Liquid treatment system
By integrating a positive pressure module into the liquid workstation, multi-step integration of sample addition, incubation, termination, and solid-liquid separation is achieved, solving the problem that the liquid workstation cannot separate solids and liquids, and improving experimental efficiency and accuracy.
Patent Information
- Application Number
- CN202520624660.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-03
- Publication Date
- 2026-02-13
- Estimated Expiration
- 2035-04-03
AI Technical Summary
Existing liquid workstations cannot perform solid-liquid separation operations, requiring the liquid to be tested to be transferred to other equipment for cumbersome separation operations, which affects experimental efficiency.
A positive pressure module is integrated into the liquid workstation, which achieves solid-liquid separation through a liftable base and pressurizing components. Combined with a pipetting robot and a plate transfer robot, the steps of sample addition, incubation, termination, and solid-liquid separation can be completed directly within the liquid workstation.
It achieves multi-step integration within the liquid workstation, reduces cumbersome liquid transfer operations, improves experimental efficiency and accuracy, and is suitable for in vitro pharmacokinetic experiments.
Smart Images
Figure CN223910875U_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The utility model relates to the field of biology especially, relate to a liquid treatment system. BACKGROUND
[0002] With the rapid development of life science technology, the research work of biochemical laboratory faces more complex research objects and increasing sample quantity, and the traditional manual operation mode cannot meet the high-throughput sample processing demand, and the liquid workstation is applied.
[0003] The liquid workstation is an automated equipment for accurately processing liquid in a laboratory or industrial environment, which has the advantages of high precision, high speed and strong adaptability, and because it is equipped with an 8-channel liquid sample adding mechanical arm and a 96-channel liquid sample adding mechanical arm, the liquid workstation can realize single-hole accurate sample suction and transfer and one-time whole-plate sample suction and transfer operation, can effectively reduce the error caused by human operation, and improve the accuracy and experimental throughput of the experiment.
[0004] In vitro pharmacokinetics (ADME) is the abbreviation of drug "absorption (Absorption), distribution (Distribution), metabolism (Metabolism) and excretion (Excretion)", which represents the body's disposal process of the drug. The ADME properties of the drug are determined by its structure, and the determination of the ADME properties of the drug can provide important reference value for predicting its bioavailability and biological activity (i.e. whether a drug can reach its target and produce corresponding therapeutic effect). In the early research and development, the research on ADME properties is mainly through the development of animal in vivo pharmacokinetic experiment, and the obtained data is used to predict the human in vivo PK behavior of the drug. Later, with the development of the pharmaceutical industry, the number of compounds that need to be screened for ADME properties has increased significantly, and the research on the ADME properties of the compounds also requires more in-depth research, and thus in vitro ADME experiment is generated. In the lead optimization (LO) and pre-clinical candidate (PCC) stages, comprehensive in vitro ADME research is usually required, such as multi-species metabolic stability, plasma protein binding, interaction of compounds and transporters, inhibition of drug metabolizing enzymes, etc., combined with animal PK data, to predict human pharmacokinetics.
[0005] The in vitro pharmacokinetic experiment generally includes the early sample processing steps such as sample adding, incubation, termination, solid-liquid separation, etc., and the subsequent sample analysis steps, and the sample analysis is completed by liquid chromatography. The current liquid workstation can only perform sample adding, incubation and termination steps, and does not have the function of solid-liquid separation. After the sample to be tested is terminated, it needs to be transferred to other equipment for solid-liquid separation, and the operation is very cumbersome. The utility model discloses a liquid processing system
[0006] In order to solve the prior art problem described above, the utility model provides a kind of liquid processing system, based on existing liquid workstation, integrate positive pressure module, sample to be measured is completed in positive pressure module and solid-liquid separation operation is completed in two steps, overcome the existing liquid workstation needs tedious step, the operation of transfer liquid.
[0007] In order to solve the above problem, the utility model provides a kind of liquid processing system, including liquid workstation, the liquid workstation is provided with working platform, the top of the working platform is provided with pipette mechanical arm for transferring liquid and plate mechanical arm for transferring hole plate, one end of the working platform is provided with CO2 incubator, the other end is provided with film sealing machine and positive pressure module, characterized in that,
[0008] The positive pressure module includes the base and the protein precipitation plate placement area and sample receiving plate placement area on the base, and the protein precipitation plate placement area and sample receiving plate placement area are used for placing the protein precipitation plate and sample receiving plate respectively, the top of the protein precipitation plate placement area is provided with a pressurizing component for applying pressure to the protein precipitation plate, and the bottom of the protein precipitation plate placement area is provided with a sample receiving plate placement area for collecting the liquid to be analyzed after purification by the protein precipitation plate.
[0009] Alternatively, the positive pressure module includes the base and the protein precipitation plate placement area and sample receiving plate placement area on the base, and the protein precipitation plate placement area and sample receiving plate placement area are used for placing the protein precipitation plate and sample receiving plate respectively, the top of the protein precipitation plate placement area is provided with a pressurizing component for applying pressure to the protein precipitation plate, and the bottom of the protein precipitation plate placement area is provided with a sample receiving plate placement area for collecting the liquid to be analyzed after purification by the protein precipitation plate.
[0010] As a preferred embodiment, the following seven functional areas are provided on the working platform:
[0011] Cell culture area is used for placing CO2 incubator for cell culture.
[0012] Reagent area is used for placing reagents used in the experiment.
[0013] Heating and shaking area is used for incubating samples in in vitro kinetics experiment.
[0014] Transfer area is used for storing cell culture plates, protein precipitation plates and sample receiving plates.
[0015] Consumable area is used for placing consumables required in the experiment.
[0016] Positive pressure area is used for placing positive pressure module for solid-liquid separation operation.
[0017] A film sealing area is arranged for placing a film sealing machine to perform a film sealing operation.
[0018] A waste area is arranged for placing waste generated in the experiment.
[0019] As another preferred embodiment, the pipetting robot arm comprises an 8-channel pipetting robot arm and a 96-channel pipetting robot arm.
[0020] As a preferred embodiment, the protein precipitation plate is a 96-well protein precipitation plate.
[0021] As a preferred embodiment, the sample receiving plate is a 96-well sample receiving plate.
[0022] As a preferred embodiment, the pressurizing component comprises an air pump and a manifold connected to the air pump, the manifold being used to deliver pressurized gas to the protein precipitation plate.
[0023] As a preferred embodiment, the liquid workstation is a Tecan Evo series, Tecan Fluent series, Hamilton Star series, Hamilton Vantage series liquid workstation.
[0024] As a preferred embodiment, the working platform is further provided with a refrigerated table top, and the temperature of the refrigerated table top is 0-20℃.
[0025] As a preferred embodiment, the bottom end of the protein precipitation plate is provided with a sieve plate and a filter filling on the sieve plate.
[0026] As another preferred embodiment, the protein precipitation plate is a Biotage or Phenomenex brand protein precipitation plate.
[0027] Advantages:
[0028] (1) The liquid treatment system of the utility model integrates a positive pressure module on the basis of the existing liquid workstation, can realize sample adding, incubation, termination and solid-liquid separation functions at the same time, and directly performs subsequent analysis steps on the processed sample to be measured without complicated liquid transfer operation, thereby providing convenience for in vitro pharmacokinetic experiments.
[0029] (2) The liquid treatment system of the utility model integrates a positive pressure module in the existing liquid workstation, occupies a small area, saves space, and is more conducive to wide promotion.
[0030] (3) The liquid treatment system of the utility model, the positive pressure module can perform termination and solid-liquid separation operations in sequence, integrates multiple steps in one device, and has a simple structure.
[0031] The utility model discloses a concept, specific structure and produced technical effect will be further described below with the drawings, to fully understand the purpose, features and effects of the utility model. BRIEF DESCRIPTION OF DRAWINGS
[0032] In order to make the technical scheme of the utility model embodiment more clearly, the drawings needed in the embodiment or prior art description will be simply introduced below, and obviously, the drawings in the following description are only some embodiments of the utility model, and for those skilled in the art, other drawings can be obtained without creative labor.
[0033] Figure 1 It is the structural schematic diagram of the liquid processing system of the utility model (left side is the back view, and right side is the front view);
[0034] Figure 2 It is the layout drawing of the liquid processing system of the utility model;
[0035] Figure 3 It is the working schematic diagram of the positive pressure module in the liquid processing system of the utility model;
[0036] Figure 4 It is the working flow chart of the positive pressure module in the liquid processing system of the utility model.
[0037] Mark explanation:
[0038] 1-CO2 incubator, 2-protein precipitation plate, 3-sample receiving plate, 4-film sealing machine, 5-working platform, 6-reagent area, 7-heating oscillation area, 8-transit area, 9-consumable area, 10-positive pressure area, 11-film sealing area, 12-waste area, 13-positive pressure module, 14-cell culture area, 15-base. DETAILED DESCRIPTION
[0039] In order to make the technical scheme of the utility model embodiment more clearly, the drawings needed in the embodiment or prior art description will be simply introduced below, and obviously, the drawings in the following description are only some embodiments of the utility model, and for those skilled in the art, other drawings can be obtained without creative labor.
[0040] The terms "first", "second", etc. are used only for the purpose of description and do not indicate or imply relative importance or a specific number of features. Thus, features defined with "first", "second" can explicitly or implicitly include at least one of the features. In the description of the present application, if the term "plurality" appears, the meaning of "plurality" is at least two, for example, two, three, etc., unless otherwise explicitly specified and limited.
[0041] In the present application, unless otherwise explicitly specified and limited, if the terms "mounting", "connecting", "connecting", "fixing" and the like appear, these terms should be interpreted broadly. For example, it can be fixedly connected, or it can be detachably connected, or it can be integrated; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium; it can be the internal communication of two elements or the interaction relationship between two elements, unless otherwise explicitly limited. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.
[0042] If an element is referred to as "fixed to" or "disposed on" another element, it can be directly on another element or there can be a middle element. If an element is considered to be "connected" to another element, it can be directly connected to another element or there can be a middle element. If present, the terms "vertical", "horizontal", "up", "down", "left", "right" and similar expressions used in the present application are for the purpose of illustration only and do not represent the only implementation.
[0043] The characteristics of in vitro pharmacokinetic experiments are high throughput, high precision and high timeliness. Compared with traditional manual experiments, liquid workstations can more accurately and efficiently complete liquid handling work such as sample addition, gradient dilution, and liquid separation. The automated operation process can effectively reduce human operation errors and improve the speed, quality and throughput of in vitro pharmacokinetic testing. However, existing liquid workstations cannot perform solid-liquid separation operations, and need to transfer the measured liquid processed by the liquid workstation to a solid-liquid separation device, which is quite cumbersome to operate.
[0044] The application provides a liquid processing system, comprising a liquid workstation, preferably a liquid workstation of Tecan Evo series, Tecan Fluent series, Hamilton Star series or Hamilton Vantage series. The liquid workstation is provided with a work platform 5, the top end of the work platform 5 is provided with a pipetting mechanical arm for transferring liquid and a plate transferring mechanical arm for transferring a well plate, the pipetting mechanical arm can be selected from an 8-channel pipetting mechanical arm and a 96-channel pipetting mechanical arm, and the pipetting mechanical arm and the plate transferring mechanical arm are both mechanical arms equipped with the liquid workstation without the need for additional installation. One end of the work platform 5 is provided with a CO2 incubator 1, and the other end is provided with a film sealing machine 4 and a positive pressure module 13.
[0045] The work platform 5 is provided with the following seven functional areas:
[0046] A cell culture area 14 for placing the CO2 incubator 1 for cell culture;
[0047] A reagent area 6 for placing reagents used in the experiment;
[0048] A heating and shaking area 7 for incubating samples in in vitro kinetics experiments;
[0049] A transfer area 8 for storing cell culture plates, protein precipitation plates 2 and sample receiving plates 3;
[0050] A consumable area 9 for placing consumables required in the experiment;
[0051] A positive pressure area 10 for placing the positive pressure module 13 for solid-liquid separation operation;
[0052] A film sealing area 11 for placing the film sealing machine 4 for film sealing operation;
[0053] A waste area 12 for placing waste generated in the experiment.
[0054] The work platform 5 is also provided with a refrigerated table top, and the temperature of the refrigerated table top is 0-20°C.
[0055] The positive pressure module 13 comprises a liftable base 15, a protein precipitation plate placing area and a sample receiving plate placing area located on the base 15, the protein precipitation plate placing area and the sample receiving plate placing area are connected by a support, and the protein precipitation plate placing area is located above the sample receiving plate placing area. The height of the base 15 is adjusted, and since the sample receiving plate placing area is directly located on the base 15, as the base 15 rises, the sample receiving plate placing area rises, and the protein precipitation plate placing area moves upward. Conversely, the height of the base 15 is lowered, and the sample receiving plate placing area and the protein precipitation plate placing area are lowered.
[0056] The protein precipitation plate placement area and the sample receiving plate placement area are respectively used for placing the protein precipitation plate 2 and the sample receiving plate 3. The top end of the protein precipitation plate placement area is provided with a pressurizing component, which includes a gas pump and a manifold connected with the gas pump, and the manifold is used for delivering pressurized gas to the protein precipitation plate 2. The bottom end of the protein precipitation plate placement area is provided with a sample receiving plate placement area, which is used for collecting the to-be-analyzed liquid purified by the protein precipitation plate 2.
[0057] The positive pressure module 13 as above is connected with the protein precipitation plate 2 through the liftable base 15. Of course, the pressurizing component can also be set as a liftable component, and the base 15 is a fixed component. Through the liftable pressurizing component, the contact between the pressurizing component and the protein precipitation plate 2 can also be achieved.
[0058] The protein precipitation plate 2 is preferably a 96-well protein precipitation plate. The bottom end of the protein precipitation plate 2 is provided with a sieve plate, and the filter filling is placed on the sieve plate. Preferably, the protein precipitation plate 2 is a protein precipitation plate 2 of Biotage or Phenomenex brand.
[0059] The sample receiving plate 3 is preferably a 96-well sample receiving plate.
[0060] Example 1
[0061] As shown in Figure 1 , Figure 2 , a liquid processing system includes a liquid workstation, which is a Hamilton Vantage series liquid workstation. The workstation software is Hamilton 4.5.0.7977 version. The liquid workstation is equipped with a workbench, and the top end of the workbench is provided with an 8-channel pipetting mechanical arm, a 96-channel pipetting mechanical arm and a plate transfer mechanical arm for transferring hole plates, so as to facilitate rapid and accurate liquid and hole plate transfer. The pipetting mechanical arm and the plate transfer mechanical arm used in the present application are both equipped with the liquid workstation itself.
[0062] One end of the workbench is provided with a heating and shaking area 7 for placing eight heating and shaking devices, which have both heating and shaking functions, and the shaking speed ranges from 0 to 1000 rpm, which meets the in vitro incubation conditions. The same side of the heating and shaking area 7 is provided with a cell culture area 14 for placing a CO2 incubator 1, and the CO2 incubator 1 is selected from the Thermo Cytomat 2C series. The other end of the workbench is provided with a positive pressure area 10 and a film sealing area 11, the positive pressure area 10 is used for placing a positive pressure module 13, and the film sealing area 11 is used for placing a film sealing machine 4, and the film sealing machine 4 is selected from the Agilent PlateLoc series.
[0063] The workbench is also equipped with a reagent area 6, a transfer area 8, a consumables area 9, and a waste area 12. Reagent area 6 is used to store reagents required for experiments, including buffer solutions, stop solutions, and dilution reagents. Transfer area 8 is used to store 96-well deep-well plates, 96-well shallow-well plates, 96-well cell culture plates, and protein precipitation plates. Consumables area 9 is used to store consumables required for experiments, including pipette tips of different ranges. Waste area 12 is used to store waste generated during experiments, including used pipette tips and protein precipitation plates after positive pressure treatment.
[0064] In addition, a cooling table is provided on the workbench, which can hold a standard 96-hole deep hole plate, with a temperature setting range of 0-20℃.
[0065] like Figure 3 , Figure 4 As shown, the positive pressure module 13 includes a height-adjustable base 15, which has a lifting function and can be adjusted manually or automatically. The base 15 is provided with a protein precipitation plate placement area and a sample receiving plate placement area, which are used to place protein precipitation plate 2 and sample receiving plate 3, respectively. The protein precipitation plate placement area and the sample receiving plate placement area are connected by a support column. The sample receiving plate placement area is located on the base 15, and the protein precipitation plate placement area is located above the sample receiving plate placement area. Both the protein precipitation plate placement area and the sample receiving plate placement area are frame structures, providing support for the protein precipitation plate 2 and the sample receiving plate 3.
[0066] A pressure device is installed at the top of the protein precipitation plate placement area. At this time, protein precipitation plate 2 is a Biotag brand 96-well protein precipitation plate, and sample receiving plate 3 is a 96-well sample receiving plate.
[0067] Protein precipitation plate 2 is stored in transfer area 8 before being used for solid-liquid separation.
[0068] The liquid workstation can perform routine incubation and culture operations. When further processing is required, 180 μL of termination reagent (such as acetonitrile, methanol, etc.) is added to a 96-well protein precipitation plate using an 8-channel or 96-channel pipetting robotic arm. Then, 60 μL of the incubated and cultured sample is added to the 96-well protein precipitation plate using the same robotic arm, mixed with the termination reagent, and agitated to produce protein precipitate. Afterwards, the protein precipitation plate 2, located in transfer zone 8, is moved to the protein precipitation plate placement area manually or using a transfer robotic arm. Similarly, the sample receiving plate 3, also located in transfer zone 8, is moved to the sample receiving plate placement area manually or using a transfer robotic arm. At this point, the protein precipitation plate 2 and sample receiving plate 3 are placed sequentially from top to bottom on the base 15.
[0069] The top of the protein precipitation plate placement area is provided with a pressurizing component, which comprises an air pump and a manifold for delivering pressurized gas to the protein precipitation plate 2, and the number of the manifold corresponds to the number of the holes of the protein precipitation plate 2.
[0070] Before pressurization, the manifold is kept a distance from the protein precipitation plate 2, the height of the base 15 is adjusted upward, the protein precipitation plate 2 and the sample receiving plate 3 are lifted, the protein precipitation plate 2 is in contact with the manifold, the air pump is turned on, the air pressure is controlled to be 10 Psi, the positive pressure is started, the air pressure is controlled to be 15 Psi after 5 seconds, and the positive pressure is ended after 20 seconds.
[0071] After the pressurization operation, the filtrate enters the sample receiving plate 3 through the protein precipitation plate 2, and the solid waste is left in the protein precipitation plate 2. The protein precipitation plate 2 is placed in the waste area 12 by hand or a plate moving mechanical arm, the sample receiving plate 3 is placed in the film sealing area 11, and film sealing storage is performed for subsequent liquid chromatography-tandem mass spectrometry analysis.
[0072] The technical features of the above embodiments can be combined in any manner. In order to make the description simple, all possible combinations of the technical features in the above embodiments are not described, but as long as the combinations of the technical features do not contradict, they should be considered as the scope of the description.
[0073] The above embodiments only express several implementation manners of the present application, the description is relatively specific and detailed, but it should not be understood as a limitation on the patent scope. It should be noted that for ordinary skilled persons in the art, without departing from the concept of the present application, a number of modifications and improvements can be made, which are all within the protection scope of the present application.
Claims
1. A liquid processing system comprising a liquid workstation, wherein the liquid workstation is provided with a working platform, a top end of the working platform is provided with a pipetting robot arm for transferring liquid and a plate transferring robot arm for transferring a well plate, one end of the working platform is provided with a CO2 incubator, and the other end is provided with a film sealing machine and a positive pressure module, characterized in that, the positive pressure module comprises a base and a protein precipitation plate placement area and a sample receiving plate placement area on the base, the protein precipitation plate placement area and the sample receiving plate placement area are respectively used for placing a protein precipitation plate and a sample receiving plate, a top end of the protein precipitation plate placement area is provided with a pressurizing component for applying pressure to the protein precipitation plate, and a bottom end of the protein precipitation plate placement area is provided with a sample receiving plate placement area for collecting the liquid to be analyzed after purification by the protein precipitation plate. Alternatively, the positive pressure module comprises a base and a protein precipitation plate placement area and a sample receiving plate placement area on the base, the protein precipitation plate placement area and the sample receiving plate placement area are respectively used for placing a protein precipitation plate and a sample receiving plate, a top end of the protein precipitation plate placement area is provided with a pressurizing component for applying pressure to the protein precipitation plate, and a bottom end of the protein precipitation plate placement area is provided with a sample receiving plate placement area for collecting the liquid to be analyzed after purification by the protein precipitation plate. The working platform is provided with the following seven functional areas:
2. The liquid treatment system of claim 1, wherein, a cell culture area for placing a CO2 incubator for cell culture; a reagent area for placing reagents used in the experiment; a heating and shaking area for incubating samples in in vitro kinetics experiments; a transfer area for storing cell culture plates, protein precipitation plates and sample receiving plates; a consumable area for placing consumables required in the experiment; a positive pressure area for placing a positive pressure module for solid-liquid separation operation; a film sealing area for placing a film sealing machine for film sealing operation; a waste area for placing waste generated in the experiment. The pipetting robot arm comprises an 8-channel pipetting robot arm and a 96-channel pipetting robot arm.
3. The liquid treatment system of claim 1, wherein, The protein precipitation plate is a 96-well protein precipitation plate.
4. The liquid treatment system of claim 1, wherein, The sample receiving plate is a 96-well sample receiving plate.
5. The liquid treatment system of claim 1, wherein, The pressurizing component comprises an air pump and a manifold connected to the air pump, and the manifold is used to deliver pressurized gas to the protein precipitation plate.
6. The liquid treatment system of claim 1, wherein, The liquid workstation is a Tecan Evo series, Tecan Fluent series, Hamilton Star series, Hamilton Vantage series liquid workstation.
7. The liquid treatment system of claim 1, wherein, The working platform is also provided with a refrigerated table top, and the temperature of the refrigerated table top is 0-20℃.
8. The liquid treatment system of claim 1, wherein, A bottom end of the protein precipitation plate is provided with a sieve plate and a filter filling on the sieve plate.
9. The liquid treatment system of claim 1, wherein, The protein precipitation plate is a Biotage or Phenomenex brand protein precipitation plate.
10. The liquid treatment system of claim 9, wherein,