Expandable biomacromolecule stability detection device

Abstract

The utility model discloses an expandable biomacromolecule stability detection device which comprises a shell with a box cover, and is characterized in that an accommodating space for a sample pool is arranged in the shell, and an input pipe and an output pipe which are coaxially arranged are respectively arranged at two ends of the accommodating space; the sample pool is detachably matched with the input pipe and the output pipe, and a filter membrane is arranged at one end, facing the output pipe, of the sample pool or in the output pipe; a semiconductor chilling plate is arranged in the shell around the accommodating space of the sample cell, the hot end of the semiconductor chilling plate faces inwards, and the cold end of the semiconductor chilling plate faces the outside of the shell. On-line integrated one-step completion of sample treatment and detection work is realized, and sample treatment and downstream detection of protein stability detection are rapidly completed; consumables of the sample pool are simple and efficient to replace, and detection time waste caused by downstream connection of a chromatographic column is avoided; the temperature is controllable, the operation is convenient, and the process optimization of protein products or medicines is effectively guided; and the sample loading ring can be replaced and can also be used at the position of a chromatographic column.

Description

Technical Field

[0001] This utility model relates to experimental instrument technology, and in particular to an expandable biomolecular stability detection device. Background Technology

[0002] The stability characterization and optimization of biomolecules such as proteins and nucleic acids is a crucial step in biopharmaceutical development and research. The complex structure and function, as well as the extreme instability of protein formulations and biopharmaceuticals, hinder rapid market approval, representing a significant common bottleneck. Therefore, a fast, inexpensive, reliable, and scalable stability testing device is needed to characterize the stability of biomolecules and guide process optimization for their stability.

[0003] In the preparation of biomacromolecules, the most commonly used technique and instrument is liquid chromatography (LC). Chromatography is a technique based on the differences in the physicochemical properties of different substances. By establishing a chromatographic system consisting of a stationary phase and a mobile phase, the mixture to be separated passes through the stationary phase with the mobile phase. Due to the differences in the physicochemical properties of each component, their ability to interact with the two phases varies, resulting in different distributions in the two phases. As the mobile phase moves forward, each component is continuously redistributed between the two phases. By collecting the eluent fractions, the individual components contained in the sample can be obtained, thereby achieving the purpose of separating the components.

[0004] Current chromatography equipment lacks the capability to detect the thermal stability of biomolecules. Therefore, on such conventional equipment, an extension component called a "biomolecule stability detection kit" can be used to achieve online and rapid sample processing and downstream detection for biomolecule stability testing, guiding process optimization for biomolecules such as protein products or drugs. However, traditional sample loading loops are merely tubing, serving only the purpose of sample flow and cannot achieve online integration, rapid consumable replacement, or complete sample processing and downstream detection for stability testing. Simultaneously, this "biomolecule stability detection kit" can also be expanded into a standalone stability testing instrument, enabling high-throughput stability characterization. Summary of the Invention

[0005] The purpose of this invention is to solve the above-mentioned problems and provide an expandable biomacromolecule stability detection device. It features online synchronous sample processing and detection, simple consumable replacement, and the ability to quickly complete sample processing and downstream detection of the target object.

[0006] The above-mentioned technical problems of this utility model are mainly solved by the following technical solution: an expandable biomacromolecule stability detection device, including a shell and a cover set on the top of the shell, characterized in that the shell has a sample cell containing space, and an input tube and an output tube arranged coaxially and cooperating with the sample cell are respectively provided at both ends of the containing space; the sample cell is detachably connected with the input tube and the output tube, and a filter membrane is provided at the end of the sample cell facing the output tube or in the output tube; a semiconductor cooling chip is provided in the containing space of the sample cell inside the shell, with the hot end of the semiconductor cooling chip facing inward and the cold end facing outward of the shell.

[0007] In the aforementioned expandable biomacromolecule stability detection device, preferably, the sample cell is a column tube structure, and sealing rings are provided at the connection points between the sample cell and the input tube and the output tube.

[0008] In the aforementioned expandable biomacromolecule stability detection device, preferably, the filter membrane is disposed inside the sealing ring at the end of the sample cell facing the output tube.

[0009] In the aforementioned expandable biomolecule stability detection device, preferably, the length of the semiconductor cooling chip is adapted to the length of the sample cell containing space, and the cold end of the semiconductor cooling chip is provided with heat dissipation fins.

[0010] In the aforementioned expandable biomacromolecule stability detection device, preferably, the hot end of the semiconductor cooling chip is provided with a heat insulation layer between the hot end and the shell, except for the surface facing the sample cell containing space.

[0011] In the aforementioned expandable biomacromolecule stability detection device, preferably, the detachable connection between the sample cell and the input and output tubes is: the input and output tubes extend into the housing and are fitted with insert-type connecting heads that fit into the sample cell.

[0012] In the aforementioned expandable biomacromolecule stability detection device, preferably, at least one of the input tube and the output tube is a telescopic tube, and both the input tube and the output tube form a sealed fit with the shell.

[0013] In the aforementioned expandable biomacromolecule stability detection device, preferably, the shell has a space for accommodating several sample cells, and an input tube and an output tube corresponding to each sample cell are respectively provided at both ends of the shell.

[0014] In the aforementioned expandable biomacromolecule stability detection device, preferably, the lid and the shell have a heat-insulating and sealed fit structure.

[0015] In the aforementioned expandable biomacromolecule stability detection device, preferably, the housing is equipped with a temperature control switch and a digital display.

[0016] This technical solution addresses the characteristics of protein stability testing by integrating heating, temperature control, and filtration processes into a single, independent housing. The housing allows for sample cell loading and replacement via an openable top cover. The housing has internal space to accommodate the sample cells, which can be configured according to the shape, size, and quantity of the samples to ensure uniform heating and convenient replacement.

[0017] Heating and temperature control are achieved through a combination of a thermoelectric cooler (TEC), temperature sensor, controller, and drive circuitry arranged around the internal space within the casing. This allows for precise temperature regulation within the casing. The entire system has a simple structure and clear control logic, making it ideal for small, enclosed spaces requiring precise temperature control. This solution utilizes the Peltier effect to achieve cooling or heating, ultimately realizing automatic temperature regulation.

[0018] The device housing has an input tube and an output tube at its left and right ends, respectively, which can be connected to chromatography equipment via connectors. The ends of the input and output tubes inside the housing are connected by insert-type end caps, creating a detachable and sealed connection between the sample cell and the feed tube. A filter membrane is placed at the end of the sample cell facing the output tube or inside the output tube to prevent the escape of heated sample particles.

[0019] This solution utilizes a detachable and sealed sample cell and delivery tube to enable sampling applications with sample cells of different sizes (such as various capacities from 10 microliters to 500 microliters).

[0020] Furthermore, according to the design principles of this scheme, the interior of the housing can be designed to accommodate multiple sample cells, and corresponding input and output tubes can be configured at the left and right ends of the housing respectively, forming a mobile detection device with multiple parallel flow paths and multiple sample cell scanning.

[0021] This device is an integrated chromatographic detection instrument design that enables one-step sample processing for the thermal stability detection of biomolecules such as proteins. It can be used in conjunction with chromatographic equipment to achieve downstream detections such as ultraviolet absorption, fluorescence, and multi-angle light scattering. This solution can complete the sample processing steps required for routine biomolecule stability detection online and perform the detection directly on the chromatographic equipment, ultimately obtaining the thermal stability information of biomolecules such as proteins, guiding the process optimization of biomolecule products or drugs.

[0022] Therefore, the beneficial effects of this utility model are: it can be used with the most common chromatography equipment to achieve online integrated sample processing and detection in one step, and quickly complete sample processing and downstream detection for biomolecular stability testing; the sample cell consumables are easy and efficient to replace, without the need for downstream connection to a chromatography column, thus avoiding wasted detection time; the temperature is controllable and the operation is convenient, effectively guiding the process optimization of products such as protein products or drugs; it can replace the sample loop and can also be used in the position of the chromatography column; it can also be expanded into an independent stability testing instrument and achieve high-throughput stability characterization. Attached Figure Description

[0023] Figure 1 This is a front view of this utility model.

[0024] Figure 2 yes Figure 1 Top view.

[0025] Figure 3 yes Figure 1 Right view (partial sectional view).

[0026] Figure 4 This is a partially enlarged structural diagram of the connection between the sample cell and the feed pipe of this utility model.

[0027] Figure 5 This is a schematic diagram of a multi-path joint measurement embodiment of this utility model.

[0028] Figure 6 This is a block diagram illustrating the working principle of the semiconductor refrigeration chip of this utility model.

[0029] In the diagram: 1-shell, 2-lid, 3-input tube, 4-output tube, 5-connector, 6-semiconductor cooling chip, 7-sample cell, 8-digital display, 9-temperature control switch, 10-sealing ring, 11-filter membrane, 12-insulation layer, 13-wire. Detailed Implementation

[0030] The technical solution of this utility model will be further described in detail below through embodiments and with reference to the accompanying drawings.

[0031] like Figures 1 to 3 As shown, an expandable biomacromolecule stability detection device is provided, which has a rectangular shell 1, and a cover 2 on the top of the shell 1. The cover 2 has a heat insulation layer, and a heat-insulating and sealing fit structure is formed between the cover 2 and the shell 1.

[0032] The housing 1 has a central space for accommodating a sample cell 7. An input pipe 3 and an output pipe 4, coaxially arranged and cooperating with the sample cell 7, are located at opposite ends of this space. The sample cell 7 is detachably connected to the input pipe 3 and output pipe 4. A filter membrane 11 is located at the end of the sample cell 7 facing the output pipe 4 or within the output pipe 4. A thermoelectric cooler 6 is located within the housing 1, surrounding the sample cell. The hot end of the thermoelectric cooler 6 faces inward, and the cold end faces outward. The length of the thermoelectric cooler 6 is greater than or equal to the length of the sample cell 7's accommodating space. The cold end of the thermoelectric cooler 6 has heat dissipation fins. Heat dissipation holes are located on the housing 1 opposite the heat dissipation fins at the cold end.

[0033] A thermoelectric cooler 6 is arranged around the housing space within the housing 1. The thermoelectric cooler 6 is a commercially available component, such as the XH-W1504, a TEC thermoelectric cooler temperature controller with automatic temperature control and automatic positive / negative switching functions; another example is the II-VI Marlow thermoelectric cooler, which has a wide heating and cooling range. The sample cell 7 housing space within the housing 1 is made of thermally conductive material, and the exterior of the housing is equipped with a thermal insulation layer, including an insulation layer 12 between the hot end of the thermoelectric cooler 6 and the housing 1.

[0034] The system components for the operation of the semiconductor cooling chip 6. For example... Figure 6 As shown: a thermoelectric cooler (TEC) is used for cooling or heating; a temperature sensor, such as an NTC thermistor or a DS18B20 digital temperature sensor, is used to monitor the temperature inside the box in real time; a controller is used to process temperature data and control the operating status of the TEC, and can be an Arduino or STM32 microcontroller; an H-bridge drive circuit is used to control the current direction of the TEC to achieve switching between cooling and heating; wire 13 of the thermoelectric cooler 6 leads out to provide the power required by the system from the laboratory power supply.

[0035] When the thermoelectric cooler 6 is working, the temperature is detected by a temperature sensor that monitors the temperature inside the chamber in real time and transmits the data to the controller; the temperature control is determined by the controller based on the difference between the set temperature value and the actual temperature value to determine the working state of the TEC (cooling or heating); the current control is achieved by controlling the current direction of the TEC through the H-bridge drive circuit to switch between cooling and heating; the heat dissipation fins or fan dissipate the heat generated by the TEC to the periphery of the sample cell 7 containing space to ensure stable system operation.

[0036] In this embodiment, directional terms such as "left," "right," "up," and "down" are as shown in the accompanying drawings and are not intended to limit technical limitations. The left and right ends of the housing 1 are respectively provided with an input pipe 3 and an output pipe 4 that mate with the sample cell 7. The portions of the input pipe 3 and output pipe 4 that pass through the wall of the housing 1 are fixed within the wall of the housing 1 and are heat-insulated. The sample cell 7 is detachably connected to the input pipe 3 and output pipe 4, and at least one of the input pipe 3 and output pipe 4 is a telescopic pipe. Both the input pipe 3 and output pipe 4 form a sealed fit with the housing 1. Furthermore, the input pipe 3 and output pipe 4 extend into the interior of the housing 1 and are provided with insert-type connecting caps that mate with the sample cell 7. The ends of the input pipe 3 and output pipe located outside the housing 1 are provided with standard connectors 5 that mate with the chromatography apparatus.

[0037] The sample cell 7, as a consumable, can be made of low-adsorption, high-temperature resistant materials such as PC, PP, quartz, and glass. In this embodiment, the sample cell 7 can be replaced with different sizes, such as 10μL, 50μL, 100μL, 200μL, and 500μL. The sample cell 7 has a column tube structure, and sealing rings 10 are provided at the connection ports between the sample cell and the input tube 3 and the output tube 4, respectively. Figure 4 As shown, a filter membrane 11 is provided at the end of the sample cell 7 facing the output tube 4 or in the output tube 4, wherein the filter membrane 11 provided at the end of the sample cell 7 is placed inside the sealing ring 10 at the end of the sample cell 7 facing the output tube 4.

[0038] The surface of the housing 1 is equipped with a temperature control switch 9 and a digital display 8, and the temperature range of the semiconductor cooling chip 6 is 1℃~95℃.

[0039] One embodiment of housing 1, such as Figure 5 As shown:

[0040] The housing 1 has space to accommodate three sample cells 7. In conjunction with the three sample cells 7, input tubes 3 and output tubes 4, corresponding one-to-one with the sample cells 7, are respectively located at the left and right ends of the housing 1, thus forming a complete detection device. It can be connected to an upstream flow control system. The middle housing 1 serves as a stability detector, while downstream continuous ultraviolet absorption, fluorescence, multi-angle light scattering, and other multi-mode scanning detection are used. It can be used independently of the chromatography system and can achieve high throughput.

[0041] Working principle and application:

[0042] The expandable biomolecular stability detection device can be connected to a protein chromatography equipment, replacing the sample loop or being used at the position of the chromatography column. The thermoelectric cooler 6 is heated and kept at a constant temperature within the range of 1℃ to 95℃ via a temperature control switch 9 and a digital display 8. The collected protein sample passes through the sample cell 7 and then through the filter membrane 11, achieving an integrated "heating," "temperature control," and "filtration" operation. The sample processing steps required for routine protein stability testing can be completed online, and UV absorption, fluorescence, and multi-angle light scattering detection can be performed directly on the chromatography equipment, ultimately obtaining thermal stability information for proteins and other samples to guide the process optimization of protein-based products or drugs.

[0043] The above embodiments are illustrative of the present invention and not intended to limit it. Although the present invention has been described in conjunction with preferred embodiments, it should be understood that the present invention is not limited to the preferred embodiments. Those skilled in the art can make various equivalent modifications and substitutions to the technical solutions of the present invention based on its teachings. Therefore, the scope of the present invention should be defined by the claims, and all such equivalent modifications and substitutions fall within the protection scope of the present invention.

Claims

1. A device for detecting the stability of biological macromolecules, comprising a shell (1), a box cover (2) arranged on the top of the shell, characterized in that The shell has a containing space with a sample cell (7), and an input tube (3) and an output tube (4) are coaxially arranged at both ends of the containing space and matched with the sample cell; the sample cell is detachably matched with the input tube and the output tube, and a filter membrane (11) is arranged at one end of the sample cell towards the output tube or in the output tube; a semiconductor refrigerating sheet (6) is arranged around the containing space of the sample cell in the shell, and the hot end of the semiconductor refrigerating sheet faces inwards and the cold end faces outwards of the shell.

2. The device of claim 1, wherein, The sample cell (7) is in a column tube structure, and sealing rings (10) are arranged at the connecting port parts of the sample cell with the input tube (3) and the output tube (4).

3. The device of claim 2, wherein the device is capable of detecting the stability of a biological macromolecule. The filter membrane (11) is arranged inside the sealing ring (10) at one end of the sample cell (7) towards the output tube (4).

4. The expandable biomacromolecule stability detection device of claim 1, wherein, The length of the semiconductor refrigerating sheet (6) is matched with the length of the containing space of the sample cell (7), and the cold end of the semiconductor refrigerating sheet is provided with a heat dissipation fin.

5. The expandable biomacromolecule stability detection device of claim 1, wherein, The hot end of the semiconductor refrigerating sheet (6) is provided with a heat preservation layer (12) between the other surfaces of the semiconductor refrigerating sheet and the shell except the direction of the containing space of the sample cell (7).

6. The expandable biomacromolecule stability detection device of claim 1, wherein, The detachable matching between the sample cell (7) and the input tube (3) and the output tube (4) is a plug-in type connection head that the input tube and the output tube are inserted into the shell and matched with the sample cell.

7. The device of claim 6, wherein the device is capable of detecting the stability of a biological macromolecule. At least one of the input tube (3) and the output tube (4) is a telescopic tube, and the input tube and the output tube are both sealed and matched with the shell (1).

8. The expandable biomacromolecule stability detection device of claim 1, wherein, The shell (1) has a plurality of containing spaces for sample cells (7), and a plurality of input tubes and output tubes are arranged at both ends of the shell and matched with the sample cells one by one.

9. The expandable biomacromolecule stability detection device of claim 1, wherein, The box cover (2) and the shell (1) are in a heat insulation and sealing matching structure.

10. The expandable biomacromolecule stability detection device of claim 1, wherein, The shell (1) is provided with a temperature control switch (9) and a digital display (8).

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