Flow cytometer driven by microfluid

Abstract

The utility model discloses a microfluid driven flow cytometer, which comprises a substrate, an optical fiber element and a waste liquid discharge part, the substrate is provided with a sample introduction area, a sample introduction channel and a groove, the sample introduction area is communicated with the sample introduction channel, a plurality of rectangular arrays are arranged in the sample introduction channel, the density of the rectangular arrays is gradually increased towards the direction far away from the sample introduction area, and the groove is communicated with the sample introduction area. A wettability gradient is formed in the sample introduction channel, liquid drops are subjected to unbalanced interfacial tension at the front end and the rear end on the wettability gradient surface so as to obtain driving force for spontaneous movement, and the liquid drops move towards a wetter and high-surface-energy direction, so that spontaneous movement of the liquid drops can be realized; the optical fiber element is arranged in the groove and is limited through the groove, so that the installation precision requirement is low, and the stability is high; the waste liquid discharge part is arranged at the tail end of the substrate and is obliquely arranged relative to the substrate, and the obliquely arranged waste liquid discharge part can directly discharge the liquid drops, so that the liquid drops can be conveniently and continuously detected.

Description

Technical Field

[0001] The utility model relates to the technical field of cell detection and analysis, in particular to a microfluid-driven flow cytometer. Background Art

[0002] Flow cytometry is a cell analysis technique that was first used in the 1950s to measure cell volume. It detects cells as they pass through an observation hole in a straight line with a fast-flowing fluid. Traditional flow cytometers are mainly composed of four parts: a flow chamber and a fluid flow system, a laser source and an optical system, a photoelectric tube and an electronic system, and a computer and an analysis system. The fluid is driven by the fluid flow system, and the cells in the fluid are observed by the photoelectric tube. This setup has a complex instrument structure, requires high precision in the alignment and installation of optical components, and is difficult to manufacture. Utility Model Content

[0003] The utility model aims to solve at least one of the technical problems existing in the prior art. To this end, the utility model proposes a microfluid-driven flow cytometer with a simple structure, low precision requirements, and low design and manufacturing difficulty.

[0004] A microfluidic driven flow cytometer according to the first embodiment of the utility model comprises:

[0005] A substrate, wherein the substrate is provided with an injection area, an injection channel and a groove, and the injection area is connected to the injection channel;

[0006] An optical fiber element, the optical fiber element is used to detect cells, and the optical fiber element is arranged in the groove;

[0007] A waste liquid discharge component, wherein the waste liquid discharge component is arranged at the end of the substrate and is inclined relative to the substrate;

[0008] Wherein, a plurality of rectangular arrays are arranged in the injection channel, and the density of the rectangular arrays gradually increases in a direction away from the injection area, so as to form a wettability gradient in the injection channel.

[0009] A microfluidic-driven flow cytometer according to an embodiment of the first aspect of the utility model has at least the following beneficial effects: a microfluidic-driven flow cytometer of the utility model comprises a substrate, an optical fiber element and a waste liquid discharge component, the substrate is provided with an injection area, an injection channel and a groove, the injection area is connected to the injection channel, a plurality of rectangular arrays are provided in the injection channel, the density of the rectangular arrays gradually increases in the direction away from the injection area, an infiltration gradient is formed in the injection channel, and droplets on the surface of the infiltration gradient are subjected to unbalanced front and rear end interfacial tension to obtain a driving force for spontaneous movement, and move in a direction of more wetting and high surface energy, thereby realizing the spontaneous movement of droplets; the optical fiber element is arranged in the groove, and the optical fiber element is limited by the groove, so that the installation precision requirement is low and the stability is strong; the waste liquid discharge component is arranged at the end of the substrate, and the waste liquid discharge component is arranged obliquely relative to the substrate, and the obliquely arranged waste liquid discharge component can directly discharge the droplets, which is convenient for continuous detection of the droplets.

[0010] According to some embodiments of the present invention, the rectangular array includes a first rectangular array, a second rectangular array, a third rectangular array, a fourth rectangular array and a fifth rectangular array arranged in sequence in a direction away from the sampling area, and the density of the first rectangular array, the second rectangular array, the third rectangular array, the fourth rectangular array and the fifth rectangular array increases in sequence.

[0011] According to some embodiments of the present invention, the optical fiber element includes an incident optical fiber, a front scattering optical fiber and a side scattering optical fiber. The incident optical fiber and the front scattering optical fiber are arranged on both sides of the injection channel opposite to each other and perpendicular to the injection channel. The side scattering optical fiber is arranged obliquely on one side of the front scattering optical fiber, and the inclination angle between the side scattering optical fiber and the front scattering optical fiber is 45°.

[0012] According to some embodiments of the present invention, the shape of the injection area is set to be circular, the shape of the injection channel is set to be groove-shaped, and the width of the injection channel is smaller than the diameter of the injection area.

[0013] According to some embodiments of the present invention, the injection area, the injection channel and the groove are formed by laser engraving.

[0014] According to some embodiments of the present invention, an injection component is further included, and the injection component includes an injection head, and the injection head is arranged toward the injection area.

[0015] According to some embodiments of the utility model, the waste liquid discharge component is provided with a discharge channel connected to the injection channel, and a discharge rectangular array is provided in the discharge channel, and the density of the discharge rectangular array is the same as the density of the rectangular array with the largest density in the injection channel.

[0016] According to some embodiments of the present invention, the rectangular array is formed by photoresist etching.

[0017] According to some embodiments of the present invention, the depth of the injection area, the injection channel and the groove is 200um.

[0018] According to some embodiments of the present invention, the material of the substrate includes polymethyl methacrylate.

[0019] Additional aspects and advantages of the present invention will be given in part in the following description, and in part will become apparent from the following description, or will be learned through the practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0021] Figure 1 It is a structural schematic diagram of a microfluid-driven flow cytometer according to an embodiment of the utility model. DETAILED DESCRIPTION

[0022] The embodiments of the present invention are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and cannot be understood as limiting the present invention.

[0023] In the description of the present invention, it should be understood that descriptions involving orientation, such as up, down, front, back, left, right, inside, outside, etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0024] In the description of the present utility model, "several" means one or more, "more" means more than two, "greater than", "less than", "exceed" etc. are understood to exclude the number itself, and "above", "below", "within" etc. are understood to include the number itself. If there is a description of "first" or "second", it is only used for the purpose of distinguishing the technical features, and cannot be understood as indicating or implying the relative importance or implicitly indicating the number of the indicated technical features or implicitly indicating the order of the indicated technical features.

[0025] In the description of the present invention, unless otherwise clearly defined, terms such as setting, installing, connecting, assembling, and matching should be understood in a broad sense, and technicians in the relevant technical field can reasonably determine the specific meanings of the above terms in the present invention based on the specific content of the technical solution.

[0026] Refer to the following Figure 1 A microfluidic driven flow cytometer according to an embodiment of the utility model is described.

[0027] A microfluid-driven flow cytometer according to an embodiment of the utility model, such as Figure 1 As shown, it includes a substrate 100, an optical fiber element and a waste liquid discharge component 500. The substrate 100 is provided with a sampling area 210, a sampling channel 220 and a groove. The sampling area 210 is connected to the sampling channel 220. After the droplet enters the sampling area, it flows to the sampling channel 220. A plurality of rectangular arrays are arranged in the sampling channel 220. The density of the rectangular array gradually increases in the direction away from the sampling area 210. A wettability gradient is formed in the sampling channel 220. The droplet is subjected to the unbalanced front and rear end interfacial tension on the wettability gradient surface and obtains the driving force for spontaneous movement. The droplet moves in a more wetting and high surface energy direction, and can realize the spontaneous movement of the droplet. The optical fiber element is used to detect cells. The optical fiber element is arranged in the groove. The optical fiber element is limited by the groove. The installation precision requirement is low, the design and production difficulty is low, and the stability is strong. The waste liquid discharge component 500 is disposed at the end of the substrate 100. The waste liquid discharge component 500 is tilted relative to the substrate 100. The tilted waste liquid discharge component 500 can directly discharge the droplets, which is convenient for continuous detection of the droplets.

[0028] According to some embodiments of the utility model, the rectangular array includes a first rectangular array 310, a second rectangular array 320, a third rectangular array 330, a fourth rectangular array 340 and a fifth rectangular array 350 which are sequentially arranged in a direction away from the injection area 210, and the density of the first rectangular array 310, the second rectangular array 320, the third rectangular array 330, the fourth rectangular array 340 and the fifth rectangular array 350 increases sequentially. A plurality of rectangular arrays are arranged in the injection channel 220, specifically, the rectangular array includes a first rectangular array 310, a second rectangular array 320, a third rectangular array 330, a fourth rectangular array 340 and a fifth rectangular array 350, and the first rectangular array 310, the second rectangular array 320, the third rectangular array 330, the fourth rectangular array 340 and the fifth rectangular array 350 are sequentially arranged in a direction away from the injection area 210, and the density of the rectangular array gradually increases in the direction away from the injection area 210, that is, the first rectangular array 310, the second rectangular array 320, the third rectangular array 330, the fourth rectangular array 340 and the fifth rectangular array 350 increase sequentially. The density of the first rectangular array 330, the fourth rectangular array 340, and the fifth rectangular array 350 increases in sequence. When the droplet enters the injection channel 220, the first rectangular array 310 with a large density is arranged on the side close to the sampling area, and the fifth rectangular array 350 with a small density is arranged on the side away from the sampling area. A wettability gradient is formed in the injection channel 220. The droplet is subjected to the unbalanced front and rear end interfacial tension on the wettability gradient surface and obtains the driving force for spontaneous movement. The droplet moves from the first rectangular array 310 toward the fifth rectangular array 350 with a more wet surface and high surface energy, thereby realizing the spontaneous movement of the droplet. It can be understood that in some embodiments, the pattern densities of the first rectangular array 310, the second rectangular array 320, the third rectangular array 330, the fourth rectangular array 340, and the fifth rectangular array 350 are 0.5, 0.6, 0.7, 0.8, and 0.9, respectively. It can be understood that the width of the injection channel 220 and the size of the rectangular array are related to the particle size of the cell suspension to be tested. In some embodiments, when measuring 6-10um red blood cells, the width of the injection channel 220 is set to 50um, and the array side lengths of the first rectangular array 310, the second rectangular array 320, the third rectangular array 330, the fourth rectangular array 340 and the fifth rectangular array 350 are set to 32um, 23um, 16um, 14um and 6um respectively.

[0029] According to some embodiments of the utility model, the optical fiber element includes an incident optical fiber 410, a front scattering optical fiber 420 and a side scattering optical fiber 430. The incident optical fiber 410 and the front scattering optical fiber 420 are arranged on both sides of the injection channel 220 and perpendicular to the injection channel 220. The side scattering optical fiber 430 is arranged obliquely on one side of the front scattering optical fiber 420, and the inclination angle between the side scattering optical fiber 430 and the front scattering optical fiber 420 is 45°. The optical fiber element is used to detect cells, and the optical fiber element is arranged in a groove. Specifically, the optical fiber element includes an incident optical fiber 410, a front scattering optical fiber 420 and a side scattering optical fiber 430. The incident optical fiber 410, the front scattering optical fiber 420 and the side scattering optical fiber 430 are all arranged in the groove. The optical fiber element is limited by the groove, and the installation precision requirement is low and the stability is strong. The incident optical fiber 410 and the forward scattering optical fiber 420 are arranged on both sides of the injection channel 220 opposite to each other. The front scattering optical fiber 420 is arranged opposite to the incident optical fiber 410 and is used for collecting forward scattered light. The intensity of the forward scattered light can reflect the volume of the cell; the side scattering optical fiber 430 is arranged obliquely on one side of the front scattering optical fiber 420, and the inclination angle between the side scattering optical fiber 430 and the front scattering optical fiber 420 is 45°. The side scattering optical fiber 430 is used for collecting side scattered light. The more complex the internal structure of the cell, the stronger the intensity of its side scattered light.

[0030] According to some embodiments of the utility model, the shape of the injection area 210 is set to be circular, the shape of the injection channel 220 is set to be groove-shaped, and the width of the injection channel 220 is smaller than the diameter of the injection area 210. The injection area 210 is connected to the injection channel 220, the shape of the injection area 210 is set to be circular, the shape of the injection channel 220 is set to be groove-shaped, and the width of the injection channel 220 is smaller than the diameter of the injection area 210. After the droplet enters the sampling area, it will flow to the injection channel 220, and the detection operation of the cell will be completed in the injection channel 220.

[0031] According to some embodiments of the present invention, the sampling area 210, the sampling channel 220 and the groove are formed by laser engraving. Specifically, the sampling area 210, the sampling channel 220 and the groove are engraved on the surface of the substrate 100 by laser. In some embodiments, the depth of the sampling area 210, the sampling channel 220 and the groove formed by laser engraving is 200um. In some embodiments, the material of the substrate 100 is set to polymethyl methacrylate (PMMA).

[0032] According to some embodiments of the utility model, an injection component 600 is further included, and the injection component 600 includes an injection head, and the injection head is arranged toward the injection area 210. The injection component 600 is used to inject droplets into the injection area 210. Specifically, the injection component 600 includes an injection head, and the injection head is arranged from top to bottom toward the injection area 210. The injection head injects liquid downward, and the droplets fall into the injection area 210. The injection area 210 is connected to the injection channel 220. After the droplets enter the sampling area, they flow to the injection channel 220, and the detection operation of the cells is completed in the injection channel 220.

[0033] According to some embodiments of the utility model, the waste liquid discharge component 500 is provided with a discharge channel 510 connected to the injection channel 220, and a discharge rectangular array 520 is provided in the discharge channel 510, and the density of the discharge rectangular array 520 is the same as the density of the rectangular array with the highest density in the injection channel 220. The waste liquid discharge component 500 is used for the discharge of waste liquid, and the waste liquid discharge component 500 is provided with a discharge channel 510, and the discharge channel 510 is connected to the injection channel 220, and a discharge rectangular array 520 is provided in the discharge channel 510, and the density of the discharge rectangular array 520 is the same as the density of the rectangular array with the highest density in the injection channel 220, and the rectangular array with the highest density in the injection channel 220 is arranged at the end of the injection channel 220, so that the discharge channel 510 and the end of the injection channel 220 have consistent wettability, which is convenient for the discharge of waste liquid.

[0034] According to some embodiments of the present invention, the rectangular arrays are formed by etching photoresist. Specifically, a 90 nm thick epoxy SU-8 photoresist is spin-coated on the substrate 100, and the photoresist is baked, exposed, developed, etched and cleaned to obtain a plurality of rectangular arrays.

[0035] The embodiments of the present invention are described in detail above in conjunction with the accompanying drawings, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge scope of ordinary technicians in the relevant technical field without departing from the purpose of the present invention.

Claims

1. A microfluidic driven flow cytometer, characterized in that: include: A substrate, wherein the substrate is provided with an injection area, an injection channel and a groove, and the injection area is connected to the injection channel; An optical fiber element, the optical fiber element is used to detect cells, and the optical fiber element is arranged in the groove; A waste liquid discharge component, wherein the waste liquid discharge component is arranged at the end of the substrate and is inclined relative to the substrate; Wherein, a plurality of rectangular arrays are arranged in the injection channel, and the density of the rectangular arrays gradually increases in a direction away from the injection area, so as to form a wettability gradient in the injection channel.

2. A microfluidic driven flow cytometer according to claim 1, characterized in that: The rectangular array includes a first rectangular array, a second rectangular array, a third rectangular array, a fourth rectangular array and a fifth rectangular array arranged in sequence in a direction away from the sampling area, and the density of the first rectangular array, the second rectangular array, the third rectangular array, the fourth rectangular array and the fifth rectangular array increases in sequence.

3. A microfluidic driven flow cytometer according to claim 1, characterized in that: The optical fiber element includes an incident optical fiber, a front scattering optical fiber and a side scattering optical fiber. The incident optical fiber and the front scattering optical fiber are arranged on both sides of the injection channel opposite to each other and perpendicular to the injection channel. The side scattering optical fiber is arranged obliquely on one side of the front scattering optical fiber, and the inclination angle between the side scattering optical fiber and the front scattering optical fiber is 45°.

4. A microfluidic driven flow cytometer according to claim 1, characterized in that: The shape of the injection area is set to be circular, the shape of the injection channel is set to be groove-shaped, and the width of the injection channel is smaller than the diameter of the injection area.

5. A microfluidic driven flow cytometer according to claim 1, characterized in that: The injection area, the injection channel and the groove are formed by laser engraving.

6. A microfluidic driven flow cytometer according to claim 1, characterized in that: It also includes an injection component, which includes an injection head, and the injection head is arranged toward the injection area.

7. A microfluidic driven flow cytometer according to claim 1, characterized in that: The waste liquid discharge component is provided with a discharge channel connected to the injection channel, and a discharge rectangular array is provided in the discharge channel. The density of the discharge rectangular array is the same as the density of the rectangular array with the largest density in the injection channel.

8. A microfluidic driven flow cytometer according to claim 1, characterized in that: The rectangular array is formed by etching photoresist.

9. A microfluidic driven flow cytometer according to claim 1, characterized in that: The depths of the injection area, the injection channel and the groove are 200 um.

10. A microfluidic driven flow cytometer according to claim 1, characterized in that: The material of the substrate includes polymethyl methacrylate.

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