;</span>}}_{\mathrm{<span\; class="notranslate">\; c</span>}}<span\; class="notranslate">\; +</span>{\mathrm{<span\; class="notranslate">\; \&rho;</span>}}_{\mathrm{<span\; class="notranslate">\; w</span>}}}<span\; class="notranslate">\; -</span>\frac{{\mathrm{<span\; class="notranslate">\; \&beta;</span>}}_{\mathrm{<span\; class="notranslate">\; c</span>}}}{{\mathrm{<span\; class="notranslate">\; \&phi;</span>}}_{\mathrm{<span\; class="notranslate">\; w</span>}}}<span\; class="notranslate">\; ;</span>$

Among them, p ₀ represents the amplitude of the standing wave, V _c represents the volume of the microsphere, β _c represents the compressibility coefficient of the microsphere, β _w represents the compressibility coefficient of the surrounding liquid, ρ _c represents the density of the microsphere, and ρ _w represents the density of the surrounding liquid density, λ is the wavelength of the surface acoustic wave, k is the wave number, and x is the distance from the microsphere to the nearest node in the standing wave field.

The surface acoustic wave-based microsphere manipulation device of the present invention will be further described in detail below.

In the microsphere manipulating device of this embodiment, the substrate is made of piezoelectric material, and when an alternating current signal is applied to the electrodes on the substrate, the piezoelectric substrate generates mechanical strain. Surface acoustic waves are excited on the surface. The characteristics of piezoelectric materials determine the performance of surface acoustic waves. When selecting piezoelectric materials, performance parameters such as material orientation, electromechanical coupling coefficient, temperature stability, beam deflection, propagation loss, and dielectric constant should be considered. In this embodiment, the piezoelectric material is a piezoelectric single crystal material, and the piezoelectric single crystal material that can be used includes quartz, lithium niobate (LiNbO ₃ ), lithium tantalate (LiTaO ₃ ) or lanthanum gallium silicate (La ₃ Ga ₅ SiO ₁₄ ).

In the microsphere manipulating device of this embodiment, at least two electrode parts arranged oppositely along one direction and centered on the target area are arranged in the plane of the substrate, through two electrode parts arranged oppositely along one direction centered on the microsphere sample , the surface acoustic waves generated by excitation can manipulate the microspheres to move in one dimension.

In a preferred embodiment, in the plane of the substrate, at least two electrode parts are arranged opposite to the target area along the first direction, and two electrode parts are arranged opposite to the target area along the second direction. , through the action of surface acoustic waves in two directions, the movement of microspheres in a two-dimensional plane can be realized.

Preferably, the first direction and the second direction are vertically arranged, as shown in FIG. 2 , as can be seen from the figure, in the plane of the substrate 1, electrode parts 2 are respectively arranged along the first direction and the second direction perpendicular to each other. .

In another embodiment, on the basis of the previous embodiment, two electrode parts are arranged oppositely along the third direction and centered on the target area in the plane of the substrate, the third direction is the same as the Both the first direction and the second direction intersect. Through the action of the surface acoustic waves propagating in three directions, the displacement of the microspheres in the plane can be controlled more precisely. Wherein, the included angle between the third direction and the first direction and the second direction can be flexibly adjusted.

In this embodiment, the structure of the electrode part 2 can be set in the following manner. Refer to FIG. 2 and FIG. The electrodes 20 are arranged in a permanent manner, and the electrodes 20 are perpendicular to the bus line 21, wherein a cycle electrode includes two groups of electrodes that are alternately connected to the bus lines 21 on both sides, that is, in a cycle electrode, a group of electrodes is connected to the bus line on one side , the other set of electrodes is connected to the bus on the other side.

The electrodes 20 are energized through the bus 21 .

In this embodiment, the centerline axis of each electrode part 2 points to the target area, so that the surface acoustic wave generated by the excitation propagates in a direction pointing to the target area.

The main parameters of the electrode part in this embodiment include the electrode period, the number of electrode pairs and the aperture. The electrode period refers to the distance between the electrodes connected to the bus on the same side in two adjacent period electrodes, and the electrode period determines the wavelength of the surface acoustic wave generated by the excitation.

The number of electrode pairs refers to the number of electrodes included in each group of electrodes in each period of electrodes. Wherein, a group of electrodes may include one electrode or two electrodes connected to the bus on the same side. A group of electrodes includes an electrode connected to the bus on the same side. The structure of this electrode is simple, and the requirements for photolithography accuracy are relatively low during fabrication. The surface acoustic waves generated by the excitation can satisfy the control of the movement of microspheres. A group of electrodes includes two electrodes connected to the bus on the same side. This electrode structure is mainly used in occasions that require more precise control of the frequency of the sound wave.

Aperture refers to the distance between adjacent electrodes within a period of electrodes. In addition, the performance of the surface acoustic wave generated by the excitation of the electrode part is also affected by factors such as the thickness of the electrode, the material of the substrate, and the tangential direction of the crystal.

Exemplarily, in a specific embodiment, in the microsphere manipulator shown in Figure 3, the electrode period is set to 300 μm, the width of the electrode is 75 μm, and the height is 150 μm, correspondingly the wavelength of the surface acoustic wave generated by the excitation is 300 μm .

The fabrication method of the surface acoustic wave-based microsphere manipulation device of this embodiment will be described in detail below. Please refer to FIG. 4 and FIG. 5. FIG. 4 is a flow chart of a manufacturing method of a surface acoustic wave-based microsphere manipulation device provided in this embodiment, and FIG. 5 is a schematic diagram of a manufacturing method of a surface acoustic wave-based microsphere manipulation device in this embodiment. , including the steps:

S1: A piezoelectric material is used to make a substrate, and a metal layer is deposited on one side of the substrate.

Select piezoelectric material and electrode material according to requirements. Exemplarily, in this embodiment, lithium niobate (LiNbO ₃ ) single crystal is used as the piezoelectric material, and metal Cr/Au is used to make the electrode. The specific manufacturing process includes: using lithium niobate (LiNbO ₃ ) single crystal to form After the substrate, both sides of the substrate are polished, and then a Cr/Au metal layer is deposited on one side of the substrate by vapor deposition.

S2: Forming a mask with electrode patterns on the metal layer of the substrate.

Before performing this step, first design a mask plate with electrode patterns, and design the required electrode pattern structure through AutoCAD, CorelDraw12 and other software.

Then, make a mask plate with electrode pattern on the metal layer of the substrate, and then form the mask plate pattern by ultraviolet lithography exposure. The main process operations include: pre-treatment-glue removal-pre-baking-exposure-post-baking- Post-exposure-developing.

S3: forming an electrode pattern on the metal layer by dry etching, removing the photoresist, and forming an electrode portion on the substrate.

By dry etching, the metal layer forms an electrode pattern, and then the photoresist covering the electrode can be removed with acetone, and the electrode part is formed on the substrate.

S4: Bonding the metal wire and the bus of the electrode part with cured silver paste, and curing the bonding point through drying treatment. The device can be placed in an oven to cure the bonding point firmly.

In this embodiment, the surface acoustic wave-based microsphere manipulator is applied to the microscopic imaging system for microsphere applications. The standing wave formed by the surface acoustic wave is used to manipulate the microsphere to move in the plane, and the sample is scanned and imaged in a wide field of view. During imaging, the formation of imaging blind areas is avoided, and the entire area of the sample is guaranteed to be imaged. The microsphere manipulation device of this embodiment has the advantages of simple structure and low cost, and can be widely and widely used.

Correspondingly, an embodiment of the present invention also provides an imaging system, including:

Optical microscopes including eyepieces and objectives;

A microsphere manipulator as described above disposed on the stage of the optical microscope.

When performing microscopic imaging observation on samples in practical applications, first place the prepared microsphere manipulation device on the stage of the optical microscope, and adjust the magnification of the objective lens and eyepiece of the optical microscope to the appropriate value; then, place the The sample is placed on the target area of the substrate of the manipulator, and a suspension containing medium microspheres is dripped on the sample. Optionally, the diameter of the medium microspheres used is 2-9 μm, and the refractive index is 1.3-1.9. For example, silica spheres (n=1.46) with a diameter of 5 μm can be used. During the scanning imaging process, the microspheres are manipulated by changing the applied alternating current signal of the electrode part. Two-dimensional imaging of the sample is realized by point-by-point scanning.

In the microscopic imaging system of this embodiment, in the super-resolution imaging technology applied to microspheres, the standing waves generated by acoustic surface acoustic waves are used to manipulate the movement of microspheres in the liquid, avoiding the formation of imaging blind spots in scanning imaging, and can form imaging of the entire area of the sample . Therefore, in the imaging system of this embodiment, the nano-cone effect of the dielectric microspheres is used to realize the imaging of the nano-hyperfine structure. Realize super-resolution imaging, and use surface acoustic waves to manipulate the movement of microspheres. Combining surface acoustic wave acoustic tweezers and microsphere super-resolution technology, wide-field rapid scanning imaging of micro-nano structures is realized.

The surface acoustic wave-based microsphere manipulation device, its manufacturing method, and imaging system provided by the present invention have been described above in detail. In this paper, specific examples are used to illustrate the principle and implementation of the present invention, and the descriptions of the above embodiments are only used to help understand the method and core idea of the present invention. It should be pointed out that for those skilled in the art, without departing from the principle of the present invention, some improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims (10)

1. A microsphere manipulation device based on surface acoustic waves, comprising a substrate and a plurality of electrode parts; The substrate is made of piezoelectric material; The plurality of electrode parts are located in the plane of the substrate, and the plurality of electrode parts include at least two electrode parts arranged oppositely along the first direction and centered on the target area, and the target area is used to place micro Ball samples. 2 . The device according to claim 1 , wherein the plurality of electrode portions further includes at least two electrode portions disposed opposite to each other along the second direction and centered on the target area. 3 . 3. The device according to claim 2, wherein the first direction is perpendicular to the second direction. 4. The device according to claim 3, wherein the plurality of electrode portions further include two electrode portions disposed opposite to each other along a third direction and centered on the target area, the third direction Intersects both the first direction and the second direction. 5. The device according to claim 1, characterized in that, the electrode part comprises parallel bus lines on both sides, and periodically arranged electrodes located in the middle area of the bus lines on both sides, and the electrodes are connected to the bus lines on both sides. Vertically, a period of electrodes includes two groups of electrodes respectively connected to the bus lines on both sides alternately, and the central line axis of the electrode part points to the target area. 6 . The device according to claim 5 , wherein, among the electrodes of each cycle, a group of electrodes includes one electrode or two electrodes connected to the bus on the same side. 7 . 7. The device according to claim 1, wherein the piezoelectric material comprises quartz, lithium niobate, lithium tantalate, or gallium lanthanum silicate. 8. An imaging system, characterized in that, comprising: Optical microscopes including eyepieces and objectives; The microsphere manipulation device according to any one of claims 1-7 arranged on the stage of the optical microscope. 9. A method for manufacturing a surface acoustic wave-based microsphere manipulation device, comprising: A piezoelectric material is used to make a substrate, and a metal layer is deposited on one side of the substrate; forming a mask plate with electrode patterns on the metal layer of the substrate; An electrode pattern is formed on the metal layer by dry etching, the photoresist is removed, and an electrode portion is formed on the substrate. 10 . The manufacturing method according to claim 9 , further comprising: using cured silver paste to bond the metal wire and the bus line of the electrode part, and curing the bonding point through drying treatment. 11 .