Probe assembly and single cell manipulation device

By designing a probe assembly including a slender hollow structure probe and a clamp, the problem of complex structure and cumbersome operation of microtube probe clamping in the prior art is solved, and the stable clamping and rapid replacement of the probe are achieved, improving the user experience and sealing.

CN119490902BActive Publication Date: 2025-04-01SINBODA BIOTECH (ZHEJIANG) CO LTD
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Patent Information

Application Number
CN202510073456.9
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-01-17
Publication Date
2025-04-01
Estimated Expiration
2045-01-17

AI Technical Summary

Technical Problem

In the prior art, the clamping structure of the microtube probe is designed in complex and the installation process is cumbersome. When replacing the microtube probe, it is necessary to remove the clamping structure and re-debug, which is inconvenient to operate.

Method used

A probe assembly is designed, including an elongated hollow structure probe and a clamp, which consists of a housing, a lock core, an elastic member and an extruder. Through the relative movement of the head and body, the extruder acts on the elastic member to realize clamping and release of the probe.

Benefits of technology

Through structural optimization, stable clamping and rapid replacement of probes are achieved, operating procedures are simplified, user experience is improved, and the sealing of probe components is achieved through elastic parts.

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Abstract

The present application discloses a probe assembly and a single-cell manipulation device, wherein the probe assembly includes: a probe, which is an elongated hollow structure, having a front end and a rear end, and the aperture of the front end is relatively reduced; a clamp, including a shell and a lock core, the shell including a head and a body that are axially relatively movable, and the rear end of the probe passes through the head and extends into the body; the lock core includes an elastic member and an axially movable extrusion member, and the elastic member and the extrusion member have a center hole for the probe to pass through; when the head and the body move toward each other, the extrusion member is driven to act on the elastic member, so that the center hole of the elastic member is reduced, thereby clamping the probe; when the head and the body move in opposite directions, the elastic member is restored due to the removal of external force, and its center hole is enlarged to release the probe. The present application optimizes the structure of the probe assembly, and simultaneously realizes the clamping of the probe and the sealing of the entire probe assembly through the elastic member, thereby improving the integrity, realizing the rapid replacement of the probe, and improving the user experience.
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Description

Technical Field

[0001] The present application relates to the field of cell manipulation technology, and in particular to a probe assembly and a single cell manipulation device. Background Art

[0002] When conducting cell research, it is necessary to observe the specific morphology of the cells and extract the target cells separately for research. The commonly used method for single-cell operation is in situ extraction, which specifically uses a suction needle to suck in a single cell for spatial position transfer. During the operation, the front end opening of the microtube probe used for cell extraction is about 1 to 20 microns, and the extraction and release of a single cell is achieved through changes in air pressure inside the microtube. Therefore, the microtube probe needs to be stably clamped.

[0003] In the prior art, the clamping structure of the microtube probe is complex in design, and the installation process requires repeated debugging to ensure clamping stability and sealing. When replacing the microtube probe, the clamping structure needs to be disassembled and re-debugged, which is cumbersome. Summary of the invention

[0004] In order to solve the above technical problems, the present application discloses a probe assembly, comprising:

[0005] The probe is an elongated hollow structure having a front end and a rear end opposite to each other, and the aperture of the front end is relatively reduced;

[0006] The holder comprises a housing and a lock core assembled inside the housing, wherein the housing comprises a head and a body that are axially movable relative to each other, and the rear end of the probe passes through the head and extends into the body; the lock core comprises an elastic member and an axially movable extrusion member, and the elastic member and the extrusion member are provided with a central hole for the probe to pass through;

[0007] When the head and the body move toward each other, the extrusion member is driven to act on the elastic member, so that the central hole of the elastic member is reduced, thereby clamping the probe;

[0008] When the head and the body move in opposite directions, the elastic member is restored due to the removal of external force, and the central hole thereof is enlarged, thereby releasing the probe.

[0009] Several optional methods are also provided below, but they are not intended to be additional limitations on the above-mentioned overall solution, but are merely further supplements or preferences. Under the premise that there are no technical or logical contradictions, each optional method can be combined with the above-mentioned overall solution separately, and multiple optional methods can also be combined.

[0010] In one embodiment, the head has an adapting groove, the bottom surface of the adapting groove is provided with a mounting groove adapted to the lock core, and the body extends into the adapting groove and contacts the lock core.

[0011] In one embodiment, the elastic member is arranged at the bottom of the installation groove, the extrusion member is movably arranged in the installation groove, one end of the extrusion member is an extrusion end that cooperates with the elastic member, and the other end is a driving end that cooperates with the body.

[0012] In one embodiment, the driving end is abutted against the body through a seal, and the seal has a center hole for the probe to pass through. When the head and the body move toward each other, the extrusion member and the body squeeze the seal, causing the center hole of the seal to shrink, thereby clamping the probe; when the head and the body move away from each other, the seal recovers due to the removal of external force, and its center hole enlarges, thereby releasing the probe.

[0013] In one embodiment, there are multiple elastic members, and the probe sequentially passes through the multiple elastic members and the sealing members to enter the body. When the head and the body move toward each other, the center holes of the multiple elastic members and the sealing members shrink synchronously and clamp and seal different parts of the probe respectively, forming a sealed channel between the front end of the probe and the body.

[0014] In one embodiment, a propulsion unit is fixed on the body, and when the body rotates relative to the head, the propulsion unit drives the head and the body to move toward each other.

[0015] In one embodiment, the head is provided with an anti-slipping piece, and the anti-slipping piece limits the maximum distance that the head and the body can move in opposite directions.

[0016] In one embodiment, a limiting portion is provided inside the body, the probe extends into the body and the rear end is positioned at the limiting portion, and a pressure channel connected to the inside of the probe is provided on the limiting portion.

[0017] In one embodiment, the body is a multi-layer structure and comprises:

[0018] A first cylinder, located in the outer layer and open at both ends, one end being a clamping end extending into the head, and the other end being a pressure end connected to a peripheral device;

[0019] A second cylinder body, located inside the first cylinder body, the second cylinder body comprising an open end close to the clamping end and a closed end located inside the first cylinder body, the closed end forming the limiting portion;

[0020] The third cylinder is located inside the first cylinder and is open at both ends, one end of which is against the closed end of the second cylinder and the other end is close to the pressure end of the first cylinder.

[0021] The present application also discloses a single cell operation device, comprising:

[0022] A stage for fixing the container carrying the sample;

[0023] A probe assembly, which is the probe assembly described in this application;

[0024] a control assembly, including a moving platform for moving the probe assembly in space to adjust the position of the probe;

[0025] A microscopic imaging component, providing a window for positioning the probe;

[0026] An air pressure source assembly is connected to the probe via the holder to provide positive or negative air pressure to the probe in the form of pulses.

[0027] The technical solution disclosed in the present application optimizes the structure of the probe assembly and simultaneously achieves probe clamping and sealing of the entire probe assembly through elastic parts, thereby improving the integrity, improving the probe clamping stability, and providing a structural basis for achieving rapid replacement of the probe, thereby improving the user experience.

[0028] The specific beneficial technical effects will be further explained in the specific implementation methods in combination with specific structures or steps. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is a schematic diagram of the structure of a probe assembly in one embodiment of the present application;

[0030] Figure 2 It is a schematic diagram of the matching between the clamp and the lock core;

[0031] Figure 3 It is a schematic diagram of the internal coordination of the probe assembly;

[0032] Figure 4 A schematic diagram of the cooperation between the clamp and the lock core in another embodiment;

[0033] Figure 5 A schematic diagram of the internal coordination of a probe assembly in another embodiment;

[0034] Figure 6 A schematic diagram of the gas path of the gas pressure source assembly of the single-cell manipulation device in one embodiment of the present application;

[0035] Figure 7 Schematic diagram of generating pulses for the plunger;

[0036] Figure 8 Schematic diagram of the single-cell manipulation device.

[0037] The reference numerals in the figures are described as follows:

[0038] 10. stage; 21. optical microscope objective lens; 22. image detection unit; 23. light source; 50. mobile platform; 60. air pressure source assembly; 61. plunger pump; 61a. inlet end; 61b. outlet end; 61c. plunger; 62. solenoid valve; 62a. common end; 62b. normally open end; 62c. normally closed end; 63. three-way connector; 64. first one-way valve; 65. second one-way valve; 66. air filter; 67. silencer; 68. plug; 70. control system;

[0039] 100. Probe;

[0040] 200, holder;

[0041] 211, head; 2111, adapter slot; 2112, mounting slot; 2113, anti-dropping member;

[0042] 212, body; 2121, propulsion part; 2122, limit part; 2123, pressure channel; 2124, first cylinder; 2125, second cylinder; 2126, third cylinder; 2127, clamping end; 2128, pressure end;

[0043] 220, lock core; 221, elastic member; 222, extrusion member; 2221, extrusion end; 2222, driving end; 223, center hole; 224, sealing member. DETAILED DESCRIPTION

[0044] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0045] It should be noted that when a component is referred to as being "connected" to another component, it may be directly connected to the other component or there may be a central component. When a component is referred to as being "disposed on" another component, it may be directly disposed on the other component or there may be a central component at the same time.

[0046] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0047] Reference Figure 1 To Attachment Figure 3As shown, the present application discloses a probe assembly, including a probe 100 and a holder 200 for cooperating with the probe 100 .

[0048] The probe 100 is a slender hollow structure made of quartz, glass, etc. The probe 100 can be drawn by laser heating from a quartz capillary and has a geometric rotationally symmetrical structure. The interior is hollow and has no movable parts or embedded circuits. The probe 100 has a relative front end and a rear end, both of which are open structures. The size of the rear end is adapted to the holder 200, and the aperture of the front end is relatively reduced, with a flat micro-operation end surface to ensure that the cells will not be damaged.

[0049] The clamp 200 includes a shell and an internal lock core 220 assembled in the shell. The shell includes a head 211 and a body 212 that are axially movable relative to each other. The rear end of the probe 100 passes through the head 211 and extends into the body 212. The body 212 is connected to the interior of the probe 100 and can adjust the internal air pressure of the probe 100 to achieve cell extraction and release.

[0050] The lock core 220 is used to position the probe 100 and includes an elastic member 221 and an axially movable extrusion member 222. The elastic member 221 and the extrusion member 222 have a central hole 223 for the probe 100 to pass through. When the head 211 and the body 212 move toward each other, the extrusion member 222 is driven to act on the elastic member 221, so that the central hole of the elastic member 221 shrinks, thereby clamping the probe 100; when the head 211 and the body 212 move away from each other, the elastic member 221 recovers due to the removal of the external force, and the central hole of the elastic member 221 enlarges, thereby releasing the probe 100. The size of the central hole of the elastic member 221 is adapted to the outer diameter of the probe 100, for example, the inner diameter of the central hole of the elastic member 221 is 1 to 5 mm.

[0051] The elastic member 221 can simultaneously clamp the probe 100 and seal the entire probe assembly under the action of the extrusion member 222, reducing the number of components and improving integrity. The lock core 220 can clamp and release the probe 100 during the relative movement of the head 211 and the body 212, improving the user experience.

[0052] Reference Figure 2In the illustrated embodiment, the head 211 has an adapting groove 2111, and the bottom surface of the adapting groove 2111 is provided with a mounting groove 2112 adapted to the lock core 220, and the body 212 extends into the adapting groove 2111 and contacts the lock core 220, such as an extrusion piece 222 of the lock core 220. Further, the radial dimension of the mounting groove 2112 is smaller than the dimension of the adapting groove 2111, and the dimension of the body 212 is mutually adapted to the adapting groove 2111 and larger than the mounting groove 2112. The bottom surface of the adapting groove 2111 can limit the extreme position of the head 211 and the body 212 moving toward each other, thereby preventing the elastic member 221 from applying an excessive clamping force to the probe 100. The elastic member 221 is arranged at the bottom of the mounting groove 2112, and the extrusion piece 222 is movably arranged in the mounting groove 2112. The mounting groove 2112 and the adapting groove 2111 can both be round holes for easy processing, and the mounting groove 2112 and the adapting groove 2111 can also be set to have non-circular cross-sections to restrict the movement of the components. One end of the extrusion member 222 is an extrusion end 2221 that cooperates with the elastic member 221, and the other end is a driving end 2222 that cooperates with the body 212. Figure 2 To Attachment Figure 4 As shown, the driving end 2222 abuts against the body 212 through the sealing member 224. The sealing member 224 has a center hole for the probe 100 to pass through. When the head 211 and the body 212 move toward each other, the extruding member 222 and the body 212 squeeze the sealing member 224, so that the center hole of the sealing member 224 shrinks, thereby clamping the probe 100. When the head 211 and the body 212 move away from each other, the sealing member 224 recovers due to the removal of the external force, and its center hole enlarges, thereby loosening the probe 100. When installing the sealing member 224, it can be abutted against the bottom of the adapting groove 2111. The size of the sealing member 224 can be adapted to the cross-sectional shape of the adapting groove 2111, or it can be adapted to the cross-sectional shape of the mounting groove 2112, or it can be in between. The sealing member 224 can also refer to the attached Figure 4 As shown, in the free state, the driving end 2222 is lower than the bottom of the adapting groove 2111 to form an assembly cavity, the sealing member 224 is located in the assembly cavity, and the body 212 drives the extruding member 222 to move by pressing the portion of the sealing member 224 exposed in the adapting groove 2111. The sealing member 224 similar to the elastic member 221 can also assist in achieving the clamping of the probe 100 and the sealing of this part.

[0053] In other words, in this embodiment, the lock core 220 clamps the outer peripheral surface of the probe 100 at least at the two axial ends of the extrusion member 222, and the two clamping parts are clamped or released synchronously during the relative movement of the head 211 and the body 212. The specific structure of the sealing member 224 can be the same as that of the elastic member 221 or can be set differently. Figure 2In the embodiment, multiple elastic members 221 are provided, and the probe 100 sequentially passes through the multiple elastic members 221 to enter the body 212. When the head 211 and the body 212 move toward each other, the central holes of the multiple elastic members 221 are synchronously reduced and clamp different parts of the probe 100 respectively. In this embodiment, the elastic members 221 and the sealing members 224 are both O-rings. During the process of synchronously reducing the central holes of the multiple elastic members 221 and the sealing members 224, each elastic member 221 and the sealing member 224 clamps and seals different parts of the probe 100 respectively, and the front end of the probe 100 is sealed and connected with the channel of the body 212 of the clamp 200 through the hollow channel inside the probe 100, forming a sealed channel to facilitate adjusting the pressure inside the probe to achieve cell manipulation.

[0054] Regarding the implementation of the relative movement between the head 211 and the body 212, various methods such as sliding, rotating and advancing can be used. Figure 2 To Attachment Figure 4 In the illustrated embodiment, a propulsion portion 2121 is fixed to the body 212. When the body 212 rotates relative to the head 211, the propulsion portion 2121 drives the head 211 and the body 212 to move toward each other. Further, the propulsion portion 2121 is fixed to the outer circumference of the body 212 and is screwed with the head 211. When the body 212 rotates relative to the head 211, the propulsion portion 2121 can drive the relative movement of the body 212 and the head 211. The inner circumference of the adapter groove 2111 of the head 211 is used to be screwed with the propulsion portion 2121.

[0055] Further, the head 211 is provided with an anti-slipping piece 2113, which limits the maximum distance that the head 211 and the body 212 move in opposite directions. This arrangement can prevent the body 212 and the head 211 from accidentally separating from each other during the replacement of the probe 100 while avoiding the separation of the components of the lock core 220 caused by the back movement of the body 212 and the head 211, thereby reducing the risk of use. The anti-slipping piece 2113 can be installed detachably from the head 211 and is provided with an opening for the body 212 to pass through, and the inner edge of the opening is movably arranged with the body 212 to realize the movement of the body 212. In some embodiments, the inner edge of the opening is matched with the outer peripheral surface of the body 212 in a sliding seal or a rotating seal. When the body 212 is matched in the adapter groove 2111, the anti-slipping piece 2113 closes the adapter groove 2111 to achieve anti-slipping. In the solution in which the body 212 is screwed to the head 211, the anti-slipping piece 2113 can also be screwed to the head 211.

[0056] In addition to the constraint of the probe 100 by the elastic member 221, the holder 200 itself can also realize the constraint of the probe 100. For example, the rear end of the probe 100 mentioned above goes deep into the body 212, and the internal cavity of the body 212 can realize the matching or constraint of the outer peripheral surface and end surface of the probe 100. Figure 5In the embodiment shown, a limiting portion 2122 is provided inside the body 212, the probe 100 extends into the body 212 and the rear end is positioned at the limiting portion 2122, and a pressure channel 2123 connected to the inside of the probe 100 is provided on the limiting portion 2122. The limiting portion 2122 may be an annular structure disposed inside the body 212. In the specific implementation of the limiting portion 2122, referring to an embodiment, the body 212 is a multi-layer structure and includes:

[0057] The first cylinder 2124 is located at the outer layer and is open at both ends, one end is a clamping end 2127 extending into the head 211, and the other end is a pressure end 2128 connected to the peripheral equipment;

[0058] The second cylinder 2125 is located inside the first cylinder 2124. The second cylinder 2125 includes an open end close to the clamping end 2127 and a closed end located inside the first cylinder 2124. The closed end forms a limiting portion 2122.

[0059] The third cylinder 2126 is located inside the first cylinder 2124 and is open at both ends, with one end abutting against the closed end of the second cylinder 2125 and the other end close to the pressure end 2128 of the first cylinder 2124 .

[0060] By embedding the second cylinder 2125 and the third cylinder 2126 in the first cylinder 2124, the positioning accuracy of the limit portion 2122 compared to the probe assembly can be guaranteed while reducing the processing difficulty, thereby ensuring the spatial position of the front end of the probe 100 compared to the probe assembly, further improving the control accuracy of cell manipulation, and providing a structural basis for refined control.

[0061] Based on the above description, combined with the attached Figure 6 To Attachment Figure 8 It can be seen that an embodiment of the present application further discloses a single cell manipulation device, including:

[0062] The stage 10 is used to fix the container carrying the sample;

[0063] The probe assembly is the probe assembly in each of the above embodiments;

[0064] A control assembly, including a moving platform 50 for moving the probe assembly in space to adjust the position of the probe 100;

[0065] A microscopic imaging component, providing a viewing window for the positioning probe 100;

[0066] The air pressure source assembly 60 is connected to the probe 100 via the holder 200 to provide positive or negative air pressure to the probe 100 in the form of pulses.

[0067] The probe assembly can be implemented in combination with the above specific description, which will not be repeated here.

[0068] The air pressure source assembly 60 is used as a power source for aspirating and spitting out substances (cells, reagents, etc.). Figure 6 In the illustrated embodiment, the air pressure source assembly includes a plunger pump 61, a solenoid valve 62, a three-way connector 63, a first one-way valve 64, a second one-way valve 65, an air filter 66, a muffler 67, and a plug 68. The plunger pump 61 has an inlet end 61a, an outlet end 61b, and a plunger 61c; the solenoid valve 62 has a common end 62a, a normally open end 62b, and a normally closed end 62c; the air filter 66 has an air inlet end and an air outlet end; the first one-way valve 64 has an "IN" port and an "OUT" port; the second one-way valve 65 has an "IN" port and an "OUT" port; and the three-way connector 63 has three connection ports.

[0069] The plug 68 is screwed into the inlet end 61a of the plunger pump, tightened and sealed, and the air intake and exhaust of the plunger pump are completed through the outlet end 61b. The outlet end 61b of the plunger pump is connected to the common end 62a of the solenoid valve 62 by a pipeline; the air inlet end of the air filter 66 is connected and sealed to the muffler 67 by a threaded connection, and the air outlet end of the air filter 66 is connected to the "IN" port of the first one-way valve 64 by a pipeline; the "OUT" port of the first one-way valve 64 is connected to one of the ports of the three-way connector 63 by a pipeline, and one of the other two ports of the three-way connector 63 is connected to the normally open end 62b of the solenoid valve 62 by a pipeline, and the other port is connected to the "IN" port of the second one-way valve 65 by a pipeline; the normally closed end 62c of the solenoid valve 62 is connected to the pressure end 2128 of the probe assembly through a pipeline, and then connected to the probe 100, so that the entire air pressure source assembly is connected to the probe 100.

[0070] The air filter 66 has a muffler 67 connected to the air inlet end to reduce the noise of the air path system of the entire operating cell. The air filter 66 has an exhaust end connected to the "IN" port of the first one-way valve 64, which prevents the gas in the entire air path system from flowing back to the air filter 66; the second one-way valve 65 is used to exhaust the air in the plunger pump 61 to ensure that there is no unfiltered air in the plunger pump 61.

[0071] Before operation, the common end 62a and the normally open end 62b of the solenoid valve 62 are first connected, the normally closed end 62c is closed, and the plunger 61c first moves upward to the uppermost end, during which the residual gas in the plunger pump 61 is exhausted through the three-way joint 63 and the second one-way valve 65; then the plunger 61c moves downward to the middle position of the plunger pump 61, during which the air is filtered by the air filter 66 and enters the plunger pump 61 through the first one-way valve 64 and the three-way joint 63. The initial stop position of the plunger 61c is set at the middle of the plunger pump, and it can move downward to provide negative air pressure, and can also move upward to provide positive air pressure.

[0072] In some embodiments, Figure 7 As shown, the plunger pump 61 provides positive or negative air pressure to the probe 100 in the form of pulses, and the plunger 61c moves intermittently within a single working stroke. When the plunger 61c moves intermittently upward, each movement distance is d1, and multiple positive air pressure pulses can be generated, the air pressure value of the positive air pressure pulse is P1, and the pulse period is T1; when the plunger 61c moves intermittently downward, each movement distance is d2, and multiple negative air pressure pulses can be generated, the air pressure value of the negative air pressure pulse is P2, and the pulse period is T2.

[0073] Figure 7 The origin O in the figure indicates that the plunger 61c is in the initial position, and the air pressure value in the plunger is close to the atmospheric pressure. Generally speaking, the pulse air pressure value is selected to be -10Kpa-10Kpa, and the period is less than 1s, preferably 0.5s-1s. The air pressure value and period of the pulse are adjustable to meet different practical needs.

[0074] The following uses cell extraction as an example to introduce the working principle of the air pressure source component:

[0075] The solenoid valve 62 is energized, the normally open end 62b is closed, and the normally closed end 62c is opened, so that the plunger pump 61 is connected to the probe 100, and the plunger 61c in the plunger pump 61 is controlled to move downward. At this time, the plunger pump 61 provides a negative air pressure pulse to the probe 100, and the probe 100 can suck the cells in the culture dish. If a single pulse cannot suck the cells into the probe 100, multiple pulses can be sent continuously until the cells are sucked in. During the process of the probe 100 sucking the cells, when the internal and external air pressures are balanced, the cells no longer move, so they can be kept in the probe 100.

[0076] After the cells are sucked in, if the plunger 61c has not moved to the limit position, it can continue to move to provide pulses to suck in more cells.

[0077] When the plunger 61c moves downward to the limit position, the normally closed end 62c of the solenoid valve 62 is closed and the normally open end 62b is connected, and the plunger 61c moves upward to reset. During the reset process, the gas in the plunger pump 61 is discharged through the three-way connector 63 and the second one-way valve 65. After the plunger 61c is reset, the normally open end 62b is closed and the normally closed end 62c is opened, and cells can be continuously sucked in. The reciprocating operation can be repeated to suck more cells at different sites into the probe 100 in batches.

[0078] After the cells are sucked in, the plunger 61c is reset first (or not reset), and the plunger 61c in the plunger pump 61 is controlled to move upward, and a positive air pressure pulse is provided to the probe 100 at this time, and the probe 100 spits out the cells into the culture dish. Since the positive air pressure is also provided in the form of pulses, the cells can be spewed out one by one until all of them are spewed out. The working process is opposite to the process of sucking cells, and will not be repeated here.

[0079] By using positive or negative air pressure pulses, at most one cell can be ejected or sucked in each operation. Providing a negative air pressure pulse may prevent the cell from entering the probe due to insufficient suction. By continuously outputting multiple pulses, the cell can eventually enter the probe 100. The ejection of cells is similar to this.

[0080] Since the probe has a large space inside, it can temporarily store more cells. The probe 100 can continuously suck in multiple cells and then spit out the cells at once, which significantly improves the operation efficiency. In addition, the pulse probe 100 can spit out cells one by one, so that multiple cells are distributed in different positions, eliminating the redistribution operation.

[0081] It can be seen that the solenoid valve 62 serves as a pressure balancing device for the entire system. After the normally open end 62b is closed and the normally closed end 62c is opened, the plunger pump 61 does not work, and the gas path system connecting the probe 100 and the plunger pump 61 can maintain pressure balance, and the extracted cells can be completely preserved in the probe 100. The plunger 61c can then move again to generate new pulses. After the normally open end 62b is opened and the normally closed end 62c is closed, since the pressure has been balanced at this time, the plunger pump 61 performs a reset operation, which does not affect the cells preserved in the probe 100.

[0082] The microscopic imaging assembly includes a light source 23, an optical microscope objective lens 21, and an image detection unit 22 (such as a CCD camera). The light source 23 is generally disposed directly above the stage 10 and is as shown in FIG. Figure 8 The light source 23 emits light in the direction indicated by the arrow below. The optical microscope objective lens 21 and the image detection unit 22 are located below the stage. Figure 8 The light is transmitted in the direction indicated by the arrow between the optical microscope objective lens 21 and the image detection unit 22 and imaged on the image detection unit 22, and the image detection unit 22 communicates with the control system 70. The control system 70 can be a terminal device such as a computer, and the plunger pump 61, the solenoid valve 62, the motor in the mobile platform 50, and the motor in the stage 10 in the air pressure source assembly 60 are controlled by the control system. The control system also has an imaging display unit, that is, the probe 100 and the target cells can be displayed on the screen through the imaging system, and the operator can perform real-time operations.

[0083] Other details of the single-cell manipulation device can be implemented in combination with existing technologies and will not be described in detail here.

[0084] The technical features of the above-mentioned embodiments can be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification. When the technical features in different embodiments are embodied in the same figure, it can be regarded that the figure also discloses the combination examples of the various embodiments involved.

[0085] The above-mentioned embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the patent application. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application.

Claims

1. A probe assembly, characterized in that include: The probe is an elongated hollow structure having a front end and a rear end opposite to each other, and the aperture of the front end is relatively reduced; A clamper comprises a shell and a lock core assembled inside the shell, wherein the shell comprises a head and a body which are axially movable relative to each other, wherein the body is a multi-layer structure and comprises a first cylinder, a second cylinder and a third cylinder; the first cylinder is located in the outer layer and is open at both ends, one end is a clamping end extending into the head, and the other end is a pressure end connected to a peripheral device; the second cylinder is located inside the first cylinder, the second cylinder comprises an open end close to the clamping end and a closed end located inside the first cylinder, the closed end forms a limiting portion, and a pressure channel connected to the inside of the probe is provided on the limiting portion; the third cylinder is located inside the first cylinder and is open at both ends, wherein one end abuts against the closed end of the second cylinder, and the other end is close to the pressure end of the first cylinder; the rear end of the probe passes through the head and extends into the body and is positioned at the limiting portion; the lock core comprises an elastic member and an axially movable extrusion member, wherein the elastic member and the extrusion member have a center hole for the probe to pass through; When the head and the body move toward each other, the extrusion member is driven to act on the elastic member, so that the central hole of the elastic member is reduced, thereby clamping the probe; When the head and the body move in opposite directions, the elastic member is restored due to the removal of external force, and the central hole thereof is enlarged, thereby releasing the probe.

2. The probe assembly according to claim 1, characterized in that: The head portion has an adapting groove, the bottom surface of the adapting groove is provided with a mounting groove adapted to the lock core, and the body portion extends into the adapting groove and contacts the lock core.

3. The probe assembly according to claim 2, characterized in that: The elastic member is arranged at the bottom of the installation groove, the extrusion member is movably arranged in the installation groove, one end of the extrusion member is an extrusion end cooperating with the elastic member, and the other end is a driving end cooperating with the body.

4. The probe assembly according to claim 3, characterized in that: The driving end is pressed against the body through a seal, and the seal has a center hole for the probe to pass through. When the head and the body move toward each other, the extrusion member and the body squeeze the seal, causing the center hole of the seal to shrink, thereby clamping the probe; when the head and the body move away from each other, the seal is restored due to the removal of external force, and its center hole is enlarged, thereby releasing the probe.

5. The probe assembly according to claim 4, characterized in that: There are multiple elastic members, and the probe passes through the multiple elastic members and the sealing members in sequence to enter the body. When the head and the body move toward each other, the central holes of the multiple elastic members and the sealing members shrink synchronously and clamp and seal different parts of the probe respectively, forming a sealed channel between the front end of the probe and the body.

6. The probe assembly according to claim 1, characterized in that: A propulsion unit is fixed on the body, and when the body rotates relative to the head, the propulsion unit drives the head and the body to move toward each other.

7. The probe assembly according to claim 1, characterized in that: The head is provided with an anti-slipping piece, and the anti-slipping piece limits the maximum distance that the head and the body can move in opposite directions.

8. A single cell manipulation device, characterized in that: include: A stage for fixing the container carrying the sample; A probe assembly, which is the probe assembly according to any one of claims 1 to 7; a control assembly, including a moving platform for moving the probe assembly in space to adjust the position of the probe; A microscopic imaging component, providing a window for positioning the probe; An air pressure source assembly is connected to the probe via the holder to provide positive or negative air pressure to the probe in the form of pulses.

Citation Information

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