A microfluidic chip, method and system for quickly locating sample observation area

Abstract

The present invention belongs to the field of optical technology and discloses a microfluidic chip, a method and a system for quickly locating a sample observation area. The microfluidic chip provided by the present invention includes a channel microstructure and a positioning microstructure. The channel microstructure includes a microfluidic channel for sample flow, and the positioning microstructure is used to guide the position adjustment of the microfluidic chip to locate the sample observation area. The present invention uses the positioning microstructure in the above-mentioned microfluidic chip to guide the position adjustment of the microfluidic chip to locate the sample observation area. The present invention can solve the problem that the existing technology is difficult to quickly locate the sample observation area, can reduce the difficulty of quickly locating the observation area, and realize rapid and accurate positioning of the sample observation area.

Description

Technical Field

[0001] The present invention belongs to the field of optical technology, and more specifically, relates to a microfluidic chip, a method for quickly locating a sample observation area, and a system. Background Art

[0002] Time-stretched single-cell imaging is a novel cell imaging method that uses a broadband pulsed laser as a light source. This pulsed laser is temporally stretched and spatially dispersed to illuminate cells. The collected signal is decoded to recover a clear cell image. This imaging method boasts extremely high image acquisition speeds (tens to billions of FPS), making it ideal for examining large cell samples.

[0003] Since time-domain stretch imaging of cells requires the cells to pass through the laser spot at high speed, the microfluidic system will try to reduce the length of the narrow channel used to observe the cells. However, this will greatly increase the difficulty of the time-domain stretch imaging system in finding the observation position. Time-domain stretch imaging cannot directly obtain an image. Before starting the detection, it is usually necessary to adjust the focal length of the system first, find the approximate position of the side wall of the channel by the fluctuation of the waveform, and then move the chip to the other side wall of the other channel. The distance between the two walls is used to determine whether it is the observation area. Since the observation area of ​​the ultra-high-speed flow chip is very small and the position of the microfluidic chip in three dimensions needs to be adjusted, there is great uncertainty. It is extremely difficult to quickly locate the observation area. It is very easy to locate the channel in front of the observation area. The speed of the cells here has not yet accelerated to the predetermined speed, and it is very easy to obtain a distorted image. Summary of the Invention

[0004] The present invention solves the problem in the prior art that it is difficult to quickly locate a sample observation area by providing a microfluidic chip, a method for quickly locating a sample observation area, and a system.

[0005] In a first aspect, the present invention provides a microfluidic chip comprising: a channel microstructure and a positioning microstructure; the channel microstructure comprises a microfluidic channel for sample flow; the positioning microstructure is used to guide the position adjustment of the microfluidic chip to locate the sample observation area.

[0006] Preferably, the positioning microstructure includes two groups of positioning components, which are respectively located in the outer areas of the two side walls of the microfluidic channel corresponding to the sample observation area, and the two groups of positioning components are symmetrically arranged about the microfluidic channel corresponding to the sample observation area; the two groups of positioning components are respectively used to locate the positions of the two side walls.

[0007] Preferably, each group of the positioning components includes a first structure arranged along a first direction and a second structure arranged along a second direction, the two side walls of the microfluidic channel corresponding to the sample observation area extend along the first direction, and the second direction is perpendicular to the first direction; the first structure is a continuous structure, which includes a first straight line segment, an indication change segment and a second straight line segment arranged in sequence along the first direction; the second structure is a string structure, which includes a plurality of blocks arranged at equal intervals along the second direction, and the string structure is located between the indication change segment and a side wall of the microfluidic channel corresponding to the sample observation area.

[0008] Preferably, the total length of the first structure is 1 to 3 mm, the width of the straight section in the first structure is 20 to 40 um, and the height of the first structure is 30 to 60 um; the total length of the second structure is 1 to 3 mm, the blocks are rectangular structures, and the length of each block is 20 to 40 um, the width is 20 to 40 um, and the height is 30 to 60 um.

[0009] Preferably, the indication change section is a triangular concave structure, the outer concave vertex of the triangular concave structure extends toward the second direction and points to the second structure; the distance between the first block in the second structure and the indication change section is greater than or equal to the spacing between two adjacent blocks, and the distance between the last block in the second structure and the sample observation area is greater than or equal to the spacing between two adjacent blocks.

[0010] In second aspect, the present invention provides a method for quickly locating a sample observation area, obtaining a microfluidic chip comprising a channel microstructure and a positioning microstructure, wherein the channel microstructure comprises a microfluidic channel for sample flow, and utilizing the positioning microstructure to guide the position adjustment of the microfluidic chip to locate the sample observation area.

[0011] Preferably, the positioning microstructure includes two groups of positioning components, which are respectively located in the outer areas of the two side walls of the microfluidic channel corresponding to the sample observation area, and the two groups of positioning components are symmetrically arranged about the microfluidic channel corresponding to the sample observation area; according to the differences in the waveforms of the time domain stretching imaging corresponding to each group of positioning components in two mutually perpendicular directions, the two groups of positioning components are used to respectively find the positions of the two side walls of the microfluidic channel corresponding to the sample observation area.

[0012] Preferably, each group of the positioning components includes a first structure arranged along a first direction and a second structure arranged along a second direction, the two side walls of the microfluidic channel corresponding to the sample observation area extend along the first direction, and the second direction is perpendicular to the first direction; the first structure is a continuous structure, which includes a first straight line segment, an indication change segment and a second straight line segment arranged in sequence along the first direction; the indication change segment is a triangular concave structure, the outer concave vertex of the triangular concave structure extends toward the second direction and points to the second structure; the second structure is a string structure, which includes a plurality of blocks arranged at equal intervals along the second direction, and the string structure is located between the indication change segment and a side wall of the microfluidic channel corresponding to the sample observation area.

[0013] Preferably, finding the position of the side wall comprises the following steps:

[0014] Step 1: visually adjusting the microfluidic chip so that the positioning microstructure moves to the light spot; adjusting the relative position of the positioning microstructure and the light spot until a waveform observer displays a double-trough waveform;

[0015] Step 2: Move the microfluidic chip and determine whether the current light spot falls on the first structure or the second structure based on the first waveform change characteristic and the second waveform change characteristic;

[0016] The first waveform change characteristic includes: when the microfluidic chip is moved laterally, the light spot maintains a double-trough waveform while moving within the straight section of the positioning microstructure, with the two troughs being designated as a first trough and a second trough, respectively; when the light spot moves from one end of the straight section to the indication change section, the second trough gradually moves along a third direction and eventually disappears as displayed on a waveform viewer; the first trough initially remains unchanged and then gradually moves along the third direction; after reaching a first specific position, if the microfluidic chip is continued to be moved, the first trough gradually moves in a direction opposite to the third direction as displayed on the waveform viewer, with the first specific position covering an inner concave apex of the indication change section; after reaching the first specific position, the microfluidic chip is moved longitudinally, causing the light spot to move from the first specific position to a second specific position, resulting in the first trough disappearing and the second trough reappearing, with the second specific position covering an outer concave apex of the indication change section;

[0017] The second waveform variation characteristic includes: a pair of troughs intermittently appearing during the movement of the microfluidic chip;

[0018] Step 3: If the light spot falls on the first structure, the light spot is first moved to the second specific position based on the first waveform variation characteristic, and then the microfluidic chip is continued to move along the current movement direction so that the light spot moves to the second structure;

[0019] If the light spot falls on the second structure, the microfluidic chip is moved based on the second waveform change characteristics so that a pair of troughs appear intermittently. Then, after the last pair of troughs that conform to the second waveform change characteristics disappears, the microfluidic chip continues to be moved along the current moving direction until another trough appears, and the position of the trough corresponds to the position of a side wall.

[0020] In a third aspect, the present invention provides a system for rapidly positioning a sample observation area, comprising: a position adjustment device, a laser, a time-domain stretch imaging detection device, a photodetector, and a waveform observer; the position adjustment device is used to control the movement of a microfluidic chip, the laser is used to generate light pulses, the time-domain stretch imaging detection device is used to obtain a detection light signal, the photodetector is used to convert the detection light signal into an analog electrical signal, and the waveform observer is used to convert the analog electrical signal into a digital electrical signal and display the signal waveform;

[0021] The system for rapidly locating a sample observation area is used to implement the steps in the method for rapidly locating a sample observation area.

[0022] One or more technical solutions provided in the present invention have at least the following technical effects or advantages:

[0023] The microfluidic chip provided by the present invention includes a channel microstructure and a positioning microstructure. The channel microstructure contains a microfluidic channel for sample flow, and the positioning microstructure is used to guide the position adjustment of the microfluidic chip to locate the sample observation area. The present invention uses the positioning microstructure in the above-mentioned microfluidic chip to guide the position adjustment of the microfluidic chip to locate the sample observation area. The present invention not only provides a design method for a microfluidic chip, but also provides a method and system for quickly locating the sample observation area using the above-mentioned microfluidic chip. The present invention can reduce the difficulty of quickly locating the observation area and achieve rapid and accurate positioning. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 A schematic structural diagram of a microfluidic chip provided in Example 1 of the present invention;

[0025] Figure 2 A schematic structural diagram of a positioning component in a microfluidic chip provided in Example 1 of the present invention;

[0026] Figure 3A schematic diagram of a light spot at multiple moving positions and their corresponding waveforms in a method for quickly locating a sample observation area in Example 2 of the present invention is provided. DETAILED DESCRIPTION

[0027] In order to better understand the above technical solution, the above technical solution will be described in detail below with reference to the accompanying drawings and specific implementation methods.

[0028] Example 1:

[0029] Example 1 provides a microfluidic chip, see Figure 1 , including: a channel microstructure 120 and a positioning microstructure 110; the channel microstructure 120 includes a microfluidic channel for sample flow; the positioning microstructure 110 is used to guide the position adjustment of the microfluidic chip to locate the sample observation area 121.

[0030] The channel microstructure 120 and the positioning microstructure 110 are located in the same plane. When preparing the microfluidic chip, the positioning microstructure 110 can be drawn on a mask together with the channel microstructure 120 to ensure that there is no error.

[0031] The positioning microstructure includes two sets of positioning components, each located outside the two sidewalls of the microfluidic channel corresponding to the sample observation area. The two sets of positioning components are symmetrically arranged about the microfluidic channel corresponding to the sample observation area. Based on the differences in the waveforms of time-domain stretch imaging corresponding to each set of positioning components in two mutually perpendicular directions, the two sets of positioning components can be used to respectively locate or locate the positions of the two sidewalls.

[0032] Since the present invention utilizes the positioning microstructure to guide the observer to adjust the three-dimensional position of the microfluidic pipeline to the observation area, the positioning microstructure designed by the present invention is close to the pipeline microstructure and has direction specificity. At the same time, since the position of the positioning microstructure can be visually determined, the present invention distributes the positioning microstructures within a larger, visually detectable range. That is, the size of a group of the positioning components in two degrees of freedom of movement (see Figure 2 The total length (L) and total width (W) in the diagram are set to a range that can be visually observed.

[0033] See also Figure 2Each set of positioning components includes a first structure arranged along a first direction and a second structure arranged along a second direction. The two sidewalls of the microfluidic channel corresponding to the sample observation area extend along the first direction, and the second direction is perpendicular to the first direction. The first structure is a continuous structure, which includes a first straight segment, an indicator change segment, and a second straight segment arranged in sequence along the first direction. The second structure is a series structure, which includes a plurality of blocks arranged at equal intervals along the second direction. The series structure is located between the indicator change segment and a sidewall of the microfluidic channel corresponding to the sample observation area. In other words, the positioning component is similar to a T-shape, consisting of a horizontally continuous long strip structure and a series of vertical blocks perpendicular to it. There is a structural change somewhere in the middle of the long strip structure along the length direction to point to a series of vertical block structures. The series of block structures guides the sidewall to move to the light spot.

[0034] To address the limited field of view of time-domain stretch imaging, and considering that the narrowest dimension of the microfluidic channel is approximately 100 μm, the present invention sets the width of the straight segments in the first structure and the width of the blocks in the second structure to less than 100 μm. This ensures that two troughs can appear simultaneously on the waveform, ensuring accurate positioning. For example, the total length of the first structure is 1 to 3 mm, the width of the straight segments in the first structure is 20 to 40 μm, and the height of the first structure is 30 to 60 μm; the total length of the second structure is 1 to 3 mm, the blocks are rectangular structures, and each block has a length of 20 to 40 μm, a width of 20 to 40 μm, and a height of 30 to 60 μm.

[0035] The indicator change section is a triangular concave structure (e.g., a right-angled concave structure), with the outer concave vertex of the triangular concave structure extending in the second direction, pointing toward the second structure; the distance between the inner and outer concave vertices of the triangular concave structure is greater than the spot size. The distance between the first block in the second structure and the indicator change section is greater than or equal to the spacing between two adjacent blocks, and the distance between the last block in the second structure and the sample observation area is greater than or equal to the spacing between two adjacent blocks.

[0036] The following provides a method for quickly locating a sample observation area using the microfluidic chip described in Example 1.

[0037] Example 2:

[0038] Example 2 provides a method for quickly locating a sample observation area. First, a microfluidic chip comprising a channel microstructure and a positioning microstructure is obtained. The channel microstructure comprises a microfluidic channel for sample flow. Then, the positioning microstructure is used to guide the position adjustment of the microfluidic chip to locate the sample observation area.

[0039] Specifically, finding the position of the side wall includes the following steps:

[0040] Step 1: visually adjust the microfluidic chip to move the positioning microstructure to the light spot; adjust the relative position of the positioning microstructure and the light spot until a waveform observer displays a double-trough waveform.

[0041] By visual inspection, the microfluidic chip is adjusted in the plane of the first direction and the second direction so that the positioning microstructure moves to the light spot; based on the waveform displayed by the waveform observer, the microfluidic chip is moved in the plane of the first direction and the second direction, and in a direction perpendicular to the plane of the first direction and the second direction, to find the waveform with double troughs. Specifically, during the process of adjusting the relative position of the positioning microstructure and the light spot, the waveform is displayed as follows: Figure 3 When the waveform corresponding to position A or position E is obtained, it is considered that the light spot has been positioned on a certain block structure of the first structure or the second structure.

[0042] Step 2: Move the microfluidic chip and determine whether the current light spot falls on the first structure or the second structure based on the first waveform change characteristic and the second waveform change characteristic.

[0043] The first waveform change characteristic includes: when the microfluidic chip is moved laterally, the light spot will keep the double trough waveform unchanged in the process of moving in the straight section of the positioning microstructure, and the two troughs will be recorded as the first trough and the second trough respectively; when the light spot moves from one end side of the straight section to the indication change section, see Figure 3For the waveform corresponding to position B and the waveform corresponding to position C in the waveform viewer, the display position of the second trough on the waveform viewer will gradually move along the third direction (for example, from left to right in the waveform viewer) and eventually disappear. The display position of the first trough on the waveform viewer will remain unchanged at first, and then gradually move along the third direction. After reaching the first specific position, if the microfluidic chip continues to be moved, the display position of the first trough on the waveform viewer will move in the direction opposite to the third direction (for example, from right to left in the waveform viewer). The first specific position covers the inner concave apex of the indicating change section. After reaching the first specific position, the microfluidic chip is moved longitudinally so that the light spot moves from the first specific position to the second specific position. The first trough disappears and the second trough reappears. That is, the position of the microfluidic chip is continued to be adjusted in a direction perpendicular to the previous movement direction. The previous trough disappears and a new trough appears in the movement direction. See Figure 3 In the waveform corresponding to the middle D position, the second specific position covers the outer concave apex of the indication change section.

[0044] The second waveform variation characteristic includes: a pair of troughs appearing intermittently during the movement of the microfluidic chip.

[0045] Step 3: If the light spot falls on the first structure, the light spot is first moved to the second specific position based on the first waveform change characteristic, and then the microfluidic chip is continued to move along the current moving direction to move the light spot to the second structure.

[0046] If the light spot falls on the second structure, the microfluidic chip is moved based on the variation characteristics of the second waveform, so that a pair of troughs appear intermittently. That is, after entering the area where a series of discontinuous block structures are located, troughs with equal spacing will continue to move on the waveform when the microfluidic chip is moved. Figure 3 then after the last pair of troughs that conform to the second waveform variation characteristics disappear, continue to move the microfluidic chip along the current moving direction until another trough appears, where the position of the trough corresponds to the position of a side wall.

[0047] According to the above method, after adjusting the microfluidic chip to find the position of the other side wall, the midpoint of the two side walls can be further located as the observation point.

[0048] A system corresponding to the method provided in Example 2 is provided below.

[0049] Example 3:

[0050] Example 3 provides a system for rapidly positioning a sample observation area, comprising: a position adjustment device, a laser, a time-domain stretch imaging detection device, a photodetector, and a waveform observer. The position adjustment device is used to control the movement of the microfluidic chip, the laser is used to generate light pulses, the time-domain stretch imaging detection device is used to obtain a detection light signal, the photodetector is used to convert the detection light signal into an analog electrical signal, and the waveform observer is used to convert the analog electrical signal into a digital electrical signal and display the signal waveform.

[0051] The time domain stretch imaging detection device includes a spatial dispersion element, a time domain dispersion element, and other optical elements necessary for time domain stretch imaging, which are not described in detail here.

[0052] Because the structure of the pipe sidewall is significantly different from that of the adjacent areas, the waveform observer captures the intensity signal waveform of light at different spatial locations (time-domain stretching technology aligns time and space). When light strikes the pipe sidewall, the intensity of the light spot at that location decreases. Therefore, the waveform observer's time-domain waveform will have a trough at the corresponding location, corresponding to the decrease in light intensity. The present invention utilizes this feature to quickly locate the time-domain stretching cell observation area.

[0053] The system for rapidly locating the sample observation area provided in Example 3 can implement the method for rapidly locating the sample observation area described in Example 2. That is, the ultrafast cell flow cytometry system based on time-domain stretch imaging can rapidly locate the time-domain stretch cell detection area.

[0054] In summary, the present invention not only provides a design of a microfluidic chip that is conducive to the rapid positioning of the sample observation area, but also provides a method and system for quickly positioning the sample observation area using the above-mentioned microfluidic chip, which can overcome the problems existing in the existing technology and achieve rapid and accurate positioning of the sample observation area.

[0055] Finally, it should be noted that the above specific implementation methods are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail with reference to examples, those skilled in the art should understand that the technical solutions of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A microfluidic chip, characterized in that: include: A channel microstructure and a positioning microstructure; the channel microstructure comprises a microfluidic channel for sample flow; the positioning microstructure is used to guide the position adjustment of the microfluidic chip to locate the sample observation area; The positioning microstructure includes two sets of positioning components, the two sets of positioning components are respectively located in the outer areas of the two side walls of the microfluidic channel corresponding to the sample observation area, and the two sets of positioning components are symmetrically arranged with respect to the microfluidic channel corresponding to the sample observation area; the two sets of positioning components are respectively used to locate the positions of the two side walls; Each group of positioning components includes a first structure arranged along a first direction and a second structure arranged along a second direction. The two side walls of the microfluidic channel corresponding to the sample observation area extend along the first direction, and the second direction is perpendicular to the first direction; the first structure is a continuous structure, which includes a first straight line segment, an indication change segment and a second straight line segment arranged in sequence along the first direction; the second structure is a string structure, which includes a number of blocks arranged at equal intervals along the second direction, and the string structure is located between the indication change segment and a side wall of the microfluidic channel corresponding to the sample observation area.

2. The microfluidic chip according to claim 1, characterized in that The total length of the first structure is 1~3 mm, the width of the straight section in the first structure is 20~40 um, and the height of the first structure is 30~60 um; the total length of the second structure is 1~3 mm, the blocks are rectangular structures, and the length of each block is 20~40 um, the width is 20~40 um, and the height is 30~60 um.

3. The microfluidic chip according to claim 1, characterized in that The indication change section is a triangular concave structure, the outer concave vertex of the triangular concave structure extends toward the second direction and points to the second structure; the distance between the first block in the second structure and the indication change section is greater than or equal to the spacing between two adjacent blocks, and the distance between the last block in the second structure and the sample observation area is greater than or equal to the spacing between two adjacent blocks.

4. A method for quickly locating a sample observation area, characterized in that: Obtaining a microfluidic chip comprising a channel microstructure and a positioning microstructure, wherein the channel microstructure comprises a microfluidic channel for sample flow, and using the positioning microstructure to guide position adjustment of the microfluidic chip to locate a sample observation area; The positioning microstructure includes two sets of positioning components, the two sets of positioning components are respectively located in the outer regions of the two side walls of the microfluidic channel corresponding to the sample observation area, and the two sets of positioning components are symmetrically arranged with respect to the microfluidic channel corresponding to the sample observation area; based on the differences in the waveforms of the time-domain stretch imaging corresponding to each set of positioning components in two mutually perpendicular directions, the two sets of positioning components are used to respectively locate the positions of the two side walls of the microfluidic channel corresponding to the sample observation area; Each group of positioning components includes a first structure arranged along a first direction and a second structure arranged along a second direction. The two side walls of the microfluidic channel corresponding to the sample observation area extend along the first direction, and the second direction is perpendicular to the first direction; the first structure is a continuous structure, which includes a first straight line segment, an indication change segment and a second straight line segment arranged in sequence along the first direction; the indication change segment is a triangular concave structure, and the outer concave vertex of the triangular concave structure extends toward the second direction and points to the second structure; the second structure is a string structure, which includes a number of blocks arranged at equal intervals along the second direction, and the string structure is located between the indication change segment and a side wall of the microfluidic channel corresponding to the sample observation area.

5. The method for rapidly locating a sample observation area according to claim 4, characterized in that: Finding the location of the sidewalls involves the following steps: Step 1: visually adjusting the microfluidic chip so that the positioning microstructure moves to the light spot; adjusting the relative position of the positioning microstructure and the light spot until a waveform observer displays a double-trough waveform; Step 2: Move the microfluidic chip and determine whether the current light spot falls on the first structure or the second structure based on the first waveform change characteristic and the second waveform change characteristic; The first waveform change characteristic includes: when the microfluidic chip is moved laterally, the light spot maintains a double-trough waveform while moving within the straight section of the positioning microstructure, with the two troughs being designated as a first trough and a second trough, respectively; when the light spot moves from one end of the straight section to the indication change section, the second trough gradually moves along a third direction and eventually disappears as displayed on a waveform viewer; the first trough initially remains unchanged and then gradually moves along the third direction; after reaching a first specific position, if the microfluidic chip is continued to be moved, the first trough gradually moves in a direction opposite to the third direction as displayed on the waveform viewer, with the first specific position covering an inner concave apex of the indication change section; after reaching the first specific position, the microfluidic chip is moved longitudinally, causing the light spot to move from the first specific position to a second specific position, resulting in the first trough disappearing and the second trough reappearing, with the second specific position covering an outer concave apex of the indication change section; The second waveform variation characteristic includes: a pair of troughs intermittently appearing during the movement of the microfluidic chip; Step 3: If the light spot falls on the first structure, the light spot is first moved to the second specific position based on the first waveform variation characteristic, and then the microfluidic chip is continued to move along the current movement direction so that the light spot moves to the second structure; If the light spot falls on the second structure, the microfluidic chip is moved based on the second waveform change characteristics so that a pair of troughs appear intermittently. Then, after the last pair of troughs that conform to the second waveform change characteristics disappears, the microfluidic chip continues to be moved along the current moving direction until another trough appears, and the position of the trough corresponds to the position of a side wall.

6. A system for rapidly locating a sample observation area, characterized in that: include: Position adjustment device, laser, time domain stretch imaging detection device, photodetector and waveform observer; The position adjustment device is used to control the movement of the microfluidic chip, the laser is used to generate light pulses, the time domain stretch imaging detection device is used to obtain a detection light signal, the photodetector is used to convert the detection light signal into an analog electrical signal, and the waveform observer is used to convert the analog electrical signal into a digital electrical signal and display the signal waveform; The system for rapidly positioning a sample observation area is used to implement the steps in the method for rapidly positioning a sample observation area according to any one of claims 4 to 5.

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