A liquid chromatograph with a new diaphragm pump head structure

Abstract

The present invention provides a liquid chromatograph with a brand-new diaphragm pump head structure, wherein the liquid phase pump is composed of at least one diaphragm component in a manner including but not limited to parallel or series connection; the liquid phase pump composed of the diaphragm pump head structure can avoid the problems of wear and leakage of the plunger rod, reduce maintenance costs, and have a more stable mobile phase delivery performance, which can effectively reduce pressure fluctuations and flow fluctuations, and improve the accuracy and repeatability of analysis; at the same time, it can also reduce the pressure fluctuations generated when the plunger circulates and reciprocates to pump the liquid, and achieve a better balance between the small flow rate control accuracy and the pump output.

Description

Technical Field

[0001] The invention relates to the technical field of liquid chromatographs, and in particular to a liquid chromatograph with a brand-new diaphragm pump head structure. Background Art

[0002] At present, most high-pressure gradient pumps in liquid chromatographs adopt plunger structures. Due to the advantages of high rated pressure, compact structure, high efficiency and convenient flow regulation, plunger pumps are widely used in high pressure and flow regulation occasions. There are two one-way valves on a plunger pump, and the directions are opposite. When the plunger moves in one direction, negative pressure appears in the cylinder. At this time, one one-way valve opens and the liquid is sucked into the cylinder. When the plunger moves in the other direction, the liquid is compressed and the other one-way valve is opened, and the liquid sucked into the cylinder is discharged. This method realizes the suction and discharge of liquid by the change of the sealed working volume when the plunger reciprocates in the plunger hole. According to the different arrangement directions of the plunger, it is divided into two categories: axial piston pumps and radial piston pumps. The common scheme on liquid chromatographs is a radial piston pump in which the motor and cam drive the plunger rod to reciprocate. The pressure resistance range of the pump head is generally around 6000-18000psi, and the infusion rate of 0.001-10.0 mL / min can be achieved according to the size of the cavity volume.

[0003] However, plunger pumps generally have the following disadvantages: (1) The plunger rod and sealing ring in the plunger pump are in direct contact with the pumped liquid, and the types of liquid chromatography mobile phases are diverse, requiring resistance to acid, alkali, salt and organic solvent corrosion. The sealing ring is prone to aging and cracking, causing the mobile phase to leak into the pump body. Since the plunger rod is in contact with the solution, salt crystals will precipitate after the solution on the surface of the plunger rod dries up. As the plunger rod reciprocates, the crystal particles rub against the surface of the plunger rod, causing wear on the plunger rod or the sealing gasket. The above two points are the most common types of failures of plunger pumps; (2) The flow rate range and flow rate accuracy of the plunger pump are determined by the pump cavity capacity and motor speed. If the cavity capacity is small, the control accuracy of the pump output flow rate is high, but the upper limit of the flow rate is low; if the cavity capacity is large, the upper limit of the pump output flow rate is high, but the flow rate control accuracy is low, and it is easy to stall at low speed; (3) The reciprocating motion of the plunger is prone to pressure fluctuations.

[0004] Therefore, it is urgent to find a new pump head structure suitable for liquid chromatograph, which can avoid wear and leakage of the plunger rod while maintaining the performance of the liquid pump, reduce maintenance costs; reduce the pressure fluctuations generated when the plunger reciprocates to pump the liquid; and achieve a better balance between small flow rate control accuracy and pump output. Summary of the invention

[0005] In order to solve the problems existing in the prior art, the present invention provides a liquid chromatograph with a brand-new diaphragm pump head structure. The binary pump composed of the diaphragm pump head structure can avoid the problems of wear and leakage of the plunger rod while maintaining the performance of the liquid phase pump, thereby reducing maintenance costs; at the same time, it can also reduce the pressure fluctuations generated when the plunger circulates and reciprocates to pump the liquid, thereby achieving a better balance between the small flow rate control accuracy and the pump output.

[0006] In order to achieve the above object, the present invention adopts the following scheme:

[0007] On the one hand, the present invention provides a liquid chromatograph, comprising a pump body, wherein the pump body comprises any one of a binary pump, a quaternary pump or a multi-element pump; the pump head of the pump body adopts a diaphragm pump head, wherein the diaphragm pump head is a series diaphragm pump or a parallel diaphragm pump, and the diaphragm pump head comprises a diaphragm assembly and a coaxial linkage assembly; in the series diaphragm pump, the diaphragm assemblies are connected in series to form an integrated structure through the coaxial linkage assembly; in the parallel diaphragm pump, the diaphragm assemblies are connected in parallel to form an integrated structure through the coaxial linkage assembly;

[0008] The diaphragm assembly is used to prevent the plunger from contacting the mobile phase and realize automatic suction and discharge of liquid under low pressure fluctuations;

[0009] The coaxial linkage assembly is used to connect different diaphragm assemblies so that the diaphragm assemblies can move synchronously.

[0010] In the prior art, there are many types of pump bodies in liquid chromatographs, including binary pumps, quaternary pumps and other multi-element pumps (such as ternary pumps, quinary pumps and other pump body structures of various different numbers of elements). The present invention makes innovative improvements to the pump head structure of the liquid chromatograph. In the process of explanation, binary pumps and quaternary pumps are used as examples for detailed description. However, the protection scope of the present invention is not limited to the two specific pump body types of binary pumps and quaternary pumps, but covers all multi-element pumps used in liquid chromatographs. Regardless of the number of elements of the pump body, as long as it has the technical features involved in the present invention, it belongs to the protection scope of the present invention. This design aims to provide a comprehensive and universal technical solution that can be widely used in liquid chromatographs with various multi-element pump bodies to achieve specific technical effects and meet different needs in practical applications. The liquid phase pump described in the present invention is composed of at least one diaphragm assembly in a manner including but not limited to parallel or series connection.

[0011] In some embodiments, the present invention designs a new diaphragm pump head structure, including a double diaphragm assembly series diaphragm pump and a six diaphragm assembly star-type parallel diaphragm pump. In the double diaphragm assembly series diaphragm pump, the coaxial linkage assembly drives the plungers in the first diaphragm assembly and the second diaphragm assembly to reciprocate at the same time, thereby realizing automatic liquid suction and discharge. In the six diaphragm assembly star-type parallel diaphragm pump, the coaxial linkage assembly drives the plungers in the six diaphragm assemblies to reciprocate at the same time, and the six diaphragm assemblies are in different motion states, thereby realizing automatic liquid suction and discharge.

[0012] Furthermore, the series diaphragm pump includes a first diaphragm assembly, a second diaphragm assembly, a coaxial linkage assembly, a liquid inlet, a channel, and a liquid outlet; the first diaphragm assembly and the second diaphragm assembly are connected in series through the coaxial linkage assembly to form an integrated structure.

[0013] Furthermore, the diaphragm assembly includes a first one-way valve, a second one-way valve, a seal, a diaphragm, a diaphragm cavity, a plunger, and a plunger cavity; the first one-way valve and the second one-way valve are arranged on one side of the diaphragm cavity; when the first one-way valve is turned on, the second one-way valve is closed; or when the second one-way valve is turned on, the first one-way valve is closed; the first one-way valve and the second one-way valve are used to prevent liquid leakage or backflow.

[0014] Furthermore, a diaphragm is arranged in the middle of the diaphragm cavity, and the diaphragm is an elastic composite film with wide pH tolerance, salt resistance and organic reagent resistance, and deforms with changes in pressure on both sides.

[0015] Furthermore, a plunger is arranged on one side of the diaphragm, and the plunger rod of the plunger is an integrated structure with the coaxial linkage assembly; the plunger reciprocates in the plunger cavity through the coaxial linkage assembly, and the reciprocating motion of the plunger drives the deformation of the diaphragm to realize automatic suction and discharge of liquid.

[0016] Furthermore, the volume of the diaphragm cavity of the first diaphragm assembly is twice that of the diaphragm cavity of the second diaphragm assembly.

[0017] In some embodiments, the diaphragm cavity volume of the first diaphragm assembly is twice that of the second diaphragm assembly, that is, the volume pumped by the plunger of the first diaphragm assembly in one cycle is twice that of the second diaphragm assembly. Since the first diaphragm assembly and the second diaphragm assembly alternately complete the "liquid suction-liquid discharge" process, when the first diaphragm assembly is in the liquid suction process, the second diaphragm assembly is in the liquid discharge process. After the first diaphragm assembly completes the liquid suction process, liquid is transported to the second diaphragm assembly. Since the pumping volume of the first diaphragm assembly is larger than the cavity capacity of the second diaphragm assembly, part of the liquid will be discharged from the outlet along the flow path. The design ensures that liquid output can still be maintained when the second diaphragm assembly is in the liquid suction cycle, greatly reducing the large pressure fluctuations caused by the continuous switching of "liquid suction-liquid discharge", so that the pressure fluctuations during the "liquid suction-liquid discharge" switching process are significantly reduced and tend to be stable.

[0018] Furthermore, the parallel diaphragm pump includes a liquid outlet component, a liquid outlet component sealing gasket, a liquid outlet channel, a liquid outlet channel gasket, a liquid inlet component, a liquid inlet component sealing gasket, a diaphragm cavity B, a housing fixing screw, a first one-way valve, a second one-way valve, a diaphragm cavity A, 6 diaphragm assemblies, and a coaxial linkage assembly; the 6 diaphragm assemblies are connected in parallel to form an integrated structure through the coaxial linkage assembly.

[0019] Furthermore, the parallel connection method adopts a star-shaped six-way parallel connection, and the star-shaped six-way parallel connection is that 6 diaphragm components are radially distributed with the center point as the symmetry center.

[0020] Furthermore, the liquid inlet component and the liquid inlet component sealing gasket are fixedly connected to the diaphragm cavity B.

[0021] Furthermore, the liquid inlet component is provided with a circular hole channel for liquid to enter, which is fixedly connected to the liquid inlet pipeline.

[0022] Furthermore, a groove is provided on one side surface of the diaphragm cavity B, and the first one-way valve, the first diaphragm assembly, and the second one-way valve are fixed in the groove.

[0023] Furthermore, the one-way valve on the side close to the center of the diaphragm cavity B is a first one-way valve, and the one-way valve on the side away from the center of the diaphragm cavity B is a second one-way valve.

[0024] Furthermore, the diaphragm cavity B and the diaphragm cavity A are detachably connected.

[0025] Furthermore, the first one-way valve, the second one-way valve and the diaphragm assembly are fixed in the accommodation space between the diaphragm cavity B and the diaphragm cavity A.

[0026] On the other hand, the present invention provides a use of a series diaphragm pump for reducing pressure fluctuations in a liquid chromatograph or improving detection accuracy, wherein the liquid chromatograph is as described in any one of the above technical solutions.

[0027] In some embodiments, two diaphragm assemblies are connected in series, and the reciprocating motion of the plunger is controlled by a coaxial drive assembly to achieve automatic suction and discharge of the liquid. Compared with traditional plunger pumps, this has a more stable mobile phase delivery performance, can effectively reduce pressure fluctuations and flow fluctuations, and improve the accuracy and repeatability of analysis; at the same time, the flexibility of the diaphragm makes the pump run more smoothly, greatly reduces noise and mechanical wear, and extends the service life of the equipment.

[0028] Compared with using a single diaphragm assembly to construct a diaphragm pump head, the present invention uses a double diaphragm assembly in series to construct a diaphragm pump, which can significantly reduce pressure fluctuations during use, while also improving flow control accuracy and significantly improving the accuracy and reliability of detection results.

[0029] Compared with using multiple diaphragm assemblies in series to construct a diaphragm pump head, the present invention uses double diaphragm assemblies in series to construct a diaphragm pump, which achieves a better balance between performance and cost, can meet most application requirements, and has higher reliability and practicality.

[0030] In yet another aspect, the present invention provides a parallel diaphragm pump for use in reducing pressure fluctuations in a liquid chromatograph or improving detection accuracy, wherein the liquid chromatograph is as described in any one of the above technical solutions.

[0031] In some embodiments, six diaphragm assemblies are connected in star parallel to miniaturize a single diaphragm cavity, and the reciprocating motion of the plunger is controlled by a coaxial drive assembly to achieve automatic suction and discharge of the liquid. Compared with traditional plunger pumps, it has a more stable mobile phase delivery performance, can effectively reduce pressure fluctuations and flow fluctuations, and improve the accuracy and repeatability of analysis; at the same time, due to the small capacity of a single diaphragm chamber, the pump can achieve precise control of small flow rate changes, and the six diaphragm assemblies working at the same time can provide a larger flow rate, so that the pump has a wider controllable flow rate range, thereby achieving a better balance between accuracy and output; at the same time, when one of the diaphragm assemblies fails, the other diaphragm assemblies can continue to work, thereby improving the reliability of the pump; and the application range is wide, and some corrosive, viscous or particle-containing media can also be well handled.

[0032] Compared with the diaphragm pump constructed with a double diaphragm assembly in series, the star-parallel structure of six diaphragm assemblies has better performance. On the one hand, the star-parallel structure of six diaphragm assemblies can provide a larger flow rate, while the double diaphragm assembly in series may be relatively limited in flow output; on the other hand, the star-parallel structure of six diaphragm assemblies can better disperse pressure fluctuations, making the pressure more uniform and stable, and achieving a better balance between the accuracy and output of the pump; at the same time, the star-parallel structure of six diaphragm assemblies has higher reliability, and the failure of a single diaphragm assembly has less impact on the whole, and the reliability is higher, while a problem with one diaphragm assembly in the double diaphragm assembly in series may have a more obvious impact on the entire system.

[0033] On the other hand, the present invention provides a diaphragm pump head structure, the diaphragm pump head structure includes a diaphragm pump head in a liquid chromatograph as described in any one of the above technical solutions, the diaphragm pump head is a series diaphragm pump or a parallel diaphragm pump, and the diaphragm pump head includes a diaphragm assembly and a coaxial linkage assembly; in the series diaphragm pump, the diaphragm assemblies are connected in series to form an integrated structure through the coaxial linkage assembly; in the parallel diaphragm pump, the diaphragm assemblies are connected in parallel to form an integrated structure through the coaxial linkage assembly;

[0034] The diaphragm assembly is used to prevent the plunger from contacting the mobile phase and realize automatic suction and discharge of liquid under low pressure fluctuations;

[0035] The coaxial linkage assembly is used to connect different diaphragm assemblies so that the diaphragm assemblies can move synchronously.

[0036] The beneficial effects of the present invention are:

[0037] 1. The present invention provides a liquid chromatograph with a new diaphragm pump head structure, wherein the diaphragm pump head is composed of a double diaphragm assembly in series or 6 diaphragm assemblies in star parallel connection; the series diaphragm pump has a more stable mobile phase delivery performance compared to a traditional plunger pump, can effectively reduce pressure fluctuations and flow fluctuations, and improve the accuracy and repeatability of analysis; at the same time, the diaphragm prevents the plunger from directly contacting the mobile phase, avoids common fault problems such as plunger rod wear, and the flexibility of the diaphragm makes the pump run more smoothly, greatly reduces noise and mechanical wear, and extends the service life of the equipment; the parallel diaphragm pump, compared to Compared with traditional plunger pumps, it has more stable mobile phase delivery performance, can effectively reduce pressure fluctuations and flow fluctuations, and improve the accuracy and repeatability of analysis; at the same time, due to the small capacity of a single diaphragm chamber, the pump can achieve precise control of small flow rate changes, and the six diaphragm components working at the same time can provide a larger flow rate, so that the pump has a wider controllable flow rate range, thereby achieving a better balance between accuracy and output; at the same time, when one of the diaphragm components fails, the other diaphragm components can continue to work, which improves the reliability of the pump; and it has a wide range of applications, and can also handle some corrosive, viscous or particle-containing media well.

[0038] 2. In the series diaphragm pump provided by the present invention, the diaphragm cavity volume of the first diaphragm assembly is twice that of the second diaphragm assembly, so that when the second diaphragm assembly is in the suction cycle, the first diaphragm assembly is still discharging liquid. And because the diaphragm cavity volume of the first diaphragm assembly is large, it can provide sufficient liquid output to maintain a stable flow of the system, thereby slowing down the pressure fluctuation. At the same time, half of the liquid is sucked into the diaphragm cavity by the second diaphragm assembly and stored in the diaphragm cavity, and the part exceeding the capacity of the second diaphragm assembly will flow out directly from the outlet, so that the rear end maintains a higher pressure level. That is, the second diaphragm assembly can continuously output liquid to the rear end regardless of whether it is in the process of suction or discharge, thereby significantly reducing pressure fluctuations. And when the diaphragm cavity volume of the first diaphragm assembly is twice that of the second diaphragm assembly, the frequency of "suction-discharge" switching can also be reduced, further reducing pressure fluctuations. It is conducive to achieving smoother liquid delivery, improving the performance and stability of the system, and at the same time, it can also extend the service life of the instrument and reduce maintenance costs.

[0039] 3. In the parallel diaphragm pump provided by the present invention, on the basis of a single diaphragm assembly structure, a single diaphragm cavity is miniaturized, wherein the volume of each diaphragm cavity is 100μL ~ 1000μL, and a star-shaped six-way parallel structure is adopted, and a single set of motors is used to drive 6 groups of diaphragm assemblies. Since the capacity of a single diaphragm assembly is small, the pump can achieve precise control of small flow rate changes; at the same time, the 6 diaphragm assemblies are connected in parallel, so that the overall output of the pump after the motor rotates one circle is not inferior to that of a plunger pump with a large cavity capacity, so that the pump has a wide controllable flow rate range. And because the 6 diaphragm assemblies are in different working states, the pressure fluctuations generated by one stroke of the plunger will be significantly reduced compared to traditional plunger reciprocating pumps. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 It is a schematic structural diagram of a single diaphragm assembly of the present invention.

[0041] Figure 2 It is a three-dimensional structural diagram of a series-connected diaphragm pump composed of double diaphragm assemblies connected in series according to the present invention.

[0042] Figure 3 It is an exploded view of a series diaphragm pump composed of double diaphragm assemblies connected in series according to the present invention.

[0043] Figure 4 It is an exploded view of a series diaphragm pump composed of double diaphragm assemblies connected in series according to the present invention (the structures are all reversed).

[0044] Figure 5 It is a structural schematic diagram of a series diaphragm pump composed of double diaphragm components connected in series according to the present invention.

[0045] Figure 6 It is a three-dimensional structural diagram of a parallel diaphragm pump composed of six diaphragm assemblies connected in star parallel in the present invention.

[0046] Figure 7 It is an exploded view of a parallel diaphragm pump composed of six diaphragm assemblies connected in star-shaped parallel connection according to the present invention.

[0047] Figure 8 It is an exploded view of a parallel diaphragm pump composed of six diaphragm assemblies connected in star-shaped parallel connection according to the present invention (the structures are all reverse).

[0048] Fig. 9 It is a structural schematic diagram of a parallel diaphragm pump composed of six diaphragm assemblies connected in star-shaped parallel connection according to the present invention.

[0049] Fig.10 It is a schematic structural diagram of the liquid chromatograph of the present invention.

[0050] Fig.11 It is a schematic diagram of the flow path process when the binary pump of the present invention is working.

[0051] Fig.12It is a schematic diagram of the flow path process when the quaternary pump of the present invention is working.

[0052] Fig.13 This is a comparison chart of pressure fluctuations of different pumps (single plunger pump, single diaphragm pump, series diaphragm pump, star parallel diaphragm pump).

[0053] Fig.14 This is a result diagram of the pressure fluctuation ratio of the total output flow path using a traditional plunger reciprocating pump and a star-type parallel structure of six diaphragm assemblies of the present invention.

[0054] Fig.15 This is a diagram showing the simulation results of pressure fluctuations using a conventional plunger reciprocating pump and the star-type parallel structure of six diaphragm assemblies of the present invention.

[0055] Fig.16 The structures of the isomers sulfa-metamethoxine (left) and sulfa-paramethoxine (right).

[0056] Fig.17 It is a comparison chart of the separation effects of a traditional plunger binary pump and the diaphragm binary pump of the present invention on sulfamethoxazole and sulfamethoxazole. DETAILED DESCRIPTION

[0057] The present invention will be further described in detail below in conjunction with the examples. It should be pointed out that the examples described below are intended to facilitate the understanding of the present invention and do not have any limiting effect on the present invention.

[0058] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0059] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0060] In the present invention, there are slight differences in the structural descriptions of a single diaphragm assembly and diaphragm assemblies in a series or parallel structure, and corresponding adjustments are made according to the requirements of actual equipment installation.

[0061] In the present invention, the liquid inlet is set as the first one-way valve, and the liquid outlet is set as the second one-way valve; the liquid is the mobile phase.

[0062] Example 1 A new diaphragm pump head structure provided by the present invention

[0063] 1. Basic structure of a single diaphragm assembly in a diaphragm pump head

[0064] In order to solve the shortcomings of the plunger reciprocating pump, a new diaphragm pump head is designed in this embodiment. The pump head adopts a diaphragm structure, specifically including double diaphragm components in series and multiple diaphragm components in parallel. When working, the piston can not be directly in contact with the corrosive liquid, and the cavity and the liquid are separated by a diaphragm. The structure of the single diaphragm components is the same, specifically as follows Figure 1 As shown. Figure 1 It can be seen that the structure of the single diaphragm assembly includes: a first one-way valve 1, a second one-way valve 2, a first seal 3, a second seal 4, a diaphragm 5, a diaphragm cavity 6, a plunger 7, a plunger cavity 8 and a pressure mass transfer medium input port 9. The first one-way valve 1 and the second one-way valve 2 are arranged on the left side of the diaphragm cavity 6, and the control liquid can only be sucked from the first one-way valve 1 below, enter the diaphragm cavity 6, and then be discharged from the second one-way valve 2 above; the first seal 3 is arranged on the side of the liquid inlet in contact with the first one-way valve 1, and the second seal 4 is arranged near the diaphragm cavity 6 of the second one-way valve 2 (the seal can be arranged on the side of the liquid inlet in contact with the first one-way valve 1 according to actual conditions, or on the side of the second one-way valve 2 near the diaphragm cavity 6) to prevent liquid leakage or backflow. The diaphragm 5 is arranged in the middle of the diaphragm cavity 6, which is specifically an elastic composite film with wide pH tolerance (pH1~14), salt resistance and organic reagent resistance, and can be deformed with the change of pressure on both sides. The left side of the diaphragm 5 is the mobile phase liquid, and the right side is the liquid pressure mass transfer medium. A plunger 7 is arranged on the right side of the diaphragm cavity 6, and the right side of the liquid pressure mass transfer medium is in direct contact with the plunger 7. The space where the plunger 7 reciprocates is the plunger cavity 8. The reciprocating motion of the plunger 7 causes the pressure of the pressure mass transfer medium on the diaphragm 5 to change, driving the deformation of the diaphragm 5 to generate liquid flow; the upper end of the plunger cavity 8 is the pressure mass transfer medium input port 9.

[0065] The specific working principle of the reciprocating motion of the plunger 7 driving the deformation of the diaphragm 5 to generate liquid flow is as follows: when the plunger 7 moves to the right, the volume of the plunger cavity 8 increases, the pressure transfer medium flows back to the right, negative pressure occurs, and the diaphragm 5 bends and deforms to the right. At this time, the first one-way valve 1 below opens, the second one-way valve 2 above closes, and the liquid is sucked from the first one-way valve 1 into the diaphragm cavity 6; when the plunger 7 moves to the left, the volume of the plunger cavity 8 decreases, the pressure increases, and the pressure transfer medium is pushed to the left, causing pressure on the diaphragm 5. After the diaphragm 5 is subjected to pressure, it bends and deforms to the left (mobile phase liquid side), thereby reducing the volume of the diaphragm cavity 6; because the volume of the diaphragm cavity 6 decreases, the pressure therein increases, and at this time the second one-way valve 2 above opens, and the first one-way valve 1 below closes, causing the liquid to be discharged from the diaphragm cavity 6 to the second one-way valve 2.

[0066] Through the reciprocating motion of the plunger 7, the volume and pressure of the diaphragm cavity 6 are continuously changed, thereby realizing the suction and discharge of liquid, and further realizing the precise delivery and control of the liquid; and the thermal conductivity of liquid is better than that of gas, and the heat generated by the reciprocating motion of the plunger 7 can be conducted to the outside along with the transmission medium.

[0067] 2. The diaphragm pump head is a double diaphragm assembly in series structure

[0068] 1. Series structure

[0069] The series diaphragm pump provided in this embodiment, which is composed of a double diaphragm assembly series structure, is specifically as follows: Figure 2-Figure 5 shown.

[0070] from Figure 2~Figure 5 It can be seen that the series diaphragm pump includes a liquid inlet 10, a first diaphragm assembly 11, a channel 12, a second diaphragm assembly 13, a coaxial linkage assembly 14, a motor and a motor bracket 15, a liquid outlet 16, and a housing 33. The first diaphragm assembly 11 includes a first one-way valve 1, a second one-way valve 2, a first seal 3, a second seal 4, a diaphragm 5, a diaphragm cavity 6, a plunger 7, a plunger cavity 8 and a pressure mass transfer medium input port 9; the second diaphragm assembly 13 has the same structure as the first diaphragm assembly 11, including a third one-way valve 17, a fourth one-way valve 18, a second seal 4, a second diaphragm 19, a second diaphragm cavity 20, a second plunger 21, a second plunger cavity 22 and a second pressure mass transfer medium input port 23.

[0071] The liquid inlet 10 is connected to the first one-way valve 1, the second one-way valve 2 is connected to the third one-way valve 17 through the channel 12, the first diaphragm assembly 11 and the second diaphragm assembly 13 are fixedly connected through the coaxial linkage assembly 14, and the coaxial linkage assembly 14 controls the reciprocating motion of the plunger 7 of the first diaphragm assembly 11 and the second plunger 21 of the second diaphragm assembly 13, thereby realizing the flow of liquid; the motor and the motor bracket 15 are fixed at the rear of the coaxial linkage assembly 14, and the output shaft of the motor is connected to the coaxial linkage assembly 14. The first one-way valve 1 and the second one-way valve 2 are respectively installed at the inlet and outlet of the diaphragm cavity 6, the first sealing member 3 is installed on both sides of the first one-way valve 1 and the second one-way valve 2 close to the diaphragm cavity 6, and the diaphragm 4 is installed in the middle of the diaphragm cavity 5, dividing the diaphragm cavity 5 into two spaces, one side close to the first one-way valve 1 and the second one-way valve 2 is a space for the flow of mobile phase liquid, and the other side is a space for placing liquid pressure mass transfer medium; a plunger cavity 7 is set on the other side of the diaphragm cavity 6, and a plunger 7 is installed in the plunger cavity 7, and one side of the liquid pressure mass transfer medium is in direct contact with the plunger 7, and the plunger 7 can reciprocate in the plunger cavity 8, and the upper end of the plunger cavity 8 is the pressure mass transfer medium input port 9. The coaxial linkage assembly 14 pushes the plunger 7 to reciprocate in the plunger cavity 8, thereby driving the diaphragm 5 to deform, thereby realizing the suction and discharge of the liquid (mobile phase).

[0072] At the same time, in this embodiment, the volume of the diaphragm cavity 6 of the first diaphragm assembly 11 is twice that of the second diaphragm assembly 13, that is, the volume pumped by the plunger 7 of the first diaphragm assembly 11 in one cycle is twice that of the second diaphragm assembly 13. Since the first diaphragm assembly 11 and the second diaphragm assembly 13 alternately complete the "liquid suction-liquid discharge" process, when the first diaphragm assembly 11 is in the liquid suction process, the second diaphragm assembly 13 is in the liquid discharge process. After the first diaphragm assembly 11 completes the liquid suction process, liquid begins to be transported to the second diaphragm assembly 13. Since the pumping volume of the first diaphragm assembly 11 is greater than the capacity of the diaphragm cavity 6 of the second diaphragm assembly 13, part of the liquid will be discharged from the liquid outlet 16 along the flow path. The design ensures that the liquid output can still be maintained when the second diaphragm assembly 13 is in the liquid suction cycle, greatly reducing the large pressure fluctuation caused by the continuous switching of "liquid suction-liquid discharge", so that the pressure fluctuation during the "liquid suction-liquid discharge" switching process is significantly reduced and tends to a stable state.

[0073] 2. Working principle of the double diaphragm assembly series structure

[0074] like Figure 5As shown, the working principle of the double diaphragm assembly series structure of the present invention is specifically as follows: the motor drives the coaxial linkage assembly 14 to rotate, and the coaxial linkage assembly 14 drives the plunger 7 in the first diaphragm assembly 11 and the second plunger 21 in the second diaphragm assembly 13 to reciprocate. When the coaxial linkage assembly 14 rotates, the plunger 7 of the first diaphragm assembly 11 moves to the left, negative pressure appears in the plunger cavity 8, and the diaphragm 5 bends and deforms to the left. At this time, the first one-way valve 1 opens, the second one-way valve 2 closes, and the liquid is sucked from the first one-way valve 1 into the diaphragm cavity 6; and when the plunger 7 of the first diaphragm assembly 11 moves to the right, the pressure in the plunger cavity 8 increases, and the diaphragm 5 bends and deforms to the right. At this time, the second one-way valve 2 opens, the first one-way valve 1 closes, and the liquid is discharged from the diaphragm cavity 6 and enters the channel 12; at this time, according to the coaxial linkage assembly 14, the second one-way valve 2 of the second diaphragm assembly 13 The plug 21 moves to the left, negative pressure appears in the second plunger cavity 22 of the second diaphragm assembly 12, the second diaphragm 19 bends and deforms to the left, the third one-way valve 17 of the second diaphragm assembly 13 opens, and the liquid in the channel 12 is sucked into the second plunger cavity 22 of the second diaphragm assembly 13; when the second plunger 21 of the second diaphragm assembly 13 moves to the right, the second diaphragm 19 bends and deforms to the right, at this time the fourth one-way valve 18 of the second diaphragm assembly 13 opens, the third one-way valve 17 closes, and the liquid is discharged from the second diaphragm cavity 20 of the second diaphragm assembly 13 and flows out from the liquid outlet 16.

[0075] When the coaxial linkage assembly 14 rotates, the liquid passes through the liquid inlet 10, the first diaphragm assembly 11, the channel 12, the second diaphragm assembly 13, and the liquid outlet 16 in sequence. There is a one-way valve structure and a liquid flow path between the diaphragm pump A surface 40 and the diaphragm pump B surface 41 to prevent liquid backflow, ensuring that the liquid enters from the inlet pipeline and flows out from the outlet pipeline. In the whole process, the coaxial linkage assembly 14 ensures that the actions of the two plunger pumps are coordinated to maintain a stable liquid flow state; at the same time, it ensures that the sealing of each connection part is good to prevent liquid leakage.

[0076] 3. The role of different structures in the series structure of double diaphragm components

[0077] (1) Liquid inlet 10: one end is connected to a container containing a mobile phase, and the other end is connected to a first diaphragm assembly 11;

[0078] (2) The first diaphragm assembly 11 includes a first one-way valve 1, a second one-way valve 2, a first sealing member 3, a second sealing member 4, a diaphragm 5, a diaphragm cavity 6, a plunger 7, and a plunger cavity 8. The first one-way valve 1 and the second one-way valve 2 control the liquid to flow into the first one-way valve 1 only from the liquid inlet 10, enter the diaphragm cavity 6, and then be discharged from the second one-way valve 2 below; when the first one-way valve 1 is opened, the second one-way valve 2 is closed; when the second one-way valve 2 is opened, the first one-way valve 1 is closed to ensure the correct flow direction of the liquid and prevent the liquid from flowing back; the first one-way valve 1 and the second one-way valve 2 are provided with a first seal 3 and a second seal 4 near the diaphragm cavity 6 to prevent liquid leakage or backflow; a diaphragm 5 is provided in the middle of the diaphragm cavity 6, specifically an elastic composite film with wide pH tolerance (pH 1-14), salt resistance and organic reagent resistance, which can be deformed with the change of pressure on both sides; a plunger 7 is provided on one side of the diaphragm cavity 6, and the upper end of the plunger cavity 8 is a pressure transfer medium input port 9, and the liquid pressure transfer medium is in direct contact with the plunger 7, and the reciprocating motion of the plunger 7 causes the pressure of the pressure transfer medium on the diaphragm 5 to change, driving the deformation of the diaphragm 5 to generate liquid flow, thereby controlling the suction and discharge of the liquid;

[0079] (3) Channel 12: The channel through which the liquid (mobile phase) passes after being discharged from the second one-way valve 2 of the first diaphragm assembly 11 and before entering the third one-way valve 17 of the second diaphragm assembly 13, ensuring that the liquid has a stable flow state;

[0080] (4) The second diaphragm assembly 13: has the same structure and function as the first diaphragm assembly 11. The differences are as follows: A. It includes a third one-way valve 17 and a fourth one-way valve 18, and the fourth one-way valve 18 is connected to the liquid outlet 16; B. The volume of the diaphragm cavity 6 of the first diaphragm assembly 11 is twice that of the second diaphragm cavity 20 of the second diaphragm assembly 13, ensuring that the liquid output can be maintained when the second diaphragm assembly 13 is in the liquid suction cycle, greatly reducing the large pressure fluctuation caused by the continuous switching of "liquid suction-liquid discharge", so that the pressure fluctuation during the "liquid suction-liquid discharge" switching process is significantly reduced and tends to a stable state;

[0081] (5) Coaxial linkage assembly 14: connects the first diaphragm assembly 11 and the second diaphragm assembly 13 together so that they can maintain the same movement frequency and stroke during operation and perform synchronous movement, thereby avoiding the movement inconsistency between the two diaphragm assemblies, thereby improving the efficiency and performance of the pump; at the same time, it plays a role of balance and stability, reducing the vibration and noise of the pump during operation; and facilitates maintenance and servicing, thereby increasing the service life of the pump;

[0082] (6) Motor and motor bracket 15: The motor is used to provide power to drive the coaxial linkage assembly 14 to move, thereby driving the reciprocating motion of the first diaphragm assembly 11 and the second diaphragm assembly 13 to achieve the suction and discharge of liquid; the motor bracket is used to fix, support and protect the motor;

[0083] (7) Liquid outlet 16: one end is connected to the fourth one-way valve 18, and the other end is connected to the chromatographic column.

[0084] 3. The diaphragm pump head is a parallel structure of multiple diaphragm components

[0085] 1. Multiple diaphragm components in parallel

[0086] The parallel diaphragm pump provided in this embodiment, which is composed of 6 diaphragm assemblies in parallel, is specifically as follows: Figure 6-Figure 9 shown.

[0087] from Figure 6~Figure 9 It can be seen that the parallel diaphragm pump includes a liquid outlet component 24, a liquid outlet component sealing gasket 25, a liquid outlet channel 26, a liquid outlet channel gasket 27, a liquid inlet component 28, a liquid inlet component sealing gasket 29, a diaphragm cavity B 30, a housing fixing screw 31, a first one-way valve 1, a second one-way valve 2, a diaphragm cavity A 32, a first diaphragm assembly 11, a coaxial linkage assembly 14, a motor and a motor bracket 15, and a housing 33, and the above-mentioned different structures are fixed in sequence.

[0088] The liquid inlet component 28 and the sealing gasket 29 of the liquid inlet component are fixedly connected to the diaphragm cavity B 30. A circular hole channel for liquid to enter is set in the center of the liquid inlet component 28, which is fixedly connected to the liquid inlet pipeline 34; the sealing gasket 29 of the liquid inlet component is provided with a star-shaped six-way groove, and the center of the star-shaped six-way groove is a circular hole channel for liquid to pass through, which is consistent with the size of the circular hole channel in the center of the liquid inlet component 28; the side of the diaphragm cavity B 30 that directly contacts the sealing gasket 29 of the liquid inlet component is provided with a star-shaped six-way groove consistent with the size of the sealing gasket 29 of the liquid inlet component and a circular hole channel for liquid to pass through, and the circular hole channel is connected with the circular hole channel in the center of the sealing gasket 29 of the liquid inlet component and is consistent in size;

[0089] A circular hole channel is arranged along the center of the other side of the diaphragm cavity B 30, and a star-shaped six-way groove is arranged along the outside. A liquid flow channel is arranged between the circular hole channel in the center of the diaphragm cavity B 30 and each of the grooves; and the star-shaped six-way grooves are arranged outside the circular hole channel, and each of the grooves is respectively fixed with a first one-way valve 1, a first diaphragm assembly 11, and a second one-way valve 2. The size and shape of each of the grooves are consistent with the one-way valve (including the first one-way valve 1 and the second one-way valve 2) and the first diaphragm assembly 11. The one-way valve close to the central circular hole of the diaphragm cavity B 30 is the first one-way valve 1, and the one-way valve away from the central circular hole of the diaphragm cavity B 30 is the second one-way valve 2. The diaphragm cavity B 30 and the diaphragm cavity A 32 are fixedly connected by the housing fixing screws 31, and the one-way valve and the diaphragm assembly are fixed in the accommodation space between the diaphragm cavity B 30 and the diaphragm cavity A 32. The diaphragm cavity A 32 is also provided with a space for accommodating the one-way valve and the diaphragm assembly, and its size and shape are consistent with the one-way valve and the diaphragm assembly;

[0090] The plungers 7 of the six diaphragm assemblies are all fixed on the coaxial linkage assembly 14, the coaxial linkage assembly 14 is fixedly connected to the motor, and the motor bracket is used to fix the motor. When the coaxial linkage assembly 14 rotates, the plungers 7 of the six diaphragm assemblies are in different working states, and the plunger 7 of each diaphragm assembly moves, driving the diaphragm 5 to deform, thereby achieving the suction and discharge of the liquid (mobile phase);

[0091] A liquid circular hole channel connected to the six liquid outlets of the second one-way valve 2 is provided on one side of the diaphragm cavity B 30 (the side where the sealing gasket 29 of the liquid inlet component is located) (the rest are fixing screws between different structures), and is fixedly connected to the liquid outlet channel gasket 27 through screws, and the other side of the liquid outlet channel gasket 27 is fixedly connected to the liquid outlet channel 26, and a vertical groove is provided on one side of the liquid outlet channel 26; the liquid inlet component 28 and the liquid inlet sealing gasket 29 are fixed between the liquid outlet channel gasket 27 and the diaphragm cavity B 30, wherein the liquid inlet pipeline 34 of the liquid inlet component 28 passes through the liquid outlet channel gasket 27 and is fixed in the vertical groove of the liquid outlet channel 26; the liquid outlet channel gasket 27 and the liquid outlet channel 26 are both provided with a circular hole channel of the same size connected to the diaphragm cavity B 30. The other side of the liquid outlet channel 26 is fixedly connected to the liquid outlet component sealing gasket 25, and the other side of the liquid outlet component sealing gasket 25 is fixed with the liquid outlet component 24, and a circular through hole is arranged in the center of the liquid outlet component 24, which is tightly connected with the drainage pipe 35; the liquid outlet component sealing gasket 25 is provided with a star-shaped six-way groove, and a circular through hole is arranged in the center, and the outer edge of the groove is tightly connected with the circular hole channel of the liquid outlet channel 26, and the liquid flows along the outer edge of the groove to the circular through hole in the center of the liquid outlet component sealing gasket 25, and converges, and flows out from the through hole in the center of the liquid outlet component 24 through the circular through hole along the drainage pipe 35.

[0092] 2. Working principle of multiple diaphragm components in parallel

[0093] The working principle of the parallel structure of multiple diaphragm assemblies of the present invention is specifically as follows: a single diaphragm assembly is miniaturized, and six diaphragm assemblies are connected in a star-shaped six-way parallel structure, and six groups of diaphragm assemblies are driven simultaneously by a single motor. The motor drives the coaxial linkage assembly to rotate, and the coaxial linkage assembly drives the plungers in the six diaphragm assemblies to reciprocate simultaneously. When the coaxial linkage assembly rotates, the plungers 7 of the six diaphragm assemblies move different distances respectively, so that the six diaphragm assemblies are in different motion states, and at every moment, there are diaphragm assemblies that are absorbing and discharging liquid respectively.

[0094] (For ease of understanding, Figure 7-Figure 9As an example, it is understood that the actual structure of the present invention is not limited by the orientation in the accompanying drawings.) Taking one of the diaphragm assemblies as an example, when the plunger 7 of the diaphragm assembly is pulled to the right, negative pressure is formed in the diaphragm cavity 6, causing the diaphragm 5 to bend and deform to the right. At this time, the first one-way valve 1 close to the side of the central circular hole of the diaphragm cavity B 30 is opened, and the second one-way valve 2 away from the side of the central circular hole of the diaphragm cavity B 30 is closed. The liquid passes through the liquid inlet component 28, the liquid inlet component sealing gasket 29, and the central circular hole channel of the diaphragm cavity B 30 in sequence, and enters the diaphragm cavity 6 from the first one-way valve 1; and when the plunger 7 of the diaphragm assembly moves to the left, the pressure in the plunger cavity 8 increases, and the diaphragm 5 bends and deforms to the right. At this time, the second one-way valve 2 is opened, the first one-way valve 1 is closed, and the liquid is discharged from the diaphragm cavity 6. After being discharged through the second one-way valve 2, it passes through the diaphragm cavity B 30 in sequence. 30. The liquid outlet channel gasket 27 and the circular through holes on the outer edge of the liquid outlet channel 26 enter the outer edge of the groove of the sealing gasket 29 of the liquid outlet component and converge to the circular through hole in the center, and finally flow out from the through hole in the center of the liquid outlet component 24 along the drainage pipeline 35 through the circular through hole and enter the chromatographic column.

[0095] When the coaxial linkage assembly 14 rotates, the six diaphragm assemblies are driven to be in different working states respectively. Compared with a single plunger reciprocating pump, the pressure fluctuation generated by one stroke of the plunger 7 in the diaphragm assembly will be significantly reduced; at the same time, the volume of a single diaphragm cavity 6 is set to 100μL~1000μL. Since the capacity of a single diaphragm cavity 6 is small, the pump can achieve precise control of small flow rate changes, and the six diaphragm cavities 6 are connected in parallel, so that the overall output of the pump after the motor rotates one circle is not inferior to that of a plunger pump with a large cavity capacity, thereby making the pump have a wider controllable flow rate range.

[0096] 3. The role of different structures in the parallel structure of multiple diaphragm components

[0097] (1) Liquid inlet component 28: comprising a liquid inlet pipeline 34, one end of which is connected to a container containing a mobile phase;

[0098] (2) Liquid inlet component sealing gasket 29: installed between the liquid inlet component 28 and the diaphragm cavity B 30. The central through holes of the three structures have the same size, and the star-shaped six-way groove of the liquid inlet component sealing gasket 29 has the same size and shape as the star-shaped six-way groove on the side that directly contacts the diaphragm cavity B 30. It is used to fill the small gap between the contact surface of the liquid inlet component 28 and the diaphragm cavity B 30, thereby preventing liquid from leaking from the connection between the liquid inlet component 28 and the diaphragm cavity B 30 and achieving sealing; and the liquid can only flow in from the central through hole to avoid the backflow of the liquid and the escape to the six grooves; at the same time, it can also help maintain the pressure in the system, prevent the entry of external impurities, reduce the wear between the liquid inlet component 28 and the diaphragm cavity B 30, and make the installation and removal of the liquid inlet component 28 more convenient;

[0099] (3) Diaphragm cavity B 30: The side where the liquid enters is tightly connected to the sealing gasket 29 of the liquid inlet component, and the other side is tightly connected to the diaphragm cavity A 32 to form a complete star-shaped six-way groove, each of which accommodates the first one-way valve 1, the diaphragm assembly and the second one-way valve 2; a liquid circular hole channel connected to the liquid discharge port of the second one-way valve 2 is provided on the outer edge of each groove, and is fixedly connected to the liquid outlet channel gasket 27 by screws;

[0100] (4) First one-way valve 1: arranged on the side close to the central circular hole of the diaphragm cavity B 30, controlling the liquid to be smoothly sucked into the diaphragm cavity. A first sealing member 3 is arranged on the side of the first one-way valve 1 close to the diaphragm cavity 6 to prevent liquid leakage or backflow. When liquid flows in, the first one-way valve 1 opens and the second one-way valve 2 closes; when liquid is discharged, the second one-way valve 2 opens and the first one-way valve 1 closes.

[0101] (5) Diaphragm assembly: comprising a diaphragm 5, a diaphragm cavity 6, a plunger 7 and a plunger cavity 8. The coaxial linkage assembly 14 drives the plunger 7 to reciprocate, causing the diaphragm 5 to deform in different states, thereby achieving continuous suction and discharge of liquid (for ease of understanding, the first one-way valve 1, the second one-way valve 2 and the diaphragm assembly are introduced separately);

[0102] (6) Second one-way valve 2: arranged on the side away from the central circular hole of diaphragm cavity B 30, controlling the liquid to be smoothly discharged from diaphragm cavity 6, and a second sealing member 4 is arranged on the side of the second one-way valve 2 close to diaphragm cavity 6 to prevent liquid leakage or backflow; when liquid flows in, the first one-way valve 1 opens and the second one-way valve 2 closes; when liquid is discharged, the second one-way valve 2 opens and the first one-way valve 1 closes;

[0103] (7) Diaphragm cavity A 32: tightly connected with diaphragm cavity B 30 to form a complete star-shaped six-way groove, each of which accommodates the first one-way valve 1, the diaphragm assembly and the second one-way valve 2;

[0104] (8) Liquid outlet channel gasket 27: installed between the liquid outlet channel 26 and the diaphragm cavity B 30. The liquid outlet channel gasket 27 and the liquid outlet channel 26 are both provided with a circular hole channel of the same size that is connected to the diaphragm cavity B 30, so that the liquid can only flow along the diaphragm cavity B 30 to the liquid outlet channel 26, thereby preventing the backflow and leakage of the liquid and achieving sealing. At the same time, it can also help maintain the pressure in the system, prevent the entry of external impurities, reduce the wear between the liquid outlet channel 26 and the diaphragm cavity B 30, and make the installation and removal of the liquid outlet channel 26 more convenient;

[0105] (9) Liquid outlet channel 26: one side is provided with a receiving groove for receiving the liquid inlet pipeline 34 of the liquid inlet component 28, and the other side is tightly connected with the liquid outlet component sealing gasket 25, and is provided with a circular hole channel of the same size connected with the liquid outlet channel gasket 27 and a star-shaped six-way groove connected with the circular hole channel, so that the liquid converges from the edge circular hole along the groove to the central through hole, flows through the liquid outlet component sealing gasket 25, and finally flows out from the liquid outlet component 24;

[0106] (10) Liquid outlet component sealing gasket 25: installed between the liquid outlet component 24 and the liquid outlet channel 26. The central through holes of the three structures are of the same size, and the star-shaped six-way groove of the liquid outlet component sealing gasket 25 is of the same size and shape as the star-shaped six-way groove on the side that directly contacts the liquid outlet channel 26. It is used to fill the tiny gap between the contact surfaces of the liquid outlet component 24 and the liquid outlet channel 26, thereby preventing liquid from leaking from the connection between the liquid outlet component 24 and the liquid outlet channel 26 and achieving sealing; and the liquid can only flow in from the central through hole to avoid backflow of the liquid and escape to the six grooves; at the same time, it can also help maintain the pressure in the system, prevent external impurities from entering, reduce the wear between the liquid outlet component and the liquid outlet channel 26, and make the installation and removal of the liquid outlet component 24 more convenient;

[0107] (11) Liquid outlet component 24: comprising a liquid discharge pipe 35, one end of which is connected to the chromatographic column, and the other end is tightly connected to the liquid outlet component sealing gasket 25 to ensure smooth discharge of the liquid;

[0108] (12) Coaxial linkage assembly 14: The six diaphragm assemblies are connected together in a star-shaped six-way parallel manner, so that the six diaphragm assemblies are in different working states respectively, so that the diaphragm assembly is sucking and discharging liquid at every moment. At the same time, compared with a single diaphragm assembly, the pressure fluctuation is significantly reduced, the balance and stability are played, and the vibration and noise of the pump during operation are reduced; it is also easy to carry out maintenance and increase the service life of the pump;

[0109] (13) Motor and motor bracket 15: The motor is used to provide power to drive the coaxial linkage assembly 14 to move, thereby driving the reciprocating motion of the plungers 7 in the six diaphragm assemblies to achieve the suction and discharge of liquid; the motor bracket is used to fix, support and protect the motor.

[0110] Compared with the existing plunger pump, the present invention provides a new diaphragm pump head structure, including a double diaphragm assembly in series and a structure of 6 diaphragm assemblies in star parallel. On the one hand, in the diaphragm pump head structure provided by the present invention, the plunger in the diaphragm assembly is not in direct contact with the liquid (mobile phase), but the automatic suction and discharge of the liquid is achieved by the deformation of the diaphragm, while maintaining the performance of the liquid phase pump, avoiding the wear of the plunger and the plunger stem and leakage, thereby reducing the equipment maintenance cost; on the other hand, compared with the traditional plunger pump, the pressure fluctuation of the present invention is significantly reduced when the liquid is pumped reciprocatingly; at the same time, in the parallel structure, due to the small capacity of a single diaphragm cavity, the pump can achieve precise control of small flow rate changes, and the parallel connection of 6 cavities makes the overall output of the pump not inferior to that of a plunger pump with a large cavity capacity, so that the pump has a wider controllable flow rate range, so that the diaphragm pump head structure of the present invention achieves a better balance between small flow rate control accuracy and pump output.

[0111] Example 2 A liquid chromatograph provided by the present invention having a new diaphragm pump head structure

[0112] The present embodiment provides a liquid chromatograph having a brand-new diaphragm pump head structure, specifically as follows Fig.10 As shown, from Fig.10 It can be seen that the liquid chromatograph containing the new diaphragm pump head structure includes: a solvent tray 42, a binary pump 36, an automatic sampler 37, a column oven 38 and a detector 39. The binary pump 36 is composed of two pump heads, and the outlet of the binary pump 36 is connected to the inlet of the automatic sampler 37 through a pipeline so as to transport the mobile phase to the automatic sampler 37. The automatic sampler 37 is responsible for automatically injecting the sample into the chromatographic column. The inlet of the automatic sampler 37 is connected to the outlet of the binary pump 36 through a pipeline so as to receive the mobile phase; the outlet of the automatic sampler 37 is connected to the inlet of the chromatographic column through a pipeline so as to inject the sample into the chromatographic column. The column oven 38 is responsible for controlling the temperature of the chromatographic column, and the inlet and outlet of the column oven 38 are usually connected to the inlet and outlet of the chromatographic column through a pipeline so as to put the chromatographic column into the column oven 38 for temperature control. The detector 39 is responsible for detecting the separation of the sample in the chromatographic column. The inlet of the detector 39 is connected to the outlet of the chromatographic column through a pipeline to receive the separated sample. The outlet of the detector 39 is usually connected to the waste liquid bottle through a pipeline to discharge the waste liquid.

[0113] The binary pump 36 includes two pump heads, each of which includes a diaphragm pump composed of a series of double diaphragm assemblies as described in Example 1 or a diaphragm pump composed of six diaphragm assemblies connected in star parallel. The specific structure is as described in Example 1. The flow path process of the binary pump 36 when working is as follows: Fig.11 As shown, specifically: the four mobile phases A1, A2, B1, and B2 flow in from the four inlets (oval) in the solvent selection valve ① device, and there is an electromagnetic valve inside to switch the flow path, ensuring that one of A1 and A2 flows out from the upper outlet (circular), and one of B1 and B2 flows out from the lower outlet (circular). After the solution is degassed by the vacuum degasser ②, it enters the diaphragm pump heads ③ and ④ respectively. After leaving the two diaphragm pump heads, it enters the electromagnetic discharge valve ⑤ through two inlets (oval). The electromagnetic valve controls the flow path in the electromagnetic discharge valve ⑤ to flow out from the upper outlet (circular) into the waste liquid, or flow out from the lower outlet (circular) and enter the mixer ⑥. After the two liquids are fully mixed inside the mixer, they are output to the automatic sampler 37.

[0114] In liquid chromatographs, in addition to binary pumps, quaternary pumps are also commonly used pump types. Binary pumps and quaternary pumps have certain similarities in structure and function, and both have the important task of transporting mobile phases. They both require precise control of the transport of mobile phases to meet the requirements of liquid chromatography analysis. In addition, the diaphragm pump head structure of the present invention has a significant optimization effect on both.

[0115] The quaternary pump includes two pump heads, each of which also includes a diaphragm pump composed of a series of double diaphragm assemblies as described in Example 1 or a diaphragm pump composed of six diaphragm assemblies connected in star parallel. The specific structure is as described in Example 1. The flow path process of the quaternary pump when working is as follows Fig.12 As shown, specifically: the four mobile phases A, B, C, and D are degassed by the vacuum degasser ① device and enter the four inlets of the electromagnetic proportional valve ② respectively. The electromagnetic proportional valve determines the composition ratio of the four items A, B, C, and D in the outlet solution. After flowing out from the middle outlet (circular), they enter the diaphragm pump heads ③ and ④ in turn. The two diaphragm pump heads belong to a series structure. After leaving the diaphragm pump head ④, it enters the ⑤ six-way valve. The six-way valve can switch different flow path conduction states to allow the liquid to flow out from one of the two outlets as needed, one of which leads to the automatic sampler and the other to the waste liquid.

[0116] The advantages of installing the new diaphragm pump head structure of the present invention in the liquid chromatograph are: on the one hand, it can better maintain the balance of system pressure, significantly reduce pressure fluctuations in the system, reduce the impact of pressure fluctuations on analysis results, and improve the accuracy of detection results; on the other hand, it helps to achieve precise control of small flow rate changes, and also makes the pump controllable flow rate range wider, so that the diaphragm pump head structure of the present invention achieves a better balance between accuracy and pump output; at the same time, the plunger sealing ring structure in the pump head is not in direct contact with the mobile phase, avoiding common fault problems such as sealing ring aging and plunger rod wear, thereby reducing the cost of use and maintenance; and using multiple diaphragm assemblies to work in coordination can significantly speed up the solvent delivery speed, thereby improving analysis efficiency; at the same time, under the parallel structure, even if individual diaphragm assemblies fail, other diaphragm assemblies can still work normally, significantly reducing the risk of system downtime; and the new diaphragm pump head structure designed by the present invention, through a distributed working mode, effectively reduces the workload of a single diaphragm assembly, thereby effectively extending the overall service life of the pump head.

[0117] Example 3 Structural optimization of a new diaphragm pump head provided by the present invention

[0118] Traditional reciprocating piston pumps have the following defects: (1) Long-term direct contact between the piston rod and the sealing ring with the mobile phase causes the piston rod or the sealing ring to wear, resulting in piston pump failure; (2) It is impossible to balance the flow rate control accuracy and pump output at low flow rates; (3) When the piston reciprocates to pump the liquid, obvious pressure fluctuations are generated, thereby reducing the accuracy of the final test results.

[0119] The plunger reciprocating pump is the most widely used constant flow pump in liquid chromatographs. It has a simple structure and is cheap. The moving distance of the piston is variable, and the flow rate is determined by the moving distance of the piston. Because the eccentric wheel generally rotates 50-60 times per minute, that is, the pumping and discharging of the mobile phase changes periodically at a frequency of 50-60 times per minute, the pulses generated are very significant. Compared with the plunger pump, the piston of the diaphragm pump does not directly contact the mobile phase, so there is no contamination of the mobile phase by the wear of the piston seal. In addition, the dead volume of the diaphragm pump is small, so the balance is fast after changing the mobile phase, which is conducive to gradient elution. However, the basic structure of its drive is similar to that of the plunger reciprocating pump, so it will also produce obvious pulses. Only because of the deformation characteristics of the diaphragm and the compressibility of the transmission liquid, the pressure fluctuation during operation is slightly improved.

[0120] Therefore, in this embodiment, multiple pump units are combined to smooth the pressure fluctuation during operation. Compared with the double-unit series connection, the multiple pump units in parallel can provide better pressure fluctuation performance. Fig.13 As shown, Fig.13In the figure, the black line is the pressure fluctuation diagram of a single plunger pump, with an amplitude of 250~350 psi; the blue line is the pressure fluctuation diagram of a single diaphragm pump, with an amplitude of 250~300 psi; the yellow line is the pressure fluctuation diagram of two diaphragm pumps connected in series, with an amplitude reduced to 80~150psi; the green line is the pressure fluctuation diagram of a star-parallel connection, with a higher amplitude frequency than the series connection, but its amplitude is reduced to 50~100 psi.

[0121] Therefore, in order to successfully solve the above problems and improve the detection performance of the liquid chromatograph, a new diaphragm pump head is designed in the present invention. The diaphragm pump head includes a diaphragm pump composed of double diaphragm components connected in series and a diaphragm pump composed of 6 diaphragm components connected in star parallel. The specific optimization process is as follows:

[0122] 1. Optimization of the structure of a single diaphragm assembly

[0123] In this embodiment, the traditional plunger pump structure is optimized, and the pump head is designed to be a hydraulic diaphragm pump structure. In the hydraulic diaphragm pump structure, a new diaphragm assembly is designed: the diaphragm assembly is divided into a diaphragm cavity and a plunger cavity, a diaphragm is arranged in the diaphragm cavity, and the diaphragm is an elastic composite film with wide pH tolerance (pH1~14), salt resistance and organic reagent resistance; there are two spherical one-way valves on the left side of the diaphragm, which can control the mobile phase to be sucked in only from the bottom, and then discharged from the top after entering the diaphragm cavity; the right side of the diaphragm is a liquid pressure mass transfer medium, and a plunger is arranged on the right side of the liquid pressure mass transfer medium. The reciprocating motion of the plunger in the plunger cavity causes the pressure of the pressure mass transfer medium on the diaphragm to change, driving the deformation of the diaphragm to generate liquid flow, thereby realizing automatic suction and discharge of liquid.

[0124] In the structural design, direct contact between the mobile phase and the plunger is avoided, thereby avoiding plunger wear and leakage caused by plunger wear, and greatly reducing the maintenance cost of the instrument.

[0125] 2. Double diaphragm assembly series structure

[0126] 1. Optimization of the series structure of double diaphragm components

[0127] In this embodiment, on the basis of a single diaphragm assembly structure, a double diaphragm assembly series design is adopted to obtain a new diaphragm pump head, and the number of diaphragm assemblies in series is compared and screened. In the diaphragm pump head obtained by the double diaphragm assembly series design, the diaphragm cavity volume of the first diaphragm assembly is designed to be twice the diaphragm cavity volume of the second diaphragm assembly, that is, the volume pumped by the plunger of the first diaphragm assembly in one cycle is twice that of the second diaphragm assembly, thereby ensuring that the liquid output can still be maintained when the second diaphragm assembly is in the liquid suction cycle, greatly reducing the large pressure fluctuation caused by the continuous switching of "liquid suction-liquid discharge".

[0128] This is because the chromatographic column is connected to the liquid outlet. When the second diaphragm assembly pumps liquid to the outlet, it is blocked by the particles in the chromatographic column, generating back pressure, causing the pressure to rise. If the two diaphragm assemblies deliver the same volume of liquid, when the second diaphragm assembly completes the liquid absorption and is ready to start pumping liquid outward, the first diaphragm assembly just discharges the liquid in the diaphragm cavity. Then the two diaphragm assemblies start their respective movements. The first diaphragm assembly begins to absorb liquid from the container. This process does not produce pressure effects on the outside. The second diaphragm assembly pumps liquid outward. Due to the presence of the one-way valve, the liquid can only flow out from the flow path outlet and will not flow back to the first diaphragm assembly. As the liquid flows to the rear end, the pressure gradually rises until the liquid in the second diaphragm assembly is completely discharged from the diaphragm cavity. The first diaphragm assembly completes the liquid absorption. Due to the series structure, it begins to deliver liquid to the second diaphragm assembly. When the second diaphragm assembly begins the process of absorbing liquid, since the second diaphragm assembly does not output any liquid during the liquid absorption process, the pressure at the rear end will continue to fall until the liquid absorption process is completed and returns to the initial state. As a result, the liquid cannot be effectively replenished during the absorption and discharge process of the two diaphragm components, resulting in a lack of sufficient buffering and transition during the switching process, causing large fluctuations in pressure changes, which will also cause instability in flow and pressure.

[0129] On the other hand, when the volumes of the two diaphragm cavities are constant and the same, the diaphragm cavities will frequently become empty and full. The pressures applied to the diaphragm cavities in the empty and full states are completely different. When the cavity changes rapidly from full to empty or from empty to full, the pressure on the diaphragm will change rapidly (the variable stress on the diaphragm will increase). Moreover, when the instrument is working for a long time, the pressure changes rapidly frequently, which significantly increases the frequency with which the diaphragm is subjected to variable stress. Over a long period of time, this may lead to fatigue damage or breakdown of the diaphragm, which is not conducive to the maintenance and service life of the instrument.

[0130] When the volume of the diaphragm cavity of the first diaphragm assembly is twice that of the second diaphragm assembly, the first diaphragm assembly is still discharging liquid when the second diaphragm assembly is in the liquid suction cycle. And because the volume of the diaphragm cavity of the first diaphragm assembly is large, it can provide sufficient liquid output to maintain the stable flow of the system, thereby reducing pressure fluctuations. At the same time, half of the liquid is sucked into the diaphragm cavity by the second diaphragm assembly and stored in the diaphragm cavity, and the part that exceeds the capacity of the second diaphragm assembly will flow out directly from the outlet, so that the rear end maintains a higher pressure level. That is, the second diaphragm assembly can continuously output liquid to the rear end regardless of whether it is in the process of suction or discharge, thereby significantly reducing pressure fluctuations. And when the volume of the diaphragm cavity of the first diaphragm assembly is twice that of the second diaphragm assembly, the frequency of "suction-discharge" switching can also be reduced, further reducing pressure fluctuations. It is conducive to achieving smoother liquid delivery, improving the performance and stability of the system, and at the same time, it can also extend the service life of the instrument and reduce maintenance costs.

[0131] The advantages of the double diaphragm assembly in series of the present invention are further compared and explained below:

[0132] (1) Advantages of double diaphragm components in series compared to traditional plunger pumps:

[0133] Two diaphragm assemblies are connected in series, and the reciprocating motion of the plunger is controlled by a coaxial drive assembly to achieve automatic suction and discharge of liquid. Compared with traditional plunger pumps, it has more stable mobile phase delivery performance, can effectively reduce pressure fluctuations and flow fluctuations, and improve the accuracy and repeatability of analysis; at the same time, the flexibility of the diaphragm makes the pump run more smoothly, greatly reduces noise and mechanical wear, and extends the service life of the equipment.

[0134] (2) Advantages of double diaphragm components in series compared to single diaphragm components:

[0135] When a diaphragm pump head is constructed using a single diaphragm assembly, although basic fluid delivery can be achieved, its pressure stability is poor. When a single diaphragm assembly is working, its pressure output is not uniform and stable enough, and large pressure fluctuations are prone to occur, thus affecting the accuracy and reliability of liquid delivery; secondly, a single diaphragm assembly is difficult to accurately control and adjust the flow rate, which may cause large fluctuations in the flow rate, and therefore cannot meet some application scenarios with high requirements for flow accuracy, such as differential refractive index detectors, whose baseline is easily affected by pressure fluctuations and drifts, affecting quantitative accuracy. Therefore, in this embodiment, it is preferred to construct a diaphragm pump in series with two diaphragm assemblies, which can significantly reduce pressure fluctuations during use, while also improving the flow control accuracy and significantly improving the accuracy and reliability of the test results.

[0136] (3) Advantages of double diaphragm assemblies in series compared to multiple diaphragm assemblies in series:

[0137] When three or more diaphragm assemblies are used in series to build a diaphragm pump, on the one hand, the manufacturing cost of the pump will increase significantly, including the cost of the diaphragm assembly itself and the cost of assembly and maintenance; at the same time, the complexity of the pump structure is increased, thereby increasing the difficulty of troubleshooting and repair. Multiple diaphragm assemblies in series require higher coordination and cooperation during operation, so there may be asynchrony or mutual interference, affecting the stable performance of the pump; at the same time, due to overly complex structures and coordination problems, the overall efficiency may be inferior to that of double diaphragm assemblies in series, such as a decrease in response speed, energy utilization efficiency, etc.; and when multiple diaphragm assemblies are used in series, more space will be occupied, which is not suitable for application scenarios with space restrictions. In contrast, the structure of two diaphragm assemblies in series achieves a better balance between performance and cost, can meet most application requirements, and has higher reliability and practicality.

[0138] Therefore, in this embodiment, it is preferred to construct a diaphragm pump by connecting double diaphragm components in series.

[0139] 3. Multi-diaphragm assembly parallel structure

[0140] 1. Optimization of parallel structure of multi-diaphragm components

[0141] In this embodiment, on the basis of a single diaphragm assembly structure, a single diaphragm cavity is miniaturized, wherein the volume of each diaphragm cavity is 100μL ~ 1000μL, and a star-shaped six-way parallel structure is adopted, and a single set of motors is used to drive 6 groups of diaphragm assemblies. Since the capacity of a single diaphragm assembly is small, the pump can achieve precise control of small flow rate changes; at the same time, the 6 diaphragm assemblies are connected in parallel, so that the overall output of the pump after the motor rotates one circle is not inferior to that of a plunger pump with a large cavity capacity, so that the pump has a wide controllable flow rate range. And because the 6 diaphragm assemblies are in different working states, the pressure fluctuation generated by one stroke of the plunger will be significantly reduced compared with the traditional plunger reciprocating pump.

[0142] Fig.14 It is a result diagram of the pressure fluctuation ratio of the total output flow path using the traditional plunger reciprocating pump and the star-shaped parallel structure of the six diaphragm assemblies of the present invention, wherein the black line is the pressure change diagram when the traditional plunger reciprocating pump outputs liquid; the pressure fluctuation on the total flow path after the six diaphragm assemblies are connected in parallel is the superposition of the states of the six colored curves; Fig.15 This is a simulation result of the pressure fluctuation using a traditional piston reciprocating pump and the star-shaped parallel structure of six diaphragm assemblies of the present invention. The orange color represents the pressure fluctuation output by the traditional piston reciprocating pump, and the blue color represents the pressure fluctuation output by the star-shaped parallel structure of six diaphragm assemblies. Fig.14 and Fig.15 It can be seen that compared with the traditional plunger reciprocating pump with a single plunger, the present invention uses 6 diaphragm assemblies connected in a star-parallel manner to achieve that 3 units output liquid to the outside at every moment. There is no period when the pressure drops significantly during the suction process when there is a single diaphragm assembly, so the pressure fluctuation will be significantly reduced.

[0143] The advantages of the double diaphragm assembly in series of the present invention are further compared and explained below:

[0144] (1) The advantages of a diaphragm pump head composed of six diaphragm components connected in star parallel compared to traditional plunger pumps are:

[0145] Six diaphragm assemblies are connected in star parallel to miniaturize a single diaphragm cavity, and the reciprocating motion of the plunger is controlled by a coaxial drive assembly to achieve automatic suction and discharge of the liquid. Compared with traditional plunger pumps, it has more stable mobile phase delivery performance, can effectively reduce pressure fluctuations and flow fluctuations, and improve the accuracy and repeatability of analysis; at the same time, due to the small capacity of a single diaphragm chamber, the pump can achieve precise control of small flow rate changes, and the simultaneous operation of six diaphragm assemblies can provide a larger flow rate, so that the pump has a wider controllable flow rate range, thereby achieving a better balance between accuracy and output; at the same time, when one of the diaphragm assemblies fails, the other diaphragm assemblies can continue to work, which improves the reliability of the pump; and it has a wide range of applications, and can also handle some corrosive, viscous or particle-containing media well.

[0146] Therefore, in this embodiment, it is preferred that the diaphragm pump is constructed by connecting six diaphragm assemblies in star parallel.

[0147] (2) Advantages of six diaphragm assemblies in star parallel connection compared to the double diaphragm assembly series structure:

[0148] Compared with the diaphragm pump constructed with a double diaphragm assembly in series, the star-parallel structure of six diaphragm assemblies has better performance. On the one hand, the star-parallel structure of six diaphragm assemblies can provide a larger flow rate, while the double diaphragm assembly in series may be relatively limited in flow output; on the other hand, the star-parallel structure of six diaphragm assemblies can better disperse pressure fluctuations, making the pressure more uniform and stable, and achieving a better balance between the accuracy and output of the pump; at the same time, the star-parallel structure of six diaphragm assemblies has higher reliability, and the failure of a single diaphragm assembly has less impact on the whole, and the reliability is higher, while a problem with one diaphragm assembly in the double diaphragm assembly in series may have a more obvious impact on the entire system.

[0149] Therefore, in this embodiment, it is preferred that the diaphragm pump is constructed by connecting six diaphragm assemblies in star parallel.

[0150] (3) Selection of the number of diaphragm components in the star-type parallel structure of 6 diaphragm components

[0151] ① When fewer diaphragm assemblies are used to form a star-shaped parallel structure (such as 2-5), on the one hand, due to the reduction in the number of diaphragm assemblies, the overall output flow may not be as large as when 6 diaphragm assemblies are connected in parallel; on the other hand, the effect of maintaining pressure stability is not as ideal as when 6 diaphragm assemblies are used, and more obvious pressure fluctuations will occur. This may be because when the number of diaphragm assemblies is small, such as 2-5, its ability to share and adjust pressure during operation is relatively weak. During the fluid transportation process, due to pressure fluctuations caused by various factors (such as changes in inlet pressure, changes in fluid properties, etc.), fewer diaphragm assemblies may be difficult to coordinate and balance in a timely and sufficient manner, resulting in relatively obvious pressure fluctuations; while 6 diaphragm assemblies can provide more pressure adjustment points and a wider pressure distribution, can better cooperate and complement each other, and respond more quickly and finely to pressure changes, thereby performing better in maintaining pressure stability.

[0152] ② When more (more than 6) diaphragm assemblies are used to form a star-type parallel structure, on the one hand, too many diaphragm assemblies will make the overall structure extremely complicated, increasing the difficulty and cost of manufacturing, installation and maintenance; on the other hand, to ensure that a larger number of diaphragm assemblies work synchronously and coordinately, higher requirements are placed on the control system, which is prone to asynchrony or coordination problems; at the same time, when more diaphragm assemblies are used, a larger installation space is required, which may be difficult to use in some space-constrained environments.

[0153] Therefore, in this embodiment, it is preferred that the diaphragm pump is constructed by connecting six diaphragm assemblies in star parallel.

[0154] (4) Selection of parallel connection method in the star-type parallel structure of 6 diaphragm components

[0155] In the present invention, the parallel connection methods are also screened, and it is found that compared with other parallel connection methods, such as linear parallel connection, ring parallel connection, etc., on the one hand, the star parallel connection has better pressure balance, each branch can share the pressure more evenly, the pressure distribution is more balanced, and the pressure fluctuation and local pressure that is too high or too low can be reduced more effectively; on the other hand, the star parallel connection method can more flexibly adjust the flow distribution of each branch according to demand, so as to better adapt to the flow requirements under different working conditions; at the same time, the collaborative working effect between the branches is better, and the overall performance can be exerted more efficiently.

[0156] Therefore, in this embodiment, it is preferred that the diaphragm pump is constructed by connecting six diaphragm assemblies in star parallel.

[0157] Example 4 A new diaphragm pump head provided by the present invention significantly improves detection sensitivity, accuracy and precision

[0158] In liquid chromatography analysis, insufficient separation leading to partial overlap of chromatographic peaks is a common problem, which manifests itself as two or more adjacent chromatographic peaks not being completely separated and having some overlapping areas. Its direct impact is that it is difficult to accurately determine the peak area and concentration of each component, resulting in inaccurate quantitative analysis results. At the same time, it will also affect qualitative analysis, making it difficult to determine the specific components in the mixture.

[0159] For example, sulfamethoxazole (left) and sulfamethoxazole (right) are a pair of isomers, and the only difference between the two is the methoxyl group connection site (the specific structures of the two are as follows Fig.16 As shown, the left picture is sulfamethoxazole and the right picture is sulfamethoxazole), so the mass spectrometry conditions of the two are exactly the same, and separation can only be carried out on liquid chromatography based on different polarities.

[0160] Table 1. Mass spectrometry parameters of sulfamethoxazole and sulfamethoxazole

[0161]

[0162] Therefore, in order to test the detection sensitivity, accuracy and precision of a new diaphragm pump head provided by the present invention, sulfamethoxazole and sulfamethoxazole are used in this embodiment, and comparative tests are carried out using a traditional plunger reciprocating pump and a single diaphragm pump of the present invention, a diaphragm pump head of the present invention in series, and a diaphragm pump head of the present invention in star parallel. By comparing the peak areas, recoveries and relative standard deviations (RSDs) of compounds Peak 1 and Peak 2, the instrument response signal, the accuracy of measuring the compound content in the sample, and the repeatability of the analytical method are evaluated, and the detection sensitivity, accuracy and precision are further evaluated.

[0163] The liquid phase conditions used in this experiment are as follows:

[0164] Mobile phase A: water (containing 0.1% formic acid and 2 mmol / L ammonium acetate);

[0165] Mobile phase B: methanol (containing 0.1% formic acid and 2mmol / L ammonium acetate);

[0166] The chromatographic column was Durashell C18 2.1*150mm; 3μm; 150A, and the injection volume was 10 μL;

[0167] The liquid phase gradient conditions are shown in Table 2:

[0168] Table 2. Liquid phase gradient conditions

[0169]

[0170] When conducting liquid chromatography analysis, the conventional plunger binary pump was compared with the single diaphragm pump of the present invention, the diaphragm pump head of the present invention in series connection, and the diaphragm pump head of the present invention in star parallel connection. The same gradient separation method was run on the conventional plunger binary pump, the single diaphragm pump of the present invention, the diaphragm pump head of the present invention in series connection, and the diaphragm pump head of the present invention in star parallel connection, and the test calculation results are specifically shown in Table 3 (detection recovery and precision results). The test results of the conventional plunger binary pump and the single diaphragm pump of the present invention are shown in Table 3. Fig.17 As shown, the upper figure is the result of the traditional plunger binary pump, and the lower figure is the result of the single diaphragm pump of the present invention. Fig.17 It can be seen that Peak 1 and Peak 2 cannot reach the level of baseline separation on the traditional plunger binary pump, while on the single diaphragm pump, although the separation degree is not significantly improved, baseline separation is basically achieved.

[0171] Table 3. Test results of the recovery rate of compounds under the conventional plunger pump and different diaphragm pumps of the present invention

[0172] From Table 3, we can get the following results:

[0173]

[0174] 1. From the perspective of test result accuracy (i.e. peak area measurement error):

[0175] 1. Traditional plunger pump: The chromatographic peaks are not completely separated, and the recovery rate in the sample has exceeded the conventional allowable range of 60% to 120%. At this time, parts of the adjacent peaks overlap with each other, making it difficult to accurately determine the start and end points of each peak, resulting in errors in the measurement of peak area. For example, Fig.17 As shown in the figure, two partially overlapping peaks may be mistaken for a larger single peak, or during the integration process, the peak area calculation may be too large or too small due to the existence of the overlapping area. This inaccurate peak area measurement will directly affect the results of quantitative analysis, because in liquid chromatography quantification, the content of each component in the sample is usually determined based on the relationship between peak area and concentration. If the peak area measurement is inaccurate, the accuracy of the quantitative result will be greatly reduced. When the standard sample contains both Peak 1 and Peak 2, then Fig.17 The peak areas of the two compounds in the conventional plunger binary pump in the middle and upper part will be larger due to partial overlap. Fig.17 The single diaphragm pump of the present invention in the middle and lower part is smaller, according to the calculation formula:

[0176]

[0177] Where A is the peak area of ​​the compound in the sample, and As is the peak area of ​​the compound in the standard. When As is too small due to peak overlap, the measured content of the compound in the sample will be too large, resulting in unqualified sample recovery test results in this experiment.

[0178] 2. Single diaphragm pump of the present invention: When the liquid chromatography system adopts the single diaphragm pump of the present invention, baseline separation is basically achieved, so that the recovery rate meets the conventional detection standard. This may be because when the single diaphragm pump of the present invention is adopted, the pressure fluctuation is slightly improved, thereby improving the liquid phase separation effect and the recovery rate reaches the qualified standard. However, since the pressure fluctuation has not been significantly improved, the recovery rate still does not reach the ideal result, making the detection result not accurate.

[0179] 3. The serial diaphragm pump head and the star-type parallel diaphragm pump head of the present invention: When the liquid chromatography system adopts the serial diaphragm pump head and the star-type parallel diaphragm pump head of the present invention, the accuracy of the pump infusion volume is significantly improved and the pressure fluctuation is significantly reduced, thereby significantly improving the liquid phase separation effect and the recovery rate results, thereby achieving more accurate quantitative analysis results.

[0180] 2. From the perspective of the precision of the test results (i.e. repeatability results: RSD):

[0181] 1. Traditional plunger pump: When the liquid chromatography system uses a traditional plunger pump, the baseline cannot be separated, resulting in poor precision of the compound. This may be because when baseline separation cannot be achieved, the chromatogram obtained from each analysis will be different, especially when the overlapping area is large. This will lead to poor repeatability, that is, the results of multiple analyses of the same sample will vary greatly. For example, in different analysis batches, due to the instability of separation, the measured value of the peak area may fluctuate greatly, thus affecting the precision of the quantitative analysis. The decrease in precision will reduce the reliability of the analysis results and make it difficult to meet quality control and research requirements.

[0182] Table 3 shows the RSD (relative standard deviation) of the results of 10 repeated injections of the same sample under the same analytical conditions using four systems (conventional plunger pump, single diaphragm pump of the present invention, serial diaphragm pump head of the present invention, and star-type parallel diaphragm pump head). Since single samples are generally not tested repeatedly in actual use, poor precision will lead to a high probability that a single measurement result is too high or too low, affecting the accuracy of the results.

[0183] 2. Single diaphragm pump of the present invention: When the liquid chromatography system adopts the single diaphragm pump of the present invention, baseline separation is basically achieved, so that the detection precision is improved. This may be because when the single diaphragm pump of the present invention is adopted, the pressure fluctuation is slightly improved, thereby improving the liquid phase separation effect, reducing the fluctuation of the measured value of the peak area, and thus improving the precision. However, since the pressure fluctuation has not been significantly improved, the RSD result is still large.

[0184] 3. The serial diaphragm pump head and the star-parallel diaphragm pump head of the present invention: When the liquid chromatography system adopts the serial diaphragm pump head and the star-parallel diaphragm pump head of the present invention, the accuracy of the pump infusion volume is significantly improved and the pressure fluctuation is significantly reduced, so that the liquid phase separation effect is significantly improved and the RSD results are also significantly reduced.

[0185] 3. From the perspective of the impact of interfering substances

[0186] Incompletely separated peaks may contain other interfering substances, which will be measured together with the target component, resulting in a high quantitative result. For example, in drug analysis, if the peak of the active ingredient is not completely separated from the impurity peak, then when quantifying the active ingredient, the presence of impurities will cause the measurement result to be high, thus affecting the accurate judgment of the drug purity.

[0187] 4. From the perspective of impaired method reliability (limited linear range)

[0188] Failure to achieve baseline separation affects the linear range of the quantitative method. In the case of partial overlap, the degree of peak overlap may change as the concentration changes, thereby destroying the linear relationship between peak area and concentration. For example, at low concentrations, the peak overlap may not be obvious, but as the concentration increases, the overlapping area increases, causing a deviation from the linear relationship. A limited linear range will narrow the scope of application of the quantitative method, and it may not be possible to accurately perform quantitative analysis for samples with large concentration changes.

[0189] Therefore, it can be seen that when establishing a liquid chromatography quantitative method, method validation is required to ensure that the accuracy, precision, linearity and other performance of the method meet the requirements. If baseline separation cannot be achieved or the baseline separation effect is poor, method validation will become difficult because insufficient separation will affect multiple validation indicators. For example, in accuracy validation, due to the error in peak area measurement, the quantitative results may not meet the accuracy requirements; in precision validation, repeatability and reproducibility may not meet the standards due to separation issues. Failure of method validation will question the reliability of the quantitative method and cannot be used for the analysis of actual samples. After adopting the series diaphragm pump or parallel diaphragm pump of the present invention, the detection performance is significantly improved, thereby significantly improving the separation effect of the compound, greatly reducing various problems caused by separation, and improving the accuracy and efficiency of the analysis work.

[0190] In summary, it can be seen that: (1) The serial diaphragm pump head and parallel diaphragm pump head structures of the present invention have significant advantages in separation performance, and the advantages of the parallel diaphragm pump head structure are more significant: in liquid chromatography analysis, the traditional plunger binary pump has the problem of insufficient separation, resulting in Peak 1 and Peak 2 being unable to achieve baseline separation, while the serial and star-type parallel diaphragm pump heads of the present invention can achieve better separation effects, significantly improving the detection results. This good separation performance is due to the fact that the serial diaphragm pump and parallel diaphragm pump of the present invention both have more stable mobile phase delivery performance, which can effectively reduce pressure fluctuations and flow fluctuations, thereby making the separation of compounds in the chromatographic column more complete, providing a basis for accurate quantitative and qualitative analysis; and the parallel diaphragm pump of the present invention has the best accuracy, sensitivity and reliability in the detection results. (2) The serial diaphragm pump head and parallel diaphragm pump head structures of the present invention significantly improve the detection sensitivity: By comparing the peak areas of compound Peak 1 and Peak 2 under different pump heads, it can be seen that the serial diaphragm pump head and parallel diaphragm pump head structures of the present invention can make the peak area of ​​the compound larger and more stable. The larger and more stable the peak area, the higher the detection sensitivity of the instrument to the compound. This is because stable mobile phase delivery can ensure better retention and separation of the compound in the chromatographic column, thereby improving the detection sensitivity. (3) The serial diaphragm pump head and parallel diaphragm pump head structures of the present invention significantly improve the detection accuracy: ① Recovery rate: From the recovery rate data, the recovery rate of the compound under the traditional plunger pump exceeds the conventional range, while under the diaphragm pump head structure of the present invention, whether it is a diaphragm binary pump or a serial and star-type parallel diaphragm pump head, the recovery rate of the compound is closer to the true value and within a reasonable range, and the advantages of the serial and parallel diaphragm pump head structures are more significant. This shows that the diaphragm pump head structure of the present invention can more accurately measure the content of compounds in the sample and improve the detection accuracy; ② Interference substances: Due to insufficient separation, the traditional plunger pump may cause the incompletely separated peaks to contain interference substances, thereby making the quantitative results biased high. The diaphragm pump head structure of the present invention can achieve better separation, reduce the influence of interference substances on the quantitative results, and further improve the detection accuracy. (4) The serial and parallel diaphragm pump head structures of the present invention significantly improve the detection precision: By repeatedly injecting the same sample with different pump heads under the same conditions and calculating the RSD, it can be seen that the RSD value of the traditional plunger pump is large, indicating that its repeatability is poor and the precision is low. Under the diaphragm pump head structure of the present invention, whether it is a diaphragm binary pump or a serial and star-parallel diaphragm pump head, the RSD value is small, indicating that it has good repeatability and high precision, and the RSD results under the serial and parallel diaphragm pump head structures are better. This is because the diaphragm pump head structure can effectively reduce pressure fluctuations and flow fluctuations, improve the repeatability of the analysis method, and thus improve the detection precision.(5) The serial and parallel diaphragm pump head structures of the present invention are superior to traditional plunger pumps in overall performance: Taking into account the detection sensitivity, accuracy and precision, the diaphragm pump head structures of the present invention show obvious advantages. Compared with traditional plunger pumps, the serial and parallel diaphragm pump head structures of the present invention can better meet the requirements of liquid chromatography analysis for instrument performance and provide a guarantee for high-quality analysis results. Therefore, the serial and parallel diaphragm pump heads of the present invention have important application value and broad application prospects in the field of liquid chromatography analysis.

[0191] In the description of the present invention, it should be understood that the terms "center", "lateral", "up", "down", "left", "right", "front", "back", "vertical", "horizontal", "top", "bottom", "inside", "outside" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present invention.

[0192] Although the present invention has been disclosed as above in the form of a preferred embodiment, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. A liquid chromatograph, characterized in that: It comprises a solvent tray, a pump body, an automatic sampler, a column oven and a detector, wherein the pump body comprises any one of a binary pump, a quaternary pump or a multi-element pump; the outlet of the pump body is connected to the inlet of the automatic sampler through a pipeline so as to deliver the mobile phase to the automatic sampler; the pump head of the pump body adopts a diaphragm pump head, and the diaphragm pump head comprises a parallel diaphragm pump composed of 6 diaphragm components connected in star parallel, wherein the parallel type adopts a star-shaped six-way parallel connection, and the star-shaped six-way parallel connection is that the 6 diaphragm components are radially distributed with the center point as the symmetry center; the diaphragm pump head comprises a diaphragm component and a coaxial linkage component; in the parallel diaphragm pump, the 6 diaphragm components are connected in parallel to form an integrated structure through the coaxial linkage component; The diaphragm assembly is used to prevent the plunger from contacting the mobile phase and realize automatic suction and discharge of liquid under low pressure fluctuations; The coaxial linkage assembly is used to connect different diaphragm assemblies so that the diaphragm assemblies move synchronously; The diaphragm assembly includes a first one-way valve, a second one-way valve, a sealing member, a diaphragm, a diaphragm cavity, a plunger, and a plunger cavity; the first one-way valve and the second one-way valve are arranged on one side of the diaphragm cavity; when the first one-way valve is turned on, the second one-way valve is closed; or when the second one-way valve is turned on, the first one-way valve is closed; the first one-way valve and the second one-way valve are used to prevent liquid leakage or backflow; The parallel diaphragm pump includes a liquid outlet component, a liquid outlet component sealing gasket, a liquid outlet channel, a liquid outlet channel gasket, a liquid inlet component, a liquid inlet component sealing gasket, a diaphragm cavity B, a housing fixing screw, a first one-way valve, a second one-way valve, a diaphragm cavity A, 6 diaphragm assemblies, and a coaxial linkage assembly; The liquid inlet component and the sealing gasket of the liquid inlet component are fixedly connected to the diaphragm cavity B; a circular hole channel for liquid to enter is set in the center of the liquid inlet component, which is fixedly connected to the liquid inlet pipeline; the sealing gasket of the liquid inlet component is provided with a star-shaped six-way groove, and the center of the star-shaped six-way groove is a circular hole channel for liquid to pass through, which is consistent with the size of the circular hole channel in the center of the liquid inlet component; the side of the diaphragm cavity B that directly contacts the sealing gasket of the liquid inlet component is provided with a star-shaped six-way groove consistent with the size of the sealing gasket of the liquid inlet component and a circular hole channel for liquid to pass through, and the circular hole channel is connected with the circular hole channel in the center of the sealing gasket of the liquid inlet component and is consistent in size; A circular hole channel is arranged along the center of the other side of the diaphragm cavity B, and a star-shaped six-way groove is arranged along the outside. A liquid flow channel is arranged between the circular hole channel in the center of the diaphragm cavity B and each of the grooves; the size and shape of each of the grooves are consistent with the first one-way valve, the second one-way valve and the first diaphragm assembly.

2. The liquid chromatograph according to claim 1, characterized in that A diaphragm is arranged in the middle of the diaphragm cavity. The diaphragm is an elastic composite film with wide pH tolerance, salt resistance and organic reagent resistance, and deforms with changes in pressure on both sides.

3. A parallel diaphragm pump for improving the accuracy, sensitivity or precision of liquid chromatograph detection, characterized in that: The parallel diaphragm pump is the parallel diaphragm pump in the liquid chromatograph according to any one of claims 1 to 2; the recovery rate of the compound measured by the liquid chromatograph is greater than ≥99.2%, and the RSD is ≤1.9%.

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