An integrated microfluidic circulating tumor cell sorting device

Abstract

This utility model discloses an integrated microfluidic circulating tumor cell sorting device, relating to the field of cell sorting technology. It includes a scaffold, a sample injection device, and a microfluidic chip; it also includes a closed storage box fixed to the scaffold; the microfluidic chip is disposed inside the closed storage box, and the sample injection device is partially and sealed inside the closed storage box; a gas evacuation device is used to create a negative pressure vacuum inside the closed storage box; a return gas valve and a pressure sensor are respectively fixed to the closed storage box and communicate with its interior. The advantages of this utility model are: by placing the microfluidic chip inside the closed storage box, and using the gas evacuation device to create a negative pressure vacuum inside the closed storage box, and then drawing in a suitable pressure under the detection of the pressure sensor, the pressure difference between the inside and outside of the bubble decreases sharply under a certain negative pressure, causing expansion. At this point, the bubble wall thickness thins to the critical rupture thickness and spontaneously ruptures. Furthermore, the negative pressure environment only changes the gas phase pressure, avoiding microjets lost due to ultrasonic cavitation, resulting in low impact on cells and good protection.

Description

Technical Field

[0001] This utility model relates to the field of cell sorting technology, and more specifically to an integrated microfluidic circulating tumor cell sorting device. Background Technology

[0002] Circulating tumor cells (CTCs) are tumor cells that detach from the primary tumor and enter the body fluids to circulate within the body. Regular CTC testing helps in the early detection and treatment of cancer, preventing the disease from worsening. Before testing, CTCs need to be separated from the body fluids (blood) for later use.

[0003] Currently, microfluidic chips are generally used to separate circulating tumor cells from body fluids. The sorted body fluid sample is injected into the microfluidic chip through a syringe. The microfluidic chip uses physical principles to sort different particles in the sample, thereby sorting out circulating tumor cells.

[0004] In actual operation, air bubbles are easily present in microfluidic chips, which can affect the sorting results. Although the existing "Application No.: CN202223324473.6, Circulating Tumor Cell Sorting Device" can remove air bubbles in microfluidic chips, the ultrasonic treatment method used may have cavitation effect, which has the disadvantage of greatly damaging the integrity of cell membranes. Utility Model Content

[0005] The purpose of this invention is to provide an integrated microfluidic circulating tumor cell sorting device in order to solve the above-mentioned technical problems.

[0006] To achieve the above objectives, this utility model specifically adopts the following technical solution:

[0007] This invention proposes an integrated microfluidic circulating tumor cell sorting device, comprising:

[0008] support;

[0009] The injection device is fixedly mounted on the bracket;

[0010] A microfluidic chip is fixed to a sample injection device to inject a sample into the microfluidic chip;

[0011] It also includes a closed storage box, which is fixed on a bracket; the microfluidic chip is located inside the closed storage box, and the sample injection device is partially sealed inside the closed storage box.

[0012] The venting device is fixed between the bracket and the closed storage box to create a negative pressure vacuum inside the closed storage box.

[0013] The return valve and pressure sensor are fixedly mounted on the closed storage box and connected to its interior.

[0014] As a preferred technical solution of this utility model, the gas venting device includes a suction pipe fixed at one end to the closed storage box and connected to the inside of the closed storage box, a one-way valve fixed between the suction pipes, and a vacuum pump fixed to the other end of the suction pipe, the vacuum pump being fixed on a bracket.

[0015] As a preferred technical solution of this utility model, the closed storage box includes a top-opening shell fixed on the bracket, a shell cover disposed at the top of the top-opening shell to seal it, and a stabilizing device fixed between the top-opening shell and the shell cover to fix it. The extraction pipe, the return valve and the pressure sensor are fixed on the top-opening shell.

[0016] As a preferred technical solution of this utility model, the stabilizing device includes an annular groove at the top of the top opening shell, a plug ring fixed at the bottom of the shell cover, a lower plate fixed on the outside of the top opening shell, an upper plate fixed on the outside of the shell cover, and a bolt threaded through the upper plate and the lower plate. A rubber layer is fitted and fixed in the annular groove, and the plug ring extends into the annular groove to press and fit the rubber layer.

[0017] As a preferred technical solution of this utility model, the injection device includes a pusher and a syringe fixed on the support, a hose with one end connected to and fixed to the discharge end of the syringe, and a connector fixed between the shell cap and the hose. The output end of the pusher is attached to the pressure end of the syringe, and the other end of the hose is connected to and fixed to the discharge end of the microfluidic chip.

[0018] As a preferred technical solution of this utility model, the tapping assembly includes a through hole that penetrates the shell cover to connect the inside and outside of the closed storage box, an inner connector that is threaded to the through hole, a pressure ring that is fixed to the outside of the inner connector, a sealing gasket that fits between the pressure ring and the inside of the shell cover, and an outer connector that is located on the outside of the shell cover. The outer connector is threaded to the inside of the inner connector, and the outer connector and the inner connector are respectively connected and fixed between the hoses.

[0019] As a preferred technical solution of this utility model, it also includes a controller, which is fixedly mounted on the bracket.

[0020] The beneficial effects of this utility model are as follows:

[0021] By placing a microfluidic chip in a closed storage chamber and using a vacuum device to create a negative pressure vacuum inside the chamber, and then using a pressure sensor to draw in a suitable pressure, the pressure difference between the inside and outside of the bubble decreases sharply under a certain negative pressure, causing it to expand. When the bubble wall thickness is reduced to the critical rupture thickness, it spontaneously ruptures. Moreover, the negative pressure environment only changes the gas phase pressure, avoiding microjets that are lost due to ultrasonic cavitation, resulting in low impact on cells and good protection. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the structure of this utility model;

[0023] Figure 2 yes Figure 1 A schematic diagram of the local structure A;

[0024] Figure 3 yes Figure 1 A schematic diagram of the local structure B.

[0025] Reference numerals: Support-1, Injection device-2, Microfluidic chip-3, Closed storage box-4, Gas venting device-5, Return gas valve-6, Pressure sensor-7, Controller-8, Pusher-21, Syringe-22, Tube-23, Tap assembly-24, Top-opening shell-41, Shell cover-42, Stabilizing device-43, Pull tube-51, One-way valve-52, Vacuum pump-53, Perforation-241, Inner connector-242, Pressure ring-243, Sealing gasket-244, Outer connector-245, Ring groove-431, Insert ring-432, Lower plate-433, Upper plate-434, Bolt-435. Detailed Implementation

[0026] like Figures 1-3 As shown, this utility model proposes: an integrated microfluidic circulating tumor cell sorting device, comprising;

[0027] Bracket 1;

[0028] The injection device 2 is fixedly mounted on the bracket 1;

[0029] The microfluidic chip 3 is fixedly connected to the injection device 2 to inject a sample into the microfluidic chip 3;

[0030] The controller 8 is fixedly mounted on the bracket 1. The controller 8 is connected to an external power source and electrical components to control their opening and closing.

[0031] It also includes a closed storage box 4, which is fixed on the bracket 1; the microfluidic chip 3 is located inside the closed storage box 4, and the sample injection device 2 is partially sealed inside the closed storage box 4.

[0032] The air evacuation device 5 is fixed between the bracket 1 and the closed storage box 4 to draw a negative pressure vacuum inside the closed storage box 4.

[0033] The return air valve 6 and the pressure sensor 7 are respectively fixed on the closed storage box 4 and connected to its interior; the return air valve 6 is an electromagnetic switch valve used to replenish air to the closed storage box 4; the pressure sensor 7 can be a gas pressure sensor or a pressure transmitter, etc. The model of the pressure transmitter can be: MIK-PX300, used to detect the gas pressure in the closed storage box 4.

[0034] After the microfluidic chip 3 is placed in the closed storage box 4, the closed storage box 4 is evacuated by the gas evacuation device 5. Under the detection of the pressure sensor 7, the appropriate pressure is drawn to make the pressure difference between the inside and outside of the bubble decrease sharply under a certain negative pressure, which in turn causes expansion. At this time, the bubble wall thickness is reduced to the critical rupture thickness and spontaneous rupture occurs. Moreover, the negative pressure environment only changes the gas phase pressure, avoiding the microjets lost by ultrasonic cavitation, and has a low impact on cells.

[0035] The specific structure of the air venting device 5 is shown below:

[0036] The gas venting device 5 includes a suction pipe 51 fixed at one end to the closed storage box 4 and connected to the inside of the closed storage box 4, a one-way valve 52 fixed between the suction pipes 51, and a vacuum pump 53 fixed at the other end of the suction pipes 51. The vacuum pump 53 is fixed on the bracket 1. The vacuum pump 53 is an oil-sealed rotary vane vacuum pump or a dry screw vacuum pump.

[0037] The vacuum pump 53 is started to generate a suction force in the suction tube 51. This suction force is transmitted to the closed storage box 4 through the one-way valve 52 to draw out the gas in the closed storage box 4.

[0038] The specific structure of the closed storage box 4 is shown below:

[0039] The closed storage box 4 includes a top-opening shell 41 fixed on the bracket 1, a shell cover 42 located at the top of the top-opening shell 41 to seal it, and a stabilizing device 43 fixed between the top-opening shell 41 and the shell cover 42 to fix it. The extraction pipe 51, the return air valve 6 and the pressure sensor 7 are fixed on the top-opening shell 41.

[0040] Separating the top-opening shell 41 by using the shell cover 42 facilitates the placement and removal of the microfluidic chip 3, and the stabilizing device 43 can stabilize the shell cover 42 on the top-opening shell 41 to make the interior of the top-opening shell 41 sealed.

[0041] Furthermore: the stabilizing device 43 includes an annular groove 431 at the top of the top opening shell 41, a plug ring 432 fixed at the bottom of the shell cover 42, a lower plate 433 fixed on the outside of the top opening shell 41, an upper plate 434 fixed on the outside of the shell cover 42, and a bolt 435 threaded through the upper plate 434 and the lower plate 433. A rubber layer is fitted and fixed in the annular groove 431, and the plug ring 432 extends into the annular groove 431 to press the rubber layer tightly.

[0042] A ring groove 431 is centrally located on the annular top of the top opening shell 41. An insert ring 432 is fixed at the bottom of the shell cover 42. The insert ring 432 is aligned with the annular groove 431 and inserted to press and seal the shell. Multiple sets of lower plates 433 are evenly fixed in a ring on the upper side of the top opening shell 41. Multiple sets of upper plates 434 are evenly fixed in a ring around the outer periphery of the shell cover 42. Each set of upper plates 434 and lower plates are aligned vertically and connected by bolts 435 through threads. This is how the positions of the top opening shell 41 and the shell cover 42 are fixed.

[0043] The specific structure of the closed-box sample injection device 2 is shown below:

[0044] The injection device 2 includes a pusher 21 and a syringe 22 fixed on the bracket 1, a hose 23 with one end connected to and fixed to the discharge end of the syringe 22, and a tap assembly 24 fixed between the shell cap 42 and the hose 23. The output end of the pusher 21 is in contact with the pressure end of the syringe 22, and the other end of the hose 23 is connected to and fixed to the discharge end of the microfluidic chip 3.

[0045] The pusher 21 provides a pushing force to the syringe 22. The pusher 21 can be a pushing component (injection pump) for moving the piston of the syringe as proposed in the background art "CN202223324473.6". In this way, the sample in the syringe 22 can be placed into the microfluidic chip 3 through the tubing 23 for sorting.

[0046] Furthermore, the tap assembly 24 includes a through hole 241 penetrating the housing cover 42 to connect the inside and outside of the closed storage box 4, an inner connector 242 threadedly connected to the through hole 241, a pressure ring 243 surrounding the inner connector 242, a sealing gasket 244 fitting between the pressure ring 243 and the inner side of the housing cover 42, and an outer connector 245 located on the outside of the housing cover 42. The outer connector 245 is threadedly connected to the inner side of the inner connector 242, and the outer connector 245 and the inner connector 242 are respectively connected and fixed between the hoses 23. The sealing gasket 244 is made of rubber, and the tap assembly 24 is made of a rigid material such as stainless steel (e.g., 304 or 316L), polypropylene (PP), or polycarbonate (PC).

[0047] A through hole 241 is pre-set on the cover 42, through which the top and bottom threads pass. The hose 23 is divided into two sections, one inside the closed storage box 4 and the other at the top of the cover 42. Both the inner connector 242 and the outer connector 245 are provided with tube passage cavities. The top of the inner connector 242 and the bottom of the outer connector 245 are connected to and fix the two sections of the hose 23 respectively. The inner connector 242 is surrounded by a ring-shaped fixing pressure ring 243. The top of the pressure ring 243 is attached to and fixed with a sealing gasket 244. The inner side of the inner connector 242 is also provided with threads. First, the inner connector 242 is threaded into the through hole 241 at the bottom of the cover 42 until the sealing gasket 244 contacts the cover 42 and is pressed tightly. Then, the outer connector 245 is threaded into the inner connector 242 at the top of the cover 42. This structure can ensure sealing and is easy to disassemble and replace.

[0048] The foregoing has shown and described the basic principles, main features, and advantages of this utility model. It will be apparent to those skilled in the art that this utility model is not limited to the details of the exemplary embodiments described above, and that it can be implemented in other specific forms without departing from the spirit or basic characteristics of this utility model. Therefore, the embodiments should be considered exemplary and non-limiting in all respects. The scope of this utility model is defined by the appended claims rather than the foregoing description, and thus all variations falling within the meaning and scope of equivalents of the claims are intended to be included within this utility model. No reference numerals in the claims should be construed as limiting the scope of the claims.

[0049] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. An integrated microfluidic circulating tumor cell sorting device, comprising: Support (1); The injection device (2) is fixedly mounted on the bracket (1); The microfluidic chip (3) is fixed to the injection device (2) to inject a sample into the microfluidic chip (3); Its features are, It also includes a closed storage box (4), which is fixed on the bracket (1); the microfluidic chip (3) is located inside the closed storage box (4), and the sample injection device (2) is partially sealed inside the closed storage box (4); The air evacuation device (5) is fixed between the bracket (1) and the closed storage box (4) to draw a negative pressure vacuum inside the closed storage box (4); The return valve (6) and the pressure sensor (7) are fixedly mounted on the closed storage box (4) and connected to its interior.

2. The integrated microfluidic circulating tumor cell sorting device according to claim 1, characterized in that, The gas venting device (5) includes a suction pipe (51) fixed at one end to the closed storage box (4) and connected to the inside of the closed storage box (4), a one-way valve (52) fixed between the suction pipes (51), and a vacuum pump (53) fixed at the other end of the suction pipes (51). The vacuum pump (53) is fixed on the bracket (1).

3. The integrated microfluidic circulating tumor cell sorting device according to claim 2, characterized in that, The closed storage box (4) includes a top-opening shell (41) fixed on the bracket (1), a shell cover (42) located at the top of the top-opening shell (41) to seal it, and a stabilizing device (43) fixed between the top-opening shell (41) and the shell cover (42) to fix it. The extraction pipe (51), the return air valve (6) and the pressure sensor (7) are fixed on the top-opening shell (41).

4. The integrated microfluidic circulating tumor cell sorting device according to claim 3, characterized in that, The stabilizing device (43) includes an annular groove (431) at the top of the top opening shell (41), a plug ring (432) fixed at the bottom of the shell cover (42), a lower plate (433) fixed on the outside of the top opening shell (41), an upper plate (434) fixed on the outside of the shell cover (42), and a bolt (435) threaded through the upper plate (434) and the lower plate (433). A rubber layer is fitted and fixed in the annular groove (431), and the plug ring (432) extends into the annular groove (431) to press the rubber layer tightly.

5. The integrated microfluidic circulating tumor cell sorting device according to claim 4, characterized in that, The injection device (2) includes a pusher (21) and a syringe (22) fixed on the bracket (1), a hose (23) with one end connected to and fixed to the discharge end of the syringe (22), and a connector (24) fixed between the shell cap (42) and the hose (23). The output end of the pusher (21) is attached to the pressure end of the syringe (22), and the other end of the hose (23) is connected to and fixed to the discharge end of the microfluidic chip (3).

6. The integrated microfluidic circulating tumor cell sorting device according to claim 5, characterized in that, The tap assembly (24) includes a through hole (241) that passes through the cover (42) to connect the inside and outside of the storage box (4), an inner connector (242) that is threaded to the through hole (241), a pressure ring (243) that is fixed to the outside of the inner connector (242), a sealing gasket (244) that fits between the pressure ring (243) and the inside of the cover (42), and an outer connector (245) that is located outside the cover (42). The outer connector (245) is threaded to the inside of the inner connector (242), and the outer connector (245) and the inner connector (242) are respectively connected and fixed between the hoses (23).

7. The integrated microfluidic circulating tumor cell sorting device according to claim 1, characterized in that, It also includes a controller (8), which is fixed on the bracket (1).

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