Membraneless dialysis microfluidic chip with parallel structure

Abstract

The present invention discloses a membraneless dialysis microfluidic chip with a parallel structure, comprising a plurality of dialysis components, and the plurality of dialysis components are arranged in parallel, and the dialysis components alternately form a cleaning section and a separation section along the direction of blood flow; the dialysis component comprises a blood channel and a dialysate channel, and the blood channel and the dialysate channel meet in the cleaning section and separate in the separation section; in the cleaning section, the blood and the dialysate contact at the center of the cleaning section channel, and when entering the next cleaning section, the contact surface of the blood and the dialysate is the outer fluid of the previous cleaning section. In addition to solving the problems of low efficiency and large cell loss in existing dialysis, effectively increasing dialysis efficiency and reducing blood cell loss, the membraneless dialysis microfluidic chip also utilizes its parallel honeycomb network structure to achieve the purpose of increasing the chip working capacity and reducing the volume of the artificial kidney, thereby increasing the dialysate utilization efficiency.

Description

Technical Field

[0001] The invention relates to a membrane-free dialysis microfluidic chip with a parallel structure. Background Art

[0002] At present, there are nearly 800,000 dialysis patients in my country. With the accelerated progress of my country's aging population, the continuous improvement of dialysis quality and dialysis treatment rate, and the improvement and perfection of medical insurance, the number of dialysis patients continues to grow at a rate of about 10% per year. It is estimated that the number of patients requiring dialysis treatment will exceed 3 million in 2030. Dialysis is one of the effective measures to prolong the life of patients and improve the quality of life of terminal patients. The hemodialysis machine, commonly known as the "artificial kidney", is an extracorporeal hemodialysis device that can replace part of the kidney function, remove harmful substances in the blood, correct electrolytes in the body and maintain acid-base balance.

[0003] Most of the existing dialysis devices are membrane dialysis, and the dialysis effect depends on the physical and chemical properties of the dialysis membrane. At present, there are three types of dialysis membranes commonly used in clinical practice: regenerated cellulose membrane, modified cellulose membrane, and synthetic polymer membrane. They all have good biocompatibility, can have a high clearance rate for solutes, and can prevent the passage of "macromolecules", such as red blood cells, proteins in the blood flow, and bacteria and viruses in the dialysate. However, there are still some problems with the use of dialysis membranes. First, all dialysis membranes have more or less "rejection", and the surface of the dialysis membrane will react non-physiologically with the cells and plasma components of the blood. Secondly, the blood layer in direct contact with the dialysis membrane is stationary relative to the dialysis membrane. Once this layer of blood is exchanged with the dialysis membrane, it becomes an obstacle to the subsequent transportation and exchange of blood, making transportation more difficult and slow. Finally, the membrane surface will cause membrane contamination after a period of use. During the entire treatment period, the dialysis membrane interface remains in a fixed position, and any material attached to the interface tends to remain unchanged. Over time, the surface will be contaminated and its effectiveness will decrease. Portable dialysis devices (or artificial kidneys) can be carried around and become part of the patient's body like a pacemaker, serving as an auxiliary device for the patient to continue life. The development and improvement of artificial kidney microfluidic chips is one of the bottleneck issues of artificial kidneys.

[0004] Although microfluidic chips have a simple structure and can smoothly and efficiently separate harmful components such as small molecule viruses from the blood and reduce cell loss through reflective columns, the channels of a single chip are at the micron level and the flow of the liquid is in a laminar state. Therefore, its working capacity is small and the amount of blood processed per unit time is limited. Summary of the invention

[0005] To solve this problem, the present invention provides a microfluidic chip with a honeycomb network parallel structure to solve the working capacity problem. The number of parallel channels can be selected according to the actual artificial kidney flow rate. At the same time, the present invention can use the honeycomb network structure and the shunt channel to alternately clean the laminar flow blood from the left and right sides, so that the blood can be fully dialyzed and the dialysate can be fully utilized.

[0006] In addition to solving the problems of low efficiency and large cell loss in existing dialysis, effectively increasing dialysis efficiency and reducing blood cell loss, this membraneless dialysis microfluidic chip also uses its parallel honeycomb network structure to increase the chip's working capacity and reduce the volume of the artificial kidney, thereby increasing the efficiency of dialysate utilization.

[0007] To achieve the above-mentioned purpose, the present invention provides the following technical solutions: a membraneless dialysis microfluidic chip with a parallel structure, comprising a plurality of dialysis components, and the plurality of dialysis components are arranged in parallel, and the dialysis components alternately form a cleaning section and a separation section along the direction of blood flow; the dialysis component comprises a blood channel and a dialysate channel, and the blood channel and the dialysate channel meet in the cleaning section and separate in the separation section; in the cleaning section, the blood and the dialysate contact in the center of the cleaning section channel, and when entering the next cleaning section, the contact surface of the blood and the dialysate is the outer fluid of the previous cleaning section.

[0008] Starting from the entrance, blood and dialysate flow together along the cleaning section. Due to the microflow and laminar flow, the blood and dialysate diffuse harmful substances through the concentration gradient of the contact surface, so that the blood is cleaned. Reflection columns are installed in the cleaning section to enhance the mass transfer process. After the blood and dialysate flow out of the cleaning section, they flow in the separation section respectively. When entering the next cleaning section, the contact surface of the blood and dialysate is the outer fluid of the previous cleaning section. In this way, the two sides of the blood are cleaned alternately, the concentration gradient of the contact surface is increased, and the cleaning efficiency is improved. The parallel design of the cleaning section and the separation section forms a honeycomb network structure, which can greatly increase the working capacity.

[0009] Preferably, in the 2n+1th cleaning segment, the blood channel and the dialysate channel in the same dialysis component meet; in the 2nth cleaning segment, in two adjacent dialysis components, the blood channel of one dialysis component meets the dialysate channel of the other dialysis component.

[0010] Preferably, a plurality of reflective columns are provided on the cleaning section.

[0011] Preferably, the distance between two adjacent reflective columns is 200-500 μm, and the diameter of the reflective column is 80-120 μm.

[0012] Preferably, the inlet angles of blood and dialysate are both 30-90°; the outlet angles of blood and dialysate are both 30-90°.

[0013] Preferably, the angle between the blood inlet and the dialysate inlet is 20 to 90°; the angle between the blood outlet and the dialysate outlet is 20 to 90°.

[0014] Preferably, the width of the blood channel and the dialysate channel is 140-160 μm, and the width of the dialysate channel is 90-110 μm.

[0015] Preferably, the length of the cleaning section is 11500-13500 μm, and the distance between the cleaning sections is 10000-12000 μm.

[0016] In summary, the present invention has the following beneficial effects:

[0017] 1. The present invention utilizes a parallel honeycomb network structure and a diversion channel to wash the laminar flow blood alternately from the left and right sides, so that the blood can be fully dialyzed and the dialysate can be fully utilized;

[0018] 2. The present invention utilizes a parallel honeycomb network structure to increase the working capacity of the chip and reduce the size of the artificial kidney. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The membraneless dialysis chip of the parallel honeycomb network structure of the present invention and the principle diagram of the microfluidic channel;

[0020] Figure 2 This is a schematic diagram of the membraneless dialysis chip with a parallel honeycomb network structure of the present invention, the inlet and outlet dimensions, and the central reflection column of the cleaning section.

[0021] Figure numerals: 1. blood inlet; 2. dialysate inlet; 3. cleaning section; 4. separation section; 5. blood outlet; 6. dialysate outlet; 7. reflection column. DETAILED DESCRIPTION

[0022] The present invention will be further described with reference to the accompanying drawings.

[0023] This embodiment discloses a membraneless dialysis microfluidic chip with a parallel structure, such as Figure 1 and Figure 2As shown, it includes a plurality of dialysis components, and the plurality of dialysis components are arranged in parallel, and the dialysis components alternately form a cleaning section 3 and a separation section 4 along the direction of blood flow; the dialysis component includes a blood channel and a dialysate channel, and the blood channel and the dialysate channel meet in the cleaning section 3 and separate in the separation section 4; in the cleaning section 3, the blood and the dialysate contact at the center of the cleaning section 3 channel, and when entering the next cleaning section 3, the contact surface of the blood and the dialysate is the outer fluid of the previous cleaning section 3. Among them, the blood inlet 1, the dialysate inlet 2, the cleaning section 3, the separation section 4, the blood outlet 5, and the dialysate outlet 6 are all installed in the chip housing, and the blood inlet 1 and the dialysate inlet 2 are symmetrically installed at the entrance of the cleaning section 3. Starting from the entrance, it flows along the cleaning section 3 and flows into the separation section 4 at the outlet of the cleaning section 3.

[0024] Starting from the entrance, blood and dialysate flow together along the cleaning section 3. Since it is a microflow and in a laminar flow state, blood and dialysate diffuse harmful substances through the concentration gradient of the contact surface, so that the blood is cleaned. A reflective column 7 is installed in the cleaning section 3 to enhance the mass transfer process. After the blood and dialysate flow out of the cleaning section 3, they flow in the separation section 4 respectively. When entering the next cleaning section 3, the contact surface of the blood and the dialysate is the outer fluid of the previous cleaning section 3. In this way, the two sides of the blood are alternately cleaned, the concentration gradient of the contact surface is increased, and the cleaning efficiency is improved. The parallel design of the cleaning section 3 and the separation section 4 forms a honeycomb network structure, which can greatly increase the working capacity. Due to the laminar flow, the lateral diffusion is slow. At the center of this cleaning section 3, there is a large concentration gradient, which improves the cleaning effect of the blood.

[0025] In some embodiments, in the 2n+1th cleaning segment 3, the blood channel and the dialysate channel in the same dialysis component meet; in the 2nth cleaning segment 3, in two adjacent dialysis components, the blood channel of one dialysis component meets the dialysate channel of the other dialysis component. Where n is a natural number.

[0026] As an embodiment, the membraneless dialysis microfluidic chip includes three cleaning stages and two separation stages. In the second cleaning stage 3, in two adjacent dialysis components, the blood channel of one dialysis component meets the dialysate channel of the other dialysis component.

[0027] Preferably, the cleaning section 3 is provided with a plurality of reflective columns 7. The specific structure of the reflective columns 7 can be found in Chinese patent CN113855886A. Thus, the reflective columns 7 are installed at the midline position of the cleaning section 3 to strengthen the mass transfer process. Figure 2As shown, a reflective column 7 is placed in the middle of the cleaning section 3, and blood and dialysate flow through both sides of the reflective column 7, respectively. By utilizing the FL effect (Fhrus-Lindqvist effect), a cell-free layer is formed around the reflective column 7. The cell-free layer contacts the dialysate, and small molecular harmful substances in the blood are transferred to the dialysate and taken away, thereby achieving the purpose of "purifying" the blood. Furthermore, the distance between two adjacent reflective columns 7 is 200-500 μm, and the diameter of the reflective column 7 is 80-120 μm.

[0028] In some embodiments, the inlet angles of blood and dialysate are both 30-90° (preferably 60°); the outlet angles of blood and dialysate are both 30-90° (preferably 60°).

[0029] The angle between the blood inlet 1 and the dialysate inlet 2 is 20-90° (preferably 60°); the angle between the blood outlet 5 and the dialysate outlet 6 is 20-90° (preferably 60°). Furthermore, the width of the blood channel and the dialysate channel is 140-160 μm (preferably 150 μm), and the width is 90-110 μm (preferably 100 μm). The length of the cleaning section 3 is 11500-13500 μm (preferably 12500 μm), and the distance between the cleaning sections 3 is 10000-12000 μm (preferably 12000 μm). The horizontal distance between the blood and dialysate inlets is 5300 μm, and the aperture at the connection between the inlet and outlet is 500 μm. The chip size can also be changed according to actual needs.

[0030] The workflow of the present invention is as follows:

[0031] Blood enters from the blood inlet 1, and dialysate enters from the dialysate inlet 2. The two liquids enter the cleaning section 3. Due to the laminar flow in the microchannel, they flow on both sides of the flow channel of the cleaning section 3. During the flow, the blood flows through the reflective column 7. The shear gradient and wall effect lift caused by the reflective column 7 push the cells away from the column surface, so that the part of the blood in contact with the dialysate does not contain large molecules such as blood cells and proteins, and only small molecular harmful substances are transferred to the dialysate and taken away. Compared with the dialysis method in which the blood is in direct contact with the dialysate, this reduces the loss of blood cells. The blood and dialysate flow to the cleaning section 3. 3 outlets, they enter the separation section 4 flow channel respectively and maintain a laminar flow state; at the next cleaning section 3 entrance, the outer fluid of the previous cleaning section 3 is introduced into the center of the cleaning section 3 through the separation section 4, and the blood is efficiently cleaned by using the concentration gradient; then after passing through several cleaning section 3 flow channels and diversion section flow channels, it enters the last cleaning section 3; thereafter, the blood and dialysate flow out from the blood outlet 5 and the dialysate outlet 6 respectively, completing the blood purification process; since multiple microchannels work in parallel, the working capacity of the microfluidic chip is greatly improved; since the two sides of the blood are cleaned alternately, the amount of dialysate used is greatly reduced, and the dialysis efficiency is improved.

[0032] The specified directions in this specific embodiment are only for the convenience of describing the positional relationship and the coordination relationship between the components. The above is only a preferred embodiment of the present invention. The protection scope of the present invention is not limited to the above embodiment. All technical solutions under the concept of the present invention belong to the protection scope of the present invention. It should be pointed out that for ordinary technicians in this technical field, some improvements and modifications without departing from the principle of the present invention should also be regarded as the protection scope of the present invention.

Claims

1. A membraneless dialysis microfluidic chip with a parallel structure, characterized by: The invention comprises a plurality of dialysis components, and the plurality of dialysis components are arranged in parallel, and the dialysis components alternately form a cleaning section (3) and a separation section (4) along the direction of blood flow; the dialysis components comprise a blood channel and a dialysate channel, and the blood channel and the dialysate channel meet in the cleaning section (3) and separate in the separation section (4); in the cleaning section (3), the blood and the dialysate contact at the center of the channel of the cleaning section (3), and when entering the next cleaning section (3), the contact surface between the blood and the dialysate is the outer fluid of the previous cleaning section (3); In the 2n+1th cleaning segment (3), the blood channel and the dialysate channel in the same dialysis component meet; in the 2nth cleaning segment (3), in two adjacent dialysis components, the blood channel of one dialysis component meets the dialysate channel of the other dialysis component.

2. The membraneless dialysis microfluidic chip with a parallel structure according to claim 1, characterized in that: A plurality of reflective columns (7) are arranged on the cleaning section (3).

3. The membraneless dialysis microfluidic chip with a parallel structure according to claim 2, characterized in that: The distance between two adjacent reflection columns (7) is 200-500 μm, and the diameter of the reflection column (7) is 80-120 μm.

4. The membraneless dialysis microfluidic chip with a parallel structure according to claim 1, characterized in that: The inlet angles of blood and dialysate are both 30~90°; the outlet angles of blood and dialysate are both 30~90°.

5. The membraneless dialysis microfluidic chip with a parallel structure according to claim 1, characterized in that: The included angle between the blood inlet (1) and the dialysate inlet (2) is 20 to 90 degrees; the included angle between the blood outlet (5) and the dialysate outlet (6) is 20 to 90 degrees.

6. The membraneless dialysis microfluidic chip with a parallel structure according to claim 1, characterized in that: The width of the blood channel and the dialysate channel is 140~160μm, and the width is 90~110μm.

7. The membraneless dialysis microfluidic chip with a parallel structure according to claim 1, characterized in that: The length of the cleaning section (3) is 11500-13500 μm, and the distance between the cleaning sections (3) is 10000-12000 μm.

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