CN113189358A - Semi-contact type sample applicator and preparation method of micro-cantilever sensor chip - Google Patents
Semi-contact type sample applicator and preparation method of micro-cantilever sensor chip Download PDFInfo
- Publication number
- CN113189358A CN113189358A CN202110492715.3A CN202110492715A CN113189358A CN 113189358 A CN113189358 A CN 113189358A CN 202110492715 A CN202110492715 A CN 202110492715A CN 113189358 A CN113189358 A CN 113189358A
- Authority
- CN
- China
- Prior art keywords
- micro
- sensor chip
- sample liquid
- spotted
- cantilever sensor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
- G01N2035/1037—Using surface tension, e.g. pins or wires
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
According to the semi-contact sample applicator and the preparation method of the micro-cantilever sensor chip, the liquid level of the sample liquid in the capillary needle is controlled to form the convex liquid level through the injection pump, the convex sample liquid is contacted with the micro-cantilever sensor chip to be subjected to sample application through controlling the moving platform, sample liquid drops are formed on the micro-cantilever sensor chip to be subjected to sample application under the action of tension, and the sample liquid can be prevented from splashing to cause device failure and sample waste. And by using the syringe pump to provide pressure for pumping in/out the sample liquid, the sample liquid does not need to be extruded out of the needle point, and the syringe is suitable for viscous sample liquid. In addition, the sample applicator has simple integral structure and low cost.
Description
Technical Field
The invention relates to the field of preparation of sensing chips, in particular to a semi-contact type sample applicator and a preparation method of a micro-cantilever sensing chip.
Background
The Micro cantilever is a Mechanical structure in the shape of a strip prepared by a Micro Electro Mechanical System (MEMS) process, and one end of the structure is suspended while the other end is fixed, and is often used as a biochemical sensor. When the micro-cantilever is used as a biochemical sensor, there are two different working modes, one is a static working mode, i.e. a stress working mode, and the other is a dynamic working mode, i.e. a resonance working mode. Regardless of the working mode, the sensitive material is required to be uploaded to the sensitive area at the suspension end of the micro-cantilever through spotting. Since the area of the sensitive area of the microcantilever is very small, typically 100 microns x 100 microns, the loading of the sensitive material must be done with the help of a spotter.
The traditional sample applicator generally adopts a non-contact type spraying sample application method, and a piezoelectric nozzle is utilized to control the spraying amount of sensitive materials. The working principle of the piezoelectric nozzle is that a cavity and a fine nozzle are etched on a silicon chip, piezoelectric ceramics are attached to the back of the cavity, voltage is applied to the piezoelectric ceramics during working, the piezoelectric ceramics deform and drive the silicon chip to bend and deform in a concave-convex mode, so that the volume of the cavity changes rapidly, and liquid droplets are ejected. However, this kind of sampling method has the following disadvantages:
(1) due to the action of the surface tension of the liquid, the liquid drops ejected by the method are often large in size, and sensitive materials are easily wasted;
(2) splashing often occurs when the piezoelectric nozzle contacts the surface of the device, so that sensitive materials are adhered to the non-sensitive area of the micro-cantilever beam, and further the failure of the device is caused;
(3) the requirement on a sample is high, and smooth injection is difficult to realize for viscous liquid or particle suspension;
(4) the spotting apparatus is expensive and increases the manufacturing cost.
Disclosure of Invention
The embodiment of the application provides a preparation method of a semi-contact type sample applicator and a micro-cantilever sensor chip, which can prevent device failure and sample waste caused by splashing of sample liquid, does not need to extrude the sample liquid out of a needle point, and is suitable for viscous sample liquid.
The embodiment of the application provides a half contact type spotting instrument, this spotting instrument includes: the injection device comprises a mobile platform and an injection system arranged on the mobile platform;
the injection system comprises an injection pump, a connecting pipe, a needle holder, a clamp holder and a capillary needle;
one end of the connecting pipe is connected with the injection pump, the other end of the connecting pipe is connected with the needle holder, the holder is connected with the outer wall of the needle holder, and the capillary needle is arranged at the end part of the needle holder;
the injection pump is used for providing pressure for pumping in/pushing out sample liquid, the capillary needle is provided with an injection section, an included angle between the injection section and an axial plane of the capillary needle is smaller than 90 degrees, and the holder is used for adjusting the inclination angle of the injection section of the capillary needle relative to the micro-cantilever sensor chip to be spotted;
the moving platform is used for bearing the micro-cantilever sensor chip to be spotted and adjusting the relative position between the micro-cantilever sensor chip to be spotted and the capillary needle.
Further, the capillary needle includes:
the accommodating cavity is used for accommodating sample liquid;
the needle head is arranged at the end part of the accommodating cavity and is provided with an injection section;
the needle head is used for sucking the sample liquid into the accommodating cavity through the injection section under the pressure action of pumping the sample liquid provided by the injection pump, and injecting the sample liquid onto the micro-cantilever sensor chip to be spotted through the injection section under the pressure action of pushing out the sample liquid provided by the injection pump.
Furthermore, the inclination angle between the injection section of the capillary needle and the micro-cantilever sensor chip to be spotted is in the interval of [5 degrees, 75 degrees ].
Further, the diameter of the inner wall of the needle is within the interval [10 μm,100 μm ].
Further, the mobile platform comprises a base, a left mobile platform, an object stage and a lifting rotating assembly;
the left moving platform is arranged on the base;
the objective table and the lifting rotating assembly are both arranged on the left moving platform;
the lifting rotating assembly is connected with the holder;
the objective table is used for bearing a micro-cantilever sensor chip to be spotted;
the lifting and rotating component is used for adjusting the relative position between the micro-cantilever sensor chip to be spotted and the capillary needle and the inclination angle of the injection section of the capillary needle relative to the micro-cantilever sensor chip to be spotted.
Further, the lifting and rotating assembly comprises a movable lifting platform and a rotating platform;
the movable lifting platform is used for adjusting the relative position between the micro-cantilever beam sensing chip to be spotted and the capillary needle;
the rotating platform is used for adjusting the inclination angle of the injection section of the capillary needle relative to the micro-cantilever sensor chip to be spotted.
Furthermore, a first rotating rod, a second rotating rod and a third rotating rod are arranged on the movable lifting platform;
the first rotating rod is used for controlling the movable lifting platform to translate along a first direction;
the second rotating rod is used for controlling the movable lifting platform to translate along a second direction;
the third rotating rod is used for controlling the movable lifting platform to translate along a third direction;
the first direction, the second direction and the third direction are vertical to each other.
Further, the spotting instrument also comprises a microscopic observation system;
the microscopic observation system comprises a microscopic lens, a focusing knob and a display screen;
the focusing knob is connected with the microscope lens;
the display screen is connected with the micro lens;
the focusing knob is used for adjusting the focal length between the microscope lens and the micro-cantilever sensor chip to be spotted;
the display screen is used for displaying the capillary needle, the sample liquid and the micro-cantilever sensor chip to be spotted.
Furthermore, the left moving platform is used for moving the micro-cantilever sensor chip to be spotted under the microscope lens, so that the capillary needle, the sample liquid and the micro-cantilever sensor chip to be spotted are displayed on the display screen.
Correspondingly, the embodiment of the application also provides a preparation method of the micro-cantilever sensor chip, which is realized based on a half-contact type sample applicator and comprises the following steps:
mounting a capillary needle at the end of a needle holder;
under the pressure action of pumping sample liquid provided by the injection pump, sucking the sample liquid into the accommodating cavity of the capillary needle through the injection section of the needle head on the capillary needle;
placing a micro-cantilever sensor chip to be spotted on an object stage of a moving platform, controlling a moving lifting platform of the moving platform to move, and moving the micro-cantilever sensor chip to be spotted under a microscope lens of a microscopic observation system;
adjusting a moving lifting platform of the moving platform and a focusing knob of the microscopic observation system, and adjusting the relative position between the micro-cantilever sensor chip to be spotted and the capillary needle so as to display the micro-cantilever sensor chip to be spotted on a display screen of the microscopic observation system;
controlling a rotating platform of the moving platform to drive the capillary needle to leave the micro-cantilever sensor chip to be spotted, and adjusting the inclination angle of the injection section of the capillary needle and the micro-cantilever sensor chip to be spotted within a range of [5 degrees, 75 degrees ];
injecting the sample liquid through the injection section of the needle head on the capillary needle under the pressure provided by the injection pump for pushing out the sample liquid, wherein the sample liquid is protruded relative to the injection section;
controlling a left moving platform of the moving platform to enable the protruded sample liquid to be in contact with the micro-cantilever sensor chip to be spotted, and forming sample liquid drops on the micro-cantilever sensor chip to be spotted under the action of tension;
driving the rotating platform of the moving platform to drive the capillary needle to leave the micro-cantilever sensor chip to be spotted, so that the sample liquid drop is disconnected with the injection section of the capillary needle;
after the solute in the sample liquid drops on the micro-cantilever sensor chip to be spotted volatilizes, repeating the steps: and controlling the left moving platform of the moving platform to enable the convex sample liquid to be in contact with the micro-cantilever sensor chip to be subjected to sample application, forming sample liquid drops on the micro-cantilever sensor chip to be subjected to sample application under the action of tension until the sample liquid drops on the micro-cantilever to be subjected to sample application are in a preset sample liquid drop quantity interval, and obtaining the micro-cantilever sensor chip subjected to sample application.
The embodiment of the application has the following beneficial effects:
according to the semi-contact sample applicator and the preparation method of the micro-cantilever sensor chip, the liquid level of the sample liquid in the capillary needle is controlled to form the convex liquid level through the injection pump, the convex sample liquid is contacted with the micro-cantilever sensor chip to be subjected to sample application through controlling the moving platform, sample liquid drops are formed on the micro-cantilever sensor chip to be subjected to sample application under the action of tension, and device failure and sample waste caused by splashing of the sample liquid can be prevented. And by using the syringe pump to provide pressure for pumping in/out the sample liquid, the sample liquid does not need to be extruded out of the needle point, and the syringe is suitable for viscous sample liquid. In addition, the sample applicator has simple integral structure and low cost.
Drawings
In order to more clearly illustrate the technical solutions and advantages of the embodiments of the present application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a schematic diagram of a spotting instrument provided in an embodiment of the present application;
FIG. 2a is a schematic diagram of a sample liquid protruding from an injection section according to an embodiment of the present disclosure;
FIG. 2b is a schematic diagram of the formation of a sample liquid droplet on a micro-cantilever sensor chip to be spotted according to the embodiment of the present application;
fig. 2c is a schematic diagram of a sample liquid droplet broken from an injection section of a capillary needle according to an embodiment of the present application.
Description of the drawings: the method comprises the following steps of 1-an injection system, 11-an injection pump, 12-a connecting pipe, 13-a needle holder, 14-a holder, 15-a capillary needle, 2-a moving platform, 21-a base, 22-a left moving platform, 23-an object stage, 24-a lifting rotating assembly, 241-a moving lifting platform, 242-a rotating platform, 3-a microscopic observation system, 31-a microscope lens, 32-a focusing knob, 33-a display screen and 4-a micro cantilever beam sensing chip to be spotted.
Detailed Description
To make the objects, technical solutions and advantages of the present application more clear, embodiments of the present application will be described in further detail below with reference to the accompanying drawings. It should be apparent that the described embodiment is only one embodiment of the present application and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
An "embodiment" as referred to herein relates to a particular feature, structure, or characteristic that may be included in at least one implementation of the present application. In the description of the embodiments of the present application, it should be understood that the terms "upper", "lower", "left", "right", and the like indicate orientations or positional relationships based on those shown in the drawings, and are only used for convenience in describing the present application and simplifying the description, but do not indicate or imply that the device/system or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present application. The terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Moreover, the terms "first," "second," and the like are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used is interchangeable under appropriate circumstances such that the embodiments of the application described herein are capable of operation in other sequences than described or illustrated herein. Furthermore, the terms "comprises," "comprising," and "has" and any variations thereof, are intended to cover non-exclusive inclusions, such that a structure comprising a list of elements or components, a method comprising a list of steps, is not necessarily limited to those elements, components, or steps which are expressly listed, but may include elements or components which are not expressly listed or inherent to such structure and steps which are inherent to such method.
Fig. 1 is a schematic structural view of a printer according to the present embodiment, and the present specification provides the components as shown in the embodiment or the schematic structural view, but more or less devices or components can be included based on conventional or non-inventive labor.
As shown in fig. 1, the spotting instrument may comprise a moving platform 2, an injection system 1 disposed on the moving platform 2, and a microscopic observation system 3 disposed on the moving platform 2. The sample applicator has simple integral structure and low cost.
In an embodiment of the present application, the injection system 1 may comprise a syringe pump 11, a connecting tube 12, a needle holder 13 and a capillary needle 15. One end of the connecting tube 12 can be connected with the syringe pump 11, the other end of the connecting tube 12 can be connected with the needle holder 13, that is, the connecting tube 12 can connect the needle holder 13 and the syringe pump 11, the holder 14 can be connected with the outer wall of the needle holder 13, that is, the holder 14 can be used for fixing the needle holder 13, and the capillary needle 15 can be installed at the end of the needle holder 13. The syringe pump 11 can be used to provide the pressure for pumping in/out the sample liquid, the capillary needle has an injection section, the injection section can form an angle smaller than 90 degrees with the axial plane of the capillary needle 15, i.e. the injection section forms an acute angle with the length direction of the capillary needle 15, and the holder 14 can be used to adjust the inclination angle of the injection section of the capillary needle 15 with respect to the micro-cantilever sensor chip 4 to be spotted. The liquid level of sample liquid forms convex liquid level in the capillary needle 15 through injection pump 11 control to through control moving platform 2, make convex sample liquid and treat the contact of sample application micro cantilever beam sensing chip 4, under the tension effect, treat to form the sample liquid droplet on the sample application micro cantilever beam sensing chip 4, can prevent that sample liquid from splashing the waste that causes. By using the syringe pump 11 to provide pressure for pumping in/out the sample fluid, it is not necessary to push the sample fluid out of the needle tip, and this is suitable for viscous sample fluids.
In an alternative embodiment, the capillary needle 15 may include a containing cavity and a whole body disposed at an end of the containing cavity, wherein the containing cavity may be used for containing the sample liquid, the needle has an injection section, and the needle may be used for sucking the sample liquid into the containing cavity through the injection section under the pressure effect of pumping the sample liquid provided by the injection pump 11. Particularly, can absorb sample liquid through the injection tangent plane for sample liquid is full of half capillary needle 15, can reduce sample liquid and be full of the sample liquid waste that whole holding chamber caused, also can improve the handling nature of being convenient for of sample application. The needle head can also be used for injecting the sample liquid to the micro-cantilever sensor chip 4 to be spotted through the injection section under the pressure action of pushing out the sample liquid provided by the injection pump 11, namely, the sample can be spotted in the sensitive area of the micro-cantilever sensor chip 4 to be spotted through the injection section.
In an alternative embodiment, the injection section of the capillary needle 15 may be inclined to the micro-cantilever sensor chip 4 to be spotted at an angle within the interval [7 °,75 ° ].
In an alternative embodiment, the diameter of the inner wall of the needle may be in the range of tens to hundreds of microns, in particular in the interval [10 μm,100 μm ]. Because the inner wall diameter of this syringe needle is great, use the particle turbid liquid also difficult to take place stifled needle phenomenon, even stifled needle, the cost of changing the syringe needle of capillary needle 15 is far less than piezoelectric nozzle, can practice thrift manufacturing cost.
In this embodiment, the moving platform 2 may be configured to support the micro-cantilever sensor chip 4 to be spotted, and adjust the relative position between the micro-cantilever sensor chip 4 to be spotted and the capillary needle 15.
In an alternative embodiment, the mobile platform 2 may include a base 21, a left mobile platform 22, a stage 23, and a lifting and lowering rotation assembly 24. Wherein, left moving platform 22 can set up on base 21, objective table 23 and lift rotating assembly all can set up on left moving platform 22, lift rotating assembly 24 can be connected with holder 14, objective table 23 can be used for bearing and treats sample application micro cantilever sensor chip 4, lift rotating assembly 24 can be used for adjusting the relative position between treating sample application micro cantilever sensor chip 4 and capillary needle 15 to and capillary needle 15's injection tangent plane is for treating sample application micro cantilever sensor chip 4's inclination. That is, the mobile platform 2 may include the vibration isolation base 21, and the material of this vibration isolation base 21 may be stainless steel to increase weight, guarantee the stability in the process of sample application.
In an alternative embodiment, the lift-rotate assembly 24 includes a moving lift table 241 and a rotating table 242. Wherein, remove elevating platform 241 can be used for adjusting the relative position between treating sample application micro-cantilever beam sensing chip 4 and capillary needle 15, the revolving stage can be used for adjusting the injection tangent plane of capillary needle 15 for treating sample application micro-cantilever beam sensing chip 4's inclination.
In an alternative embodiment, a first rotating rod, a second rotating rod and a third rotating rod may be disposed on the moving lifting platform 241, where the first rotating rod may be used to control the moving lifting platform 241 to translate along a first direction, the second rotating rod may be used to control the moving lifting platform 241 to translate along a second direction, and the third rotating rod may be used to control the moving lifting platform 241 to translate along a third direction, where the first direction, the second direction and the third direction are perpendicular to each other two by two. Namely, the relative position between the micro-cantilever sensor chip 4 to be spotted and the capillary needle 15 and the inclination angle of the injection section of the capillary needle 15 relative to the micro-cantilever sensor chip 4 to be spotted can be adjusted by adjusting the three rotating rods on the rotating component, and the precision can be controlled within 1 micron.
In this embodiment, the above-mentioned microscopic observation system 3 can include microscope lens 31, focusing knob 32 and display screen 33, wherein, focusing knob 32 can be connected with microscope lens 31, display screen 33 can be connected with microscope lens 31, focusing knob 32 can be used for adjusting microscope lens 31 and the focus of waiting to sample application micro-cantilever sensor chip 4 within a definite time, display screen 33 can be used for showing capillary needle 15, sample liquid and waiting to sample application micro-cantilever sensor chip 4. The left moving platform 22 can be used to move the micro-cantilever sensor chip 4 to be spotted under the microscope lens, so that the capillary needle 15, the sample liquid and the micro-cantilever sensor chip 4 to be spotted are displayed on the display screen 33. By integrating the microscopic observation system 3 on the sample applicator, the real-time imaging observation can be carried out on the sample application process, and the sample application result can be judged.
Adopt the half-contact type spotting instrument that this application embodiment provided, the liquid level of sample liquid forms convex liquid level in the control capillary needle 15 through syringe pump 11, and left moving platform 22 through control moving platform 2, make convex sample liquid and treat the contact of sample application micro cantilever beam sensing chip 4, under the tension effect, treat to form the sample liquid droplet on the sample application micro cantilever beam sensing chip 4, can prevent that the device that sample liquid splashes and cause from becoming invalid and the sample is extravagant, be applicable to thick sample liquid or particulate matter turbid liquid, it is extensive to be suitable for the scene, and overall structure is simple, low in manufacturing cost.
The embodiment of the application also provides a preparation method of the micro-cantilever sensor chip, and the preparation method can be realized based on a semi-contact sample applicator.
Wherein, the semi-contact type spotting instrument can comprise a moving platform 2, an injection system 1 arranged on the moving platform 2 and a microscopic observation system 3 arranged on the moving platform 2. Wherein, the injection system 1 can include an injection pump 11, a connecting pipe 12, a needle holder 13, a holder 14 and a capillary needle 15, one end of the connecting pipe 12 can be connected with the injection pump 11, the other end of the connecting pipe 12 can be connected with the needle holder 13, the holder 14 can be connected with the outer wall of the needle holder 13, the capillary needle 15 can be installed at the end of the needle holder 13, the injection pump 11 can be used for providing the pressure for pumping in/pushing out the sample liquid, the capillary needle 15 has an injection section, the included angle between the injection section and the axial plane of the capillary needle 15 can be smaller than 90 degrees, the holder 14 can be used for adjusting the inclination angle of the injection section of the capillary needle 15 relative to the micro-cantilever sensor chip 4 to be spotted, the mobile platform 2 can be used for bearing the micro-cantilever sensor chip 4 to be spotted, and adjusting the relative position between the micro-cantilever sensor chip 4 to be spotted and the capillary needle 15.
The capillary needle 15 may include: the holding chamber, the holding chamber can be used for holding sample liquid, sets up the syringe needle at the tip in holding chamber, and the syringe needle has the injection tangent plane, and the syringe needle can be used for absorbing sample liquid to the holding intracavity through the injection tangent plane under the pressure effect of the pump income sample liquid that syringe pump 11 provided to and under the pressure effect of the release sample liquid that syringe pump 11 provided, inject sample liquid to waiting on the sample application micro cantilever sensor chip 4 through the injection tangent plane. The inclination angle between the injection section of the capillary needle 15 and the micro-cantilever sensor chip 4 to be spotted can be within the interval of [5 degrees, 75 degrees ]. The diameter of the inner wall of the needle may be in the interval [10 μm,100 μm ]. The volume of the sample liquid sucked into the accommodating cavity by the needle head can be one half of the volume of the accommodating cavity.
Moving platform 2 can include base 21, left moving platform 22, objective table 23 and lift rotating assembly 24, left side moving platform 22 can set up on base 21, objective table 23 and lift rotating assembly 24 can set up on left moving platform 22, lift rotating assembly 24 can be connected with holder 14, objective table 23 can be used for bearing the little cantilever beam sensor chip 4 of waiting to sample, lift rotating assembly 24 can be used for adjusting the relative position between little cantilever beam sensor chip 4 of waiting to sample and capillary needle 15, and the injection tangent plane of capillary needle 15 is for the inclination of the little cantilever beam sensor chip 4 of waiting to sample. The lifting and rotating assembly 24 may include a movable lifting stage 241 and a rotating stage 242, the movable lifting stage 241 may be used to adjust the relative position between the micro-cantilever sensor chip 4 to be spotted and the capillary needle 15, and the rotating stage 242 may be used to adjust the inclination angle of the injection section of the capillary needle 15 relative to the micro-cantilever sensor chip 4 to be spotted. The lifting rotating assembly 24 can be provided with a first rotating rod, a second rotating rod and a third rotating rod, the first rotating rod can be used for controlling the lifting rotating assembly 24 to translate along a first direction, the second rotating rod can be used for controlling the lifting rotating assembly 24 to translate along a second direction, the third rotating rod can be used for controlling the lifting rotating assembly 24 to translate along a third direction, and the first direction, the second direction and the third direction are pairwise perpendicular.
The microscopic observation system 3 can comprise a microscope lens 31, a focusing knob 32 and a display screen 33, wherein the focusing knob 32 is connected with the microscope lens 31, the display screen 33 is connected with the microscope lens 31, the focusing knob 32 is used for adjusting the focal length between the microscope lens 31 and the micro-cantilever sensor chip 4 to be spotted, and the display screen 33 is used for displaying the capillary needle 15, the sample liquid and the micro-cantilever sensor chip 4 to be spotted. The left moving platform 22 is used for moving the micro-cantilever sensor chip 4 to be spotted under the microscope lens, so that the capillary needle 15, the sample liquid and the micro-cantilever sensor chip 4 to be spotted are displayed on the display screen 33.
The embodiment of the application also provides a preparation method of the micro-cantilever sensor chip, which is realized based on a half-contact sample applicator and comprises the following steps:
a capillary needle 15 is mounted at the end of the needle holder 13.
Under the pressure of the sample liquid pumped by the injection pump 11, the sample liquid is sucked into the accommodating cavity of the capillary needle 15 through the injection section of the needle head on the capillary needle 15.
The micro-cantilever sensor chip 4 to be spotted is placed on the objective table 23 of the moving platform 2, the moving lifting table 241 of the moving platform 2 is controlled to move, and the micro-cantilever sensor chip 4 to be spotted is moved to the position below the microscope lens 31 of the microscope observation system 3.
And adjusting the moving lifting platform 241 of the moving platform 2 and the focusing knob 32 of the microscopic observation system 3, and adjusting the relative position between the micro-cantilever sensing chip 4 to be spotted and the capillary needle 15, so that the micro-cantilever sensing chip 4 to be spotted is displayed on the display screen 33 of the microscopic observation system 3.
The rotating platform 242 of the moving platform 2 is controlled to further drive the capillary needle to leave the micro-cantilever sensor chip to be spotted, and the inclination angle between the injection section of the capillary needle 15 and the micro-cantilever sensor chip 4 to be spotted is adjusted within the interval [5 degrees, 75 degrees ].
Under the pressure action of pushing out the sample liquid provided by the injection pump 11, injecting the sample liquid through the injection section of the needle head on the capillary needle 15, wherein the sample liquid protrudes relative to the injection section; fig. 2a is a schematic diagram of a sample liquid protruding from an injection section according to an embodiment of the present disclosure.
Controlling a left moving platform 22 of the moving platform 2 to enable the protruded sample liquid to be in contact with the micro-cantilever sensor chip 4 to be spotted, and forming sample liquid drops on the micro-cantilever sensor chip 4 to be spotted under the action of tension; fig. 2b is a schematic diagram of forming a sample liquid droplet on the micro-cantilever sensor chip 4 to be spotted according to the embodiment of the present application.
The rotating platform 242 of the moving platform 2 is driven to drive the capillary needle 15 to leave the micro-cantilever sensor chip 4 to be spotted, so that the sample liquid droplet is disconnected with the injection section of the capillary needle 15; fig. 2c is a schematic diagram of the sample liquid droplet and the injection section of the capillary needle 15 provided in the embodiment of the present application.
After the solute in the sample liquid drops on the micro-cantilever sensor chip 4 to be spotted volatilizes, the steps are repeated: and controlling the left moving platform 22 of the moving platform 2 to enable the convex sample liquid to be in contact with the micro-cantilever sensor chip 4 to be subjected to sample application, and forming sample liquid drops on the micro-cantilever sensor chip 4 to be subjected to sample application under the action of tension until the sample liquid drops on the micro-cantilever 4 to be subjected to sample application are in a preset sample liquid drop number interval to obtain the micro-cantilever sensor chip subjected to sample application.
By adopting the preparation method of the micro-cantilever sensor chip provided by the embodiment of the application, the injection pump 11 is used for controlling the liquid level of the sample liquid in the capillary needle 15 to form a convex liquid level, and the left moving platform 22 of the moving platform 2 is controlled, so that the convex sample liquid is contacted with the micro-cantilever sensor chip 4 to be subjected to sample application, and under the action of tension, sample liquid drops are formed on the micro-cantilever sensor chip 4 to be subjected to sample application, thereby preventing the device failure and sample waste caused by the splashing of the sample liquid.
The embodiment of the preparation method of the semi-contact type sample applicator or the micro-cantilever sensor chip provided by the application can be seen that the liquid level of the sample liquid in the capillary needle is controlled to form a convex liquid level by the injection pump, and the convex sample liquid is contacted with the micro-cantilever sensor chip to be sampled by controlling the moving platform, so that sample liquid drops are formed on the micro-cantilever sensor chip to be sampled under the action of tension, and the waste caused by splashing of the sample liquid can be prevented. And by using the syringe pump to provide pressure for pumping in/out the sample liquid, the sample liquid does not need to be extruded out of the needle point, and the syringe is suitable for viscous sample liquid. In addition, the sample applicator has simple integral structure and low cost.
In the present invention, unless otherwise expressly stated or limited, the terms "connected" and "connected" are to be construed broadly, e.g., as meaning either a fixed connection or a removable connection, or an integral part; can be mechanically or electrically connected; either directly or indirectly through intervening media, either internally or in any other relationship. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.
It should be noted that: the foregoing sequence of the embodiments of the present application is for description only and does not represent the superiority and inferiority of the embodiments, and the specific embodiments are described in the specification, and other embodiments are also within the scope of the appended claims. In some cases, the actions or steps recited in the claims can be performed in the order of execution in different embodiments and achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown or connected to enable the desired results to be achieved, and in some embodiments, multitasking and parallel processing may also be possible or may be advantageous.
All the embodiments in the present specification are described in a progressive manner, and the same and similar parts among the embodiments may be referred to each other, and each embodiment is described with emphasis on differences from other embodiments.
While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention.
Claims (10)
1. A semi-contact spotting apparatus, comprising: a mobile platform (2) and an injection system (1) arranged on the mobile platform;
the injection system (1) comprises an injection pump (11), a connecting pipe (12), a needle holder (13), a clamp holder (14) and a capillary needle (15);
one end of the connecting pipe (12) is connected with the injection pump (11), the other end of the connecting pipe (12) is connected with the needle holder (13), the holder (14) is connected with the outer wall of the needle holder (13), and the capillary needle (15) is installed at the end part of the needle holder (13);
the injection pump (11) is used for providing pressure for pumping in/out sample liquid, the capillary needle (15) is provided with an injection section, the included angle between the injection section and the axial plane of the capillary needle (15) is less than 90 degrees, and the holder (14) is used for adjusting the inclination angle of the injection section of the capillary needle (15) relative to the micro-cantilever sensor chip (4) to be spotted;
the moving platform (2) is used for bearing the micro-cantilever sensor chip (4) to be spotted and adjusting the relative position between the micro-cantilever sensor chip (4) to be spotted and the capillary needle (15).
2. Spotting instrument according to claim 1, characterized in that the capillary needle (15) comprises:
the holding cavity is used for holding sample liquid;
the needle head is arranged at the end part of the accommodating cavity and is provided with the injection tangent plane;
the needle head is used for sucking the sample liquid to the accommodating cavity through the injection section under the pressure action of pumping the sample liquid provided by the injection pump (11), and injecting the sample liquid to the micro-cantilever sensor chip (4) to be spotted through the injection section under the pressure action of pushing out the sample liquid provided by the injection pump.
3. Spotting instrument according to claim 1, characterized in that the injection section of the capillary needle (15) is inclined with respect to the micro-cantilever sensor chip to be spotted (4) within the interval [5 °,75 ° ].
4. Spotting apparatus according to claim 2 characterized in that the diameter of the inner wall of the needle is within the interval [10 μm,500 μm ].
5. Printer according to claim 1 characterized in that the moving platform (2) comprises a base (21), a left moving platform (22), a stage (23) and a lifting and rotating assembly (24);
the left moving platform (22) is arranged on the base (21);
the object stage (23) and the lifting and rotating assembly (24) are arranged on the left moving platform (22);
the lifting rotating assembly (24) is connected with the clamper (14);
the objective table (23) is used for bearing the micro-cantilever sensor chip (4) to be spotted;
the lifting and rotating component (24) is used for adjusting the relative position between the micro-cantilever sensor chip (4) to be spotted and the capillary needle (15), and the injection section of the capillary needle (15) is relative to the inclination angle of the micro-cantilever sensor chip (4) to be spotted.
6. Spotting apparatus according to claim 5, characterized in that said elevation and rotation assembly (24) comprises a mobile elevation stage (241) and a rotation stage (242);
the movable lifting platform (241) is used for adjusting the relative position between the micro-cantilever sensor chip (4) to be spotted and the capillary needle (15);
the rotating platform (242) is used for adjusting the inclination angle of the injection section of the capillary needle (15) relative to the micro-cantilever sensor chip (4) to be spotted.
7. Spotting apparatus according to claim 6 characterized in that the mobile lifting stage (241) is provided with a first rotary bar, a second rotary bar and a third rotary bar;
the first rotating rod is used for controlling the movable lifting platform (241) to translate along a first direction;
the second rotating rod is used for controlling the movable lifting platform (241) to translate along a second direction;
the third rotating rod is used for controlling the movable lifting platform (241) to translate along a third direction;
the first direction, the second direction and the third direction are perpendicular to each other.
8. Spotting instrument according to claim 6, characterized in that it further comprises a microscopic observation system (3);
the microscopic observation system (3) comprises a microscope lens (31), a focusing knob (32) and a display screen (33);
the focusing knob (32) is connected with the micro lens (31);
the display screen (33) is connected with the micro lens (31);
the focusing knob (32) is used for adjusting the focal length between the microscope lens (31) and the micro-cantilever sensor chip (4) to be spotted;
the display screen (33) is used for displaying the capillary needle (15), the sample liquid and the micro-cantilever sensor chip (4) to be spotted.
9. Printer according to claim 8 characterized in that the left movement stage (22) is used to move the micro-cantilever sensor chip to be printed (4) under the microscope lens (31) so that the capillary needle (15), the sample liquid and the micro-cantilever sensor chip to be printed (4) are displayed on the display screen.
10. A preparation method of a micro-cantilever sensor chip is characterized in that the preparation method is realized based on a half-contact type sample applicator and comprises the following steps:
mounting a capillary needle at the end of a needle holder;
under the pressure action of pumping sample liquid provided by the injection pump, sucking the sample liquid into the accommodating cavity of the capillary needle through the injection section of the upper needle head of the capillary needle;
placing a micro-cantilever sensor chip to be spotted on an object stage of a moving platform, controlling a moving lifting platform of the moving platform to move, and moving the micro-cantilever sensor chip to be spotted under a microscope lens of the microscopic observation system;
adjusting the movable lifting table of the movable platform and a focusing knob of the microscopic observation system, and adjusting the relative position between the micro-cantilever sensor chip to be spotted and the capillary needle so as to display the micro-cantilever sensor chip to be spotted on a display screen of the microscopic observation system;
controlling a rotating platform of the moving platform to drive a clamp holder to rotate, and adjusting the inclination angle of the injection section of the capillary needle and the micro-cantilever sensor chip to be spotted within a range of [5 degrees, 75 degrees ];
injecting the sample liquid through the injection section of the needle head on the capillary needle under the pressure provided by the injection pump for pushing out the sample liquid, wherein the sample liquid is protruded relative to the injection section;
controlling the left moving platform of the moving platform to enable the protruded sample liquid to be in contact with the micro-cantilever sensor chip to be spotted, and forming sample liquid drops on the micro-cantilever sensor chip to be spotted under the action of tension;
driving the rotating platform of the moving platform to drive the capillary needle to leave the micro-cantilever sensor chip to be spotted, so that the sample liquid drop is disconnected with the injection section of the capillary needle;
and after the solute in the sample liquid drops on the micro-cantilever sensor chip to be spotted volatilizes, repeating the following steps: control moving platform's left side moving platform makes the convex sample liquid with treat the little cantilever beam sensing chip contact of application of sample, under the tension effect, treat to form the sample liquid droplet on the little cantilever beam sensing chip of application of sample, until treat the sample liquid droplet on the little cantilever beam of application of sample and in predetermineeing sample liquid droplet quantity interval, obtain the little cantilever beam sensing chip after the application of sample.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110492715.3A CN113189358B (en) | 2021-05-06 | 2021-05-06 | Semi-contact sample application instrument and preparation method of micro-cantilever sensing chip |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110492715.3A CN113189358B (en) | 2021-05-06 | 2021-05-06 | Semi-contact sample application instrument and preparation method of micro-cantilever sensing chip |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113189358A true CN113189358A (en) | 2021-07-30 |
| CN113189358B CN113189358B (en) | 2023-05-30 |
Family
ID=76983776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110492715.3A Active CN113189358B (en) | 2021-05-06 | 2021-05-06 | Semi-contact sample application instrument and preparation method of micro-cantilever sensing chip |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113189358B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113189357A (en) * | 2021-05-06 | 2021-07-30 | 中国科学院上海微***与信息技术研究所 | Preparation method of dipping type sample applicator and micro-cantilever sensor chip |
| CN116477566A (en) * | 2023-03-23 | 2023-07-25 | 清华大学 | Single-particle microelectrode preparation method based on microcapillary injection |
| CN116539685A (en) * | 2023-03-23 | 2023-08-04 | 清华大学 | Single-particle microelectrode preparation device based on microcapillary injection |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2316045A1 (en) * | 2000-08-16 | 2001-01-30 | University Health Network | Devices and methods for producing microarrays of biological samples |
| US20050266149A1 (en) * | 2004-04-30 | 2005-12-01 | Bioforce Nanosciences | Method and apparatus for depositing material onto a surface |
| US20100028902A1 (en) * | 2007-02-26 | 2010-02-04 | Brown Scott C | Living cell force sensors and methods of using same |
| CN103954786A (en) * | 2014-04-21 | 2014-07-30 | 浙江大学 | Semi-contact under-oil continuous droplet sample applying and liquid adding method |
| CN104492508A (en) * | 2014-11-13 | 2015-04-08 | 浙江大学 | Ultramicro droplets manipulator based on liquid residues and method thereof |
| CN110172399A (en) * | 2019-05-27 | 2019-08-27 | 哈尔滨工业大学 | A kind of ultramicron injection detection based on no lens imaging technology and control device and its method |
| CN111665111A (en) * | 2020-07-03 | 2020-09-15 | 上海百傲科技股份有限公司 | Sample applicator |
| CN111766692A (en) * | 2020-06-18 | 2020-10-13 | 苏州大学 | Automatic fluid infusion microsphere super-resolution microscopic imaging system |
| CN112345524A (en) * | 2020-11-12 | 2021-02-09 | 河北工业大学 | Execution and sensing integrated method and system based on micro-scale bubbles |
-
2021
- 2021-05-06 CN CN202110492715.3A patent/CN113189358B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2316045A1 (en) * | 2000-08-16 | 2001-01-30 | University Health Network | Devices and methods for producing microarrays of biological samples |
| US20050266149A1 (en) * | 2004-04-30 | 2005-12-01 | Bioforce Nanosciences | Method and apparatus for depositing material onto a surface |
| US20100028902A1 (en) * | 2007-02-26 | 2010-02-04 | Brown Scott C | Living cell force sensors and methods of using same |
| CN103954786A (en) * | 2014-04-21 | 2014-07-30 | 浙江大学 | Semi-contact under-oil continuous droplet sample applying and liquid adding method |
| CN104492508A (en) * | 2014-11-13 | 2015-04-08 | 浙江大学 | Ultramicro droplets manipulator based on liquid residues and method thereof |
| CN110172399A (en) * | 2019-05-27 | 2019-08-27 | 哈尔滨工业大学 | A kind of ultramicron injection detection based on no lens imaging technology and control device and its method |
| CN111766692A (en) * | 2020-06-18 | 2020-10-13 | 苏州大学 | Automatic fluid infusion microsphere super-resolution microscopic imaging system |
| CN111665111A (en) * | 2020-07-03 | 2020-09-15 | 上海百傲科技股份有限公司 | Sample applicator |
| CN112345524A (en) * | 2020-11-12 | 2021-02-09 | 河北工业大学 | Execution and sensing integrated method and system based on micro-scale bubbles |
Non-Patent Citations (3)
| Title |
|---|
| 李永海: "生物芯片高效点样微悬臂梁探针的微细加工", 《生物工程学报》, vol. 21, no. 2, 31 March 2005 (2005-03-31) * |
| 王伟: "基于压电振荡原理的微阵列点样***的研制", no. 04 * |
| 贾振中等: "接触式点样机器人及相关技术研究进展", 《机器人》, no. 02, 28 March 2007 (2007-03-28) * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113189357A (en) * | 2021-05-06 | 2021-07-30 | 中国科学院上海微***与信息技术研究所 | Preparation method of dipping type sample applicator and micro-cantilever sensor chip |
| CN116477566A (en) * | 2023-03-23 | 2023-07-25 | 清华大学 | Single-particle microelectrode preparation method based on microcapillary injection |
| CN116539685A (en) * | 2023-03-23 | 2023-08-04 | 清华大学 | Single-particle microelectrode preparation device based on microcapillary injection |
| CN116539685B (en) * | 2023-03-23 | 2024-01-30 | 清华大学 | Single-particle microelectrode preparation device based on microcapillary injection |
| CN116477566B (en) * | 2023-03-23 | 2024-04-09 | 清华大学 | Single-particle microelectrode preparation method based on microcapillary injection |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113189358B (en) | 2023-05-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113189358A (en) | Semi-contact type sample applicator and preparation method of micro-cantilever sensor chip | |
| US9387492B2 (en) | Liquid droplet dispenser | |
| Laurell et al. | Design and development of a silicon microfabricated flow-through dispenser for on-line picolitre sample handling | |
| EP3171985B1 (en) | Piezoelectric dispenser with a longitudinal transducer and replaceable capillary tube | |
| US20040072365A1 (en) | Method and apparatus for liquid dispensing | |
| WO2000001798A2 (en) | Tip design and random access array for microfluidic transfer | |
| KR100736059B1 (en) | Interface patch clamping | |
| WO2010012423A1 (en) | A probe arrangement for exchanging in a controllable way liquids with micro-sized samples of material like biological cells | |
| WO2001048475A1 (en) | Apparatus for and method of making electrical measurements on an object | |
| CN111766692B (en) | Automatic fluid infusion microsphere super-resolution microscopic imaging system | |
| CN113189357A (en) | Preparation method of dipping type sample applicator and micro-cantilever sensor chip | |
| US20090220387A1 (en) | Micro pump device | |
| Bergkvist et al. | Miniaturized flowthrough microdispenser with piezoceramic tripod actuation | |
| JP2002162404A (en) | Liquid dispenser | |
| WO2001019518A1 (en) | Surface tension loading inertial release droplet device and method | |
| CN112874158B (en) | Liquid ejecting unit and liquid ejecting apparatus | |
| JP2004108862A (en) | Dispensing system | |
| CN113164961A (en) | Piezoelectric micropipettor | |
| JP2004239844A (en) | Liquid dispensing device and liquid dispensing method | |
| JP2005040696A (en) | Liquid application method | |
| JP7245135B2 (en) | Pre-wash method, liquid aspirator and pipette | |
| JP2007198166A (en) | Liquid material supply device | |
| JP2021145630A (en) | Droplet discharge unit and droplet discharge device | |
| WO2022093014A1 (en) | Precise fluid manipulation in the femtolitre range | |
| JP6600308B2 (en) | Apparatus for spreading fluid over the entire width of a substrate and method of use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |