JP7133411B2 - CTC collection system and method of operating CTC collection system - Google Patents

Description

The present invention relates to a CTC collection system suitable for collection of peripheral blood circulating tumor cells circulating in the blood and a method of operating the CTC collection system .

In the process of tumor cell proliferation, tumor cells may invade blood vessels, partly detach and flow into the blood, and circulate in the blood. Such tumor cells circulating in the blood are also called peripheral blood circulating tumor cells (CTC: Circulating Tumor Cells, hereinafter referred to as CTC). Early detection of tumors and diagnosis of malignancy of tumors can be performed by detecting CTCs.

However, the amount of CTC contained in blood is very small. In early-stage tumors, the percentage of CTCs in all blood cells in collected blood is very low, on the order of 10 ^-6 to 10 ^-8 . Therefore, it is required to select and collect a very small amount of CTC from a large number of blood cells.

As a method for identifying or collecting such minute amounts of tumor cells circulating in peripheral blood, a method using an antibody (for example, EpCAM) that reacts with a specific antigen contained in CTCs has been proposed (Patent Document 1).

JP 2017-104116 A

However, it is difficult to collect CTCs to which antibodies are not bound by conventional methods of collecting CTCs using antibodies. In addition, among tumor cells, only CTCs expressing specific antigens can be detected, and there is a risk of failure to detect them. Furthermore, since the number of CTCs obtained is small, there is a problem that errors are likely to occur in the measurement results.

An object of the present invention is to provide a CTC collection system capable of collecting a large amount of CTCs to which antibodies are not attached, and a method of operating the CTC collection system .

One aspect of the present invention is a blood component separation device that collects blood from a patient and separates the collected blood into red blood cells, buffy coat , and plasma; a CTC separation unit that has a separation filter that blocks the CTC, separates the CTCs attached to the separation filter with a washing liquid, and pours the separated CTCs into a CTC collection bag , wherein the CTC separation unit further includes the separation A concentration filter having a surface area smaller than that of the filter is provided, and the CTC separation unit separates the CTCs attached to the separation filter by backflowing a first amount of washing liquid to attach them to the concentration filter. In the CTC collection system, the CTCs adhering to the concentration filter are detached with a second amount of washing liquid that is smaller than the first amount, and the CTCs are poured into the CTC collection bag .
Another aspect of the present invention is a buffy coat container containing a buffy coat obtained by separating the components of a patient's blood, and allowing leukocytes to pass through the buffy coat supplied from the buffy coat container. On the other hand, a CTC separation unit that has a separation filter that prevents passage of CTCs, separates the CTCs attached to the separation filter with a cleaning liquid, and pours the separated CTCs into a CTC collection bag, wherein the CTCs are separated. The unit further has a concentration filter having a surface area smaller than that of the separation filter, and the CTC separation unit causes a first amount of washing liquid to flow backward to detach the CTCs adhering to the separation filter to the concentration filter. In the CTC collection system, after being deposited, the CTCs deposited on the concentration filter are detached with a second amount of washing liquid smaller than the first amount and poured into the CTC collection bag.

Another aspect of the present invention is a blood component separator that collects blood from a patient and separates the collected blood into red blood cells, buffy coat, and plasma; Operation of a CTC collection system comprising: a CTC separation unit that has a separation filter that blocks the passage of CTCs, separates the CTCs adhering to the separation filter with a cleaning liquid, and pours the separated CTCs into a CTC collection bag. A blood component separation step in which the blood component separation device operates to separate blood , which has flowed from a blood collection/blood return unit having a blood collection needle, into red blood cells, buffy coat, and plasma; and the CTC separation unit. However, a CTC separation step in which the buffy coat is passed through a separation filter that allows leukocytes to pass through but blocks the passage of CTCs, thereby causing the CTCs to adhere to the separation filter; and a CTC recovery step of removing the CTCs adhering to the filter with a cleaning liquid and recovering the separated CTCs, wherein the CTC separation unit adheres to the separation filter in the CTC recovery step. a step of detaching the CTCs by backflowing a first amount of washing liquid to adhere the CTCs to a concentration filter having a smaller area than the separation filter; and and detaching the CTCs adhering to the concentration filter with a second amount of cleaning liquid, which is smaller than the amount of cleaning liquid, and collecting the CTCs in a CTC collection bag.

According to the CTC collection system and the operating method of the CTC collection system of the above aspects, blood components are separated into red blood cells, buffy coat and plasma. Since CTCs are collected in the buffy coat portion, CTCs to which antibodies are not attached can be efficiently collected by passing only the buffy coat through the separation filter. In addition, since unnecessary red blood cells and plasma can be returned to the patient's body, the amount of blood collected can be increased without increasing the burden on the patient, and a large amount of CTCs can be collected.

1 is a schematic configuration diagram of a CTC collection system according to a first embodiment; FIG. FIG. 2 is an explanatory diagram showing the blood sampling operation of the CTC sampling system of FIG. 1; FIG. 2 is an explanatory diagram showing the blood separation operation of the CTC collection system of FIG. 1; FIG. 2 is an explanatory diagram showing the blood return operation of the CTC collection system of FIG. 1; FIG. 2 is an explanatory diagram showing the CTC separation operation of the CTC collection system of FIG. 1; FIG. 2 is an explanatory diagram showing the CTC concentration operation of the CTC collection system of FIG. 1; FIG. 2 is an explanatory diagram showing the CTC collection operation of the CTC collection system of FIG. 1; FIG. 2 is a schematic configuration diagram of a CTC collection system according to a second embodiment; FIG. FIG. 9 is an explanatory diagram showing the CTC separation operation of the CTC collection system of FIG. 8; FIG. 9 is an explanatory diagram showing the CTC collection operation of the CTC collection system of FIG. 8; FIG. 11 is a schematic configuration diagram of a CTC collection system according to a third embodiment;

Preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

(First embodiment)
A CTC collection system 10 according to this embodiment includes a blood component separator 12 and a CTC separator 14, as shown in FIG. The blood component separator 12 collects blood from a patient, centrifuges it, and separates it into plasma, buffy coat, and red blood cells according to the difference in specific gravity. Blood component separator 12 is configured to supply a buffy coat to CTC separator 14 . The buffy coat contains CTCs (peripheral blood circulating tumor cells) 80 along with white blood cells and platelets. The CTC separation unit 14 is configured to separate and collect CTCs 80 from the buffy coat. Each part of the CTC collection system 10 is further described below.

The blood component separator 12 is configured as a system that collects blood (whole blood) from a patient, centrifuges it, collects a buffy coat, and returns the remaining blood components to the patient.

The blood component separation device 12 has a centrifuge 15 , a blood processing section 16 , an ACD solution bag 18 , a blood collection/return section 22 having a blood collection needle 20 , and a reservoir 24 . The blood processing unit 16 is detachably attached to the centrifugal separator 15 and configured to separate blood components by centrifugal force from the centrifugal separator 15 . The ACD liquid bag 18 contains an ACD liquid, which is an anticoagulant.

The blood collecting/returning section 22 is connected to the blood processing section 16 via a connector 32 and a tube 42 and connected to the ACD liquid bag 18 via a connector 32 and a tube 40 .

The blood processing unit 16 can be attached to the centrifugal rotor of the centrifugal separator 15, and is formed in a container shape so that blood can be introduced, flowed, and discharged. The blood processing unit 16 is connected to the reservoir 24 via red blood cell transfer tube 44 and plasma transfer tube 46 . Also, the blood processing section 16 is connected to the CTC separation section 14 via a buffy coat transfer tube 50 .

Reservoir 24 is connected to blood processing section 16 via red blood cell transfer tube 44 and plasma transfer tube 46 . Red blood cells and plasma sent out from the blood processing section 16 are stored in the reservoir 24 . The reservoir 24 is also connected to the blood collecting/returning section 22 via a tube 48 and a connector 32 . The tube 48 is provided with a blood return pump 65 that returns the red blood cells and plasma stored in the reservoir 24 to the blood collection/blood return section 22 .

The tube 40 is provided with an ACD pump 64 that pumps out the ACD liquid from the ACD liquid bag 18 . Further, the tube 42 is provided with a blood collection pump 66 that transfers the blood collected by the blood collection/blood return section 22 together with the ACD liquid toward the blood processing section 16 .

The ACD pump 64 is a pump that transfers the ACD liquid from the ACD liquid bag 18 to the blood processing section 16 and is configured to flow the ACD liquid by pressing the tube 40 . The blood collection pump 66 is a pump that sucks blood from a patient and sends the blood to the blood processing section 16, and is configured to cause the blood to flow by pressing the tube 42. As shown in FIG. The blood return pump 65 is a pump that returns the blood components temporarily stored in the reservoir 24 to the patient, and is configured to cause the blood components to flow by pressing the tube 48 .

A plasma pump 68 is provided on the plasma transfer tube 46 . The plasma pump 68 is a pump that feeds the plasma separated in the blood processing section 16 toward the reservoir 24, and presses the plasma transfer tube 46 to cause the plasma to flow.

The CTC separation section 14 is connected to the blood component separation device 12 via a buffy coat transfer tube 50 . The CTC separation section 14 has a waste liquid storage section 26 , a washing liquid bag 28 , a CTC collection bag 30 , a separation filter 60 and a concentration filter 62 . A buffy coat transfer pump 69 is provided in the buffy coat transfer tube 50 , and the buffy coat separated by the blood component separator 12 is sent through the buffy coat transfer pump 69 .

Buffy coat transfer pump 69 is connected to separation filter 60 via joint 34 and tube 51 . The separation filter 60 can be a perforated plate in which a plurality of fine holes (through holes) are homogeneously formed in a metal thin plate (filter film) made of titanium, stainless steel, nickel, or the like. Specifically, the separation filter 60 is formed with a through hole having a diameter smaller than 10 μm, which is the typical size of the CTC 80 . Such through-holes of the separation filter 60 are produced by, for example, lithography and etching.

The separation filter 60 allows leukocytes that are relatively deformable and platelets that are smaller in diameter than the through-holes to pass through, while blocking the passage of CTCs 80 that are harder than blood cells and are likely to be caught in the through-holes. The separation filter 60 captures the separated CTCs 80 on the non-penetrating surface (outside the through holes), and the CTCs 80 are detachably attached to the separation filter 60 . The separation filter 60 is connected downstream of the separation filter 60 to the drainage storage section 26 via a tube 52 , a joint 36 and a tube 53 . Also, the washing liquid bag 28 is connected to the downstream side of the separation filter 60 via the tube 52 , the joint 36 and the tube 54 .

The cleaning liquid bag 28 contains cleaning liquid for cleaning the separation filter 60 and concentrating the CTCs 80 . A cleaning liquid pump 70 is provided in the tube 54 between the cleaning liquid bag 28 and the joint 36 to pump out the cleaning liquid.

Concentration filter 62 is made of a perforated plate similar to separation filter 60 . The concentration filter 62 is configured to block passage of the CTCs 80 separated from the separation filter 60 together with the washing liquid. However, the concentration filter 62 is set to have a surface area smaller than that of the separation filter 60, and is configured to capture the attached CTCs 80 with a smaller amount of cleaning liquid than the separation filter 60.

One end of the concentration filter 62 is connected to the joint 34 via the tube 55 and the other end of the concentration filter 62 is connected to the joint 38 via the tube 56 . The joint 38 is connected to the joint 36 via a tube 57 and is connected to the drainage container 26 via a tube 58 . That is, the concentration filter 62 is connected to the cleaning liquid bag 28 via the tubes 56 , 57 and 54 , and is connected to the waste liquid container 26 via the tubes 56 and 58 .

CTC collection bag 30 is connected to joint 34 via tube 59 . That is, the CTC collection bag 30 is connected to the concentration filter 62 via the tube 59 , joint 34 and tube 55 .

The CTC separation section 14 is provided with clamps 72 to 76 as its channel opening/closing mechanism. That is, when the clamps 72 to 76 are operated, the tube, which is the channel provided with the clamps, is closed. Clamp 72 is provided on tube 59 connecting CTC collection bag 30 and joint 34 . A clamp 73 is provided on the tube 52 connecting the separation filter 60 and the joint 36 . The clamp 74 is provided on the tube 53 that connects the joint 36 and the drainage container 26 . The clamp 75 is provided on the tube 58 that connects the joint 38 and the drainage container 26 . A clamp 76 is provided on a tube 57 connecting the joints 36 and 38 .

Pumps 64, 65, 66, 68, 69, 70 and clamps 72, 73, 74, 75, 76 of CTC collection system 10, and centrifuge 15 operate under the control of a controller, not shown.

Next, the CTC extraction method according to this embodiment will be described together with the operation of the CTC extraction system 10 described above.

In preparation for collecting CTCs 80 from a patient using the CTC collection system 10 shown in FIG. Also, the blood collection needle 20 is punctured by the patient.

Next, when the CTC collection system 10 is instructed to start operation by the user's operation, it operates as shown in FIG. First, the ACD pump 64 operates to prime the centrifugal separator 15 with the ACD liquid.

Next, the centrifugal rotor of the centrifugal separator 15 is rotated to apply a centrifugal force to the blood processing unit 16, and the blood collection pump 66 is operated to extract blood (whole blood) from the patient and introduce blood into The blood introduced into the blood processing section 16 is separated into red blood cells (concentrated red blood cells), buffy coat and plasma by centrifugal force. CTC80 is collected in the buffy coat.

Next, as shown in FIG. 3, the red blood cells separated in the blood processing section 16 are transferred to the reservoir 24 via the red blood cell transfer tube 44 . Also, the plasma separated in the blood processing section 16 is transferred to the reservoir 24 via the plasma transfer tube 46 .

As shown in FIG. 4, blood component separation device 12 returns to the patient the blood components temporarily stored in reservoir 24 during centrifugation. The blood collecting operation for collecting blood from the patient shown in FIGS. 2 and 3 and the blood returning operation for returning blood components to the patient shown in FIG. 4 are repeated multiple times. The blood collection operation and blood return operation are performed until a sufficient amount of buffy coat is collected in the blood processing section 16 . Since the red blood cells and plasma are returned to the patient, the burden on the patient can be reduced, and more buffy coat can be collected from the blood than the limit (for example, 400 cc) for collecting whole blood.

When a sufficient amount of buffy coat is collected in the blood processing section 16, the buffy coat in the blood processing section 16 is transferred to the CTC separation section 14 as shown in FIG. The buffy coat is transferred to the CTC separation section 14 through the buffy coat transfer tube 50 under the operation of the buffy coat transfer pump 69 , and the CTCs 80 are separated by the separation filter 60 . At this time, in the CTC separating section 14, the clamps 72, 75 and 76 are closed, the clamps 73 and 74 are opened, and the washing liquid pump 70 is stopped. At this time, the blood component separation device 12 repeats blood collection and return operations from the patient, transfers the buffy coat to the CTC separation unit 14, and returns red blood cells and plasma to the patient. Although the illustrated example shows the blood sampling operation, the blood sampling operation and the blood returning operation are alternately performed. Moreover, it is the same also in FIG.

The buffy coat sent out by the buffy coat transfer pump 69 flows through the buffy coat transfer tube 50 , the joint 34 and the tube 51 and is sent to the separation filter 60 . Platelets and white blood cells contained in the buffy coat pass through the separation filter 60, and CTC80 is blocked. As a result, the CTC 80 adheres and remains on the surface of the separation filter 60 . Also, the buffy coat that has passed through the separation filter 60 flows into the drainage container 26 through the tube 52 , the joint 36 and the tube 53 . Separation filter 60 is formed with a sufficient surface area to allow the buffy coat to pass through without clogging.

After the transfer of the buffy coat and the separation operation by the separation filter 60 are completed, the concentration operation of the CTC 80 is performed as shown in FIG. In this step, clamps 72, 74 and 76 of CTC separator 14 are closed and clamps 73 and 75 are opened. Also, the buffy coat transfer pump 69 is stopped and the cleaning liquid pump 70 is operated. At this time, the blood component separation device 12 performs blood collection and blood return operations in parallel.

The wash solution in wash solution bag 28 flows back through separation filter 60 via tube 54 , joint 36 and tube 52 under the action of wash solution pump 70 . As a result, the CTC 80 separates from the separation filter 60 and flows out together with the cleaning liquid. The cleaning liquid containing CTC 80 flows through tube 51 , joint 34 and tube 55 into concentration filter 62 . The concentration filter 62 blocks the CTC 80 contained in the cleaning liquid, and the CTC 80 adheres to the concentration filter 62 . The cleaning liquid that has passed through the concentration filter 62 is collected in the drainage container 26 via the tube 56 , the joint 38 and the tube 58 . The cleaning of the separation filter 60 is performed with a first amount of cleaning liquid sufficient to wash away the CTCs 80 adhering to the separation filter 60 . That is, the cleaning liquid pump 70 operates until it pumps out the first amount of cleaning liquid.

Thereafter, as shown in FIG. 7, the CTC separation unit 14 performs a CTC recovery operation of transferring the CTCs 80 adhering to the concentration filter 62 to the CTC collection bag 30 together with the cleaning liquid. In this step, the clamps 73, 74, 75 of the CTC separator 14 are closed and the clamps 72, 76 are opened. Also, the buffy coat transfer pump 69 is stopped and the washing liquid pump 70 is operated.

The cleaning liquid in the cleaning liquid bag 28 is sent to the concentration filter 62 through tube 54 , joint 36 , tube 57 , joint 38 and tube 56 in this order under the action of cleaning liquid pump 70 . When the cleaning liquid flows back through the concentration filter 62, the CTCs 80 are removed together with the cleaning liquid. The CTCs 80 then flow into the CTC collection bag 30 via the tube 55, joint 34 and tube 59 together with the cleaning fluid. Since the concentration filter 62 has a smaller surface area than the separation filter 60 , the CTCs 80 can be recovered with a second amount of washing liquid that is less than the first amount required to wash the separation filter 60 . That is, by using the concentration filter 62, the concentration of the CTCs 80 can be increased compared to the case where the CTCs 80 are recovered directly from the separation filter 60. FIG. As described above, the CTCs 80 are collected in the CTC collection bag 30, and the collection of the CTCs 80 by the CTC collection system 10 of the present embodiment is completed.

According to the CTC collection system 10 and the CTC collection method described above, the following effects are obtained.

In CTC collection system 10, blood component separator 12 collects blood while returning red blood cells and plasma to the patient. As a result, the amount of collected blood can be increased without increasing the burden on the patient, and a large amount of CTC80 can be collected.

In the CTC collection system 10, the blood component separator 12 may separate blood by centrifugation. As a result, a widely used centrifugal separator can be used, and the CTC collection system 10 can be constructed at low cost.

In the CTC collection system 10 , the CTC separation section 14 may cause the cleaning liquid to flow back to the separation filter 60 to detach the CTCs 80 adhering to the separation filter 60 . Thereby, CTC80 separated from the buffy coat can be collected by a simple operation.

The CTC collection system 10 may also include a concentration filter 62 having a smaller surface area than the separation filter 60 . In this case, the CTC separation unit 14 removes the CTCs 80 adhering to the separation filter 60 with a first amount of cleaning liquid and adheres them to the concentration filter 62, and then uses a second amount of cleaning liquid that is less than the first amount. The CTCs 80 adhering to the concentration filter 62 may be detached and poured into the CTC collection bag 30 . As a result, the concentration of CTCs 80 collected in the CTC collection bag 30 can be increased. Moreover, since the surface area of the separation filter 60 can be increased, a large amount of buffy coat can be processed without clogging.

In the CTC collection system 10, the separation filter 60 may have a structure in which a filter membrane and a plurality of through-holes having a diameter smaller than that of the CTCs 80 are formed through the filter membrane in the thickness direction. According to such a separation filter 60, since the CTCs 80 only adhere to the planar surface of the filter membrane, the CTCs 80 can be easily removed by the cleaning liquid. As a result, the CTCs 80 can be efficiently recovered from the separation filter 60 .

In the CTC collection system 10, the blood component separator 12 and the separation filter 60 may be connected via a tube 50 for transferring the buffy coat. As a result, the buffy coat collected by the blood component separator 12 can be efficiently sent to the separation filter 60 .

In addition, the CTC collection method may include a blood return step of returning the red blood cells and plasma to the patient between the blood component separation steps. As a result, the amount of collected blood can be increased without increasing the burden on the patient, and a large amount of CTC80 can be collected.

In the CTC collection method, blood may be separated by centrifugation in the blood component separation step. As a result, the CTC collection method can be carried out at low cost because a widely used centrifugal separator can be used.

In the CTC collecting method, the CTCs 80 adhering to the separation filter 60 may be detached by flowing back the washing liquid to the separation filter 60 in the CTC collection step. Thereby, CTC80 separated from the buffy coat can be collected by a simple operation.

In the CTC collection method, the CTC recovery step includes a step of removing the CTC 80 attached to the separation filter 60 with a first amount of washing liquid to attach the CTC 80 to the concentration filter 62 having a smaller area than the separation filter 60; and collecting the CTCs 80 in the CTC collection bag 30 by removing the CTCs 80 adhering to the concentration filter 62 with a second amount of cleaning liquid that is smaller than the amount. As a result, the concentration of CTCs 80 collected in the CTC collection bag 30 can be increased.

(Second embodiment)
A CTC collection system 10A according to the second embodiment, as shown in FIG. 8, includes a blood component separation device 12 and a CTC separation section 14A. In the CTC extraction system 10A, the same components as those of the CTC extraction system 10 shown in FIG. As shown, the blood component separation device 12 is similar to the CTC collection system 10 of FIG. This embodiment includes a CTC separation section 14A that is more simplified than the CTC separation section 14 in the first embodiment.

The CTC separation section 14A includes a drainage storage section 26, a cleaning liquid bag 28, a CTC collection bag 30, and a separation filter 60. As shown in FIG. The blood component separation device 12 and the CTC separation section 14A are connected by a buffy coat transfer tube 50. FIG. A buffy coat transfer pump 69 is provided in the buffy coat transfer tube 50 .

Buffy coat transfer tube 50 is connected to separation filter 60 via joint 34 and tube 51 . A CTC collection bag 30 is connected to the joint 34 via a tube 59 . The separation filter 60 is connected to the drainage container 26 via the tube 52 , the joint 36 and the tube 53 , and is connected to the cleaning liquid bag 28 via the tube 52 , the joint 36 and the tube 54 .

A clamp 72 is provided on the tube 59 connected between the joint 34 and the CTC collection bag 30 . A clamp 74 is provided on the tube 53 connected between the joint 36 and the drainage container 26 . Furthermore, a cleaning liquid pump 70 is provided on the tube 54 that connects the joint 36 and the cleaning liquid bag 28 .

Next, the CTC extraction method according to this embodiment will be described together with the operation of the CTC extraction system 10A.

First, blood (whole blood) is collected from a patient by the blood component separator 12, and only the buffy coat is collected. Blood components other than the buffy coat are returned to the patient. Since the operation up to this point is the same as the operation described with reference to FIGS. 2 to 4, the description thereof will be omitted.

After that, as shown in FIG. 9, the CTC collection system 10A transfers the buffy coat to the CTC separation section 14A under the operation of the buffy coat transfer pump 69 to separate the CTCs 80 from the buffy coat. At this time, the clamp 72 is closed, the clamp 74 is opened, and the washing liquid pump 70 is stopped. The buffy coat is sent to separation filter 60 via joint 34 and tube 51 . At the separation filter 60, the CTCs 80 are blocked and separated from the buffy coat.

After that, as shown in FIG. 10, the cleaning liquid is allowed to flow back through the separation filter 60 to recover the CTCs 80 . That is, clamp 74 is closed and clamp 72 is opened. Also, the buffy coat transfer pump 69 is stopped and the washing liquid pump 70 is operated. The cleaning liquid in the cleaning liquid bag 28 is pumped through the tube 54 , the joint 36 and the tube 52 to the separation filter 60 under the action of the cleaning liquid pump 70 . The cleaning liquid flows back through the separation filter 60 to remove the CTCs 80 adhering to the separation filter 60 . A wash solution containing CTCs 80 is collected in the CTC collection bag 30 via the tube 51 , joint 34 and tube 59 . The washing liquid is supplied in an amount (first amount) sufficient to remove the CTCs 80 adhering to the separation filter 60 . Acquisition of the CTC 80 is completed by the above operation.

According to the CTC collection system 10A according to the present embodiment described above, the filter of the CTC separation unit 14A is configured only by the separation filter 60, so the device configuration is simplified. Moreover, according to the CTC collection method according to the present embodiment, since the concentration operation is not required, the CTC collection operation can be simplified.

(Third embodiment)
A CTC collection system 10B according to the third embodiment includes a CTC separation unit 14 . The configuration of the CTC separation unit 14 is similar to that of the CTC separation unit 14 of the CTC extraction system 10 shown in FIG.

In the CTC collection system 10B of the present embodiment, a buffy coat container 82 containing buffy coat is connected to the CTC separation section 14 . The buffy coat in the buffy coat container 82 is previously collected from the patient's blood by the blood component separator 12 (see FIG. 1). That is, the blood component separation device 12 and the CTC separation section 14 are connected via the buffy coat container 82 .

The buffy coat container 82 is connected to the joint 34 via the connecting tube 50B. The buffy coat container 82 is configured to be sent to the CTC separation section 14 via the buffy coat transfer pump 69 attached to the connection tube 50B. The CTC separation unit 14 collects the CTCs 80 into the CTC collection bag 30 by the same operation as described with reference to FIGS. 5 to 7. FIG.

According to the CTC collection system 10B according to the present embodiment, the buffy coat container 82 for containing the buffy coat collected by the blood component separation device 12 is provided. supplied. Accordingly, the blood component separation device 12 and the CTC collection system 10B can be installed separately. Therefore, for example, a buffy coat collected from a patient using the blood component separation apparatus 12 of another facility is stored in the buffy coat container 82, and the CTC collection system 10B according to the present embodiment stores the buffy coat container 82. It is also possible to collect CTC80 by carrying it to the facility where it is installed.

Further, according to the CTC collection method of the present embodiment, there is a step of storing the buffy coat separated by the blood component separation device 12 in the buffy coat container 82. In the CTC separation step, the buffy coat in the buffy coat container 82 is The coat is passed through separation filter 60 . Thus, by using the buffy coat container 82, the CTC separation process can be performed at a different place and at a different time from the blood component separation process.

Although the preferred embodiments of the present invention have been described above, the present invention is not limited to the above embodiments, and it goes without saying that various modifications can be made without departing from the scope of the present invention. stomach.

10, 10A, 10B... CTC collection system 12... Blood component separator 14, 14A... CTC separation unit 15... Centrifugal separator 16... Blood processing unit 18... ACD solution bag 22... Blood collection/blood return unit 24... Reservoir 26... Drainage storage unit 28 Cleaning liquid bag 30 CTC collection bag 60 Separation filter 62 Concentration filter

Claims (11)

a blood component separator that collects blood from a patient and separates the collected blood into red blood cells, buffy coat, and plasma;
Separation of CTCs by separating the CTCs from the buffy coat by having a separation filter that allows leukocytes to pass through but prevents the passage of CTCs, detaching the CTCs adhering to the separation filter with a washing solution, and pouring the detached CTCs into a CTC collection bag. and
The CTC separation unit further has a concentration filter with a smaller surface area than the separation filter,
The CTC separation unit separates the CTC from the separation filter by backflowing a first amount of washing liquid to adhere the CTC to the concentration filter, and then removes the CTC from the separation filter by a second amount that is smaller than the first amount. A CTC collection system in which the CTCs adhering to the concentration filter are detached with a washing liquid and poured into the CTC collection bag. 2. The CTC collection system according to claim 1, wherein said blood component separation device collects said blood while sending said red blood cells and said plasma back to the patient. 3. The CTC collection system according to claim 1, wherein said blood component separator separates said blood by centrifugation. The CTC collection system according to any one of claims 1 to 3, wherein the separation filter includes a filter membrane and a plurality of through-holes passing through the filter membrane in the thickness direction and having a diameter smaller than that of the CTCs. A CTC collection system being formed. 5. The CTC collection system according to any one of claims 1 to 4, wherein said blood component separation device and said separation filter are connected via a tube for transferring said buffy coat. 5. The CTC collection system according to any one of claims 1 to 4, further comprising a buffy coat container for containing the buffy coat collected by the blood component separation device, and A CTC collection system in which the separation filter is supplied with a buffy coat. a buffy coat container containing a buffy coat obtained by separating the components of a patient's blood;
The buffy coat supplied from the buffy coat container has a separation filter that allows passage of leukocytes while blocking passage of CTCs, and the CTCs adhered to the separation filter are removed with a washing liquid, and the separated said a CTC separation unit for pouring the CTCs into the CTC collection bag;
The CTC separation unit further has a concentration filter with a smaller surface area than the separation filter,
The CTC separation unit separates the CTC from the separation filter by backflowing a first amount of washing liquid to adhere the CTC to the concentration filter, and then removes the CTC from the separation filter by a second amount that is smaller than the first amount. A CTC collection system in which the CTCs adhering to the concentration filter are detached with a washing liquid and poured into the CTC collection bag. a blood component separator that collects blood from a patient and separates the collected blood into red blood cells, buffy coat, and plasma;
Separation of CTCs by separating the CTCs from the buffy coat by having a separation filter that allows leukocytes to pass through but prevents the passage of CTCs, detaching the CTCs adhering to the separation filter with a washing solution, and pouring the detached CTCs into a CTC collection bag. Department and
A method of operating a CTC collection system comprising:
a blood component separation step in which the blood component separation device operates to separate blood flowing in from a blood collection/blood return unit having a blood collection needle into red blood cells, buffy coat, and plasma;
a CTC separation step in which the CTC separation unit passes the buffy coat through a separation filter that allows leukocytes to pass through but blocks the passage of CTCs, thereby causing the CTCs to adhere to the separation filter;
a CTC recovery step in which the CTC separation unit operates to separate the CTCs adhering to the separation filter with a cleaning liquid and recover the separated CTCs;
The CTC recovery step includes
a step in which the CTC separating unit separates the CTCs adhering to the separation filter by backflowing a first amount of washing liquid to cause the CTCs to adhere to a concentration filter having a smaller area than the separation filter; ,
a step of operating the CTC separation unit to separate the CTCs adhering to the concentration filter with a second amount of washing liquid that is smaller than the first amount and collect the CTCs in a CTC collection bag;
A method of operating a CTC collection system comprising: 9. The method of operating a CTC collection system according to claim 8, wherein said blood component separation device sends said red blood cells and said plasma back to said blood collection/return unit between said blood component separation steps. A method of operating a CTC collection system comprising the step of operating. 10. The operating method of the CTC collection system according to claim 8 or 9, wherein the blood component separation device comprises a centrifuge, and in the blood component separation step, the centrifuge separates the blood by centrifugation. A method of operating a CTC collection system that operates as follows. 11. The operating method of the CTC collection system according to any one of claims 8 to 10, wherein the blood component separation device accommodates the buffy coat separated in the blood component separation step in a buffy coat container . A method of operating a CTC collection system , wherein in the CTC separation step, the CTC separation section operates to pass the buffy coat of the buffy coat container through the separation filter.

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