Probe pressing type chromatography sample injection structure

Abstract

The application discloses a probe pressing type chromatographic sample injection structure, which comprises a probe for injecting a sample into a chromatographic column, a sample chip for placing the sample, and a bearing support for placing the sample chip, at least one of the sample chip and the bearing support being elastic. The probe pressing type chromatographic sample injection structure is characterized in that at least one of the sample chip and the bearing support is elastic, and when the probe is pressed on the sample chip, the elastic structure of the sample chip and the bearing support which is elastic is elastically deformed, and the pressing force is compensated by the elasticity of the sample chip or the bearing support bearing the sample chip. The technical scheme of the application can solve the problem that the pressing force is reduced due to the deformation of the sample chip in the probe pressing type sample injection, and it is difficult to maintain the high working pressure required by sampling, chromatographic sample injection and chromatographic separation for a long time.

Description

Technical Field

[0001] This invention belongs to the field of liquid chromatography technology, specifically relating to a probe-press chromatographic injection structure. Background Technology

[0002] Currently, the most commonly used injection methods for liquid chromatography are injection valve injection and autosampler injection.

[0003] For example, invention application CN114878731A discloses a volume-selectable micro-volume injection valve for liquid chromatography, including a push rod, a turntable, and a tank. The turntable is rotatably mounted on one end of the push rod. The tank has a groove into which the turntable can extend, and the two surfaces of the turntable are respectively attached to the two side walls of the groove. The turntable has multiple measuring holes and multiple drain holes of different sizes. Each measuring hole is equipped with a drain hole. The two are arranged in pairs along the radial direction of the turntable and are located on the same side of the center of the turntable. The tank has inlet / outlet holes and injection holes that penetrate the two side walls of the groove. The distance between the inlet / outlet holes and the injection holes is equal to the distance between the paired measuring holes and the drain holes.

[0004] The utility model patent with authorization announcement number CN217655065U discloses an autosampler for high performance liquid chromatography analysis, including a quantitative loop, and several adjusting loops of different capacities are fixedly connected to the quantitative loop, and the adjusting loops are all connected in parallel with the quantitative loop; each adjusting loop is provided with a valve at both ends; both the adjusting loop and the quantitative loop include a body and an observation window, the observation window extends from one end of the quantitative loop to the other end along the length direction of the quantitative loop, and the observation window extends from one valve to another along the length direction of the adjusting loop.

[0005] However, valve-based injection has limitations, such as a large dead volume at the interface, meaning the actual sample consumption is often much greater than the actual injection volume. Automatic samplers, on the other hand, inevitably suffer sample loss due to adsorption or residue in the sample vial or inner tube, and are generally only suitable for micro-volume samples.

[0006] In recent years, the applicant has developed a liquid chromatography injection method for trace samples based on an in-situ sampling probe—the Petrel probe (Shi SW, Lou Q, Fang Q, Petrel probe: an integrated in situ sampling and injection interface for fast, high-efficiency liquid chromatography-mass, Analytical Chemistry, 2021, 93, 10114-10121). This method enables in-situ sampling, in-situ chromatographic injection, and chromatographic separation of trace samples under high pressure. This method achieves sealing by pressing the in-situ sampling probe against the sample chip, which has a certain degree of elasticity, through the relative displacement between the in-situ sampling probe and the sample chip, thus maintaining the high-pressure environment required for sampling, injection, and separation. However, because the sample chip deforms under continuous pressure, the pressing pressure decreases with the deformation of the sample chip; therefore, this type of press-type seal is difficult to maintain for a long time. Summary of the Invention

[0007] This invention addresses the problem in existing technologies where the pressure decreases due to the deformation of the sample chip in probe-press injection, making it difficult to maintain the high working pressure required for sampling, chromatographic injection, and chromatographic separation for extended periods. It provides a probe-press chromatographic injection structure that compensates for the pressure by utilizing the elasticity of the sample chip or the support structure supporting the sample chip.

[0008] A probe-pressable chromatographic injection structure includes a probe for injecting a sample into a chromatographic column and a sample chip for placing the sample. The probe has three interfaces: a first interface, a second interface, and a third interface. The first interface is used to inject buffer solution into the probe, the second interface is used to connect to the chromatographic column, and the third interface is used for sample injection. The third interface faces downward and is used for injecting the sample from the sample chip in a press-press manner. The probe-pressable chromatographic injection structure also includes a support for placing the sample chip. At least one of the sample chip and the support is elastic.

[0009] When the probe is pressed onto the sample chip, the elastic structure in the sample chip and the support bracket undergoes elastic deformation.

[0010] Preferably, the sample chip is elastic, and the support bracket includes a support column for placing the sample chip, with one end of the sample chip fixed to the support column and the other end having a micro-pit for supporting the sample; or the middle part of the sample chip is fixed to the support column, and the outer periphery of the sample chip has a micro-pit for supporting the sample.

[0011] When the probe is pressed onto the sample chip, the sample chip undergoes elastic deformation.

[0012] More preferably, the distance between the point where the probe presses onto the sample chip and the point where the support post supports the sample chip is not less than 3 cm.

[0013] More preferably, the sample chip is made of an elastic polymer. For example, the sample chip is made of polytetrafluoroethylene or polyetheretherketone.

[0014] Preferably, the support bracket is elastic, and includes a support column and a placement platform disposed on the support column. One end of the placement platform is fixed to the support column, and the top surface of the other end is used to place the sample chip.

[0015] When the probe is pressed onto the sample chip, the placement stage undergoes elastic deformation.

[0016] More preferably, the distance between the point of action of the probe pressing on the sample chip and the support point of the support post on the placement stage is not less than 3 cm.

[0017] More preferably, the placement platform is made of a flexible polymer or metal. For example, the placement platform is made of polytetrafluoroethylene, polyetheretherketone, or stainless steel.

[0018] Preferably, the support bracket is elastic, and includes a stage for placing the sample chip and a spring disposed under the sample stage for supporting the sample stage.

[0019] When the probe is pressed onto the sample chip, the spring undergoes elastic deformation.

[0020] More preferably, one end of the placement stage is fixed to the spring, and the top surface of the other end is used to place the sample chip.

[0021] When the probe is pressed onto the sample chip, the placement stage and the spring undergo elastic deformation together.

[0022] Preferably, when the probe is pressed onto the sample chip, the pressure between the two is not less than 6N.

[0023] Preferably, the probe is a capillary-based seagull probe, with the first interface and the second interface at both ends, the middle of the seagull probe has a V-shaped structure, and the bottom of the V-shaped structure has the third interface;

[0024] Alternatively, the probe may be a T-connector, with one of the T-connectors facing downwards and forming a tip, the tip of which is the third interface.

[0025] The probe-pressing chromatographic injection structure of this invention features an elastic component in at least one of the sample chip and the support. When the probe is pressed onto the sample chip, the elastic component in either the sample chip or the support undergoes elastic deformation, and the pressing force is compensated by the elasticity of the sample chip or the support. This invention solves the problem of decreased pressing force due to sample chip deformation in probe-pressing injection, making it difficult to maintain the high operating pressure required for sampling, chromatographic injection, and chromatographic separation over extended periods. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the structure of the seagull probe.

[0027] Figure 2 This is a schematic diagram of the needle-press chromatographic injection structure in Example 1.

[0028] Figure 3 This is a schematic diagram of the needle-press chromatographic injection structure in Example 2.

[0029] Figure 4 This is a schematic diagram of the needle-press chromatographic injection structure in Example 3.

[0030] Figure 5 This is a schematic diagram of the needle-press chromatographic injection structure in Example 4. Detailed Implementation

[0031] A probe-pressable chromatographic injection structure includes a probe for injecting a sample into a chromatographic column and a sample chip for placing the sample. The probe has three interfaces: a first interface, a second interface, and a third interface. The first interface is used to inject buffer solution into the probe, the second interface is used to connect to the chromatographic column, and the third interface is used for sample injection. The third interface faces downward and is used for injecting the sample from the sample chip in a press-press manner. The probe-pressable chromatographic injection structure also includes a support for placing the sample chip. At least one of the sample chip and the support is elastic.

[0032] When the probe is pressed onto the sample chip, the elastic structure in the sample chip and the support bracket undergoes elastic deformation.

[0033] Preferably, when the probe is pressed onto the sample chip, the pressure between the two is not less than 6N.

[0034] like Figure 1 As shown, the probe is a capillary-based seagull probe 4, with the first interface and the second interface at both ends, the middle of the seagull probe 4 has a V-shaped structure, and the bottom of the V-shaped structure has the third interface.

[0035] Alternatively, the probe may be a T-connector, with one of the T-connectors facing downwards and forming a tip, the tip of which is the third interface.

[0036] In one embodiment, the sample chip is elastic, and the support bracket includes a support post for placing the sample chip; one end of the sample chip is fixed to the support post, and the other end has a micro-pit for supporting the sample; or the middle part of the sample chip is fixed to the support post, and the outer periphery of the sample chip has a micro-pit for supporting the sample. When the probe is pressed onto the sample chip, the sample chip undergoes elastic deformation. The elasticity of the sample chip compensates for the decrease in pressing force caused by the deformation of the pressed area of ​​the sample chip. Preferably, the distance between the point of application of the probe pressing on the sample chip and the support point of the support post is not less than 3 cm. Preferably, the sample chip is made of an elastic polymer, such as polytetrafluoroethylene or polyetheretherketone.

[0037] In one embodiment, the support bracket is elastic and includes a support column and a placement stage disposed on the support column. One end of the placement stage is fixed to the support column, and the top surface of the other end is used to place the sample chip. When the probe presses against the sample chip, the placement stage undergoes elastic deformation. The elasticity generated by the deformation of the placement stage compensates for the decrease in pressing force caused by the deformation of the pressed area of ​​the sample chip. The distance between the point of application of the probe pressing on the sample chip and the support point of the support column on the placement stage is not less than 3 cm. The placement stage is made of an elastic polymer or metal. For example, the placement stage is made of polytetrafluoroethylene, polyetheretherketone, or stainless steel.

[0038] In one embodiment, the support bracket is elastic and includes a stage for placing the sample chip and a spring disposed under the sample stage for supporting the sample stage. When the probe presses against the sample chip, the spring undergoes elastic deformation. The spring force compensates for the decrease in pressing force caused by deformation of the pressed area of ​​the sample chip. Preferably, one end of the stage is fixed to the spring, and the top surface of the other end is used to place the sample chip. When the probe presses against the sample chip, the stage and the spring undergo elastic deformation together. The spring constant needs to be selected based on the working pressure required for liquid chromatography injection and chromatographic separation, as well as the probe position control accuracy; generally, a spring with a spring constant greater than 1000 N / m should be selected.

[0039] Example 1

[0040] like Figure 2As shown, a probe-press chromatographic injection structure includes a probe for injecting a sample into a chromatographic column, a sample chip 3 for placing the sample, and a support for placing the sample chip 3.

[0041] The probe is a capillary-based Seagull Probe 4, with a first interface and a second interface at each end. The middle of the Seagull Probe 4 has a V-shaped structure, and a third interface is located at the bottom of the V-shaped structure. The first interface is used to introduce buffer solution into the Seagull Probe 4, the second interface is used to connect to the chromatographic column, and the third interface faces downward and is used for injection of sample from the sample chip in a press-type manner.

[0042] The sample chip 3 is elastic, and the support frame includes a support post 1 for placing the sample chip 3. When the probe is pressed onto the sample chip 3, the sample chip 3 undergoes elastic deformation. The sample chip 3 is made of an elastic polymer, such as polytetrafluoroethylene or polyetheretherketone. The sample chip 3 can be fixed at one end to the support post 1, with a micro-pit formed at the other end (3 cm away from the support post) to support the sample; alternatively, the sample chip 3 can be fixed in the middle area to the support post 1, with micro-pits formed around its perimeter (3 cm away from the support post) to support the sample.

[0043] In one implementation, a 100 pL-10 μL sample droplet is generated on a polytetrafluoroethylene (PTFE) sample chip larger than 5 × 5 cm, and one side of the sample chip is fixed to a support. The probe (with an elliptical inlet approximately 200 μm long and 75 μm wide at the bottom) is moved, or the support is fixed, so that the sampling port at the bottom of the probe is aligned with the sample droplet on the sample chip away from the support, with the distance between the sample droplet and the center of the support being greater than 3 cm. This causes the bottom of the probe to contact and press against the sample chip on the support platform, generating a pressing force greater than 6 N. The pressed area of ​​the sample chip deforms under this pressure, but the elasticity of the PTFE sample chip compensates for the decrease in pressing force caused by this deformation. After turning on the liquid chromatography mobile phase, ensuring the mobile phase pressure is below 300 bar, the system will complete subsequent sampling, chromatographic injection, and chromatographic separation without leakage.

[0044] Example 2

[0045] like Figure 3 As shown, a probe-press chromatographic injection structure includes a probe for injecting a sample into a chromatographic column, a sample chip 3 for placing the sample, and a support for placing the sample chip 3.

[0046] The probe is a capillary-based Seagull Probe 4, with a first interface and a second interface at each end. The middle of the Seagull Probe 4 has a V-shaped structure, and a third interface is located at the bottom of the V-shaped structure. The first interface is used to introduce buffer solution into the Seagull Probe 4, the second interface is used to connect to the chromatographic column, and the third interface faces downward and is used for injection of sample from the sample chip in a press-type manner.

[0047] The support frame is elastic and includes a support column 1 and a placement stage 2 mounted on the support column 1. One end of the placement stage 2 is fixed to the support column 1, and the top surface of the other end is used to place the sample chip 3. When the probe is pressed onto the sample chip 3, the placement stage 2 undergoes elastic deformation. The distance between the point of application of the probe on the sample chip 3 and the support point of the support column 1 on the placement stage 2 is not less than 3 cm. The placement stage 2 is made of an elastic polymer or metal, such as polytetrafluoroethylene, polyetheretherketone, or stainless steel.

[0048] In one implementation, a stainless steel support platform is fixed to a support bracket on one side. A 100 pL-10 μL sample droplet is then generated on a PTFE sample chip, and the sample chip is fixed to the opposite side of the support platform away from the support bracket, with the distance between the sample chip droplet and the center of the support bracket exceeding 6 cm. The probe (containing an elliptical inlet 180-220 μm long and 75 μm wide) or the support bracket is moved so that the sampling port at the bottom of the probe is aligned with the sample droplet on the sample chip. The probe bottom then contacts and presses against the sample chip on the support platform, generating a pressing force greater than 6 N. The sample chip deforms under this pressure, but the elasticity of the stainless steel support platform compensates for the decrease in pressing force caused by this deformation. After turning on the liquid chromatography mobile phase and ensuring the mobile phase pressure is below 300 bar, the system will complete subsequent sampling, chromatographic injection, and chromatographic separation.

[0049] Example 3

[0050] like Figure 4 As shown, a probe-press chromatographic injection structure includes a probe for injecting a sample into a chromatographic column, a sample chip 3 for placing the sample, and a support for placing the sample chip 3.

[0051] The probe is a capillary-based Seagull Probe 4, with a first interface and a second interface at each end. The middle of the Seagull Probe 4 has a V-shaped structure, and a third interface is located at the bottom of the V-shaped structure. The first interface is used to introduce buffer solution into the Seagull Probe 4, the second interface is used to connect to the chromatographic column, and the third interface faces downward and is used for injection of sample from the sample chip in a press-type manner.

[0052] The support bracket is elastic and includes a stage 2 for placing the sample chip 3 and a spring 6 located under the sample stage 2 to support it. The bottom surface of the stage 2 is fixed to the spring 6. When the probe is pressed onto the sample chip 3, the spring 6 undergoes elastic deformation.

[0053] In one implementation, the support platform is fixed to a spring. A 100 pL-10 μL sample droplet is then generated on the sample chip, which is then fixed to the support platform. The probe or spring is moved so that the sampling port at the bottom of the probe aligns with the sample droplet on the sample chip, causing the bottom of the probe to contact and press against the sample chip on the support platform, generating pressure. The sample chip deforms under this pressure, and the elasticity of the spring beneath the support platform compensates for the decrease in pressure caused by this deformation. After the liquid chromatography mobile phase is turned on, the system completes subsequent sampling, chromatographic injection, and chromatographic separation.

[0054] Example 4

[0055] like Figure 5 As shown, a probe-press chromatographic injection structure includes a probe for injecting a sample into a chromatographic column, a sample chip 3 for placing the sample, and a support for placing the sample chip 3.

[0056] In this embodiment, the sample chip 3 and the support bracket are the same as in Example 2, but the probe is different. In this embodiment, the probe is a three-way connector, which includes three interfaces: a first interface, a second interface, and a third interface. The first interface is used to introduce buffer solution into the probe, the second interface is used to connect the chromatographic column, and the third interface is used for sample injection. One of the connectors of the three-way connector faces downward and forms a tip, and the tip is the third interface.

[0057] In one implementation, a stainless steel support platform is fixed to a support bracket on one side. A 100 pL-10 μL sample droplet is then generated on a PTFE sample chip, and the sample chip is fixed to the opposite side of the support platform away from the support bracket, with the distance between the sample chip droplet and the center of the support bracket exceeding 6 cm. The support bracket, based on a stainless steel three-way probe (with a circular inlet at the bottom with an outer diameter of 1-1.5 cm and an inner diameter of 0.7-1 cm), is moved so that the sampling port at the bottom of the probe is aligned with the sample droplet on the sample chip. This causes the bottom of the probe to contact and press against the sample chip on the support platform, generating a pressing force greater than 10 N. The sample chip will deform under this pressure, but the elasticity of the stainless steel support platform will compensate for the decrease in pressing force caused by this deformation. After turning on the liquid chromatography mobile phase and ensuring the mobile phase pressure is below 300 bar, the system will complete subsequent sampling, chromatographic injection, and chromatographic separation.

[0058] Example 5

[0059] A probe-pressing chromatographic injection structure is provided, with the overall structure being the same as in Example 3. However, one end of the stage is fixed to a spring, and the top surface of the other end is used to place the sample chip. When the probe is pressed onto the sample chip, the stage and the spring undergo elastic deformation together.

Claims

1. A probe-pressable chromatographic injection structure, comprising a probe for injecting sample into a chromatographic column and a sample chip for placing the sample, the probe having three interfaces: a first interface, a second interface, and a third interface, wherein the first interface is used for injecting buffer solution into the probe, the second interface is used for connecting to the chromatographic column, and the third interface is used for sample injection, the third interface facing downwards and used for injecting sample from the sample chip in a press-press manner, characterized in that... The probe-press chromatographic injection structure also includes a support bracket for placing the sample chip. The sample chip is elastic, and the support bracket includes a support column for placing the sample chip; one end of the sample chip is fixed on the support column, and the other end is provided with a micro-pit for supporting the sample; when the probe is pressed on the sample chip, the sample chip undergoes elastic deformation. Alternatively, the support bracket is elastic, and the support bracket includes a support column and a placement stage disposed on the support column. One end of the placement stage is fixed to the support column, and the top surface of the other end is used to place the sample chip. When the probe is pressed on the sample chip, the placement stage undergoes elastic deformation.

2. The probe-pressing chromatographic injection structure according to claim 1, characterized in that, The sample chip is made of an elastic polymer.

3. The probe-pressing chromatographic injection structure according to claim 2, characterized in that, The sample chip is made of polytetrafluoroethylene or polyetheretherketone.

4. The probe-pressing chromatographic injection structure according to claim 1, characterized in that, The distance between the point where the probe presses onto the sample chip and the support point of the support column on the placement stage is not less than 3 cm.

5. The probe-pressing chromatographic injection structure according to claim 1, characterized in that, The placement platform is made of a flexible polymer or metal.

6. The probe-pressing chromatographic injection structure according to claim 5, characterized in that, The placement platform is made of polytetrafluoroethylene, polyetheretherketone, or stainless steel.

7. The probe-pressing chromatographic injection structure according to claim 1, characterized in that, When the probe is pressed onto the sample chip, the pressure between the two is not less than 6 N.

8. The probe-pressing chromatographic injection structure according to claim 1, characterized in that, The probe is a capillary-based seagull probe, with the first interface and the second interface at both ends, and the middle part of the seagull probe has a V-shaped structure, with the third interface at the bottom of the V-shaped structure. Alternatively, the probe may be a T-connector, with one of the T-connectors facing downwards and forming a tip, the tip of which is the third interface.

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