CN216093734U - Red blood cell and platelet micro-separation device with mixed-shape electrodes - Google Patents

Abstract

The utility model belongs to the field of microfluidics, and particularly discloses a semicircular electrode erythrocyte and platelet micro-separation device which comprises two inlets, two outlets, a microfluid channel, two buffer chambers, two rectangular electrodes, three semicircular electrodes and two triangular electrodes. A certain number of positive and negative staggered electrodes are applied above the microfluidic channel, the electrodes can generate an uneven electric field in the space of the microfluidic channel, and when red blood cells and platelets in fluid pass through the electric field, the red blood cells and the platelets can be subjected to different dielectrophoresis forces due to the properties of the red blood cells and the platelets, so that the red blood cells and the platelets can be displaced in different directions. The red blood cells and the platelets in the blood can be separated by the displacement of the red blood cells and the platelets in different directions under the action of the force. The utility model has the advantages that: the separation speed is high, the separation particles are fine, red blood cells and platelets do not need to be marked, and the damage to a separated object is small; the design structure is simple and easy to realize.

Description

Red blood cell and platelet micro-separation device with mixed-shape electrodes

Technical Field

The utility model relates to an electrode red blood cell and platelet micro-separation device with a novel rectangular, semicircular and triangular mixed structure, and the method is a direct-current dielectrophoresis micro-nano control technology.

Background

Microfluidics refers to the science and technology involved in systems that process or manipulate tiny fluids (nanoliters to attoliters in volume) using microchannels (tens to hundreds of microns in size), and is an emerging interdiscipline that involves chemical, fluid physics, microelectronics, new materials, biology, and biomedical engineering. Because of the characteristics of miniaturization, integration, and the like, microfluidic devices are generally called microfluidic chips, also called lab-on-a-chip and micro total analysis systems; the micro-fluidic chip can integrate basic operation units such as sample preparation, reaction, separation, detection and the like in the biological, medical and chemical analysis processes to a micron-level chip, and automatically complete the whole analysis process.

The cell capture and separation is a process of separating one or more cells from a liquid by means of physics, chemistry, biology and the like, and is an important experimental content in the aspects of biology, medical diagnosis, toxicology monitoring and the like, which is always a hotspot of laboratory research.

Traditional cell separation methods are mainly divided into two categories: the first type is separation depending on the size and gravity characteristics of cells, such as a centrifugal method, a gravity sedimentation method and the like, and the method has the advantages of low separation precision, long separation time, complex operation and great influence on cell activity; the other type of method is a method which requires indirect charging of cells or addition of magnetic substances and finally cell separation under the action of an electric field or a magnetic field, such as electrophoresis, magnetic separation and the like. Meanwhile, expensive professional equipment and professional operators are required, so that the wide application of the equipment is limited.

The dielectrophoresis technology is used as an effective micro-nano particle control method, and an antibody does not need to be marked, so that the biological property change of cells caused by antibody reaction in the separation process can be avoided; the low-intensity electric field used is non-destructive to the cell. The dielectrophoresis separation method is flexible to use, the electric field intensity, the frequency and the phase position are easy to regulate and control, the automation operation is convenient, and meanwhile, the dielectrophoresis separation method can be combined with other methods to achieve the optimal cell separation detection effect.

Disclosure of Invention

The utility model aims to provide a red blood cell and platelet micro-separation device with a mixed-shape electrode with a novel structure, which is used for optimizing a micro-flow channel structure, reducing damage to cells and improving the separation efficiency of red blood cells and platelets.

The technical scheme of the utility model is as follows: a mixed-shape red blood cell and platelet micro-separation device comprises a first inlet of blood to be separated, a first inlet of carrier fluid, a first buffer chamber, a microfluidic channel, seven electrodes, a second buffer chamber, a first outlet of red blood cells and a first outlet of platelets; injecting blood to be separated from a first inlet of the blood to be separated, injecting a carrier fluid (potassium chloride solution) from the first inlet of the carrier fluid, and enabling the blood to be separated and the carrier fluid to flow through a first buffer chamber, a microfluidic channel and a second buffer chamber in sequence after meeting; the separated red blood cells flow out from the red blood cell first outlet, and the platelets flow out from the platelet first outlet.

The benefits of the utility model are: compared with other micro-separation devices, the micro-separation device has the advantages that in order to ensure that fragile red blood cells and blood platelets are damaged less in the flowing process, the first electrode (1) at the head end is cut, so that a part of space is reserved to be used as a buffer chamber, the blood and the blood platelets to be separated cannot be damaged greatly due to sudden change of the structure when passing through the electrodes, and the integrity of the cells is ensured. The seventh electrode (10) at the tail end is also cut to form a second buffer chamber together with the red blood cell outlet, the platelet outlet and the microfluidic channel. Five electrodes positioned between the first electrode and the seventh electrode are formed by sequentially arranging semicircular electrodes and triangular electrodes, and the optimized electrode shape and arrangement sequence greatly increase the cell separation efficiency, so that the separated red blood cells are purer.

Drawings

FIG. 1 is a schematic diagram of a two-dimensional planar structure of a red blood cell and platelet microdiapheresis device with mixed-shape electrodes, wherein each structure comprises: the blood separating device comprises a first inlet (1) for blood to be separated, a first inlet (2) for carrier fluid, a first buffer chamber (3), a first electrode (4), a second electrode (5), a third electrode (6), a fourth electrode (7), a fifth electrode (8), a sixth electrode (9), a seventh electrode (10), a second buffer chamber (11), a first outlet (12) for red blood cells, a first outlet (13) for platelets and a microfluidic channel (14).

FIG. 2 is a two-dimensional potential distribution diagram of a semicircular electrode red blood cell and platelet micro-separation device, wherein the lightest color is positive 5V, the darkest color is negative 1V, and the potentials are uniformly arranged in a microfluidic channel in a positive-negative staggered mode, so that non-uniform electric fields are formed after particles in a solution pass through the microfluidic channel.

FIG. 3 is a two-dimensional diagram of the separation effect of a triangular electrode red blood cell and platelet micro-separation device, wherein small-diameter particles are platelets and flow out from an upper platelet outlet, large-diameter particles are red blood cells and flow out from a lower red blood cell outlet, and the separation effect is expected.

Detailed Description

The present invention will be further described with reference to the accompanying drawings, but the embodiments of the present invention are not limited thereto.

As shown in the attached figure 1, the triangular electrode red blood cell and platelet micro-separation device comprises a first inlet (1) for blood to be separated, a first carrier fluid inlet (2), a first buffer chamber (3), a first electrode (4), a second electrode (5), a third electrode (6), a fourth electrode (7), a fifth electrode (8), a sixth electrode (9), a seventh electrode (10), a second buffer chamber (11), a first red blood cell outlet (12), a first platelet outlet (13) and a microfluidic channel (14).

Specifically, the blood inlet (1) to be separated, the carrier fluid inlet (2) and the microfluidic channel (5) can be synchronously designed and simultaneously manufactured by a Micro-Electro-Mechanical System (MEMS) micromachining process, which is an industrial technology integrating a microelectronic technology and a Mechanical engineering, and the operating range is in a micrometer range.

Specifically, blood to be separated is injected from a first inlet (1) of the blood to be separated, and the initial flow rate is 100 mu m/s; the specific preparation method comprises the steps of taking a proper amount of purified water, adding a proper amount of potassium chloride into the purified water, and detecting that the conductivity of the solution meets the requirement by using a conductivity meter; the carrier fluid was injected from the carrier fluid inlet at an initial flow rate of 900 μm/s.

Specifically, the nonuniform electric field in the microfluidic channel is generated by applying different potentials to different electrodes, specifically, the potentials applied to the first electrode (4), the third electrode (6), the fifth electrode (8) and the seventh electrode (10) are 5V, the potentials applied to the second electrode (6), the fourth electrode (7) and the sixth electrode (9) are-5V, and the applied alternating current frequency is 100 kHz; the spatially non-uniform electric field distribution is shown in figure 2.

Specifically, the platelet conductivity was σ 1 =0.25S/m, and the dielectric constant was 50; red blood cell conductivity σ 1 =0.31S/m, dielectric constant 59; if the red blood cells and the platelets are considered as micro-nano particles, the density of the micro-nano particles in blood is 1050kg/m & lt 3 & gt; the dynamic viscosity of blood was 0.001 pas.

Specifically, its characterized in that: the length of the three-dimensional structure of the micro-fluid channel (13) is 560 mu m, the width is 40 mu m, and the height is 40 mu m; the separation device is of a bilateral symmetry structure, and the total length of the microfluidic channel (13) is 832 micrometers. The electrode structure mainly falls into 3, and one is the rectangle electrode, includes: a first electrode (5) and a seventh electrode (7); an electrode in a semicircular configuration, comprising: a second electrode (5), a fourth electrode (7), and a sixth electrode (9); the other one is a triangular electrode, and the two-dimensional structures of the third electrode (6), the fifth electrode (8) and the fifth electrode (8) have the following main geometric parameters in the horizontal direction: width of the rectangular electrode: diameter of semicircular electrode: the width of the triangular electrode is as follows: electrode spacing = 1: 1: 1: 1; the dimensional relationship in the vertical direction is that the rectangular electrode is very high: the semicircular electrode is high: triangular electrode high = 1: 1: 1.

specifically, the length of the microfluidic channel is not limited to this, and the length of the microfluidic channel can be appropriately shortened or lengthened according to actual needs, so as to correspondingly reduce or increase the number of the triangular electrodes and the semicircular electrodes.

Specifically, the specific structures of the first buffer chamber (3) and the second buffer chamber (12) should not obstruct or excessively influence the dielectrophoresis movement of the red blood cells and the platelets, and should ensure that the red blood cells and the platelets are impacted as little as possible during the movement process, thereby protecting the fragile cells.

The utility model is not to be considered as being limited to the details shown, since various modifications and equivalent arrangements may be made without departing from the spirit and scope of the utility model.

Claims (5)

1. An electrode red blood cell and platelet micro separation device having a mixed shape, comprising: the device comprises a blood inlet (1) to be separated, a carrier fluid inlet (2), a first buffer chamber (3), a first electrode (4), a second electrode (5), a third electrode (6), a fourth electrode (7), a fifth electrode (8), a sixth electrode (9), a seventh electrode (10), a second buffer chamber (11), a red blood cell outlet (12), a platelet outlet (13) and a microfluidic channel (14); the blood to be separated is injected from a blood inlet (1) to be separated, and a potassium chloride solution is used as a carrier fluid and is injected from a carrier fluid inlet (2); after being converged at the junction of the blood inlet (1) to be separated and the carrier fluid inlet (2), the blood to be separated and the carrier fluid sequentially flow through a first buffer chamber (3), a micro-fluid channel (14) and a second buffer chamber (11); the separated red blood cells flow out from a red blood cell outlet (12), and the platelets flow out from a platelet outlet (13).

2. The red blood cell and platelet micro-separation device with mixed shape according to claim 1, wherein: the blood inlet (1) to be separated, the carrier fluid inlet (2), the microfluidic channel (14), the red blood cell outlet (12) and the platelet outlet (13) are made of polydimethylsiloxane or polymethyl methacrylate by a template hot pressing method or a template pouring technology.

3. The red blood cell and platelet micro-separation device with mixed shape according to claim 1, wherein: the length of the three-dimensional structure of the micro-fluid channel (14) is 560 mu m, the width is 40 mu m, and the height is 40 mu m; the separation device is of a bilateral symmetry structure, and the total length of the microfluidic channel (14) is 832 micrometers.

4. The red blood cell and platelet micro-separation device with mixed shape according to claim 1, wherein: the electrode structure mainly falls into 3, and one is the rectangle electrode, includes: a first electrode (4) and a seventh electrode (10); an electrode in a semicircular configuration, comprising: a second electrode (5), a fourth electrode (7), and a sixth electrode (9); the other one is a triangular electrode, and the two-dimensional structures of the third electrode (6) and the fifth electrode (8) have the following main geometric parameters in the horizontal direction: width of the rectangular electrode: diameter of semicircular electrode: the width of the triangular electrode is as follows: electrode spacing = 1: 1: 1: 1; the dimensional relationship in the vertical direction is that the rectangular electrode is very high: the semicircular electrode is high: triangular electrode high = 1: 1: 1.

5. the red blood cell and platelet micro-separation device with mixed shape according to claim 1, wherein: the included angle between the axial line of the blood inlet (1) and the platelet outlet (13) to be separated and the axial line of the microfluid channel (14) is 45 degrees; the included angle between the axial lines of the carrier fluid inlet (2) and the erythrocyte outlet (12) and the axial line of the microfluid channel (14) is 45 degrees; the blood inlet (1) and the carrier fluid inlet (2) to be separated, the red blood cell outlet (12) and the platelet outlet (13) are geometrically symmetrical with respect to the axis of the microfluidic channel (14), respectively.

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