JP2010256304A - Circulation type corpuscle separation filter chip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To solve a problem of a conventionally used corpuscle separation filter (wear filter, membrane filter and pillar filter) wherein blood flows in the direction perpendicular to the filter and jamming of the filter in the midway of corpuscle separating considered to originate in a fact that the corpuscle components that cannot permeate the filter are stacked on a surface of the filter and pressurized causes hemolysis. <P>SOLUTION: This circulation type corpuscle separation filter chip includes an inflow port for making blood flow in, an inner circular channel that is connected to the inflow port and is used for circulating the flowing-in blood, a cross-flow filter that can permeate a part of blood components and constitutes the outer periphery of the inner circular channel, an outer circular channel adjacent to the inner circular channel using the cross-flow filter as the inner periphery, and an outflow port that is connected to the outer circular channel and ejects a part of blood components having permeated the cross-flow filter. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a circulating blood cell separation filter chip that uses a circular cross-flow filter to separate blood cells while blood circulates in a circular flow path.

In clinical examinations and the like, blood collected from a subject is separated into a blood cell component and a plasma component (or serum component), and only the plasma component is used. For this reason, it is necessary to perform blood cell separation processing on blood collected from the subject before the examination.
Blood cell separation techniques can be broadly classified into centrifugation and membrane separation. A commonly used blood cell separation method is a centrifugation method. However, the centrifuge method has problems such as requiring skillful techniques, a centrifuge device being large and expensive, requiring a relatively large amount of blood, and taking time to work. . On the other hand, the membrane separation method is a method of filtering blood cell components from whole blood by adhesion and adhesion of blood cells using a functional membrane or the like. Since it is simple and inexpensive to operate, it has been applied to several microchemical chips. Specifically, there is a method using (a) a wear filter, (b) a membrane filter, (c) a pillar filter, as shown in FIG. However, in the method using these various filters, there is a problem that the filter is clogged during blood cell separation, blood cell separation cannot be performed, and hemolysis occurs. This is considered due to the fact that blood cell components are stacked on the surface of the filter and pressure is applied.

  In addition, the size of blood cell components ranges from several microns to tens of microns at most (red blood cells are approximately 8 μm). When a filter for separating the blood cell components is used, its structure is fine and complex, difficult to process, and industrial. Difficult to manufacture. Even if possible, there remains a cost problem.

Hong Miao, et al., The 10th International Conference on Miniaturized Systems for Chemistry and Life Science., November 5-9, 2006, 323-324

  Therefore, a crossflow filter has been developed as a method for avoiding clogging of the filter (Non-Patent Document 1). FIG. 12 shows a conceptual diagram of a method for separating blood cell components using a cross flow filter.

  The blood flowing in from the inflow port (1201) flows through the blood flow path (1202). At this time, the blood cell component flows through the blood channel (1202) without being laminated on the surface of the cross flow filter (1203), and only the permeate flows out to the permeation channel (1204) and flows out from the outlet (1205). Is done. That is, in this method, blood flows parallel to the crossflow filter (1203) (1207), and the permeate passes through the crossflow filter at a right angle (1208). Therefore, clogging of the filter can be made difficult to occur.

  However, even in this method, the blood flow stops at the end point (1206) of the blood flow path (1202), and a blood cell component accumulates in the portion, so that pressure is applied and the problem of hemolysis has not been solved. Also, many red blood cells with high deformability pass through the cross flow filter even during circulation.

  In addition, as in the conventional method, the structure is fine and complicated, so that it is difficult to process a filter of several microns with commonly used glass or rigid plastic material. But there was a cost problem. It has also been difficult to downsize the blood cell separation device itself. Therefore, for example, it is portable with a small-sized dispensing device such as a “micro dispensing device” according to a patent application (Japanese Patent Application No. 2008-209555) filed by the present inventor, and used together with the dispensing device. It was difficult to make blood tests easier.

  Therefore, the present invention provides a circulating blood cell separation filter chip that separates blood cell components including red blood cells using a cross flow filter and has a simple structure and is small and portable.

  (1) The present invention is connected to an inflow port for inflowing blood, an inner circular channel for circulating the inflowing blood, and a part of blood components can be permeated. A cross flow filter constituting the outer circumference of the inner circular flow path, an outer circular flow path adjacent to the inner circular flow path with the cross flow filter as the inner circumference, and a cross-flow filter connected to the outer circular flow path and passing through the cross flow filter. And a circulation type blood cell separation filter chip comprising an outlet for flowing out blood components of the part.

  (2) The present invention is connected to an inflow port for inflowing blood, an inner circular channel for circulating the inflowed blood, and a part of blood components can be permeated. A cross flow filter that constitutes the outer circumference of the inner circular flow path, an outer circular flow path that is adjacent to the inner circular flow path with the cross flow filter as the inner circumference, and a blood component that is partially permeable to the outside. A second cross flow filter constituting the outer periphery of the circular flow channel, a second outer circular flow channel adjacent to the outer circular flow channel with the second cross flow filter as an inner periphery, and a second outer circular flow channel connected to the second outer circular flow channel. There is provided a circulation type blood cell separation filter chip comprising an outlet for flowing out a part of blood components that have passed through a two-cross flow filter.

  (3) In the present invention, a combination of a cross flow filter and an outer circular channel is repeatedly provided on the outside of the second outer circular channel in the same manner as described above, and the outermost outer circular channel is connected to the outlet. A circulating blood cell separation filter chip according to (2) is provided.

  (4) The present invention provides the circulation type blood cell separation filter chip according to any one of (1) to (3), wherein the inflow port is disposed in a circular region surrounded by an inner circular flow path.

  (5) The present invention includes an orifice provided in the inner circular flow path in the vicinity of the blood flowing in from the inlet so that the blood flowing in from the inlet circulates in one direction in the inner circular flow path ( A circulating blood cell separation filter chip according to any one of 1) to (4) is provided.

  (6) In the present invention, the crossflow filter includes a column repeatedly arranged and a transmission hole formed between the columns, and the transmission hole has a size such that a red blood cell component cannot be transmitted. To (5) The circulating blood cell separation filter chip according to any one of the above is provided.

  (7) The present invention provides the circulation type blood cell separation filter chip according to any one of the above (1) to (6), wherein the volume of the inner circular channel is larger than the volume of the other circular channel.

  (8) The circulating blood cell separation filter chip according to any one of (1) to (7), wherein the transmission hole has a height of 5 μm or less and a width of 2 μm or less. .

  According to the circulation type blood cell separation filter chip of the present invention, clogging of the filter can be suppressed, and separation can be performed at a red blood cell level in a short time. Moreover, since it has a very simple structure, it can be mass-produced at a small size and at a low cost.

Conceptual diagram of circulating blood cell separation filter chip according to the first embodiment Schematic diagram of columns and transmission holes constituting the crossflow filter of the first embodiment Schematic diagram of columns and transmission holes constituting the crossflow filter of the first embodiment Conceptual diagram of inner circular channel and outer circular channel of embodiment 1 Schematic diagram of circulating blood cell separation filter chip of embodiment 2 Conceptual diagram of pillars and transmission holes constituting the crossflow filter of the second embodiment Schematic diagram of circulating blood cell separation filter chip of Embodiment 3 Schematic diagram of circulating blood cell separation filter chip of embodiment 4 Schematic diagram of circulating blood cell separation filter chip of embodiment 4 The figure which shows the blood cell isolation | separation of Example 2. Conceptual diagram of a blood cell separation filter that has been used in the past Conceptual diagram of a conventional blood cell separation crossflow filter

Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. In addition, this invention should not be limited to these embodiments at all, and can be implemented in various modes without departing from the gist thereof. The first embodiment relates to claims 1, 6 to 8. The second embodiment relates to claim 2 and the like. The third embodiment relates to claim 3 and the like. The fourth embodiment relates to claims 4 and 5.
<< Embodiment 1 >>
<Embodiment 1: Overview>

  In the present embodiment, while the inflowing blood circulates in the inner circular channel, a part of the blood component passes through the cross flow filter constituting the outer periphery of the inner circular channel, and a part of the blood component is the outer circular channel A circulating blood cell separation filter chip configured to flow out from the flow outlet will be described.

The circulation type blood cell separation filter chip of the present embodiment can suppress hemolysis due to filter clogging and can separate a part of blood components in a short time. Moreover, since it has a very simple structure, it can be miniaturized, can be finely processed, and can be industrially manufactured at a lower cost.
<Embodiment 1: Configuration>

FIG. 1 shows a conceptual diagram of this embodiment. The circulation type blood cell separation filter chip of this embodiment includes an inflow port (0101), an inner circular channel (0102), and a cross flow filter (0103).
And an outer circular channel (0104) and an outlet (0105).

  “Circulating blood cell separation filter chip” refers to a blood component (mainly flowing through an inner circular flow path (0102) that does not pass through a perforation hole of a crossflow filter (0103) and flows from an inlet (0101) described later. The blood cell component) is circulated in the inner circular flow path. In other words, there is nothing corresponding to the end point (1206) of the blood flow path (1202) of the cross-flow filter shown in FIG. 12, and it is configured to continue to circulate. Therefore, it is possible to prevent blood components (mainly blood cell components) circulating in the inner circular flow path (0102) from stagnating in the inner circular flow path. Therefore, it is possible to prevent hemolysis that occurs when pressure is applied to blood cell components.

  The “inlet” (0101) is for inflowing blood. Here, “blood” includes not only whole blood but also blood from which some components are removed. For example, some blood components are removed in advance using a centrifugal separator or various filters. In such a case, the white blood cells are mainly removed by prior treatment, and then the remaining white blood cells and red blood cells are separated using the circulating blood cell separation filter chip of the invention.

  Further, a blood collection needle mounting portion for mounting a blood collection needle for collecting blood may be provided at the end of the inflow port. In such a case, the collected blood flows directly into the inlet without requiring a blood collection tube or the like, so that convenience is increased and the blood is not contaminated.

  The “inner circular flow path” (0102) is a flow path that is connected to the inflow port (0101) and circulates and circulates the blood flowing in from the inflow port (0101). “Connected to the inlet” means that the inlet and the inner circular flow path are connected directly or indirectly. “Directly connected” means that the blood that has flowed in from the inlet flows directly into the inner circular flow path. Further, “indirectly connected” means that the blood flowing in from the inflow port flows in a substantially straight line as shown in FIG. 1 or an arcuate flow as shown in FIGS. This refers to the case of flowing into the inner circular flow path through a path. When indirectly connected, the blood flows in the inner circular flow path with directionality, which is preferable in that it can smoothly circulate and flow in one direction in the inner circular flow path. The reason will be described in the fourth embodiment described later. In addition, since some of the blood components permeate the cross flow filter (0103), which will be described later, and flow into the outer circular channel (0104), which will be described later, Blood components that do not pass through the crossflow filter (0103) remain.

In addition, the volume of the inner circular flow path needs to be large enough not to apply pressure to the blood in the entire process in which the blood flowing in from the inlet is separated while circulating in the inner circular flow path.
This is to prevent the cross flow filter (0103) from being clogged by applying pressure to the blood in the inner circular flow path, and at the same time to allow blood to circulate and flow smoothly in the inner circular flow path. is there.

  The “cross flow filter” (0103) is a filter that can transmit a part of the blood components and constitutes the outer periphery of the inner circular flow path (0102). Here, the “partial blood component” means a relatively small blood component (mainly a plasma component) that can pass through the perforation hole of the crossflow filter (0103) among the blood components flowing in from the inlet (0101). ).

  The “partial blood component” flows out from the outflow port (0105) through the outer circular channel (0104) described later, and is used for blood analysis and the like. Therefore, it is preferable that it is composed only of plasma components (or serum components) that do not contain blood cell components such as white blood cells and red blood cells. However, blood cell components may be included as long as they do not hinder blood analysis. Further, “to configure the outer circumference of the inner circular flow path” means to configure the outer wall of the inner circular flow path as shown in the enlarged view of FIG.

  FIG. 2 shows a conceptual diagram of the crossflow filter. (A) is a partial enlarged view of the transverse cross-sectional view of the circulation type blood cell separation filter chip, and (b) is a perspective cross-sectional view of a portion surrounded by 0200a in the drawing of (a). The “cross flow filters” (0201a, 0201b) are configured by columns (0202a, 0202b) repeatedly arranged and transmission holes (0203a, 0203b) provided between the columns. The columns (0202a, 0202b) and the transmission holes (0203a, 0203b) are repeatedly arranged so as to form a circle sandwiched between the inner circular channel (0204a, 0204b) and the outer circular channel (0205a, 0205b). Thus, a single-layer cross flow filter (0201a, 0201b) is formed. In addition, the part enclosed with the dotted line in (b) comprises the ceiling surface of a circulation type blood cell separation filter chip. The same applies to FIGS. 3B, 4B, and 3C.

  Therefore, only a part of blood components that can permeate through the permeation holes (0203a, 0203b) of the “cross flow filters” (0201a, 0201b) out of the blood flowing in from the inflow port enter the outer circular channels (0205a, 0205b). The component that flows in and cannot pass through the permeation holes (0203a, 0203b) circulates and circulates through the inner circular flow paths (0204a, 0204b). Accordingly, the permeation holes (0203a, 0203b) may be of a size that does not allow the blood cell component to be separated using the circulating blood cell separation filter chip of the present embodiment, and depending on the type of the blood cell component to be separated. The size of the transmission holes (0203a, 0203b) may be determined as appropriate. For example, in blood cell separation for blood tests such as medical examinations, it is necessary to separate red blood cells as well as white blood cells, so that the permeation holes (0203a, 0203b) of a size in which relatively small red blood cells cannot pass are formed. Just do it. Preferably, the permeation hole has a height (0206b) of approximately 5 μm and a width (0207a, 0207b) of approximately 2 μm, assuming that red blood cells are deformed by pressure. If it is a cross flow filter comprised of permeation holes of the size, red blood cells can be separated without leakage. More preferably, the height (0206b) of the transmission hole is approximately 2 μm, and the widths (0207a, 0207b) are approximately 2 μm. In such a case, even if pressure is applied and the red blood cells are deformed, the separation is effective.

  FIG. 2 (c) is a conceptual diagram showing that red blood cells (0208c) circulating in the inner circular flow path (0204c) approach sideways with respect to the transmission hole (0203c) of the cross flow filter (0201c). is there. Red blood cells (0208c) have a disk shape with a recessed central part, and have a diameter of about 6 to 8 μm and a thickness of about 2 μm. And it has high deformability and also passes through capillaries that are thinner than the diameter of red blood cells. Therefore, by configuring the transmission hole (0203c) to the above size, the red blood cell (0208c) approaches the transmission hole (0203c) sideways. This prevents not only the disk-shaped red blood cells but also red blood cells deformed by some action from passing through the transmission hole (0203c) of the crossflow filter (0201c). In the figure, 0209c indicates a lid of the circulating blood cell separation filter chip.

  The shape of the transmission hole may be as shown in FIGS. 3A and 3C as long as the blood cell component to be separated can be separated. (A) is a partially enlarged view of a transverse cross-sectional view of a circulating blood cell separation filter chip, and (b) is a perspective cross-sectional view of a portion surrounded by 0300 in (a). By providing pillars (0302a, 0302b) and transmission holes (0303a, 0303b) so that the transmission direction is smaller than 90 degrees with respect to the flow direction of the inner circular flow paths (0304a, 0304b), a part of the flow direction can be made more smoothly. Blood components can penetrate and blood cells can be separated in a short time.

  Further, the shape of the pillar (0301c) may be changed as shown in (c). In such a case, the blood cell component that has been directed to the permeation hole (0303c) flows along the column (0301c), and returns to the inner circular flow path (0304c) to circulate. This is effective in that transmission through 0301c) can be suppressed.

  The “outer circular flow path” (0104) is a flow path adjacent to the inner circular flow path (0102) with the cross flow filter (0103) as an inner circumference. “Adjacent to the inner circular flow path with the cross flow filter as the inner circumference” means that the cross flow filter forms the inner wall of the outer circular flow path, and the inner circular flow path and the outer circular flow path are cross-flowed. It is adjacent through a filter. The “partial blood component” flows through the outer circular flow path.

  The volume of the outer circular channel (0104) may be approximately the same as that of the inner circular channel (0102), or may be configured smaller than that. This is because the inner circular channel is a channel into which all the blood flowing in from the inlet flows, and the inner circular channel does not have a discharge port. Further, since the blood component circulating in the inner circular flow path has a large proportion of blood cell components, the volume is increased so that the blood can be circulated more smoothly and clogging of the cross flow filter can be suppressed. FIG. 4A shows an inner circular flow path (0401a), an outer circular flow path (0402a) constituting the circulation type blood cell separation filter chip of the present embodiment, a column (0403a) constituting the cross flow filter, and a permeation hole ( 0404a) is a partially enlarged view, and (b) and (c) are perspective sectional views of a portion surrounded by 0400a in (a). As shown in (b), the flow path height of the inner circular flow path (0401b) may be made larger than the flow path height of the outer circular flow path (0402b) to increase the volume of the inner circular flow path. . In such a case, the amount of blood that can flow from the inlet can be increased, the clogging of the cross flow filter can be prevented, and smooth circulation can be achieved. Also, as shown in (c), the inner circular flow path (0401c) and the outer circular flow path (0401c) have the same flow path height, and the width is changed to increase the volume of the inner circular flow path. It may be configured.

  The “outlet” (0105) is connected to the outer circular channel and flows out a part of blood component that has passed through the cross flow filter. “Connected to the outer circular flow path” means that the outlet (0105) and the outer circular flow path (0104) are directly or indirectly connected. “Directly connected” means that a part of blood components flowing out from the outer circular flow channel flows directly into the outlet. In addition, “indirectly connected” means that a portion of the blood component flowing out from the outer circular flow channel flows into the outflow port before the substantially straight flow channel as shown in FIGS. This refers to the case of flowing into the outlet through the flow path on the bow.

The outlet (0105) may be provided on the opposite side of the outlet (0101a) as shown in FIG. 1 (a) (0105a), and the outlet (0101b) as shown in (b). (0105b). Moreover, it is not limited to these, The position of an outflow port can be changed suitably. In the case of FIG. 1 (b), since the flow direction (arrow in the figure) of a part of blood components in the outer circular flow path (0104b) and the outflow direction are the same, blood cells can be separated in a shorter time. Become.
<Embodiment 1: Effect>

According to the circulation type blood cell separation filter chip of this embodiment, hemolysis due to filter clogging is suppressed, and separation with blood cells can be performed in a short time and with high accuracy. Moreover, since it has a very simple structure, it can be finely processed and can be industrially manufactured at low cost.
<< Embodiment 2 >>
<Embodiment 2: Overview>

  In this embodiment, while blood flowing in from the inflow port circulates in the inner circular flow path, a part of the blood component passes through the cross flow filter that forms the outer periphery of the inner circular flow path, and passes through the cross flow filter. A circulation type in which a part of the blood component further passes through the second cross-flow filter constituting the outer periphery of the outer circular flow path, flows into the second outer circular flow path, and flows out from the outlet. The blood cell separation filter chip will be described.

The circulation type blood cell separation filter chip of the present embodiment can separate blood cells that have passed through the cross flow filter with the second cross flow filter, and can avoid outflow of blood cell components from the outflow port.
<Embodiment 2: Configuration>

  FIG. 5 shows a conceptual diagram of this embodiment. The circulation type blood cell separation filter chip of this embodiment includes an inflow port (0501), an inner circular flow path (0502), a cross flow filter (0503), an outer circular flow path (0504), and a second cross flow filter. (0505), a second outer circular channel (0506), and an outlet (0507). Here, the configuration other than the outer circular channel (0504), the second cross flow filter (0505), the second outer circular channel (0506), and the outlet (0507) is as described in the first embodiment. Therefore, explanation here is omitted.

  In the present embodiment, the cross flow filter (0503) is referred to as a “first cross flow filter” for convenience. Similarly, the outer circular channel (0504) will be described as a “first outer circular channel”.

  The “second crossflow filter” (0505) refers to a crossflow filter that can transmit a part of blood components of blood components and constitutes the outer periphery of the outer circular flow channel (0504). Here, “constitute the outer circumference of the outer circular flow path” means that the “second cross flow filter” (0505) forms the outer wall of the first outer circular flow path as shown in the enlarged view of FIG. It is to be. That is, the circulation type blood cell separation filter chip of the present embodiment has a two-layer crossflow filter including a first crossflow filter (0503) and a second crossflow filter (0505) on the outer side. With this configuration, since the blood cell component that has passed through the first crossflow filter can be separated by the second crossflow filter, blood cell separation can be performed with higher accuracy.

  The permeation hole of the first crossflow filter and the permeation hole of the second crossflow filter may have such a size that blood cell components to be separated by using the circulation type blood cell separation filter chip of this embodiment cannot be finally transmitted. What is necessary is just to determine the magnitude | size of a permeation | transmission hole suitably according to the kind of the said blood cell component. Here, “finally impenetrable” means that even the blood cell component that has passed through the first crossflow filter cannot pass through the second crossflow filter. Therefore, for example, when separating red blood cells together with white blood cells, it is only necessary that at least the permeation hole of the second cross-free filter has a size that does not allow a relatively small red blood cell component to pass therethrough. Preferably, it is a perforation hole having a height of 5 μm and a width of 2 μm, assuming that red blood cells are deformed by pressure. If it is a cross flow filter comprised of permeation holes of the size, red blood cells can be separated without leakage. More preferably, the height of the transmission hole is 2 μm and the width is 2 μm. Even when red blood cells are deformed by pressure or the like, it is effective in that they can be separated.

  The size and / or shape of the transmission hole of the first crossflow filter and the transmission hole of the second crossflow filter may be different from each other. An example is shown in FIG.

  In FIG. 6A, the transmission hole (0603a) of the first crossflow filter (0601a) is relatively large, and the transmission hole (0604a) of the second crossflow filter (0602a) is relatively small. . In such a configuration, blood cells can be separated step by step so that a relatively large blood cell component is separated by the first crossflow filter (0601a) and a relatively small blood cell component is separated by the second crossflow filter (0602a). Therefore, the first and second crossflow filters can be prevented from being clogged as compared with the case where a relatively small blood cell component is to be separated from the first crossflow filter. In addition, blood cells can be separated with higher accuracy in a shorter time. For example, a configuration in which white blood cells are separated by a first crossflow filter and red blood cells are separated by a second crossflow filter is conceivable.

  Further, FIG. 6B shows that the transmission hole (0603b) of the first cross flow filter is provided so that the transmission direction (0605b) is smaller than about 90 degrees with respect to the flow direction of the inner circular flow path. The transmission hole (0604b) of the cross flow filter is provided so that the transmission direction (0606b) is approximately 90 degrees with respect to the flow direction of the first outer circular flow path. In such a configuration, the first crossflow filter (0601b) is smoothly transmitted, and the separation target blood cell component can be steadily separated by the second crossflow filter (0602b). Therefore, clogging of each crossflow filter can be prevented and blood cell separation can be performed in a shorter time and with higher accuracy.

  The “second outer circular channel” (0506) refers to a circular channel adjacent to the first outer circular channel (0504) with the second cross flow filter (0505) as an inner circumference. Here, “adjacent to the outer circular flow path with the second cross flow filter as the inner circumference” means that the second cross flow filter (0505) constitutes the inner wall of the second outer circular flow path (0506). The first outer circular channel (0504) and the second outer circular channel (0506) are adjacent to each other via the second cross flow filter (0505). That is, the circulation type blood cell separation filter chip according to the present embodiment has three circular flow paths: an inner circular flow path (0502), a first outer circular flow path (0504), and a second outer circular flow path (0506). . The inner circular channel (0502) and the first outer circular channel (0504) are adjacent to each other via the first crossflow filter (0503), and the first outer circular channel (0504) and the second outer circular channel are adjacent to each other. It is adjacent to the flow path (0506) through the second cross flow filter (0505). Therefore, the blood flowing in from the inflow port (0501) circulates and flows through the inner circular flow path (0502), and a part of the blood components permeate the first cross flow filter (0503), thereby passing through the first outer circular flow path. (0504), and a part of that passes through the second cross flow filter (0505), enters the second outer circular flow path (0506), and finally flows out from the outlet (0507) described later.

  The volumes of the three circular flow paths are not particularly limited as long as no pressure is applied to the first and second cross flow filters, and the volumes of the inner circular flow paths may be the same. Only the first and second outer circular flow paths may be configured larger than the inner circular flow path, the first outer circular flow path, and the second outer circular flow path in order of decreasing volume. Good.

The “outer circular flow path” (0504) of this embodiment is not connected to the “outlet” (0507) but is a circulation flow path, and other configurations are the same as those of the first embodiment. The “outlet” (0507) is connected to the second outer circular flow path, and the other configuration is the same as that of the first embodiment.
<Embodiment 2: Effect>

According to the circulation type blood cell separation filter chip of the present embodiment, since it is composed of a two-layer cross flow filter, blood cells can be separated with higher accuracy. Further, by appropriately combining the sizes and shapes of the permeation holes of each crossflow filter, hemolysis due to filter clogging can be suppressed and blood cells can be separated in a short time.
<< Embodiment 3 >>
<Embodiment 3: Overview>

  In this embodiment, the second outer circular channel of the second embodiment is further provided with a combination of a cross flow filter and an outer circular channel on the outer side, and the outermost outer circular channel is connected to the outlet. The constructed circulating blood cell separation filter chip will be described.

The circulating blood cell separation filter chip of this embodiment can more reliably separate blood cells.
<Embodiment 3: Configuration>

  “Repeatedly providing a combination of the cross flow filter and the outer circular flow path” means that one cross flow filter and one outer circular flow path are set as one set, and further outside the second outer circular flow path of the second embodiment. Means that one or more such sets are provided. The repetition frequency may be one or more, and may be appropriately determined according to the required separation accuracy. As the repetition frequency increases, it is difficult to reduce the size of the apparatus and increase the speed of separation, but the separation accuracy increases. On the other hand, the smaller the repetition frequency, the lower the separation accuracy, but the device can be made smaller and the separation speeded up.

  In the present embodiment, the cross flow filter is referred to as a “first cross flow filter” for convenience. Similarly, the outer circular channel is referred to as a “first outer circular channel”. Further, for the cross flow filter and the outer circular flow path provided outside the second outer circular flow path, from the inner side toward the outer side, "third cross flow filter", "fourth cross flow filter", ..., Alternatively, “third outer circular channel”, “fourth outer circular channel”,...

  FIG. 7 shows a conceptual diagram of a circulating blood cell separation filter chip provided with one combination of a cross flow filter and an outer circular flow path as an example of this embodiment. The circulation type blood cell separation filter chip includes an inflow port (0701), an inner circular flow path (0702), a first cross flow filter (0703), a first outer circular flow path (0704), and a second cross flow filter. (0705), a second outer circular channel (0706), a third cross flow filter (0707), a third outer circular channel (0708), and an outlet (0709). Here, since the configuration other than the third cross flow filter (0707), the third outer circular flow path (0708), and the outlet (0709) is as described in the first embodiment, the description here is as follows. Omitted.

  The “third cross-flow filter” (0707) is similar to the first cross-flow filter (0703) and the second cross-flow filter (0705), and can transmit a part of blood components. A cross flow filter that constitutes the outer periphery of the outer circular flow path (0706). As shown in the enlarged view of FIG. 7, the “third cross flow filter” (0707) constitutes the outer wall of the second outer circular flow path (0706). In other words, the circulation type blood cell separation filter chip of FIG. 7 includes a three-layer crossflow including a third crossflow filter (0707) further outside the first crossflow filter (0703) and the second crossflow filter (0705). Has a filter. With this configuration, blood cell components that have passed through the first cross flow filter and the second cross flow filter can also be separated by the third cross flow filter, so that blood cells can be separated with higher accuracy.

  As in the second embodiment, the transmission hole of the first crossflow filter (0703), the transmission hole of the second crossflow filter (0705), and the transmission hole of the third crossflow filter (0707) are the circulation type shown in FIG. It is sufficient that the blood cell component to be separated by using the blood cell separation filter chip can be finally transmitted, and the size of the transmission hole may be appropriately determined according to the type of the blood cell component. That is, it is sufficient that at least the transmission hole of the third cross-free filter has such a size that the blood cell component to be separated cannot be finally transmitted.

  In addition, about another structure, it applies to Embodiment 1 and 2.

  The “third outer circular channel” (0708) refers to a circular channel adjacent to the second outer circular channel (0706) with the third cross flow filter (0707) as an inner circumference. Here, “adjacent to the second outer circular flow path with the third cross flow filter as the inner circumference” means that the third cross flow filter constitutes the inner wall of the third outer circular flow path, The second outer circular channel and the third outer circular channel are adjacent to each other through a cross flow filter. That is, the circulating blood cell separation filter chip of FIG. 7 includes an inner circular channel (0702), a first outer circular channel (0704), a second outer circular channel (0706), and a third outer circular channel (0708). And four circular flow paths. The inner circular channel (0702) and the first outer circular channel (0704) are adjacent to each other via the first cross flow filter (0703), and the first outer circular channel (0704) and the second outer circular channel are adjacent to each other. The flow path (0706) is adjacent to the second cross flow filter (0705), and the second outer circular flow path (0706) and the third outer circular flow path (0708) are connected to the third cross flow filter (0708). 0707). Accordingly, the blood flowing in from the inflow port (0701) circulates and flows through the inner circular flow path (0702), and a part of the blood components permeate the first cross flow filter (0703), thereby passing through the first outer circular flow path. (0704), and a part of it passes through the second cross flow filter (0705) and enters the second outer circular flow path (0706), and a part of the third cross flow filter (0707). , Enters the third outer circular channel (0708), and finally flows out from an outlet (0709) described later.

  The volumes of the four circular flow paths are not particularly limited as long as no pressure is applied to the first, second, and third cross flow filters. Only the volume of the path may be configured to be larger than the first, second, and third outer circular channels, and the inner circular channel, the first outer circular channel, the second outer circular channel, and the third outer circle The volume may be made smaller in the order of the flow path. In addition, about another structure, it applies to Embodiment 1 and 2.

  Note that the “outlet” (0709) in FIG. 7 is connected to the third outer circular flow path, and other configurations are the same as those in the first embodiment.

In addition, what is necessary is just to follow the case where two or more combinations of a cross flow filter and an outer side circular flow path are provided repeatedly when one said combination is provided.
<Embodiment 3: Effect>

According to the circulation type blood cell separation filter chip of the present embodiment, since it is composed of three or more layers of crossflow filters, blood cells can be separated with higher accuracy. Further, by appropriately combining the sizes and shapes of the permeation holes of each crossflow filter, hemolysis due to filter clogging can be suppressed and blood cells can be separated in a short time.
<< Embodiment 4 >>
<Embodiment 4: Overview>

  This embodiment demonstrates the circulation type blood cell separation filter chip | tip arrange | positioned in the circular area | region where an inflow port is enclosed by an inner side circular flow path.

  In addition, the present embodiment is a circulation type blood cell provided with an orifice in the inner circular flow path in the vicinity of the blood flowing in from the inflow port so that the blood flowing in from the inflow port circulates in one direction in the inner circular flow path. The separation filter chip will be described.

The circulation type blood cell separation filter chip of the present embodiment circulates and flows smoothly in one direction in the inner circular flow path because the blood flowing in from the inflow port is prevented, and thus the clogging of the cross flow filter is prevented. In addition, blood cells can be separated in a short time.
<Embodiment 4: Configuration>

In FIG. 8, the conceptual diagram of the circulation type blood cell separation filter chip | tip of this embodiment is shown. Inlet (0801), inner circular flow path (0802), cross flow filter (0803), outer circular flow path (0804), second cross flow filter (0805), second outer circular flow path ( 0806) and an outlet (0807).
Since the configuration other than the inlet (0801) is as described in the second embodiment, description thereof is omitted here.

  The “inflow port” (0801) of the present embodiment is disposed in a circular region surrounded by the inner circular flow path (0802). This is because the blood flowing in from the inlet is circulated in one direction in the inner circular channel. Also, by providing an arcuate channel (0808) between the inlet and the inner circular channel, the blood flowing into the inner circular channel (0802) from the arcuate channel (0808) has a certain orientation. (Arrow in the figure) occurs. In such a case, the blood that has entered the inner circular channel from the arcuate channel does not flow through the inner circular channel in both directions. Smooth distribution in the direction of the arrow in the figure. Therefore, circulation circulation of the inner circular flow path is performed smoothly, and clogging of the cross flow filter can be suppressed.

Further, as shown in FIG. 9, an orifice (0908) may be provided in the inner circular flow path (0902). The orifice (0908) can further suppress the blood flowing from the inlet (0901) from traveling in both directions through the inner circular channel (0902). If the orifice (0908) is provided near the point where the arcuate channel and the inner circular channel intersect, the effect is greater. Needless to say, the orifice is an inner circular flow path for circulating blood, and is provided on the near side of the joining position with the inlet.
<Embodiment 4: Effect>

  According to the circulation type blood cell separation filter chip of the present embodiment, the blood can smoothly circulate and circulate through the inner circular flow path, so that the clogging of the cross flow filter can be prevented. Moreover, blood cells can be separated in a shorter time.

  The circulation type blood cell separation filter chip according to the present invention is made using polydimethylsiloxane (PDMS) as a material and utilizing photolithographic technology, and the state of separation when blood cells are separated from whole blood is shown in FIG. Show. In addition, the produced circulation type blood cell separation filter chip has a configuration having the two-layer cross flow filter described in the second embodiment (first cross flow filter and second cross flow filter). The inner circular channel and the channel width were about 100 μm, the channel height of the first outer circular channel and the second outer circular channel was 2 μm, and the volume of the inner circular channel was larger than the other channels.

  FIG. 10 shows a state in which blood cell separation gradually proceeds from (a) to (c). The circulation type blood cell separation filter chip of this embodiment uses PDMS as a material, and includes an inner circular flow path (1001), a first cross flow filter (1002), a first outer circular flow path (1003), and a second. It has a two-layered crossflow filter consisting of a crossflow filter (1004) and a second outer circular channel (1005). In the figure, blood circulates from right to left.

  (A) shows a state in which blood (1006a) flowing in from the inflow port circulates in the inner circular channel (1001a). Here, it is not possible to confirm that the plasma component is still passing through the first or second crossflow filter (1002a, 1004a). In addition, since the blood component which distribute | circulates an inner side circular flow path (1001a) contains red blood cells, it is exhibiting red.

  In (b), the blood (1006b) filling the inner circular flow path (1001b) circulates and flows, and a part of the blood component (1007b) permeates the first cross flow filter (1002b). It can be seen that the air flows into the outer circular channel (1003b). Here, since the inner circular flow path (1001b) is red and a part of blood components flowing into the first outer circular flow path (1003b) is almost transparent, the red blood cells are the inner circular flow path (1001b). It can be confirmed that it is in circulation.

  In (c), a part of the blood component (1008c) of the blood component flowing through the first outer circular flow channel (1003c) permeates the second cross flow filter (1004c), and the second outer circular flow channel (1004c) 1005c) can be seen flowing and circulating. As in (b), the inner circular flow channel (1001c) is red, and the first outer circular flow channel (1003c) and the second outer circular flow channel (1005c) are almost transparent. It can be confirmed that it does not pass through the cross flow filters (1002c, 1004c) of the layers and circulates in the inner circular flow path (1001c).

  From the above, it was shown that the circulating blood cell separation filter chip according to the present invention can separate blood cells.

  The material to be used is not particularly limited as long as it can be finely processed. Preferably, the glass is hard to be deformed by curing or a highly rigid plastic, but the PDMS used in this embodiment can be used. Here, PDMS is easy to process, but is prone to deformation, so when used as a material for the circulating blood cell separation filter chip of the present invention, there was a concern that there was a problem in blood cell separation ability. In the examples, it was shown that there was no problem in blood cell separation ability.

0901 Inflow port 0902 Inner circular flow path 0903 Cross flow filter 0904 Outer circular flow path 0905 Second cross flow filter 0906 Second outer circular flow path 0907 Outlet 0908 Orifice

Claims (8)

An inlet for inflow of blood;
An inner circular flow path connected to the inflow port and circulating the inflowed blood;
A cross flow filter that is capable of transmitting some blood components of the blood components and constitutes the outer circumference of the inner circular flow path;
An outer circular channel adjacent to the inner circular channel with the crossflow filter as the inner circumference;
An outlet that is connected to the outer circular channel and flows out part of the blood component that has passed through the cross flow filter;
A circulating blood cell separation filter chip comprising: An inlet for inflow of blood;
An inner circular flow path connected to the inflow port and circulating the inflowed blood;
A cross flow filter that is capable of transmitting some blood components of the blood components and constitutes the outer circumference of the inner circular flow path;
An outer circular channel adjacent to the inner circular channel with the crossflow filter as the inner circumference;
A second cross flow filter that is capable of transmitting some blood components of the blood components and that forms the outer periphery of the outer circular flow path;
A second outer circular channel adjacent to the outer circular channel with the second cross-flow filter as the inner circumference;
An outlet that is connected to the second outer circular channel and flows out a part of the blood component that has passed through the second cross flow filter;
A circulating blood cell separation filter chip comprising:   The circulation type according to claim 2, wherein a combination of a cross flow filter and an outer circular channel is repeatedly provided on the outer side of the second outer circular channel, and the outermost outer circular channel is connected to the outlet. Blood cell separation filter chip.   The circulating blood cell separation filter chip according to any one of claims 1 to 3, wherein the inflow port is disposed in a circular region surrounded by an inner circular flow path.   5. The orifice according to claim 1, further comprising an orifice in the inner circular flow path in the vicinity of the blood flowing in from the inlet so that the blood flowing in from the inlet circulates in one direction in the inner circular flow path. The circulating blood cell separation filter chip according to 1.   6. The cross flow filter includes columns that are repeatedly arranged and a permeation hole formed between the columns, and the permeation hole has a size that prevents red blood cell components from passing therethrough. Circulation type blood cell separation filter chip.   The circulating blood cell separation filter chip according to any one of claims 1 to 6, wherein a volume of the inner circular channel is larger than a volume of another circular channel.   The circulating blood cell separation filter chip according to any one of claims 1 to 7, wherein the transmission hole has a height of 5 µm or less and a width of 2 µm or less.