KR20230009048A - Separating blood apparatus comprising cartridge provided with pneumatic pressure - Google Patents

Abstract

The present invention relates to a blood isolation apparatus that isolates leukocytes from the whole blood, which comprises: a cartridge including a buffer storage unit capable of storing a buffer and a blood storage unit capable of storing blood; a microfluidic chip mounted on the cartridge and selectively communicating with the buffer storage unit and the blood storage unit, where the buffer and the blood are introduced; and a pneumatic pressure provision unit providing pneumatic pressure to the buffer storage unit and the blood storage unit in the cartridge, wherein the cartridge has the buffer storage unit and the blood storage unit that are separately defined to have the independent space and independently provided with pneumatic pressure by the pneumatic pressure provision unit. Accordingly, the process required for driving the microfluid can be simplified because pneumatic pressure is provided to the cartridge including the microfluidic chip.

Description

Blood separation device including a cartridge supplied with pneumatics {SEPARATING BLOOD APPARATUS COMPRISING CARTRIDGE PROVIDED WITH PNEUMATIC PRESSURE}

The present invention relates to a blood separation device including a cartridge supplied with pneumatic pressure.

Blood is a fluid suspension consisting of particles and liquid. Blood is largely composed of blood cells, including red blood cells, white blood cells, and platelets, and plasma, a solution in which they float. The volume occupied by blood cells in the whole blood is called the hematocrit. It is 45-53% for women and 35-45% for women. 97% of blood cells are composed of red blood cells, which are red in color, and carry oxygen and nutrients throughout the body.

Leukocytes, as one element included in blood, are separated from a predetermined amount of blood as needed, and when separation from a large amount of blood is required, as a method of separating leukocytes, a centrifugal separation method using a specific gravity solution using ficoll However, a centrifugal separation method using hydroxyethyl starch as an erythrocyte sedimentation agent is being implemented. However, it is a reality that such a method has limitations in increasing the capacity of blood that can be processed, and in the case of the white blood cell separation method using centrifugation, the processing process is somewhat complicated, requiring a considerable amount of time and labor, and separation The state of the isolated leukocytes is not intact, and the isolated product may contain relatively large amounts of impurities.

On the other hand, microfluidic channels are generally used for the operation, control, and manipulation of fluids limited by structures of less than 1 mm. It is different from a large-scale flow channel in that it dominates. Microfluidic channels are characterized by their small size and low energy consumption, and perform functions such as mixing and particle manipulation. In addition, in order to drive the microfluidic channel, fluid contained in a syringe is generally injected into the channel using an accessory such as a tube, so there is a limit to simplifying the fluid driving equipment.

Republic of Korea Patent Registration No. 10-1615746 (2016. 04. 20)

An object of the present invention is to provide a large-capacity fluid to a microfluidic chip without a separate connection process, and use can be simplified by directly connecting pneumatic pressure to a cartridge including a general-purpose microfluidic chip.

An embodiment of the present invention may include a cartridge through which blood passes in a process of introducing blood into a microfluidic chip in order to separate desired components from blood.

An embodiment of the present invention is to allow blood and a buffer to flow in at a time difference in a microfluidic chip and to discharge air in a channel, thereby forming a laminar flow simultaneously with the inflow of the buffer and blood, thereby preventing malfunction of the microfluidic chip. do.

An object of one embodiment of the present invention is to determine the flow rate by providing the same pneumatic pressure to the buffer and the blood in independent channels.

The present invention relates to a blood separation device for separating leukocytes from blood, comprising: a cartridge including a buffer accommodating part accommodating a buffer and a blood accommodating part accommodating blood; a microfluidic chip mounted on the cartridge and selectively communicating with the buffer receiving unit and the blood receiving unit so that the buffer and the blood can be introduced; and a pneumatic supply unit for supplying air pressure to the buffer accommodation unit and the blood accommodation unit in the cartridge, wherein the cartridge is formed as an independent space by partitioning the buffer accommodation unit and the blood accommodation unit from each other, and receiving the buffer by the air pressure supply unit. A blood separation device is provided in which pneumatic pressure is independently supplied to the unit and the blood receiving unit.

The cartridge may include a buffer accommodating portion and a through hole opening upward of the blood accommodating portion, respectively, and the pneumatic supply unit may include a first connection portion connected to the buffer accommodating portion and a second connection portion connected to the blood accommodating portion through the through hole. there is.

Also, the first connection unit may provide air pressure before the second connection unit, and the buffer may be filled in the microfluidic channel before blood by the air pressure provided by the first connection unit.

In addition, the air pressure provided from the first connection part and the second connection part may be generated as the same air pressure by one providing part.

In addition, the buffer formed on the microfluidic chip and the width of the channel through which the blood flows may be determined according to the viscosity of the blood.

In addition, a first valve provided on the side of the first connection portion and a second valve provided on the side of the second connection portion may be further included so that the air pressure supplied from the first connection portion and the second connection portion is provided at a predetermined time interval.

The controller may further include a control unit controlling opening timings of the first valve and the second valve, and the controller may determine opening timings of the first valve and the second valve based on values input to the firmware.

In addition, in the microfluidic chip, at least a coupling portion coupled to the cartridge is formed of an elastic body, and the coupling state with the cartridge can be maintained by the elastic restoring force of the elastic body.

According to one embodiment of the present invention. Air pressure can be provided to the cartridge containing the microfluidic chip without a separate connection configuration, and the process required for driving the microfluidic can be simplified.

According to one embodiment of the present invention, the cartridge has versatility capable of driving a desired microfluidic chip embedded therein, and a blood separation device can be provided according to an embodiment of the present invention.

According to one embodiment of the present invention, it is possible to provide a blood separation device that determines the flow rate by providing the same pneumatic pressure to the buffer and the blood in each independent channel through one providing unit.

According to one embodiment of the present invention, since the buffer is pre-inflowed and the bubbles do not occur in the microfluidic chip from the point at which the blood flows into the channel, the microfluidic chip is prevented from malfunctioning due to bubbles. A blood separation device is provided can do.

1 shows a blood separation device according to an embodiment of the present invention, FIG. 1 (a) is a view showing an enlarged view of a pneumatic supply unit and an assembly in which an assembly is seated, and FIG. 1 (b) is a view showing the assembly being removed. A drawing showing the pneumatic supply unit,
2 is a view showing a head part and an assembly including a first connection part and a second connection part according to an embodiment of the present invention;
Figure 3 (a) is a view showing that the head portion is spaced apart from the assembly according to an embodiment of the present invention, Figure 3 (b) is a view showing that the first connection portion and the second connection portion of the head portion are connected to the through hole, respectively,
Figure 4 is a view showing the coupling between the microfluidic chip and the cartridge according to an embodiment of the present invention, Figure 4 (a) is an exploded perspective view, Figure 4 (b) is a view showing an assembled perspective view,
Figure 5 is a schematic diagram showing the configuration to explain the control of the pneumatic supply unit according to an embodiment of the present invention,
6 is a diagram illustrating a path of a fluid moving inside a microfluidic chip according to an embodiment of the present invention.

Hereinafter, specific embodiments of the present invention will be described with reference to the drawings. However, this is only an example and the present invention is not limited thereto.

In describing the present invention, if it is determined that a detailed description of the known technology related to the present invention may unnecessarily obscure the subject matter of the present invention, the detailed description will be omitted. In addition, terms to be described later are terms defined in consideration of functions in the present invention, which may vary according to the intention or custom of a user or operator. Therefore, the definition should be made based on the contents throughout this specification.

The technical spirit of the present invention is determined by the claims, and the following examples are only one means for efficiently explaining the technical spirit of the present invention to those skilled in the art to which the present invention belongs.

According to an embodiment of the present invention, large-capacity fluid (eg, blood) can be controlled (handling), and the pneumatic pressure is directly connected to the microfluid side, so that the delivery of pneumatic pressure is more intuitive and the convenience in the process is improved. can

A blood separation device according to an embodiment of the present invention may be a device that separates a specific substance included in blood by allowing it to pass through a channel provided with a fine structure. Here, since the channel structure can be changed according to the physical properties of a specific material, the microfluidic chip ( 110 in FIG. 1 ) can be configured to correspond to a desired material. However, in the present invention, the cartridge 120, which is a structure that communicates with the microfluidic chip 110, unlike providing blood or buffer directly to the microfluidic chip 110 through a cable, is provided to the microfluidic chip 110. ), and then blood and buffer flow into the microfluidic chip 110 by applying pressure to the cartridge 120. A detailed description in this regard will be described later through FIGS. 1 to 6 below.

1 shows a blood separation device (hereinafter referred to as a separation device) according to an embodiment of the present invention, and FIG. 1 (a) enlarges the pneumatic supply unit 200 and the assembly 100 in which the assembly 100 is seated. 1 (b) is a view showing the pneumatic supply unit 200 from which the assembly 100 is removed.

Referring to Figure 1, the separator includes an assembly 100 and a pneumatic supply unit 200 to which the assembly 100 is seated and fixed. The pneumatic supply unit 200 may supply air to the assembly 100 to move fluid within the assembly 100 through pneumatic pressure. The moving fluid may be separately collected as leukocytes are separated by the structure of the moving path.

Specifically, the assembly 100 is mounted on the cartridge 120 and the cartridge 120 including a buffer accommodating portion 121 capable of accommodating a buffer and a blood accommodating portion 122 accommodating blood, and optionally a buffer accommodating portion ( 121) and the microfluidic chip 110 through which buffers and blood can flow in communication with the blood receiving unit 122. Also, the air pressure supply unit 200 may provide air pressure to the buffer accommodation unit 121 and the blood accommodation unit 122 provided in the cartridge 120 .

Here, the pneumatic supply unit 200 is provided with a holder 230 so that the cartridge 120 can be seated and fixed. The holder 230 may fix the assembly 100 so that it cannot move laterally and downwardly. The head part 210 may descend toward the assembly 100 fixed by the holder 230 and approach it. This is to provide air pressure by approaching the respective through holes 121c and 122c of the buffer accommodating portion 121 and the blood accommodating portion 122 formed in the cartridge 120, and to provide air pressure, the head portion 210 and the above Each of the through holes 121c and 122c may maintain airtightness to a predetermined level.

Here, the assembly 100 may be placed in the holder 230 to receive a buffer and blood in the buffer accommodating part 121 and the blood accommodating part 122, respectively, before pneumatic pressure is applied. The blood and buffer provided as described above may be delivered to the microfluidic chip 110 by air pressure and separated into the receiving part 11 and the collecting part 12 via the inside of the microfluidic chip 110 . Here, the collection unit 12 may collect leukocytes, and the accommodation unit 11 may accommodate fluids other than leukocytes from a fluid in which a buffer and blood are mixed.

As described above, the blood accommodating part 122 and the buffer accommodating part 121 are indicated as the configuration for accommodating the fluid, but these are only examples, and the cartridge 120 may be provided with more accommodating parts. That is, two or more fluid accommodating units may be provided, and a microfluidic chip 110 capable of interlocking with them may be provided.

2 is a view showing the head part 210 and the assembly 100 including the first connection part 41 and the second connection part 42 according to an embodiment of the present invention.

Referring to FIG. 2, as described above, the cartridge 120 is provided with through holes 121c and 122c that open upwards of the buffer accommodating part 121 and the blood accommodating part 122, respectively, and the pneumatic pressure supply part 200 may include a first connection part 41 connected to the buffer accommodating part 121 and a second connection part 42 connected to the blood accommodating part 122 through through holes 121c and 122c. Here, the first connection part 41 and the second connection part 42 may be located vertically upward corresponding to the through holes 121c and 122c of the assembly 100 fixed to the holder 230, and the head part 210 It may come into contact with the through holes 121c and 122c by moving in the vertical direction. Here, the connection parts 41 and 42 and the through holes 121c and 122c may maintain airtightness due to the connection between the first connection part 41 and the second connection part 42 and the through holes 121c and 122c, respectively. Through this, air pressure supplied from the first connection part 41 and the second connection part 42 may be transmitted to the buffer accommodation part 121 and the blood accommodation part 122 . Therefore, the buffer and blood may be transferred to the microfluidic chip 110 by pneumatic pressure.

The first connection part 41 and the second connection part 42 may be provided with a soft elastic body at an end to be connected to the through holes 121c and 122c in an airtight state, and the elastic body responds to a predetermined pressing force. Airtightness can be maintained by the restoring force that is elastically deformed and restored by elasticity. That is, the air pressure is air pressure that exceeds atmospheric pressure, and may be provided within a level range at which an airtight state can be maintained. Specifically, pneumatic pressure may be used to transfer blood and buffer to the microfluidic chip 110 .

Figure 3 (a) is a view showing that the head portion 210 according to an embodiment of the present invention is spaced apart from the assembly 100, Figure 3 (b) is a first connection portion 41 of the head portion 210, and It is a view showing that the second connection portion 42 is connected to the through holes 121c and 122c, respectively.

Referring to FIG. 3 , the first connection part 41 and the second connection part 42 may be positioned to correspond to the through holes 121c and 122c as the head part 210 descends. Here, the buffer accommodating unit 121 and the blood accommodating unit 122 may be partitioned and separated from each other, and the buffer and blood accommodated in each may be transported by air pressure and joined in the microfluidic chip 110 to form a laminar flow. there is.

Figure 4 is a view showing the coupling between the microfluidic chip 110 and the cartridge 120 according to an embodiment of the present invention, Figure 4 (a) is an exploded perspective view, Figure 4 (b) is a view showing an assembled perspective view .

Referring to FIG. 4 , in the microfluidic chip 110, at least a coupling portion coupled to the cartridge 120 is formed of an elastic body, and can maintain a coupled state with the cartridge 120 by the elastic restoring force of the elastic body. Therefore, it is possible to maintain the coupled state as shown in FIG. 4(b). Referring to FIG. 4(a) , the cartridge 120 is connected to the first inlet hole 111a of the microfluidic chip 110, and the first connection hole is hollow so that the buffer can be transferred to the microfluidic chip 110. 121a, and a hollow second connection hole 121b connected to the second inlet hole 111b of the microfluidic chip 110 so that blood can be transferred to the microfluidic chip 110. In addition, the cartridge 120 is connected to the first outlet hole 112a of the microfluidic chip 110 so that a part of the fluid passing through the microfluidic chip 110 can be discharged to the outside. A hollow device that includes a hole 122a and is connected to the second outlet hole 112b of the microfluidic chip 110 so that the remaining part of the fluid passing through the microfluidic chip 110 can be discharged to the outside. 2 includes a discharge hole (122b).

Here, the part may be a fluid other than leukocytes, and the other part may be leukocytes. That is, the fluid other than the white blood cells discharged through the first discharge hole 122a is accommodated in the above-described receiving part 11, and the white blood cells are discharged through the second discharge hole 122b to supply the white blood cells to the collecting part 12. can be collected At this time, there is only one providing unit 10 that provides air pressure for transferring the buffer and blood to the microfluidic chip 110, and the same air pressure can be provided by the same providing unit 10. When the buffer and the blood are transported by the pneumatic pressure generated by the plurality of providing units 10, the buffer and the blood are transported by different pneumatic pressures, which may affect the flow rate ratio between the buffer and the blood. Separation of leukocytes from the pre-designed microfluidic chip 110 may be difficult because the flow rate at which blood is injected is greater than or less than a predetermined rate.

Specifically, the cross-sectional area of the flow path in the microfluidic chip 110 can be designed to obtain a desired flow rate after mixing with the buffer according to the viscosity of the blood of the test subject by determining the path through which the buffer and the blood pass, respectively. there is. That is, the flow rate of the buffer and the blood can be adjusted by adjusting the flow rate according to the design of the flow path formed inside the microfluidic chip 110 (cross-sectional area of the fluid passage), and the flow rate can be adjusted so as not to affect the flow rate. Pneumatic pressure may be provided through one providing unit 10 so that the provided pressure may be maintained the same.

5 is a diagram schematically illustrating configurations for explaining the control of the pneumatic supply unit 200 according to an embodiment of the present invention.

Referring to FIG. 5 , as described above, the air pressure supplied to the cartridge 120 from the first connecting portion 41 and the second connecting portion 42 may be generated at the same air pressure by one providing portion 10 . Furthermore, the air pressure provided from the first connection part 41 and the second connection part 42 may be provided with a predetermined time difference.

Specifically, the first valve 31 may be provided on the side of the first connection part 41 , and the second valve 32 may be provided on the side of the second connection part 42 . That is, the first valve 31 is located between the supply unit 10 generating the pneumatic pressure and the first connection unit 41, and the second valve 32 is located between the supply unit 10 and the second connection unit 42. can be located. The first valve 31 and the second valve 32 are opened at different times so that air pressure can be transmitted to the cartridge 120 through the first connection part 41 and the second connection part 42 .

More specifically, air pressure is generated from the supply unit 10, and the first valve 31 and the second valve 32 may be maintained in a closed state by the control unit 20. When the air pressure generated from the supply unit 10 increases and reaches a predetermined air pressure, the control unit 20 may open the first valve 31 . When the first valve 31 is opened, the first connection part 41 may provide air pressure to the buffer accommodating part 121 . Of course, since the buffer accommodating portion 121 and the blood accommodating portion 122 are partitioned and separated from each other, air pressure can act only on the buffer accommodating portion 121 . The buffer may flow into the microfluidic chip 110 by the action of the pneumatic pressure. When the buffer is filled up to a significant portion of the passage formed in the microfluidic chip 110, the controller 20 may control the opening of the second valve 32.

The opening of the second valve 32 means that the air pressure provided from the supply unit 10 is transmitted to the blood receiving unit 122 through the second connection unit 42, which means that the blood is transferred to the microfluidic chip 110. to be transported to The transferred blood can join the already filled buffer to form a laminar flow. This is to form a stable flow of fluid by preferentially forming the flow of the buffer and joining the flow of the blood to form a laminar flow without generating microbubbles at the confluence point M where the buffer and the blood are combined.

Specifically, when pneumatic pressure is provided at predetermined time intervals to introduce the buffer and blood into the microfluidic chip 110 with a time difference, when the buffer flows into the microfluidic chip 110 first, the microfluidic chip 110 ) The air filled in the channel formed in the buffer can be discharged by the inflow of the buffer. Air discharged here may be discharged from the channel toward the first discharge hole 122a or the second discharge hole 122b. Directions open from the channel may be the second connection hole 121a, the first discharge hole 122a, and the second discharge hole 122b. Since the connection part 42 is in contact with it, relative pneumatic pressure is formed and air cannot enter, and since the first discharge hole 121a is a place where white blood cells are separated and collected, they are easily discharged to the second discharge hole due to the complexity of the channel structure. do.

For example, when the microbubbles are generated, it may be difficult for the separation function to function normally in the process of separating leukocytes through the flow inside the microfluidic chip 110, so to induce laminar flow formation to prevent this malfunction. can be said to be for

Furthermore, the control unit 20 for controlling the opening time of the first valve 31 and the second valve 32 opens the first valve 31 and the second valve 32 by values input to the firmware. An opening point may be determined, and a value input and determined by firmware may be displayed on the display 220 shown in FIG. 1 . Of course, although not shown, the input unit may be provided separately or the display 220 may simultaneously perform the function of the input unit inputted through the touch method.

6 is a diagram showing a path of fluid moving inside the microfluidic chip 110 according to an embodiment of the present invention.

Referring to FIG. 6, as described above, the first connection portion 41 provides pneumatic pressure to the cartridge 120 prior to the second connection portion 42 by opening the first valve 31, and the first connection portion 41 ), the buffer may be filled in the microfluidic channel before the blood by the pneumatic pressure provided.

Here, the shape of the buffer formed on the microfluidic chip 110 and the channel through which the blood flows may be determined according to the viscosity of the blood.

As described above, since the air pressure is transmitted in the same size from the same supply unit 10, it is not a factor that can independently determine the flow rate for each channel. Therefore, the flow rate of each channel through which blood and buffer flow is determined based on the hydrodynamic resistance according to the design of the channel.

For example, when the buffer-to-blood flow rate is 2:1, the cross-sectional area of the first microchannel F1 may be twice that of the second microchannel F2. Here, the section of the first micro-passage F1 and the second micro-passage F2 means a passage formed from the first connection hole 121a and the second connection hole 121b to the junction point M. The cross-sectional area of the fluid passage formed in the extension direction of the passage after the confluence point M may flow with each passage cross-sectional area within the passage after the confluence point M. The passage below the confluence point M may be designed differently depending on flow velocity, viscosity, surface friction (no slip condition) of the passage, and the like.

Although representative embodiments of the present invention have been described in detail above, those skilled in the art will understand that various modifications are possible to the above-described embodiments without departing from the scope of the present invention. . Therefore, the scope of the present invention should not be limited to the described embodiments and should not be defined, and should be defined by not only the claims to be described later, but also those equivalent to these claims.

10: provision department
11: receiving part
12: collection department
20: control unit
31: first valve
32: second valve
41: first connection part
42: second connection part
100: assembly
110: microfluidic chip
111a: first inlet hole
111b: second inlet hole
112a: first outflow hole
112b: second outflow hole
120: cartridge
121: buffer receiving unit
121a: first connecting hole
121b: second connecting hole
121c, 122c: through hole
122: blood reception unit
122a: first discharge hole
122b: second discharge hole
125: discharge hole
126: collector
200: Pneumatic supply unit
210: head part
220: display
230: holder
M: point of confluence
F1: 1st microchannel
F2: 2nd microchannel

Claims (8)

a cartridge including a buffer accommodating part accommodating a buffer and a blood accommodating part accommodating blood;
a microfluidic chip mounted on the cartridge and selectively communicating with the buffer accommodating part and the blood accommodating part, through which the buffer and the blood can flow; and
A pneumatic pressure providing unit providing air pressure to the buffer accommodating unit and the blood accommodating unit provided in the cartridge;
the cartridge,
The blood separation device, wherein the buffer accommodating part and the blood accommodating part are partitioned from each other to form independent spaces, and air pressure is independently supplied to the buffer accommodating part and the blood accommodating part by the air pressure providing part.
The method of claim 1,
The buffer accommodating portion and the through hole opening upwardly of the blood accommodating portion are respectively provided,
The blood separation device, wherein the pneumatic supply unit includes a first connection part connected to the buffer accommodating part through the through hole and a second connection part connected to the blood accommodating part.
The method of claim 2,
The pneumatic,
Provided earlier than the second connection portion through the first connection portion,
The blood separation device, wherein the microfluidic channel is filled with the buffer before the blood by the pneumatic pressure provided through the first connection part.
The method of claim 2,
Wherein the air pressure supplied from the first connection part and the second connection part is generated as the same air pressure by one providing part.
The method of claim 4,
The blood separation device, wherein the flow rate of the buffer and the blood formed in the microfluidic chip is determined according to the structure of the channel and the viscosity of the buffer and blood.
The method of claim 3,
The blood separation device further comprises a first valve provided on the side of the first connection part and a second valve provided on the side of the second connection part so that the air pressure supplied from the first connection part and the second connection part is supplied at a predetermined time interval.
The method of claim 6,
Further comprising a control unit for controlling an opening time point at which the first valve and the second valve are opened, wherein the control unit determines an opening time point of the first valve and the second valve based on values input to firmware. separator.
The method of claim 1,
The microfluidic chip,
The blood separation device of claim 1 , wherein at least an engaging portion coupled to the cartridge is formed of an elastic body, and maintains a coupled state with the cartridge by an elastic restoring force of the elastic body.

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