Microfluidic system for electrical impedance measurement

Abstract

The utility model relates to the technical field of cell electrical impedance measurement, and provides a micro-fluidic system for electrical impedance measurement, which comprises a micro-fluidic chip, the micro-fluidic chip comprises a lower layer chip, the lower layer chip comprises a lower bottom plate, an inlet, a groove and a seven-electrode structure, the groove is arranged on the inner side wall of the lower bottom plate, one end of the groove is provided with the inlet, and the other end of the groove is provided with the seven-electrode structure. According to the multi-electrode micro-fluidic chip disclosed by the utility model, the inflow height of a sample can be accurately detected, and meanwhile, the detection sensitivity is improved.

Description

Technical Field

[0001] The utility model relates to the technical field of cell electrical impedance measurement, in particular to a microfluidic system for electrical impedance measurement. Background Art

[0002] Single-cell characterization provides basic cell structure, functional information and pathological state, plays an important role in revealing cell heterogeneity, and is of great significance to life science research, disease diagnosis and personalized medicine. Fluorescence labeling has always been the main tool for single-cell analysis and imaging. It identifies the components and their states in cells by using molecularly specific detection labels (such as fluorescent dyes, quantum dots, magnetic beads and stable isotopes) for cell labeling. Fluorescence labeling of cells not only requires prior knowledge of cell specificity, but also the invasive operation of the labeling process will change the cell state, complicate the analysis process and limit subsequent analysis. In contrast, the biophysical properties of single cells (such as electrical properties) are also related to the molecular composition of the cell. At present, studies have shown that changes in the biophysical properties of single cells are closely related to the physiological and pathological mechanisms of cells, the malignancy of tumor cells, etc., and the characterization of biophysical properties does not require cell labeling. The cell state remains unchanged during the characterization process, and the characterized cells still maintain their original activity for the next step of operation and analysis.

[0003] As one of the biological characteristics of single cells, electrical and physical properties play a very important role in characterizing the size, vitality and geometry of single cells. The basic principle of characterizing the electrical characteristics of single cells is that the impedance of the detected area changes when a single cell sample flows into the detection area, and the electrical and physical characteristics of the single cell are obtained by calculating the real part, imaginary part and other data parameters of the single cell electrical impedance signal obtained by detection. The impedance signal caused by the same single cell at different heights in the microchannel is different. Therefore, the uncertainty of position brings errors to the measurement of electrical parameters, and the precise positioning of single cells is crucial for the accurate measurement of the electrical parameters of cells (such as cell impedance). In order to avoid the influence of spatial position on impedance measurement, the traditional single cell impedance method is used to measure the current change caused by a cell passing through a channel with a similar or smaller diameter, and this method is very easy to cause blockage. At present, it has been proposed to use the sheath flow method to focus on the cell position, making the cell inflow position a controllable factor, but the manufacture of this microdevice is very complicated, making it impossible to apply it in practice, so identifying the height of the inflow cell becomes the key to eliminating the height dependence. Utility Model Content

[0004] The utility model aims to solve at least one of the technical problems existing in the related art. To this end, the utility model provides a microfluidic system for electrical impedance measurement, which can accurately detect the inflow height of the sample and improve the sensitivity of the detection.

[0005] The utility model provides a microfluidic system for electrical impedance measurement, comprising: a microfluidic chip, the microfluidic chip comprising a lower chip, the lower chip comprising a lower base plate, an inlet, a groove and a seven-electrode structure, the groove is opened on the inner side wall of the lower base plate, one end of the groove is provided with an inlet, the inlet is communicated with the groove, the seven-electrode structure is connected to the side of the groove, and is embedded in the lower base plate.

[0006] According to a microfluidic system for electrical impedance measurement provided by the utility model, the groove includes a first groove, a second groove, a third groove and a fourth groove, the first groove, the second groove, the third groove and the fourth groove are connected, one side of the first groove, the second groove, the third groove and the fourth groove is flush, and the opposite side is arranged in a stepped manner in sequence.

[0007] According to a microfluidic system for electrical impedance measurement provided by the utility model, the seven-electrode structure includes a first seven-electrode structure, a second seven-electrode structure, a third seven-electrode structure and a fourth seven-electrode structure, the first seven-electrode structure is arranged on the side of the first groove, the second seven-electrode structure is arranged on the side of the second groove, the third seven-electrode structure is arranged on the side of the third groove, and the fourth seven-electrode structure is arranged on the side of the fourth groove.

[0008] According to a microfluidic system for electrical impedance measurement provided by the utility model, the tops of the first seven-electrode structure, the second seven-electrode structure, the third seven-electrode structure and the fourth seven-electrode structure are higher than the upper surface of the lower base plate.

[0009] According to a microfluidic system for electrical impedance measurement provided by the utility model, the microfluidic chip also includes an upper chip, and the upper chip includes an upper base plate, a through hole and a receiving groove, the through hole is arranged on one side of the upper base plate, and the through hole is connected to the inlet, and the receiving groove is opened on the inner side wall of the upper base plate and is adapted to the seven-electrode structure.

[0010] According to the utility model, a microfluidic system for electrical impedance measurement further includes a driving device, wherein the driving device is connected to the through hole and is suitable for driving the sample to enter the inlet through the through hole.

[0011] According to a microfluidic system for electrical impedance measurement provided by the utility model, the seven-electrode structure is slidably arranged in the extension direction of the containing groove.

[0012] According to a microfluidic system for electrical impedance measurement provided by the utility model, the seven-electrode structure is composed of seven metal modules, and the wiring of the seven metal modules sequentially selects negative excitation voltage, floating electrode, ground electrode, positive excitation voltage, ground electrode, floating electrode, and negative excitation voltage.

[0013] According to a microfluidic system for electrical impedance measurement provided by the utility model, the cross section of the metal module is square.

[0014] According to the utility model, a microfluidic system for electrical impedance measurement also includes an image detection component, which includes any one or a combination of the following: an optical microscope, a differential interference microscope, and an electron microscope.

[0015] The above one or more technical solutions in the embodiments of the utility model have at least one of the following technical effects:

[0016] According to a microfluidic system for electrical impedance measurement in an embodiment of the utility model, by setting a seven-electrode structure on the side of the groove, the observation of the inflow height of a single cell in the detection area is achieved after the microfluidic chip is laid flat, and accurate images can be extracted through the image detection component, thereby achieving accurate detection of the inflow height of the sample and improving the detection sensitivity.

[0017] 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

[0018] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0019] Figure 1 It is a stereoscopic diagram of a microfluidic chip of a microfluidic system for electrical impedance measurement provided by the utility model.

[0020] Figure 2 It is a stereoscopic diagram of the lower chip of the microfluidic chip of the microfluidic system for electrical impedance measurement provided by the utility model.

[0021] Figure 3 It is a stereoscopic diagram of an upper chip of a microfluidic chip of a microfluidic system for electrical impedance measurement provided by the utility model.

[0022] Figure 4The utility model provides a wiring diagram of a seven-electrode structure of a microfluidic system for electrical impedance measurement.

[0023] Figure 5 It is a schematic diagram of single cell inflow impedance signal detection of a microfluidic system for electrical impedance measurement provided by the utility model.

[0024] Reference numerals:

[0025] 1. Microfluidic chip; 11. Lower chip; 111. Lower base plate; 112. Inlet; 113. Groove; 1131. First groove; 1132. Second groove; 1133. Third groove; 1134. Fourth groove; 114. Seven-electrode structure; 1141. First seven-electrode structure; 1142. Second seven-electrode structure; 1143. Third seven-electrode structure; 1144. Fourth seven-electrode structure; 12. Upper chip; 121. Upper base plate; 122. Through hole; 123. Receiving groove; 2. Image detection component. DETAILED DESCRIPTION

[0026] In order to make the purpose, technical solution and advantages of the utility model clearer, the technical solution in the utility model will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model. The following embodiments are used to illustrate the utility model, but cannot be used to limit the scope of the utility model.

[0027] In the description of the embodiments of the present utility model, it should be noted that the terms "center", "longitudinal", "lateral", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the embodiments of the present utility model and simplifying the description, rather than indicating or implying 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 limiting the embodiments of the present utility model. In addition, the terms "first", "second", and "third" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance.

[0028] In the description of the embodiments of the present utility model, it should be noted that, unless otherwise clearly specified and limited, the terms "connected" and "connection" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium. For ordinary technicians in this field, the specific meanings of the above terms in the embodiments of the present utility model can be understood according to specific circumstances.

[0029] In the embodiments of the present invention, unless otherwise clearly specified and limited, the first feature being "above" or "below" the second feature may mean that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, the first feature being "above", "above" and "above" the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. The first feature being "below", "below" and "below" the second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.

[0030] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the utility model embodiment. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0031] In the related art, there is a problem that the inflow height of a single cell cannot be accurately measured. In order to solve this problem, a seven-electrode structure is set on the side of the groove, and the groove is set in a stepped shape. It can be achieved that when a single cell flows in different areas, the distance from the single cell to the seven-electrode structure changes. The cross-section of the metal module of the seven-electrode structure is set to be square, so that the signals of the single cell in different directions parallel to the detection section remain consistent, and finally the accurate measurement of the inflow height of the single cell can be achieved.

[0032] Figure 1 It is a stereoscopic diagram of a microfluidic chip of a microfluidic system for electrical impedance measurement provided by the utility model. Figure 2 It is a stereoscopic diagram of the lower chip of the microfluidic chip of the microfluidic system for electrical impedance measurement provided by the utility model.

[0033] The utility model provides a microfluidic system for electrical impedance measurement, such as Figure 1~Figure 2 As shown, the microfluidic system for electrical impedance measurement includes: a microfluidic chip 1, the microfluidic chip 1 includes a lower chip 11, the lower chip 11 includes a lower base plate 111, an inlet 112, a groove 113 and a seven-electrode structure 114, the groove 113 is opened on the inner wall of the lower base plate 111, one end of the groove 113 is provided with an inlet 112, the inlet 112 is connected to the groove 113, and the inlet 112 is provided to facilitate the flow of the sample into the groove 113, the seven-electrode structure 114 is connected to the side of the groove 113, and is embedded in the lower base plate 111.

[0034] In this embodiment, by setting the seven-electrode structure 114 on the side of the groove 113, the observation of the flow height of a single cell in the detection area after the microfluidic chip 1 is laid flat can be achieved, and accurate images can be extracted through the image detection component, thereby accurately detecting the flow height of the sample and improving the detection sensitivity.

[0035] According to some embodiments of the utility model, the structure of the microfluidic chip 1 takes into account the convenience of optical observation, and the microfluidic chip 1 is set as a two-layer structure. The lower chip 11 includes a lower base plate 111, and an inlet 112 is opened on the lower base plate 111 to connect with the groove 113. The single cell enters the groove 113 through the inlet 112, and the single cell flows in the groove 113. The seven-electrode structure 114 is arranged on the side of the groove 113 to realize the input and output of the AC signal when the single cell flows in.

[0036] According to some embodiments of the utility model, the side electrodes of the microfluidic chip 1 structure are arranged so that the distance between a single cell and the electrode in the detection area under the plane field of view is the single cell inflow height in the microfluidic detection, thereby avoiding the inaccuracy of data recognition and obtaining the accurate distance between the single cell and the electrode provided by the image.

[0037] According to some embodiments of the present invention, the microfluidic chip 1 adopts a high-speed charge-coupled chip.

[0038] According to a microfluidic system for electrical impedance measurement provided by the utility model, Figure 1~Figure 2 As shown, the groove 113 includes a first groove 1131, a second groove 1132, a third groove 1133 and a fourth groove 1134, the first groove 1131, the second groove 1132, the third groove 1133 and the fourth groove 1134 are connected, one side of the first groove 1131, the second groove 1132, the third groove 1133 and the fourth groove 1134 are flush, and the opposite sides are arranged in a stepped manner in sequence.

[0039] In this embodiment, by setting the grooves 113 to different regions and arranging them in a step-like manner, the distance between the single cell and the seven-electrode structure 114 is changed when the single cell flows in different regions.

[0040] According to some embodiments of the utility model, during the single cell inflow process, the single cell flows through the first groove 1131, the second groove 1132, the third groove 1133 and the fourth groove 1134 respectively. When the single cell flows through the first groove 1131, the distance between the single cell and the detection area of ​​the seven electrodes is h1, and h2, h3 and h4 are obtained in the same way. Since the groove 113 of the microfluidic chip 1 is designed as a stepped groove 113, the distance between the single cell and the electrode changes when the single cell flows through different areas. Using the imaging obtained by the single cell flowing through different areas, the precise inflow heights h1, h2, h3 and h4 of the single cell can be obtained using the MATLAB cftool module.

[0041] According to a microfluidic system for electrical impedance measurement provided by the utility model, Figure 1~Figure 2 As shown, the seven-electrode structure 114 includes a first seven-electrode structure 1141, a second seven-electrode structure 1142, a third seven-electrode structure 1143 and a fourth seven-electrode structure 1144, the first seven-electrode structure 1141 is arranged on the side of the first groove 1131, the second seven-electrode structure 1142 is arranged on the side of the second groove 1132, the third seven-electrode structure 1143 is arranged on the side of the third groove 1133, and the fourth seven-electrode structure 1144 is arranged on the side of the fourth groove 1134.

[0042] In this embodiment, by setting the first seven-electrode structure 1141 on the side of the first groove 1131, the second seven-electrode structure 1142 on the side of the second groove 1132, the third seven-electrode structure 1143 on the side of the third groove 1133, and the fourth seven-electrode structure 1144 on the side of the fourth groove 1134, it is possible to detect the change in impedance signal when a single cell flows through different areas.

[0043] According to a microfluidic system for electrical impedance measurement provided by the utility model, Figure 1~Figure 2 As shown, the tops of the first seven-electrode structure 1141 , the second seven-electrode structure 1142 , the third seven-electrode structure 1143 and the fourth seven-electrode structure 1144 are higher than the upper surface of the lower base plate 111 , which is suitable for preventing sample loss.

[0044] In this embodiment, the tops of the first seven-electrode structure 1141, the second seven-electrode structure 1142, the third seven-electrode structure 1143 and the fourth seven-electrode structure 1144 are higher than the upper surface of the lower base plate 111, which can avoid fluid loss due to processing errors.

[0045] Figure 3 It is a stereoscopic diagram of an upper chip of a microfluidic chip of a microfluidic system for electrical impedance measurement provided by the utility model.

[0046] According to a microfluidic system for electrical impedance measurement provided by the utility model, Figure 3 As shown, the microfluidic chip 1 also includes an upper chip 12, and the upper chip 12 includes an upper base plate 121, a through hole 122 and a receiving groove 123. The through hole 122 is arranged on one side of the upper base plate 121, and the through hole 122 is connected to the inlet 112. The receiving groove 123 is opened on the inner wall of the upper base plate 121 and is adapted to the seven-electrode structure 114. The receiving groove 123 is suitable for sealing the seven-electrode structure 114.

[0047] According to a microfluidic system for electrical impedance measurement provided by the utility model, the microfluidic system for electrical impedance measurement further includes a driving device, which is connected to the through hole 122 and is suitable for driving the sample to enter the inlet 112 through the through hole 122 .

[0048] In this embodiment, a driving device is provided to be connected to the through hole 122 so as to facilitate the flow of single cells inside the microfluidic chip 1 .

[0049] According to some embodiments of the present invention, the driving device drives the sample into the inlet 112 by connecting with the through hole 122 , and then into the groove 113 to flow.

[0050] According to some embodiments of the present invention, the flow rate of a single cell passing through the measuring area of ​​the microfluidic chip 1 is controlled by a driving device.

[0051] According to a microfluidic system for electrical impedance measurement provided by the utility model, the seven-electrode structure 114 is slidably arranged in the extension direction of the receiving groove 123 .

[0052] In this embodiment, by arranging the seven-electrode structure 114 to be slidable, the microfluidic chip 1 can be adjusted according to actual needs and has a wider application range.

[0053] Figure 4 The utility model provides a wiring diagram of a seven-electrode structure of a microfluidic system for electrical impedance measurement. Figure 5It is a schematic diagram of single cell inflow impedance signal detection of a microfluidic system for electrical impedance measurement provided by the utility model.

[0054] According to a microfluidic system for electrical impedance measurement provided by the utility model, Figure 4~Figure 5 As shown, the seven-electrode structure 114 is composed of seven metal modules, and the seven metal modules are connected in sequence to select negative excitation voltage, floating electrode, ground electrode, positive excitation voltage, ground electrode, floating electrode, and negative excitation voltage.

[0055] In this embodiment, a specific signal is obtained by acquiring a difference with the ground electrode.

[0056] According to some embodiments of the present invention, the excitation voltage adopts a frequency selected as 100K~40MHz.

[0057] According to some embodiments of the present invention, a sinusoidal alternating current with an initial phase of 0 is input.

[0058] According to a microfluidic system for electrical impedance measurement provided by the utility model, the cross section of the metal module is square, so that the signals of the sample in different directions parallel to the detection cross section remain consistent.

[0059] According to some preferred embodiments of the present invention, the measuring cross section of the metal electrode is designed to be 0.5 mm wide and 0.5 mm long.

[0060] According to a microfluidic system for electrical impedance measurement provided by the utility model, Figure 5 As shown, the microfluidic system for electrical impedance measurement also includes an image detection component, which includes any one or a combination of the following: an optical microscope, a differential interference microscope, and an electron microscope.

[0061] According to some preferred embodiments of the present invention, the image detection component adopts an electron microscope.

[0062] According to some embodiments of the present invention, after the microfluidic chip 1 is laid flat, the image detection component 2 processes the detected image to obtain the inflow height of the inflow sample.

[0063] Compared with the prior art, the microfluidic system for electrical impedance measurement in the embodiment of the utility model has the following technical effects:

[0064] (1) Based on the single-cell electrical impedance measurement, the utility model proposes the accurate detection of the single-cell inflow height and the elimination of the impedance signal height dependence. The utility model method avoids the problem that the existing 3D floating electrode cannot accurately detect the single-cell inflow height measurement and cannot eliminate the height dependence.

[0065] (2) The utility model can accurately detect the inflow height of a single cell, so that the seven-electrode structure can achieve high detection sensitivity while also accurately measuring the inflow height of a single cell, thereby eliminating height dependence.

[0066] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the utility model, rather than to limit it. Although the utility model has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the utility model.

Claims

1. A microfluidic system for electrical impedance measurement, characterized in that: include: A microfluidic chip, the microfluidic chip includes a lower chip, the lower chip includes a lower base plate, an inlet, a groove and a seven-electrode structure, the groove is opened on the inner wall of the lower base plate, one end of the groove is provided with an inlet, the inlet is connected to the groove, the seven-electrode structure is connected to the side of the groove and embedded in the lower base plate.

2. The microfluidic system for electrical impedance measurement according to claim 1, characterized in that: The grooves include a first groove, a second groove, a third groove and a fourth groove, the first groove, the second groove, the third groove and the fourth groove are connected, one side of the first groove, the second groove, the third groove and the fourth groove is flush, and the opposite side is arranged in a stepped manner in sequence.

3. The microfluidic system for electrical impedance measurement according to claim 2, characterized in that: The seven-electrode structure includes a first seven-electrode structure, a second seven-electrode structure, a third seven-electrode structure and a fourth seven-electrode structure. The first seven-electrode structure is arranged on the side of the first groove, the second seven-electrode structure is arranged on the side of the second groove, the third seven-electrode structure is arranged on the side of the third groove, and the fourth seven-electrode structure is arranged on the side of the fourth groove.

4. The microfluidic system for electrical impedance measurement according to claim 3, characterized in that: The tops of the first seven-electrode structure, the second seven-electrode structure, the third seven-electrode structure and the fourth seven-electrode structure are higher than the upper surface of the lower base plate.

5. The microfluidic system for electrical impedance measurement according to claim 1, characterized in that: The microfluidic chip also includes an upper chip, which includes an upper base plate, a through hole and a receiving groove. The through hole is arranged on one side of the upper base plate, and the through hole is connected to the inlet. The receiving groove is opened on the inner wall of the upper base plate and is adapted to the seven-electrode structure.

6. The microfluidic system for electrical impedance measurement according to claim 5, characterized in that: It also includes a driving device, which is connected to the through hole.

7. The microfluidic system for electrical impedance measurement according to claim 5, characterized in that: The seven-electrode structure is slidably arranged in the extending direction of the accommodating groove.

8. The microfluidic system for electrical impedance measurement according to claim 1, characterized in that: The seven-electrode structure is composed of seven metal modules, and the seven metal modules are connected in sequence to select negative excitation voltage, floating electrode, ground electrode, positive excitation voltage, ground electrode, floating electrode, and negative excitation voltage.

9. The microfluidic system for electrical impedance measurement according to claim 8, characterized in that: The cross section of the metal module is a square.

10. The microfluidic system for electrical impedance measurement according to claim 1, characterized in that: It also includes an image detection component, which includes any one or a combination of the following: an optical microscope, a differential interference microscope, and an electron microscope.

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