Flow type electrical impedance detection device for three-dimensional printing manufacturing

Abstract

A flow type electrical impedance detection device manufactured through three-dimensional printing comprises an upper electrode layer, a flow channel layer and a lower electrode layer from top to bottom, an inlet, an outlet and four parallel upper detection electrodes of a device are arranged on the upper electrode layer, a direct flow channel with a rectangular section is arranged on the flow channel layer, and four parallel lower detection electrodes are arranged on the lower electrode layer. The upper detection electrode and the lower detection electrode are positioned at the tail end of the straight flow channel and are arranged in parallel up and down in a face-to-face manner; and the four parallel upper detection electrodes respectively comprise an excitation electrode and an induction electrode. The substrates of the upper electrode layer and the lower electrode layer and the flow channel layer are printed by adopting a non-conductive material, electrodes in the upper electrode layer and the lower electrode layer are printed by adopting a metal material, and the flow type electrical impedance detection device manufactured by three-dimensional printing can automatically realize nondestructive detection of cells and biological particles in a non-marking manner at high flux, so that the detection efficiency is greatly improved. The method has extremely high detection accuracy, and a brand new method is provided for rapid and low-cost diagnosis of clinical diseases.

Description

Technical Field

[0001] The present invention relates to the technical field of three-dimensional printing of heterogeneous materials, and specifically to a flow-type electrical impedance detection device manufactured by three-dimensional printing. Background Art

[0002] High-throughput label-free detection of biological particles such as cells is of great significance in the fields of life sciences, clinical medicine, chemistry and chemical engineering. At present, the mainstream detection method of biological particles still mainly relies on the immunolabeling method, that is, the use of specific biological reagents to achieve the identification of biological particles. This method has the defects of high cost and long time consumption. In addition, this method often requires trained professionals to operate, and this method often causes apoptosis of biological particles, which is not conducive to its subsequent biochemical research. In recent years, with the advancement of Wiener processing technology, flow impedance detection technology has made great progress in the detection of biological particles. Taking cells as an example, flow impedance detection technology realizes label-free detection of cells by analyzing the disturbance of the electric field when cells pass through the electric field area. For example, there are large differences between white blood cells and tumor cells in the amplitude and phase of the impedance signal. However, the electrodes of the existing flow impedance detection device are usually coplanar or face-to-face electrode structures. Since the electric field attenuation is greater the farther away from the electrode, the position of the biological particles in the detection area has a greater interference with the detection signal, thereby causing inaccurate detection. Therefore, how to eliminate the detection error caused by the position of biological particles such as cells in the flow impedance detection device is the key to achieving high-throughput and accurate detection of biological particles, and has great application value in disease diagnosis, single-cell physical properties research and other fields. Summary of the invention

[0003] In order to solve the above technical problems, the present invention proposes a flow cytometry impedance detection device manufactured by three-dimensional printing, which is a flow cytometry impedance detection device that can achieve high-throughput, non-labeling and precise detection of biological particles such as cells. Its manufacturing method is based on the technology of three-dimensional printing of heterogeneous materials.

[0004] To achieve the above object, the technical solution adopted by the present invention is: A flow type electrical impedance detection device manufactured by three-dimensional printing, which comprises three parts from top to bottom, an upper electrode layer, a flow channel layer, and a lower electrode layer, wherein the upper electrode layer is provided with four detection electrodes; the upper electrode layer is provided with a small positioning mark and a large positioning mark of the upper electrode layer, so as to facilitate mutual alignment between the upper electrode layer, the flow channel layer, and the lower electrode layer; the upper electrode layer is provided with a sample inlet and a sample outlet, so as to respectively realize the input and output of the sample; the flow channel layer is provided with a flow channel inlet, a flow channel outlet, an outlet flow channel, a large flow channel layer positioning mark, a detection flow channel, and an inlet flow channel; wherein the flow channel inlet and the flow channel outlet are respectively aligned with The sample inlet and sample outlet on the upper electrode layer are opposite to each other; the inlet flow channel and the large positioning mark of the flow channel layer correspond to the large positioning mark of the upper electrode layer on the upper electrode layer, so as to realize the precise alignment between the upper electrode layer and the flow channel layer; four detection electrodes are arranged on the lower electrode layer; the lower electrode layer is provided with a number of small positioning marks of the lower electrode layer and large positioning marks of the lower electrode layer, so as to facilitate the mutual alignment between the upper electrode layer, the flow channel layer and the lower electrode layer; after alignment, the detection electrodes on the upper electrode layer and the lower electrode layer are distributed face to face and in parallel, and the end of the detection flow channel in the flow channel layer is located in the middle of the detection electrodes in the upper electrode layer and the lower electrode layer.

[0005] Preferably, four detection electrodes are arranged on the upper electrode layer, the front ends of the four detection electrodes are thinner, and their size matches the size of biological particles such as cells, and the tail ends of the four detection electrodes are thicker, and their larger size facilitates their connection with external circuits; the upper electrode layer is provided with a number of small positioning marks and large positioning marks, which facilitate the mutual alignment between the upper electrode layer, the flow channel layer, and the lower electrode layer; the upper electrode layer is provided with a sample inlet and a sample outlet, which respectively realize the input and output of samples.

[0006] Preferably, four detection electrodes are arranged on the lower electrode layer, the front ends of the four detection electrodes are thinner and their size matches the cell size, and the tail ends of the four detection electrodes are thicker and their larger size facilitates their connection with the external circuit; a number of small positioning marks and large positioning marks are arranged on the lower electrode layer to facilitate the mutual alignment between the upper electrode layer, the flow channel layer and the lower electrode layer; after alignment, the detection electrodes on the upper electrode layer and the lower electrode layer are distributed face to face and in parallel, and the end of the detection channel in the flow channel layer is located in the middle of the detection electrodes in the upper electrode layer and the lower electrode layer.

[0007] Preferably, the detection flow channel is a straight flow channel or a serpentine flow channel with a high aspect ratio, and tiny biological particles such as cells are precisely focused in the flow channel and are respectively distributed on the upper and lower sides of the detection flow channel.

[0008] Preferably, the flow channel layer is provided with a flow channel inlet, a flow channel outlet, an outlet flow channel, a large positioning mark, a detection flow channel, and an inlet flow channel; wherein the flow channel inlet and the flow channel outlet are respectively opposite to the sample inlet and the sample outlet on the upper electrode layer; the inlet flow channel and the outlet flow channel are wider than the detection flow channel, which is convenient for high-throughput sampling; the large positioning mark corresponds to the large positioning mark on the upper electrode layer to achieve precise alignment between the upper electrode layer and the flow channel layer; the structure of the detection flow channel is a straight channel or a serpentine flow channel shape, which is used to achieve precise focusing of tiny biological particles, so that the biological particles pass through the detection area at a fixed position, thereby increasing the accuracy of electrical impedance detection.

[0009] Preferably, the external circuit of the electrical impedance detection also includes two transimpedance amplifiers TA, a differential amplifier Diff, a signal generator SG, a mixer Mixer, a low-pass filter LPF, and a phase inverter PI. The upper electrode layer detection electrode one, the upper electrode layer detection electrode two and the lower electrode layer detection electrode three and the lower electrode layer detection electrode four are excitation electrodes and are applied with an electric field. The upper electrode layer detection electrode three, the upper electrode layer detection electrode four and the lower electrode layer detection electrode one and the lower electrode layer detection electrode two are sensing electrodes to realize the reception of the sensing signal. The signal generator SG sends out a detection signal, which is applied to the upper electrode layer detection electrode one and the upper electrode layer detection electrode two and the lower electrode layer detection electrode three and the lower electrode layer detection electrode four respectively after passing through the phase inverter PI, that is, the upper electrode layer detection electrode The electric field applied to electrode one and the upper electrode layer detection electrode two and the electric field applied to the lower electrode layer detection electrode three and the lower electrode layer detection electrode four are of the same magnitude and opposite phase; the upper electrode layer detection electrode three and the lower electrode layer detection electrode two are short-circuited and then amplified by the transimpedance amplifier TA; the upper electrode layer detection electrode four and the lower electrode layer detection electrode one are short-circuited and then amplified by the transimpedance amplifier TA, wherein the upper electrode layer detection electrode three and the lower electrode layer detection electrode two are short-circuited, and the upper electrode layer detection electrode four and the lower electrode layer detection electrode one are short-circuited as the first differential; the signal after the first differential is then connected to the differential amplifier Diff for the second differential, and then the signal is amplified by the phase-locked amplifier composed of a signal generator SG, a mixer Mixer, and a low-pass filter LPF, and finally a weak electrical impedance signal is obtained.

[0010] Since the detection channel of the flow-type electrical impedance detection device proposed in the present invention is a straight channel or a serpentine channel with a high aspect ratio, tiny biological particles such as cells are precisely focused in the channel and distributed on the upper and lower sides of the detection channel, that is, Figure 5 (2) As shown in positions #1 and #2, when biological particles pass through positions #1 and #2, electric field disturbances will be generated. Due to the original electric signal differential method of the present invention as described above, the signals generated by the same biological particle at positions #1 and #2 are equal in size and centrally symmetrical in shape, thereby avoiding inaccurate detection due to uneven electric field distribution.

[0011] Preferably, the upper electrode layer and the lower electrode layer are made of heterogeneous materials by three-dimensional printing, the electrode part is a conductive material, the non-electrode part is an insulating material, and the flow channel layer is made of non-conductive materials by three-dimensional printing. When the upper electrode layer, the flow channel layer, and the lower electrode layer are assembled from top to bottom, they are sealed by a hot pressing process or by a sealant.

[0012] Principle description: In the detection channel, the sample liquid containing biological particles is injected into the detection channel through the sample liquid inlet. The detection channel is a straight channel or a serpentine channel with a high aspect ratio. Under the inertial flow of a limited flow rate, the biological particles can be focused at two equilibrium positions above and below the channel, so as to pass through the detection area at a specific position. The principle is that the channel is affected by the inertial lift in the straight channel with a high aspect ratio, so the biological particles are focused at two equilibrium positions at the upper and lower ends of the channel; in the serpentine channel with a high aspect ratio, the biological particles are affected by the inertial lift and the Dean drag, so the cells can balance faster at the two equilibrium positions at the upper and lower ends of the channel; therefore, in the detection channel, the biological particles can pass through the detection area at two specific positions.

[0013] In the detection area of ​​the present invention, the basic principle is that when cells pass through the electric field area, electric field disturbance will be generated. By analyzing the disturbance effect of different cells on the electric field, cell counting and type identification can be achieved. In order to realize the simultaneous and accurate detection of the two equilibrium positions, the upper and lower positions, in the detection channel, a new current differential method is designed in the present invention. In addition to the flow impedance detection device itself, the external circuit of the electrical impedance detection also includes two transimpedance amplifiers, a differential amplifier, a signal generator, a mixer, a low-pass filter, and a phase inverter; the two electrodes on the left side of the upper detection electrode and the two electrodes on the right side of the lower detection electrode are excitation electrodes and are applied with an electric field, and the two electrodes on the right side of the upper detection electrode and the two electrodes on the left side of the lower detection electrode are sensing electrodes to realize the reception of the sensing signal; the signal generator sends out a detection signal, which is applied to the two electrodes on the left side of the upper electrode and the two electrodes on the right side of the lower electrode after passing through the phase inverter, that is, the electric field applied to the two electrodes on the left side of the upper electrode and the electric field applied to the two electrodes on the right side of the lower electrode are the same in magnitude and opposite in phase; the sensing electrodes are short-circuited and amplified by the transimpedance amplifier to form the first differential; the signal after the first differential is then connected to the differential amplifier for the second differential, and then the signal is amplified by the phase-locked amplifier composed of the signal generator, the mixer, and the low-pass filter, and finally a weak electrical impedance signal is obtained. Since the detection channel of the flow-type electrical impedance detection device proposed in the present invention is a straight channel or a serpentine channel with a high aspect ratio, tiny biological particles such as cells are precisely focused in the channel and are distributed on the upper and lower sides of the detection channel respectively. When the biological particles pass through these two positions, electric field disturbances will be generated. Due to the original electric signal differential method of the present invention as described above, the signals generated by the same biological particle at the two positions are equal in size and centrally symmetrical in shape, thereby avoiding inaccurate detection due to uneven electric field distribution. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 It is an exploded schematic diagram of the assembly of a flow-type electrical impedance detection device manufactured by three-dimensional printing according to the present invention; Figure 2 is a detailed structural diagram of the upper electrode layer; Figure 3 It is a detailed structural diagram of the flow channel layer; Figure 4 is a detailed structural diagram of the lower electrode layer; Figure 5 It is a schematic diagram of the structure of the device after assembly, the detection principle and the detection results.

[0015] Marking Description: 1. Upper electrode layer; 11. Detection electrode one of the upper electrode layer; 12. Detection electrode two of the upper electrode layer; 13. Detection electrode three of the upper electrode layer; 14. Detection electrode four of the upper electrode layer; 15. Small positioning mark; 16. Sample outlet; 17. Large positioning mark of the upper electrode layer; 18. Sample inlet; 2. Flow channel layer; 21. Flow channel inlet; 22. Flow channel outlet; 23. Outlet flow channel; 24. Large positioning mark of the flow channel layer; 25. Detection flow channel; 26. Inlet flow channel; 3. Lower electrode layer; 31. Detection electrode one of the lower electrode layer; 32. Detection electrode two of the lower electrode layer; 33. Detection electrode three of the lower electrode layer; 34. Detection electrode four of the lower electrode layer; 35. Small positioning mark of the lower electrode layer; 36. Large positioning mark of the lower electrode layer. DETAILED DESCRIPTION

[0016] The present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments: like Figure 1 As shown, the novel flow-type electrical impedance detection device of the present invention is assembled from top to bottom by an upper electrode layer 1, a flow channel layer 2, and a lower electrode layer 3, wherein the electrode layer 1, the flow channel layer 2, and the lower electrode layer 3 are aligned and sealed in sequence, so that the liquid can pass through the flow channel without leakage; like Figure 2 As shown, the upper electrode layer 1 is provided with four detection electrodes, namely, upper electrode layer detection electrode 1 11, upper electrode layer detection electrode 2 12, upper electrode layer detection electrode 3 13 and upper electrode layer detection electrode 4 14. The four detection electrodes are thinner at the head ends, and their sizes match the cell sizes. The four detection electrodes are thicker at the tail ends, and their larger sizes facilitate their connection with external circuits. The upper electrode layer 1 is provided with a number of small positioning marks 15 and large positioning marks 17, which facilitate mutual alignment between the upper electrode layer 1, the flow channel layer 2 and the lower electrode layer 3. The upper electrode layer 1 is provided with a sample inlet 18 and a sample outlet 16, which respectively realize the input and output of samples. like Figure 3 As shown, the flow channel layer 2 is provided with a flow channel inlet 21, a flow channel outlet 22, an outlet flow channel 23, a flow channel layer large positioning mark 23, a detection flow channel 24, an inlet flow channel 25, and an inlet flow channel 26; wherein the flow channel inlet 21 and the flow channel outlet 22 are respectively opposite to the sample inlet 18 and the sample outlet 16 on the upper electrode layer 1; the inlet flow channel 25 and the outlet flow channel 23 are wider than the detection flow channel 24, which is convenient for high-throughput sampling; the flow channel layer large positioning mark 23 corresponds to the upper electrode layer large positioning mark 17 on the upper electrode layer 1, so as to achieve precise alignment between the upper electrode layer 1 and the flow channel layer 2; the structure of the detection flow channel 24 is a straight flow channel or a serpentine flow channel shape, which is used to achieve precise focusing of tiny biological particles, so that the biological particles pass through the detection area at a fixed position, thereby increasing the accuracy of electrical impedance detection; like Figure 4As shown, four detection electrodes are arranged on the lower electrode layer 3, namely, lower electrode layer detection electrode 1 31, lower electrode layer detection electrode 2 32, lower electrode layer detection electrode 3 33 and lower electrode layer detection electrode 4 34. The four detection electrodes are thinner at the head ends, and their sizes match the cell sizes. The four detection electrodes are thicker at the tail ends, and their larger sizes facilitate their connection with the external circuit. The lower electrode layer 3 is provided with a plurality of lower electrode layer small positioning marks 35 and lower electrode layer large positioning marks 36, which facilitate mutual alignment between the upper electrode layer 1, the flow channel layer 2 and the lower electrode layer 3. After alignment, the detection electrodes on the upper electrode layer 1 and the lower electrode layer 3 are distributed face to face and in parallel, and the end of the detection channel 24 in the flow channel layer 2 is located in the middle of the detection electrodes in the upper electrode layer 1 and the lower electrode layer 3. like Figure 5 The figure shows the assembly result, detection principle and detection result of the flow impedance detection device manufactured by 3D printing. The result of the device in the XY plane after the upper electrode layer 1, the flow channel layer 2 and the lower electrode layer 3 are assembled is shown in FIG. Figure 5 As shown in (1), the first section of the detection channel of the upper electrode layer 1 and the lower electrode layer 3 are accurately aligned. Figure 5(2) is a schematic diagram of the detection principle of the detection area in the XZ plane. The upper and lower detection electrodes are aligned up and down respectively. In addition to the flow impedance detection device itself, the external circuit of the electrical impedance detection also includes two transimpedance amplifiers (TA), a differential amplifier (Diff), a signal generator (SG), a mixer (Mixer), a low-pass filter (LPF), and a phase inverter (PI). In this embodiment, the upper electrode layer detection electrode 1 11, the upper electrode layer detection electrode 2 12 and the lower electrode layer detection electrode 3 33, the lower electrode layer detection electrode 4 34 are excitation electrodes and are applied with an electric field. The upper electrode layer detection electrode 3 13, the upper electrode layer detection electrode 4 14 and the lower electrode layer detection electrode 1 31, the lower electrode layer detection electrode 2 32 are sensing electrodes to realize the reception of sensing signals. The signal generator (SG) sends out a detection signal, which is applied to the upper electrode layer detection electrode 1 11, the upper electrode layer detection electrode 2 12 and the lower electrode layer detection electrode 3 33, and the lower electrode layer detection electrode 4 34 respectively after passing through the phase inverter (PI). The electric field applied to the detection electrode three 33 and the lower electrode layer detection electrode four 34, that is, the electric field applied to the upper electrode layer detection electrode one 11 and the upper electrode layer detection electrode two 12 and the electric field applied to the lower electrode layer detection electrode three 33 and the lower electrode layer detection electrode four 34 are of the same magnitude and opposite phase; the upper electrode layer detection electrode three 13 and the lower electrode layer detection electrode two 32 are short-circuited and then amplified by a transimpedance amplifier (TA), and the sensing upper electrode layer detection electrode four 14 and the lower electrode layer detection electrode one 31 are short-circuited and then amplified by a transimpedance amplifier (TA), wherein the upper electrode layer detection electrode three 13 and the lower electrode layer detection electrode two 32 are short-circuited, and the upper electrode layer detection electrode four 14 and the lower electrode layer detection electrode one 31 are short-circuited as the first differential; the signal after the first differential is then connected to the differential amplifier (Diff) for the second differential, and then the signal is amplified by a phase-locked amplifier composed of a signal generator (SG), a mixer (Mixer), and a low-pass filter (LPF), and finally a weak electrical impedance signal is obtained. Figure 5 As shown in (1-3), since the detection channel 24 of the flow-type electrical impedance detection device proposed in the present invention is a straight channel or a serpentine channel with a high aspect ratio, tiny biological particles such as cells are precisely focused in the channel and are distributed on the upper and lower sides of the detection channel, that is, Figure 5 (2) At positions #1 and #2, when a biological particle passes through positions #1 and #2, an electric field disturbance will be generated. Due to the unique electric signal differential method of the present invention as described above, the signals generated by the same biological particle at positions #1 and #2 are equal in size and centrally symmetrical in shape (e.g. Figure 5 (3)), thereby avoiding inaccurate detection caused by uneven electric field distribution.

[0017] In this embodiment, the upper electrode layer 1 and the lower electrode layer 3 are made of heterogeneous materials by three-dimensional printing, the electrode part is a conductive material, the non-electrode part is an insulating material, and the flow channel layer 2 is made of non-conductive materials by three-dimensional printing. When the upper electrode layer 1, the flow channel layer 2, and the lower electrode layer 3 are assembled from top to bottom, they are sealed by a hot pressing process or by a sealant.

[0018] The above description is only a preferred embodiment of the present invention and does not constitute any other form of limitation to the present invention. Any modification or equivalent change made based on the technical essence of the present invention still falls within the scope of protection required by the present invention.

Claims

1. A flow type electrical impedance detection device manufactured by three-dimensional printing, characterized in that: The device comprises three parts, from top to bottom, namely, an upper electrode layer (1), a flow channel layer (2), and a lower electrode layer (3). The upper electrode layer (1) is provided with four detection electrodes. The upper electrode layer (1) is provided with a small positioning mark (15) and an upper electrode layer large positioning mark (17) to facilitate mutual alignment between the upper electrode layer (1), the flow channel layer (2), and the lower electrode layer (3). The upper electrode layer (1) is provided with a sample inlet (18) and a sample outlet (16) to respectively implement sample input and output. The flow channel layer (2) is provided with a flow channel inlet (21), a flow channel outlet (22), an outlet flow channel (23), a flow channel layer large positioning mark (24), a detection flow channel (25), and an inlet flow channel (26). The flow channel inlet (21) and the flow channel outlet (22) are respectively connected to the upper electrode layer (1). The sample inlet (18) and the sample outlet (16) on the upper electrode layer (1) are opposite to each other; the inlet flow channel (26), the flow channel layer large positioning mark (24) and the upper electrode layer large positioning mark (17) on the upper electrode layer (1) correspond to each other, so as to achieve accurate alignment between the upper electrode layer (1) and the flow channel layer (2); four detection electrodes are arranged on the lower electrode layer (3); a plurality of lower electrode layer small positioning marks (35) and lower electrode layer large positioning marks (36) are arranged on the lower electrode layer (3), so as to facilitate mutual alignment between the upper electrode layer (1), the flow channel layer (2) and the lower electrode layer (3); after alignment, the detection electrodes on the upper electrode layer (1) and the lower electrode layer (3) are arranged face to face and in parallel, and the end of the detection flow channel (24) in the flow channel layer (2) is located in the middle of the detection electrodes in the upper electrode layer (1) and the lower electrode layer (3).

2. A three-dimensional printed flow impedance detection device according to claim 1, characterized in that: The upper electrode layer (1) is provided with four detection electrodes, namely, upper electrode layer detection electrode 1 (11), upper electrode layer detection electrode 2 (12), upper electrode layer detection electrode 3 (13) and upper electrode layer detection electrode 4 (14). The four detection electrodes are thinner at the front ends, and their sizes match the cell size, while the four detection electrodes are thicker at the rear ends.

3. The three-dimensional printed flow impedance detection device according to claim 1, characterized in that: The lower electrode layer (3) is provided with four detection electrodes, namely, lower electrode layer detection electrode 1 (31), lower electrode layer detection electrode 2 (32), lower electrode layer detection electrode 3 (33) and lower electrode layer detection electrode 4 (34). The four detection electrodes have thin ends, the size of which matches the size of the cells, and thick ends, which facilitate connection with an external circuit.

4. The three-dimensional printed flow impedance detection device according to claim 1, characterized in that: The detection flow channel (24) is a straight flow channel or a serpentine flow channel with a high aspect ratio.

5. The three-dimensional printing flow type electrical impedance detection device according to claim 1, characterized in that: The external circuit of the electrical impedance detection also includes two transimpedance amplifiers TA, a differential amplifier Diff, a signal generator SG, a mixer Mixer, a low-pass filter LPF, and a phase inverter PI. The upper electrode layer detection electrode 1 (11), the upper electrode layer detection electrode 2 (12), the lower electrode layer detection electrode 3 (33), and the lower electrode layer detection electrode 4 (34) are excitation electrodes and are applied with an electric field. The upper electrode layer detection electrode 3 (13), the upper electrode layer detection electrode 4 (14), the lower electrode layer detection electrode 1 (31), and the lower electrode layer detection electrode 2 (32) are sensing electrodes to realize the reception of sensing signals. The signal generator SG sends out a detection signal, which is applied to the upper electrode layer detection electrode 1 (11) and the upper electrode layer detection electrode 2 (12) and the lower electrode layer detection electrode 3 (33) and the lower electrode layer detection electrode 4 (34) respectively after passing through the phase inverter PI, that is, the upper electrode layer detection electrode The electric field applied to the upper electrode layer detection electrode 1 (11) and the upper electrode layer detection electrode 2 (12) and the electric field applied to the lower electrode layer detection electrode 3 (33) and the lower electrode layer detection electrode 4 (34) are of the same magnitude and opposite phase; the upper electrode layer detection electrode 3 (13) and the lower electrode layer detection electrode 2 (32) are short-circuited and then amplified by the transimpedance amplifier TA; the upper electrode layer detection electrode 4 (14) and the lower electrode layer detection electrode 1 (31) are short-circuited and then amplified by the transimpedance amplifier TA, wherein the upper electrode layer detection electrode 3 (13) and the lower electrode layer detection electrode 2 (32) are short-circuited, and the upper electrode layer detection electrode 4 (14) and the lower electrode layer detection electrode 1 (31) are short-circuited as the first differential; the signal after the first differential is then connected to the differential amplifier Diff for the second differential, and then the signal is amplified by the phase-locked amplifier composed of the signal generator SG, the mixer Mixer, and the low-pass filter LPF, and finally a weak electrical impedance signal is obtained.

6. The three-dimensional printing flow type electrical impedance detection device according to claim 1, characterized in that: The upper electrode layer (1) and the lower electrode layer (3) are made of heterogeneous materials by three-dimensional printing, the electrode part is a conductive material, the non-electrode part is an insulating material, and the flow channel layer (2) is made of non-conductive material by three-dimensional printing. When the upper electrode layer (1), the flow channel layer (2), and the lower electrode layer (3) are assembled from top to bottom, they are sealed by a hot pressing process or by a sealant.

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