Drying device for magnetic beads in kit for nucleic acid extraction

Abstract

According to the drying device for the magnetic beads in the kit for nucleic acid extraction, the magnetic beads are located at the bottom of a longitudinal channel of the kit, an adsorption magnet is arranged on the outer side of the kit, and the drying device is provided with a heating module composed of an ultrasonic probe, a driving motor and an ultrasonic module at the bottom of the kit. The ultrasonic probe is driven by the ultrasonic module, outputs frequency-adjustable ultrasonic waves, is connected with an output shaft of the driving motor, intermittently contacts the bottom of the kit where the magnetic beads are located, and indirectly heats and ultrasonically atomizes the liquid reagent in gaps of the magnetic beads. According to the drying device, the problem of magnetic bead atomization drying in a fully-closed occasion is solved, the difference caused by visual observation of different experimenters is avoided, the drying standard and effect are unified, the guarantee of time and stability for achieving the required drying effect is provided, and the adaptability and portability of diversified use scenes are improved; meanwhile, aerosol pollution can be prevented, and the risk of false positive in a laboratory is greatly reduced.

Description

Technical Field

[0001] The present invention relates to a structural optimization of a nucleic acid extraction device, and in particular to a drying device for magnetic beads in a closed reagent kit used for nucleic acid extraction. Background Art

[0002] In today's mainstream nucleic acid extraction process, the cleaning solution contains alcohol. After washing the magnetic beads, the elution step cannot be performed immediately. The magnetic beads need to be dried to completely evaporate the alcohol on the surface of the beads, otherwise it will affect the effect of nucleic acid extraction and amplification.

[0003] Currently in the industry, during the nucleic acid extraction process, the washed magnetic beads are generally adsorbed by magnetic rods and then dried naturally for 5 minutes, using the ambient temperature and airflow to drive the alcohol to evaporate to the required degree of dryness, and then proceed to the next nucleic acid extraction and purification step. However, this method takes a long time, and the empty drying state brings the probability of aerosol contamination, which will bring uncertain effects to the extraction process and large differences. At the same time, for fully enclosed, especially integrated card boxes that integrate extraction and amplification processes, the traditional direct drying process cannot be used. Summary of the invention

[0004] The purpose of the present invention is to provide a drying device for magnetic beads in a closed reagent kit used for nucleic acid extraction, so as to solve the problem of atomization drying of magnetic beads in a fully closed environment.

[0005] To achieve the above-mentioned purpose, the present invention provides the following technical solutions: a drying device for magnetic beads in a reagent kit used for nucleic acid extraction, wherein the magnetic beads are located in a reaction chamber at the bottom of a longitudinal channel of the reagent kit, and an adsorption magnet is provided on the outside of the reagent kit, and the drying device is provided with a heating module consisting of an ultrasonic probe, a driving motor, and an ultrasonic module at the bottom of the reagent kit, wherein the ultrasonic probe is driven by the ultrasonic module and outputs ultrasonic waves with adjustable frequency, and the ultrasonic probe is connected to the output shaft of the driving motor and intermittently contacts the bottom of the reagent kit where the magnetic beads are located, and the ultrasonic probe uses its own heat to indirectly heat the liquid reagent in the magnetic beads to accelerate its volatilization, and simultaneously uses the ultrasonic cavitation effect to atomize and dry the liquid reagent inside the magnetic beads into a closed cavity space.

[0006] Furthermore, the ultrasonic module is integrated with a driving circuit and a signal enhancement circuit for emitting a PWM pulse signal, which are used to adjust the duty cycle and frequency of the PWM pulse. The PWM pulse signal is input into the driving motor, and the ultrasonic probe is moved closer to or away from the bottom of the reagent box through positive drive or negative drive.

[0007] Furthermore, the root of the ultrasonic probe is sleeved with an elastic outward tension spring.

[0008] Further, the kit is provided with a container plunger rod in the longitudinal channel. The container plunger rod is connected to an external moving motor and is driven to slide back and forth in a piston-like manner along the longitudinal channel to extract dry air or discharge humid air.

[0009] Furthermore, the container plunger rod is made of heat-conducting metal and is externally connected to a heat source. A heat-conducting piston is sleeved at the top of the container plunger rod, and a precision temperature probe is embedded. The heat-conducting piston is slidably and sealingly fitted with the inner wall of the longitudinal channel to directly heat the internally enclosed magnetic beads and humid air.

[0010] Further, at least one ventilation window is provided at the top of the kit, and the ventilation window is connected to the bottom of the reaction chamber through a U-shaped gas path. The inner side of the ventilation window is provided with a drying layer and a nucleic acid extraction filter element in layers from inside to outside.

[0011] Further, an infrared heater is also provided on the magnet bracket of the kit near the reaction chamber on the outside to indirectly assist in heating the magnetic beads.

[0012] Compared with the prior art, the beneficial effects of the present drying device are as follows:

[0013] 1) By using controllable ultrasonic waves, no manual intervention is required during the drying process, and stable drying of magnetic beads can be achieved with fixed drying steps; there is no need for laboratory technicians to visually inspect the drying effect, and the differences brought by different laboratory technicians' visual inspections are also avoided, unifying the drying standards and effects.

[0014] 2) By using the contact heat transfer of the bottom ultrasonic probe, the indirect heating of the infrared heater, and combining with the direct heating of the container plunger rod and the heat-conducting piston, there is no need to wait for a long time during the drying process, providing a guarantee for the time and stability to achieve the required drying effect.

[0015] 3) The drying device is designed modularly and is easy to independently adjust various action parameters during the drying process, improving the adaptability and portability of different analytical reagent usage scenarios.

[0016] 4) The heating part of the device is separated from the magnetic beads and samples, etc., and rapid drying treatment is achieved through the combination of indirect heating, ultrasonic atomization, and air flow dehumidification technologies. A special medical-grade filter element and a dust-free desiccant are provided in the ventilation window to prevent aerosol contamination, greatly reducing the risk of false positives in the laboratory. Description of the Drawings

[0017] Figure 1 is a schematic structural diagram of the drying device for magnetic beads in the kit used for nucleic acid extraction.

[0018] Figure 2 is a schematic circuit diagram of the ultrasonic module in the present drying device.

[0019] Figure 3 It is a schematic diagram of the forward drive of the ultrasonic probe in this drying device.

[0020] Figure 4 It is a schematic diagram of the reverse drive of the ultrasonic probe in this drying device. Specific implementation manners

[0021] The following will further elaborate on the specific implementation manners of this with reference to the accompanying drawings of the embodiments, so that this technical solution can be more easily understood and mastered, thereby making the protection scope of this more clearly defined.

[0022] In view of the many deficiencies in the existing closed kits for nucleic acid extraction, such as the long time-consuming drying of magnetic beads and the risk of aerosol contamination, the designer innovatively proposed a new type of drying device, which can achieve rapid drying of magnetic beads in a relatively closed environment without repeatedly taking them out of the kit and leaving them to dry in the air.

[0023] With the continuous innovation of nucleic acid extraction equipment in technology and the improvement of efficiency in related fields, it can meet the increasing requirements for nucleic acid detection. Especially for the integrated one-piece cartridge with extraction and amplification processes, during use, the magnetic beads need to be washed with alcohol first and then the elution operation is completed after the surface is completely dry. The time that can be compressed in this process is attributed to the drying of the magnetic beads. Therefore, the present utility model proposes a technical improvement for the kit and provides a new way to solve the problem of rapid drying of magnetic beads.

[0024] Such as Figure 1As shown in the figure, it is a schematic structural diagram of the drying device for the magnetic beads proposed in this case. As can be seen from the figure, the magnetic beads 4 are located in the reaction chamber at the bottom of a longitudinal channel 11 of the reagent kit 1, and an adsorption magnet 2 is provided on the outer side beside the reagent kit 1 to adsorb and fix the position of the magnetic beads during the magnetic bead drying operation. As a key point of improvement, the drying device is provided with a heating module 3 composed of an ultrasonic probe 31, a driving motor 32, and an ultrasonic module (not shown) at the bottom of the reagent kit. Among them, the ultrasonic probe 31 is driven by the ultrasonic module to output ultrasonic waves with adjustable frequencies towards the longitudinal channel 11. Moreover, the ultrasonic probe 31 is connected to the output shaft of the driving motor and intermittently contacts the bottom of the reagent kit where the magnetic beads are located to indirectly heat the magnetic beads 4. Therefore, it should be understood that the ultrasonic probe is electrically driven to output ultrasonic waves, transmit high-frequency oscillations to the reaction chamber, and utilize the ultrasonic cavitation effect to achieve the atomization function on the surface and periphery of the magnetic beads. As the core innovation of this application, by using electronic high-frequency oscillation (the oscillation frequency is 1.7 MHz or 2.4 MHz, beyond the human auditory range and harmless to humans and animals), through the high-frequency resonance of the ceramic atomization sheet, the liquid water molecules are broken up to generate natural floating water mist. This technology does not require heating or adding any chemical reagents. Compared with the traditional heating atomization method, 90% of the energy is saved. At the same time, the ultrasonic probe itself generates local heat (measured up to 65 °C), which has an auxiliary heating effect on the magnetic beads, enabling the liquid reagent therein to volatilize faster. On the other hand, from a mechanical perspective, the ultrasonic probe does not continuously contact the bottom of the reagent kit, but separates and then makes hard contact from time to time to prevent the bottom of the reagent kit from deforming due to overheating.

[0025] Although the above ultrasonic probe is ultrasonic through a container and does not directly contact the magnetic beads and the humid environment inside the container, if the ultrasonic probe does not closely fit the object to be ultrasonicated, the transmitted energy will be reduced. Therefore, the device also optimizes the implementation of pre-pressing for the ultrasonic probe, that is, a tension spring 33 with elastic outward expansion is sleeved on its root, and the selected spring has a tension coefficient that can closely contact the bottom of the reagent kit without deforming it.

[0026] From a more refined feature perspective, the ultrasonic module is integrated with Figure 2The shown driving circuit and signal enhancement circuit for generating PWM pulse signals achieve the output power and frequency conversion control of the ultrasonic probe by adjusting the duty cycle and frequency of the PWM pulses. The PWM pulse signals are input to the driving motor, and by positive driving or negative driving, the ultrasonic probe approaches or moves away from the bottom of the kit. By transmitting energy to the container filled with nucleic acid extraction magnetic beads, especially the generated temperature rise and high-frequency oscillation with the contact time, the ultrasonic atomization is realized to accelerate the drying effect. By precisely controlling the temperature by controlling three parameters: the output frequency of the ultrasonic probe, the continuous opening time, and the contact time with the object to be ultrasonically treated (the bottom of the kit), the side effects caused by continuous ultrasound are avoided (although continuous ultrasound can heat the ultrasonically treated liquid, it is easy to damage the biological samples in the liquid, such as the severe breakage of nucleic acid macromolecular chains, which in turn affects the further amplification experiment).

[0027] The above realizes ultrasonic atomization by transmitting energy from the outside of the kit to the inside. At the same time, it is also necessary to form an air flow inside the kit, especially in the longitudinal channel, in order to achieve local ventilation for quickly removing the humid and hot air. Therefore, the kit 1 is provided with a container plunger rod 5 in the longitudinal channel 11. The container plunger rod 5 is connected to an external moving motor 6 and is driven to slide back and forth piston-style along the longitudinal channel to extract dry air or discharge the humid and hot air. Moreover, at least one ventilation window 12 is provided at the top of the kit 1, and the ventilation window 12 is connected to the bottom of the reaction chamber through a U-shaped air path (a fine groove structure at the bottom of the box, not shown in detail). A drying layer 7 and a nucleic acid extraction filter element 8 are provided in layers from the inside to the outside on the inner side of the ventilation window 12. Thus, the container plunger rod is used to repeatedly extract the air in the longitudinal channel to take away the atomized alcohol around the magnetic beads. At the same time, the special nucleic acid extraction filter element and the desiccant sandwich layer provided in the ventilation window are conducive to quickly absorbing the moisture of the residual reagent after washing the magnetic beads pushed by the container plunger rod to prevent nucleic acid aerosol contamination.

[0028] The specific operation process of the drying device is as follows: The washed magnetic beads stay at the bottom of the extraction container (i.e., the kit). At this time, the ultrasonic module is turned on in advance at a certain ultrasonic frequency to quickly preheat the ultrasonic probe for a certain period of time, then the ultrasonic frequency is changed, and the ultrasonic probe is moved to intermittently contact the bottom of the extraction container to conduct heat and atomize the residual liquid on the surface of the magnetic beads at a high frequency. At the same time, the moving motor pushes the container plunger rod to move up and down to make the air around the magnetic beads flow regularly. The ventilation window provided at the bottom of the extraction container is used for external connection, and the hot air flow is used to achieve the effect of quickly drying the magnetic beads.

[0029] As an optional drying and heating design, the above-mentioned container plunger rod is made of heat-conducting metal and is externally connected to a heat source. A piston with a high heat-conductivity coefficient for isolating reagents is sleeved at the top of the container plunger rod 5, named as the heat-conducting piston 6. The heat-conducting piston 6 is slidably and sealed with the inner wall of the longitudinal channel 11. Thus, the driving ability of the air flow in the longitudinal channel is retained, and heat can be transported to the air around the magnetic beads through the heat-conducting piston. In addition, an infrared heater can be provided on the magnet support near the reaction chamber on the outer side of the reagent kit to indirectly assist in heating the magnetic beads in another auxiliary way.

[0030] In summary, as detailed in the embodiments of the drying device for magnetic beads in the reagent kit for nucleic acid extraction of the present utility model, this solution has substantial features and progressiveness, and its technical effects are as follows.

[0031] 1). By using controllable ultrasonic waves, no manual intervention is required during the drying process, and stable drying of the magnetic beads can be achieved with fixed drying steps; there is no need for laboratory technicians to visually inspect the drying effect, and the differences caused by different laboratory technicians' visual inspection are also avoided, unifying the drying standards and effects.

[0032] 2). By utilizing the contact heat transfer of the bottom ultrasonic probe, the indirect heating of the infrared heater, and combining with the direct heating of the container plunger rod and the heat-conducting piston, there is no need to wait for a long time during the drying process, providing a guarantee for the time and stability to achieve the required drying effect.

[0033] 3). The drying device is designed modularly and is easy to independently adjust various action parameters during the drying process, improving the adaptability and portability for different usage scenarios of analysis reagents.

[0034] 4). The heating part of the device is separated from the magnetic beads and the samples, etc., and rapid drying treatment is achieved through the combination of indirect heating, ultrasonic atomization, and air flow dehumidification technologies. In addition, a dedicated medical-grade filter element and a desiccant without dust shedding are provided in the ventilation window to prevent aerosol contamination, greatly reducing the risk of false positives in the laboratory.

[0035] In addition to the above embodiments, the present invention may also have other implementation manners. Any technical solutions formed by equivalent replacement or equivalent transformation fall within the scope of protection required by the present invention.

Claims

1. A drying device for magnetic beads in a kit for nucleic acid extraction, wherein the magnetic beads are located in a reaction chamber at the bottom of a longitudinal channel of the kit, and an adsorption magnet is provided on the outside of the kit, characterized in that: The drying device is provided with a heating module consisting of an ultrasonic probe, a driving motor, and an ultrasonic module at the bottom of the reagent box. The ultrasonic probe is driven by the ultrasonic module and outputs ultrasonic waves with adjustable frequency. The ultrasonic probe is connected to the output shaft of the driving motor and intermittently contacts the bottom of the reagent box where the magnetic beads are located, thereby indirectly heating and ultrasonically atomizing the liquid reagent in the gaps between the magnetic beads.

2. The drying device for magnetic beads in the kit for nucleic acid extraction according to claim 1, characterized in that: The ultrasonic module is integrated with a driving circuit and a signal enhancement circuit that emit PWM pulse signals, which are used to adjust the duty cycle and frequency of the PWM pulses. The PWM pulse signals are input into a driving motor, and the ultrasonic probe is driven close to or away from the bottom of the reagent box through positive or negative driving.

3. The drying device for magnetic beads in the kit for nucleic acid extraction according to claim 1, characterized in that: The root of the ultrasonic probe is sleeved with an elastic tension spring.

4. The drying device for magnetic beads in the kit for nucleic acid extraction according to claim 1, characterized in that: The reagent box is provided with a container plunger rod in the longitudinal channel, and the container plunger rod is connected to an external moving motor and is driven to slide back and forth in a piston-like manner along the longitudinal channel.

5. The drying device for magnetic beads in the kit for nucleic acid extraction according to claim 4, characterized in that: The container plunger rod is made of heat-conducting metal and is connected to an external heat source. The top end of the container plunger rod is sleeved with a heat-conducting piston and a precision temperature probe is embedded in it. The heat-conducting piston is slidably sealed with the inner wall of the longitudinal channel to directly heat the magnetic beads and humid air enclosed inside.

6. The drying device for magnetic beads in the kit for nucleic acid extraction according to claim 1, characterized in that: The top of the reagent box is provided with at least one ventilation window, and the ventilation window is connected with the bottom of the reaction chamber through a U-shaped air path, and the inner side of the ventilation window is provided with a drying layer and a nucleic acid extraction filter element from the inside to the outside.

7. The drying device for magnetic beads in the kit for nucleic acid extraction according to claim 1, characterized in that: The outer side of the reagent box is also provided with an infrared heater on the magnet support close to the reaction chamber to indirectly assist in heating the magnetic beads.

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