Cell surface friction force measuring device manufactured by three-dimensional printing
The cell surface friction measurement device manufactured through 3D printing, combined with flow impedance detection and inertial microfluidics technology, solves the problems of low detection throughput and high cost in existing technologies, and realizes high-throughput detection of cell surface friction, which is suitable for disease diagnosis and single-cell physical property research.
Patent Information
- Application Number
- CN202510822648.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-19
- Publication Date
- 2025-09-12
AI Technical Summary
Existing cell surface friction measurement methods have low detection throughput and high cost, making it difficult to achieve high-throughput detection. Flow impedance detection devices are also difficult to achieve high-throughput detection of biological particle surface friction.
The cell surface friction measurement device is manufactured using 3D printing. The device consists of a flow channel layer and an electrode layer. It combines flow impedance detection technology and inertial microfluidics technology. It is produced through 3D printing technology of heterogeneous materials, and a specific flow channel and electrode structure are designed. Electric field perturbation is used to analyze cell friction.
It achieves high-throughput detection of cell surface friction, reduces detection costs, and is suitable for disease diagnosis and single-cell physical property research.
Smart Images
Figure CN120628955A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of flow impedance detection technology, and in particular to a cell surface friction force measurement device manufactured by three-dimensional printing. Background Art
[0002] Measuring the surface friction of biological particles, such as cells, is of great significance in fields such as life sciences, clinical medicine, and chemistry. Currently, the mainstream method for measuring cell surface friction still relies primarily on image detection, whereby a high-speed camera continuously captures deformed biological particles and analyzes the image to determine their surface friction. However, this method has an extremely low detection throughput, typically only capturing one image per few seconds, making it difficult to apply to high-throughput detection of cells with a large background. Furthermore, such methods often rely on expensive high-speed cameras and require specialized personnel to operate, resulting in high detection costs. In recent years, with advances in microfluidics, flow-based electrical impedance detection has made significant progress in the detection of biological particles. Taking cells as an example, flow-based electrical impedance detection enables label-free cell detection by analyzing the disturbances caused by the electric field as cells pass through it. For example, this method can distinguish between white blood cells and tumor cells. However, existing flow-based electrical impedance detection devices generally struggle to achieve high-throughput detection of the surface friction of biological particles. Given that flow impedance cytometry has the advantages of high throughput and non-labeling in the detection of biological particles, it is of great significance to develop a device based on flow impedance cytometry that can measure the surface friction of biological particles. It has great application value in the fields of disease diagnosis, single cell physical properties research, etc. Summary of the Invention
[0003] The purpose of the present invention is to propose a cell surface friction measurement device manufactured by three-dimensional printing, which is mainly designed based on flow impedance detection technology and inertial microfluidics technology, and its production method involves 3D printing technology of heterogeneous materials.
[0004] To achieve the above object, the technical solution adopted by the present invention is: A cell surface friction measurement device manufactured by 3D printing consists of a flow channel layer and an electrode layer. The flow channel layer is provided with a sample inlet, a sample outlet, a waste liquid outlet, a focusing channel, a detection channel, a friction channel, and a waste liquid channel. The detection channel is obliquely connected to the friction channel and the waste liquid channel. After being focused by the focusing channel, the cells are balanced in a fixed position. The electrode layer is provided with a detection electrode 1, a detection electrode 2, a detection electrode 3 and a detection electrode 4. The detection electrode 1 and the detection electrode 4 are sensing electrodes, the detection electrode 2 and the detection electrode 3 are excitation electrodes, and the detection electrode 2 and the detection electrode 3 are connected together. The detection electrode 1 and the detection electrode 2 are perpendicular to the detection flow channel, and the detection electrode 3 and the detection electrode 4 are perpendicular to the friction flow channel. The detection channel, detection electrode 1, and detection electrode 2 together constitute detection area 1, the friction channel, detection electrode 3, and detection electrode 4 together constitute detection area 2, and the end of the detection channel and the middle part of the friction channel and waste liquid channel together constitute the friction area.
[0005] As a further improvement of the present invention, the focusing flow channel is an asymmetric sinusoidal flow channel with a rectangular cross-section, and the detection flow channel, friction flow channel, and waste liquid flow channel are all straight flow channels with a rectangular cross-section.
[0006] As a further improvement of the present invention, the detection flow channel is connected to the friction flow channel and the waste liquid flow channel at an angle, and the angle range is 85-90 degrees.
[0007] As a further improvement of the present invention, there are flow channel alignment marks on the flow channel layer, and there are electrode alignment marks on the electrode layer. The electrode alignment marks on the electrode layer correspond to the flow channel alignment marks on the flow channel layer, ensuring that the flow channel layer and the electrode layer are aligned up and down.
[0008] As a further improvement of the present invention, all electrode sizes are matched with cell sizes.
[0009] As a further improvement of the present invention, the electrode layer is made of heterogeneous materials by three-dimensional printing, the electrode part is a conductive material, and the non-electrode part is an insulating material, and the flow channel layer is made of non-conductive materials by three-dimensional printing.
[0010] As a further improvement of the present invention, when the flow channel layer and the electrode layer are assembled from top to bottom, they are sealed by a hot pressing process or by using a sealant.
[0011] Principle description: In this device, a sample solution containing cells is injected into the device's flow channel through the device's inlet. The front end of the flow channel is a focusing channel, specifically an asymmetric sinusoidal flow channel with a high aspect ratio. Under inertial flow at a limited flow rate, the cells can be focused at a specific position in the flow channel, thereby passing through the shape detection area (detection area one) at a specific position. The principle is that the cells in the asymmetric sinusoidal flow channel with a high aspect ratio are affected by the inertial lift and Dean drag force and are focused at a specific position in the flow channel. Subsequently, the cells pass through the focusing flow channel and detection area one at a fixed position, thereby reducing detection errors caused by cell position errors. Subsequently, the focused cells will collide with the connection between the friction flow channel and the waste liquid flow channel and slide a certain distance in the friction flow channel. Due to the different friction forces, the sliding distances of different cells are also different.
[0012] In the detection area of the present invention, the basic principle is that when cells pass through the electric field area, electric field disturbances will be generated. By analyzing the disturbance effect of cells on the electric field, the size and surface friction of biological particles can be measured. When the cells are in detection area one, the information on the shape and internal characteristics of the cells can be obtained by analyzing the amplitude and phase of the impedance signal in this area. When the biological particles are in detection area two, the information on the shape and internal characteristics of the cells can also be obtained. The time of cell friction slip can be obtained by analyzing the distance between the signal peaks in detection areas one and two. Different types of cells have different friction slip times due to their different surface friction. As Figure 6 As shown in Figure 1, the distances between the signal peaks in detection areas 1 and 2 differ for cells a and b due to their different surface friction. Furthermore, because the impedance signal can reveal cell size information, this information can be used to correct the unit friction value on the cell surface. BRIEF DESCRIPTION OF THE DRAWINGS
[0013] Figure 1 This is an exploded view of the assembly of the cell surface friction force measurement device manufactured by three-dimensional printing of the present invention; Figure 2 It is a detailed structural diagram of the flow channel layer; Figure 3 is a detailed structural diagram of the electrode layer; Figure 4 is a schematic diagram of the inspection area after assembly; Figure 5 It is a schematic diagram of the detection principle; Figure 6 It is the original signal of the biological particle surface friction measurement of the device of the present invention; The specific component names are as follows: 1. Flow channel layer; 11. Sample inlet; 12. Sample outlet; 13. Waste liquid outlet; 14. Focusing flow channel; 15. Detection flow channel; 16. Friction flow channel; 17. Flow channel alignment mark; 18. Waste liquid flow channel; 2. Electrode layer; 21. Detection electrode one; 22. Detection electrode two; 23. Detection electrode three; 24. Detection electrode four; 25. Electrode alignment mark. DETAILED DESCRIPTION
[0014] In order to further understand the content of the present invention, the present invention is described in detail with reference to the accompanying drawings and embodiments.
[0015] like Figure 1 As shown, the cell surface friction force measurement device manufactured by three-dimensional printing of the present invention is composed of a flow channel layer 1 and an electrode layer 2, and the flow channel layer 1 and the electrode layer 2 are sealed from top to bottom to prevent leakage; like Figure 2 As shown, the flow channel layer 1 is provided with a sample inlet 11, a sample outlet 12, a waste liquid outlet 13, a focusing flow channel 14, a detection flow channel 15, a friction flow channel 16, a flow channel alignment mark 17, and a waste liquid flow channel 18. The focusing flow channel 14 is an asymmetric sinusoidal flow channel with a rectangular cross-section. After the cells are focused by the focusing flow channel 14, they are balanced at a specific position. The detection flow channel 15, the friction flow channel 16, and the waste liquid flow channel 18 are all straight flow channels with rectangular cross-sections. Since the detection flow channel 15 is obliquely connected to the friction flow channel 16 and the waste liquid flow channel 18 (the angle is about 85-90 degrees), the focused cells will collide with the middle of the friction flow channel 16 and the waste liquid flow channel 18 and slide a distance in the friction flow channel 16. Different cells will slide a different distance due to different friction forces. The waste liquid flow channel 18 is used to discharge cell-free waste liquid.
[0016] like Figure 3 As shown, the electrode layer 2 is provided with a detection electrode 1 21, a detection electrode 2 22, a detection electrode 3 23, a detection electrode 4 24, and an electrode alignment mark 25. The detection electrode 1 21 and the detection electrode 4 24 are sensing electrodes, the detection electrode 2 22 and the detection electrode 3 23 are excitation electrodes, and the detection electrode 2 22 and the detection electrode 3 23 are connected together. The detection electrode 1 21 and the detection electrode 2 22 are perpendicular to the detection channel 15, and the detection electrode 3 23 and the detection electrode 4 24 are perpendicular to the friction channel 16. The electrode alignment mark 25 corresponds to the flow channel alignment mark 17 on the flow channel layer 1 to ensure that the flow channel layer 1 and the electrode layer 2 are precisely aligned up and down. All electrode sizes match the cell size.
[0017] like Figure 4As shown, the detection channel 15, detection electrode 1 21, and detection electrode 2 22 collectively constitute detection region 1, while the friction channel 16, detection electrode 3 23, and detection electrode 4 24 collectively constitute detection region 2. The end of the detection channel 15, along with the middle portion of the friction channel 16 and waste channel 18, constitute the friction region. Focused cells first pass through detection region 1, then, after collision and friction, pass through detection region 2.
[0018] like Figure 5 As shown, due to the action of the focusing channel 14, the cells enter the detection channel 15 at a fixed position and pass through the detection area 1; since the detection channel 15 is obliquely connected to the friction channel 16 and the waste liquid channel 18, the focused cells will collide in the middle of the friction channel 16 and the waste liquid channel 18, and will slide a certain distance in the friction area. Different types of cells have different sliding distances due to different surface friction forces. The detection area 1 and the detection area 2 can respectively detect the impedance signals before and after the cell friction slip. In order to ensure the accuracy of the detection, the distance between the detection area 1 and the detection area 2 and the friction area should not be too long, and it has been experimentally determined to be about 50-100 microns. The circuit connection method of the device of the present invention is as follows Figure 5 As shown in the figure, the signal generator of the phase-locked amplifier emits an excitation electric field, which is a multi-frequency AC electric field, and is respectively connected to the excitation electrodes of detection areas one and two, namely, detection electrode two 22 and detection electrode three 23. The detection electrode one 21 of detection area one and the electrode four 24 of detection area two are respectively connected to the transimpedance amplifier. The two currents in the transimpedance amplifier are again connected to the phase-locked amplifier to demodulate the weak signal, and finally the morphology and deformation signals of the biological particles are obtained.
[0019] like Figure 6 As shown in the figure, when the cell is in detection area 1, the shape and internal characteristics of the cell can be obtained by analyzing the amplitude phase of the impedance signal in this area. When the biological particle is in detection area 2, the shape and internal characteristics of the cell can also be obtained. By analyzing the distance between the peaks of the signals in detection areas 1 and 2, the friction slip time of the cell can be obtained. Different types of cells have different friction slip times due to their different surface friction. Figure 6 As shown in Figure 1, the distances between the signal peaks in detection areas 1 and 2 differ for cells a and b due to their different surface friction. Furthermore, because the impedance signal can reveal cell size information, this information can be used to correct the unit friction value on the cell surface.
[0020] In this embodiment, the flow channel layer 1 is 3D-printed from a non-conductive material, while the electrode layer 2 is 3D-printed from a heterogeneous material. The electrode portion is conductive, while the non-electrode portion is insulating. When the flow channel layer 1 and electrode layer 2 are assembled from top to bottom, they are sealed using a hot press process or a sealant.
[0021] The above description is merely a preferred embodiment of the present invention and does not constitute any other form of limitation to the present invention. Any modification or equivalent variation based on the technical essence of the present invention shall still fall within the scope of protection claimed by the present invention.
Claims
1. A cell surface friction force measurement device manufactured by three-dimensional printing, characterized in that: The device is composed of a flow channel layer (1) and an electrode layer (2). The flow channel layer (1) is provided with a sample inlet (11), a sample outlet (12), a waste liquid outlet (13), a focusing flow channel (14), a detection flow channel (15), a friction flow channel (16), and a waste liquid flow channel (18). The detection flow channel (15) is connected to the friction flow channel (16) and the waste liquid flow channel (18) at an angle, and the cells are focused by the focusing flow channel (14) and then balanced at a fixed position. The electrode layer (2) is provided with a detection electrode 1 (21), a detection electrode 2 (22), a detection electrode 3 (23) and a detection electrode 4 (24), wherein the detection electrode 1 (21) and the detection electrode 4 (24) are sensing electrodes, the detection electrode 2 (22) and the detection electrode 3 (23) are excitation electrodes, and the detection electrode 2 (22) and the detection electrode 3 (23) are connected together, the detection electrode 1 (21) and the detection electrode 2 (22) are perpendicular to the detection flow channel (15), and the detection electrode 3 (23) and the detection electrode 4 (24) are perpendicular to the friction flow channel (16); The detection channel (15), detection electrode one (21), and detection electrode two (22) together constitute detection area one; the friction channel (16), detection electrode three (23), and detection electrode four (24) together constitute detection area two; the end of the detection channel (15) and the middle part of the friction channel (16) and waste liquid channel (18) together constitute the friction area.
2. The cell surface friction force measurement device manufactured by three-dimensional printing according to claim 1, characterized in that: The focusing flow channel (14) is an asymmetric sinusoidal flow channel with a rectangular cross section, and the detection flow channel (15), friction flow channel (16), and waste liquid flow channel (18) are all straight flow channels with rectangular cross sections.
3. The cell surface friction force measurement device manufactured by three-dimensional printing according to claim 2, characterized in that: The detection flow channel (15) is connected to the friction flow channel (16) and the waste liquid flow channel (18) at an angle, with an angle ranging from 85 to 90 degrees.
4. The cell surface friction force measurement device manufactured by three-dimensional printing according to claim 1, characterized in that: The flow channel layer (1) has a flow channel alignment mark (17), and the electrode layer (2) has an electrode alignment mark (25). The electrode alignment mark (25) on the electrode layer (2) corresponds to the flow channel alignment mark (17) on the flow channel layer (1), ensuring that the flow channel layer (1) and the electrode layer (2) are aligned vertically.
5. The cell surface friction force measurement device manufactured by three-dimensional printing according to claim 1, characterized in that: All electrode dimensions are matched to the cell dimensions.
6. The cell surface friction force measurement device manufactured by three-dimensional printing according to claim 1, characterized in that: The electrode layer (2) is made of heterogeneous materials by three-dimensional printing, the electrode part is a conductive material, and the non-electrode part is an insulating material, and the flow channel layer (1) is made of non-conductive materials by three-dimensional printing.
7. The cell surface friction force measurement device manufactured by three-dimensional printing according to claim 1, characterized in that: When the flow channel layer (1) and the electrode layer (2) are assembled from top to bottom, they are sealed by a hot pressing process or by a sealant.