CN114966124A - Structure of dual-mode detection probe and manufacturing method thereof - Google Patents
Structure of dual-mode detection probe and manufacturing method thereof Download PDFInfo
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- G01Q60/00—Particular types of SPM [Scanning Probe Microscopy] or microscopes; Essential components thereof
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Abstract
本发明涉及微纳检测设备技术领域，具体涉及一种双模式检测探针的结构及其制造方法，该双模式检测探针的结构包括双模式检测探针的针尖，针尖上开设有缺口，缺口延伸至针尖的末端，针尖被缺口分设为具有AFM扫描功能的寻址尖端和铆钉生物分子微尺度平台，具有AFM扫描功能的寻址尖端指向针尖的顶端，铆钉生物分子微尺度平台沿针尖的横截面延伸，铆钉生物分子微尺度平台的台面设有修饰层，修饰层能与带特定基团的生物分子连接，该双模式检测探针能精确地实现单分子操纵和能稳定地连接待测生物分子，并具有生物分子数量可控、扫描精度高的优点；该双模式检测探针由聚焦离子束技术和薄膜沉积技术在AFM探针的单根悬臂梁上的针尖加工而成。
The invention relates to the technical field of micro-nano detection equipment, in particular to a structure of a dual-mode detection probe and a method for manufacturing the same. Extending to the end of the needle tip, the needle tip is divided into an addressing tip with AFM scanning function and a rivet biomolecule microscale platform by a notch. The cross section is extended, and the surface of the rivet biomolecule microscale platform is provided with a modified layer. The modified layer can be connected with biomolecules with specific groups. The dual-mode detection probe can accurately realize single-molecule manipulation and can stably connect to the organism to be tested. It has the advantages of controllable number of biomolecules and high scanning accuracy; the dual-mode detection probe is processed by focusing ion beam technology and thin film deposition technology on the tip of a single cantilever beam of the AFM probe.
Description
Technical Field
The invention relates to the technical field of micro-nano detection equipment, in particular to a structure of a dual-mode detection probe and a manufacturing method thereof.
Background
The study of important biomolecules in vivo, such as DNA, RNA, and proteins, at the single molecule level is important for disease diagnosis, gene therapy, and drug screening. In recent decades, nanopore sensors with single-molecule resolution have been widely used in the research of biomolecules such as DNA, RNA, and protein by virtue of their advantages of label-free, ultrasensitive, low cost, rapid detection, etc., and are expected to become a next-generation sequencing platform.
The sensitivity of nanopores derives from their limited nanoscale space. When biomolecules pass through the pores, ionic current blocking in solution occurs due to the partial blocking of the nanopores by the biomolecules. By analyzing the magnitude and duration of the ionic current blockages, low concentrations of even sub-nanometer sized molecules can be detected. This blocking phenomenon is more pronounced when the nanopore size is comparable to the biomolecule size.
Nanopore sensors are mainly divided into biological nanopores and solid-state nanopores. Among them, solid-state nanopores are becoming powerful tools for single-molecule analysis following biological nanopores due to their excellent robustness, easily adjustable pore size, and wide range of processing methods and material selection. Unfortunately, the ultra-fast speed of pore formation of biomolecules such as DNA, RNA, and proteins presents a great challenge to the precise detection of solid-state nanopores. To this end, some researchers have attempted to use single molecule manipulation methods based on AFM probes. According to the method, a biomolecule is directly modified and connected to the tip of an AFM probe, and then the up-down/left-right translation of the AFM probe is controlled to control the biomolecule through hole and control the through hole speed. However, this method does not belong to true single-molecule manipulation, because the entire tip of the AFM probe has a modification layer, so that the entire tip of the AFM probe modifies a plurality of biomolecules uncontrollably, thereby causing simultaneous passing of a plurality of biomolecules and affecting the detection accuracy of a single molecule. In addition, the scanning accuracy of the AFM probe is reduced by modifying the biomolecule by the tip, the imaging and addressing accuracy of the solid-state nanopore is influenced, and the biomolecule is directly connected to the tip of the AFM probe, so that the biomolecule is in friction contact with a device in the processes of scanning imaging and addressing of the solid-state nanopore, the biomolecule is easy to fall off from the tip of the AFM probe, and the detection accuracy is also influenced.
Disclosure of Invention
It is an object of the present invention to provide a dual-mode detection probe which can precisely perform single-molecule manipulation and can stably link biomolecules to be detected, and which has advantages of controllable number of biomolecules and high scanning accuracy, while avoiding the disadvantages of the prior art.
The second objective of the present invention is to provide a structure of a dual-mode detection probe and a method for manufacturing the same.
In order to achieve one of the above purposes, the invention provides the following technical scheme:
the utility model provides a dual mode detection probe, including dual mode detection probe's needle point, the breach has been seted up on the needle point, the breach extends to the top of needle point, the needle point quilt the breach is divided into addressing most advanced and rivet biomolecule microscale platform that has AFM scanning function, the pointing of addressing most advanced the top of needle point, rivet biomolecule microscale platform edge the cross section of needle point extends, the mesa of rivet biomolecule microscale platform is equipped with the modification layer, the modification layer can be connected with the biomolecule who takes specific group.
In some embodiments, the finishing layer comprises any one of a gold substrate finishing layer, a silver substrate finishing layer, or a copper substrate finishing layer.
In some embodiments, the dual-mode detection probe is made of any one of silicon, silicon nitride, silicon oxide, or quartz.
In some embodiments, the shape of the tip of the dual mode sensing probe before processing is any one of a triangular pyramid, a rectangular pyramid, or a cone.
In some embodiments, the dual-mode detection probe is provided with a plurality of cantilever beams, and each cantilever beam is provided with a needle tip.
The dual-mode detection probe has the beneficial effects that:
(1) the dual-mode detection probe of the invention is characterized in that the probe tip of the AFM probe is divided into an addressing tip with AFM scanning function and a rivet biomolecule micro-scale platform by forming a notch on the probe tip of a single cantilever beam of the AFM probe, because the addressing tip does not expose the modification layer and the rivet biomolecule micro-scale platform exposes the modification layer with a preset area, so that the biomolecule with the specific group is only connected on the micro-scale platform of the rivet biomolecule and not connected on the addressing tip, therefore, on one hand, the scanning imaging function of the addressing tip is prevented from being interfered by biomolecules, on the other hand, the quantity of the connected biomolecules can be accurately controlled by controlling the table area of the biomolecules in the rivet and exposing the modification layer with the preset area, so that the accurate single-biomolecule control through hole is realized, and the problem that the detection interference is caused by the fact that the single-biomolecule control through hole cannot be realized in the prior art is solved.
(2) According to the dual-mode detection probe, the rivet biomolecule micro-scale platform and the addressing tip with the AFM scanning function have a certain distance, so that even if the addressing tip moves in the scanning imaging and addressing processes of a device, biomolecules on the rivet biomolecule micro-scale platform cannot touch or rub the device, the problem that the biomolecules are easy to touch or rub and fall off in the prior art is avoided, the connection stability of the biomolecules is improved, and the detection stability is ensured.
In order to achieve the second purpose, the invention provides the following technical scheme:
there is provided a method of manufacturing a dual-mode detection probe, comprising the steps of,
s1, presetting the sizes of the addressing tip with the AFM scanning function and the rivet biomolecule micro-scale platform according to the imaging resolution and the scanning precision;
s2, milling the tip of the AFM probe according to the preset sizes of the addressing tip with the AFM scanning function and the rivet biomolecule micro-scale platform to form the addressing tip with the AFM scanning function and the rivet biomolecule micro-scale platform;
s3, depositing a modification layer on the needlepoint processed in the S2;
s4, depositing an isolation layer on the needle tip processed in the S3, wherein the isolation layer covers the modification layer;
s5, milling the isolation layer on the platform surface of the rivet biomolecule micro-scale platform to expose the modification layer with a preset area, wherein the preset area is determined by the size, shape and number of biomolecules, and the rest isolation layer covers the rest part of the needle tip.
In some embodiments, the tip of the AFM probe and/or the isolation layer are milled by a focused ion beam, which is any one of a focused gallium ion beam, a focused helium ion beam, or a focused neon ion beam.
In some embodiments, the modifying layer and/or the isolating layer are deposited by a thin layer deposition technique, which is any one of a physical vapor deposition technique, a chemical vapor deposition technique, or an atomic layer deposition technique.
In some embodiments, the modification layer has a thickness of 10nm to 1000 nm.
In some embodiments, the spacer layer has a thickness of 10nm to 1000 nm.
In some embodiments, the material of the isolation layer is aluminum oxide or titanium oxide.
The using method of the dual-mode detection probe has the following beneficial effects:
according to the manufacturing method of the dual-mode detection probe, the addressing tip with the AFM scanning function and the rivet biomolecule microscale platform with the preset area modification layer exposed are quickly and accurately manufactured on the needle point of the single cantilever beam of the AFM probe through the milling and deposition technology, the preset area is preset according to the biomolecule group, the control of the number of connected biomolecules is facilitated, and single molecule operation is realized; the isolation layer on the addressing tip does not generate coupling reaction with the biomolecule group, so that the addressing tip is not connected with the biomolecule and the scanning imaging function is kept; the micro-scale platform of the biological molecules of the rivet has a certain distance with the addressing tip, so that the problem that the biological molecules are easy to touch or rub off in the prior art can be avoided, the connection stability of the biological molecules is improved, and the detection stability is further ensured.
Drawings
FIG. 1 is a schematic diagram and a partially enlarged schematic diagram of a prior art AFM probe and its tip.
Figure 2 is a schematic diagram of a prior art cantilever beam and needle tip configuration.
Fig. 3 is a schematic view of a tip structure after a notch is milled according to an embodiment of the present invention.
Fig. 4 is a schematic diagram of a tip structure after a modification layer is deposited according to an embodiment of the invention.
Fig. 5 is a schematic diagram of a tip structure after a modification layer and an isolation layer are deposited according to an embodiment of the invention.
Fig. 6 is a schematic diagram of a tip structure after milling an isolation layer according to an embodiment of the present invention.
FIG. 7 is a schematic diagram of the working state of the tip of the needle connected with biomolecules after milling the isolation layer according to the embodiment of the present invention.
FIG. 8 is a SEM low-power side view of a tip after milling a notch according to an embodiment of the invention.
FIG. 9 is a SEM high-power side view of a tip after milling a notch according to an embodiment of the invention.
FIG. 10 is another side view of a tip SEM magnification after milling a notch according to an embodiment of the present invention.
Reference numerals
An AFM probe 1; a needle tip 2; an addressing tip 3 having an AFM scanning function; a rivet biomolecular micro-scale platform 4; a finishing layer 5; a cantilever beam 6; an isolation layer 7; a biomolecule 8.
Detailed Description
Preferred embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. While the preferred embodiments of the present invention are shown in the drawings, it should be understood that the present invention may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items.
It is to be understood that, although the terms first, second, third, etc. may be used herein to describe various information, such information should not be limited by these terms. These terms are only used to distinguish one type of information from another. For example, first information may also be referred to as second information, and similarly, second information may also be referred to as first information, without departing from the scope of the present invention. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present invention, "a plurality" means two or more unless specifically defined otherwise.
Example 1
Since the entire tip 2 of the AFM probe 1 shown in fig. 1 to 2 has the modification layer, the entire tip 2 of the AFM probe 1 may be uncontrollably connected to a plurality of biomolecules, which may cause simultaneous passing of a plurality of biomolecules and affect the detection accuracy of a single molecule. In addition, the scanning accuracy of the AFM probe 1 is reduced by modifying the biomolecule by the tip 2, the imaging and addressing accuracy of the solid-state nanopore is influenced, and the biomolecule is directly connected to the tip 2 of the AFM probe 1, so that the biomolecule is in friction contact with the device in the scanning imaging and addressing process of the tip 2 on the device, the biomolecule is easy to fall off from the tip 2 of the AFM probe 1, and the detection accuracy is also influenced.
In order to solve the technical problem, the present embodiment discloses a dual-mode detection probe, which is shown in fig. 3 and 6-7 and comprises a needle tip 2 of an AFM probe 1, a notch is formed in the needle tip 2, the notch extends to the tail end of the needle tip 2, the needle tip 2 is divided into an addressing tip 3 with an AFM function and a rivet biomolecule micro-scale platform 4 by the notch, the addressing tip 3 points to the top end of the needle tip 2, the rivet biomolecule micro-scale platform 4 extends along the cross section of the needle tip 2, a modification layer 5 is arranged on the table top of the rivet biomolecule micro-scale platform 4, and the modification layer 5 can be connected with a biomolecule 8 with a specific group.
According to the AFM probe 1, the needle point 2 of the probe is divided into the addressing tip 3 with the AFM scanning function and the rivet biomolecule micro-scale platform 4 by forming the notch on the needle point 2 of the probe, the modification layer 5 is not exposed out of the addressing tip 3, the modification layer 5 is exposed out of the rivet biomolecule micro-scale platform 4, the modification layer 5 of the rivet biomolecule micro-scale platform 4 can be subjected to coupling reaction with the biomolecule 8 group to form a stable chemical bond, and the biomolecule 8 with the specific group is only connected to the rivet biomolecule micro-scale platform 4 but not to the addressing tip 3, so that the biomolecule 8 is prevented from interfering with the addressing function of the addressing tip 3, and accurate imaging and addressing of the solid-state nanopore are realized. On the other hand, the quantity of the connected biomolecules 8 can be quantitatively and accurately controlled by controlling the table area of the rivet biomolecule micro-scale platform 4 and the exposed area of the modification layer, so that the accurate single biomolecule control via hole is realized, and the problem of detection interference caused by the fact that the single biomolecule control via hole cannot be realized in the prior art is solved; because the rivet biomolecule micro-scale platform 4 and the addressing tip 3 with the AFM scanning function have a certain distance, even if the addressing tip 3 carries out scanning imaging and addressing movement processes on the device, the biomolecule 8 on the rivet biomolecule micro-scale platform 4 can not touch or rub the device, the problem that the biomolecule 8 is easy to touch or rub to fall off in the prior art is avoided, the connection stability of the biomolecule 8 is improved, and the detection stability is ensured.
In this embodiment, the modification layer 5 includes any one of a gold substrate modification layer, a silver substrate modification layer, or a copper substrate modification layer 5. The principle that the rivet biomolecule micro-scale platform 4 can be connected with the biomolecules 8 through the modification layer 5 is as follows: self-assembled monomolecular films (SAMs) are thermodynamically stable, highly oriented, tightly packed monolayer ordered molecular films and lowest-energy ordered films formed by spontaneous adsorption of organic functional molecules on liquid-solid or gas-solid interfaces through chemical bonding. The method for preparing SAMs by spontaneous adsorption on the solid surface through chemical bond interaction is simple and efficient, and has extremely high stability. Based on this, assuming that the group of the biomolecule is a thiol group, the thiol group can form a chemical bond such as a gold-sulfur bond or a silver-sulfur bond with a solid substrate such as gold or silver (recognition principle), and self-assemble to form a dense and strong monolayer. For example, a biomolecule solution containing a thiol group is directly dropped on the gold-modified layer, and the biomolecule is stably modified on the gold-modified layer by rinsing after the biomolecule solution is self-assembled overnight.
In this embodiment, the AFM probe 1 is made of any one of silicon, silicon nitride, silicon oxide, and quartz. The AFM probe 1 can be made of other materials according to practical applications, and is not limited herein.
In this embodiment, the tip 2 of the AFM probe 1 has any one of a triangular pyramid, a rectangular pyramid and a cone. Other shapes of tip 2 of the AFM probe 1 can be used depending on the application, and are not limited herein.
Example 2
It will be appreciated that an embodiment of a dual mode detection probe is provided for illustration, and in practice, the dual mode detection probe is provided with a plurality of cantilever beams 6, each cantilever beam 6 having a tip 2.
The AFM probe 1 is provided with the cantilever beams 6, and the needle tips 2 are arranged on the cantilever beams 6, so that the double-mode detection probe is endowed with a plurality of needle tips 2, and the working efficiency of the double-mode detection probe is improved.
Example 3
In order to obtain the dual mode detection probe 1, the method for manufacturing the dual mode detection probe described in the presently disclosed embodiment 1, comprises the steps of,
and S1, presetting the sizes of the addressing tip with the AFM scanning function and the rivet biomolecule micro-scale platform according to the imaging resolution and the scanning precision. Imaging resolution and scan accuracy are measured by aspect ratio, and high aspect ratio tips generally have good imaging resolution and scan accuracy.
S2, milling the tip 2 of the AFM probe 1 according to the preset mesa areas of the addressing tip 3 and the rivet biomolecule micro-scale platform 4 with the AFM scanning function to form the addressing tip 3 and the rivet biomolecule micro-scale platform 4 (shown in figure 3), wherein the addressing tip 3 and the rivet biomolecule micro-scale platform 4 are manufactured through SEM scanning, and the contour of the addressing tip 3 and the contour of the rivet biomolecule micro-scale platform 4 are clearly visible as shown in figures 8-10;
s3, depositing a modification layer 5 (shown in FIG. 4) on the needlepoint 2 processed by the S2;
s4, depositing an isolation layer 7 on the needlepoint 2 processed by the S3, wherein the isolation layer 7 covers the modification layer 5 (shown in FIG. 5);
s5, milling the isolation layer 7 on the surface of the rivet biomolecule micro-scale platform 4 to expose the modification layer 5 with a preset area on the rivet biomolecule micro-scale platform 4, wherein the preset area is determined by the size, shape and number of the biomolecules 8, and the rest isolation layer covers the rest part of the needlepoint 2 (shown in figure 6). The exposed area of the modification layer is determined according to the size, shape, modification number and the like of the modified biomolecule. If the size of the biomolecule is 2nm and the number of the biomolecules to be modified is 1, ensuring that the exposed modification layer can only modify 1 biomolecule with the size of 2 nm; if the number of modifications required is 2, it is ensured that the exposed modification layer can only modify 2 biomolecules with a size of 2 nm.
The manufacturing method of the dual-mode detection probe can quickly and accurately manufacture the addressing tip 3 with the AFM scanning function and the rivet biomolecule micro-scale platform 4 with the exposed modification layer 5 on the needle point 2 on the single cantilever beam of the AFM probe 1 through the milling and deposition technology; the isolation layer 7 on the addressing tip 3 does not couple to the biomolecule 8 groups, ensuring that the addressing tip 3 does not couple to the biomolecule 8 and maintaining the addressing function. That is, the addressing tip 3 with AFM function and the rivet biomolecule micro-scale platform 4 are simultaneously obtained on the tip 2 of the single cantilever of the AFM probe 1. And then, depositing a modification layer 5 on the focused ion beam milled needle point 2 by a thin film deposition technology, wherein the modification layer 5 can perform a coupling reaction with a biomolecule 8 group to form a stable chemical bond. And then, covering a layer of isolating layer 7 on the modification layer 5 by a thin film deposition technology, wherein the isolating layer 7 does not generate coupling reaction with the biomolecule 8 group. Finally, the isolating layer 7 on the plane is modified by the biomolecules 8 through focused ion beam milling until the modifying layer 5 with the preset area is exposed. The predetermined area is determined by the size, shape and number of modifications of the group of the modified biomolecule 8.
The dual-mode detection probe prepared by the method has the functions of addressing solid-state nano holes and quantitatively modifying and manipulating biomolecules 8 on the needle tip 2. The addressing tip 3 of the structure can realize accurate addressing of the solid-state nano-pores, and meanwhile, the biomolecule 8 modification plane can realize quantitative modification of the biomolecule 8 and prevent the biomolecule 8 from falling off possibly in the AFM manipulation process.
In this embodiment, the tip 2 of the AFM probe 1 is milled and/or the isolation layer 7 is milled by a focused ion beam, which is any one of a focused gallium ion beam, a focused helium ion beam, and a focused neon ion beam. The focused Ion beam fib (focused Ion beam) is a beam having a higher energy and generated by an Ion source (such as gallium ions, helium ions, neon ions, and the like, among which gallium ions are the most commonly used Ion source) under a vacuum condition, and is used for processing by a collision effect, a sputtering effect, an implantation effect, a deposition effect, and the like, which are generated when the Ion beam acts on a sample surface. The main functions of the focused ion beam are sputtering and deposition. Among them, sputtering is the most important function of ion beam processing, and is the phenomenon that incident ions transfer energy to solid target material atoms, so that the atoms obtain enough energy to escape from the solid surface. The focused ion beam processing has incomparable advantages compared with any other processing means, and can realize the maskless processing with ultra-high precision below sub-nanometer. The ion beam bombards the target material to finally expose the modification layer with the preset area by adjusting parameters such as ion species, ion beam current, ion energy, incident angle and the like on the target material.
In this embodiment, the modification layer 5 and/or the isolation layer 7 are/is deposited by a thin layer deposition technique, which is any one of a physical vapor deposition technique, a chemical vapor deposition technique, or an atomic layer deposition technique. Physical Vapor Deposition (PVD) typically includes thermal evaporation deposition and sputtering deposition, among others. Thermal evaporation deposition is divided into resistance thermal evaporation, electron beam evaporation deposition and the like according to different evaporation methods. Among them, electron beam evaporation deposition is a method of using electron beam to bombard a film material to realize evaporation, and is an ideal evaporation approach. The method not only greatly improves the bonding force with the substrate, the material purity, the universality and the like, but also has obvious advantages in the aspects of deposition directionality, accurate controllability, film deposition rate and film quality. The electron beam evaporation method is widely applied to the preparation of various film materials, metal oxides and high-temperature superconducting films. Sputter-deposited films refer to the phenomenon of having sufficiently high particles bombarding a solid target surface causing atoms to be sputtered and deposited onto the substrate surface to form a film. The thin film deposited by sputtering has good adhesiveness with the substrate, high purity of the thin film, good compactness, wide material application range, and good controllability and repeatability.
Chemical Vapor Deposition (CVD) is a method of forming a thin film by depositing reactants on a surface of a substrate using a chemical reaction of gases under vacuum conditions and at an appropriate temperature. However, the CVD process needs to be performed at a higher temperature, which limits the choice of substrate materials. The Plasma Enhanced Chemical Vapor Deposition (PECVD) method is commonly used in micro-nano processing, the introduction of the plasma can greatly improve the deposition efficiency, a compound film material can be obtained at a much lower temperature, the deposition rate is high, and the film forming quality is good.
Atomic Layer Deposition (ALD) is a method of plating a substance from a monoatomic film, layer by layer, onto a substrate surface. ALD is similar to CVD, but in ALD only one layer of atoms is deposited per reaction, achieving ultra-thin film deposition of a few nanopores in a highly precisely controlled manner is a true nanotechnology.
In this embodiment, the thickness of the modification layer 5 is 10nm to 1000 nm. The thickness of the isolation layer 7 is 10 nm-1000 nm. The thickness of the decorative layer 5 and the thickness of the isolation layer 7 can be adjusted according to actual conditions, and are not limited herein.
In this embodiment, the material of the isolation layer 7 is aluminum oxide or titanium oxide. The isolation effect of the aluminum oxide or the titanium oxide is good.
The working principle of the structure of the dual-mode detection probe and the manufacturing method thereof of the invention is as follows: the dual-mode detection probe comprises an addressing tip with AFM scanning function and a rivet biomolecule micro-scale platform. The addressing tip with the AFM scanning function is used for scanning and imaging the solid-state nano-pores, and the rivet biomolecule micro-scale platform is used for stably connecting the biomolecules to be detected and controlling the connection quantity of the biomolecules. The dual-mode detection probe is formed by processing a focused ion beam technology and a thin film deposition technology on a needle tip of a single cantilever of an AFM probe. Firstly, milling a tip of an AFM probe through a focused ion beam, dividing the tip into an addressing tip with an AFM scanning function and a rivet biomolecule micro-scale platform, wherein the sizes of the tip and the platform are determined according to the imaging resolution and the scanning precision. And then, depositing a modification layer on the needle tip by a thin film deposition technology, wherein the modification layer can perform coupling reaction with a group of the biomolecule to form a stable chemical bond, so that the stable connection of the biomolecule is realized. Subsequently, a layer of isolating layer is deposited on the modifying layer by thin layer deposition technique, the isolating layer does not have coupling reaction with the biological molecules. And finally, milling the isolation layer on the micro-scale platform of the biological molecules of the rivet by focused ion beams to expose the modification layer with a preset area, wherein the preset area is determined by the size, the shape and the quantity of the biological molecules, and the quantity controllable connection of the biological molecules is realized. The dual-mode detection probe is suitable for the researches in the aspects of single-molecule manipulation, single-molecule force spectroscopy, nano-scale manufacturing and the like.
The relative arrangement of the components and steps, the numerical expressions and numerical values set forth in these embodiments do not limit the scope of the present invention unless specifically stated otherwise. Meanwhile, it should be understood that the sizes of the respective portions shown in the drawings are not drawn in an actual proportional relationship for the convenience of description. Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate. In all examples shown and discussed herein, any particular value should be construed as merely illustrative, and not limiting. Thus, other examples of the exemplary embodiments may have different values. It should be noted that: like reference numbers and letters refer to like items in the following figures, and thus, once an item is defined in one figure, further discussion thereof is not required in subsequent figures.
In the description of the present invention, it is to be understood that the directions or positional relationships indicated by the directional terms such as "front, rear, upper, lower, left, right", "lateral, vertical, horizontal" and "top, bottom", etc., are generally based on the directions or positional relationships shown in the drawings, and are for convenience of description and simplicity of description only, and in the case of not making a reverse description, these directional terms do not indicate and imply that the device or element referred to must have a particular orientation or be constructed and operated in a particular orientation, and therefore, should not be considered as limiting the scope of the present invention; the terms "inner and outer" refer to the inner and outer relative to the profile of the respective component itself.
Spatially relative terms, such as "above … …," "above … …," "above … …," "above," and the like, may be used herein for ease of description to describe one device or feature's spatial relationship to another device or feature as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is turned over, devices described as "above" or "on" other devices or configurations would then be oriented "below" or "under" the other devices or configurations. Thus, the exemplary term "above … …" can include both an orientation of "above … …" and "below … …". The device may be otherwise variously oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
It should be noted that the terms "first", "second", and the like are used to define the components, and are only used for convenience of distinguishing the corresponding components, and unless otherwise stated, the terms have no special meaning, and therefore, the scope of the present invention should not be construed as being limited.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
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