Portable liquid chromatograph based on microchip, detection system and method

Abstract

The invention discloses a portable liquid chromatograph based on a microchip, a detection system and a detection method, and relates to the technical field of liquid chromatography detection.The chromatographic separation module comprises a chromatographic microchip and a movable clamping device used for carrying the chromatographic microchip; the chromatographic microchip comprises a chip body, a mobile phase driving module and a mobile phase driving module, the first chromatographic column switching valve is arranged on a communication channel of the mobile phase driving module and the ion chromatographic column, and the second chromatographic column switching valve is arranged on a communication channel of the mobile phase driving module and the reversed-phase chromatographic column; and the sample injector is communicated with the ion chromatographic column and the reversed-phase chromatographic column, so that gradient liquid chromatography separation of different mechanisms can be respectively carried out, and the technical problem that the existing portable liquid chromatograph with a small-inner-diameter chromatographic column is single in separation mechanism is solved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of liquid chromatography detection, and particularly relates to a portable liquid chromatograph based on a microchip, a detection system and a method. BACKGROUND

[0002] Liquid chromatography technology is an important separation and analysis technology, which is widely used in chemical detection, biological detection, pharmaceutical preparation and environmental detection fields. The basic principle of liquid chromatography technology is to use the difference in distribution ratio of a mixture between liquid-solid or two immiscible liquids to separate and analyze the mixture. Since the advent of liquid chromatography technology, it has gradually developed from classical column chromatography to paper chromatography, and then to high-performance liquid chromatography.

[0003] With the rise of miniaturized analysis technology, the combination of micro total analysis systems and silicon chips has attracted widespread attention. In the early days, researchers tried to integrate chromatography technology on silicon chips, which integrated all modules of a chromatograph on a silicon chip. However, the initial integrated liquid chromatography chip had many challenges in efficiency and other aspects. With the advent of capillary liquid chromatography and nanoflow liquid chromatography, the separation efficiency was significantly improved by reducing the inner diameter of the column to form a portable liquid chromatograph with a small inner diameter column, which effectively overcame the disadvantages of large solvent consumption and large volume of traditional liquid chromatography. The portable liquid chromatograph with a small inner diameter column has many advantages, such as low reagent consumption, short analysis time, and easy combination with mass spectrometry, especially in reducing the contact between operators and hazardous substances.

[0004] However, the existing portable liquid chromatograph with a small inner diameter column has the following problems in use:

[0005] First, the function is single, only one separation mechanism can be realized, and gradient elution mode cannot be performed;

[0006] Second, since people have not studied the pressure loss in the existing portable liquid chromatograph with a small inner diameter column, a larger initial pressure (a larger pump pressure is selected) is usually provided, which causes the working pressure of the entire system to be unstable, resulting in oscillation and affecting the detection result. That is, the existing portable liquid chromatograph with a small inner diameter column has the technical problems of single separation mechanism and unstable working pressure.

[0007] Therefore, it is necessary to develop and design a portable liquid chromatograph based on a microchip, a detection system and a method to solve the technical problem of single separation mechanism of the existing portable liquid chromatograph with a small inner diameter column. SUMMARY

[0008] In order to solve the above problems, the application provides a portable liquid chromatograph based on a microchip, a detection system and a method, which solve the technical problem of single separation mechanism of the existing portable liquid chromatograph with a small inner diameter chromatographic column.

[0009] In order to achieve the above-mentioned purpose, the application provides the following solutions.

[0010] A portable liquid chromatograph based on a microchip, comprising a mobile phase driving module, a chromatographic separation module in communication with the mobile phase driving module, and a component detection module for signal acquisition of a sample in the chromatographic separation module.

[0011] The chromatographic separation module comprises a chromatographic microchip and a moving clamping device for carrying the chromatographic microchip, the chromatographic microchip comprising a chip body, an ion chromatographic column and a reverse phase chromatographic column arranged on the chip body and in communication with the mobile phase driving module at one end and corresponding to the component detection module at the other end, a first chromatographic column switching valve arranged on a communication channel between the mobile phase driving module and the ion chromatographic column, a second chromatographic column switching valve arranged on a communication channel between the mobile phase driving module and the reverse phase chromatographic column, and a sample injector in communication with the ion chromatographic column and the reverse phase chromatographic column.

[0012] Preferably, the mobile phase driving module comprises a bottom plate, a support and a driving motor arranged on the bottom plate, a lead screw arranged at the output end of the driving motor, a lead screw nut threadedly connected with the lead screw, a syringe with one end connected with the lead screw nut and the other end in communication with a micro three-way valve, and a mobile phase reagent bottle in communication with the micro three-way valve, and the barrel of the syringe is arranged on the support.

[0013] The piston rod of the syringe is connected with the lead screw nut, the liquid outlet end of the syringe is in communication with the first connecting port of the micro three-way valve, the mobile phase reagent bottle is in communication with the second connecting port of the micro three-way valve, and the first chromatographic column switching valve and the second chromatographic column switching valve are in communication with the third connecting port of the micro three-way valve.

[0014] Preferably, the mobile phase driving module is provided as two.

[0015] Preferably, the chromatographic separation module further comprises a mixing part, the mixing part comprising a first liquid inlet, a second liquid inlet, and a spiral flow channel with one end in communication with the first liquid inlet and the second liquid inlet and the other end in communication with the first chromatographic column switching valve and the second chromatographic column switching valve, the first liquid inlet being in communication with the third connecting port in one of the mobile phase driving modules, and the second liquid inlet being in communication with the third connecting port in the other mobile phase driving module.

[0016] Preferably, the moving clamping device comprises a linear slide rail, a slide rail locking nut seat arranged on the linear slide rail and slidable on the linear slide rail, a two-dimensional horizontal micro-adjustment frame arranged on the slide rail locking nut seat, and a chip clamp arranged on the two-dimensional horizontal micro-adjustment frame for clamping the chromatographic microchip.

[0017] Preferably, the chromatographic microchip further comprises a filling valve arranged on the chip body and in communication with the ion chromatographic column and the reversed-phase chromatographic column, and a first Z-shaped detection cell and a second Z-shaped detection cell in communication with the ion chromatographic column and the reversed-phase chromatographic column, respectively, the first Z-shaped detection cell and the second Z-shaped detection cell being in communication with the component detection module.

[0018] Preferably, the component detection module comprises a detector housing, an optical sleeve and a photodiode arranged on the detector housing, an optical system arranged inside the optical sleeve, an optical slit arranged at an exit end of the optical sleeve, and a light shield fixedly connected at an opening of the optical sleeve, the photodiode being arranged above the optical sleeve.

[0019] The optical system comprises an LED light source, and a filter, a focusing lens and a collimating lens arranged in sequence at an exit end of the LED light source from far away from the photodiode to close to the photodiode, the optical slit being arranged opposite to the collimating lens.

[0020] The application further discloses a microchip-based portable liquid chromatography detection system, comprising the microchip-based portable liquid chromatograph, a data acquisition module electrically connected with the component detection module, a waste liquid collection module in communication with the chromatographic separation module, a micro-flow meter in communication with the waste liquid collection module, and a data processing module electrically connected with the data acquisition module.

[0021] The application further discloses a microchip-based portable liquid chromatography detection method, which applies the microchip-based portable liquid chromatography detection system, and comprises the following steps:

[0022] According to the detection requirement, a separation mechanism is selected, and a corresponding ion chromatographic column or reversed-phase chromatographic column is selected through the first chromatographic column switching valve or the second chromatographic column switching valve.

[0023] The flow phase driving module drives the flow phase into the corresponding ion chromatographic column or reversed-phase chromatographic column.

[0024] The component detection module is used for signal acquisition of the sample in the ion chromatographic column or reversed-phase chromatographic column.

[0025] The data processing module is used for analyzing and processing the signal to obtain the concentration of the substance component.

[0026] The detected waste liquid enters the waste liquid collection module to collect the waste liquid.

[0027] Preferably, the calculation formula of the flow phase driving module driving pressure is:

[0028] P = ΔP1 + ΔP2

[0029]

[0030] ΔP1 is the pressure drop of the ion chromatography column or the reverse phase chromatography column, unit: MPa; ΔP2 is the loss pressure drop, unit: MPa; Φ is the resistance factor; η is the viscosity of the flow phase, unit: MPa·s; L is the length of the ion chromatography column or the reverse phase chromatography column, unit: m; Q is the flow of the flow phase in the ion chromatography column or the reverse phase chromatography column, unit: μL / min; ε is the porosity of the stationary phase in the ion chromatography column or the reverse phase chromatography column; A is the cross-sectional area of the ion chromatography column or the reverse phase chromatography column, mm 2 ; d P The particle size of the stationary phase in the ion chromatography column or the reverse phase chromatography column, unit: μm.

[0031] The present application has the following technical effects relative to the prior art:

[0032] By arranging the ion chromatography column and the reverse phase chromatography column on the same chromatography microchip, and by the first chromatography column switching valve and the second chromatography column switching valve to switch the ion chromatography column and the reverse phase chromatography column, for example, when ion chromatography column analysis is needed, the first chromatography column switching valve is opened, the second chromatography column switching valve is closed, the flow phase and the sample are both pushed into the ion chromatography column, and the ion chromatography column is analyzed by the component detection module, and correspondingly, when reverse phase chromatography column analysis is needed, the second chromatography column switching valve is opened, the first chromatography column switching valve is closed, the flow phase and the sample are both pushed into the reverse phase chromatography column, and the reverse phase chromatography column is analyzed by the component detection module, which can separately perform gradient liquid chromatography separation of different mechanisms, thereby solving the technical problem of single separation mechanism of the existing small inner diameter chromatography column portable liquid chromatograph. BRIEF DESCRIPTION OF DRAWINGS

[0033] In order to more clearly illustrate the technical solutions in the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments. Obviously, the drawings described below are only some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0034] The Figure 1 The overall structure schematic diagram of the portable liquid chromatograph based on microchip disclosed by the present application after removing the flow phase driving module;

[0035] Figure 1 is a schematic diagram of the overall structure of a chromatographic separation module in a microchip-based portable liquid chromatograph disclosed in the present application; Figure 2 Figure 2 is a schematic diagram of the overall structure of a chromatographic microchip in a microchip-based portable liquid chromatograph disclosed in the present application;

[0036] Figure 3 is a schematic diagram of the overall structure of a mobile phase driving module in a microchip-based portable liquid chromatograph disclosed in the present application; Figure 3 Figure 4 is a schematic diagram of the overall structure of a component detection module in a microchip-based portable liquid chromatograph disclosed in the present application;

[0037] Figure 5 is a schematic diagram of the overall structure of a chromatographic separation module in a microchip-based portable liquid chromatograph disclosed in the present application; Figure 4 Figure 6 is a schematic diagram of the overall structure of a chromatographic microchip in a microchip-based portable liquid chromatograph disclosed in the present application;

[0038] Figure 5 Figure 7 is a schematic diagram of the overall structure of a mobile phase driving module in a microchip-based portable liquid chromatograph disclosed in the present application;

[0039] 1, mobile phase driving module; 101, driving motor; 102, bracket; 103, screw nut; 104, syringe; 105, capillary; 106, micro three-way valve; 107, mobile phase reagent bottle;

[0040] 2, chromatographic separation module; 201, linear slide rail; 202, slide rail locking nut seat; 203, two-dimensional horizontal micro adjustment frame; 204, chip clamp; 205, chromatographic microchip; 2051, first chromatographic column switching valve; 2052, packing valve; 2053, ion chromatographic column; 2054, reverse phase chromatographic column; 2055, first Z-shaped detection cell; 2056, second Z-shaped detection cell; 2057, first liquid inlet; 2058, second liquid inlet; 2059, second chromatographic column switching valve; 2030, sampler; 2031, mixing part;

[0041] 3, component detection module; 301, optical sleeve; 302, LED light source; 303, light shield; 304, optical filter; 305, focusing lens; 306, collimating lens; 307, detector housing; 308, optical slit; 309, photodiode. DETAILED DESCRIPTION

[0042] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0043] The present application aims to provide a microchip-based portable liquid chromatograph, a detection system and a method, and solve the technical problem of single separation mechanism in the existing portable liquid chromatograph with small inner diameter chromatographic column.​

[0044] In order to make the above objectives, features and advantages of the present application more obvious and easy to understand, the present application will be further described in detail below with reference to the drawings and specific embodiments.

[0045] With reference to Figures 1-3 The portable liquid chromatograph based on the microchip disclosed in the embodiments of the present application at least comprises a mobile phase driving module 1, the mobile phase driving module 1 is communicated with a chromatographic separation module 2, the mobile phase driving module 1 is used to push the mobile phase into the chromatographic separation module 2, and is used to provide the pressure for driving the mobile phase, the pressure for driving the mobile phase provided by the mobile phase driving module 1 matches the pressure required by the chromatographic separation module 2, and a component detection module 3 for collecting signals of the sample in the chromatographic separation module 2 is further arranged on one side of the chromatographic separation module 2;

[0046] The chromatographic separation module 2 comprises a chromatographic microchip 205 and a moving clamping device for carrying the chromatographic microchip 205, the chromatographic microchip 205 is arranged on the moving clamping device, and the movement of the chromatographic microchip 205 can be realized, the chromatographic microchip 205 comprises a chip body, an ion chromatographic column 2053 and a reversed-phase chromatographic column 2054 are arranged on the chip body, the ion chromatographic column 2053 and the reversed-phase chromatographic column 2054 are connected in parallel, one end of the ion chromatographic column 2053 or the reversed-phase chromatographic column is communicated with the mobile phase driving module 1, the other end of the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054 corresponds to the component detection module 3, a first chromatographic column switching valve 2051 is arranged on the communication channel of the ion chromatographic column 2053 and the mobile phase driving module 1, a second chromatographic column switching valve 2059 is arranged on the communication channel of the reversed-phase chromatographic column 2054 and the mobile phase driving module 1, and a sample injector 2030 for pushing the sample is arranged on the ion chromatographic column 2053 and the reversed-phase chromatographic column 2054, by arranging the ion chromatographic column 2053 and the reversed-phase chromatographic column 2054 on the same chromatographic microchip 205, and by the first chromatographic column switching valve 2051 and the second chromatographic column switching valve 2059 to realize the switching of the ion chromatographic column 2053 and the reversed-phase chromatographic column 2054, for example, when ion chromatographic column 2053 analysis is needed, the first chromatographic column switching valve 2051 is opened, the second chromatographic column switching valve 2059 is closed, the mobile phase and the sample are pushed into the ion chromatographic column 2053, and the ion chromatographic column 2053 is detected and analyzed by the component detection module 3, correspondingly, when reversed-phase chromatographic column 2054 analysis is needed, the second chromatographic column switching valve 2059 is opened, the first chromatographic column switching valve 2051 is closed, the mobile phase and the sample are pushed into the reversed-phase chromatographic column 2054, and the reversed-phase chromatographic column 2054 is detected and analyzed by the component detection module 3, different mechanism gradient liquid chromatography separation can be carried out respectively, thereby solving the technical problem of single separation mechanism of the existing portable liquid chromatograph with small inner diameter chromatographic column.

[0047] Reference Figure 4 In an embodiment, the flow phase driving module 1 comprises a base plate, a support 102 and a driving motor 101 are arranged on the base plate, the output end of the driving motor 101 is rotationally connected with a lead screw, a lead screw nut 103 is sleeved on the lead screw, the lead screw nut 103 is threadedly connected with the lead screw, further comprising a syringe 104, the piston rod on the syringe 104 is connected with the lead screw nut 103, the liquid outlet end of the syringe 104 is communicated with a capillary tube 105, the barrel of the syringe 104 is arranged on the support 102 to complete the support of the syringe 104, the end of the capillary tube 105 away from the syringe 104 is connected with a micro three-way valve 106, the micro three-way valve 106 comprises a first connecting port, a second connecting port and a third connecting port, the first connecting port is communicated with the capillary tube 105, the second connecting port is communicated with a flow phase reagent bottle 107, the third connecting port is communicated with a first chromatographic column switching valve 2051 and a second chromatographic column switching valve 2059, when ion chromatographic column 2053 or reverse phase chromatographic column 2054 analysis is needed, the third connecting port is closed, the first connecting port and the second connecting port are opened, the driving motor 101 drives the rotation of the lead screw, and the linear motion of the driving motor 101 is converted into the linear motion by the lead screw nut 103, so that the syringe 104 sucks the flow phase in the flow phase reagent bottle 107, after the sucking is completed, the second connecting port is closed, the third connecting port is opened, and the flow phase is pushed into the ion chromatographic column 2053 or the reverse phase chromatographic column 2054.

[0048] It should be noted that the third connecting port is provided with a connecting main pipe between the first chromatographic column switching valve 2051 and the second chromatographic column switching valve 2059, so as to realize the communication of the third connecting port with the first chromatographic column switching valve 2051 and the second chromatographic column switching valve 2059 at the same time.

[0049] The capillary tube 105 is a PEEK capillary tube 105, the driving motor 101 is a step motor with a magnetic encoder, the lead screw nut 103 is driven by the driving motor 101, so as to drive the piston rod of the syringe 104 to push the flow phase, the barrel of the syringe 104 is made of high-pressure resistant glass, and the push or retreat of the flow phase can be controlled by switching the forward and reverse rotation of the driving motor 101 and switching the micro three-way valve 106.

[0050] The stepping motor with a magnetic encoder is an execution structure converting pulse signal instructions into corresponding rotating angle movement. The motor controller receives speed (displacement) signal and direction signal and other parameters from the host computer (data processing module) and analyzes them. The signal is transmitted to the motor driver by using PWM (pulse width modulation) signal control technology. The motor driver, usually a power amplifier, provides driving signal for the stepping motor. The signal from the motor controller is converted into pulse signal and direction signal by the H-bridge driving circuit. The pulse signal is used to control the stepping angle of the stepping motor each time it rotates, and the direction signal is used to control the rotating direction of the stepping motor. The stepping motor performs corresponding actions according to the received pulse signal and direction signal, realizing precise stepping movement. The encoder used in the closed-loop control of the stepping motor is a high-precision magnetic encoder. Compared with traditional encoders, this encoder has higher positioning accuracy, stable control, smooth movement, low noise, etc. The resolution can reach 20000p / r, which can provide accurate position accuracy, and the positioning error is ±1 pulse (0.018°). When the stepping motor is working, the high-precision magnetic encoder generates an analog signal corresponding to the change of the magnetic pole. After the analog signal is converted into a pulse signal by a circuit, the rotating angle and position information can be represented. The actual running state is fed back to the ARM controller (motor controller). By receiving the pre-set target value and the feedback actual value, the ARM controller (motor controller) compares the two values and calculates the deviation. The ARM controller (motor controller) runs the PID algorithm according to the deviation, calculates the output relying on the position loop PID + integral anti-windup algorithm, generates the corresponding PWM control signal, and the stepping motor completes the operation. The fluid mechanics analysis of the chromatographic microchip 205 chromatographic separation process is carried out. In order to meet the working flow rate requirement of 10 μL / min ~ 30 μL / min on the chromatographic microchip 205, the stepping motor parameters need to be accurately matched, and the calculation formula is:

[0051] P = ΔP1 + ΔP2

[0052]

[0053] ΔP1 is the pressure drop of the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054, unit: MPa; ΔP2 is the loss pressure drop, unit: MPa; Φ is the resistance factor, dimensionless, the wet filling value is 300 ~ 500, and the value in the application is 300; η is the viscosity of the mobile phase, unit: MPa·s; L is the length of the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054, unit: m; Q is the flow rate of the mobile phase in the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054, unit: μL / min; ε is the porosity of the stationary phase in the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054, dimensionless, generally taking the value of 0.7; A is the cross-sectional area of the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054, mm2 ; d P is the particle size of the stationary phase in the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054, in units of μm, and the particle size is preferably 5 μm porous silica gel particles.

[0054] Through calculation, it is found that when the working pressure of the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054 reaches 1.6 MPa, the thrust required to be provided by the injection pump needs to reach 65 N, and the rated torque of the stepping motor is 0.012 N·m. In the condition of ensuring the filling load in the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054, the selected large-torque stepping motor can still stably operate. According to the motor torque data, the torque output is greater than 0.3 N·m under low-speed working conditions, and the large-torque output ensures the reliability of fluid delivery under high load.

[0055] The present application selects a mobile phase driving module 1 matched with the pressure required by the chromatographic separation module 2, avoids that the pressure provided by the mobile phase driving module 1 is too large, and ensures the pressure stability of the chromatographic separation module 2, thereby solving the technical problem of unstable working pressure of the existing chromatographic separation module 2.

[0056] In order to strictly control the volume and weight of the injector 104, the bracket 102 is manufactured by using a light-cured 3D printing technology of a future 8200 black resin material (tensile film amount 2.6 GPa). The bracket 102 is processed with a through hole for fixing the inside of the injector 104, and the bottom plate is processed with a connecting rib for fixing the driving motor 101, thereby further enhancing the structural strength and stability of the driving motor 101. The stability and reliability of the injection pump during operation are ensured by the lead screw nut 103. The mechanical structure design of the injector 104 is compact, the assembly connection transmission efficiency is high, and the requirements of small volume, light weight and high precision of the entire chromatograph are met.

[0057] Reference Figure 4 As a preferred mode, the mobile phase driving module 1 is provided as two, and the two mobile phase driving modules 1 are the same in structure and can simultaneously introduce two different mobile phases into the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054.

[0058] Reference Figure 2 and Figure 3As an implementation form, the chromatographic separation module 2 further comprises a mixing part 2031, the mixing part 2031 comprises a first liquid inlet 2057, a second liquid inlet 2058 and a spiral flow channel, one end of the spiral flow channel is communicated with the first liquid inlet 2057 and the second liquid inlet 2058, the other end of the spiral flow channel is communicated with the first chromatographic column switching valve 2051 and the second chromatographic column switching valve 2059, the first liquid inlet 2057 is communicated with the third connecting port in one of the mobile phase driving modules 1, the second liquid inlet 2058 is communicated with the third connecting port in the other mobile phase driving module 1, when the two mobile phases are pushed into the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054 through the two mobile phase driving modules 1, the mobile phases flowing out from the two third connecting ports enter the spiral flow channel from the first liquid inlet 2057 and the second liquid inlet 2058 respectively, and are mixed in the spiral flow channel, realizing uniform mixing of the mobile phases, ensuring that the mobile phases entering the ion chromatographic column 2053 or the reversed-phase chromatographic column 2054 are stable in composition and accurate in proportion, so as to guarantee the accuracy, repeatability and separation efficiency of chromatographic analysis.

[0059] With reference to Figure 2 As a preferred form, the moving clamping device comprises a linear slide rail 201, a slide rail locking nut seat 202 arranged on the linear slide rail 201, the slide rail locking nut seat 202 being in sliding connection with the linear slide rail 201, the linear slide rail 201 being provided with a guide rod guiding the slide rail locking nut seat 202, a locking screw being arranged on the slide rail locking nut seat 202, one end of the locking screw being in abutment with the guide rod, and the locking screw being in threaded connection with the slide rail locking nut, when it is needed to move the slide rail locking nut seat 202 on the linear slide rail 201, the locking screw is rotated to make the abutment end of the locking screw disengage from the guide rod, so that the movement of the slide rail locking nut can be realized, when it is needed to fix the slide rail locking nut, the locking screw is rotated to make the locking screw abut against the guide rod, so that the slide rail locking nut seat 202 is locked on the linear slide rail 201, the slide rail locking nut seat 202 is provided with a two-dimensional horizontal micro adjustment frame 203, the two-dimensional horizontal micro adjustment frame 203 is provided with a chip clamp 204 for clamping the chromatographic microchip 205, the two-dimensional horizontal micro adjustment frame 203 can realize the movement of the chip clamp 204 in the X direction and the Y direction, by arranging the moving clamping device, the movement of the chromatographic microchip 205 can be realized, and the clamping and fixing of the chromatographic microchip 205 can also be realized.

[0060] It should be noted that the two-dimensional horizontal micro-adjusting frame 203 comprises a first guide rail arranged along the X direction, a first slider arranged on the first guide rail, a second guide rail arranged along the Y direction arranged on the first slider, a second slider arranged on the second guide rail, and a chip clamp 204 arranged on the second slider. The chip clamp 204 comprises a receiving groove for penetrating the chromatographic microchip 205, and an abutting bolt penetrating the receiving groove and threadedly connected with the receiving groove for abutting the chromatographic microchip 205.

[0061] Or the chromatographic microchip 205 is inserted into the chip clamp 204 and connected by a luer joint under high pressure.

[0062] In order to improve the separation efficiency and reduce the spectral band broadening effect, it is necessary to reduce the connection distance and dead volume between each module on the chromatographic microchip 205. Therefore, the mixing part 2031, the sample injector 2030, the ion chromatographic column 2053, the reverse phase chromatographic column 2054, the first Z-shaped detection cell 2055 and the second Z-shaped detection cell 2056 on the chromatographic microchip 205 are compactly arranged and connected, and the channels of the ion chromatographic column 2053 and the reverse phase chromatographic column 2054 are both 500 μm x 500 μm.

[0063] Reference Figure 3 As a preferred mode, the chromatographic microchip 205 further comprises a filling valve 2052 arranged on the chip body and communicating with the ion chromatographic column 2053 and the reverse phase chromatographic column 2054. The filling valve 2052 is used to introduce a stationary phase. The ion chromatographic column 2053 and the reverse phase chromatographic column 2054 are arranged close to one end of the component detection module 3 and are provided with a first Z-shaped detection cell 2055 and a second Z-shaped detection cell 2056 respectively communicating with the ion chromatographic column 2053 and the reverse phase chromatographic column 2054. The first Z-shaped detection cell 2055 and the second Z-shaped detection cell 2056 communicate with the component detection module 3. The first Z-shaped detection cell 2055 or the second Z-shaped detection cell 2056 is aligned with the light exit light path of the optical slit 308 in the component detection module 3. When the ion chromatographic column 2053 is detected, the first Z-shaped detection cell 2055 is aligned with the light exit light path of the optical slit 308 in the component detection module 3. When the reverse phase chromatographic column 2054 is detected, the second Z-shaped detection cell 2056 is aligned with the light exit light path of the optical slit 308 in the component detection module 3.

[0064] It should be noted that the two-dimensional horizontal micro-adjustment frame 203 is used to finely adjust the position of the chromatographic microchip 205 in the X direction and the Y direction, so that the first Z-shaped detection cell 2055 or the second Z-shaped detection cell 2056 on the chromatographic microchip 205 can be aligned with the light path of the optical slit 308 of the component detection module 3 to realize accurate measurement. The cooperation of the straight line slide rail 201 and the slide rail locking nut seat 202 facilitates the installation and disassembly of the chromatographic microchip 205. When it is necessary to realize the disassembly of the chromatographic microchip 205, the chromatographic microchip 205 is withdrawn from the component detection module 3 through the cooperation of the main line slide rail and the slide rail locking nut seat 202.

[0065] Reference Figure 5 As an embodiment, the component detection module 3 includes a detector housing 307, an optical sleeve 301 and a photodiode 309 arranged on the detector housing 307, an optical system arranged inside the optical sleeve 301, an optical slit 308 arranged at the exit end of the optical sleeve 301, and a light shield 303 fixedly connected at the opening of the optical sleeve 301. The photodiode 309 is arranged above the optical sleeve 301, and there is a gap between the optical sleeve 301 and the photodiode 309 for the first Z-shaped detection cell 2055 and the second Z-shaped detection cell 2056 to pass through. When the component detection module 3 corresponds to the position of the first Z-shaped detection cell 2055, the light source emitted by the optical system is irradiated on the first Z-shaped detection cell 2055 through the optical slit 308, and the photodiode 309 is arranged close to the first Z-shaped detection cell 2055 for capturing the light signal reflected by the first Z-shaped detection cell 2055 and converting the light signal into an electrical signal. When the component detection module 3 corresponds to the position of the second Z-shaped detection cell 2056, the light source emitted by the optical system is irradiated on the second Z-shaped detection cell 2056 through the optical slit 308, and the photodiode 309 is arranged close to the second Z-shaped detection cell 2056 for capturing the light signal reflected by the second Z-shaped detection cell 2056 and converting the light signal into an electrical signal. The light shield 303 is fixedly connected with the opening of the optical sleeve 301 for shielding light.

[0066] The component detection module 3 limits the propagation path of the light beam by arranging the optical slit 308, so as to ensure that only the light from the target light source (LED light source 302) can reach the detection system, further improve the sensitivity of the system to the target signal, and reduce the interference that may be caused by non-target light sources.

[0067] The optical system comprises an LED light source 302, and a filter 304, a focusing lens 305 and a collimating lens 306 arranged in sequence at the exit end of the LED light source 302 from far to close to the photodiode 309, and an optical slit 308 arranged opposite the collimating lens 306. The focusing lens 305 and the collimating lens 306 focus and collimate the light spot, so that the collimated light spot is a parallel light beam with a radius less than 300 μm, the light intensity of the light emitted from the optical slit 308 is improved, and the measurement accuracy is enhanced.

[0068] The component detection module 3 is arranged in two groups, and the optical sleeve 301 and the photodiode 309 are fixedly connected to the detector housing 307. Specifically, the optical sleeve 301 and the photodiode 309 of the two component detection modules 3 are fixedly connected to the same detector housing 307 in parallel, and a photodiode 309 support is arranged on the detector housing 307. The optical sleeve 301 is fixedly connected to the photodiode 309 through the photodiode 309 support, and the optical sleeve 301 is snap-connected to the photodiode 309 support with a spacing of 8 mm, which can accommodate a chromatographic microchip 205 with a thickness of 8 mm or less, thereby realizing integrated packaging and improving the integration of the entire portable double-separation mechanism gradient liquid chromatograph based on the microchip, forming a portable double-separation mechanism gradient liquid chromatograph based on the microchip.

[0069] The LED light source 302 emits light with wavelengths of 415 nm and 450 nm respectively, and the light shield 303 is used to shield the light emitted at a large angle. The light beam passing through the light shield 303 is filtered by the specific wavelength filter 304, and only the light with the specified wavelengths of 415 nm and 450 nm is retained. Subsequently, the light is focused and collimated by the focusing lens 305 and the collimating lens 306 to form a parallel light beam with a light spot radius less than 300 μm. The parallel light beam passes through the first Z-shaped detection cell 2055 or the second Z-shaped detection cell 2056 and is received by the photodiode 309. The optical slit 308 is arranged on the surface of the chromatographic microchip 205 to shield stray light and further improve the detection sensitivity.

[0070] The detector housing 307 and the photodiode support thereof are processed by light-curing 3D printing, and a future 8100 black resin material is selected for processing. The tensile strength is 50 MPa, the elongation at break is 5%-10%, the heat distortion temperature is 60℃, the surface is smooth and has high precision, and it has waterproof and moisture-proof properties. The detector housing 307 provides a sealed environment for the detection process, effectively isolates the stray light interference in the environment, and eliminates the deviation of the detection signal caused by the stray light as much as possible.

[0071] The photoelectric diode 309 is arranged close to the first Z-shaped detection pool 2055 or close to the second Z-shaped detection pool 2056, so that the integration degree of the component detection module 3 is improved, the detection of small volume and portability is realized on the chromatographic microchip 205, and a portable microchip-based portable double-separation mechanism gradient liquid chromatograph is formed.

[0072] The application further discloses a microchip-based portable liquid chromatography detection system, which comprises the microchip-based portable liquid chromatograph, a data acquisition module electrically connected with the component detection module 3, a waste liquid collection module in communication with the chromatographic separation module 2, a micro-flow meter in communication with the waste liquid collection module, and a data processing module electrically connected with the data acquisition module.

[0073] The data processing module is electrically connected with the photoelectric diode 309 through the data acquisition module, the data acquisition module is used for acquiring the electrical signal of the photoelectric diode 309 and sending the electrical signal to the data processing module, the data processing module is used for analyzing and processing the electrical signal through the Lambert-Beer law to obtain the concentration of the material component, that is, the detection result, the waste liquid collection module is in communication with the first Z-shaped detection pool 2055 and the second Z-shaped detection pool 2056, and is used for collecting the waste liquid detected by the first Z-shaped detection pool 2055 and the second Z-shaped detection pool 2056, and the micro-flow meter is arranged on a communication pipeline between the waste liquid collection module and the first Z-shaped detection pool 2055 or a communication pipeline between the waste liquid collection module and the second Z-shaped detection pool 2056, and is used for monitoring the flow of the detected waste liquid.

[0074] By arranging the micro-flow meter, the liquid detected on the chromatographic microchip 205 flows through the micro-flow meter, so that the real-time monitoring of the liquid flow can be realized; and the waste liquid collection module is used for collecting and recycling the detected liquid, so that the influence of the detected waste liquid on the environment is avoided.

[0075] The chromatographic microchip 205 refers to a chromatographic chip used for flowing phase flow, and the channel size of the chromatographic microchip 205 is in the micron level, the sample / reagent consumption in the chromatographic microchip 205 is extremely low, and high-efficiency separation can be realized.

[0076] The liquid chromatography detection system is integrated in the instrument shell to form a structure with a volume of only 29*29*18cm 3 , a weight of about 3.5kg, a metal sticker attached to the surface of the instrument shell for shielding and isolating electromagnetic interference, a power switch and a USB interface arranged on the back of the instrument shell, a sealing design realized through the instrument shell to prevent dust and water vapor from entering the interior and damaging various modules, and a lightweight characteristic.

[0077] The application further discloses a microchip-based portable liquid chromatography detection method.

[0078] According to the detection requirement, a corresponding chromatographic column, i.e., an ion chromatographic column 2053 or a reversed-phase chromatographic column 2054, is selected through a chromatographic column switching valve;

[0079] The driving motor 101 drives the syringe 104 to inject the mobile phase into the corresponding chromatographic column through the screw nut 103, and the different components in the mobile phase are separated through the stationary phase in the chromatographic column, and the separated mobile phase enters the corresponding first Z-shaped detection cell 2055 or second Z-shaped detection cell 2056;

[0080] The light source emitted by the LED light source 302 is sequentially subjected to light filtering treatment through the optical filter 304, the focusing lens 305 and the collimating lens 306, and the light rays with wavelengths of 415 nm and 450 nm are reserved, the light rays are irradiated on the corresponding first Z-shaped detection cell 2055 or second Z-shaped detection cell 2056 after passing through the optical slit 308, the light signals reflected by the first Z-shaped detection cell 2055 or second Z-shaped detection cell 2056 are collected by the corresponding photodiode 309, and the photodiode 309 converts the light signals into electrical signals;

[0081] The photodiode 309 sends the electrical signals to the data processing module through the data acquisition module, the data processing module analyzes and processes the electrical signals according to the Lambert-Beer law, and the concentration of the material component is obtained, i.e., the detection result;

[0082] The waste liquid after detection enters the waste liquid collection module through the micro-flow meter, and the waste liquid is collected, the flow of the waste liquid is detected in real time through the micro-flow meter, and the flow entering the chromatographic column is detected in real time through the flow of the waste liquid.

[0083] It should be noted that, for those skilled in the art, it is obvious that the present application is not limited to the details of the above exemplary embodiments, and the present application can be realized in other specific forms without departing from the spirit or essential characteristics of the present application. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-limiting, and the scope of the present application is defined by the appended claims rather than the above description, and therefore all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be included in the application. Any reference signs in the claims should not be regarded as limiting the claims involved.

Claims

1. A microchip-based portable liquid chromatograph characterized by, The chromatographic separation module comprises a chromatographic microchip and a moving clamping device for carrying the chromatographic microchip, the chromatographic microchip comprises a chip body, ion chromatographic columns and reverse phase chromatographic columns arranged on the chip body and in communication with the mobile phase driving module and the component detection module, a first chromatographic column switching valve arranged on a channel in communication with the mobile phase driving module and the ion chromatographic column, a second chromatographic column switching valve arranged on a channel in communication with the mobile phase driving module and the reverse phase chromatographic column, and a sample injector in communication with the ion chromatographic columns and the reverse phase chromatographic columns. The mobile phase driving module comprises a bottom plate, a support and a driving motor arranged on the bottom plate, a lead screw arranged at the output end of the driving motor, a lead screw nut threadedly connected with the lead screw, a syringe having one end connected with the lead screw nut and the other end in communication with a micro three-way valve, and a mobile phase reagent bottle in communication with the micro three-way valve, and a barrel of the syringe is arranged on the support.

2. The microchip-based portable liquid chromatograph according to claim 1, wherein, The piston rod of the syringe is connected with the lead screw nut, the liquid outlet of the syringe is in communication with the first connecting port of the micro three-way valve, the mobile phase reagent bottle is in communication with the second connecting port of the micro three-way valve, and the first chromatographic column switching valve and the second chromatographic column switching valve are in communication with the third connecting port of the micro three-way valve. The mobile phase driving module is provided in two.

3. The microchip-based portable liquid chromatograph according to claim 2, wherein, The chromatographic separation module further comprises a mixing part comprising a first liquid inlet, a second liquid inlet, and a spiral flow channel having one end in communication with the first liquid inlet and the second liquid inlet and the other end in communication with the first chromatographic column switching valve and the second chromatographic column switching valve, the first liquid inlet is in communication with the third connecting port of one of the mobile phase driving modules, and the second liquid inlet is in communication with the third connecting port of the other mobile phase driving module.

4. The microchip-based portable liquid chromatograph according to claim 3, wherein The moving clamping device comprises a linear slide rail, a slide rail locking nut seat arranged on the linear slide rail and slidable on the linear slide rail, a two-dimensional horizontal micro-adjusting rack arranged on the slide rail locking nut seat, and a chip clamp arranged on the two-dimensional horizontal micro-adjusting rack for clamping the chromatographic microchip.

5. The microchip-based portable liquid chromatograph according to claim 1, wherein The chromatographic microchip further comprises a filling valve arranged on the chip body and in communication with the ion chromatographic column and the reverse phase chromatographic column, and a first Z-shaped detection cell and a second Z-shaped detection cell in communication with the ion chromatographic column and the reverse phase chromatographic column, respectively, the first Z-shaped detection cell and the second Z-shaped detection cell are in communication with the component detection module.

6. The microchip-based portable liquid chromatograph according to claim 4, wherein The component detection module comprises a detector housing, an optical sleeve and a photodiode arranged on the detector housing, an optical system arranged inside the optical sleeve, an optical slit arranged at the exit end of the optical sleeve, and a light shield fixedly connected at the opening of the optical sleeve, and the photodiode is arranged above the optical sleeve.

7. The microchip-based portable liquid chromatograph according to claim 6, wherein ​ The optical system comprises an LED light source, and a filter, a focusing lens and a collimating lens arranged in sequence at the exit end of the LED light source from far away from the photodiode to close to the photodiode, and the optical slit is arranged opposite to the collimating lens.

8. A microchip-based portable liquid chromatography detection system, characterized by, The portable microchip-based liquid chromatograph comprises a microchip-based portable liquid chromatograph according to any one of claims 1-7, a data acquisition module electrically connected with the component detection module, a waste liquid collection module in communication with the chromatographic separation module, a micro-flow meter in communication with the waste liquid collection module, and a data processing module electrically connected with the data acquisition module.

9. A microchip-based portable liquid chromatography detection method using the microchip-based portable liquid chromatography detection system according to claim 8, characterized by, The method comprises the following steps: According to the detection requirements, the separation mechanism is selected, and the corresponding ion chromatographic column or reverse phase chromatographic column is selected through the first chromatographic column switching valve or the second chromatographic column switching valve; The flow phase driving module drives the flow phase into the corresponding ion chromatographic column or reverse phase chromatographic column; The component detection module is used for signal acquisition of the sample in the ion chromatographic column or reverse phase chromatographic column; The data processing module is used for analyzing and processing the signal to obtain the concentration of the substance component; The waste liquid after detection is collected in the waste liquid collection module.

10. The microchip-based portable liquid chromatography detection method according to claim 9, wherein, The calculation formula of the driving pressure of the flow phase driving module is: P = ΔP1 + ΔP2 ΔP1 is the pressure drop of the ion chromatographic column or reverse phase chromatographic column, and the unit is MPa; ΔP2 is the loss pressure drop, and the unit is MPa; Φ is the resistance factor; η is the viscosity of the flow phase, and the unit is MPa·s; L is the length of the ion chromatographic column or reverse phase chromatographic column, and the unit is m; ​ Q is the flow rate of the mobile phase in the ion chromatography column or the reversed-phase chromatography column, in units of μL / min; ε is the porosity of the stationary phase in the ion chromatography column or the reversed-phase chromatography column; A is the cross-sectional area of the ion chromatography column or the reversed-phase chromatography column, in mm 2 ; d P is the particle size of the stationary phase in the ion chromatography column or the reversed-phase chromatography column, in units of μm.

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