CN113567397A - 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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Publication number
CN113567397A
CN113567397A CN202110927521.1A CN202110927521A CN113567397A CN 113567397 A CN113567397 A CN 113567397A CN 202110927521 A CN202110927521 A CN 202110927521A CN 113567397 A CN113567397 A CN 113567397A
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channel
micro
positioning
microfluidic chip
light spot
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CN113567397B (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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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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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 and a second positioning marking; the micro channels are longitudinally arranged at intervals; the initial positioning frame is arranged on the right side of the micro channel; the first positioning marking line is arranged on the left side of the top of the initial positioning frame, and is arranged on one side of the center 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 marked line, and the second positioning marked line is arranged on the other side of the center extension line of the micro-channel and is used for positioning the leftmost position of the micro-channel. According to the invention, the initial positioning precision of the whole equipment structure can be reduced through the arranged micro-fluidic chip structure.

Description

Microfluidic chip, microfluidic chip channel positioning structure and positioning method
Technical Field
The invention relates to a microfluidic chip, a microfluidic chip channel positioning structure and a positioning method, and relates to the technical field of biological detection.
Background
The micro-fluidic chip technology integrates basic operation units of sample preparation, reaction, separation, detection and the like in the processes of biological, chemical and medical analysis on a micron-scale chip, and automatically completes the whole analysis process. Due to its great potential in the fields of biology, chemistry, medicine and the like, the method has been developed into a new research field crossing the disciplines of biology, chemistry, medicine, fluid, electronics, materials, machinery and the like.
Optical focus positioning is carried out in medical micro-fluidic equipment, and most of the existing equipment is produced through equipment, and the focus position is not adjusted any more after the focus is positioned through a structure, so that a problem is caused.
In the prior art, the matching of the width of a chip channel and a light spot is theoretically calculated, and the relative position of an 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 adjusted through vertical movement any more, although the structure is simple, the optical probe is close to the chip, and the optical probe is in a position which is easy to touch after the chip is removed, but the optical probe is a device which needs high cleanliness, so that the optical probe is easy to pollute, the light spot is dispersed, and the positioning and testing effects are influenced; in addition, when only the optical probe is fixed and a chip is placed, the size of a light spot is changed with the size of a channel due to corresponding difference of positions (structure positioning precision and chip processing precision) every time, the size of the light spot on the channel is different every time of testing, and the difference of the positioning of the channel and the fluorescence excitation intensity in the testing can be influenced (the light intensity is influenced by the absorption of liquid drops, the more concentrated the light spot is, the larger the area of the covered liquid drops is, and the stronger the light intensity is). 2) The vertical direction of the optical probe can be moved, and the optical probe is fixed in each movement, so that the optical probe can be moved downwards to a position where the optical probe cannot be contacted, and the optical probe is effectively prevented from being polluted. But also in the process of moving in the vertical direction, the position of each time is different and the uncertainty is larger due to the influence of the precision of the moving 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 entire device structure.
The second purpose of the present invention is to provide a microfluidic chip channel positioning structure capable of positioning all microfluidic channels, so that the droplets flowing through the microfluidic channels are completely covered by the focusing light spots to the greatest extent.
The invention also aims to provide a method for positioning the channel of the microfluidic chip.
In order to achieve the purpose, the 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 initial positioning frame is arranged on the right side of the micro channel;
the first positioning marking line is arranged on the left side of the top of the initial positioning frame, and is arranged on one side of the center 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 marked line, and the second positioning marked line is arranged on the other side of the center extension line of the micro-channel and is used for positioning the leftmost position of the micro-channel.
Furthermore, the microchannel adopts a structure with a narrow middle part and two wide sides, and the sizes of the channels on the two sides of the wide side of each microchannel are the same.
Furthermore, the initial positioning frame adopts a square channel structure, and the upper left frame of the square channel structure and the first positioning marked line are both positioned on the central extension line of the narrow side of the microchannel.
Furthermore, the first positioning marked line is a cross marked line, and the second positioning marked line is a straight marked line.
In a second aspect, the present invention also provides a microfluidic chip channel positioning structure for positioning the microfluidic chip, the structure comprising:
the chip pressing and photoelectric conversion module is arranged above the microfluidic chip and used for acquiring optical signals emitted by a light source and irradiating different positions of the microfluidic chip by light spots 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 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 signal 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 position of the micro-channel.
Further, the process of corresponding the focus of the focused light spot to the position of the micro-channel comprises the following steps:
optical signals generated when the light spots pass through the micro-channel are collected and converted into electric signals, and quantitative data collection is carried out through an AD data collection module;
the micro-motion module is close to or far away from the micro-channel through a Z axis, adjusts the size of the light spot at the position of the micro-channel, moves through an X axis, and records an optical corresponding curve of the light spot passing through the micro-channel;
and analyzing the position of the light spot according to the relation between the position of the light spot and the waveform acquired by the AD data acquisition module.
Further, the relationship between the position of the light spot and the waveform acquired by the AD data acquisition module is as follows:
in the 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;
in the 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 becomes narrow, and the amplitude value becomes high;
in the 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 double-peak state, the width of the AD data acquisition waveform is approximately equal to that of the light spot irradiated on the micro-channel, and the amplitude of the AD data acquisition waveform is larger.
Furthermore, the chip stitching and photoelectric conversion module adopts three silicon photocells to collect optical signals.
In a third aspect, the present invention further provides a method for positioning a microfluidic chip based on the microfluidic chip channel positioning structure, including the steps of:
the microfluidic chip channel positioning structure is arranged on the microfluidic 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 microfluidic chip;
moving to the upper left corner of the frame A of the initial positioning frame, moving along the X axis, and searching a first positioning marking line and a second positioning marking line to ensure that the moving direction of the optical probe and the microfluidic chip have no angular deviation;
moving the optical probe along the Y axis, checking the waveform of the optical probe from the beginning to the end of the optical probe passing through the upper frame of the initial positioning frame to the waveform 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 so, ending the optical focus positioning;
wherein, the XY direction is parallel to the micro-channel chip plane, and the Z axis is vertical to the micro-channel chip plane.
Further, the AD data acquisition waveform feedback is used as a judgment basis for judging whether the movement is finished or not in the moving process of the optical probe.
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 and a second positioning marking, and the initial positioning precision of the whole equipment structure can be reduced through the structural design of the micro-fluidic chip;
2. the microfluidic 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 positions of the optical probe and a microfluidic chip channel are changed by controlling the movement of the optical probe, so that the focus of a focusing light spot corresponds to the position of the micro-channel, and liquid drops flowing through the micro-channel are enabled to be completely covered by the focusing light spot to emit optical signals at different positions of the microfluidic chip to the greatest extent;
3. the method for positioning the microfluidic chip can meet the requirement of positioning the microchannel in the microfluidic chip by using a light diffraction and reflection method, so that the aim of positioning all the microfluidic 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 reference numerals refer to like parts throughout the drawings. In the drawings:
FIG. 1 is a schematic structural diagram of a microfluidic chip according to an embodiment of the present invention;
FIG. 2 is a schematic view of a positioning structure according to an embodiment of the present invention;
FIG. 3 is a hardware system framework diagram of an embodiment of the invention;
FIG. 4 is a diagram 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 of an embodiment of the present invention;
FIG. 6 is an optical diagram of a positioning structure according to an embodiment of the present invention;
FIG. 7 is a diagram illustrating a relationship between spot positions and AD data acquisition waveforms according to an embodiment of the present invention;
FIG. 8 is a diagram illustrating a relationship between spot positions and AD data acquisition waveforms according to an embodiment of the present invention;
FIG. 9 is a diagram illustrating a relationship between spot positions 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 according to an embodiment of the present invention;
FIG. 11 is a chip channel state diagram of an embodiment of the invention;
FIG. 12 is a diagram illustrating positioning of microfluidic channels according to an embodiment of the present invention;
FIG. 13 is a waveform diagram for data acquisition according to an embodiment of the present invention;
FIG. 14 is a waveform diagram for data acquisition according to an embodiment of the present invention;
FIG. 15 is a waveform diagram for 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 invention are shown in the drawings, it should be understood that the invention can 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" may be intended to include the plural forms as well, unless the context clearly indicates otherwise. The terms "comprises," "comprising," "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 specifically identified as an order of performance. It should also be understood 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 convenience 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 and a second positioning marking; a plurality of micro-channels are longitudinally arranged at intervals; an initial positioning frame is arranged on the right side of the micro-channel; a first positioning marking line is arranged on the left side of the top of the initial positioning frame, and the first positioning marking line is arranged on one side of a center extension line of the micro-channel and is used for positioning the rightmost position of the micro-channel; the left side of the micro-channel is provided with a second positioning marking line, and the second positioning marking line is arranged on the other side of the center extension line of the micro-channel and is used for positioning the leftmost position of the micro-channel. According to the invention, the initial positioning precision of the whole equipment structure can be reduced through the arranged micro-fluidic chip structure.
Example one
As shown in fig. 1, the microfluidic chip provided in this embodiment includes an initial positioning frame a, a positioning cross mark B, a plurality of microchannels C, and a positioning line mark D.
The micro-channels C are longitudinally arranged at intervals, the right sides of the micro-channels C are provided with initial positioning frames A, the left sides of the tops of the initial positioning frames A are provided with positioning cross marked lines B, and the positioning cross marked lines B are arranged on the extension lines on one side of the centers of the micro-channels C and are used for positioning the rightmost positions of the micro-channels C. The left side of the micro-channel C is provided with a positioning line-shaped marking D, and the positioning line-shaped marking D can be arranged on the extension line of the other side of the center of the micro-channel C and is used for positioning the leftmost position of the micro-channel C.
In some preferred embodiments of the present invention, the longitudinal interval between adjacent microchannels C may be set to 100um, the microchannels C adopt a channel structure with a narrow middle and wide two sides, the channel sizes of both sides of the microchannels C are the same, and may be 20um, and the channel size of the middle of the microchannels C may be 10 um.
In some preferred embodiments of the present invention, the initial positioning frame a may adopt a square channel frame, in this embodiment, a square with an outer side length of 0.2mm is adopted, and the channel size width may be 20um, which is taken as an example and not limited thereto, and may be determined according to actual needs.
In some preferred embodiments of the present invention, the positioning cross mark B and the positioning line D are used to determine whether there is angular displacement between the microfluidic chip channel and the moving platform, the positioning cross mark B has a length of 0.1mm in the transverse direction and the longitudinal direction, the positioning line D has a length of 0.1mm, and the positioning cross mark B and the positioning line D have a channel size of 20 um.
Example two
As shown in fig. 2 and 3, the microfluidic chip channel positioning structure provided in this embodiment is used for positioning the microfluidic chip provided in the first embodiment, and positioning the size of the focusing spot and the microfluidic chip channel, and includes a chip stitching and photoelectric conversion module 1, a chip support 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.
And the chip pressing and photoelectric conversion module 1 is arranged above the microfluidic chip and used for acquiring optical signals emitted by the light source and irradiating different positions of the microfluidic chip by light spots and converting the optical signals into analog electric signals.
And the chip supporting structure 2 is arranged below the microfluidic chip and used for supporting and fixing the microfluidic chip.
And the optical probe 3 is arranged below the microfluidic chip and used for focusing an optical signal emitted by the light source.
And the micromotion 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 correspondingly move along the XY and focusing Z axes. Wherein, fine motion module 4 can adopt current structure, including fine motion platform, motor drive and motor controller, and computer control motor controller sends out the instruction and arrives motor drive, drives the motor in the fine motion platform, makes the fine motion platform carry out the removal of corresponding direction, and this is prior art, so does not give unnecessary details.
And the AD data acquisition module 5 is used for acquiring the electric signals of the chip pressing and photoelectric conversion module 1.
And the data analysis module 6 is used for analyzing the electric signals of the AD data acquisition module 5.
And the motor control module 7 is used for controlling the optical probe 3 to move and changing the relative position of the optical probe 3 and the microfluidic chip channel, so that the focus of the focused light spot corresponds to the position of the micro-channel, and specifically, the focused light spot can move along the 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 the Z direction (change the distance between the micro-channel chip and the optical probe) so as to change the size of the light spot at the position of the chip.
In some preferred embodiments of the present invention, the chip stitching and photoelectric conversion module 1 converts the light intensity into a voltage signal by sensing light, so as to facilitate the AD data acquisition module 5 to acquire data, where the acquired light signal is a light source that 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 bonding and photoelectric conversion module 1 may adopt three silicon photocells for collecting optical signals, a light source emits parallel laser, an optical probe 3 focuses light spots and determines a relative vertical position of a focal point, and when light passes through a non-channel position of the microchannel chip, the silicon photocells (photoelectric conversion) have no voltage feedback and are always noise-reduced. When light penetrates through the channel position of the micro-channel chip, if the channel is vertical to the 2#3# silicon photocell, the 2#3# silicon photocell has corresponding waveforms, and if the channel is parallel to the 2#3# silicon photocell, the 1# silicon photocell has corresponding waveforms, and optical signal acquisition through three silicon photocells is the prior art and is not described herein again.
In some preferred embodiments of the present invention, focusing the focus of the focusing light source to the channel of the microfluidic chip, and automatically corresponding the focus of the focusing light spot to the position of the microchannel specifically means that the diameter of the focusing light spot falling on the channel position by the optical probe 3 is consistent with the width of the microchannel, so that the droplet flowing through the microchannel is completely covered by the focusing light spot to the greatest extent, and the process comprises:
when the light spot passes through the micro-channel, the light signal generated by the reflection grating (the reflection grating is formed by irradiating the light spot of the light source on the channel of the micro-fluidic chip) is converted into an analog electrical signal through the silicon photocell, and the AD data acquisition module 5 is used for acquiring the quantitative data.
The micro-motion module 4 is close to or far from the micro-channel through a Z axis, adjusts the position size of the light spot in the micro-channel, moves through an X axis, and records an optical corresponding curve of the light spot passing through the micro-channel by using a silicon photocell and an AD data acquisition module 5, wherein, as shown in figure 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 conversion of the optical signal into the digital signal.
And analyzing the position of the light spot through the relation between the position of the light spot 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 position of the focal point and the micro-channel is adjusted in the Z direction by moving the micro-motion module. By moving the micromotion module X, the size of the light spot formed at the position of the micro-channel when the light passes through the micro-channel is judged.
Further, the correspondence between the spot position and the waveform acquired by the AD data acquisition module 5 includes:
in the first case: as shown in fig. 7, the size of the light spot irradiated on the microchannel is larger than that of the microchannel, and when the size of the light spot irradiated on the microchannel is larger than that of the microchannel, the waveform is wider.
In the second case: as shown in fig. 8, the size of the light spot irradiated on the microchannel is equal to that of the microchannel, and when the size of the light spot irradiated on the microchannel is equal to that of the microchannel, the AD acquisition waveform becomes narrow and the amplitude becomes high.
In the third case: as shown in fig. 9, the spot size of the light irradiated on the microchannel is smaller than that of the microchannel. 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 double-peak state, the width of the AD data acquisition waveform is approximately equal to that of the light spot irradiated on the micro-channel, and the amplitude of the AD data acquisition waveform is larger.
In summary, when the size of the light spot irradiated on the micro-channel can be obtained by the droplet passing, the width, amplitude and peak number presented by the waveform can be acquired from the AD data, and the width, amplitude and peak number can be obtained by corresponding logic. As shown in fig. 10, the final spot size required to achieve the present invention is consistent with the width of the microchannel. 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 from the laser module on this channel position.
EXAMPLE III
The method for positioning the microfluidic chip channel of the first embodiment based on the positioning structure of the second embodiment of the invention comprises the following steps:
s1, installing the micro-fluidic chip channel positioning structure on the micro-fluidic chip
Specifically, when the microfluidic chip channel positioning structure of this embodiment is installed, 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 shown in fig. 3. And the rotation angle of the micro-fluidic chip is within a preset acceptable range. Preferably, the rotation angle in the acceptance range can be manually confirmed by the structure firstly, and can be judged by the moving waveform from the point locating point to the point locating point secondly, as shown in fig. 12.
S2, moving the optical probe along the Z axis to enable the light spot to move to the initial positioning frame A
As shown in fig. 12, the light spot is moved to an initial positioning point (r) in the initial positioning frame a, and it is confirmed whether the position of the initial positioning point (r) is correct: and controlling the light spot to move a certain distance leftwards from the initial positioning point I, analyzing the AD data acquisition waveform feedback in real time, judging whether the light spot is as shown in FIG. 14, if so, returning to the initial positioning point I, moving upwards for a certain distance, checking the AD data acquisition waveform, judging whether the light spot is as shown in FIG. 13, and if so, confirming the initial positioning point I.
S3, moving the optical probe along the Y axis and finding the upper border of the initial positioning frame A of the microfluidic chip, namely moving the light spot from the initial positioning point I to the positioning point II, and after the light spot moves from the positioning point I to the positioning point II and passes through the border, the waveform is as shown in FIG. 13.
And controlling light spots, moving from the position of an initial positioning point I to the position of a positioning point II, monitoring and analyzing AD data acquisition waveform feedback in real time during the period, checking whether the waveform of the figure 13 appears, stopping moving the optical probe in the reverse direction after the waveform of the figure 13 appears until the positioning point II is found, wherein the waveform of the positioning point II is the maximum position of the vertical coordinate of the waveform of the figure 13.
S4, moving to the upper left corner of the frame A of the initial positioning frame, moving along the X axis, and finding the positioning point position III and the positioning point position IV: and controlling the light spots from the positioning point position II to the positioning point position III, monitoring and analyzing the acquired AD data in real time during the period to acquire waveform feedback, checking whether the waveform is as shown in the figure 15, and finding a positioning cross mark B if the waveform is the same as the waveform. And continuing to move leftwards, checking whether the waveform is the same as that in FIG. 15, and finding a positioning straight mark line D, wherein the positioning cross mark line B and the positioning straight mark line D are used for confirming whether the moving direction of the platform is angularly offset from the chip.
S5, moving the optical probe along the Y axis, looking up the waveform of the optical probe from the beginning to the end of passing through the upper border of the a frame to the end of leaving the upper border of the a frame, determining whether the current focus is on the microfluidic channel, if not, moving the Z axis, if the optical focus is positioned at the end, specifically:
and (3) searching a right channel a of a positioning linear marking line D, returning to a positioning point II, skipping a positioning cross marking line B through a waveform of the positioning point II shown in figure 15 and moving to a point A, when the waveform of figure 14 appears, proving that the rightmost channel is found in the moving process to find the position of the point A, the position of the point A is a cross point behind the maximum waveform of the silicon photocell 2 and the silicon photocell 3, and sequentially searching other channels after moving to the channel A.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the same; although the present 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: it is to be understood that modifications may be made to the above-described arrangements in the embodiments or equivalents may be substituted for some of the features of the embodiments without departing from the spirit or scope of the present invention.

Claims (10)

1. A micro-fluidic chip is characterized by comprising 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 initial positioning frame is arranged on the right side of the micro channel;
the first positioning marking line is arranged on the left side of the top of the initial positioning frame, and is arranged on one side of the center 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 marked line, and the second positioning marked line is arranged on the other side of the center extension line of the micro-channel and is used for positioning the leftmost position of the micro-channel.
2. The microfluidic chip according to claim 1, wherein the microchannel has a structure with a narrow middle and two wide sides, and the channels on the two sides of the wide side of each microchannel have the same size.
3. The microfluidic chip according to claim 1, wherein the initial positioning frame has a square channel structure, and the upper left frame of the square channel structure and the first positioning mark line are located on the central extension line of the narrow side of the microchannel.
4. The microfluidic chip according to claim 1, wherein the first positioning mark is a cross mark, and the second positioning mark is a straight mark.
5. A microfluidic chip channel positioning structure for positioning a microfluidic chip according to any one of claims 1 to 4, the structure comprising:
the chip pressing and photoelectric conversion module is arranged above the microfluidic chip and used for acquiring optical signals emitted by a light source and irradiating different positions of the microfluidic chip by light spots 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 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 signal 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 position of the micro-channel.
6. The microfluidic chip channel positioning structure of claim 5, wherein the process of corresponding the focus of the focused light spot to the position of the microchannel comprises:
optical signals generated when the light spots pass through the micro-channel are collected and converted into electric signals, and quantitative data collection is carried out through an AD data collection module;
the micro-motion module is close to or far away from the micro-channel through a Z axis, adjusts the size of the light spot at the position of the micro-channel, moves through an X axis, and records an optical corresponding curve of the light spot passing through the micro-channel;
and analyzing the position of the light spot according to the relation between the position of the light spot and the waveform acquired by the AD data acquisition module.
7. The microfluidic chip channel positioning structure of claim 6, wherein the relationship between the position of the light spot and the waveform collected by the AD data collection module is as follows:
in the 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;
in the 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 becomes narrow, and the amplitude value becomes high;
in the 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 double-peak state, the width of the AD data acquisition waveform is approximately equal to that of the light spot irradiated on the micro-channel, and the amplitude of the AD data acquisition waveform is larger.
8. The microfluidic chip channel positioning structure of claim 6, wherein the chip stitching and photoelectric conversion module adopts three silicon photocells for optical signal acquisition.
9. The method for positioning the microfluidic chip according to any one of claims 1 to 4 based on the structure for positioning the microfluidic chip channel according to any one of claims 6 to 8, comprising the steps of:
the microfluidic chip channel positioning structure is arranged on the microfluidic 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 microfluidic chip;
moving to the upper left corner of the frame A of the initial positioning frame, moving along the X axis, and searching a first positioning marking line and a second positioning marking line to ensure that the moving direction of the optical probe and the microfluidic chip have no angular deviation;
moving the optical probe along the Y axis, checking the waveform of the optical probe from the beginning to the end of the optical probe passing through the upper frame of the initial positioning frame to the waveform 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 so, ending the optical focus positioning;
wherein, the XY direction is parallel to the micro-channel chip plane, and the Z axis is vertical to the micro-channel chip plane.
10. The method for positioning a microfluidic chip according to claim 9, wherein the AD data acquisition waveform feedback is used as a judgment basis for judging whether the movement is finished or not during the movement of the optical probe.
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