Microfluidic channel potential measurement system

Abstract

Embodiments of the present invention relate to a potential measurement system for a microfluidic channel, and the potential measurement system for a microfluidic channel according to embodiments of the present invention may include: a microchannel into which a sample solution containing a sample is injected; a reservoir into which a buffer solution is injected; a probe channel formed extending from at least a portion of the reservoir and having an end connected to the microchannel and including an ion exchange membrane; a measuring electrode electrically connected to the reservoir; and a measuring unit that applies a feedback voltage to the reservoir via the measuring electrode and measures the potential at a target position in the microchannel based on the applied feedback voltage.

Description

Technical Field

[0001] Embodiments of the present invention relate to a potential measurement system for microfluidic channels.

Background Art

[0002] From the technology of measuring the potential value at any point in a microfluidic channel, information such as the concentration and electric field at that point can be inferred, and it can be widely utilized in various application fields using microfluidic systems.

[0003] However, the smaller the size of the microfluidic channel and the lower the concentration of the electrolyte, the greater the electrical resistance value. Therefore, when the input impedance of the measuring instrument has a magnitude similar to or smaller than the channel resistance, there is a limit that the accuracy of potential measurement decreases due to current distribution inside the measuring instrument.

[0004] Due to various other characteristics of microfluidic channels, it has been difficult to accurately measure the potential at a specific point using conventional general potential measurement methods.

Summary of the Invention

Problems to be Solved by the Invention

[0005] Embodiments of the present invention provide a potential measurement system for microfluidic channels that can more accurately measure the potential at a specific point within a microfluidic channel.

Means for Solving the Problems

[0006] The microfluidic channel potential measurement system according to the present invention may include: a microchannel into which a sample solution containing a sample is injected; a reservoir into which a buffer solution is injected; a probe channel formed extending from at least a portion of the reservoir and having an end connected to the microchannel and including an ion exchange membrane; a measuring electrode electrically connected to the reservoir; and a measuring unit that applies a feedback voltage to the reservoir via the measuring electrode and measures the potential at a target position in the microchannel based on the applied feedback voltage.

[0007] In a microfluidic channel potential measurement system according to one embodiment, the ion exchange membrane can have cation-selective permeability.

[0008] In one embodiment of a microfluidic channel potential measurement system, the ion exchange membrane may be Nafion.

[0009] In a microfluidic channel potential measurement system according to one embodiment, the ion exchange membrane can have anion-selective permeability.

[0010] In one embodiment of a microfluidic channel potential measurement system, the measurement electrode may be an Ag / AgCl reference electrode.

[0011] In one embodiment of a microfluidic channel potential measurement system, the buffer solution may also contain KCl.

[0012] In one embodiment of a microfluidic channel potential measurement system, multiple probes may be provided.

[0013] In a microfluidic channel potential measurement system according to one embodiment, the ion exchange membrane may be connected to the microchannel such that its end covers at least a portion of the outer surface of the microchannel.

[0014] In a microfluidic channel potential measurement system according to one embodiment, the cross-section of the microchannel is formed in a rectangular shape, and the ion exchange membrane may be connected to the microchannel such that its ends cover at least three surfaces of the outer surface of the microchannel.

[0015] In a microfluidic channel potential measurement system according to one embodiment, the measurement unit can apply a feedback voltage to the reservoir so that the current in the ion exchange membrane becomes zero. [Effects of the Invention]

[0016] According to an embodiment of the present invention, a microfluidic channel potential measurement system is provided that can more accurately measure the potential at a specific point within the microfluidic channel. [Brief explanation of the drawing]

[0017] [Figure 1] This figure illustrates a potential measurement system for microfluidic channels according to one embodiment of the present invention. [Figure 2] This figure shows a potential measurement system equipped with multiple probe channels according to one embodiment of the present invention. [Figure 3] This figure provides a detailed explanation of the connection relationship between an ion exchange membrane and a microchannel according to one embodiment of the present invention. [Figure 4] This is a diagram showing a cross-section in direction A of Figure 3. [Figure 5] This figure shows a potential measurement system equipped with multiple probe channels according to one embodiment of the present invention, and the voltage measured at each target position of the system over time. [Figure 6] This figure shows an example of measuring the concentration of a sample solution injected into a microchannel using a potential measurement system according to one embodiment of the present invention. [Modes for carrying out the invention]

[0018] The structural or functional descriptions of the embodiments disclosed in this specification or application are merely exemplified for the purpose of explaining the embodiments according to the technical idea of the present invention. The embodiments according to the technical idea of the present invention may be implemented in various forms other than the embodiments disclosed in this specification or application, and the technical idea of the present invention is not construed as being limited to the embodiments described in this specification or application.

[0019] FIG. 1 is a diagram for explaining a potential measurement system of a microfluidic channel according to an embodiment of the present invention.

[0020] Referring to FIG. 1, a potential measurement system 10 of a microfluidic channel according to an embodiment of the present invention may include a microchannel 100, a probe channel 200 including a reservoir 210 and an ion exchange membrane 220, a measurement electrode 310, and a measurement unit 300.

[0021] In one embodiment, a sample solution containing a sample may be injected into the microchannel 100.

[0022] The sample may be, without limitation, a protein, a fluorescent particle, a lipid nanoparticle, a microbead, or an exosome, and the diameter of the particle may be in the range of several nm to several tens of μm. The sample solution may include the sample and a buffer solution. The buffer solution may be, without limitation, KCl, NaCl, PBS (Phosphate Buffered Saline), TBS (Tris Buffered Saline), or a mixture thereof.

[0023] In one embodiment, the microchannel 100 may include an inlet for injecting a sample solution at one end 101. The microchannel 100 may also include an outlet for the sample solution at the other end 102. As a non-limiting example, the microchannel 100 may have a shape that extends long in one direction so that the sample solution can easily move along the path. In this case, the microchannel 100 has a shape that extends long in one direction, and the cross-section perpendicular to the direction of extension at any point may be rectangular, square, circular, elliptical, trapezoidal, or triangular, but is not necessarily limited to these. The direction of extension of the microchannel 100 may be a straight line or a curve.

[0024] In this application, the term "microchannel 100" is used, but the above microchannel 100 can be a general term for a microfluidic channel structure in which a sample solution is contained and fluid flow is possible by electric force or capillary force, and can mean all nano or microscale channels without shape restrictions. In one embodiment, if the cross-section of the microchannel 100 is rectangular, square, triangular, or trapezoidal, the width may be 10 μm to 1000 μm and the height may be 0.5 μm to 1000 μm, and if the cross-section of the microchannel 100 is elliptical or circular, the major axis may be 10 μm to 1000 μm and the minor axis may be 0.5 μm to 1000 μm, but is not necessarily limited to these.

[0025] In one embodiment, the microchannel 100 may include a flexible polymer material or a rigid plastic. For example, a flexible polymer such as PDMS or a rigid plastic such as acrylic or polycarbonate can be used as the material for the microchannel 100.

[0026] In one embodiment, a reference voltage (V) is applied to one end 101 of the microchannel 100. H A reference voltage (V) can be applied. H) may be a fixed voltage or a variable voltage. The other end 102 of the microchannel 100 has a control voltage (V) that changes in voltage according to the control. CTRL ) is applied, or ground voltage (V GND A voltage can be applied to the microchannel 100. Electrodes (not shown) may be connected to one end 101 and the other end 102 of the microchannel 100 to apply the reference voltage and control voltage as described above. However, this is not necessarily the only option, and a potential difference can be formed across both ends of the microchannel 100 by various conditions, such as applying current or flow rate to the microchannel 100 as needed.

[0027] Thus, the microchannel 100 can form a potential difference at both ends under various conditions as described above for the separation, concentration, and extraction of a sample substance injected into the microchannel 100, thereby creating an electric field within the microchannel 100 due to the potential difference at both ends. The potential difference due to the potential applied to both ends and the flowing fluid such as the sample solution inside can cause any point within the microchannel 100 to exhibit a specific potential value at a given time, and this can change in real time. From the potential value at any point within the microchannel 100, various information such as the electric field at that point and the sample concentration of the sample solution passing through that point can be inferred.

[0028] In one embodiment, the probe channel 200 may include a reservoir 210 into which a buffer solution is injected, and an ion exchange membrane 220 extending from at least a portion of the reservoir 210, with its end connected to the microchannel 100. The probe channel 200 can be connected to the microchannel 100 by the end of the ion exchange membrane 220 being connected to the microchannel 100. The point in the microchannel 100 where the end of the ion exchange membrane 220 is connected to the microchannel 100 can be the target position in the microchannel 100 where potential measurement is to be performed.

[0029] In one embodiment, a buffer solution can be injected into the reservoir 210. The buffer solution can be injected into the reservoir 210 and contained within it. The buffer solution may be, but is not limited to, KCl, NaCl, PBS (Phosphate Buffered Saline), TBS (Tris Buffered Saline), or a mixture thereof. The buffer solution injected into the reservoir 210 may be an electrolyte with a composition corresponding to the buffer solution injected into the microchannel 100, and may also be a buffer solution with a corresponding concentration.

[0030] In one embodiment, the reservoir 210 may be a sphere, cube, rectangular prism, cone, cylinder, truncated pyramid, pyramid, or prism, or may have a shape that includes two or more of these shapes, as needed. The reservoir 210 may contain a flexible polymer material or a rigid plastic. For example, a flexible polymer such as PDMS or a rigid plastic such as acrylic or polycarbonate can be used as the material for the reservoir 210.

[0031] In one embodiment, the ion exchange membrane 220 is formed extending from at least a portion of the reservoir 210, and its end can be connected to the microchannel 100. The ion exchange membrane 220 may have a shape that extends long in one direction, and its extension direction may be straight or curved. The ion exchange membrane 220 may have the form of a membrane.

[0032] The ion exchange membrane 220 is in communication with the reservoir 210, allowing the buffer solution injected into and contained in the reservoir 210 to move along the ion exchange membrane 220 and reach the connection point with the microchannel 100.

[0033] The ion exchange membrane 220 can be configured such that zero or extremely low current flows through it, mediated by ion movement, thereby suppressing the ion concentration polarization (ICP) phenomenon due to ion exchange. This can be achieved by the shape and patterning method of the ion exchange membrane 220, as described later.

[0034] In one embodiment, the ion exchange membrane 220 can have ion-selective permeability.

[0035] In one embodiment, the ion exchange membrane 220 can have cation-selective permeability. This cation-selective permeability means that cations can permeate through the boundary of the ion exchange membrane 220, but anions cannot. Therefore, the ion exchange membrane 220 can be described as a cation exchange membrane.

[0036] In one embodiment, the cation exchange membrane may be Nafion, PEDOT:PSS, CSH (Cation Selective Hydrogel), Neosepta CMX, or Fumapem (CEM). In a specific embodiment, the cation exchange membrane may be Nafion.

[0037] In one embodiment, the ion exchange membrane 220 can have anion-selective permeability. This anion-selective permeability means that anions can permeate through the boundary of the ion exchange membrane 220, but cations cannot. Therefore, the ion exchange membrane 220 can be described as an anion exchange membrane.

[0038] In one embodiment, the anion exchange membrane may be ASH (anion selective hydrogel), Neosepta AMX, Fumapem (AEM), or AEM-Pention.

[0039] Figure 2 shows a system 10 in which a plurality of probe channels 200 are provided in one embodiment of the present invention for measuring the potential of a microfluidic channel.

[0040] Referring to Figure 2, in one embodiment of the present invention, the microfluidic channel potential measurement system 10 can include one or more probe channels 200. When the system 10 includes one or more probe channels 200, the ion exchange membranes 220 of one or more probe channels 200 can be connected to the microchannel 100 at different target positions. Depending on the configuration of the connected probe channels 200, the potentials at multiple target positions to which the ion exchange membranes 220 of each probe channel 200 are connected can be measured.

[0041] Figure 3 is a diagram illustrating in detail the connection relationship between the ion exchange membrane 220 and the microchannel 100 according to one embodiment of the present invention.

[0042] Figure 4 shows a cross-section in direction A of Figure 3.

[0043] Figures 3 and 4 are diagrams illustrating in detail the connection relationship between the ion exchange membrane 220 and the microchannel 100 according to one embodiment.

[0044] In one embodiment of the present invention, the microfluidic channel potential measurement system 10 may, in one embodiment, have the ion exchange membrane 220 connected to the microchannel 100 such that its end covers at least a portion of the outer surface of the microchannel 100.

[0045] Referring to Figures 3 and 4, in one embodiment, the cross-section of the microchannel 100 is formed in a rectangular shape, and the ion exchange membrane 220 may be connected to the microchannel 100 such that its ends cover at least three surfaces of the outer surface of the microchannel 100. Here, the cross-section can mean a surface that contains a vector perpendicular to the extension direction at any point on the microchannel 100.

[0046] The connection relationship described above minimizes the interfacial resistance generated at the connection point between the edge of the ion exchange membrane 220 and the microchannel 100, allowing for more accurate measurement of the potential at the target location. This is because the interfacial energy is reduced when the connection is made in the manner described above, compared to when the connection between the edge of the ion exchange membrane 220 and the microchannel 100 is simply point contact, line contact, or one-surface contact. Furthermore, the shape of the ion exchange membrane 220 and the connection relationship with the microchannel 100 described above allows for smooth optical observation.

[0047] Referring to Figure 1, the microfluidic channel potential measurement system 10 according to one embodiment of the present invention may also include a measurement electrode 310 electrically connected to the reservoir 210, and a measurement unit 300 that applies a feedback voltage to the reservoir 210 via the measurement electrode 310 and measures the potential at a target position in the microchannel 100 based on the applied feedback voltage.

[0048] In one embodiment, the measuring electrode 310 may be electrically connected to the reservoir 210. Here, the electrical connection of the measuring electrode 310 to the reservoir 210 can mean that the measuring electrode 310 provides a specific electrical environment (such as a specific potential) to the reservoir 210, or that it is connected in such a way that parameters relating to the electrical environment within the reservoir 210 can be measured.

[0049] In one embodiment, the measuring electrode 310 may be an Ag / AgCl reference electrode (silver chloride reference electrode).

[0050] In one embodiment, the measurement unit 300 applies a feedback voltage to the reservoir 210 via the measurement electrode 310, and can measure the potential at the target position within the microchannel 100 based on the applied feedback voltage.

[0051] In one embodiment, the measurement unit 300 can apply a feedback voltage to the reservoir 210 so that the current in the ion exchange membrane 220 becomes zero current.

[0052] In one embodiment, if a plurality of probe channels 200 are provided, the measurement unit 300 may be provided so that each probe channel 200 corresponds to one of them on a one-to-one basis. In this case, the measurement unit 300 that corresponds to each probe channel 200 on a one-to-one basis can apply each feedback voltage to the reservoir 210 of the corresponding probe channel 200 and measure the potential at each target position based on the feedback voltage applied to each reservoir 210.

[0053] Alternatively, if multiple probe channels 200 are provided, the measurement unit 300 may be configured to correspond to multiple groups, each containing one or more probe channels 200. In this case, the measurement unit 300 corresponding to each group can apply a feedback voltage to one or more probe channels 200 included in the corresponding group and measure the potential at each target position based on the applied feedback voltage.

[0054] Alternatively, if multiple probe channels 200 are provided, only one measurement unit 300 may be provided. In this case, the measurement unit 300 can apply a feedback voltage to each probe channel 200 and measure the potential at each target position based on the applied feedback voltage.

[0055] The following describes the method for measuring the potential of the target position within the microchannel 100 using the measurement unit 300.

[0056] As described above, the end of the ion exchange membrane 220 may be connected to the target position within the microchannel 100. On the other hand, the other side of the ion exchange membrane 220 is connected to a reservoir 210, which can be electrically connected to the measuring electrode 310.

[0057] The measurement unit 300 can apply current or voltage to the reservoir 210 via the measurement electrode 310. When a voltage is applied to the reservoir 210, a current can be generated due to the potential difference between the reservoir 210 and the target position in the microchannel 100. The current generated at this time can be due to the movement of ions in the buffer solution between the reservoir 210 and the ion exchange membrane 220.

[0058] The measurement unit 300 can measure the current generated in the ion exchange membrane 220 or the reservoir 210 when a voltage is applied to the reservoir 210. This may be measured via a current measuring means such as an ammeter connected separately to the ion exchange membrane 220 or the reservoir 210, or it may be measured directly in the reservoir 210.

[0059] The measurement unit 300 can change the voltage applied to the reservoir 210 based on the measured current value. That is, it can apply a feedback voltage to the reservoir 210. At this time, the measurement unit 300 can apply the feedback voltage so that the current measured in the ion exchange membrane 220 or the reservoir 210 becomes 0 or very close to 0, that is, zero current.

[0060] The measurement unit 300 can measure the potential at the target position based on the feedback voltage. When the current measured in the ion exchange membrane 220 or reservoir 210 becomes zero depending on the stage of the feedback voltage application, it means that the total movement of active ions in the ion exchange membrane 220 connected to the target position of the microchannel 100 is zero or very close to zero. In this case, the potential difference between the potential of the reservoir 210 and the potential at the target position becomes zero or close to zero, and the potential at the target position can be measured by approximating the feedback voltage applied to the reservoir 210.

[0061] If the probe connected to the target position described above consists of a general metal electrode, unlike in one embodiment of the present invention, the current generated by the potential difference across the probe during the voltage application stage is due to the movement of electrons, which can cause unwanted side reactions at the electrode interface. For example, the chemical species injected into the microchannel 100 may be unnecessarily oxidized or reduced at the electrode interface, generating byproducts that contaminate the sample solution in the microchannel 100, or bubbles may be generated that disrupt the connection within the microchannel 100. Such side reactions can further locally alter or destabilize the electrical environment at the target position within the microchannel 100, potentially making accurate potential measurement at the target position extremely difficult.

[0062] In one embodiment of the present invention, the probe channel 200 connected to the target position consists of an ion exchange membrane 220, and when a potential difference is generated across both ends, ions other than electrons begin to move. Therefore, accurate potential measurement at the target position can be achieved without the risk of the side reactions described above.

[0063] According to one embodiment of the present invention, if the ion exchange membrane 220 has cation-selective permeability, only cations can move in an environment where a potential difference exists between the reservoir 210 and the target position. According to one embodiment of the present invention, if the ion exchange membrane 220 has anion-selective permeability, only anions can move in an environment where a potential difference exists between the reservoir 210 and the target position.

[0064] The measurement unit 300 may, but is not limited to, include a source measure unit such as a KEITHLEY unit. It may also include, combine, or add at least one of the following devices as needed: a multimeter, voltage supply, current source, pulse generator, or loader.

[0065] Figure 5 shows a potential measurement system equipped with multiple probe channels 200 according to one embodiment of the present invention, and a diagram showing the voltage measured at each target position of the system over time.

[0066] Specifically, 10V is applied across the microchannel 100 described above. pp Figure (a) shows the configuration of four probe channels 200 connected to four points when a 100 mHz square wave is applied, and (b) shows the feedback voltage measured in the reservoir 210 of each probe channel 200 when a zero current is applied to each target point. Here, each voltage V1, V2, V3, and V4 may be the feedback voltage applied to each reservoir 210. As shown in Figure 5, it was confirmed that the potential measurement system according to one embodiment of the present invention can perform accurate potential measurements at each point according to the voltage distribution at that point.

[0067] Figure 6 shows an example of measuring the concentration of a sample solution injected into a microchannel 100 using a potential measurement system according to one embodiment of the present invention.

[0068] Figure 6(a) shows a system in which a microchannel 100 is connected to a pair of probe channels 200 for potential measurement and an ion-selective permeable membrane 400. When a voltage is applied across the microchannel 100, the ion depleted zone gradually expands, and the resulting change in ion concentration within the microchannel 100 allows for the observation of a potential change at the corresponding point. By applying a zero current to each of a pair of probe channels 200 separated by an arbitrary distance L, and measuring the potential at the target position of each probe channel 200 in real time, the potential difference ΔV in the local region between the separated probe channels 200 can be measured, and the electrical conductivity of the local region can be calculated. Figure 6(b) is a graph showing how the electrical conductivity σ changes over time in the local region using the system described above. This allows for real-time measurement of changes in electrolyte concentration in the local region within the microchannel 200.

[0069] The potential measurement system according to one embodiment of the present invention may be applied to a device including a single microchannel 100. Alternatively, the potential measurement system according to one embodiment of the present invention may be applied to a device including multiple microchannels 100. Alternatively, the potential measurement system according to one embodiment of the present invention may be applied to a device including a network structure of microchannels 100. As an example, it can be applied to a device having a radial network structure in which multiple microchannels 100 share one end.

[0070] The present invention has been described above with reference to embodiments, but these are provided only to further aid in understanding the overall invention, and the invention is not limited to the above examples. Various modifications and variations can be made from this description by those with ordinary skill in the art to which the invention pertains.

[0071] Therefore, the concept of the present invention can be said to fall within the scope of not only the attached claims, but also all equivalent or comparable modifications to these claims.

Claims

1. A microchannel into which a sample solution containing the sample is injected, A probe channel comprising a reservoir into which a buffer solution is injected, and an ion exchange membrane formed extending from at least a portion of the reservoir, with its end connected to the microchannel, A measuring electrode electrically connected to the above reservoir, A microfluidic channel potential measurement system, comprising: a measurement unit that applies a feedback voltage to the reservoir via the above-mentioned measurement electrode and measures the potential at a target position within the microchannel based on the applied feedback voltage.

2. The potential measurement system for a microfluidic channel according to claim 1, wherein the ion exchange membrane has cation-selective permeability.

3. The microfluidic channel potential measurement system according to claim 2, wherein the ion exchange membrane is Nafion.

4. The ion exchange membrane has anion-selective permeability, as described in claim 1, for the potential measurement system of a microfluidic channel.

5. The microfluidic channel potential measurement system according to claim 1, wherein the above-mentioned measurement electrode is an Ag / AgCl reference electrode.

6. The above buffer solution contains KCl, the microfluidic channel potential measurement system according to claim 1.

7. The potential measurement system for a microfluidic channel according to claim 1, wherein a plurality of the above-mentioned probe channels are provided.

8. The microfluidic channel potential measurement system according to claim 1, wherein the ion exchange membrane is connected to the microchannel such that its end covers at least a portion of the outer surface of the microchannel.

9. The microfluidic channel potential measurement system according to claim 8, wherein the cross-section of the microchannel is formed in a rectangular shape, and the ion exchange membrane is connected to the microchannel such that its ends cover at least three surfaces of the outer surface of the microchannel.

10. The microfluidic channel potential measurement system according to claim 1, wherein the measurement unit applies a feedback voltage to the reservoir so that the current in the ion exchange membrane becomes zero.

Images