CN115078363A - Microfluidic liquid-transfering observation instrument - Google Patents
Microfluidic liquid-transfering observation instrument Download PDFInfo
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- CN115078363A CN115078363A CN202210993075.9A CN202210993075A CN115078363A CN 115078363 A CN115078363 A CN 115078363A CN 202210993075 A CN202210993075 A CN 202210993075A CN 115078363 A CN115078363 A CN 115078363A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/84—Systems specially adapted for particular applications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
Abstract
The application discloses micro-fluidic liquid-transfering visualizer relates to micro-fluidic technique, especially relates to a micro-fluidic liquid-transfering visualizer, and it includes: the device comprises a microfluidic core machine, a sample pumping and injecting mechanism, a controller, a fixed bottom plate and an observation device; the observation device comprises a microscope moving mechanism and a coaxial microscope arranged on the microscope moving mechanism; the microfluidic core machine is arranged on the objective table; the controller is respectively connected with the microfluidic core machine, the sample pumping and injecting mechanism and the observation device and is used for generating corresponding control signals, controlling the microfluidic core machine to control the microfluidic chip, controlling the sample pumping and injecting mechanism to complete pumping and injecting and controlling the observation device to complete shooting of observation images; the sample injection and suction operations aiming at the microfluidic chip can be automatically completed, the complex and repeated sample injection and sampling operations can be replaced by manpower, and the heat dissipation controller can rapidly switch the microfluidic chip in different temperature fields to achieve the temperature conditions required by different reactions.
Description
Technical Field
The application relates to a microfluidic technology, in particular to a microfluidic liquid transfer observation instrument.
Background
With the rapid development of life science and technology, the research work of biochemical laboratories is faced with more complex research objects and increasing sample quantities, the traditional manual operation mode cannot meet the requirements of high efficiency, accuracy and safety in the high-throughput sample processing process, and the automatic operation of part or the whole process in the experimental operation process becomes a necessary trend.
In the prior art, a pipetting workstation can realize the fusion of automatic operation and liquid treatment and the operation of automatic sample adding, reagent distribution and the like of a sample, but cannot perform experiments on a microscopic level, such as screening, culturing and the like of single cells, based on the lack of the application of a digital microfluidic system.
In the prior art, the liquid transfer workstation can not basically finish the experiment of comparing the microscopic level, and is difficult to observe the microscopic level of the reaction product in time.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide the microfluidic core machine which can enable a chip to quickly finish experiments with different temperature requirements.
The purpose of the invention is realized by the following technical scheme:
a microfluidic pipetting scope comprising: the device comprises a microfluidic core machine, a sample pumping and injecting mechanism, a controller, a fixed bottom plate and an observation device; the sample drawing and injecting mechanism, the controller and the observation device are respectively fixedly connected with the fixed bottom plate; the observation device includes: the microscope moving mechanism is arranged on the microscope moving mechanism; the microscope moving mechanism includes: the device comprises a support frame, a focal length adjusting mechanism and a microscope support; the supporting frame is connected with the microscope bracket through a focal length adjusting mechanism; the coaxial microscope is fixed on the microscope bracket; the sample extracting and injecting mechanism comprises a first shaft displacement mechanism, a second shaft displacement mechanism and a vertical shaft displacement mechanism; the vertical shaft displacement mechanism is arranged on the first shaft displacement mechanism, and an electric liquid-transferring gun is also arranged on the vertical shaft displacement mechanism; the second shaft displacement mechanism is connected with an objective table, and a sample box is arranged on the objective table; the microfluidic core machine is arranged on the objective table; the microfluidic core machine is provided with a microfluidic chip; the controller is respectively connected with the microfluidic core machine, the sample pumping and injecting mechanism and the observation device and is used for generating corresponding control signals, controlling the microfluidic core machine to control the microfluidic chip, controlling the sample pumping and injecting mechanism to complete pumping and injecting and controlling the observation device to complete shooting of observation images.
Specifically, the focal length adjusting mechanism comprises a focusing slide rail, a slide rail mounting part and a connecting slide block; the slide rail mounting part is fixedly connected with one end of the focusing slide rail; the sliding rail mounting part is fixedly connected with the supporting frame; the focusing slide rail is connected with the connecting slide block in a sliding way; the connecting slide block is fixedly connected with the microscope bracket.
More specifically, the sample drawing and injecting mechanism further comprises a third axial displacement mechanism; the moving direction of the third axis displacement mechanism is parallel to the moving direction of the first axis displacement mechanism; the objective table is connected with the second shaft displacement mechanism through the third shaft displacement mechanism.
In another specific aspect, the microscope moving mechanism includes a moving platform; the support frame is fixedly connected with the mobile platform; the movable platform comprises a first platform slide rail and a first sliding plate; first platform slide rail fixed mounting is on PMKD, first platform slide rail and first slide sliding connection.
More specifically, the mobile platform further comprises a second platform slide rail and a second sliding plate; the second platform sliding rail is fixedly arranged on the first sliding plate and is connected with the second sliding plate in a sliding manner; the second sliding plate is arranged above the first sliding plate, and the shape and the size of the second sliding plate are matched; the first platform slide rail and the second platform slide rail are respectively arranged on a first side edge and a second side edge of the first sliding plate, and the first side edge and the second side edge are perpendicular to each other; fixedly connected with fixed station on the second slide, fixed station and support frame fixed connection.
More specifically, the mobile platform further comprises a first sub-motor and a second sub-motor, and the focusing slide rail is further connected with a focusing motor; the controller is respectively and independently connected with the first sub motor, the second sub motor and the focusing motor; respectively controlling the positive rotation and the negative rotation of the first sub motor, the second sub motor and the focusing motor; the first sliding plate, the second sliding plate and the first connecting sliding block respectively do reciprocating motion on the first platform sliding rail, the second platform sliding rail and the focusing sliding rail according to the positive rotation and the negative rotation of the first sub motor, the second sub motor and the focusing motor.
In the above, the first axial displacement mechanism includes a first slide rail and a first mounting plate slidably connected to the first slide rail; the vertical shaft displacement mechanism is fixedly connected with the first mounting plate; the vertical shaft displacement mechanism comprises a vertical slide rail and a third mounting plate which is connected with the vertical slide rail in a sliding manner; the electric pipette is fixedly connected with the third mounting plate; the second shaft displacement mechanism comprises a second slide rail and a second mounting plate which is connected with the second slide rail in a sliding manner; the second mounting plate is fixedly connected with the objective table; the first slide rail, the second slide rail and the vertical shaft slide rail are mutually vertical.
Specifically, the vertical axis displacement mechanism further comprises a buffer assembly, an industrial camera, a first group of plates and a second group of plates; the vertical sliding rail is fixedly connected with one side of the first group of plates, and the other side of the first group of plates is fixedly connected with the first mounting plate; one side of the second group of plates is fixedly connected with the third mounting plate, and the other side of the second group of plates is fixedly connected with the industrial camera and the buffer assembly respectively; the buffer assembly comprises a buffer plate, and the electric liquid-transferring gun is fixedly connected with the buffer plate.
In another embodiment, the first axial displacement mechanism further comprises a first motor; the second shaft displacement mechanism further comprises a second motor; the vertical shaft displacement mechanism also comprises a third motor; the controller is respectively and independently connected with the first motor, the second motor and the third motor; respectively controlling the positive rotation and the negative rotation of the first motor, the second motor and the third motor; the first mounting plate, the second mounting plate and the third mounting plate respectively do reciprocating motion on the first slide rail, the second slide rail and the vertical slide rail according to the positive rotation and the negative rotation of the first motor, the second motor and the third motor.
The microfluidic core machine comprises a heat dissipation device and a temperature control platform; the temperature control table comprises a heat dissipation table base, a semiconductor heating sheet and a temperature-equalizing copper sheet which are sequentially overlapped; a thermocouple is arranged in the temperature-equalizing copper sheet; the micro-fluidic chip is arranged on the temperature-equalizing copper sheet; the heat dissipation device comprises a heat dissipation controller, a heat dissipation fan and a plurality of heat dissipation copper pipes; one end of the heat dissipation copper pipe is used for dissipating heat through the heat dissipation fan, and the other end of the heat dissipation copper pipe is arranged in the heat dissipation table base and is fixedly connected with the heat dissipation table base; the heat dissipation controller is respectively and independently connected with the heat dissipation fan, the semiconductor heating plate and the thermocouple; the thermocouple is used for acquiring temperature information of the temperature-equalizing copper sheet; the heat dissipation controller is used for respectively controlling the working states of the heat dissipation fan and the semiconductor heating sheet.
Specifically, a heat-conducting silica gel sheet is arranged between the uniform-temperature copper sheet and the microfluidic chip; the semiconductor heating sheet is tightly connected with the heat dissipation platform base and the temperature-equalizing copper sheet through heat-conducting silicone grease.
In another embodiment, the heat dissipation fan comprises a first heat dissipation fan and a second heat dissipation fan, and the heat dissipation copper pipe is arranged between the first heat dissipation fan and the second heat dissipation fan; and a heat dissipation fin is arranged between the first heat dissipation fan and the second heat dissipation fan and fixedly connected with the heat dissipation copper pipe.
The invention achieves the following beneficial effects: a microfluidic pipetting scope comprising: the device comprises a microfluidic core machine, a sample pumping and injecting mechanism, a controller, a fixed bottom plate and an observation device; the observation device comprises a microscope moving mechanism and a coaxial microscope arranged on the microscope moving mechanism; the microfluidic core machine is arranged on the objective table; the microfluidic core machine is provided with a microfluidic chip; the controller is respectively connected with the microfluidic core machine, the sample pumping and injecting mechanism and the observation device and is used for generating corresponding control signals, controlling the microfluidic core machine to control the microfluidic chip, controlling the sample pumping and injecting mechanism to complete pumping and injecting and controlling the microscope to complete shooting of observation images; the sample injection and suction operations aiming at the microfluidic chip can be automatically completed through the electric pipette which is cooperatively installed by the first shaft displacement mechanism, the second shaft displacement mechanism and the vertical shaft displacement mechanism; the electric pipette can accurately suck a target sample and then inject the target sample into the chip to replace manual work to finish complicated and repeated sample injection and sampling operations, the heat dissipation controller is used for respectively controlling the working states of the heat dissipation fan and the semiconductor heating sheet, so that the micro-fluidic chip can be rapidly switched in different temperature fields to reach temperature conditions required by different reactions, and the temperature control and heat dissipation efficiency is higher; the coaxial microscope can move quickly and stably in the using process of the coaxial microscope through the mobile platform; the height of the microscope can be adjusted in real time by the arranged focal length adjusting mechanism, and the height adjusting mechanism is suitable for the change of the object distance possibly occurring between the microscope and the microfluidic chip. In the scheme of the application, two modes of automatic liquid transfer and automatic control microscope observation are organically combined together, so that the automation of the whole flow of liquid transfer and observation of micro-fluidic is realized; based on the automation of the whole process, the device can be cleanly operated in a closed space in the using process, and the pollution and the external influence are reduced.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present application, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
Fig. 1 is a schematic diagram of an overall structure of a microfluidic pipetting scope according to an embodiment of the present application;
fig. 2 is a schematic structural installation diagram of a sample pumping and injecting mechanism of a microfluidic pipetting scope according to an embodiment of the present application;
FIG. 3 is an exploded view of a microfluidic sample pumping and injecting mechanism according to an embodiment of the present disclosure;
fig. 4 is a schematic diagram of an overall structure of a microfluidic core machine of a microfluidic pipetting scope according to an embodiment of the present application;
fig. 5 is a schematic diagram of an internal structure of a microfluidic core machine of a microfluidic pipetting scope according to an embodiment of the present application;
fig. 6 is a schematic cross-sectional view of an internal structure of a microfluidic core machine of a microfluidic pipetting scope according to an embodiment of the present application;
fig. 7 is an exploded view of the overall structure of a microfluidic core machine of a microfluidic pipetting scope according to an embodiment of the present application;
fig. 8 is a schematic diagram of a first explosion structure of an observation device of a microfluidic pipetting observation instrument according to an embodiment of the present application;
fig. 9 is a schematic diagram of the overall structure of an observation device of a microfluidic pipetting observation instrument according to an embodiment of the present application;
fig. 10 is a schematic rear sectional view of a microfluidic pipetting scope according to an embodiment of the present application;
fig. 11 is a schematic diagram of a second exploded structure of an observation device of a microfluidic pipetting observation instrument according to an embodiment of the present application;
among them, in fig. 1 to 11, include:
1. a microfluidic core machine;
101. a compression cover; 102. arranging flexible wires; 103. injecting a sample hole; 104. a microfluidic chip; 105. positioning the mounting post;
106. positioning the mounting hole; 111. a heat dissipation station base; 112. a temperature-equalizing copper sheet; 113. a semiconductor heating sheet;
114. a thermocouple; 115. a heat-conducting silica gel sheet; 121. a heat dissipation copper pipe; 122. a heat radiation fan; 123. a heat dissipation controller;
124. heat dissipation fins; 131. a main control panel;
2. a sample drawing and injecting mechanism;
200. a first axis displacement mechanism; 201. a first mounting bracket; 202. a first slide rail; 203. a first mounting plate;
204. a first motor;
210. a second shaft displacement mechanism; 211. a second mounting bracket; 212. a second slide rail; 213. a second mounting plate;
214. a connecting plate; 215. an object stage; 216. a slider; 217. a boss portion; 218. A second motor;
220. a vertical axis displacement mechanism; 221. a first set of plates; 222. a vertical slide rail; 223. a third mounting plate;
224. a second set of plates; 225. an industrial camera; 226. a buffer plate; 227. a buffer spring; 228. an electric pipette;
229. a third motor;
230. a gun head box; 231. a sample cartridge; 232. a waste material box;
3. a controller;
4. fixing the bottom plate; 401. a supporting seat; 402. a carrying slide rail; 403. a support column;
411. an upper base plate; 412. a lower base plate; 413. an empty barrier layer;
5. a coaxial microscope; 51. a microscope camera; 52. a camera lens barrel; 53. a microscope objective lens; 54. a microscope light source;
55. a light source barrel; 56. an objective lens rotating table; 57. a lens barrel connecting part;
6. a microscope moving mechanism; 61. a mobile platform; 611. a first platform slide rail; 612. a second platform slide rail;
613. a first sub-motor; 614. a second sub-motor; 615. a fixed table; 616. a first slide plate; 617. a second slide plate;
62. a support frame;
63. a focal length adjustment mechanism;
631. a focusing slide rail; 632. a focusing motor; 633. connecting the sliding block; 634. a slide rail mounting part;
64. a microscope stand; 641. and (4) fixing the ring.
Detailed Description
In order to make the purpose, technical solutions and advantages of the present application clearer, the technical solutions of the present application will be clearly and completely described below through embodiments with reference to the accompanying drawings in the embodiments of the present application, and it is obvious that the described embodiments are some embodiments of the present application, but 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.
Example 1
As shown in fig. 1 to 9, one of the implementation methods of the microfluidic pipetting scope of the present application includes: the device comprises a microfluidic core machine 1, a sample drawing and injecting mechanism 2, a controller 3, a fixed bottom plate 4 and an observation device. The microfluidic core machine 1, the sample drawing and injecting mechanism 2 and the controller 3 are all arranged on the fixed bottom plate 4.
Specifically, as shown in fig. 3, a plurality of supporting seats 401 are disposed on the fixed base plate 4, and each supporting seat 401 is fixedly connected to a corresponding supporting pillar 403.
The sample drawing and injecting mechanism 2 comprises: a first axis displacement mechanism 200, a second axis displacement mechanism 210, and a vertical axis displacement mechanism 220. The first axis displacement mechanism 200, the second axis displacement mechanism 210, and the vertical axis displacement mechanism 220 are reciprocated in three different axial directions, respectively.
The first axis displacement mechanism 200 includes: a first mounting bracket 201, a first slide rail 202, a first mounting plate 203, and a first motor 204. Two ends of the first mounting rack 201 are respectively and fixedly connected with the corresponding supporting columns 403, and the first sliding rail 202 and the first motor 204 are fixedly mounted on the first mounting rack 201; the first mounting plate 203 is slidably connected to the first slide rail 202.
The vertical axis displacement mechanism 220 includes: a first set of plates 221, vertical slide rails 222, a third mounting plate 223, a second set of plates 224, and a third motor 229. The vertical slide rail 222 and the third motor 229 are fixedly connected to one side of the first group plate 221, and the other side of the first group plate 221 is fixedly connected with the first mounting plate 203; one side of the third mounting plate 223 is slidably connected with the vertical slide rail 222; one side of the second group of plates 224 is fixedly connected with the other side of the third mounting plate 223, and the other side of the second group of plates 224 is fixedly provided with an industrial camera 225 and a buffer assembly. Wherein, the buffer assembly comprises a buffer shaft, a buffer plate 226 and a buffer spring 227; the buffer plate 226 is provided with a shaft portion, and the buffer shaft passes through the shaft portion and the buffer spring 227. An electric pipette 228 is fixedly mounted on the buffer plate 226.
The second shaft displacement mechanism 210 includes: a second mounting bracket 211, a second slide rail 212, a second mounting plate 213, a connecting plate 214, and a second motor 218. Two ends of the second mounting bracket 211 are respectively and fixedly connected with the corresponding supporting columns 403, and the second sliding rail 212 and the second motor 218 are fixedly mounted on the second mounting bracket 211; the second mounting plate 213 is slidably connected to the second slide rail 212.
The second mounting plate 213 is fixedly connected to the stage 215 via a connecting plate 214. The object stage 215 is provided with a protrusion 217 and a plurality of mounting slots. The mounting clamping groove is used for fixing the operation box, and the bulge 217 is used for fixing the position of the microfluidic core machine 1. The operation box comprises a sample box 231, a gun head box 230 and a waste box 232.
Further, a carrying slide rail 402 is further arranged on the fixed bottom plate 4, and the sliding direction of the carrying slide rail 402 is the same as that of the second slide rail 212; the object stage 215 is further provided with a plurality of sliding blocks 216, and the sliding blocks 216 are slidably connected with the object slide rails 402.
Further, the controller 3 is separately connected to the first motor 204, the second motor 218, and the third motor 229; the controller 3 is configured to control forward and reverse rotations of the first motor 204, the second motor 218, and the third motor 229, respectively. The first mounting plate 203, the second mounting plate 213 and the third mounting plate 223 respectively reciprocate on the first slide rail 202, the second slide rail 212 and the vertical slide rail 222 according to the forward and reverse rotation of the first motor 204, the second motor 218 and the third motor 229. The first slide rail 202, the second slide rail 212 and the vertical slide rail 222 are perpendicular to each other.
Wherein, the electric pipette 228 realizes the reciprocating motion in the X-axis direction by the first axis displacement mechanism 200, and realizes the reciprocating motion in the Z-axis direction by the vertical axis displacement mechanism 220; the stage 215 is reciprocated in the Y-axis direction by the second axis displacement mechanism 210; and further, the electric pipette 228 can move in three axial directions relative to the stage 215, so that the electric pipette 228 can sample or inject the sample into the microfluidic chip 104.
Specifically, the microfluidic core machine 1 is fixed with a microfluidic chip 104, and a sample injection hole 103 is arranged above the microfluidic chip 104, and the sample injection hole 103 has a positioning and guiding function to a gun head of the electric pipetting gun 228. When injecting samples, the gun head of the electric pipette 228 and the sample injection hole 103 need a certain pressure to seal in a stroke way, and the injection is completed, so a buffer assembly is arranged between the vertical axis displacement mechanisms 220. The vertical axis displacement mechanism 220 drives the electric pipette 228 to move downwards, when the pressure between the electric pipette 228 and the sample injection hole 103 reaches a preset value, the buffer spring 227 starts to compress, the pressure of the electric pipette 228 on the sample injection hole 103 is reduced, the micro-fluidic chip 104 is protected, and then an experimenter can know that the electric pipette 228 is in sealing contact with the sample injection hole 103 according to the phenomenon that the buffer spring 227 is further compressed.
The controller 3 is further internally provided with an upper computer, the electric pipetting gun 228 is connected with the upper computer, and the upper computer is used for adjusting control parameters according to different requirements of the microfluidic chip 104.
The controller 3 controls the sample drawing and injecting mechanism 2 to make the electric pipetting gun 228 and the industrial camera 225 move in a first axial direction and a vertical direction and the object stage 215 move in a second axial direction, so that the electric pipetting gun 228 and the industrial camera 225 move in a third axial direction relative to the object stage 215 to complete the operation of replacing a gun head, sampling or sampling.
The industrial camera 225 is used for providing a full-field instant visual field for the operation of the microfluidic chip 104, and is used for programming or positioning a gun head when adjusting a zero position, so as to further realize automatic sample injection and sampling of the microfluidic chip 104, replace manual completion of complex and repeated sample injection and sampling operations, reduce the manual operation error rate in sample injection and sampling, and improve the experimental efficiency.
More specifically, as shown in fig. 4 to 7, the microfluidic core machine 1 further includes: heat abstractor, temperature control platform and chip controlling means.
The chip control device is connected with the microfluidic chip 104 through the flexible line row 102, and is used for controlling the liquid drops on the microfluidic chip 104. The chip control device includes a main control board 131, and the main control board 131 is connected to the microfluidic chip 104 through the flexible line 102. The main control board 131 is further provided with a power interface and a data interface.
The temperature control platform comprises a heat dissipation platform base 111, a semiconductor heating sheet 113 and a temperature-equalizing copper sheet 112 which are sequentially overlapped. The thermocouple 114 is arranged in the temperature equalizing copper sheet 112, and the thermocouple 114 is used for acquiring temperature information of the temperature equalizing copper sheet 112. The upper surface of the temperature-equalizing copper sheet 112 is concave to form a limit table; the shape and size of the limiting table are matched with those of the microfluidic chip 104. The microfluidic chip 104 is arranged in a limiting table on the temperature-equalizing copper sheet 112. And a heat-conducting silica gel sheet 115 is arranged between the temperature-equalizing copper sheet 112 and the microfluidic chip 104. The semiconductor heating sheet 113 and the heat sink base 111, and the semiconductor heating sheet 113 and the temperature-equalizing copper sheet 112 are tightly connected by heat-conducting silicone grease.
A pressing cover 101 is also arranged on the temperature control table. The pressing cover 101 is provided with a plurality of sample injection holes 103 and a plurality of positioning mounting columns 105, and magnets are arranged in the positioning mounting columns 105. In addition, the microfluidic core machine 1 is further provided with a plurality of positioning and mounting holes 106, the shape, size and position of which are respectively matched with the positioning and mounting columns 105. The pressing cover 101 can tightly press the microfluidic chip 104 on the core machine by using the attraction force of the magnet, and ensure the contact with the heat-conducting silica gel pad.
The heat dissipation device comprises a heat dissipation controller 123, a heat dissipation fan 122 and a plurality of heat dissipation copper pipes 121; one end of the heat dissipation copper pipe 121 dissipates heat through the heat dissipation fan 122, and the other end is sleeved in the heat dissipation platform base 111 (i.e., arranged on the back of the semiconductor heating sheet 113) and is fixedly connected with the heat dissipation platform base 111; the heat dissipation controller 123 is separately connected to the heat dissipation fan 122, the semiconductor heating plate 113, and the thermocouple 114; the heat radiation controller 123 is configured to control the operating states of the heat radiation fan 122 and the semiconductor heating chip 113, respectively.
Specifically, the heat dissipation fan 122 includes a first heat dissipation fan and a second heat dissipation fan, and the heat dissipation copper pipe 121 is disposed between the first heat dissipation fan and the second heat dissipation fan. More specifically, a heat dissipation fin 124 is disposed between the first heat dissipation fan and the second heat dissipation fan, and the heat dissipation fin 124 is fixedly connected to the heat dissipation copper tube 121.
Additionally, the thermocouple 114 is model number PT-1000; the semiconductor heating chip 113 is of the type DHC 19912.
The semiconductor heating sheet 113 is used for carrying heat on both sides of the front and back sides, and when the current direction is reversed, the direction of carrying the heat can be changed, so that the purposes of heating and refrigerating can be achieved without an additional mechanical structure. The heat dissipating copper pipes 121 disposed on the back surface of the semiconductor heating sheet 113 can transport excess heat from the back surface of the semiconductor heating sheet 113 in time while manufacturing a suitable heat dissipating air duct, or supplement enough heat, so that the temperature difference between the front surface and the back surface of the semiconductor heating sheet 113 is reduced, thereby improving the cooling or heat dissipating efficiency of the front surface of the semiconductor heating sheet 113.
Because the semiconductor heating plate 113 does not have a temperature detection function, and meanwhile, due to the reasons of process and the like, the temperature uniformity of the surface of the semiconductor heating plate cannot be well guaranteed, in order to solve the problem, the temperature-equalizing copper sheet 112 is added between the semiconductor heating plate 113 and the microfluidic chip 104, the thermocouple 114 is added in the middle of the temperature-equalizing copper sheet 112, the heat dissipation controller 123 can obtain the temperature of the temperature-equalizing copper sheet 112 arranged below the microfluidic chip 104 by reading a resistance signal of the thermocouple 114, and an estimated value of the current temperature of the microfluidic chip 104 can be calculated according to an experimental comparison relation between the temperature of the microfluidic chip 104 and the temperature of the temperature-equalizing copper sheet 112.
The process of the isothermal copper sheet 112 requires polishing the surface with 2000 mesh sand paper to obtain a mirror surface, so as to ensure that the contact between the copper sheet and the semiconductor heating sheet 113 is close enough. In addition, both sides of the semiconductor heating plate 113 need to be coated with heat conductive silicone grease which is uniform enough and thin as possible to fill up the tiny gaps between the semiconductor heating plate 113 and the heat dissipation platform base 111 and the temperature-equalizing copper sheet 112, eliminate air gaps, ensure the heat conduction mode to be close solid contact, ensure the heat transfer efficiency between the semiconductor heating plate 113 and surrounding objects, and play a role in sticking and fixing to a certain extent. Similarly, the thermocouple 114 and the uniform-temperature copper sheet 112 have a gap required for installation, and in order to eliminate an air gap between the thermocouple 114 and the uniform-temperature copper sheet 112 and obtain the actual temperature of the uniform-temperature copper sheet 112, heat-conducting silicone grease needs to be filled in the installation hole filled with the uniform-temperature copper block of the thermocouple 114, so that an initial positioning effect of a certain degree is achieved, and subsequent adhesive fixation to the thermocouple 114 is facilitated.
Because the matched attaching process of the flexible wire row 102 and the micro-fluidic chip 104 has certain errors, the sufficient attaching degree with the temperature-equalizing copper sheet 112 can not be ensured when the micro-fluidic chip 104 is put in, and the micro-fluidic chip 104 which is a consumable needs to be frequently replaced, and the space between the micro-fluidic chip 104 and the temperature-equalizing copper sheet 112 is not suitable to be filled with heat-conducting silicone grease, a heat-conducting silicone sheet 115 with certain viscosity is attached to the temperature-equalizing copper sheet 112, so that the heat conduction form between the micro-fluidic chip 104 and the temperature-equalizing copper sheet 112 can be ensured to be solid heat conduction, and the effectiveness of the temperature control of the temperature-equalizing copper sheet 112 on the micro-fluidic chip 104 can be ensured.
The microfluidic core machine 1 mixes the microfluidic and the temperature control system, so that the microfluidic chip 104 can be rapidly switched in different temperature fields to achieve temperature conditions required by different reactions, and the efficiency of PCR, cell proliferation, screening and the like in a biological experiment can be greatly improved.
More specifically, the observation device includes: a microscope moving mechanism 6 and a coaxial microscope 5; the microscope moving mechanism 6 includes: a support frame 62, a focal length adjusting mechanism 63 and a microscope stand 64; the supporting frame 62 is connected with a microscope bracket 64 through a focal length adjusting mechanism 63; the coaxial microscope 5 is fixed to the microscope stand 64. Because the chip is not completely transparent, the upright microscope and the inverted microscope cannot allow light to penetrate through the non-transparent area of the chip, so that the microscope can only select the coaxial microscope 5 with the light source and the reflected light coaxial, and observe and polish the microfluidic chip 104 at the same side.
More specifically, the focus adjustment mechanism 63 includes a focus rail 631, a rail mounting portion 634, and a connection slider 633; the slide rail mounting part 634 is fixedly connected with one end of the focusing slide rail 631; the rail mounting portion 634 is fixedly connected with the supporting frame 62; the focusing slide rail 631 is connected with the connecting slide block 633 in a sliding manner; the connecting slide 633 is fixedly connected to the microscope stand 64. Wherein, the focusing slide rail 631 is further connected with a focusing motor 632. By controlling the forward and reverse rotation of the focus motor 632, the link block 633 can reciprocate on the focus slide 631. Because the vertical and horizontal degree of the installation of the observation device cannot completely meet the requirement of the microscope focus, the focal length adjusting mechanism 63 can adjust the height of the microscope in real time in the process of carrying out overall shooting on the microfluidic chip 104 by the coaxial microscope 5, so as to adapt to the change of the object distance possibly occurring between the focal length adjusting mechanism and the microfluidic chip 104.
Further, the microscope stand 64 includes a fixing ring 641, and the fixing ring 641 is used for fixing the coaxial microscope 5.
Further, the on-axis microscope 5 includes a microscope camera 51, a camera lens barrel 52, a barrel connecting portion 57, a microscope objective lens 53, a microscope light source 54, and a light source lens barrel 55; the microscope camera 51, the camera lens barrel 52, the lens barrel connecting part 57 and the microscope objective 53 are connected in sequence and are all arranged on a first axis; the connecting parts of the microscope objective 53, the microscope light source 54 and the light source lens barrel 55 are connected in sequence and are all arranged on the second axis; the first axis and the second axis are perpendicular to each other.
In the present embodiment, the microscope moving mechanism 6 moves the coaxial microscope 5 up and down on the Z axis only by the focal length adjusting mechanism 63; the stage 215 is reciprocated in the Y-axis direction by the second shaft displacement mechanism 210, and relative movement between the coaxial microscope 5 and the stage 215 in the Y-axis direction is realized; to further move the coaxial microscope 5 and the stage 215 in the X-axis direction, a third axis displacement mechanism (not shown) may be added.
Specifically, the moving direction of the third axis displacement mechanism is parallel to the moving direction of the first axis displacement mechanism 200, that is, the slide rail of the third axis displacement mechanism is parallel to the first slide rail 202, the stage 215 is fixedly connected to one movable end of the slide rail of the third axis displacement mechanism, and one fixed end of the slide rail of the third axis displacement mechanism is fixedly connected to the connecting plate 214, so as to realize the reciprocating motion of the stage 215 with respect to the coaxial microscope 5 along the X axis and the Y axis.
Example 2
As shown in fig. 1 to 9, the main technical solution of this embodiment is substantially the same as that of embodiment 1, and the features not explained in this embodiment adopt the explanations in embodiment 1, and are not described again here. This example differs from example 1 in that:
the microscope moving mechanism 6 further includes that the moving platform 61 includes a first platform slide rail 611 and a first slide plate 616; the first platform sliding rail 611 is fixedly installed on the fixed bottom plate 4, and the first platform sliding rail 611 is connected with the first sliding plate 616 in a sliding manner; the support frame 62 is fixedly connected to the first sliding plate 616.
In this embodiment, the coaxial microscope 5 realizes the reciprocating motion in the X-axis direction by the first platform slide rail 611, and the coaxial microscope 5 makes the up-and-down motion in the Z-axis direction by the focal length adjusting mechanism 63; the stage 215 is reciprocated in the Y-axis direction by the second shaft displacement mechanism 210, and relative movement between the coaxial microscope 5 and the stage 215 in the Y-axis direction is realized; thereby, the movement of the coaxial microscope 5 in three axial directions with respect to the stage 215 is realized (without adding the third axial displacement mechanism in embodiment 1).
Example 3
As shown in fig. 1 to 9, the main technical solution of this embodiment is substantially the same as that of embodiment 1 or embodiment 2, and the features that are not explained in this embodiment adopt the explanations in embodiment 1 or embodiment 2, which is not described herein again. This example differs from example 1 or example 2 in that:
the moving platform 61 further comprises a second platform slide rail 612, a first sub-motor 613, a second sub-motor 614, a fixed platform 615 and a second sliding plate 617.
The second platform sliding rail 612 is fixedly installed on the first sliding plate 616, and the second platform sliding rail 612 is slidably connected with the second sliding plate 617. The first sub motor 613 and the second sub motor 614 are connected to the first platform rail 611 and the second platform rail 612, respectively. By controlling the forward and reverse rotation of the first sub-motor 613 and the second sub-motor 614, the first sliding plate 616 and the second sliding plate 617 can reciprocate on the first platform sliding rail 611 and the second platform sliding rail 612, and the coaxial microscope 5 can move quickly and smoothly during use.
Wherein, the second sliding plate 617 is arranged above the first sliding plate 616, and the shape and size are matched; the first platform slide rail 611 and the second platform slide rail 612 are respectively disposed on a first side edge and a second side edge of the first sliding plate 616, and the first side edge and the second side edge are perpendicular to each other.
The second sliding plate 617 is fixedly connected with the fixed table 615; the fixing stage 615 is fixedly connected to one end of the supporting frame 62, and the other end is fixedly connected to the focus adjusting mechanism 63.
In this embodiment, the coaxial microscope 5 can independently complete three axial reciprocating motions through the first platform slide rail 611, the second platform slide rail 612 and the focusing slide rail 631, and since the single observed area of the microscope is generally small, and the whole chip of the microfluidic chip 104 can be used as a reaction area and needs to be observed, the moving platform 61 is required to ensure rapid, stable and high-precision movement, so as to realize accurate photographing of each area of the microfluidic chip 104; because the sample drawing and injecting mechanism 2 and the observation device are mutually independent, the sample drawing and injecting mechanism and the observation device can respectively and completely perform corresponding reciprocating motion in three axial directions, and the moving platform 61 can conveniently set higher control precision in the movement in the X-axis direction and the U-axis direction; in addition, because the sample sampling and injecting mechanism 2 and the observation device are independently arranged, the corresponding software script is relatively simple in control.
Additionally, the steps of photographing using the observation device are as follows:
1. and determining a movement range corresponding to the shooting range according to the size of the microfluidic chip 104 and the relative position of the coaxial microscope 5 and the microfluidic chip.
2. And determining the step length required for each picture mosaic image shooting according to the magnification factor of the microscope lens and the required observation range.
3. And determining the height condition of the microscope in the jigsaw puzzle process according to the focusing conditions of the four corners in the observation range, and automatically focusing.
4. And sequentially shooting the microfluidic chip 104 within the shooting range according to the determined step length.
5. And splicing the shot images.
Example 4
As shown in fig. 1 to 9, the main technical solution of this embodiment is substantially the same as that of embodiment 1, embodiment 2, or embodiment 3, and the characteristics that are not explained in this embodiment adopt the explanations in embodiment 1, embodiment 2, or embodiment 3, and are not described again here. This example differs from example 1 or example 2 or example 3 in that:
the controller 3 comprises an upper computer, a power supply module, a motion control module and a motor driving module. The power supply module is used for supplying power to the upper computer, the motion control module and the motor driving module; the upper computer, the motion control module and the motor driving module are connected in sequence.
The upper computer is used for sending a control instruction to the motion control module; the motion control module stores step length information or position information corresponding to each motor corresponding to each control instruction, generates a driving instruction corresponding to each motor according to the received step length information or position information corresponding to the control instruction, and respectively sends each driving instruction to the motor driving module, so as to drive the corresponding motor to perform forward rotation and reverse rotation, thereby completing corresponding coordination motion (for example, controlling the sample sampling and injecting mechanism 2 to complete sampling and sampling operations, and controlling the observation device to complete shooting operation of the microfluidic chip 104).
Example 5
As shown in fig. 10 and 11, the main technical solution of this embodiment is substantially the same as that of embodiment 1 or embodiment 2 or embodiment 3 or embodiment 4, and the characteristics that are not explained in this embodiment adopt the explanations in embodiment 1 or embodiment 2 or embodiment 3 or embodiment 4, and are not described again here. This example differs from example 1 or example 2 or example 3 or example 4 in that:
the second mounting bracket 211 is arranged at one side of the object stage 215, and the second mounting bracket 211 is fixedly connected with the fixed base plate 4; the object slide 402 is disposed on the other side of the object table 215.
Further, the fixed base plate 4 comprises an upper base plate 411 and a lower base plate 412, and a space 413 is formed between the upper base plate 411 and the lower base plate 412; the controller 3 is disposed within the air separation layer 413.
Furthermore, the movable platform 61 is fixedly connected to the lower plate 412, the upper plate 411 is provided with a microscope mounting opening (not shown), the supporting frame 62 passes through the microscope mounting opening, one end of the supporting frame 62 is fixedly connected to the movable platform 61 in the hollow partition 413, and the other end of the supporting frame 62 extends out of the microscope mounting opening of the fixed plate 4 and is fixedly connected to the focus adjusting mechanism 63.
The controller 3 and the mobile platform 61 are arranged in the space layer 413, so that the whole structure is more compact, the temporary area is reduced, and the miniaturization of equipment is facilitated.
Further, a heat dissipation fan (not shown) is disposed at a side of the fixing base plate 4 for dissipating heat from the controller 3.
Further, the coaxial microscope 5 further includes an objective lens rotating stage 56, and the objective lens rotating stage 56 is fixedly connected to the barrel connecting portion 57; the objective revolver 56 is connected to the microscope objective 53 via a rotary shaft. The microscope objective 53 includes a plurality of objective lenses, and the objective lenses can be switched according to actual needs.
It is to be noted that the foregoing is only illustrative of the preferred embodiments of the present application and the technical principles employed. It will be understood by those skilled in the art that the present application is not limited to the particular embodiments described herein, but is capable of various obvious changes, rearrangements and substitutions as will now become apparent to those skilled in the art without departing from the scope of the application. Therefore, although the present application has been described in more detail with reference to the above embodiments, the present application is not limited to the above embodiments, and may include other equivalent embodiments without departing from the spirit of the present application, and the scope of the present application is determined by the scope of the appended claims.
Claims (12)
1. A microfluidic pipetting scope, comprising: the device comprises a microfluidic core machine, a sample pumping and injecting mechanism, a controller, a fixed bottom plate and an observation device;
the observation device includes: the microscope moving mechanism is arranged on the microscope moving mechanism; the microscope moving mechanism includes: the device comprises a support frame, a focal length adjusting mechanism and a microscope support; the support frame is connected with the microscope support through the focal length adjusting mechanism; the coaxial microscope is fixed on the microscope bracket;
the sample drawing and injecting mechanism, the controller and the microscope moving mechanism are respectively fixedly connected with the fixed bottom plate;
the sample extracting and injecting mechanism comprises a first shaft displacement mechanism, a second shaft displacement mechanism and a vertical shaft displacement mechanism;
the vertical shaft displacement mechanism is arranged on the first shaft displacement mechanism, and an electric pipetting gun is also arranged on the vertical shaft displacement mechanism;
the second shaft displacement mechanism is connected with an object stage, and a sample box is arranged on the object stage; the microfluidic core machine is arranged on the objective table; the microfluidic core machine is provided with a microfluidic chip;
the controller is respectively connected with the microfluidic core machine, the sample sampling and injecting mechanism and the observation device and is used for generating corresponding control signals, controlling the microfluidic core machine to control the microfluidic chip, controlling the sample sampling and injecting mechanism to complete sampling and injecting and controlling the observation device to complete shooting of observation images.
2. A microfluidic pipetting scope as recited in claim 1 wherein:
the focal length adjusting mechanism comprises a focusing slide rail, a slide rail mounting part and a connecting slide block;
the slide rail mounting part is fixedly connected with one end of the focusing slide rail; the sliding rail mounting part is fixedly connected with the supporting frame;
the focusing slide rail is connected with the connecting slide block in a sliding manner; the connecting slide block is fixedly connected with the microscope bracket.
3. A microfluidic pipetting scope as recited in claim 2 wherein:
the sample drawing and injecting mechanism also comprises a third axial displacement mechanism;
the moving direction of the third axis displacement mechanism is parallel to the moving direction of the first axis displacement mechanism;
the object stage is connected with the second shaft displacement mechanism through the third shaft displacement mechanism.
4. A microfluidic pipetting scope as recited in claim 2 wherein:
the microscope moving mechanism comprises a moving platform;
the support frame is fixedly connected with the mobile platform;
the mobile platform comprises a first platform slide rail and a first sliding plate;
the first platform sliding rail is fixedly installed on the fixed base plate and is connected with the first sliding plate in a sliding mode.
5. A microfluidic pipetting scope as recited in claim 4 wherein:
the mobile platform also comprises a second platform slide rail and a second slide plate;
the second platform sliding rail is fixedly arranged on the first sliding plate and is connected with the second sliding plate in a sliding manner;
the second sliding plate is arranged above the first sliding plate, and the shape and the size of the second sliding plate are matched;
the first platform slide rail and the second platform slide rail are respectively arranged on a first side edge and a second side edge of the first sliding plate, and the first side edge and the second side edge are perpendicular to each other;
and the second sliding plate is fixedly connected with a fixed table, and the fixed table is fixedly connected with the support frame.
6. A microfluidic pipetting scope as recited in claim 5 wherein:
the moving platform further comprises a first sub motor and a second sub motor, and the focusing slide rail is further connected with a focusing motor;
the controller is respectively and independently connected with the first sub motor, the second sub motor and the focusing motor; the positive rotation and the negative rotation of the first sub motor, the second sub motor and the focusing motor are respectively controlled;
and the first sliding plate, the second sliding plate and the first connecting sliding block respectively reciprocate on the first platform sliding rail, the second platform sliding rail and the focusing sliding rail according to the positive rotation and the negative rotation of the first sub motor, the second sub motor and the focusing motor.
7. A microfluidic pipetting scope as recited in any of claims 1-6 wherein:
the first shaft displacement mechanism comprises a first slide rail and a first mounting plate which is connected with the first slide rail in a sliding manner;
the vertical shaft displacement mechanism is fixedly connected with the first mounting plate;
the vertical shaft displacement mechanism comprises a vertical slide rail and a third mounting plate which is connected with the vertical slide rail in a sliding manner; the electric pipette is fixedly connected with the third mounting plate;
the second shaft displacement mechanism comprises a second slide rail and a second mounting plate which is connected with the second slide rail in a sliding manner; the second mounting plate is fixedly connected with the objective table;
the first slide rail, the second slide rail and the vertical shaft slide rail are mutually vertical in pairs.
8. A microfluidic pipetting scope as recited in claim 7 wherein:
the vertical axis displacement mechanism also comprises a buffer component, an industrial camera, a first group of plates and a second group of plates;
the vertical sliding rail is fixedly connected with one side of the first group of plates, and the other side of the first group of plates is fixedly connected with the first mounting plate;
one side of the second group of plates is fixedly connected with the third mounting plate, and the other side of the second group of plates is fixedly connected with the industrial camera and the buffer assembly respectively;
the buffer assembly comprises a buffer plate, and the electric pipette is fixedly connected with the buffer plate.
9. A microfluidic pipetting scope as recited in claim 7 wherein:
the first axial displacement mechanism further comprises a first motor; the second shaft displacement mechanism further comprises a second motor; the vertical shaft displacement mechanism further comprises a third motor;
the controller is respectively and independently connected with the first motor, the second motor and the third motor; respectively controlling the positive rotation and the negative rotation of the first motor, the second motor and the third motor;
and the first mounting plate, the second mounting plate and the third mounting plate respectively do reciprocating motion on the first slide rail, the second slide rail and the vertical slide rail according to the positive rotation and the negative rotation of the first motor, the second motor and the third motor.
10. A microfluidic pipetting scope as recited in any of claims 1-6 wherein:
the microfluidic core machine comprises a heat dissipation device and a temperature control platform;
the temperature control table comprises a heat dissipation table base, a semiconductor heating sheet and a temperature-equalizing copper sheet which are sequentially overlapped; a thermocouple is arranged in the temperature-equalizing copper sheet; the micro-fluidic chip is arranged on the uniform-temperature copper sheet;
the heat dissipation device comprises a heat dissipation controller, a heat dissipation fan and a plurality of heat dissipation copper pipes; one end of the heat dissipation copper pipe is used for dissipating heat through the heat dissipation fan, and the other end of the heat dissipation copper pipe is arranged in the heat dissipation table base and is fixedly connected with the heat dissipation table base; the heat dissipation controller is respectively and independently connected with the heat dissipation fan, the semiconductor heating plate and the thermocouple;
the thermocouple is used for acquiring temperature information of the temperature-equalizing copper sheet; the heat dissipation controller is used for respectively controlling the working states of the heat dissipation fan and the semiconductor heating sheet.
11. A microfluidic pipetting scope as recited in claim 10 wherein:
a heat-conducting silica gel sheet is also arranged between the temperature-equalizing copper sheet and the microfluidic chip;
the semiconductor heating sheet is tightly connected with the heat dissipation platform base and the temperature-equalizing copper sheet through heat-conducting silicone grease.
12. A microfluidic pipetting scope as recited in claim 10 wherein:
the heat dissipation fan comprises a first heat dissipation fan and a second heat dissipation fan, and the heat dissipation copper pipe is arranged between the first heat dissipation fan and the second heat dissipation fan;
and heat dissipation fins are arranged between the first heat dissipation fan and the second heat dissipation fan and are fixedly connected with the heat dissipation copper pipe.
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Effective date of registration: 20240410 Address after: Room 203, Building 3, Software Park, No. 78 Keling Road, High tech Zone, Suzhou City, Jiangsu Province, 215163 Patentee after: Suzhou Aosu Qicheng Technology Co.,Ltd. Country or region after: China Address before: 528000 room 201-1, building A2, Foshan tongchu Logistics Co., Ltd., No. 1, Xianan Road, Guicheng Street, Nanhai District, Foshan City, Guangdong Province Patentee before: Guangdong aosu liquid core micro nano technology Co.,Ltd. Country or region before: China |