Patent ID: 12194477

DESCRIPTION OF THE EMBODIMENTS

Example 1

An example of the present invention is described below based on drawings. Moreover, in the following drawings, the same parts are designated by the same symbols and repeated description is omitted.

FIG.1is a perspective view showing an entire continuous centrifuge1according to the example. As shown inFIG.1, the continuous centrifuge1is a so-called “continuous ultra-centrifugal separator” which is used in a vaccine manufacturing process and the like, and includes two main parts, namely a centrifugal separation portion10and a control device portion50. The centrifugal separation portion10and the control device portion50are connected by a wiring/pipe group40. The continuous centrifuge1has a structure in which a rotor100suspended by a drive portion30can be taken in and out of a chamber11by operating a lift16and an arm17. The centrifugal separation portion10has: the cylindrical chamber11which is a rotor chamber; a base12which supports the chamber11; the rotor100which is accommodated in an interior of the chamber11in a way of being freely taken in and out of the chamber11and rotates at a high speed; the drive portion30which is arranged above the chamber11and rotationally drives the rotor100in a state of suspending the rotor100; a lower bearing portion20installed on a lower side of the chamber11; the lift16and the arm17for moving the drive portion30in an up-and-down direction and a back-and-forth direction; and a liquid sending pump77(seeFIG.5) that continuously supplies or discharges a sample or a sterilizing solution to the rotor100. The rotor100suspended by the drive portion30is accommodated inside the chamber11. An outer surface of the rotor100, which is a rotation body, includes a cylindrical rotor body101which is a body portion, and an upper rotor cover110and a lower rotor cover120for closing both ends of the rotor body101by screwing. An upper shaft32which is a sample passage and also serves as a rotation shaft is arranged above the upper rotor cover110, and a lower shaft105which is a sample passage and also serves as a rotation shaft is arranged below the lower rotor cover120.

Because the rotor100is rotationally driven at a high speed, during centrifugal separation, the interior of the chamber11is kept in a depressurized state for a purpose of suppressing heat generated by windage loss or frictional heat with atmosphere during operation. In order to keep the chamber11in the depressurized state, a not-shown discharge port which discharges air inside the chamber11is formed in the body portion of the chamber11, and a vacuum pump which is not shown is connected to the discharge port. The chamber11is fixed to the base12by a plurality of bolts13, and the base12is fixed to a floor surface by a plurality of bolts14.

The control device portion50accommodates a cooling device (not shown) for cooling the interior of the chamber11, the vacuum pump (not shown), a lift drive device (not shown) for moving the rotor100to a predetermined location, a centrifuge controller (a control device) (not shown) for driving and controlling the rotor100, and the like. An operation panel60which is a place for operating/inputting is arranged on an upper part of the control device portion50. The control device is configured by an electronic circuit (not shown) including a microcomputer and a storage device, and controls the entire continuous centrifuge including drive control of the rotor100, drive of the liquid sending pump, and control of a plurality of valves A to D described later.

FIG.2is a cross-sectional view showing a detailed structure of the centrifugal separation portion10ofFIG.1. In the chamber11, the rotor100in a state of being suspended by the drive portion30in the interior of the chamber11is accommodated, a cylindrical evaporator (an evaporation pipe)18is installed so as to cover a circumference of the rotor100, and a cylindrical protector19which functions as a defense wall is installed outside the evaporator18. The evaporator18is constituted by a copper pipe for circulating refrigerant gas, and can cool the accommodation space of the rotor100.

Inside the rotor100, a rotor core130is installed for introducing an injected sample into a high gravity field. The rotor core130divides the interior of the rotor100into a plurality of centrifugal separation spaces by a core body131and blade-shaped partition walls132(132ato132fdescribed later with reference toFIG.3) arranged in the body portion of the core body131. The drive portion30is mounted on a distal end portion of the lift16(seeFIG.1), and rotatably supports the upper shaft32. A sample passing hole extending in a vertical direction is formed at a position of an axial center in the interior of the upper shaft32, and forms a part of an upper sample passage. A lower end portion of the upper shaft32extends in a funnel shape, and in order to communicate the sample passing hole and a sample passage111formed in the upper rotor cover110, the upper rotor cover110is fixed to the upper shaft32by screwing a nut119and a second male screw117. Moreover, an O ring118for sealing is arranged between the upper rotor cover110and the upper shaft32. When the upper shaft32is rotated at a high speed by drive of a motor included in the drive portion30, the rotor100connected to the upper shaft32also rotates at a high speed. The lower shaft105which is the rotation shaft portion is mounted on a lower side of the rotor core130. A sample passing hole forming a part of the lower sample passage penetrates through an axial center of the lower shaft105, and the sample passing hole connects a sample passage121formed in the lower rotor cover120and a lower connection portion71.

The sample is supplied to the interior of the rotor100before the centrifugal separation. The sample is supplied as shown by arrows75band75cvia the lower pipe72connected to the lower connection portion71, passes through the lower bearing portion20, passes through the sample passing hole of the lower shaft105, and is introduced to the interior of the rotor100upward from below. Introducing the sample into the rotor100from the sample passage121on the lower side in this way is called “bottom feed”. When the sample sent out by the liquid sending pump77(described later inFIG.5) is filled in the rotor100, the sample is discharged from an upper pipe82, and thus when the state is detected by a control device51, the control device51controls a motor (not shown) of the drive portion30to accelerate the rotor100to a high centrifugal separation working rotation speed.

The sample introduced into the rotor100is moved to a high centrifugal force field by the rotor core130to be separated into a precipitate and a supernatant, and the supernatant (the waste liquid) passes through the sample passing hole of the upper shaft32from the sample passage111formed in the upper rotor cover110, passes through the interior of drive portion30, and is discharged upward from an upper connection portion81as shown by an arrow85a. The sample which has been discharged as shown by the arrow85ais sent out through the upper pipe82as shown by an arrow85b.

FIG.3is an enlarged view of the rotor100inFIG.2. The core body131is made of a synthetic resin, and six blade-shaped partition walls132ato132fprotruding in a peripheral direction are formed on the outer peripheral side of the solid and columnar core body131. The partition walls132ato132fare continuous in an axial direction and integrally formed with the core body131, and outer peripheral side end portions of the partition walls132ato132fabut the inner peripheral surface of the rotor body101, and thereby the separation space137(seeFIG.4) is evenly divided into six spaces in the peripheral direction. The core body131has a sample passing hole134at a rotation center of each of an upper surface131aand a lower surface131b, and a plurality of core end surface grooves135ato135fextending from the sample passing hole134in the radial direction are formed. The upper surface131aand the lower surface131bof the core body131are respectively in contact with a lower surface of the upper rotor cover110and an upper surface of the lower rotor cover120, and thereby six sample passages extending in the radial direction are formed between the core body131and the rotor covers. Here, the outer edges of the core end surface grooves135ato135fopen near the middle of the six partition walls132ato132farranged at equal intervals on the outer peripheral side of the core body131. A shape of the bottom surface portion of the core body131is basically the same as a shape of the upper surface. The upper rotor cover110and the rotor body101are a screwed type, a male screw114is formed on a lower end of a cylindrical surface of the upper rotor cover110, and a female screw102is formed in an upper opening101aof the rotor body101. Similarly, the lower rotor cover120and the rotor body101are a screwed type, a male screw124is formed on a upper end of a cylindrical surface of the lower rotor cover120, and a female screw (not visible in the diagram) is formed in a lower opening101bof the rotor body101.

A fitting shaft123is formed along a central rotation shaft center on an inner side of the lower rotor cover120, and the sample passage121is formed at the shaft center. An O ring125is interposed between the lower rotor cover120and the rotor body101, and an O ring126is interposed between the fitting shaft123and a fitting hole (not visible in the diagram) formed in the lower surface of the core body131. Similarly, an O ring115and an O ring133are also interposed between the upper rotor cover110and the rotor body101. Pins128aand128bwhich are fitted into positioning holes arranged on the lower surface of the core body131are attached to two places on the upper circumference of the lower rotor cover120.

FIG.4is a cross-sectional view of main portions near the bottom part of the rotor100. The cross section is a longitudinal cross-sectional view of a vertical surface passing through a rotation axis A1. A sample passage121extending along the rotation axis A1and sample branch passages122formed in a manner of obliquely branching from a way of the sample passage121are formed in the lower rotor cover120. The sample passage121communicates with a sample communication hole formed in the lower shaft105(seeFIG.2). The lower shaft105is fixed to the lower rotor cover120by a nut129. Moreover, an O ring127is arranged between the lower rotor cover120and the lower shaft105.

When the motor (not shown) of the drive portion30rotates, the upper shaft32rotates, and the entire rotor100also rotates in synchronization with the upper shaft32. Because the lower shaft105is rotatably supported by the lower bearing portion20(seeFIG.2), the lower shaft105rotates together with the rotor100. Because the plurality of sample branch passages122branching in the oblique radial direction from the way in the sample passage121are formed, the sample flowing from the sample passage121in a direction of an arrow75dflows upward and radially outward through the sample branch passages122as shown by arrows176, and reaches radial passages145. Hereinafter, the sample flows through the radial passages145in directions of arrows177, and then reaches the separation spaces137. In the separation space137, the sample continuously flows in a direction of an arrow178(upward) and the centrifugal separation working is performed. Because the sample passage121, the sample branch passage122, and the radial passage145have a small diameter and have a bent connection part, minute bubbles dissolved in the liquid are easy to accumulate in the bent part. In addition, when the sample is injected during the rotation of the rotor, bubbles having a low specific gravity are difficult to flow radially outward through the sample branch passage122and are easy to stagnate. Therefore, in the example, as described later, the flow direction of the sample is reserved at least once between bottom feed and top feed. Furthermore, an operation is performed in which a liquid sending pressure is intermittently increased even during the sample feed, and thereby the bubbles are separated from the accumulation part.

FIG.5is a piping diagram of a sample line of the centrifugal separation portion10. In the specification, a series of lines (the flow paths) from a sample tank70to a collection tank86excluding the interior of the rotor100are defined as a “sample line”. The sample to be centrifugally separated flows, from the sample tank70storing the sample through a supply pipe73in a direction of an arrow75aby the liquid sending pump77, and flows into a sample inflow point73aof a valve bridge portion90through the liquid sending pump77. A pressure sensor (a pressure gauge)76is connected on the way of the supply pipe73. The pressure sensor76measures a pressure of the liquid supplied to the sample line. A microcomputer52can control the drive of the liquid sending pump77by acquiring pressure data from the pressure sensor76, and can drive the liquid sending pump77to send the sample to the rotor100.

The valve bridge portion90is a flow path switching mechanism configured by four bridge-connected valves A to D. By the valve bridge portion90, a first flow path direction (the bottom feed) in which the sample is flowed from the lower pipe72toward the upper pipe82and a second flow path direction (the top feed) in which the sample is flowed from the upper pipe82toward the lower pipe72are switched. Among four connection points of the valve bridge portion90, two connection points on the tank side are the sample inflow point73aof the sample supplied from the sample tank70by the sample supply line and a sample discharge point83afor discharging the sample to the collection tank86via the sample supply line. The rest two connection points on the rotor100side are a lower line connection point72aconnected to the lower pipe72and an upper line connection point82aconnected to the upper pipe82. The valves A to D are respectively the same components, and can be opened and closed using high-pressure air as a drive source to control whether to open or close the flow path. The opening/closing operation of the valves A to D is performed according to an instruction of the microcomputer52included in the control device51. Moreover, the types of the valves A to D are arbitrary, and an electromagnetic valve using electric power may be used as long as the opening/closing control can be directly or indirectly executed according to the instruction of the microcomputer52. In addition, with regard to the valves A to D, a valve which can select only two positions, namely “a fully open position” or “a fully closed position”, is sufficient, and an opening adjustable valve may also be used which is capable of selecting any intermediate position such as half opening or the like.

The lower pipe72, the upper pipe82, the supply pipe73, and a discharge pipe83can be appropriately set to a pipe with elasticity such as a silicon tube, a pipe with no elasticity such as a stainless pipe, or the like. However, in order to perform an air releasing process of the application, the stainless pipe or the like with no elasticity is preferable. The control device51includes the microcomputer52, and performs, by executing a computer program, the management of the entire centrifugal separation working including the control of the delivery and discharge of the sample by the drive of the liquid sending pump77, the control of the opening and closing of the valves A to D of the valve bridge portion90, and the pressure measurement of the sample by using the pressure sensor76. The liquid sending pump77is driven by the control of the microcomputer52as shown by the dotted line. The output of the pressure sensor76is transmitted to the microcomputer52by a signal line. Although not shown here, air pipes for sending out the high-pressure air are connected to the valves A to D of the valve bridge portion90, and the opening/closing operation of the valves A to D is performed in a manner that the microcomputer52controls the supply or cutoff of the high-pressure air to each air pipe. With respect to the direction of the continuous sample injection into the interior of the rotor100during the centrifugal separation working, the so-called bottom feed is general in which the injection is performed from the lower side as shown by the arrow75cofFIG.5and the separated supernatant liquid (the supernatant) is discharged to a discharge line (not shown) from an upper side of the rotor100via a sample passing hole of the upper shaft32as shown by the arrow85a, and the injection may also be performed by the top feed.

FIG.6is a diagram showing a flow of the sample to the rotor100by the bottom feed. When the bottom feed is set in the valve bridge portion90, the sample flowed into the valve bridge portion90as shown by the arrow75apasses through the lower pipe72and flows into the interior of the rotor100from the lower bearing portion20of the rotor100as shown by the arrows75band75c. In order to form this flow path, in the valve bridge portion90, the valves A and D are closed, and the valves B and C are opened. If the valves A to D are operated in this way, the bottom feed can be realized in which the sample flows from the lower side toward the upper side in the interior of the rotor100. When the bottom feed is performed and the rotor100is rotated at a high speed, the separated supernatant (the waste liquid) flows into the drive portion30through the upper shaft32(seeFIG.1), flows from the drive portion30through the upper pipe82as shown by the arrows85aand85b, flows into the valve bridge portion90from the upper line connection point82a, passes through the sample discharge point83aand flows through the discharge pipe83as shown by an arrow85c, and reaches the collection tank86(seeFIG.5).

FIG.7is a diagram showing a flow of the sample to the rotor100by the top feed. During the top feed, in the valve bridge portion90, the valves B and C are closed, and the valves A and D are opened. If the valves A to D are operated in this way, the top feed can be realized in which the sample flows from the sample tank70as shown by arrows75a,75d, and75e, and flows from the upper side toward the lower side in the interior of the rotor100. When the top feed is performed and the rotor100is rotated at a high speed, the separated precipitate liquid flows into the lower bearing portion20through the lower shaft105(seeFIG.1), flows from the lower bearing portion20through the lower pipe72as shown by arrows85dand85e, flows into the valve bridge portion90, passes through the sample discharge point83aand flows through the discharge pipe83as shown by the arrows85fand85c, flows into the valve bridge portion90from the lower line connection point72a, passes through the sample discharge point83aand flows through the discharge pipe83as shown by the arrow85c, and reaches the collection tank86(seeFIG.5).

In a table inFIG.8, open/closed states of the valves A to D during the top feed and the bottom feed are summarized. In the switching from the top feed to the bottom feed, the open/closed state of each valve is reversed, and a state of the valves A, B, C, D=(open, closed, closed, open) may be switched to the valves A, B, C, D=(closed, open, open, closed). Similarly, in the switching from the bottom feed to the top feed, the open/closed state of each valve is reversed, and a state of the valves A, B, C, D=(closed, open, open, closed) may be switched to the valves A, B, C, D=(open, closed, closed, open). If only the switching control between the top feed and the bottom feed is performed in this way, the valves A and D may be supplied with the high-pressure air by a common air hose, and the valves B and C may be supplied with the high-pressure air by a common air hose. However, in the example, the valves A to D are configured in a manner that each of the valves A to D can be controlled to be opened/closed independently, and an operation is repeated multiple times at intervals in which a liquid pressure inside the flow path is temporarily increased by temporarily limiting (closing or throttling) a part of the valves, and the increased hydraulic pressure is immediately released. The control method is described with reference toFIG.9.

FIG.9is a diagram showing the switching operation between the top feed and the bottom feed in the example and a pressure95at that time. The horizontal axis is the passage of time (unit: sec.), and the vertical axis is the pressure measured by the pressure sensor (unit: MPa). Here, a transition of the pressure95is shown when the bottom feed and the top feed are switched twice, and the number of times Y of applying pressure fluctuations in each feed is set to 3. Before the centrifugal separation is performed, firstly the bottom feed is set in a manner that the valves A, B, C, D=(closed, open, open, closed). Next, as a preparatory process, before the rotor100is rotated, the liquid sending pump77is operated and liquids having different densities (density liquids) are sequentially added into the rotor by the bottom feed. For example, after a liquid having a low density is added, a liquid having a high density is added, and the separation space137(seeFIG.2) is filled with layers of the liquids having different densities. When the interior of the rotor100is filled with the liquid, the liquid reaches the valve bridge portion90from the upper pipe82and is discharged from the sample discharge point83a. After the state is reached, the rotor100is rotated at a low speed, for example, to 4000 rpm, and after the rotor is stabilized, the air releasing process according to the example is executed form timing t1to timing t5.

At the timing t1, while the bottom feed state is maintained, a waiting state is maintained until a certain time T1(seconds) elapses, and then the valve C is closed. That is, the valves A, B, C, D=(closed, open, closed, closed). Then, the pressure95of the liquid rapidly increases as shown by an arrow95a. Here, when the pressure95reaches a predetermined pressure threshold (a peak pressure) P2as shown by an arrow95b, the microcomputer52opens the valve C, and returns the state to the state of the valves A, B, C, D=(closed, open, open, closed). Then, the pressure of the liquid sharply decreases from P2and returns to a normal feed pressure P1as shown by an arrow95c. When the normal feed pressure P1elapses for a certain time T2(seconds), the valve C is closed again to increase the pressure, and when the pressure reaches the pressure threshold P2as shown by an arrow95d, the valve C is opened. In this way, the state, in which the valve C is closed to act as a flow path limiting mechanism for making the pressure reach the pressure threshold P2, and the pressure threshold P2is used as the peak pressure, is repeated three times as shown by the arrows95b,95d, and95e. Thereafter, the waiting state is maintained for a time T3(seconds), and the air releasing process at the time of the first feed is completed.

Next, at the timing t2, the bottom feed is switched to the top feed in a manner that the valves A, B, C, D=(open, closed, closed, open). At this time, the state may be maintained in which the liquid sending pump77is operated. A waiting state is maintained until a certain time T1(seconds) elapses from the timing t2, and then the valve D is closed. That is, the valves A, B, C, D=(open, closed, closed, closed). Then, the pressure95of the liquid rapidly increases as shown by an arrow95f. Here, when the pressure95reaches the predetermined pressure threshold P2as shown by an arrow95g, the microcomputer52opens the valve D, and returns the state to the state of the valves A, B, C, D=(open, closed, closed, open). Then, the pressure of the liquid sharply decreases from P2and returns to the normal feed pressure P1as shown by an arrow95h. When the normal feed pressure P1elapses for the certain time T2(seconds), the valve D is closed again to increase the pressure, and when the pressure reaches the pressure threshold P2as shown by an arrow95i, the valve D is opened. In this way, the state in which the valve D acting as a flow path limiting mechanism is closed to make the pressure reach the pressure threshold P2is repeated three times as shown by the arrows95g,95i, and95j. Thereafter, the waiting state is maintained for the time T3(seconds), and the air releasing process at the time of the second feed is completed.

Similarly, the top feed is switched to the bottom feed at the timing t3to produce three pressure peaks as shown by arrows95kto95mby the air releasing process at time of the third feed. Finally, the bottom feed is switched to the top feed at the timing t4to produce three pressure peaks as shown by arrows95nto95pby the air releasing process performed by the second top feed. Finally, the top feed is switched to the bottom feed at the timing is in a manner that the valves A, B, C, D=(closed, open, open, closed), and the entire air releasing process is completed. Here, the time T1, the time T2, and the time T3may be appropriately set, for example, T1, T2, and T3can be set to about several seconds.

In this way, in the example, in a sample feed which includes the valve bridge portion90performing the flow path switching, the pressure sensor76capable of measuring the line pressure, and the liquid sending pump77supplying the sample, after the rotor100is stabilized at the low-speed rotation, the first air releasing procedure by the switching operation between the bottom feed and the top feed is performed. Furthermore, in the example, after the feed direction is set, the second air releasing procedure is performed so as to generate a pressure increase which occurs in a short time once or more. During the switching, the sample is flowed by the top feed or the bottom feed, and the line pressure temporarily increases to the peak pressure which is the pressure threshold P2determined previously and does not exceed an allowable pressure Pmax of the centrifuge. That is, an air discharge mode for performing an operation is realized, and in the operation, the pressure of the liquid is increased to the threshold P2by closing one of the valves in the open operation, and after the pressure reaches the threshold P2, the valve which is temporarily closed is opened again. As a result, the bubbles contained in the sample in the rotor100can be automatically removed by the automatic control performed by the control device51. After the timing t5, the rotor100is accelerated to high-speed rotation, the sample is sent to the rotor100from the lower pipe72, and the continuous centrifugal separation working is executed by the high-speed rotation of the rotor100.

Next, a procedure of the air releasing process by the continuous centrifuge1is described with reference to a flowchart ofFIG.10. The air releasing process according to the example is a preparatory stage immediately before performing the continuous centrifugal separation working, that is, a stage in which the interior of the rotor100is filled with the sample and the rotor100is once rotated at a low speed before the high-speed rotation, and the air releasing process is conducted by the control device51(seeFIG.5) having the microcomputer52. First, the sample is set in the sample tank70, the bottom feed is set by opening the valves B and C and closing the valves A and D (Step201). Next, a counter for counting the setting number of times of the feed direction is set to 1 (Step202), the liquid sending pump77is operated for supplying the sample to the interior of the rotor100, and the sample is injected from the lower connection portion71(Step203). When the interior of the rotor100is filled with the sample, the sample comes out from the upper connection portion81, and thus when the sample comes out, the rotor100is rotated at a low speed, for example, accelerated to 4,000 rpm, and stabilized (Step204). Normally, the pressure of the liquid sending in the sample line at this time is sufficiently smaller than the allowable pressure Pmax of the continuous centrifuge1(seeFIG.9). When the sample is supplied to the rotor100in this way, the air releasing process is executed in which the valve (here is the valve C) of the two open valves which is on a downstream side in the inflow direction is temporarily closed, and the air releasing is conducted once or more (Step205). The detailed procedure of the air releasing process (Step205) is described later with reference toFIG.11.

When the air releasing process (Step205) at the time of the bottom feed is completed, the microcomputer52opens the valves A and D and closes the valves B and C, thereby switching the bottom feed to the top feed (Step206), and the counter of the setting number of times of the feed direction is increased by one (Step207). Next, the microcomputer52supplies the sample by the top feed and conducts the air releasing process conducted inFIG.9of temporarily closing the valve D (Step208). The procedure of the air releasing process (Step208) is the same as the procedure in Step205except that the object of the valve to be opened and closed is different, and the detailed procedure is described later with reference toFIG.11. When the air releasing process (Step208) is completed, the microcomputer52judges whether or not the feed direction reversal number of times N has reached the specified number of times of four times, and when the feed direction reversal number of times X does not reach the specified number of times, the bottom feed is set by opening the valves B and C and closing the valves A and D (Step210), the counter of the setting number of times is increased by one (Step211), and the process proceeds to Step205. Steps205to208are executed again, and when the feed direction reversal number of times X reaches four in Step209, the air releasing process is completed (Step212). When the air releasing process is completed, that is, when the timing t5ofFIG.9is reached, the microcomputer52executes the centrifugal separation working by making the rotor100rotate at a high speed. The control procedure of the centrifugal separation working is the same as a control procedure of a conventional continuous centrifuge, and thus the description here is omitted.

Next, the detailed procedure of the air releasing process (Step205) is described with reference toFIG.11. First, the microcomputer52clears the counter, which is set for counting the pressure increase number of times Y after the feed direction is set (Step251), to 0, and waits for T1seconds (Step252). When T1seconds elapses, the microcomputer52closes the valve C of the two open valves B and C which is on the downstream side in the flow direction (Step253). At this time, the counter is increased by one (Step254). If the valve C is closed, the flow path is closed, and thus the line pressure is gradually increased. If the pressure95reaches the threshold P2as shown by the arrow95bofFIG.9, when the microcomputer52opens the valve C, the sample remaining in the line is discharged at once (Steps255and256). By sharply changing the pressure95of the sample in a manner of P1to P2to P1in this way, even the minute bubbles accumulating in the rotor100can be effectively moved.

Next, the microcomputer52waits until the predetermined time T2elapses (Step257), judges whether or not the counter indicating the number of times that the valve C is closed reaches the specified value (here is 3), and if the counter does not reach the specified value, the process returns to Step253, and Steps253to257are repeated Y times in total. If the counter reaches the specified value of 3 in Step258, the microcomputer52waits until the predetermined time T3elapses (Step259), and the process returns to the original Step205. In this way, the bottom feed and the top feed are switched X times in total, and the pressure increase and the flow path opening operation are respectively performed Y times when each feed is executed. As described above, by repeatedly applying the pressure fluctuation in the line and arranging the “air discharge mode” for switching the flow direction, the bubbles mixed in the flow path are almost discharged from the line.

Moreover, in Step255, when the pressure threshold P2is reached, the valves which can be automatically controlled by the microcomputer52are opened and closed, and the rotation speed of the liquid sending pump77may also be controlled at the same time. By setting the rotation speed of the liquid sending pump77higher than a rotation speed used during a normal sample injection, the flow speed in the pipe can be sharply increased, and thus the air is easily released, and at the same time the time required to reach the pressure threshold P2can be shortened, and thus the tact time for completing the air releasing process performed X=4 times can be shortened.

Meanwhile, the function of the “air discharge mode” can be utilized not only in the air releasing process, but also in a stopped CIP process (a line cleaning process). In many cases, stains which are derived from the sample inside the rotor and the core after the centrifugal separation are generally line-cleaned using an alkaline aqueous solution, and are further cleaned using WFI in order that no alkaline components remain, and it is necessary to prevent stains and alkaline components from remaining in the dead space. If the above control method is adopted, the pressure, the flow direction, the flow speed, and the like of the line can be automatically changed, and the cleanability of the wetted portion after the centrifugal separation is expected to be improved. Furthermore, by combining with a method of cleaning a line while rotating a rotor at a low speed, which is shown in Japanese Patent Laid-Open 2011-177703, the cleaning effect is expected to be further improved.

Moreover, in many cases, for a sample feed system which is a separate device from the continuous centrifuge1, a four-way valve which plays a role of the valves A to D even in conventional products is adopted. The above is described in the form of controlling this 4-way valve, but instead of the sample feed system, the present invention can also be realized by arranging new valves near an upper seal portion and a lower seal portion of the continuous centrifuge1. The effects of the pressure fluctuation and the flow speed fluctuation can be expected in the case where a valve is arranged as close as possible to the centrifugal separation portion to perform the opening/closing operation. The control device responsible for the valve control may be arranged on the sample feed system side, or may be arranged on the continuous centrifuge1side.

In addition, the pipe used for connecting to the sample feed system and the continuous centrifuge1may be a tube such as a silicon tube, but in the case where an SIP is incorporated or the like, the pipe may also be a stainless pipe. An automatic pinch valve may be used if the pipe is a tube pipe, an automatic diaphragm valve may be used if the pipe is a stainless pipe, and the type of the valve does not matter as long as the pipe has a function of opening and closing the flow path. Furthermore, without being limited to a component called a valve, the same effect can be expected as long as the component has a function of blocking the flow path.

According to the example, the total number of times of the switching between the top feed and the bottom feed is set to X, the number of times of the operation of the automatic valve which is opened after the pressure is increased to the pressure threshold P is set to Y times at each switching, the opening/closing interval time of the automatic valve is set to T1, T2, and T3, and the above X, Y, and T1, T2, and T3are stored in the microcomputer52as parameters, and thereby the air releasing process can be performed fully automatically using the microcomputer52. If the bubbles remaining in the rotor are automatically removed before the high-speed rotation of the rotor100, the liquid sending pressure of the sample during the centrifugal separation working can be kept low, the continuous supply of the sample to the rotor100can be stable, and a good centrifugal separation performance can be obtained.

Although the present invention is described above on the basis of the example, the present invention is not limited to the above-described example, and various changes may be made without departing from the gist of the present invention. For example, in the continuous centrifuge1of the example described above, the example of the bottom feed in which the sample to be separated is put into the rotor100from the lower pipe72has been described, but the present invention is not limited thereto. The case of the centrifugal separation working by the top feed may also be applied similarly in which the sample is put into the rotor100from the upper pipe82and the waste liquid or the separated sample is collected into the collection tank86from the lower pipe72.