An on-line ultrasonic microtissue sample disruption device

Abstract

The present application relates to a kind of microtissue sample online ultrasonic crushing device, including shell, ultrasonic device is arranged inside shell, liquid storage and temperature control device and sample feeding device, shell includes shell and internal shell, liquid storage and temperature control device are arranged in internal shell, the ultrasonic device is arranged on internal shell, sample feeding device traverses through shell, and flow feeding is carried out to the microtissue sample to be crushed, ultrasonic device is used to provide ultrasonic energy, liquid storage and temperature control device are used to adjust the liquid internal temperature of ultrasonic crushing device, the microtissue sample to be crushed travels to ultrasonic device and liquid storage and temperature control device, and the crushing treatment of microtissue sample is completed.The present application uses water bath mode, keeps the constant temperature of sample during ultrasonic process.Using the working mode of focused ultrasonic array, multiple ultrasonic probes are focused into a core point, more ultrasonic energy is focused when sample flows through quartz connecting pipe, and sample pretreatment time is improved.

Description

Technical Field

[0001] This invention relates to the field of micro-tissue sample pretreatment technology, and more particularly to an online ultrasonic disruption device for micro-tissue samples. Background Technology

[0002] Currently, most ultrasonic disruption instruments and devices use ultrasonic probes for contact-based ultrasonic grinding. For example, CN208667732U, "An Ultrasonic Disruption Device," describes an ultrasonic device that allows for real-time monitoring of the process without removing the disruption container, enabling sampling and monitoring of the disruption effect, thus improving efficiency. However, it lacks provisions for real-time processing of micro-tissue samples during the online process, utilizing ultrasound to disrupt micro-tissue samples in a liquid flow environment. CN211801461U, "An Ultrasonic Disruption Device for Biological Tissue," describes a biological tissue ultrasonic disruption device that combines the main unit and a soundproof enclosure, providing protection, facilitating overall device movement, allowing for the placement of transparent measuring cups, and simplifying the storage and organization of connecting wires and power cords, preventing dragging or loosening. However, it lacks a design scheme for the ultrasonic probe power and control over ultrasonic energy. Therefore, a technology is needed to combine the flow process of biological samples with ultrasonic disruption.

[0003] Currently, online ultrasonic processing is not possible for flow cytometry, and efficient online ultrasonic fragmentation is not possible for micro-tissue samples cut by laser microscopy. Therefore, there is an urgent need for an efficient ultrasonic technology to perform efficient online ultrasonic sample processing during the flow of samples. Summary of the Invention

[0004] In response to the aforementioned technical problems, an online ultrasonic disruption device for micro-tissue samples is provided.

[0005] The technical means employed in this invention are as follows:

[0006] An online ultrasonic fragmentation device for micro-tissue samples includes a housing. Inside the housing are an ultrasonic device, a liquid storage and temperature control device, and a sample injection device. The housing comprises an outer shell and an inner shell. The liquid storage and temperature control device is located within the inner shell, and the ultrasonic device is mounted on the inner shell. The sample injection device traverses the housing and injects the micro-tissue sample into the liquid. The ultrasonic device provides ultrasonic energy, and the liquid storage and temperature control device regulates the internal temperature of the liquid within the ultrasonic fragmentation device. After the micro-tissue sample reaches the ultrasonic device and the liquid storage and temperature control device, the fragmentation process is completed.

[0007] Furthermore, the liquid stored in the liquid storage and temperature control device includes water.

[0008] Furthermore, the temperature control device includes a control device, a heating belt device, and a temperature sensor. Based on the temperature of the liquid in the inner shell collected by the temperature sensor, the control device controls the working state of the heating belt device.

[0009] Furthermore, a sealing device is provided between the outer shell and the inner shell, and the upper and lower ends of the outer shell are respectively provided with a liquid injection hole and a liquid outlet hole.

[0010] Furthermore, the ultrasonic device includes an ultrasonic probe, and the number of ultrasonic probes is at least one. When the number of ultrasonic probes is multiple, the ultrasonic probes are arranged in an array.

[0011] Furthermore, the sample injection device includes a quartz tube, and a spherical bubble structure with a diameter larger than the main diameter of the quartz tube is provided in the middle position of the quartz tube. The spherical bubble structure is the main structure facing the focusing of the ultrasonic device.

[0012] Furthermore, a sealing structure is provided between the sample injection device and the housing.

[0013] Furthermore, the sealing structure includes a sealing silicone tube, which is wrapped around the contact position between the quartz component and the liquid shell, and the seal is achieved by the compression of the two components.

[0014] Compared with existing technologies, this invention has the following advantages: This invention utilizes a water bath to maintain a constant temperature for the sample during the ultrasonic process. Simultaneously, it employs a focused ultrasonic array, focusing multiple ultrasonic probes onto a single core point. As the sample flows through the quartz connecting tube, more ultrasonic energy is focused onto this small point, thus greatly concentrating the energy released by the ultrasound. This method is used in high-throughput sample pretreatment, where micro-tissue samples undergo rapid ultrasonic disruption as they flow through a microchannel, significantly reducing sample pretreatment time and improving sample processing efficiency. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1 This is a half-sectional view of the present invention.

[0017] Figure 2 This is the front view of the cross-section of the present invention.

[0018] Figure 3This is an exploded view of a component of the present invention.

[0019] Figure 4 This is a schematic diagram of the external structure of the component of the present invention.

[0020] In the diagram: 1. Liquid-sealed outer shell; 2. Focused ultrasonic probe; 3. Micro-sample quartz injection device; 4. Internal heating band; 5. Sealing silicone tube; 6. Bottom sealing plug; 7. Top liquid inlet. Detailed Implementation

[0021] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other. The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0022] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the present invention or its application or use. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of exemplary embodiments according to the invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0024] Unless otherwise specifically stated, the relative arrangement, numerical expressions, and values ​​of the components and steps described in these embodiments do not limit the scope of the invention. It should also be understood that, for ease of description, the dimensions of the various parts shown in the drawings are not drawn to actual scale. Techniques, methods, and devices known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of the specification. In all examples shown and discussed herein, any specific values ​​should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values. It should be noted that similar reference numerals and letters in the following figures denote similar items; therefore, once an item is defined in one figure, it need not be further discussed in subsequent figures.

[0025] In the description of this invention, it should be understood that the orientation or positional relationship indicated by directional terms such as "front, back, up, down, left, right", "horizontal, vertical, horizontal" and "top, bottom" is generally based on the orientation or positional relationship shown in the accompanying drawings, and is only for the convenience of describing this invention and simplifying the description. Unless otherwise stated, these directional terms do not indicate or imply that the device or element referred to must have a specific orientation or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation on the scope of protection of this invention. The directional terms "inner" and "outer" refer to the inner and outer contours relative to the outline of each component itself.

[0026] For ease of description, spatial relative terms such as "above," "over," "on the upper surface of," "above," etc., are used herein to describe the spatial positional relationship of a device or feature as shown in the figures to other devices or features. It should be understood that spatial relative terms are intended to encompass different orientations in use or operation besides the orientation of the device as described in the figures. For example, if the device in the figures is inverted, a device described as "above" or "above" other devices or structures would subsequently be positioned as "below" or "under" other devices or structures. Thus, the exemplary term "above" can include both "above" and "below." The device may also be positioned in other different ways (rotated 90 degrees or in other orientations), and the spatial relative descriptions used herein will be interpreted accordingly.

[0027] Furthermore, it should be noted that the use of terms such as "first" and "second" to define components is merely for the purpose of distinguishing the corresponding components. Unless otherwise stated, the above terms have no special meaning and therefore should not be construed as limiting the scope of protection of this invention.

[0028] like Figures 1-4 As shown in the figure, an embodiment of the present invention discloses an online ultrasonic disruption device for micro-tissue samples, including a housing. The housing contains an ultrasonic device, a liquid storage and temperature control device, and a sample injection device. The housing includes an outer shell 1 and an inner shell. The liquid storage and temperature control device is disposed in the inner shell, and the ultrasonic device is disposed on the inner shell. The sample injection device passes through the housing and performs flow injection of the micro-tissue sample to be disrupted. The ultrasonic device is used to provide ultrasonic energy, and the liquid storage and temperature control device is used to adjust the internal temperature of the liquid in the ultrasonic disruption device. After the micro-tissue sample 3 to be disrupted travels to the ultrasonic device and the liquid storage and temperature control device, the micro-tissue sample disruption process is completed.

[0029] Furthermore, the liquid stored in the liquid storage and temperature control device includes water. The liquid is injected into the cavity, and the sample is ultrasonically treated in a water bath to make it more uniform.

[0030] Furthermore, the temperature control device includes a control unit, a heating belt device 4, and a temperature sensor. Based on the temperature of the liquid in the inner shell collected by the temperature sensor, the control unit controls the working state of the heating belt device. Specifically, the ultrasonic process inevitably generates heat, and an appropriate temperature is beneficial for the pretreatment of micro-tissue samples. Therefore, a temperature-adjustable heating belt kit is selected to be placed inside to adjust the internal temperature of the liquid in the ultrasonic fragmentation device. The internal temperature is adjustable and can be freely set within a range of 30-40℃. In this embodiment, a constant temperature of around 30℃ is selected.

[0031] Furthermore, a sealing device is provided between the outer shell and the inner shell. The upper and lower ends of the outer shell are respectively provided with a liquid injection hole 7 and a liquid outlet hole. Sealing plugs 6 are placed at the holes of the fluid-sealed outer shell used for liquid injection. A bottom sealing plug is placed in the lower half of the fluid-sealed outer shell to prevent liquid from flowing out during operation.

[0032] Furthermore, the ultrasonic device includes an ultrasonic probe, with at least one probe. When there are multiple ultrasonic probes, such as two, four, or more, the probes are arranged in an array to form a focused ultrasonic probe 2. The wiring terminals of the ultrasonic device are located between the outer shell and the inner shell. As an optional implementation, the outer shell is divided into upper and lower parts to facilitate installation into the ultrasonic component. The internally injected liquid can more evenly distribute energy to the vicinity of the micro-tissue sample. Taking two ultrasonic probes as an example, they are placed one above the other, with a quartz element placed at the energy intersection point of the ultrasonic transducers. A focusing ultrasonic transducer is selected, and the energy is focused to the same intersection point. The ultrasonic transducer base is fixed to the sealed outer shell.

[0033] Furthermore, the sample introduction device includes a quartz tube, with a spherical bubble structure at the center of the quartz tube, the diameter of which is larger than the main diameter of the quartz tube. This spherical bubble structure is the main structure facing the focusing of the ultrasonic device. In practical applications, the array-type ultrasonic probe is the core ultrasonic component. The constant temperature heating ensures a more uniform temperature of the sample in the water bath. After the micro-tissue sample flows in from the introduction end through the quartz optical path, it is ultrasonically broken up at the central spherical bubble structure.

[0034] Furthermore, a sealing structure is provided between the sample injection device and the housing.

[0035] Furthermore, the sealing structure includes a sealing silicone tube 5, which is wrapped around the contact position between the quartz component and the liquid shell, and the seal is achieved by the compression of the two components.

[0036] In the actual experiment, the micro-tissue sample was cut by the pretreatment device and then injected into the sample injection device. The output state of the focused ultrasonic probe was controlled according to the degree of fragmentation. During this process, the water bath temperature was kept at a preset constant temperature by the temperature control device.

[0037] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An online ultrasonic disruption device for micro-tissue samples, characterized in that, The device includes a housing, inside which are disposed an ultrasonic device, a liquid storage and temperature control device, and a sample injection device. The housing includes an outer shell and an inner shell. The liquid storage and temperature control device is disposed in the inner shell, and the ultrasonic device is disposed on the inner shell. The sample injection device passes through the housing and performs flow injection of the micro-tissue sample to be broken. The ultrasonic device is used to provide ultrasonic energy, and the liquid storage and temperature control device is used to regulate the internal temperature of the liquid in the ultrasonic breaking device. After the micro-tissue sample to be broken travels to the ultrasonic device and the liquid storage and temperature control device, the breaking process of the micro-tissue sample is completed. The ultrasonic device includes an ultrasonic probe, and the number of ultrasonic probes is at least one. When the number of ultrasonic probes is multiple, the ultrasonic probes are arranged in an array. The sample injection device includes a quartz tube, and a spherical bubble structure with a diameter larger than the main diameter of the quartz tube is provided in the middle position of the quartz tube. The spherical bubble structure is the main structure facing the focusing of the ultrasonic device.

2. The online ultrasonic disruption device for micro-tissue samples according to claim 1, characterized in that, The liquid stored in the liquid storage and temperature control device includes water.

3. The online ultrasonic disruption device for micro-tissue samples according to claim 1, characterized in that, The temperature control device includes a control unit, a heating belt device, and a temperature sensor. Based on the temperature of the liquid in the inner shell collected by the temperature sensor, the control unit controls the working state of the heating belt device.

4. The online ultrasonic disruption device for micro-tissue samples according to claim 1, characterized in that, A sealing device is provided between the outer shell and the inner shell, and the upper and lower ends of the outer shell are respectively provided with a liquid injection hole and a liquid outlet hole.

5. The online ultrasonic disruption device for micro-tissue samples according to claim 1, characterized in that, A sealing structure is provided between the sample injection device and the housing.

6. The online ultrasonic disruption device for micro-tissue samples according to claim 5, characterized in that, The sealing structure includes a sealing silicone tube, which is wrapped around the contact point between the quartz tube and the outer shell, and the seal is achieved by the compression of the two components.

Images