CN113567397B - Microfluidic chip, microfluidic chip channel positioning structure and positioning method - Google Patents

Microfluidic chip, microfluidic chip channel positioning structure and positioning method Download PDF

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CN113567397B
CN113567397B CN202110927521.1A CN202110927521A CN113567397B CN 113567397 B CN113567397 B CN 113567397B CN 202110927521 A CN202110927521 A CN 202110927521A CN 113567397 B CN113567397 B CN 113567397B
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micro
channel
positioning
chip
microfluidic chip
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CN113567397A (en
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陈谦
张路
刘泓
杜从柱
赵俊岭
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Suzhou Suozhen Biotechnology Co ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/4788Diffraction
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated

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  • Health & Medical Sciences (AREA)
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  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
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Abstract

The invention relates to a micro-fluidic chip, a micro-fluidic chip channel positioning structure and a positioning method, which are characterized in that the micro-fluidic chip comprises a plurality of micro-channels, an initial positioning frame, a first positioning marking line and a second positioning marking line; the micro channels are longitudinally arranged at intervals; the right side of the micro-channel is provided with the initial positioning frame; the left side of the top of the initial positioning frame is provided with a first positioning marking which is arranged on one side of the central extension line of the micro-channel and used for positioning the rightmost position of the micro-channel; the left side of the micro-channel is provided with a second positioning marking, and the second positioning marking is arranged on the other side of the central extension line of the micro-channel and used for positioning the leftmost position of the micro-channel. According to the invention, through the arranged micro-fluidic chip structure, the initial positioning precision of the whole equipment structure can be reduced.

Description

Microfluidic chip, microfluidic chip channel positioning structure and positioning method
Technical Field
The invention relates to a micro-fluidic chip, a micro-fluidic chip channel positioning structure and a positioning method, and relates to the technical field of biological detection.
Background
The microfluidic chip technology integrates basic operation units of sample preparation, reaction, separation, detection and the like in biological, chemical and medical analysis processes on a micron-scale chip, and automatically completes the whole analysis process. Because of its great potential in biological, chemical, medical and other fields, it has been developed into a new research field where the disciplines of biology, chemistry, medicine, fluids, electronics, materials, machinery and the like are crossed.
When optical focus positioning is performed in medical microfluidic devices, most of the devices are produced by the devices at present, after focus is positioned by a structure, the focus position is not adjusted, so that a problem is generated, if components are displaced, the focus is deviated, and test data are unstable.
In the prior art, the matching of the chip channel width and the light spot is calculated by theory, so that the relative position of the optical probe and the chip is fixed, and the method comprises two modes: 1) The vertical position of the optical probe is fixed and the size of the light spot is not regulated through vertical movement, and the mode has simple structure, but because the optical probe is close to the position of the chip, the optical probe is positioned at a position which is easy to touch after the chip is removed, but the optical probe is a device with high cleanliness, so that the optical probe is easy to be polluted, light spot divergence is caused, and positioning and testing effects are affected; in addition, when only fixing the optical probe, when placing the chip, the position at every turn all can have corresponding difference (structure positioning accuracy, chip machining accuracy) and cause the facula size to have the variation with the size of passageway, can cause the size of at every turn test facula on the passageway different, can influence the difference of the fluorescence excitation intensity in the location of passageway and the test (influenced by the absorptive light intensity of liquid drop, the more concentrated the facula, the bigger the coverage liquid drop area, the intensity of light is stronger). 2) The optical probe can move in the vertical direction, and each movement is a fixed position, so that the optical probe can be moved downwards to an inaccessible position, and the optical probe is effectively prevented from being polluted. However, in the vertical movement process, the position of the movable platform is different and the uncertainty is larger under the influence of the precision of the movable platform.
Disclosure of Invention
In view of the above problems, it is an object of the present invention to provide a microfluidic chip capable of reducing the positioning accuracy of the overall device structure.
The second object of the present invention is to provide a microfluidic chip channel positioning structure capable of positioning all microfluidic channels, so that droplets flowing in the microfluidic channels are completely covered by a focusing light spot to the greatest extent.
The invention further provides a positioning method of the microfluidic chip channel.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
In a first aspect, the present invention provides a microfluidic chip comprising a plurality of microchannels, an initial positioning frame, a first positioning reticle and a second positioning reticle;
The micro channels are longitudinally arranged at intervals;
The right side of the micro-channel is provided with the initial positioning frame;
The left side of the top of the initial positioning frame is provided with a first positioning marking which is arranged on one side of the central extension line of the micro-channel and used for positioning the rightmost position of the micro-channel;
the left side of the micro-channel is provided with a second positioning marking, and the second positioning marking is arranged on the other side of the central extension line of the micro-channel and used for positioning the leftmost position of the micro-channel.
Further, the micro-channels adopt a structure with narrow middle and wide sides, and the sizes of the channels on the two sides of the wide sides of each micro-channel are the same.
Further, the initial positioning frame adopts a square channel structure, and the upper left frame of the square channel structure and the first positioning marking are both positioned on the central extension line of the narrow side of the micro channel.
Further, the first positioning mark line adopts a cross mark line, and the second positioning mark line adopts a linear mark line.
In a second aspect, the present invention further provides a microfluidic chip channel positioning structure for positioning the microfluidic chip, where the structure includes:
the chip pressing and photoelectric conversion module is arranged above the microfluidic chip and is used for acquiring optical signals emitted by the light source and irradiated on different positions of the microfluidic chip and converting the optical signals into electric signals;
The chip supporting structure is arranged below the microfluidic chip and used for supporting and fixing the microfluidic chip;
The optical probe is used for focusing the optical signal emitted by the light source;
The micro-motion module is used for connecting the optical probe to enable the optical probe to move;
the AD data acquisition module is used for acquiring the electric signals of the chip pressing and photoelectric conversion module;
the data analysis module is used for analyzing the electric signals of the AD data acquisition module;
and the motor control module is used for controlling the optical probe to move and changing the relative position of the optical probe and the micro-fluidic chip channel so that the focus of the focusing light spot corresponds to the micro-channel position.
Further, the process of focusing the spot focus to the microchannel position includes:
the optical signals generated when the light spots pass through the micro-channels are converted into electric signals after being collected, and quantized data are collected through the AD data collecting module;
The micro-motion module is close to or far from the micro-channel through the Z axis, the position of the light spot in the micro-channel is adjusted, and the optical corresponding curve of the light spot passing through the micro-channel is recorded through the X axis movement;
And analyzing the light spot position through the relation between the light spot position and the acquired waveform of the AD data acquisition module.
Further, the relation between the light spot position and the acquired waveform of the AD data acquisition module is as follows:
first case: when the size of the light spot irradiated on the micro-channel is larger than that of the micro-channel, the AD data acquisition waveform is wider;
second case: when the size of the light spot irradiated on the micro-channel is equal to that of the micro-channel, the AD data acquisition waveform is narrowed, and the amplitude is increased;
Third case: when the size of the light spot irradiated on the micro-channel is smaller than that of the micro-channel, the AD data acquisition waveform is in a bimodal state, the width is approximately equal to that of the light spot irradiated on the micro-channel, the size of the light spot irradiated on the micro-channel is equal to that of the micro-channel, and the amplitude is larger.
Further, the chip pressing and photoelectric conversion module adopts three silicon photocells to collect light signals.
In a third aspect, the present invention further provides a method for positioning the microfluidic chip based on the positioning structure of the microfluidic chip channel, including the steps of:
the micro-fluidic chip channel positioning structure is arranged on the micro-fluidic chip;
moving the optical probe along the Z axis to enable the light spot to move to an initial positioning frame;
Moving the optical probe along the Y axis, and searching an upper frame of an initial positioning frame of the micro-fluidic chip;
Moving to the left upper corner of the initial positioning frame A, moving along the X axis, and ensuring that no angle offset exists between the moving direction of the optical probe and the microfluidic chip by searching the first positioning marking line and the second positioning marking line;
Moving the optical probe along the Y axis, checking waveforms from the beginning of the optical probe passing through the upper frame of the initial positioning frame to the end of the optical probe leaving the upper frame of the initial positioning frame, judging whether the current focus is on the microfluidic channel, if not, moving the Z axis, and if not, finishing the positioning of the optical focus;
the XY direction is parallel to the plane of the micro-channel chip, and the Z axis is perpendicular to the plane of the micro-channel chip.
Further, in the moving process of the optical probe, the AD data acquisition waveform feedback is used as a judging basis for judging whether the movement is finished or not.
Due to the adoption of the technical scheme, the invention has the following advantages:
1. The micro-fluidic chip comprises a plurality of micro-channels, an initial positioning frame, a first positioning marking line and a second positioning marking line, and the initial positioning accuracy of the whole equipment structure can be reduced through the structural design of the micro-fluidic chip;
2. The micro-fluidic chip channel positioning structure comprises a chip pressing and photoelectric conversion module, a chip supporting structure, an optical probe, a micro-motion module, an AD data acquisition module, a data analysis module and a motor control module, wherein the relative position of the optical probe and a micro-fluidic chip channel is changed by controlling the movement of the optical probe, so that a focus of a focusing light spot corresponds to the position of the micro-channel, and liquid drops flowing in the micro-channel are completely covered by the light signals of the focusing light spot and shot at different positions of the micro-fluidic chip to the greatest extent;
3. the positioning method of the microfluidic chip can be used for positioning the micro-channels in the microfluidic chip by using the diffraction and reflection method of light, so that the aim of positioning all the micro-fluidic channels is fulfilled, and misjudgment is reduced;
in conclusion, the invention can be widely applied to biological detection.
Drawings
Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the invention. Like parts are designated with like reference numerals throughout the drawings. In the drawings:
FIG. 1 is a schematic view of a microfluidic chip according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of a positioning structure according to an embodiment of the present invention;
FIG. 3 is a hardware system frame diagram of an embodiment of the invention;
FIG. 4 is a diagram illustrating a structure of a chip bonding and photoelectric conversion module according to an embodiment of the present invention;
FIG. 5 is a schematic diagram of a positioning structure according to an embodiment of the present invention;
FIG. 6 is a light path diagram of a positioning structure according to an embodiment of the present invention;
FIG. 7 is a diagram showing the correspondence between the positions of light spots and AD data acquisition waveforms according to an embodiment of the present invention;
FIG. 8 is a plot of the correspondence between spot locations and AD data acquisition waveforms in an embodiment of the present invention;
FIG. 9 is a diagram showing the correspondence between the positions of light spots and AD data acquisition waveforms according to an embodiment of the present invention;
FIG. 10 is a schematic diagram of an AD data acquisition waveform of an embodiment of the invention;
FIG. 11 is a chip channel state diagram of an embodiment of the invention;
Fig. 12 is a microfluidic channel localization map of an embodiment of the present invention;
FIG. 13 is a waveform diagram of data acquisition according to an embodiment of the present invention;
FIG. 14 is a waveform diagram of data acquisition according to an embodiment of the present invention;
fig. 15 is a waveform diagram of data acquisition according to an embodiment of the present invention.
Detailed Description
Exemplary embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. While exemplary embodiments of the present invention are shown in the drawings, it should be understood that the present invention may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
It is to be understood that the terminology used herein is for the purpose of describing particular example embodiments only, and is not intended to be limiting. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. The terms "comprises," "comprising," "includes," "including," and "having" are inclusive and therefore specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. The method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order described or illustrated, unless an order of performance is explicitly stated. It should also be appreciated that additional or alternative steps may be used.
Although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms may be only used to distinguish one element, component, region, layer or section from another region, layer or section. Terms such as "first," "second," and other numerical terms when used herein do not imply a sequence or order unless clearly indicated by the context. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the example embodiments.
For ease of description, spatially relative terms, such as "inner," "outer," "lower," "upper," and the like, may be used herein to describe one element or feature's relationship to another element or feature as illustrated in the figures. Such spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures.
The invention provides a micro-fluidic chip, a micro-fluidic chip channel positioning structure and a positioning method, wherein the micro-fluidic chip comprises a plurality of micro-channels, an initial positioning frame, a first positioning marking line and a second positioning marking line; the micro channels are longitudinally arranged at intervals; an initial positioning frame is arranged on the right side of the micro-channel; the left side of the top of the initial positioning frame is provided with a first positioning marking which is arranged on one side of a central extension line of the micro-channel and used for positioning the rightmost position of the micro-channel; the left side of the micro-channel is provided with a second positioning marking, and the second positioning marking is arranged on the other side of the central extension line of the micro-channel and used for positioning the leftmost position of the micro-channel. According to the invention, through the arranged micro-fluidic chip structure, the initial positioning precision of the whole equipment structure can be reduced.
Example 1
As shown in fig. 1, the microfluidic chip provided in this embodiment includes an initial positioning frame a, a positioning reticle B, a plurality of micro channels C, and a positioning linear reticle D.
The micro-channels C are longitudinally arranged at intervals, an initial positioning frame A is arranged on the right side of the micro-channel C, a positioning cross mark B is arranged on the left side of the top of the initial positioning frame A, and the positioning cross mark B is arranged on an extension line on one side of the center of the micro-channel C and used for positioning the rightmost position of the micro-channel C. The left side of the micro-channel C is provided with a positioning linear marking D which can be arranged on the extension line of the other side of the center of the micro-channel C and used for positioning the leftmost position of the micro-channel C.
In some preferred embodiments of the present invention, the longitudinal spacing between adjacent micro-channels C may be set to 100um, the micro-channels C adopt a channel structure with a narrow middle and wide two sides, the sizes of the channels on both sides of the micro-channels C are the same, and may be 20um, and the size of the middle channel of the micro-channels C may be 10um, which is not limited to this and may be determined according to practical needs.
In some preferred embodiments of the present invention, the initial positioning frame a may be a square channel frame, and in this embodiment, a square with an outer side length of 0.2mm is used, and the channel size may be 20um, which is not limited to this, and may be determined according to practical needs.
In some preferred embodiments of the present invention, the positioning reticle B and the positioning reticle D are used to confirm whether the microfluidic chip channel and the moving direction of the moving platform have angular displacement, the transverse and longitudinal lengths of the positioning reticle B are 0.1mm, the length of the positioning reticle D is 0.1mm, and the channel sizes of the positioning reticle B and the positioning reticle D are 20um, which is not limited thereto and can be determined according to practical needs.
Example two
As shown in fig. 2 and 3, the micro-fluidic chip channel positioning structure provided in this embodiment is used for positioning the micro-fluidic chip provided in the first embodiment, and positioning the size of a focusing light spot and a micro-fluidic chip channel, and includes a chip pressing and photoelectric conversion module 1, a chip supporting structure 2, an optical probe 3, a micro-motion module 4, an AD data acquisition module 5, a data analysis module 6, and a motor control module 7.
The chip pressing and photoelectric conversion module 1 is arranged above the microfluidic chip and is used for acquiring optical signals of light spots emitted by the light source and irradiated on different positions of the microfluidic chip and converting the optical signals into analog electric signals.
And the chip supporting structure 2 is arranged below the microfluidic chip and is used for supporting and fixing the microfluidic chip.
And the optical probe 3 is arranged below the microfluidic chip and is used for focusing the optical signals emitted by the light source.
And the micro-motion module 4 is used for connecting the optical probe 3 and driving the optical probe 3 to move so that the optical probe 3 can perform corresponding movements of XY and focusing Z axes. The micro-motion module 4 may adopt an existing structure, and includes a micro-motion platform, a motor driver and a motor controller, where the motor controller is controlled by a computer to send an instruction to the motor driver to drive a motor in the micro-motion platform, so that the micro-motion platform moves in a corresponding direction.
The AD data acquisition module 5 is used for acquiring the electric signals of the chip pressing and photoelectric conversion module 1.
The data analysis module 6 is used for analyzing the electric signals of the AD data acquisition module 5.
The motor control module 7 is configured to control the movement of the optical probe 3, and change the relative position of the optical probe 3 and the channel of the microfluidic chip, so that the focal point of the focused light spot corresponds to the position of the micro channel, specifically, the optical probe can move along XY direction (move parallel to the micro channel chip without changing the distance between the micro channel chip and the optical probe), and can move along Z direction (change the distance between the micro channel chip and the optical probe) to change the size of the light spot at the chip position.
In some preferred embodiments of the present invention, the chip pressing and photoelectric conversion module 1 converts light intensity into a voltage signal through sensing light, so as to facilitate the data acquisition of the AD data acquisition module 5, where the acquired light signal is that the light source irradiates different positions of the microfluidic chip through focused light spots, for example, different optical signals occur at different channel positions. For example, as shown in fig. 4, the chip pressing and photoelectric conversion module 1 may collect optical signals by using three silicon photocells, and emit parallel laser beams from a light source, and after the optical probe 3 focuses the light spots and determines the relative vertical position of the focus, when the light passes through the non-channel position of the micro-channel chip, the silicon photocells (photoelectric conversion) have no voltage feedback and are always noise-reduced. When light passes through the channel position of the micro-channel chip, if the channel and the 2#3 silicon photocell are in a vertical state, the 2#3 silicon photocell has corresponding waveforms, if the channel and the 2#3 silicon photocell are in a parallel state, the 1#silicon photocell has corresponding waveforms, and the light signal collection by the three silicon photocells is in the prior art, and is not repeated here.
In some preferred embodiments of the present invention, the focusing light source focuses on the micro-fluidic chip channel, and the automatic focusing light spot focus corresponds to the micro-channel position, specifically, the diameter of the focusing light spot falling on the channel position through the optical probe 3 is consistent with the width of the micro-channel, so that the liquid drop flowing in the micro-channel is completely covered by the focusing light spot to the maximum extent, and the process includes:
When the light spots pass through the micro-channel, the light signals generated by the diffraction reflection grating (the reflection grating is formed by the light signals generated by the light source light spots irradiating the channel of the micro-fluidic chip) are converted into analog electric signals through the silicon photocell, and quantized data acquisition is carried out through the AD data acquisition module 5.
The micro-motion module 4 is close to or far from the micro-channel through the Z axis, adjusts the position of the light spot in the micro-channel, and uses the silicon photocell and the AD data acquisition module 5 to record the optical corresponding curve of the light spot passing through the micro-channel through the X axis, wherein, as shown in FIG. 13, the abscissa of the optical corresponding curve is the displacement of the micro-motion module, and the ordinate is the light intensity corresponding to the optical signal converted into the digital signal.
The spot position is analyzed by the relation between the spot position and the waveform acquired by the AD data acquisition module 5.
The optical probe 3, the light source and the micro-motion module are fixed together, and the relative positions of the focus and the micro-channel are adjusted by moving the micro-motion module in the Z direction. And judging the position of the micro-channel formed when light passes through the micro-channel by moving the micro-motion module X, and the size of the light spot.
Further, the corresponding relation between the light spot position and the acquired waveform of the AD data acquisition module 5 comprises:
First case: as shown in fig. 7, the spot size irradiated on the micro-channel is larger than that of the micro-channel, and the waveform is wider when the spot size irradiated on the micro-channel is larger than that of the micro-channel.
Second case: as shown in fig. 8, the size of the spot irradiated on the micro-channel is equal to that of the micro-channel, and when the size of the spot irradiated on the micro-channel is equal to that of the micro-channel, the AD acquisition waveform becomes narrow and the amplitude becomes high.
Third case: as shown in fig. 9, the spot size of the light irradiated on the micro-channel is smaller than that of the micro-channel. When the size of the light spot irradiated on the micro-channel is smaller than that of the micro-channel, the AD data acquisition waveform is in a bimodal state, the width is approximately equal to that of the light spot irradiated on the micro-channel, the size of the light spot irradiated on the micro-channel is equal to that of the micro-channel, and the amplitude is larger.
In summary, when the droplet passes through the channel, the size of the light spot irradiated on the micro-channel can be obtained, and the width, amplitude and peak number of the waveform can be obtained from the AD data acquisition through corresponding logic. As shown in fig. 10, the spot size required to achieve the present invention is ultimately consistent with the microchannel width. As shown in fig. 11, this position is a channel for focusing the laser, and the purpose of this embodiment is to focus the focused light spot emitted by the laser module at this channel position.
Example III
The method for positioning the micro-fluidic chip channel according to the first embodiment of the present invention based on the positioning structure according to the second embodiment of the present invention includes the steps of:
s1, mounting a channel positioning structure of a microfluidic chip on the microfluidic chip
Specifically, when the micro-fluidic chip channel positioning structure of the present embodiment is installed, it is ensured that after the chip is pressed and the photoelectric conversion module 1 is pressed, the initial position of the optical probe 3 is placed in the initial positioning frame a, and the XY movement of the optical probe is ensured, as shown in the coordinates of fig. 3. And the rotation angle of the micro-fluidic chip and the micro-fluidic chip is within a preset acceptable range. Preferably, the rotation angle within the acceptance range may be manually confirmed first by the structure and second may be judged by the movement waveform from the positioning point ② to the positioning point ④ as shown in fig. 12.
S2, moving the optical probe along the Z axis to enable the light spot to move to an initial positioning frame A
As shown in fig. 12, the spot is moved to an initial positioning point ① within initial positioning frame a and it is confirmed whether the initial positioning point ① is positioned correctly: the control spot moves a distance to the left from the initial positioning point ① and analyzes the AD data acquisition waveform feedback in real time, if so, returns to the initial positioning point ① and then moves upward a certain distance, and checks whether the AD data acquisition waveform is as in fig. 13, if so, the initial positioning point ① confirms.
And S3, moving the optical probe along the Y axis, searching for the upper frame of the initial positioning frame A of the microfluidic chip, namely moving the light spot from the initial positioning point ① to the positioning point ②, and after the light spot moves from the positioning point ① to the positioning point ② and passes through the frame, the waveform is shown in figure 13.
And controlling the light spot to move from the initial positioning point ① to the positioning point ②, monitoring and analyzing AD data acquisition waveform feedback in real time during the movement, checking whether the waveform appears as shown in fig. 13, stopping moving the optical probe in the reverse direction after the waveform appears in fig. 13 until the positioning point ② is found, and enabling the waveform at the position of the positioning point ② to be the maximum position of the ordinate of the waveform in fig. 13.
S4, moving to the left upper corner of the initial positioning frame A, moving along the X axis, and finding out the position of the positioning point ③ and the position of the positioning point ④: and controlling the light spot, monitoring and analyzing the feedback of the acquisition AD data acquisition waveform in real time from the position of the positioning point ② to the position of the positioning point ③, checking whether the waveform is as shown in fig. 15, and if so, finding the positioning cross mark B. Continuing to move leftwards, looking at whether the waveform is as in fig. 15, finding a positioning word-mark line D, positioning a reticle B and positioning a word-mark line D are used to confirm whether the platform moving direction is angularly offset from the chip.
S5, moving the optical probe along the Y axis, checking waveforms of the optical probe from the beginning of passing through the upper frame of the A frame to the leaving of the upper frame of the A frame, judging whether the current focus is on the microfluidic channel, if not, moving the Z axis, and if the current focus is positioned at the end of the optical focus, specifically:
The method comprises the steps of starting to find a right channel a of a positioning line D, returning to the position of a positioning point ②, skipping a positioning cross mark B through waveforms of positioning points ② - ③ shown in fig. 15, moving the positioning cross mark B to the point a after skipping, and finding the position of the point a when the waveforms of fig. 14 appear, wherein the position of the point a is found by finding the rightmost channel in the moving process, is the intersection point after the maximum waveforms of a silicon photocell 2 and a silicon photocell 3, and sequentially finding other channels after moving to the channel a.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solution of the present invention, and not limiting thereof; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may be modified or some technical features may be replaced with other technical solutions, which may not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (8)

1. The micro-fluidic chip positioning method is characterized by comprising the following steps:
the microfluidic chip channel positioning structure is arranged on the microfluidic chip, wherein the microfluidic chip comprises a plurality of microchannels, an initial positioning frame, a first positioning marking and a second positioning marking; the micro channels are longitudinally arranged at intervals; the right side of the micro-channel is provided with the initial positioning frame; the left side of the top of the initial positioning frame is provided with a first positioning marking which is arranged on one side of a central extension line of the micro-channel and used for positioning the rightmost position of the micro-channel; the left side of the micro-channel is provided with the second positioning marking line, and the second positioning marking line is arranged on the other side of the central extension line of the micro-channel and is used for positioning the leftmost position of the micro-channel; the first positioning mark line adopts a cross mark line, and the second positioning mark line adopts a linear mark line; the initial positioning frame adopts a square channel structure, and an upper left frame of the square channel structure and the first positioning marking line are both positioned on a central extension line of the narrow side of the micro channel; the micro-fluidic chip channel positioning structure comprises a chip pressing and photoelectric conversion module arranged above the micro-fluidic chip, a chip supporting structure arranged below the micro-fluidic chip, an optical probe, a micro-motion module for driving the optical probe to move, an AD data acquisition module for acquiring electric signals of the chip pressing and photoelectric conversion module, and a motor control module for controlling the optical probe to move;
moving the optical probe along a Z axis to enable the light spot to move into the initial positioning frame;
moving the optical probe along a Y axis, and searching an upper frame of the initial positioning frame of the micro-fluidic chip;
After moving to the left upper corner of the initial positioning frame, moving along the X axis, and ensuring that the moving direction of the optical probe and the microfluidic chip have no angular offset by searching the first positioning marking and the second positioning marking;
Moving the optical probe along the X axis, checking the waveform of the optical probe from the beginning of passing through the upper frame of the initial positioning frame to the leaving of the upper frame of the initial positioning frame, judging whether the current focus is on the microfluidic channel, if not, moving the Z axis, and if not, finishing the positioning of the optical focus;
the XY plane is parallel to the plane of the microfluidic chip, and the Z axis is perpendicular to the plane of the microfluidic chip.
2. The positioning method of the microfluidic chip according to claim 1, wherein the feedback of the waveform acquired by the AD data is used as a basis for determining whether the movement is completed or not during the movement of the optical probe.
3. The method of positioning a microfluidic chip according to claim 2, wherein the focusing of the focal spot to the location of the microchannel comprises:
the optical signals generated when the light spots pass through the micro-channels are converted into electric signals after being collected, and quantized data are collected through the AD data collecting module;
The micro-motion module is close to or far from the micro-channel through the Z axis, the position of the light spot in the micro-channel is adjusted, and the optical corresponding curve of the light spot passing through the micro-channel is recorded through the X axis movement;
And analyzing the light spot position through the relation between the light spot position and the acquired waveform of the AD data acquisition module.
4. The method for positioning a microfluidic chip according to claim 2, wherein the AD data acquisition waveform is wider when the size of the spot irradiated on the microchannel is larger than that of the microchannel;
When the size of the light spot irradiated on the micro-channel is equal to that of the micro-channel, the AD data acquisition waveform is narrowed, and the amplitude is increased;
when the size of the light spot irradiated on the micro-channel is smaller than that of the micro-channel, the AD data acquisition waveform shows a double-peak state.
5. A microfluidic chip for implementing the positioning method of any one of claims 1-4, wherein the microfluidic chip comprises a plurality of micro-channels, an initial positioning frame, a first positioning reticle and a second positioning reticle;
The micro channels are longitudinally arranged at intervals;
The right side of the micro-channel is provided with the initial positioning frame;
The left side of the top of the initial positioning frame is provided with a first positioning marking which is arranged on one side of the central extension line of the micro-channel and used for positioning the rightmost position of the micro-channel;
the left side of the micro-channel is provided with a second positioning marking, and the second positioning marking is arranged on the other side of the central extension line of the micro-channel and used for positioning the leftmost position of the micro-channel.
6. The microfluidic chip according to claim 5, wherein the micro-channels have a structure with a narrow middle and wide sides, and the size of the channels on both sides of the wide side of each micro-channel is the same.
7. A microfluidic chip channel positioning structure for implementing the positioning method according to any one of claims 1 to 4, comprising:
the chip pressing and photoelectric conversion module is arranged above the microfluidic chip and is used for acquiring optical signals emitted by the light source and irradiated on different positions of the microfluidic chip and converting the optical signals into electric signals;
The chip supporting structure is arranged below the microfluidic chip and used for supporting and fixing the microfluidic chip;
The optical probe is used for focusing the optical signal emitted by the light source;
The micro-motion module is used for connecting the optical probe to enable the optical probe to move;
the AD data acquisition module is used for acquiring the electric signals of the chip pressing and photoelectric conversion module;
the data analysis module is used for analyzing the electric signals of the AD data acquisition module;
and the motor control module is used for controlling the optical probe to move and changing the relative position of the optical probe and the micro-fluidic chip channel so that the focus of the focusing light spot corresponds to the micro-channel position.
8. The microfluidic chip channel positioning structure according to claim 7, wherein the chip pressing and photoelectric conversion module uses three silicon photocells for optical signal acquisition.
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