Tissue transparentizing device

Abstract

The tissue transparentizing device comprises an oscillating unit, a sample cabin unit, a waste liquid collecting unit, a control unit and a conveying unit, the oscillation unit comprises a cabin, an oscillation mechanism and a temperature control device; the sample cabin unit comprises a sample adding unit and a sample cabin; the sample cabin is arranged on the oscillating mechanism and is positioned in the cabin; the sample adding unit comprises a sample adding pipe; the sample cabin comprises a cabin body; a plurality of operation holes are formed in the cabin body; the waste liquid collecting unit comprises a waste liquid container, a discharge pipeline and a first valve; the conveying unit comprises a plurality of reagent containers, a plurality of metering units, a conveying pipeline and a second valve arranged on the conveying pipeline; the conveying pipeline is respectively connected with each reagent container and the first valve; and the first valve is respectively connected with the discharge pipeline and the sample adding pipe. The device can realize automatic sample adding and improve the tissue transparentizing efficiency.

Description

Technical Field

[0001] The present application relates to the technical field of detection equipment, and more specifically, to a tissue transparency device. Background Art

[0002] Tissue clearing, that is, making tissue more transparent, uses chemical reagents to remove components that cause light scattering and light absorption, thereby making the optical properties and refractive index inside the tissue uniform. Currently, the commonly used clearing methods are active tissue clearing and passive tissue clearing. Among them, passive tissue clearing relies on the passive diffusion of biochemical reagents in the tissue to complete the transparency of the tissue.

[0003] The existing passive tissue clearing device is generally composed of a housing, a fluid driving mechanism, and a sample bottle, etc. However, the tissue clearing device requires manual assistance to complete the sample loading, such as manually transferring a pipette from one sample bottle to another sample bottle so that the pipette absorbs reagents in different proportions to complete the sample loading, and this process takes a long time.

[0004] Therefore, there is an urgent need for a tissue transparency device that can achieve automatic sample loading. Summary of the invention

[0005] The present application is provided to solve the above problems existing in the prior art. According to the tissue clearing device of the embodiment of the present application, automatic sample addition can be realized to improve the efficiency of tissue clearing.

[0006] The embodiment of the present application provides a tissue clearing device, comprising: an oscillation unit, a sample chamber unit, a waste liquid collection unit, a control unit, and a transport unit;

[0007] The oscillation unit comprises: a cabin, an oscillation mechanism and a temperature control device;

[0008] The sample chamber unit comprises: a sample loading unit and a sample chamber; the sample chamber is arranged on the oscillating mechanism and located in the chamber; the sample loading unit comprises: a sample loading tube; the sample chamber comprises: a chamber body; the chamber body has a plurality of operation holes;

[0009] The waste liquid collection unit comprises: a waste liquid container, a discharge pipeline and a first valve;

[0010] The delivery unit comprises: a plurality of reagent containers, a plurality of metering units, a delivery pipeline and a second valve arranged on the delivery pipeline; the delivery pipeline is respectively connected to each of the reagent containers and the first valve; the first valve is respectively connected to the discharge pipeline and the sample adding tube;

[0011] The control unit is used to control the temperature in the chamber through the temperature control device; control the oscillation of the oscillation mechanism to drive the sample chamber to oscillate; control the position of the sample tube to correspond to the operation hole; control the first valve and the second valve based on the metering unit to allow the transparent reagent stored in the reagent container to be transported to the sample tube through the transport pipeline, or to allow the cleaning liquid stored in the reagent container to be transported to the waste liquid container and the sample tube through the transport pipeline and the discharge pipeline; wherein the cleaning liquid passing through the sample tube is discharged to the waste liquid container through the discharge pipeline;

[0012] The sample adding tube is used to add the transparent reagent into the operation hole.

[0013] The tissue clearing device of each embodiment of the present application controls the first valve and the second valve based on the metering unit, so that the clearing reagent stored in the reagent container is transported to the sample tube through the delivery pipeline. The control unit can control the sample tube to correspond to the position of the operation hole, so as to add the clearing reagent to the operation hole where the tissue is stored. The clearing reagent can be realized by the control unit to control the switch of the first valve and the second valve, without the need for manual auxiliary sample addition. In addition, if the reagent container stores deionized water, the cleaning liquid stored in the reagent container can be transported to the waste liquid container and the sample tube through the delivery pipeline and the discharge pipeline by controlling the first valve and the second valve, so as to clean the sample tube and the delivery pipeline and avoid cross infection of the clearing reagent. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] In the drawings, which are not necessarily drawn to scale, the same reference numerals may describe similar parts in different views. The same reference numerals with letter suffixes or different letter suffixes may represent different instances of similar parts. The accompanying drawings generally illustrate various embodiments by way of example and not limitation, and together with the specification and claims, are used to illustrate the disclosed embodiments. When appropriate, the same reference numerals are used throughout the drawings to refer to the same or similar parts. Such embodiments are illustrative and are not intended to be exhaustive or exclusive embodiments of the present apparatus or method.

[0015] Figure 1 is a schematic diagram of a tissue clearing device provided by an embodiment of the present application;

[0016] Figure 2 is a schematic diagram of an oscillation unit provided by an embodiment of the present application;

[0017] Figure 3 is a schematic diagram of a sample capsule unit provided by an embodiment of the present application;

[0018] Figure 4is a schematic diagram of a hatch cover provided by an embodiment of the present application;

[0019] Figure 5 is a schematic diagram of a cover provided by an embodiment of the present application;

[0020] Figure 6 is a schematic diagram of a sample chamber provided by an embodiment of the present application;

[0021] Figure 7 is a schematic diagram of a cabin provided by an embodiment of the present application;

[0022] Figure 8 is a schematic diagram of a tissue container provided by an embodiment of the present application;

[0023] Fig. 9 It is a schematic diagram of a rotating mechanism of a sample chamber base provided in one embodiment of the present application. DETAILED DESCRIPTION

[0024] In order to enable those skilled in the art to better understand the technical solution of the present application, the present application is described in detail below in conjunction with the accompanying drawings and specific embodiments. The embodiments of the present application are further described in detail below in conjunction with the accompanying drawings and specific embodiments, but are not intended to limit the present application. The terms "first", "second" and "third" used in the present application are only intended to distinguish the corresponding features, do not represent the need for such an order, and do not necessarily represent only the singular form.

[0025] refer to Figure 1 An embodiment of the present application provides a tissue clearing device, including: a transport unit 000, an oscillation unit 100, a sample chamber unit 200, a waste liquid collection unit 300 and a control unit 400.

[0026] The oscillation unit 100 includes: a chamber, an oscillation mechanism and a temperature control device.

[0027] The sample chamber unit 200 comprises: a sample adding unit and a sample chamber; the sample chamber is arranged on the oscillating mechanism and is located in the chamber; the sample adding unit comprises: a sample adding tube; the sample chamber comprises: a chamber body; and a plurality of operation holes are arranged on the chamber body.

[0028] The waste liquid collection unit 300 includes: a waste liquid container, a discharge pipeline and a first valve.

[0029] The delivery unit 000 includes: multiple reagent containers, multiple metering units, a delivery pipeline and a second valve arranged on the delivery pipeline; the delivery pipeline is respectively connected to each reagent container and the first valve; the first valve is respectively connected to the discharge pipeline and the sample adding tube.

[0030] The control unit 400 is used to control the temperature in the chamber through a temperature control device; control the oscillation of the oscillation mechanism to drive the sample chamber to oscillate; control the position of the sample tube to correspond to the operation hole; control the first valve and the second valve based on the metering unit to allow the transparent reagent stored in the reagent container to be transported to the sample tube through the transport pipeline, or to allow the cleaning liquid stored in the reagent container to be transported to the waste liquid container and the sample tube through the transport pipeline and the discharge pipeline; wherein the cleaning liquid passing through the sample tube is discharged to the waste liquid container through the discharge pipeline.

[0031] Sample tube, used to add clearing reagent into the operation well.

[0032] The embodiment of the present application is based on the metering unit controlling the first valve and the second valve, so that the transparent reagent stored in the reagent container is transported to the sample tube through the delivery pipeline. The control unit can control the sample tube to correspond to the position of the operation hole, so as to add the transparent reagent to the operation hole of the storage tissue. The transparent reagent can be realized by the control unit switching control of the first valve and the second valve, without manual auxiliary sample addition. In addition, if the reagent container stores deionized water, the cleaning liquid stored in the reagent container can be transported to the waste liquid container and the sample tube through the delivery pipeline and the discharge pipeline by controlling the first valve and the second valve, so as to clean the sample tube and the delivery pipeline and avoid cross infection of the transparent reagent.

[0033] In one embodiment of the present application, the sample loading unit further includes: a cover body and a support mechanism;

[0034] The cover body is provided with a through hole, one end of the support mechanism is connected to the sample adding tube, and the other end is connected to the cover body;

[0035] The sample chamber also includes: a plurality of tissue containers and a sample chamber base; the tissue containers are hollow structures;

[0036] The cabin body is also provided with a waste liquid hole, a plurality of container holes and sample addition holes corresponding to the container holes one by one, and the bottom of the container hole is connected with the bottom of the corresponding sample addition hole and the operation hole;

[0037] The sample chamber base includes: a rotating mechanism and a waste liquid tank;

[0038] The rotating mechanism is connected to the cover body, and the discharge pipeline is connected to the waste liquid tank;

[0039] A control unit is used to control the rotating mechanism to drive the cover body to rotate so that the through hole corresponds to the position of the sample adding hole; wherein the cleaning liquid passing through the sample adding tube is stored in the waste liquid tank and discharged to the waste liquid container through the discharge pipeline;

[0040] The sample adding tube is used to add the transparent reagent into the tissue container through the through hole and the sample adding hole, or to add the cleaning liquid into the waste liquid tank through the through hole and the waste liquid hole.

[0041] The support mechanism is used to stabilize the sample tube. In this embodiment, the rotating mechanism drives the cover body to rotate so that the through hole corresponds to the position of the sample hole. In actual application scenarios, the through hole can also be driven to rotate to correspond to the position of the sample hole. In order to avoid damage to the tissue, this embodiment completes the sample loading through the sample hole to avoid adding reagents directly to the container hole. The present application controls the rotating mechanism to drive the cover body to rotate, so that the sample tube adds the tissue reagent to different operation holes, which can improve the efficiency of loading.

[0042] In one embodiment of the present application, the supporting mechanism includes: a sample adding tube joint, a lifting cantilever, a return spring, a lifting cantilever guide rod, a lifting cantilever push rod and a knob screw.

[0043] The cover body comprises: a bottom plate and columns fixed on the bottom plate.

[0044] The bottom plate is provided with a through hole and a plurality of fixing holes.

[0045] The side of the column has grooves.

[0046] The sample adding tube is sealed and connected to the sample adding tube joint, and the sample adding tube is fixedly connected to the lifting cantilever. The lifting cantilever is located in the groove, the reset spring is sleeved on the lifting cantilever guide rod, the reset spring is located above the lifting cantilever, and the lifting cantilever guide rod is inserted into the bottom plate and the lifting cantilever.

[0047] The rotating mechanism comprises: a sample compartment cover turntable flange, a driving push rod, a push rod motor, a first gear, a second gear and a turntable driving motor.

[0048] The sample compartment cover turntable flange is fixedly connected to the first gear, and the bottom plate and the sample compartment cover turntable flange are threadedly connected by knob screws and fixing holes; the push rod motor controls the driving push rod to move upward in the center hole of the sample compartment cover turntable flange, and the driving push rod pushes the lifting cantilever push rod to move upward, and the lifting cantilever moves downward under the action of the reset spring, and the turntable driving motor controls the second gear to rotate, the first gear is meshed with the second gear, the first gear drives the sample compartment cover turntable flange to rotate, and the sample compartment cover turntable flange drives the sample loading unit to rotate.

[0049] The sample tube connector can be replaced by a support component connected to the sample tube buckle, and the sample compartment cover turntable flange can also be connected to the fixing hole by a buckle. The rotating mechanism provided in this embodiment is used to drive the sample adding unit. In actual application scenarios, the rotating mechanism can be adjusted to drive the cabin. The support mechanism and rotating mechanism provided in this application can accurately move the sample tube to the corresponding position to ensure the accuracy of the sample addition.

[0050] In one embodiment of the present application, the sample chamber further comprises: a hole cover;

[0051] The hole cover comprises a sealing ring and a cover body; the cover body is threadedly connected to the cabin body, and the sealing ring is located between the cover body and the cabin body.

[0052] In practical application scenarios, the hole cover can also be formed integrally with the chamber body. Through the structural design of the present application, the sample chamber can be cleaned more conveniently.

[0053] In one embodiment of the present application, the oscillation mechanism comprises: an oscillation table drive mechanism and a horizontal oscillation platform;

[0054] The oscillation table driving mechanism is located outside the cabin. Under the control of the control unit, the oscillation table driving mechanism transmits the horizontal rotational motion to the horizontal oscillation platform through the rotating shaft, so that the horizontal oscillation platform oscillates in a horizontal circular direction.

[0055] The oscillating platform driving mechanism can also be located inside the cabin, and the horizontal oscillating platform can also reciprocate left and right under the driving of the oscillating platform driving mechanism. The oscillating mechanism can make the tissue fully contact with the transparent reagent, thereby improving the efficiency of tissue transparentization.

[0056] In one embodiment of the present application, the temperature control device includes: a refrigeration and heating device, an air duct baffle and a temperature sensor;

[0057] The refrigeration and heating device includes: a semiconductor chip refrigeration module, a circulation fan, a heater, and an evaporator;

[0058] The air duct baffle is used to divide the interlayer air duct in the cabin, and the interlayer air duct is provided with a circulation fan, a heater and an evaporator;

[0059] The semiconductor chip refrigeration module is located outside the cabin and is used to conduct cold energy to the evaporator through the cooling material;

[0060] A circulation fan, used for sucking the gas in the cabin into the sandwich air duct, and blowing the gas passing through the heater and the evaporator to the outside of the sandwich air duct;

[0061] Temperature sensor, used to collect the temperature in the cabin;

[0062] The control unit is used to control the semiconductor chip refrigeration module, circulation fan, heater and evaporator based on the temperature collected by the temperature sensor.

[0063] The embodiment of the present invention controls the temperature in the chamber through a temperature control device to improve the quality of tissue transparency. The temperature control device of this embodiment adopts gas cooling. In actual application scenarios, the temperature control device can also be implemented by liquid cooling.

[0064] Some clearing reagents need to be mixed before adding to the sample, while some clearing reagents can be added directly to the sample. For these two situations, the delivery unit may be applicable only to the former situation, only to the latter situation, or to both situations.

[0065] For the first case:

[0066] In one embodiment of the present application, the delivery unit further comprises: a premixing chamber, a first pump, and a second pump;

[0067] The second valve includes: a first solenoid valve and a plurality of second solenoid valves; the second solenoid valves correspond to the reagent containers one by one;

[0068] The delivery pipeline includes: transport pipeline and exhaust pipeline;

[0069] The second solenoid valve is respectively connected to the first pump and its corresponding reagent container through a transport pipeline, the premixing chamber is respectively connected to the first solenoid valve and the first pump through a transport pipeline, the emptying pipeline is connected to the premixing chamber, and the second pump is respectively connected to the first solenoid valve and the first valve through a transport pipeline;

[0070] A premixing chamber, used for mixing transparent reagents in multiple reagent containers;

[0071] Drain the pipeline to drain the residual liquid in the transport pipeline after cleaning;

[0072] The control unit is used to control the on and off of the second solenoid valve so that the first pump draws the transparent reagent into the premixing chamber for mixing or draws the cleaning liquid to clean the premixing chamber; controls the first solenoid valve and the second pump to deliver the transparent reagent or the cleaning liquid to the first valve.

[0073] This embodiment is suitable for scenarios where transparent reagents need to be mixed in advance. Through the embodiment of the present invention, transparent reagents in multiple reagent containers can be mixed, and the mixed transparent reagents can be automatically added to the tissue container, and the cleaning of the transport pipeline and the pre-mixing chamber can be controlled by valves.

[0074] For the second case:

[0075] In one embodiment of the present application, the second valve includes: a multi-channel switching valve;

[0076] The delivery unit includes: a third pump;

[0077] The multi-channel switching valve is respectively connected to the multiple reagent containers and the third pump through the transport pipeline, and the multi-channel switching valve is connected to the exhaust pipeline;

[0078] The third pump is connected to the first valve;

[0079] The control unit is used to control the multi-channel switching valve to access different reagent containers so that the third pump delivers the transparent reagent or the cleaning solution to the first valve.

[0080] In this embodiment, the transparent reagent to be added is switched by the multi-channel switching valve, and the transparent reagent will be mixed after being added to the operation hole. If deionized water or other cleaning liquid is added to the reagent container, the multi-channel switching valve and the transport pipeline can be cleaned.

[0081] If the device has components corresponding to the above two situations at the same time, then the device is applicable to both situations.

[0082] In one embodiment of the present application, the tissue container is a barrel-shaped hollow structure, the sides and bottom of the barrel-shaped hollow structure are hollowed out, and the top opening of the barrel-shaped hollow structure is a flange structure;

[0083] a tissue container for placing tissue;

[0084] The tissue container is connected to the sample loading hole through a flange structure.

[0085] The tissue container can be used to store tissue, so as to facilitate taking out the tissue after being transparentized.

[0086] In one embodiment of the present application, the discharge pipeline includes: a first discharge pipeline, a second discharge pipeline, and a third discharge pipeline;

[0087] The waste liquid collection unit also includes: a third valve, a fourth pump and an exhaust muffler;

[0088] One end of the first discharge pipeline is connected to the first valve, and the other end is input into the waste liquid container;

[0089] a fourth pump, used to extract air from the waste liquid container through a third exhaust pipeline extending into the waste liquid container;

[0090] Exhaust silencer, used to reduce the noise level generated during the air extraction process;

[0091] The control unit is used to control the first valve and the fourth pump to transport the cleaning liquid in the transport pipeline to the waste liquid container through the first discharge pipeline or to absorb the transparent reagent in the sample chamber unit into the waste liquid container; control the third valve and the fourth pump to transport the waste liquid in the waste liquid tank to the waste liquid container.

[0092] In this embodiment, the waste liquid after cleaning the delivery pipeline and the sample adding tube is discharged to the waste liquid container through the discharge pipeline, which is convenient for centralized treatment and avoids cross contamination of reagents in the pipeline.

[0093] In one embodiment of the present application, reference Figure 1The delivery unit 000 includes: multiple reagent containers 011-020, multiple metering units 001-010, a transport pipeline 030, an emptying pipeline 031, a first solenoid valve 026, multiple second solenoid valves 021-023, a premixing chamber 025, a first pump 024 and a second pump 027, a multi-channel switching valve 028 and a third pump 029.

[0094] The transport pipeline 030 is connected to each reagent container 011 - 020 and the first valve 303 respectively; the first valve 303 is connected to the discharge pipeline 301 and the sample adding tube 211 respectively; and the third pump 029 is connected to the first valve 303 .

[0095] The metering unit may be a weighing sensor, which can detect the remaining reagent capacity in real time by collecting the weighing sensor signal at the corresponding reagent position in real time, and can also detect the amount of reagent transported outward within a certain period of time, so as to calculate the average flow value of the reagent transported to the external pipeline. The metering unit may also be a flow meter, etc.

[0096] The premixing chamber 025 is used to premix reagents of different solubility ratios (for example: 20% stock solution 1 + deionized water, 40% stock solution 1 + deionized water, 66% stock solution 1 + 33% stock solution 2 + deionized water, etc.) according to the transparent formula standard procedure, and then transport the mixed reagents to the sample chamber for use.

[0097] The transport pipeline 030 is used to clean the remaining reagents in the pipeline and the dead volume liquid between the valve body and the rotor in the multi-channel switching valve. After the cleaning liquid passes through the transport pipeline 030, the multi-channel switching valve 028 switches to the drain pipeline 031 to discharge the residual liquid in the multi-channel to facilitate the subsequent reagents to enter the transport pipeline 030.

[0098] In one embodiment of the present application, reference Figure 1 and Figure 2 The oscillation unit 100 includes: a chamber 101, an oscillation table driving mechanism 110, a horizontal oscillation platform 111, a refrigeration and heating device 120, an air duct baffle 125 and a temperature sensor 131. The refrigeration and heating device 120 includes: a semiconductor chip refrigeration module 121, a circulation fan 122, a heater 123 and an evaporator 124.

[0099] The temperature inside the cabin 101 is collected in real time by the temperature sensor 131, and the control unit 400 performs algorithm adjustment, and outputs instructions to control the refrigeration and heating device 120 to heat or cool, so as to maintain a constant temperature inside the cabin 101. The air duct baffle 125 separates the cabin 101 into a sandwich air duct, and the circulating fan 122, the heater 123 and the evaporator 124 are installed inside the sandwich air duct.

[0100] The semiconductor chip refrigeration module 121 is placed outside the cabin 101 to facilitate heat dissipation at the hot end. It conducts cold air to the evaporator 124 through the cooling material. After the circulating fan 122 rotates, a large amount of air inside the cabin 101 can be sucked into the interlayer air duct, and the air is blown to the outside of the interlayer air duct after passing through the heater 123 and the evaporator 124. After repeated cycles, a circulating air flow channel will be formed inside the cabin 101. The working mode switching of the semiconductor chip refrigeration module 121 and the heater 123 can realize the heating and cooling control of the cabin 101 until the temperature is constant.

[0101] The oscillation platform driving mechanism 110 is placed outside the cabin 101 , and transmits the horizontal rotational motion to the horizontal oscillation platform 111 through the rotating shaft, so that the horizontal oscillation platform 111 realizes horizontal circular oscillation.

[0102] In one embodiment of the present application, reference Figure 3 The sample chamber unit 200 includes: a chamber cover 210, a sample chamber 220, and a sample chamber base 230.

[0103] In one embodiment of the present application, reference Figure 4 The hatch cover 210 includes: a sample adding tube 211, a sample adding tube joint 212, a lifting cantilever 213, a return spring 214, a lifting cantilever guide rod 215, a lifting cantilever push rod 216, a cover body 217 and a knob screw 218.

[0104] In one embodiment of the present application, reference Figure 5 The cover body 217 includes: a bottom plate 2171, a through hole 2172, a fixing hole 2173, a column 2174 fixed on the bottom plate 2171, and a groove 2175 on the side of the column.

[0105] Among them, the sample adding tube 211 and the sample adding tube joint 212 are sealed and connected, and are fixedly connected to the lifting cantilever 213. The lifting cantilever is in the groove 2175 on the side of the column in the cover body 217. The reset spring 214 is sleeved on the lifting cantilever guide rod 215. The reset spring 214 is above the lifting cantilever 213. The lifting cantilever guide rod 215 is inserted into the cover body 217 and the lifting cantilever 213. The lifting cantilever guide rod 215 and the groove 2175 jointly limit the lifting cantilever 213 to only move up and down. Under the action of the reset spring 214, the hatch cover 210 is always in the lower limit position, and the sample adding tube 211 is in the center position of being fully inserted into the through hole 2172.

[0106] In one embodiment of the present application, reference Figure 6 The sample chamber 220 includes: a chamber body 221 , a hole cover 222 , and a tissue container 223 .

[0107] In one embodiment of the present application, reference Figure 7The chamber body 221 includes: an operation hole 2211, a sample adding hole 2212, a container hole 2214, a waste liquid hole 2213, and a center hole 2215. The hole cover 222 includes: a sealing ring 2221 and a cover body 2222.

[0108] In one embodiment of the present application, reference Figure 8 The tissue container 223 includes: a small grid hole 2231 on the side, a round hole 2232 at the bottom and a flange structure 2233. The tissue sample is placed in the tissue container 223, and then the tissue container 223 is placed in the corresponding container hole 2214 in the cabin 221, and the hole cover 222 is connected and fixed to the cabin 221 through a thread. Among them, the operation hole 2211 and the hole cover 222 squeeze the sealing ring 2221 to deform it to play a sealing role.

[0109] In the embodiment of the present application, the sample addition holes, container holes and operation holes correspond one to one, so that the transparentizing reagent can penetrate the tissue sample more fully, the biological sample transparentization efficiency is high, and sample confusion is also avoided.

[0110] In one embodiment of the present application, reference Figure 3 and Fig. 9 The sample chamber base 230 includes: a waste liquid tank 231, a waste liquid tank drain connector 232, a sample chamber cover turntable flange 233, a driving push rod 234, a push rod motor 235, a first gear 236, a second gear 237, and a turntable driving motor 238. The sample chamber cover turntable flange 233 is fixedly connected to the first gear 236, and the push rod motor 235 is fixedly connected to the sample chamber cover turntable flange 233.

[0111] The hatch cover 210 is connected and fixed to the sample hatch cover turntable flange 233 by the knob screw 218 and the turntable flange thread 2331, the lifting cantilever push rod 216 contacts the driving push rod 234, the push rod motor 235 drives the push rod 234 to move upward in the center hole 2332 of the sample hatch cover turntable flange 233, the driving push rod 234 pushes the lifting cantilever push rod 216 to move upward synchronously, and the lifting cantilever 213 and the sample tube 211 move upward synchronously. The push rod motor 235 makes the driving push rod 234 move downward in the center hole 2332 of the sample hatch cover turntable flange 233, the lifting cantilever 213 moves downward under the action of the reset spring 214, the lifting cantilever push rod 216 and the driving push rod 234 always keep in contact under the action of the reset spring 214, and the lifting cantilever 213 and the sample tube 211 can move downward synchronously.

[0112] The turntable drive motor 238 drives the second gear 237 to rotate, and the second gear 237 is meshed with the first gear 236, and can transmit power to the first gear 236 for rotation. The first gear 236 then transmits power to the sample chamber cover turntable flange 233. The sample chamber cover turntable flange 233 can drive the chamber cover 210 connected thereto to rotate as a whole, and its rotation direction, rotation angle and rotation angular velocity can all be achieved by controlling the turntable drive motor 238.

[0113] The sample chamber 220 can process multiple tissue samples at the same time, and the automatic addition of reagents and automatic removal of waste liquid can be realized through the cooperation of the chamber cover 210 and the sample chamber base 230. After the sample chamber 220 is connected to the sample chamber base 230, the waste liquid hole 2213 is aligned with the axis of the waste liquid tank 231, which is used to collect the reagent liquid and the cleaning pipeline liquid remaining in the pipeline when the pipeline in the reagent delivery pipeline unit 000 is emptied, and discharged out of the chamber through the waste liquid collection unit 300.

[0114] Unscrew the knob screw 218 and remove the cabin cover 210, move the sample cabin 220 upward, and then remove the sample cabin 220 from the sample cabin base 230. Then unscrew the hole cover 222 and take out the tissue container 223 to clean the surface of the operation hole 2211 in the cabin body 221.

[0115] In one embodiment of the present application, reference Figure 1 The waste liquid collection unit 300 includes: a first discharge pipeline 301, a second discharge pipeline 302, a first valve, namely a two-position three-way solenoid valve 303, a third valve, namely a two-position two-way solenoid valve 304, a waste liquid container 305, a fourth pump 306, and an exhaust muffler 307.

[0116] The first discharge pipeline 301 and the transport pipeline 030 are connected to the inlet of the two-position three-way solenoid valve 303, and the outlet of the two-position three-way solenoid valve 303 is connected to the sample addition pipe joint 212. The state of the two-position three-way solenoid valve 303 is controlled by the control unit 400 to realize the delivery or discharge of reagents to the operation hole 2211 in the cabin 221. The second discharge pipeline 302 is connected to the waste liquid tank discharge joint 232, and the two-position two-way solenoid valve 304 is connected to the second discharge pipeline 302, which is used to extract the waste liquid in the waste liquid tank 231. The fourth pump 306 is connected to the exhaust port of the waste liquid container 305, which is used to exhaust the air in the waste liquid container to maintain negative pressure, and provide negative pressure traction suction for the first discharge pipeline 301 and the second discharge pipeline 302, so that the waste liquid is sucked into the waste liquid container 305.

[0117] The control unit 400 includes: a control circuit and a human-machine interface, and the control circuit and the human-machine interface can realize data interaction and control. The user can input the proportion of various transparent reagents, control the switch of pumps or valves, etc. through the human-machine interface.

[0118] In one embodiment of the present application, the weighing sensor signals at the corresponding reagent positions are collected in real time by weighing sensors 001 to 010, that is, the remaining reagent capacity can be detected in real time. If the reagent inventory is lower than the single sample transparency usage, the human-computer interaction interface prompts to add reagents. If the reagent inventory meets the sample transparency usage, the control unit sends a reagent premixing instruction. The premixing formula includes: 20% stock solution 1 + deionized water, 40% stock solution 1 + deionized water, 80% stock solution 1 + deionized water, 66% stock solution 1 + 33% stock solution 2 + deionized water, etc. The first pump 024 is controlled to absorb the corresponding proportion of reagents into the premixing chamber 025 for mixing. The second solenoid valves 021, 022, and 023 are responsible for the opening and closing of the deionized water, reagent stock solution 1, and reagent stock solution 2 pipelines, respectively, to facilitate the preparation of reagents in different proportions. The premixing chamber 025 has a swinging function to facilitate accelerated mixing of reagents. The premixing chamber 025 is connected to an emptying pipeline 031, the first solenoid valve 026 is responsible for opening and closing the downstream pipeline of the premixed reagent, and the second pump 027 is responsible for transporting the reagents in the premixing chamber 025 to the sample chamber. Reagents 3 to 9 do not need to be premixed, so the transport pipeline can be directly connected to the multi-channel switching valve 028. In addition, the transport pipeline 030 and the emptying pipeline 031 also need to be connected to the multi-channel switching valve 028 to clean up the remaining reagents in the pipeline and the dead volume liquid between the valve body and the rotor in the multi-channel switching valve 028. The third pump 029 is responsible for transporting the reagents upstream of the multi-channel switching valve 028 to the sample chamber.

[0119] In one embodiment of the present application, the pipeline cleaning process when premixing is required is as follows: the second solenoid valve 021 is turned on, the first pump 024 is started to transport deionized water to the premixing chamber 025, and then the second solenoid valve 021 is disconnected, the first pump 024 is stopped, and after the premixing chamber 025 swings for 30 seconds, the cabin cover 210 is rotated so that the sample tube 211 is aligned with the center of the waste liquid hole 2213, the first solenoid valve 026 is opened, the second pump 027 transports the cleaning liquid to the waste liquid tank 231, the third valve 304 is turned on, and the fourth pump 306 uses negative pressure to suck the waste liquid into the waste liquid container 305, the third valve 304 is disconnected, and the fourth pump 306 stops working.

[0120] In one embodiment of the present application, the pipeline cleaning process when premixing is not required is as follows: after the hatch 210 is rotated so that the sample addition tube 211 is aligned with the center of the waste liquid hole 2213, the multi-channel switching valve 028 is switched to the transport pipeline 030, the third pump 029 is started to transport deionized water to the waste liquid tank 231, and then the multi-channel switching valve 028 is switched to the drain pipeline 031. The third pump 029 draws external air into the pipeline to discharge the cleaning liquid in the pipeline into the waste liquid tank 231. The third valve 304 is turned on, and the fourth pump 306 draws the waste liquid into the waste liquid collection bottle 305 through negative pressure. The third valve 304 is disconnected, and the fourth pump 306 stops working.

[0121] The devices provided in the above two embodiments add the functions of pipeline cleaning and emptying, thereby reducing the problem of reagent cross contamination in the sample chamber.

[0122] In one embodiment of the present application, the reagent adding process is as follows: after the hatch 210 rotates to a position directly above a certain operating hole 2211, so that the sample tube 211 is aligned with the center of the sample hole 2212 on the cabin body 221, the lifting cantilever 213 drives the sample tube 211 to move to the lower limit position, and the two-position three-way solenoid valve 303 switches to the right position. The delivery unit 000 delivers the sampled reagent liquid to the operating hole 2211 through the pipeline. After the sample addition is completed, the delivery unit 000 stops the reagent liquid delivery, and the lifting cantilever 213 drives the sample tube 211 to move to the upper limit position.

[0123] The device provided in the embodiment of the present application automates the sample addition process, eliminates the need for manual intervention in liquid replacement, and reduces manual operation costs.

[0124] In one embodiment of the present application, the reagent discharge process is as follows: the hatch 210 rotates to the top of a certain operation hole 2211 so that the sample tube 211 is aligned with the center of the sample hole 2212 on the cabin body 221, and then the lifting cantilever 213 drives the sample tube 211 to move to the lower limit position, and the two-position three-way solenoid valve 303 is switched to the left position. The fourth pump 306 is used to discharge the air in the waste liquid container 305 to maintain a negative pressure, and the waste liquid in the operation hole 2211 is sucked into the waste liquid container 305. After the sample cabin finishes discharging the waste liquid, the fourth pump 306 stops working, and the lifting cantilever 213 drives the sample tube 211 to move to the upper limit position.

[0125] The cleaning process of the cabin body 221 is as follows: unscrew the knob screw 218 and remove the cabin cover 210, move the sample cabin 220 upward, and then remove the sample cabin 220 from the sample cabin base 230, then unscrew the hole cover 222 and take out the tissue container 223 to clean the surface of the operating hole 2211 in the cabin body 221.

[0126] The sample chamber of the device provided in the embodiment of the present application has a detachable cleaning function, which reduces the problem of cross contamination of reagents in the sample chamber.

[0127] Furthermore, although exemplary embodiments have been described herein, the scope thereof includes any and all embodiments based on the present application having equivalent elements, modifications, omissions, combinations (eg, schemes that cross various embodiments), adaptations, or changes.

[0128] The elements in the claims are to be interpreted broadly based on the language employed in the claims and are not limited to the examples described in this specification or during the prosecution of the application, which examples are to be interpreted as non-exclusive. Therefore, this specification and examples are intended to be considered as examples only, with the true scope and spirit being indicated by the claims and the full scope of their equivalents.

[0129] The above description is intended to be illustrative rather than restrictive. For example, the above examples (or one or more of them) can be used in combination with each other. For example, those of ordinary skill in the art can use other embodiments when reading the above description. In addition, in the above-mentioned specific embodiments, various features can be grouped together to simplify the application. This should not be interpreted as an intention that a disclosed feature that does not require protection is necessary for any claim. On the contrary, the subject matter of the present invention may be less than all the features of a specific disclosed embodiment. Thus, the claims are incorporated into the specific embodiments as examples or embodiments, wherein each claim is independently used as a separate embodiment, and it is considered that these embodiments can be combined with each other in various combinations or arrangements. The scope of the present invention should be determined with reference to the attached claims and the full scope of equivalent forms granted by these claims.

Claims

1. A tissue clearing device, It is characterized in that include: An oscillation unit, a sample chamber unit, a waste liquid collection unit, a control unit and a transport unit; The oscillation unit comprises: a cabin, an oscillation mechanism and a temperature control device; The sample chamber unit comprises: a sample loading unit and a sample chamber; the sample chamber is arranged on the oscillating mechanism and located in the chamber; the sample loading unit comprises: a sample loading tube; the sample chamber comprises: a chamber body; the chamber body has a plurality of operation holes; The waste liquid collection unit comprises: a waste liquid container, a discharge pipeline and a first valve; The delivery unit comprises: a plurality of reagent containers, a plurality of metering units, a delivery pipeline and a second valve arranged on the delivery pipeline; the delivery pipeline is respectively connected to each of the reagent containers and the first valve; the first valve is respectively connected to the discharge pipeline and the sample adding tube; The control unit is used to control the temperature in the chamber through the temperature control device; control the oscillation of the oscillation mechanism to drive the sample chamber to oscillate; control the position of the sample tube to correspond to the operation hole; control the first valve and the second valve based on the metering unit to allow the transparent reagent stored in the reagent container to be transported to the sample tube through the transport pipeline, or to allow the cleaning liquid stored in the reagent container to be transported to the waste liquid container and the sample tube through the transport pipeline and the discharge pipeline; wherein the cleaning liquid passing through the sample tube is discharged to the waste liquid container through the discharge pipeline; The sample adding tube is used to add the transparent reagent into the operation hole.

2. The tissue clearing device according to claim 1, It is characterized in that The sample adding unit further comprises: a cover body and a supporting mechanism; The cover body is provided with a through hole, one end of the support mechanism is connected to the sample addition tube, and the other end is connected to the cover body; The sample chamber further comprises: a plurality of tissue containers and a sample chamber base; the tissue containers are hollow structures; The cabin body is also provided with a waste liquid hole, a plurality of container holes and sample addition holes corresponding to the container holes one by one, and the bottom of the container hole and the bottom of the corresponding sample addition hole are connected to the operation hole; The sample chamber base comprises: a rotating mechanism and a waste liquid tank; The rotating mechanism is connected to the cover body, and the discharge pipeline is connected to the waste liquid tank; The control unit is used to control the rotating mechanism to drive the cover body to rotate so that the through hole corresponds to the position of the sample loading hole; wherein the cleaning liquid passing through the sample loading tube is stored in the waste liquid tank and discharged to the waste liquid container through the discharge pipeline; The sample adding tube is used to add the transparent reagent into the tissue container through the through hole and the sample adding hole, or to add the cleaning liquid into the waste liquid tank through the through hole and the waste liquid hole.

3. The tissue clearing device according to claim 2, It is characterized in that The supporting mechanism comprises: a sample adding pipe joint, a lifting cantilever, a reset spring, a lifting cantilever guide rod, a lifting cantilever push rod and a knob screw; The cover body comprises: a bottom plate, and a column fixed on the bottom plate; The bottom plate is provided with the through hole and a plurality of fixing holes; The side surface of the column is provided with a groove; The sample adding tube is sealed and connected to the sample adding tube joint, the sample adding tube is fixedly connected to the lifting cantilever, the lifting cantilever is located in the groove, the reset spring is sleeved on the lifting cantilever guide rod, the reset spring is located above the lifting cantilever, and the lifting cantilever guide rod is inserted into the bottom plate and the lifting cantilever; The rotating mechanism comprises: a sample compartment cover turntable flange, a driving push rod, a push rod motor, a first gear, a second gear and a turntable driving motor; The sample chamber cover turntable flange is fixedly connected to the first gear, and the base plate and the sample chamber cover turntable flange are threadedly connected by the knob screw and the fixing hole; the push rod motor controls the driving push rod to move upward in the center hole of the sample chamber cover turntable flange, and the driving push rod pushes the lifting cantilever push rod to move upward, and the lifting cantilever moves downward under the action of the reset spring, and the turntable driving motor controls the second gear to rotate, and the first gear is meshed with the second gear, and the first gear drives the sample chamber cover turntable flange to rotate, and the sample chamber cover turntable flange drives the loading unit to rotate.

4. The tissue clearing device according to claim 2, It is characterized in that The sample chamber further comprises: a hole cover; The hole cover comprises a sealing ring and a cover body; the cover body is threadedly connected to the cabin body, and the sealing ring is located between the cover body and the cabin body.

5. The tissue clearing device according to claim 1, It is characterized in that The oscillation mechanism comprises: an oscillation table driving mechanism and a horizontal oscillation platform; The oscillation platform driving mechanism is located outside the cabin. Under the control of the control unit, the oscillation platform driving mechanism transmits horizontal rotational motion to the horizontal oscillation platform through a rotating shaft, so that the horizontal oscillation platform oscillates in a horizontal circular direction.

6. The tissue clearing device according to claim 1, It is characterized in that The temperature control device includes: a refrigeration and heating device, an air duct baffle and a temperature sensor; The refrigeration and heating device comprises: a semiconductor chip refrigeration module, a circulation fan, a heater, and an evaporator; The air duct baffle is used to divide the interlayer air duct in the cabin, and the interlayer air duct is provided with the circulation fan, the heater and the evaporator; The semiconductor chip refrigeration module is located outside the cabin and is used to conduct cold energy to the evaporator through a cold conducting material; The circulation fan is used to suck the gas in the cabin into the interlayer air duct and blow the gas passing through the heater and the evaporator to the outside of the interlayer air duct; The temperature sensor is used to collect the temperature in the cabin; The control unit is used to control the semiconductor chip refrigeration module, the circulation fan, the heater and the evaporator based on the temperature collected by the temperature sensor.

7. The tissue clearing device according to claim 1, It is characterized in that The delivery unit further comprises: a premixing chamber, a first pump and a second pump; The second valve comprises: a first solenoid valve and a plurality of second solenoid valves; the second solenoid valves correspond one to one with the reagent containers; The delivery pipeline includes: a transport pipeline and an emptying pipeline; The second solenoid valve is respectively connected to the first pump and the corresponding reagent container through the transport pipeline, the premixing chamber is respectively connected to the first solenoid valve and the first pump through the transport pipeline, the emptying pipeline is connected to the premixing chamber, and the second pump is respectively connected to the first solenoid valve and the first valve through the transport pipeline; The pre-mixing chamber is used to mix the transparent reagents in the plurality of reagent containers; The drain pipeline is used to drain the residual liquid in the transport pipeline after cleaning; The control unit is used to control the on and off of the second solenoid valve so that the first pump draws the transparent reagent into the pre-mixing chamber for mixing or draws the cleaning liquid to clean the pre-mixing chamber; and controls the first solenoid valve and the second pump to deliver the transparent reagent or the cleaning liquid to the first valve.

8. The tissue clearing device according to claim 7, It is characterized in that The second valve further comprises: a multi-channel switching valve; The delivery unit further comprises: a third pump; The multi-channel switching valve is respectively connected to the plurality of reagent containers and the third pump through the transport pipeline, and the multi-channel switching valve is connected to the exhaust pipeline; The third pump is connected to the first valve; The control unit is used to control the multi-channel switching valve to connect to different reagent containers, so that the third pump delivers the transparent reagent or cleaning solution to the first valve.

9. The tissue clearing device according to claim 2, It is characterized in that The tissue container is a barrel-shaped hollow structure, the sides and bottom of the barrel-shaped hollow structure are hollow, and the top opening of the barrel-shaped hollow structure is a flange structure; The tissue container is used to place tissue; The tissue container is connected to the sample adding hole via the flange structure.

10. The tissue clearing device according to claim 2, It is characterized in that The discharge pipeline includes: a first discharge pipeline, a second discharge pipeline and a third discharge pipeline; The waste liquid collection unit further comprises: a third valve, a fourth pump and an exhaust muffler; One end of the first discharge pipeline is connected to the first valve, and the other end is input into the waste liquid container; The fourth pump is used to extract air from the waste liquid container through a third exhaust pipeline extending into the waste liquid container; The exhaust muffler is used to reduce the noise level generated during the air extraction process; The control unit is used to control the first valve and the fourth pump to transport the cleaning liquid in the delivery pipeline to the waste liquid container through the first discharge pipeline or to absorb the transparent reagent in the sample chamber unit into the waste liquid container; and control the third valve and the fourth pump to transport the waste liquid in the waste liquid tank to the waste liquid container through the third valve and the fourth pump.

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