Glucose electrochemical detection system integrated with electromagnetic microfluidics

Abstract

The invention relates to an integrated electromagnetic micro-fluidic glucose electrochemical detection system. The glucose electrochemical detection system is composed of a programmable magnetic control system, a micro-fluidic chip and an electrochemical detection module, a magnetic control system in the programmable magnetic control system is composed of an electromagnetic coil and a permanent magnet, and the electromagnetic coil is manufactured on a PCB bottom plate; the magnetic control system is controlled by a controller, and the glucose liquid drops are actuated by controlling a permanent magnet, so that the glucose liquid drops reach a corresponding electrochemical detection area to be analyzed. According to the invention, automatic control and electrochemical detection of a glucose sample can be realized, the consumption of reagents and samples is low, liquid drops are automatically and flexibly controlled, high-voltage driving and predefined electrode patterns are not needed, and a magnetic control system is low in loss, integrated and miniaturized during use, can be used for portable equipment, and has a good application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of microfluidics, and particularly relates to a glucose electrochemical detection system integrating electromagnetic microfluidics. Background Art

[0002] Although traditional microfluidic systems have demonstrated powerful capabilities in handling small volumes of liquids, they usually require complex microchannel structures and pump systems, which to some extent limit their integration and scalability. To overcome these limitations, digital microfluidics (DMF) technology has attracted wide attention. Various driving mechanisms have been explored in the field of droplet manipulation, aiming to precisely control the position and behavior of droplets, including driving methods such as electric fields, magnetic fields, sound fields, and light fields. Among them, DMF based on electrowetting on dielectric (EWOD) allows droplets to be manipulated by generating a local electric field on the electrodes, avoiding the need for the microchannel structures and external pumps commonly found in traditional microfluidic systems. However, existing DMF technologies still have some limitations in processing biological samples (such as glucose in sweat). They rely on complex electrode wiring and relatively high driving voltages, which may limit the processing of certain biological samples and reduce the stability of the system.

[0003] In this context, magnetic digital microfluidics (MDMF) technology has gradually emerged. This technology controls a permanent magnet or an electromagnet to generate a local magnetic field by designing an external magnetic control system, directly manipulating droplets or indirectly manipulating droplets through magnetic substances around the liquid. By applying an external controllable magnetic field, MDMF is non-invasive, and magnetic droplets can be accurately manipulated in a non-contact manner, avoiding the problems of electrode loss and sample contamination interference in traditional EWOD systems. This is of great significance for improving the reliability and applicability of the system. Most of the detection methods of existing digital microfluidic integrated detection platforms are based on optics, such as fluorescence detection, chemiluminescence, colorimetric sensing, etc. Due to the complexity of optical detection devices, the application of these methods in on-site small / portable devices is limited. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a glucose electrochemical detection system integrating electromagnetic microfluidics. By using this system, the automatic manipulation and electrochemical detection of glucose samples can be realized, with less consumption of reagents and samples, flexible automatic manipulation of droplets, no need for high-voltage driving and predefined electrode patterns, and low loss of the magnetic control system during use, being integrated, miniaturized, and applicable to portable devices, having good application prospects.

[0005] The present invention provides a glucose electrochemical detection system integrated with electromagnetic microfluidics. The glucose electrochemical detection system is composed of a programmable magnetic control system, a microfluidic chip, and an electrochemical detection module. The magnetic control system in the programmable magnetic control system is composed of an electromagnetic coil and a permanent magnet. The electromagnetic coil is fabricated on a PCB bottom plate. The magnetic control system is controlled by a controller. By controlling the permanent magnet to actuate the glucose droplet, the glucose droplet reaches the corresponding electrochemical detection area for analysis.

[0006] Preferably, the electromagnetic coil forms a planar coil structure or a multi-layer coil structure through spiral winding.

[0007] Preferably, the permanent magnet is an N52 neodymium iron boron permanent magnet.

[0008] Preferably, both the electromagnetic coil and the permanent magnet are miniaturized.

[0009] Preferably, the surface of the microfluidic chip is sprayed with a superhydrophobic coating.

[0010] Preferably, the working electrode of the electrochemical detection module is based on MoS 2 @CeO 2 / PVA hydrogel.

[0011] Preferably, the detection result of the electrochemical detection module is displayed on a computer screen in the form of a DPV curve.

[0012] The core principle of the present invention is based on the attraction of droplets by magnets. Specifically, it is programmable to control a specific coil to be energized to generate an induced magnetic field to drive the permanent magnet to move directionally. The permanent magnet is responsible for generating a locally high-intensity gradient magnetic field to actuate the magnetic droplet. The glucose droplet reaches the corresponding electrochemical detection area for analysis. Different from other systems, the present invention uses a miniaturized coil (2.737x2.737mm) and a miniaturized cylindrical permanent magnet (4x2mm), which greatly reduces the volume of the device and improves the integration degree. Although the droplet path can be reprogrammed on the EWOD platform, the path must follow the prefabricated electrode pattern, and the high-voltage drive also has a certain impact on the electrodes. In contrast, magnetic digital microfluidics does not need to follow any predefined surface pattern, and only a sufficient coil array is required to satisfy any movement of the droplet. In addition, the magnetic control system will not have excessive losses during use.

[0013] Beneficial effects

[0014] Using the present invention can realize the automatic manipulation and electrochemical detection of glucose samples, with less consumption of reagents and samples, flexible automatic manipulation of droplets, no need for high-voltage drive and predefined electrode patterns, and small loss of the magnetic control system during use, integrated and miniaturized, which can be used for portable devices and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 This is a schematic diagram of the glucose electrochemical detection system of the present invention.

[0016] Figure 2 This is a schematic diagram of the programmable magnetic control system.

[0017] Figure 3 This is a schematic diagram of the moving principle of the N52 magnet.

[0018] Figure 4 This is a schematic diagram of the force on the droplet.

[0019] Figure 5 This is a schematic diagram of droplet manipulation.

[0020] Figure 6 This is a single detection electrode based on MoS 2 @CeO 2 / PVA.

[0021] Figure 7 This is a schematic diagram of the detection principle of glucose.

[0022] Figure 8 This is the DPV curve of droplets with different glucose concentrations on the detection electrode.

[0023] Figure 9 This is a linear correlation diagram between glucose concentration and DPV response current. DETAILED DESCRIPTION OF THE INVENTION

[0024] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0025] Example 1

[0026] By Figure 1As shown in the figure, this embodiment provides a glucose electrochemical detection system integrated with electromagnetic microfluidics. The glucose electrochemical detection system is composed of a programmable magnetic control system, a microfluidic chip, and an electrochemical detection module. The magnetic control system in the programmable magnetic control system is composed of an electromagnetic coil and a permanent magnet. The electromagnetic coil is fabricated on a PCB bottom plate. The magnetic control system is controlled by a controller. By controlling the permanent magnet to actuate the glucose droplet, the glucose droplet reaches the corresponding electrochemical detection area for analysis. Different from other systems, the programmable magnetic control system consists of a miniaturized coil and a microcylindrical permanent magnet, greatly reducing the volume of the device and improving the integration degree. The controller controls a specific coil to be energized to generate an induced magnetic field to drive the permanent magnet to move. The permanent magnet is responsible for generating a locally high-intensity gradient magnetic field to actuate the magnetic droplet. The microfluidic chip is fabricated by 3D printing. In order to reduce the resistance and facilitate droplet manipulation, a superhydrophobic coating is sprayed on the chip surface, and five sample loading holes are provided. The droplet transmission path is programmable and can be reconstructed according to specific requirements. For the electrochemical detection part, in order to facilitate integration with the microfluidic chip and achieve high-sensitivity detection, a micro detection electrode is fabricated using the PCB process. The working electrode is based on MoS 2 @CeO 2 / PVA hydrogel. This platform can be used for droplet manipulation and highly sensitive electrochemical detection of target substances.

[0027] The droplet volume is set to 25 μL. If the volume is too small, it cannot cover the three electrodes and the detection cannot be completed. The permanent magnet drives the first droplet to be transported to the corresponding electrochemical end for detection, and then drives other droplets to be transported to the corresponding detection electrode ports in sequence, so as to realize the continuous injection and detection of multiple samples. After the detection is completed, the results are displayed on the computer screen in the form of a DPV (differential pulse voltammetry) curve. The glucose in sweat is detected using this platform.

[0028] The glucose electrochemical detection system integrated with electromagnetic microfluidics specifically includes:

[0029] 1. A programmable magnetic control system.

[0030] Whether the magnet can move accurately determines whether the magnetic droplet can be driven accurately. Therefore, the core of the integrated platform is the programmable magnetic control system. As Figure 2 shown, in order to facilitate programmable control of a specific coil to generate a magnetic field, it is considered to fabricate the coil on a PCB board. When adjacent coils are energized, an induced magnetic field will be generated around the coil according to Ampere's law. When the magnetic field is large enough, the permanent magnet will move to the position of the energized coil under the attraction of the magnetic force. As Figure 3As shown, when the coil 1 on the PCB is not powered on, there is no magnetic field. When current (300 mA) is applied to coil 2, an induced magnetic field is generated. According to the right-hand screw rule, the direction of the magnetic field can be determined. Since like poles attract, the permanent magnet will move from the initial position to the target position. When using the Arduino controller to program and write the switch sequence instructions to the PCB coil base plate, specific coils will be powered on individually in sequence, thereby generating induced magnetic fields in sequence to attract the permanent magnet to move along the set trajectory. At the same time, it drives the movement of the magnetic droplets in the microfluidic chip, thus completing the precise manipulation of the droplets.

[0031] (1) PCB electromagnetic coil: Using the conventional PCB manufacturing process, a planar coil structure is formed by using a spiral trace with a line width of 0.1 mm. After forming a single-layer coil structure, two or three layers of coils can be fabricated according to the selection to enhance the induced magnetic field strength after power-on. Each single coil is square, with a width of 2.737 mm, and the distance between coils is 0.1 mm. The magnetic field after the coil is powered on only controls the directional movement of the magnet above.

[0032] (2) Permanent magnet: An N52 neodymium iron boron (NdFeB) permanent magnet is selected, with a diameter of 4 mm and a height of 2 mm, and the polarization direction is the Z-axis direction. The N52 permanent magnet is a magnet that generates a stable magnetic field. When placed above the electromagnetic coil, the static magnetic field generated by the permanent magnet is responsible for attracting the magnetic droplets in the microfluidic chip. When the permanent magnet moves directionally, the magnetic droplets will be driven by it.

[0033] 2. Manipulation of magnetic droplets on the open surface.

[0034] In order to prevent the electrochemical detection electrode from being covered by other irrelevant liquids, droplet manipulation is carried out on the open surface of the microfluidic chip. The open surface needs to reach a superhydrophobic state, and the microfluidic chip is treated by spraying with a superhydrophobic reagent. The force acting on the droplet is as Figure 4 shown. On the open superhydrophobic surface, the magnetic droplet is mainly dominated by three forces: the magnetic force F m , the frictional force F f between the droplet and the substrate, and the capillary force F c generated by the deformation of the droplet on the movement. The dynamic behavior of the droplet on the platform can be described as F m - F f - F c = ma. In addition, on the superhydrophobic surface, due to the small contact area between the droplet and the surface, the contact line radius is usually small, so the capillary force is also small. The movement process of the magnetic droplet is mainly driven by the magnetic force, and the magnitude of the magnetic force depends on the concentration of magnetic particles in the droplet, the magnetic field strength of the magnet, and the distance between the droplet and the magnet. Figure 5It is a snapshot of the droplet moving horizontally over a certain distance. The changes in the advancing contact angle and the receding contact angle can be seen. The droplet deforms little and the capillary force is relatively small. The transportation speed of the droplet is generated by the movement of the magnet, and the movement speed of the magnet can be changed by setting the interval time of the coil energization, which will correspondingly change the transportation speed of the droplet.

[0035] 3. Integrated electrochemical detection:

[0036] The detection performance of the electrochemical working electrode determines the accuracy and reliability of the entire detection signal. Choose MoS 2 @CeO 2 / PVA composite material as the modification of the working electrode. The prepared MoS 2 @CeO 2 / PVA hydrogel, the SEM image taken after drying shows a three-dimensional layered structure. Among them, the oxygen vacancies of CeO 2 can improve the catalytic activity of the electrode, promote electron transfer, and thus accelerate the rate of the electrochemical reaction; MoS 2 has a layered structure similar to graphene, which has a high surface area and provides a large number of active sites, which can promote the adsorption and reaction of glucose molecules; the PVA hydrogel provides mechanical support and flexibility for the MoS 2 @CeO 2 composite material, ensuring that the electrode has good durability and stability during operation. As Figure 6 shown is the glucose sensing principle of the MoS 2 @CeO 2 / PVA electrode. The CeO 2 distributed on the surface of the MoS 2 layered structure can adsorb and detect abundant glucose molecules through redox reactions. CeO 2 gains and loses electrons during the reaction process, and promotes the transfer of electrons through the redox cycle between Ce 3+ and Ce 4+ . The high surface area of the MoS 2 @CeO 2 / PVA electrode provides a large number of active sites and has excellent electrocatalytic performance. Glucose loses electrons on the electrode surface and is oxidized to gluconic acid. The electron flow generated during the electrochemical reaction process forms a current signal.

[0037] Differential pulse voltammetry (DPV) measures the current response by applying a pulsed voltage to the electrode. It can reduce the background current and improve the resolution of the peak current signal, with high sensitivity, and can intuitively reflect the current change of the electrode reaction. Therefore, it is used as an analytical tool for glucose detection. By using differential pulse voltammetry to detect the target glucose at different concentration gradients (0.01 mM, 0.025 mM, 0.05 mM, 0.1 mM, 0.15 mM, 0.2 mM, 0.25 mM), we obtain Figure 8 the DPV response curve shown. There are obvious anodic peaks, and the current peak gradually increases with the increase of glucose concentration, indicating that the electrode material shows good response characteristics to the redox reaction of the target substance. As Figure 9 shown, the peak currents at different concentrations are plotted against the glucose concentration to form a linear relationship curve. The results show that there is a good linear relationship between the DPV peak current and the concentration, and the linear correlation coefficient R2 is 0.9937, close to 1, indicating that the electrode material has a good linear response to the detection of the target substance. The linear regression equation can be expressed as I (μA) = 64C Glucose (mM) + 6.654. The integrated electrochemical detection platform can be used to detect the glucose concentration in human sweat.

Claims

1. A glucose electrochemical detection system integrated with electromagnetic microfluidics, characterized in that: The glucose electrochemical detection system is composed of a programmable magnetic control system, a microfluidic chip and an electrochemical detection module; the magnetic control system in the programmable magnetic control system is composed of an electromagnetic coil and a permanent magnet, and the electromagnetic coil is made on a PCB bottom plate; the magnetic control system is controlled by a controller, and the permanent magnet is controlled to actuate glucose droplets so that the glucose droplets reach the corresponding electrochemical detection area for analysis.

2. The glucose electrochemical detection system according to claim 1, characterized in that: The electromagnetic coil is formed into a planar coil structure or a multi-layer coil structure by spirally winding.

3. The glucose electrochemical detection system according to claim 1, characterized in that: The permanent magnet is a N52 neodymium iron boron permanent magnet.

4. The glucose electrochemical detection system according to claim 1, characterized in that: The electromagnetic coil and the permanent magnet are both miniaturized.

5. The glucose electrochemical detection system according to claim 1, characterized in that: The surface of the microfluidic chip is sprayed with a super-hydrophobic coating.

6. The glucose electrochemical detection system according to claim 1, characterized in that: The working electrode of the electrochemical detection module is based on MoS2@CeO2 / PVA hydrogel.

7. The glucose electrochemical detection system according to claim 1, characterized in that: The detection result of the electrochemical detection module is displayed on the computer screen in the form of a DPV curve.

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