WO1997014027A2

WO1997014027A2 - Injector

Info

Publication number: WO1997014027A2
Application number: PCT/JP1996/002893
Authority: WO
Inventors: Tohru Sugawara; Shinji Kato; Shintaro Kuramochi
Original assignee: Takeda Chemical Industries, Ltd.
Priority date: 1995-10-09
Filing date: 1996-10-04
Publication date: 1997-04-17
Also published as: WO1997014027A3; AU7145896A

Abstract

An injector of the invention has a generally cylindrical body which is arranged vertically. The body is closed at its upper end with an end wall and opened at its lower end. The upper end wall has an inlet and an outlet in spaced relation to each other. A piston is accommodated within the body with its periphery slidably and sealingly engaged with an inner peripheral surface of the cylindrical body. Also, a rod is inserted into the body through the lower end and is coupled to the piston for movement together therewith. Particularly, one of the respective surfaces of the end wall and the piston which confront each other includes a groove for defining a passage communicating between the inlet and the outlet.

Description

D E S C R I P T I O N INJECTOR

FIELD OF THE INVENTION

The invention relates to an injector for dispensing a dose of fluid particularly, but not limited thereto, for use in chromatography. The invention further relates to a deaerator for removing air from a fluid to be transported in a circuit. The invention furthermore relates to an automated refining system which preferably includes the injector.

BACKGROUND OF THE INVENTION

Conventional syringe type injector is illustrated in Figs. 21A and 21B. This injector 1000 comprises a cylindrical body 1001, a head 1002 closing one open end of the body 1001, and a piston 1003 movably housed in the body 1001. The head 1002 includes therein a through-hole 1004 through which a liquid flows in and out of the cylindrical body 1001. Connected with the through-hole 1004 is a pipe 1005 which is in turn connected through a switching valve 1006 to a common pipe 1007 on an upεtream side and another common pipe 1008 in a downstream side. Arranged on the upstream common pipe 1007 are switching valves 1009, 1010, and 1011. These valves 1009, 1010, and 1011 are also connected through branch pipes 1012, 1013, and 1014 to containers 1015, 1016, and 1017, respectively. The containers 1015, 1016, and 1017 accommodate therein respective samples to be tested. Connected with the downstream side common pipe 1008 on the other hand is a switching valve 1018 which is in turn connected with branch pipes 1019 and 1020. The pipe 1019 is connected with a receptacle 1021 for receiving the sample to be fed through the pipe 1019 while the pipe 1020 is connected with another receptacle 1022 for receiving a waste liquid.

The piston 1003 is drivingly connected with a driving mechanism (not shown) so that, when it moves downward, a certain amount of liquid can be sucked into the syringe 1001 through the common pipe 1007 on the upstream side, but when it moves upward, the liquid in the syringe 1001 can be discharged through the common pipe 1008 on the downstream side.

This prior art injector 1000 is effective for feeding the same liquid repeatedly. However, when it comes to successive feed of different liquids in the respective containers 1015 and 1016, for example, feed of the liquid in the container 1015 followed by feed of the liquid in the container 1016, the first-fed liquid may still remain in the common pipe 1007, the pipe 1005, and the syringe 1001 at the beginning of feed of the subsequent liquid and this will result in a mixing of those different liquids. Specifically, when two different samples are fed, firstly a certain amount of liquid in any of the container is sucked through the pipes 1007, and 1005 into the syringe 1001. Then, by switching the valve 1006, the liquid is discharged from the syringe 1001 through the pipes 1005, 1008, and 1019 to the receptacle 1021. At this time, the liquid still remains in the common pipe 1007, the pipe 1005 between the valve 1006 and the syringe 1001, and further the through-hole 1004 in the head 1002. As a result, at the beginning of the feeding of the second sample, this second sample is necessarily mixed with the remaining first sample. Subsequently, at the time of rinsing the pipes and the syringe, a cleaning liquid is sucked to the syringe 1001 through the pipes 1007 and 1005 and then discharged from the syringe 1001 through the pipes 1005, 1008, and 1020 to the water waste receptacle 1022 with the remaining sample in the pipes. This procedure should be done a plurality of times for removing all the remaining sample in the pipes in order to prevent the remaining sample from being mixed with the subsequent sample to be tested.

Therefore, this procedure necessarily result in a loss of the valuable sample. Also, in chromatography, if the test sample to be tested is mixed with other sample or the cleaning liquid, components would no longer be isolated precisely in a column, which results in difficulty in detecting right peaks in an output chromatogram. Further, in the above-described prior art syringe type injector, a peripheral surface of the piston 1003 should be tightly sealed with an inner surface of the syringe 1001 to prevent the liquid in an upper chamber from leaking into a lower chamber separated by the piston 1001. However, if a pressure in the upper chamber increases as the piston moves upward to force the liquid out of the upper chamber, it may break the seal at a contact between the peripheral surface of the piston 1003 and the facing inner surface of the cylinder, which results in a leakage of the liquid from the upper chamber to the lower chamber.

This leakage can be prevented by minimizing a clearance between the piston and the inner surface of the syringe to increase a leakage resistance therein. However, this accelerates wearing of both piston and syringe surfaces, which decreases respective durabilities of the piston and the syringe and hampers a smooth elevation of the piston. Note that, a rubber ring, which is commonly used to seal the clearance, is prohibited from being arranged around the piston in the case of use of chemical sample tending to weaken the rubber seal.

The leakage is highly problematic if only a small amount of chemical sample is available. Accordingly, it has been required to provide a mechanism that can prevent the leakage, though no effective countermeasure has been available to overcome the problem.

Further, in a chemical experiment system including the above-described injector, such as an automated refining system used for chromatography, an analyzer is provided for detecting components of the sample discharged from a column. Also, based upon the result of the analyzer, the sample is divided into a plurality test tubes at a fraction collector. Such analysis of components should be done precisely. However, if the liquid discharged from the column includes air, an output signal of the analyzer includes noises and/or spurious peaks, which dramatically decreases the quality of the test. Therefore, it has been required to provide a device capable of removing air from the liquid. Furthermore, a prior art refining system used for chromatography requires experienced operators, a complicated operation, and a lot of time.

SUMMARY OF THE INVENTION

Accordingly, the primary object of the invention is to provide an improved injector which is capable of feeding a liquid remaining in flow lines into its destination, eliminating a loss of the valuable liquid, and readily rinsing and drying the flow lines.

Another object of the invention is to provide a syringe type injector which is capable of preventing the liquid from leaking between the piston and the associated inner surface of the syringe.

Still another object of the invention to provide a deaerator capable of deaerating air in the liquid. A further object of the invention is to provide a deaerator capable fo discharging the liquid with minimum diffusion .

A furthermore object of the invention to provide a system for a column chromatography, which can be used independently as a refining device or in combination with a generation reaction device as an automated synthesizing device.

To this end, an injector for measuring and then injecting a fluid of the invention has

(a) a generally cylindrical body, arranged vertical, which is closed at its upper end with an end wall and opened at its lower end, the upper end wall having an inlet and an outlet defined therein in spaced relation to each other;

(b) a piston accommodated within the cylindrical body with its periphery slidably and seaiingly engaged with an inner peripheral surface of the cylindrical body;

(c) a piston rod inserted into the cylindrical body through the bottom end and coupled to the piston for movement together therewith; and (d) one of respective surface of the upper end wall and the piston which confront with each other includes a groove for defining a passage communicating between the inlet and the outlet.

According to this injector, the fluid is sucked into the cylindrical body as the piston moves downward through the inlet. After a predetermined amount of fluid is accommodated, the fluid is then discharged from the outlet with the upward movement of the piston. Once the piston reaches its upward limit, the short-cut passage is formed by the groove to communicate between the inlet and outlet. Therefore, applying a positive pressure at the inlet or negative pressure at the outlet will discharge the fluid remaining in the inlet, outlet, and/or short-cut. Preferably, the injector may include (e) an elevating member, connected with the piston rod and having a threaded hole and a guide hole; (f) a lead screw engaged with the threaded hole;

(g) a guide member which cooperates with the guide hole to guide the elevating member; and

(h) a driving source for rotating the lead screw.

According to this injector, by the driving source, the lead screw is rotated so that the elevation member and then the piston move upward or downward. Also, a moving speed of the rod is controlled by the control of the rotation of the lead screw. Another advantage of the injector is that the elevating member is moved upward or downward in a horizontal state.

Preferably, the injector may have (i) means for detecting the piston which is in its upward limit;

(j) means for detecting the piston which is in its downward limit;

(k) means for detecting a pressure applied on the piston; and (1) means for driving the elevating member according to signals from the means (j) , (k) , and (1) .

According to this injector, the upward and downward limit of the piston are detected, respectively, which provides the piston with a safe control. Also, no excessive pressure is applied on the piston.

Suitably, this injector may have means for detecting the fluid in the vicinity of the inlet and outlet. Another embodiment of the injector of the invention includes

(a) a generally cylindrical body, arranged vertical, which includes its upper end a first wall having a first passage for introducing the fluid into the body and discharging the fluid from the body and its lower end a second wall having a second passage;

(b) a plunger which includes a rod extended through the second passage into the cylindrical body with its periphery slidably and seaiingly engaged with an inner surface of the second passage, a piston accommodated within the cylindrical body with its periphery slidably and seaiingly engaged with an inner surface of the cylindrical body, whereby an interior of the cylindrical body is divided into a first chamber between the first wall and the piston and a second chamber between the second wall and the piston; (c) an actuator for moving the plunger in a longitudinal direction of the cylindrical body;

(d) a fluid source for feeding a pressurized fluid;

(e) a valve having a first, a second, and a third ports, the first and second ports or the second and third pots being selectively communicated each other, and the third port being opened to air;

(f) a first line which communicates between the first port and the pressurized fluid source; (g) a second line which communicates between the second port and the second chamber;

(h) a controller which controls the valve so that, when the plunger moves away from the first wall for introducing the fluid into the first chamber, the εecond and the third ports are communicated each other and, when the plunger moves towards the first wall for diεcharging the fluid from the firεt chamber, the firεt and the εecond ports are communicated each other.

This injector may preferably be used in a chemical experiment for dispensing a chemical reagent or filling a sample in a chromatography column. Specifically, the injector effectively prevents a valuable and a εmall amount of chemical reagent or sample from leaking.

The rod may include therein a hollow passage, one end thereof being opened to the second chamber and the other end thereof being communicated with the second line.

Also, the cylindrical body may include an opening through which the second line is communicated with the second chamber, the opening being arranged below the downward limit of the piston.

Further the injector may have means for detecting a preεεure to be applied on the piεton so that, according to signals from the detector, the controller controls the valve.

Furthermore, the injector have means for detecting a pressure to be applied on the piston and means for controlling a presεure of the fluid to be supplied from the pressurized fluid supply source so as to keep a presεure in the second chamber equal to that in the first chamber, whereby the fluid is prevented from leaking from the first chamber to the second chamber. Moreover, the firεt passage may have an inlet hole for introducing the fluid into the body and an outlet hole for discharging the fluid from the body, and the first wall or the piston includes in its surface confronting the other a groove which defines a short-cut passage for communicating between the inlet and outlet holes when the piston meets the first wall.

Another embodiment of the injector has (a) a cylindrical body which is arranged vertically, having its upper end a first wall which includes a first passage for introducing the fluid into the body and discharging the fluid from the body and its lower end a second wall which includeε a εecond paεsage; (b) a plunger which includes a rod extending through the second passage into the cylindrical body, an outer surface thereof being continuously in close contact with the second passage, and a piston connected with the rod in the cylindrical body, a peripheral εurface of the piεton being continuously in close contact with an inner surface of the cylindrical body, whereby an interior of the cylindrical body iε divided into a firεt chamber between the firεt wall and the piεton and a εecond chamber between the εecond wall and the piεton;

(c) an actuator for moving the plunger along a longitudinal direction of the cylindrical body;

(d) a fluid source for feeding a preεεurized fluid; (e) a first line which communicates the second chamber with the pressurized fluid source;

(f) a second line which communicates the εecond chamber with air;

(g) a first valve which iε disposed on the first fluid line;

(h) a second valve which is disposed on the second fluid line;

(i) a controller which closes the first valve and opens the second valve when the plunger moves away from the first wall for introducing the fluid into the first chamber and opens the first valve and closes the second valve when the plunger moves towards the first wall for discharging the fluid from the first chamber.

The first passage may comprise an inlet hole for introducing the fluid into the body and an outlet hole for discharging the fluid from the body, and the first wall or the piston includes in its surface confronting the other a groove which defineε a εhort-cut passage for communicating between the inlet and outlet holes when the piston meets the firεt wall.

A deaerator of the invention for removing a gas from a mixture of the gas and a liquid compriseε

(a) a container for accommodating the mixture;

(b) a tube, one end thereof being inεerted in the container and having an intake which iε arranged adjacent a bottom of the container, for extracting the liquid from the container;

(c) a first detector, arranged above the intake, for detecting the liquid in the container;

(d) a supply line, communicated an interior of the container, for supplying the mixture into the container; (e) an exhaust line, arranged above the detector and communicated with the interior of the container, for exhausting the air from the container;

(f) a first valve diεposed on the extracting tube;

(g) a second valve dispoεed on the exhausting line; (h) a controller which closeε the firεt valve and opens the εecond valve when the detector doeε not detect the liquid and opens the first valve and closes the second valve when the detector detects the liquid.

According to this invention, the liquid having the gas is introduced into the container through the supply line. At this time, the first valve is closed and the second valve is opened so that the air in the fluid is removed and discharged through the exhaust line. If the first detector detects the liquid, the valves are switched, i.e., the first valve is opened and the εecond valve iε cloεed, permitting the liquid from which the air has been removed to be discharged through the extracting tube.

The dearator may includes a second detector, arranged above the first detector and below the exhaust line, for detecting the liquid. With this embodiment, the level of the liquid is controlled within the first and second detectors, which prevents a frequent switching of the valves.

The bottom of the container is preferably in the form of an inverted cone. This keeps the surface of the liquid above the intake of the extracting tube even when the container accommodates a small amount of liquid. Also, thiε preventε the dilution of componentε of the liquid and ensures the older liquid in the container to be discharged earlier than that newly supplied.

In addition, an apparatus, having a deaerator and an injector, which removes air from a liquid and then measures the liquid has (A) the deaerator, which includes (a-l) a container for accommodating the mixture;

(a-2) a tube, one end thereof being inserted in the container, the end having an intake which is arranged adjacent a bottom of the container, for extracting the liquid from the container;

(a-3) a detector, arranged above the intake, for detecting the liquid in the container;

(a-4) a supply line, communicated an interior of the container, for supplying the mixture into the container;

(a-5) an exhauεt line, arranged above the detector and communicated with the interior of the container, for exhausting the air from the container;

(a-6) a firεt valve diεposed on the extracting tube;

(a-7) ^• a second valve dispoεed on the exhauεting line;

(a-8) a controller which closes the first valve and opens the second valve when the detector does not detect the liquid and opens the firεt valve and closes the second valve when the detector detects the liquid; and (B) an injector which includes

(b-l) a cylindrical body which is arranged vertically, a top end thereof being closed by a wall and a bottom end thereof being opened, the wall including an inlet hole and an outlet hole, the inlet being communicated with the extracting tube; (b-2) a piston which is movably arranged in the cylindrical body with its peripheral εurface being in cloεe contact with an inner εurface of the body;

(b-3) a rod inserted in the cylindrical body and connected with the piston;

(b-4) wherein the wall or piston includes in a surface confronting each other a groove which communicates between the inlet and outlet holes when the piston is close contact with the wall. Still further a refining apparatus of the invention has

(a) a developer unit which mixes a plurality of developers and then delivers them;

(b) a sample unit which delivers a sample; (c) a filling unit which includeε c-1: an injector; c-2: a switching valve which firstly delivers the sample from the sample unit into the injector and secondly delivers the developers into the injector; (d) a column unit, having a stationary phase, which transportε the εample and the developers through the stationary phase;

(e) an analyzing unit for analyzing components of a liquid fed from the column unit; (f) a division unit for dividing the liquid fed from the analyzing unit; and

(g) a control unit for controlling the units (a) to ( f ) .

The developer unit may include a-l: a plurality of containers for accommodating respective developers; a-2: a gradient for extracting a plurality of developers from the containers in a certain rate; and a-3: a high performance liquid chromatography pump for delivering the developers mixed in the gradient at a certain velocity. Also, the sample supply unit may include b-l: a plurality of containers for accommodating the sampleε; and b-2: a plurality of valveε for εelectively communicating the containerε with the εwitching valve. Further, each of εample containers may be provided with at least one supplementary container for accommodating the corresponding εample.

Furthermore, the εample unit may include a connector for receiving a εample feed from other apparatus. Moreover, the injector of the refining apparatus includes an elevating member, having a threaded and a guide hole, which is connected with the rod; a lead screw engaged with the threaded hole; a guide member which cooperates with the guide hole to guide the elevating member; and a driving source for rotating the lead screw. Also, the column unit may include a plurality of columns and the filling unit supplies the selected column with the liquid.

Further, the apparatus may include a deaerator having a container for accommodating the mixture; a tube, one end thereof being inserted in the container, the end having an intake which iε arranged adjacent a bottom of the container, for extracting the liquid from the container; a firεt detector, arranged above the intake, for detecting the liquid in the container; a εupply line, communicated an interior of the container, for εupplying the mixture into the container; an exhaust line, arranged above the detector and communicated with the interior of the container, for exhauεting the air from the container; a first valve dispoεed on the extracting tube; a εecond valve disposed on the exhausting line; a controller which closeε the first valve and opens the second valve when the detector does not detect the liquid and opens the first valve and closes the second valve when the detector detects the liquid.

Furthermore, the division unit of the refining apparatus may include a first fraction collector for a peak separation of the liquid and a εecond fraction collector for a volume εeparation of the liquid, and the liquid iε supplied selectively to the first or second fraction collector.

BRIEF DESCRIPTION OF THE DRAWINGS

Theεe and other objectε and features of the present invention will become clear from the following description taken in conjunction with the preferred embodiments thereof with reference to the accompanying drawings throughout which like parts are designated by like reference numerals, and in which: Fig. 1 is a block diagram of an automated refining system;

Fig. 2 is a block diagram of a hardware section in the refining syεtem;

Fig. 3 εhowε a drive unit in the refining system; Fig. 4 is a partial enlarged view of the refining system in which three rotary valves and a plurality of flow lines connected thereto are shown;

Fig. 5A is a sectional view of an injector of the invention; Fig. 5B is a perspective view of an elevating member and its guide members of the injector shown in Fig. 5A;

Fig. 6A is a partial sectional view of a syringe in the injector in which a piston is in its downward limit; Fig. 6B is also a partial sectional view of the syringe in which the piston is in its upward limit to form a εhort-cut passage with a head member;

Fig. 7 is a front view of a deaerator;

Figs. 8A and 8B are flow charts showing a procesε of the refining εyεtem; Fig. 9A shows a state of the first rotary valve when a developer is fed from a developer unit to the injector;

Fig. 9B shows a state of the third rotary valve when a developer is fed from the injector to a column; Fig. 10 showε another embodiment in which the injector iε used as a supply unit;

Fig. 11 showε a modification of the embodiment shown in Fig. 10;

Figs. 12A and 12B are sectional views of an injector of other embodiment in which a groove is formed in the piston and Fig. 12A shows a state that the piston is in its downward limit while Fig. 12B shows another state that the piston iε in itε upward limit to form a εhort-cut passage; Fig. 13 shows a partial sectional view of an injector of other embodiment in which a pressurized gas supply unit is included;

Fig. 14 also εhowε a partial sectional view of the injector of other embodiment in which the piston is in its downward limit;

Fig. 15 is an enlarged sectional view of the injector in which the piston is formed with an opening for letting a pressurized gas in and out of the syringe;

Fig. 16 is a sectional view of the injector of other embodiment in which the pressurized gas supply pipe is directly connected with the syringe; Fig. 17 is a sectional view of the injector of other embodiment in which the presεurized supply pipe and a pressurized gas discharge pipe are directly connected with the syringe;

Figs. 18A and 18B are sectional views of the injector in which the groove is formed in a head cover of the syringe;

Fig. 19 iε a front view of the deaerator of other embodiment in which an upper εensor is eliminated;

Fig. 20 shows an apparatus in which the deaerator is used for removing air from the liquid to be delivered to the injector;

Fig. 21A showε a prior art εyεtem for meaεuring a certain amount of liquid and then deliver it to a receiver; and Fig. 21B iε a εectional view of the prior art injector uεed in the εyεtem εhown in Fig. 21A.

PREFERRED EMBODIMENTS OF THE INVENTION

1. Hardware. Software, and their Interconnections in

Automated Refining System Referring to the drawings, Fig. 1 iε a block diagram of an automated refining system for a column chromatography. The refining system generally includes a hardware section and a software section. The hardware section comprises of a drive unit I and a control unit II. The drive unit I includes a developer unit 100, a sample unit 200, a filling unit 300, a column unit 400, a deaeration unit 500, an analyzing unit 600, and a liquid division unit 700. The software section includes a refining program and a data processing program, both being stored in a central processing unit, or computer CPU, in the control unit II.

Referring to Fig. 2, the computer CPU includes an output unit which is electrically connected with such devices as magnetic valves and relays arranged in the units 100 to 700 of the drive unit II, an input unit which is electrically connected with valve sensors for detecting locations of rotorε in the valves and liquid sensors for detecting the liquid, an analogue to digital converter which is electrically connected with a voltage output of each of the detectors, a communicating circuit RS232C connected with the detectors and a high performance liquid chromatography (HPLC) pump. The drive unit I thus connected is operated according to programs stored in computer CPU.

2. Details of Automated refining Device Fig. 3 showε a general construction of the drive unit I which includes units 100 to 700, each of which being described in detail below. The drive unit has a plurality of flow lines Ll to L15 made of teflon for delivering developers and sampleε and a plurality of magnetic valves VI to V15 disposed on the flows lines Ll to L15 for controlling flow of the developers and samples. It should be noted that, in each of magnetic valves VI to V15, a port shown with a black dot is normally cloεed, a port shown with a black triangle is a common port, and a port εhown without any εign is normally opened.

2-1. Developer Unit 100

The developer unit 100 includes a High Performance Liquid Chromatography (HPLC) pump 101 for delivering a predetermined amount of developer, a gradient 102 for mixing a plurality of developers at a predetermined rate, and a plurality of developer containers 1031, 1032, and 1033 for accommodating developers, or developing solvents. The HPLC pump 101 iε connected through the gradient 102 with the containers 1031, 1032, and 1033. An optical sensor PS3 for detecting the developer is disposed on a flow line Ll which connects the HPLC pump 101 with a first rotary valve 301 of the filling unit 300. In operation, certain amounts of developerε from the containers 1031, 1032, and 1033 are mixed at an certain rate according to a predetermined time sequence by the gradient 102 and then fed through the flow line Ll to the first rotary valve 301 by the HPLC pump 101. The optical εenεor PS3 detects the liquid in the flow line Ll. Further, the HPLC pump 101 and its feeding velocity of the mixed developers are controlled by the computer CPU connected through the communication circuit RS232C. Also, the computer CPU checks the pressure of the developer fed from the pump 101.

2-2. Sample Unit 200

The sample unit 200 includes two main containers

2011 and 2012 for accommodating respective liquid sampleε to be tested in chromatography. The containers 2011 and

2012 are connected through respective magnetic valves VI and V2 to the flow line L2. This line L2 is joined at its one end to the first rotary valve 301 so that each sample can be delivered through the flow line L2 to the rotary valve 301. The flow line L2 has an optical sensor PS4 for detecting the sample. The flow line L2 alεo includeε at its other end a connector 203 so that other sample from other apparatus, e.g., chemical synthesizer, another sample supply unit, or syringe (not shown) can be supplied through the valves V2 and VI to the first rotary valve 301.

The sample unit 200 also includes two supplementary sample containerε 2041 and 2042 for accommodating εupplementary samples. The container 2041 is connected through a flow line having a magnetic valve V5 to the main sample container 2011 while the container 2042 is connected through another flow line having a magnetic valve V6 to the main sample container 2012.

The εample unit further includes a container 204 for accommodating a cleaning liquid. This container 204 is connected with the main containers 2011 and 2012 through a flow line L3 having magnetic valves V3 , V4 , V5, and V6 while the main containers 2011 and 2012 are connected with the vacuum pump 307 through respective magnetic valves V7 and V8 so that upon driving the vacuum pump 307 the cleaning liquid can be sucked from the container 204 to the main sample container 2011 or 2012, selectively.

2-3. Filling Unit 300 (1) General Construction

The filling unit 300 includes three rotary valves 301, 302, and 303. The firεt and third rotary valves 301 and 303 have six portε while the εecond rotary valve 302 haε four ports. These valves 301, 302, and 303 includes εensor PSI, PS2, and PS14 each operable to detect the position of a rotor in the associated valve.

As shown in Fig. 4, of the portε in the first rotary valve 301, the ports 30la, 301b, 301c, and 301d are connected with the flow lines L2, Ll, L4, and L16, respectively. The remaining ports 301e and 301f are closed.

The flow line L4 is connected through an optical sensor PS5 with an inlet 305 formed at the top of an injector 304. The injector 304 includes at its top an outlet 306 with which a flow line L5 is connected. The other end of the flow line L5 remote from the injector 304 is connected through an optical sensor PS6 with a port 302a of the second rotary valve 302. Other port 302b of the second rotary valve 302 iε connected with the vacuum pump 307 through a flow line L6 in which a trap 308 and a magnetic valve V9 are diεposed (see Fig. 3) . The port 302c is connected through a flow line L7 with the port 303a of the third rotary valve 303. Also, the port 302d is connected through a flow line L16 with the port 301d of the first rotary valve 301. The port 303b of the third rotary valve 303 is connected with an inlet port 402 of a closed column 401 while the port 303c is connected with an outlet port 403 of the column 401 (also see Fig. 3) . Furthermore, the port 303d of the rotary valve 303 is connected through a flow line L17 with an outlet port 405 of an opened column 404 and the port 303c and 303e is connected with a flow line L8 through which the liquid discharged from the column is delivered. Referring back to Fig. 3, all the sample from the container 2011 or 2012 is once accommodated in the injector 304 and then fed into the closed column 401 through the flow line L5, second rotary valve 302, flow line L7, and the third rotary valve 303. After the sample has been completely discharged to the column, the developer from the developer unit 100 is delivered through the first rotary valve 301, flow line L4, injector 304, flow line L5, second rotary valve 302, flow line L7, and the third rotary valve 303 to the column 401. At this time, as described in detail below, the developing εolvent iε tranεported through a distinctive short-cut which connectε directly between the inlet 305 and the outlet 306, without remaining in a syringe 310 of the injector 304.

After filling the εample in the column 401, the rotary valveε 301 and 302 are εwitched to a position allowing the developer to be directly delivered through the flow line L16 to the column 401. (2) Injector 304

Referring to Figε. 5A and 5B, a εyringe 310 is supported vertically at its upper portion by a chuck 311 which is in turn fixed on a support 313 extending outwardly from a drive housing 312. The εyringe 310 houεeε therein a piston 314 capable of moving longitudinally while keeping its peripheral surface in close contact with an inner surface of the syringe 310. The piston 314 is connected with a rod 315 which is inserted in the syringe 310 through a bottom through-hole of the syringe 310. Also, the rod 315 is in turn connected with a base plate 316. The baεe plate 316 extends through an opening into the drive housing 312 where it is connected with an elevating member 317.

In the housing 312, extended vertically therein is a lead screw 320 in the form of rod 319 which is rotatably joined at its lower portion to a lower base plate 318. On the other hand, the elevating member 317 has a threaded hole 321 in which the lead screw 321 is engaged. Joined at the upper end of the screw rod 319 is a stepper motor 322 so that upon rotation of the motor 322 the lead screw 319 rotates to move both the elevating member 321 in the housing 312 and the piston 314 in the syringe 310 upward or downward. The stepper motor 322 is secured on the upper base plate 323 which is fixed in the housing 312.

As shown in Fig. 5B, four guide railε 324 are arranged vertically between the upper and lower base plates 318 and 323. These railε 324 extendε through aεεociated holeε 325 formed in the elevating member 317 εo aε to guide this member. Also, the railε 324 are arranged around the rod εcrew 319 εo that the elevating member 317 moves up and down while keeping its stability. Referring back to Fig. 5A, the syringe 310 has a detachable head member 326 at its upper portion. The head 326 includes a pair of through-holes, i.e., the inlet 305 and the outlet 306.

As shown in Figε. 6A and 6B, the head 326 alεo includes at its bottom, i.e., a bottom surface confronting the piston 314, a groove 327 which extends between the inlet 305 and outlet 306 such that if the piston 314 reaches the upward limit, the piston 314 covers the lower opening of the groove 327 to form a short-cut pasεage 328 corresponding to the groove 327 which communicates between the inlet 305 and outlet 306.

Also, by the downward movement of the piston 314, the inlet 305 and outlet 306 communicate with the interior of the εyringe 310 εo that a liquid introduced from the inlet 305 can be accommodated in the εyringe 310. On the other hand, by the upward movement of the piεton 314, the liquid in the syringe 310 is discharged from the outlet 306. Further, when the piston 314 reaches its upward limit, the inlet 305 is communicated through the εhort-cut pasεage 328 with the outlet 306 and, therefore the liquid fed from the inlet 305 iε tranεported through the short-cut pasεage 328 to the outlet 306.

Referring again to Fig. 5A, a pair of sensors PS7 and PS8 are arranged at the upper and lower portion of the syringe 310, and are operable to determine whether the piston 314 has reached the upward and downward limits, respectively. Also, a pressure sensor PS9 is mounted on the base plate 316 to detect a pressure applied on the piston 314 so that an upward speed of movement the piston 314, i.e., the rotation of the stepper motor 322, can be controlled to keep the presεure under 2 kg/cm² and, alεo, if the preεεure increaεeε over a predetermined value, e.g., 2.5 kg/cm² in thiε embodiment, the εtepper motor 322 can be switched off.

In operation of the injector 304 so constructed, when the εtepper motor 322 is driven to move the piston downward, the syringe 310 sucks the sample from the container 2011 or 2012 through the inlet 305. When a certain amount of sample has been accommodated in the syringe 310, which is detected by a signal from the sensor PS8, the stepper motor 322 is switched off. Next, the stepper motor 322 is re-driven in the opposite direction to move the piston upward to push the sample in the syringe 310 out through the outlet 306 to the second rotary valve 302 while keeping the presεure applied on the piεton under 2 kg/cm². Finally, if the piεton 314 reaches the upward limit, which is detected by the sensor PS7, the piston 314 is brought into contact with the lower surface of the head 326 to form the short-cut pasεage 328 between the inlet 305 and outlet 306. Alεo, the developer introduced from the inlet 305 iε then tranεported through the εhort-cut paεεage 328 to the flow line L5. Further, if the optical εenεors PS5 and PS6 detects the sample in the syringe 310 during the upward movement of the piston 314, the rotary valves 302 and 303 are changed to inject the sample into the column.

2-4. Column Unit 400

Referring back to Fig. 3, the column unit 400 has the closed column 401 and an opened column 404, both of which accommodate respective well-known stationary phaseε 401a and 404a. These columns 401 and 404 can be used selectively by simply changing the third rotary valve 303. Also, the opened column 404 has a container 406 and a sensor 407 for detecting the developer.

Although the column unit 400 includeε a pair of cloεed column 401 and opened column 402 in this embodiment, it may includes more closed and opened columns or only a plurality of closed on opened columns. Further, these columns can be used in any order.

2-5. Deaeration Unit 500

Referring to Fig. 7, the deaeration unit 500 includes a deaerator 501. This deaerator 501, operable to remove air in the liquid from the column unit 400, is connected with the flow line L8 leading to the port 303e of the third rotary valve 303. The deaerator 501 is also connected through the flow line L9 with an analyzer 601 in the analyzing unit 600.

The deaerator 501 includes a glaεε container 502, the bottom portion thereof being formed into an inverted cone. Connected with the upper portion of the container 502 are a supply line 503 communicated with the flow line L8 and an exhaust line 504 communicated with the flow line L10 with the magnetic valve V10. A top opening of the container 501 is covered by a cap 505 having a through-hole 506 defined at its center. Inserted through the hole 506 into the container 502 is a teflon tube 507 which terminates at itε lower end, i.e., intake 508 located near the bottom of the conical portion of the container 502. The upper end of the tube 507 on the other hand iε connected with the flow line L9 which includeε the analyzer 601 and the magnetic valve V12. The container 502 has at its outer lower portion a pair of upper and lower senεorε 509 and 510 for sensing the liquid in the container 502. These sensorε 509 and 510 εhould be disposed above the intake 508 of the tube 507. In operation of the deaerator 501 thus constructed, the liquid from the column 401 is delivered through the third rotary valve 303, flow line L8, and supply line 503 into the container 502. Then the liquid flows down along the inner εurface of the container 502. At this time, the magnetic valves V10 and V12 are opened and closed, respectively and, accordingly, the liquid is accommodated in the container 502. Also, the air having mixed in the liquid is εeparated therefrom in the container. Once the upper sensor 509 detects the liquid, the magnetic valve V10 is closed and the magnetic valve V12 is opened, thereby enabling the liquid within the container 502 to flow upwards in the flow line L9 owing to the increasing pressure in the container 502. Subsequently, when the liquid level moves down to the lower sensor 510, the magnetic valves V10 and V12 are opened and closed, respectively, thereby allowing the liquid to be accommodated in the container 502 until the upper senεor 509 senses the liquid.

Therefore, with this dearation unit 500, the air can be completely removed from the liquid, which ensures that liquid free from air can be delivered to the analyzer 601. Alεo, because the bottom portion of the container 502 is in the form of inverted cane and thereby the capacity thereof is reduced, the chemical components disεolved in the liquid can be divided clearly without any mixing together, which eventually enableε each peakε to be detected by the analyzer to be separated from others and prevents them from being widen.

2-6. Analyzing Unit 600

Referring still to Fig. 3, the analyzing unit 600 includes an analyzer 601. This analyzer 601 is disposed on the flow line L9 so as to detect components of the liquid from the deaerator 501. Also, the analyzer 601 includes a lamp (not shown) , the frequency thereof being controlled by the computer through the communication circuit RS232C. In this analyzer 601, a light such aε viεual light, ultraviolet light is illuminated into the liquid. Then the intensity of the light passing through the liquid is compared with references to determine the component. Further, the reεult iε then fed to the computer, where it is stored.

Incidentally, the analyzer 601 and its operation are well known to the person having ordinary skill in the art and, therefore, the detailed description thereof is omitted here.

2-7. Division Unit 700 Also, referring to Fig. 3, the division unit 700 includes a large-sized fraction collector 701 and a small- sized fraction collector 702. The large-sized fraction collector 701 is connected with the analyzer 601 through the flow line Lil and L12 in which a plurality of magnetic valves V12, V13, and V14 are dispoεed. The flow line L12 iε further connected through the flow line L13 to the small-εized fraction collector 702.

The large-εized fraction collector 701 preferably includeε a plurality of large-εized teεt tubeε 703 on a base frame 704 so that, in case of a peak division method, the liquid can be filled in the tubes 703. The small-εized fraction collector 702 on the other hand preferably includes a number of small-εized teεt tubeε 705 on a base frame 706 so that, in case of a time division or a weight division, the liquid is filled in the teεt tubeε 705.

If no peak iε obεerved in the test result, the liquid is to be fed to the drain tank 707 through the flow line L14 and the magnetic valve V13. The drain tank 707, which also has a glasε rod type εenεor 708 for εensing the liquid, is connected through the flow line L15 and the magnetic valve V15 with the waste water trap 308.

3. Computer CPU

The control unit II, for controlling magnetic valves VI to V15, rotary valves 301 to 303, vacuum pump

307, HPLC pump 101, motor 322, etc., employs a notebook- εize personal computer in the housing 1 as the central processing unit CPU, in order to make the unit II compact. The unit II also includes an I/O expanεion unit for sending and receiving signals between the computer CPU and the driving unit I, a parallel I/O module and A/D conversion module, and RS232C communication circuit.

The program stored in the computer CPU drives the refining syεtem provided that the operator inputs an information with reεpect to the column to be used, time, test tube number in the fraction collector, velocity of the developer, gradient condition, wavelength to be detected, code number of the teεt, etc. , by on an interactive baεiε with reference to a monitor εcreen.

The program has following features (1) to (4) : (1) Prior to start of the syεtem, the program self- checks the presence of the sample in the container, the initial set position of the injector 304, and rotational position of the rotary valves 301, 302, and 303. Then, if all the initial conditions have been met, the program starts the operation.

(2) Even in the operation of chromatography, the program checks the presence of the developer, the feeding pressure of the liquid, and whether all the test tubes in the fraction collectors has been filled with liquid, and if there is any trouble, the program interrupts the chromatography proceεε to wait an inεtruction from the operator. If the chromatography is restarted according to the instruction, the refining process can be succeeded without starting from the beginning. If the chromatography is completed or interrupted, all the test result is εtored in a hard-diεc so that the subsequent operation such as cleaning can be started immediately.

(3) The flow εpeed of the liquid and the wavelength to be detected can be changed during the chromatography operation becauεe the analyzer 601 and the HPLC pump 101 iε controlled using the communication circuit RS232C. (4) If the peak division is employed as the fraction division, the program watches the output of the analyzer 601 and illustrateε an output curve. Also, if an unusual output or slope is observed in the curve, the liquid from the analyzer is fed to the fraction collector 701 not to the drain tank 707 by changing the magnetic valve. If the output curve repreεentε εmall peakε, the liquid iε divided at each valley on the curve into different test tubes. Also, when the test tube to which the liquid iε filled in is changed at the fraction collector, a line iε drawn in the output curve on the monitor εo that the number of the test tube corresponds to the portion in the curve. In sampling the liquid according to the time division or the volume division, the analyzer 601 monitors the liquid and shows the graph similar to the peak division. All output data displayed on the monitor is recorded on a hard-disc in the computer. 4. Refining Process

Referring to Fig. 8 which showε the program stored in the computer CPU, the refining process by the driving unit I in the refining system will be described below.

Firstly, the column and the sample container 1031, 1032, and 1033 are set in the system. Secondly, the manual switch (not shown) is turned on to drive the HPLC pump 101 so aε to check whether the developers will be rightly fed to the column.

Also, when the refining syεtem iε driven independently, the εample iε εupplied using pipette in the sample container 2011 or 2012. Next, the cleaning liquid is supplied in the supplementary container 2041 or 2042. Further, if the sample is fed from the different syεtem, the magnetic valve V2 is connected with a sample container in the different syεtem through a εuitable means such as tube, if necesεary.

If the all connectionε have completed, a refining condition data is input to the computer CPU at step #1. Specifically, other data such as names of the chemical compounds, a code number, the sample container to be selected, the column to be used, a refining time, the fraction collector to be used, the number of the test tube in the fraction collectors, the flow rate of the developer, the wavelength of the light used in the analyzer are stored in the computer. After inputting the refining data, the initial condition is checked prior to the start of the refining process at step #2. Specifically, the computer checks the positions of the rotors in the rotary valves 301, 302, and 303 according to the signalε of the sensors PSI, PS2, and PS14, the position of the piston 314 in the injector 304 according to the signalε of the sensorε PS7 and PS8, and the preεence of the developers according to the signals of the sensorε PS3, PS5, and PS6. If no trouble is detected, the sample is fed from the sample container to the injector 304 at εtep #3. At this time, firstly the HPLC pump 101 is kept still, secondly the motor 322 iε driven to move the piston 314 in the injector 304 downward, and thirdly the magnetic valve VI is opened, which permits the sample to be fed through the rotary valve 301 to the injector 304. Thus, in the injector, the sample is transported through the inlet 305 into the syringe 310.

If both optical senεorε PS4 and PS5 detect the sample in reεpective flow lines L2 and L4, after a predetermined time has pasεed the piεton 314 halts its downward movement. If the senεor PS4 or PS5 fails to detect the sample or the sensor PS8 detects the piston 314, the computer interrupts the refining operation and displayε a trouble warning.

Next, the vacuum pump 307 and magnetic valveε V5 and V7 are εwitched on to allow the cleaning-liquid container 2041 to feed the cleaning liquid into the main container 2011. If all the cleaning liquid has been fed to the main container, the magnetic valves V5 and V7 are closed and the valve V9 is opened. This introduces a negative presεure into the injector 304 to thereby permit the cleaning liquid to be transported from the container 2011 through the flow line L2, the first rotary valve 301, and the flow line L4 to the injector 304. At thiε time, the remaining εample in the flow lineε are removed by the cleaning liquid. After that, if the computer has confirmed by the signal from the sensors PS4 and PS5 that there is no liquid in the flow lines, the vacuum pump 307 is εwitched off. and the magnetic valve V9 iε cloεed. By these cleaning process, all the sample in the container is fed into the syringe 310 without leaving any sample in the flow lines.

Next, the air in the εyringe 310 of the injector 304 is removed at εtep #4. Specifically, firεtly the magnetic valve V9 iε opened and then the motor 322 iε started to push the piston 314 upward. By the upward movement of the piston 314, the air in the syringe 310 is discharged through the outlet 306, flow line L5, second rotary valve 302, vacuum flow line L6, and the magnetic valve V9 to the atmosphere. The air is also discharged from the syringe 310 to the atmosphere through the inlet 305, flow line L4, firεt rotary valve 301, flow line L2, and the valveε VI and V2.

If all the air iε discharged from the syringe 310 and further the sensors PS5 and PS6 adjacent the inlet 305 and outlet 306 of the injector 310 detect the sample, the sample in the injector 304 iε filled into the column 401 at step #5. Specifically, at this step, firstly the rotors of the rotary valves 301 and 302 are rotated to change flow lines as shown in Figs. 9A and 9B, in which the flow lines L4 is disconnected from the flow line L2 and the flow line L5 is connected with the flow line L7 so that the sample from the injector 304 can be fed to the column 401 through the flow line L5, the second rotary valve 302, the flow line L7, and the third rotary valve 303. In this connection, although the flow line L4 is connected with Ll, a check valve (not shown) in the HPLC pump 101 preventε the liquid from moving from the flow line L4 to Ll.

Next, in the injector 304, the motor 322 iε driven to move the piεton 314 upward to fill the sample through the flow lines into the column 401. At filling, the pressure senεor PS9 detectε the preεsure applied on the piston 314. Based upon the output of the presεure εensor PS9, the computer controls the motor 322 to keep the pressure under 2.0 kg/cm². If the presεure increaεeε up to 2.5 kg/cm², the computer diεplays it on the monitor display. When the piston 314 reaches the upward limit in the syringe 310 and the location senεor PS7 detects the piston 314, the HPLC pump 101 and the gradient 102 are εtarted so as to feed the developer through the flow line Ll, first rotary valve 301, and the flow line L4 to the injector 304.

In the injector 304, the piston 314 at the upward limit in the syringe 310 is in a close contact with the lower surface of the head 326 to establiεh the εhort-cut flow line 328 between the inlet 305 and the outlet 306. Therefore, the developing εolvent from the inlet is transported to the outlet 306 through the short-cut 328 formed in the injector 304.

The chromatographic process starts at step #6 by starting the feeding the developer into the column 401. If all the sample remaining in the flow lines L4 and L5, and the short-cut 328 in the injector 304 has been cleaned up by the developer and then filled in the column 401, the first and second rotary valves 301 and 302 are changed as shown in Fig. 3 to feed the developer from the flow line L4 to the column 401 directly, to thereby prevent the presεure in the syringe 310 from increasing. The liquid discharged from the column 401 is fed through the third rotary valve 303 to the flow line L8 and the air in the liquid is then removed in the deaerator 501 as described above. The liquid iε then fed through the flow line L9 into the analyzer 601 for analyzing its component.

At steps #7 to #13, if the peak division is employed in the fraction, the computer always monitors the output of the analyzer 601 and presents the output as the curve on the display. Further, if the computer detects the peak and/or the inclination greater than the predetermined value, it changes the magnetic valve V13 so that the liquid can then be fed to the fraction collector 701. In this fraction collector 701, the liquid is divided into the test tubes. If all the posεible peak has been detected, the liquid division is completed.

If the time division or the volume division method is employed in the fraction collector, by changing the magnetic valve V14, the liquid is similarly fed to the fraction collector 702 and then divided into test tubes 705.

If the flow from step #7 to step #13 is completed, all the data is registered at step #14. Finally, the HPLC pump 101, detector 601, and the gradient 102 are switched off and the certain valves are changed at step #15.

Next, the sample container 2011 iε rinεed at εtep #16. Specifically, in this step, the vacuum pump 307 is driven and the magnetic valves V3 and V7 are opened to introduce the cleaning liquid from the cleaning-liquid container 204 to the sample container 2011. If the predetermined amount of cleaning liquid has been supplied in the container 2011, the magnetic valves V3 and then V7 are closed. Next, the magnetic valveε V9 and VI are opened, permitting the cleaning liquid in the container 2011 to be discharged through the first and second rotary valves 301 and 302 into the syringe 310 of the injector 304 and finally abandoned. With thiε cleaning process, the container 2011, syringe 310, valves and the flow lineε described are rinsed and then dried.

5. Different Embodiment

The injector can be used as a εupply unit for supplying a predetermined volume of liquid. For example, Fig. 10 shows an embodiment in which the injector is used for feeding a specific sample liquid selected from a plurality of sample containers 3481 to 3484 illustrated on the right side of the figure to a container or a waste tank on the left side of the same figure. In this supply unit, one common tube 341 is connected with an inlet tube 342 of the supply unit while another common tube 343 is connected with an outlet tube 344. A pressure pump 345 is communicated with a distal end of the common tube 341 remote from the injector 310.

The common tube 341 is fluid-coupled with branch tubes 3471, 3472, 3473, and 3474 through switching valves 3461, 3462, 3463, and 3464, respectively. The branch tubeε 3471, 3472, 3473, and 3474 are in turn connected with first, second, third, and fourth sample containers 3481, 3482, 3483, and 3484, respectively. The branch tubes 3471, 3472, 3473, and 3474 include optical sensors 3491, 3492 and 3493 respectively, each capable of εensing a liquid. The outlet tube 344 on the other hand is connected through a switching valve 350 with a common tube 343. This tube 343 is in turn connected through a switching valve 351 with a liquid receiver 353 such as flask through a branch tube 3521 and also with a waste tank 354 through a branch tube 3522. The waste tank 354 may be connected with a vacuum pump 355 aε εhown.

Diεcuεεion will be made to the operation in which a doεe of the first εample liquid in the container 3481 iε meaεured and then fed to the container 353 and then a doεe of the second sample liquid in the container 3482 is subsequently measured and fed to the same container 353.

In thiε operation, firεtly the valve 3461 iε switched and the valves 356 and pump 345 are cloεed εo that only the firεt εample iε fed to the injector 304 from the container 3481. Secondly, upon the rotation of the εtepper motor 322, the piston 314 in the upward limit starts it downward movement, which allows the first liquid to be supplied into the syringe 310 through the inlet 305. When the sensor PS5 detects a complete filling of a predetermined amount of sample is in the syringe 310, the downward movement of the piston 314 is halted.

Next, the valve 3461 is brought in position to disconnect between the tubes 341 and 3471 and the valve 350 is opened. Alεo, the εtepper motor 322 rotateε in a direction oppoεite to that at filling, which causes the piεton 314 to move upward. The rotation of the motor 322 is controlled so as to keep the pressure applied on the piston 314 below a predetermined value, e.g., 1.0 kg/cm². With the upward movement of the piston 314, the first sample liquid is fed through the outlet 306, tubes 344 and 343, valves 351, and the branch tube 3521 and then filled in the receiver 353.

When the piston 314 reaches the upward limit and is hence brought into contact with the head 326, the inlet 305 and the outlet 306 is communicated through the groove 327, i.e., the short-cut passage.

Also, if the sensor PS7 detects the piston 314 at its upward limit, the stepper motor halts and the valve 356 is switched so that a presεurized air from the pressure pump 345 is supplied to the short-cut 327 and the common tube 343 through the common tube 341.

The pressurized air is introduced in the passages 341, 342, 305, 327, 306, 344, 343, and 3521 so that the sample remaining in the pasεages 305, 327, and 306 can be completely fed into the receiver 353. Although the sample generally tends to remain in the upstream side of the syringe rather than in the downstream side thereof, i.e., in the tubes 341, 342, and the inlet 305, this is thoroughly removed therefrom. The fact that the sample has been removed from the syringe and/or lines is confirmed by the optical sensors PS5 and PS6.

As described above, the first sample is supplied to the receiver 353 without leaving any of it in the tubes or syringe, which also ensures the second sample in the 3482 to be measured and then transported into the receiver 353 according to the similar operation.

After the completion of the transporting operation of the first and the subsequent second sample from the containers 3481 and 3482 into the receiver 353, the flow lines are cleaned up. In this cleaning, the cleaning liquid is fed from the container 3484 into lines. Specifically, in the injector 304, the piston 314 is kept at its upward limit to meet the head 326 to maintain the short-cut passage 328. Simply by driving the vacuum pump 355, the cleaning liquid is readily sucked through the passages 341, 342, 305, 327, 306, 344, 343, and 3522 into the waste liquid tank 354 to clean up those pasεages. The cleaning and drying can be done in the εame way without using the pressure pump.

As described above, the injector measures and feeds a predetermined amount of liquid without leaving any of it in the fluid lines and passages. Particularly, this injector equally applied where the receiver 353 is a column for refining and dividing the liquid sample according to the chromatography. In this case, the sample is directly fed to the column by the injector without being forced by the subεequent developer, which preventε the εample from being diluted by the developer and alεo ensures a right division in the column. Besideε, the remaining sample is thoroughly fed to the column, which prevents the valuable εample from being lost.

As shown Fig. 11, which depicts a modification of the sample unit, a rotary type switching valve 357 may be used for selectively connecting the injector 304 to one of containerε 3581 to 3584 which εtore firεt to fourth samples or the container 3585 which stores the cleaning liquid, respectively. Note that in Fig. 11, reference numerals 3601 to 3604 represent an optical sensor for detecting the respective sample liquid. The injector can preferably be uεed for other purposes, for instance, for feeding liquids having different viscoεities. In this case, the liquid having high viscoεity iε measured in the syringe and then fed to the liquid receiver by forcing the piston, and the liquid having low viscosity is fed through the short-cut pasεage to the receiver.

6. Different Embodiment

Figε. 12A and 12B εhowε an different embodiment of the injector in which the piston 314, rather than the head 326, has a groove 361 defined therein so that, when the piston 314 reaches the upward limit, the groove 361 can be covered with the head 326 to form a short-cut paεεage which communicate the inlet 305 with the outlet 306. This embodiment can be operated in a manner similar to the previous embodiment in which the corresponding groove is formed in the head. Further, in order to prevent the piεton from rotating in the syringe and then to ensures the groove to meet with the inlet and outlet, a guide means such as at least one axial groove and asεociated member to be guided by the axial groove iε preferably employed.

7. Other Embodiment of Injector

Figε. 13 and 14 show a further different embodiment of the injector. This injector comprises a pressurized gas supply unit 365 in addition to the piston driving unit. The pressurized gas εupply unit 365 is to provide a second chamber 367 in the syringe 310 below the piston 314 with a pressure which corresponds to that in a first chamber 366 when the liguid in the first chamber is deεired to be diεcharged therefrom, εo aε to prevent the liquid in the firεt chamber from leaking into the second chamber through where the piston contacts with the inner surface of the syringe 310.

In this embodiment, the piston rod 315 is formed with a hollow cylindrical stainlesε pipe and itε interior 368 of the rod iε intended to be uεed aε a paεεage for the preεεurized gas. Further, the rod 315 has an opening 369 while its lower end extending through an through-hole 379 in a bottom wall 378 of the syringe 310 can be connected through a gas tube 370 of the gas supply unit 365 so that the pressurized gas from the unit 365 can be supplied into the second chamber 367 of the syringe 310 and the pressurized gas in the second chamber 367 is extracted therefrom. The opening 369 is so arranged as to exist in the second chamber 367 even when the piston 314 is positioned at its downward limit. Alεo, the rod 315 iε deεigned to have a diameter εubstantially equal to that of the through-hole 379 and is sealed, if necesεary, to prevent the preεsurized gas in the second chamber 367 from leaking therefrom.

The gas tube 370 connected with the rod 315 is a pressure tube which iε communicated through a εwitching valve 371 and a preεεure controller 372 with a container 373 of the preεεurized gas. The switching valve 371 and the presεure controller 372 are electrically connected with a control unit 374 εo that, baεed upon a εignal from the pressure sensor 329, the switching valve can be changed by the control unit 374 to let the presεurized gas in or out of the second chamber 367. Also, the pressure of the gas to be fed is controlled by the presεure controller 372 to keep the preεεure in the second chamber 367 substantially equal to that in the first chamber 366.

Preferably the switching valve 371 may be a three-way magnetic valve which includes three ports; the first port 3711 connected with the gas container 373 and usually closed; the second port 3712 connected with the piston rod 315 and usually opened, and the third port 3713 connected with an air-opened tube 375 and usually opened. In normal state at which no pressurized gas is introduced into the second chamber 367, the gas passage 368 in the rod 315 iε opened to the air. Only when the presεure in the firεt chamber 366 increaεeε by the upward movement of the piston 314, the switching valve iε εo changed aε to supply the pressurized gaε from the container 373 through the piεton rod 315 into the second chamber 367 of the syringe 310.

In this embodiment, the pressurized gas container 373 may be a compresεor having a filter for cleaning the gaε to be supplied. This ensures the second chamber 367 of the syringe 310 to be supplied with a clean gas. Also, the compressor is preferably equipped with a drain for extracting air.

In operation of the injector thus constructed, at sucking the liquid into the syringe, the stepper motor 322 is driven to rotate, which permits the piεton in the upward limit to move downward to introduce the liquid into the first chamber 366 of the εyringe 310 through a passage 377. At this time, if any presεurized gaε presents in the second chamber 367, the gas is discharged through the opening 369, gas passage 368, gas tube 370, switching valve 371, and further the gaε tube 375 to the air.

If the εtepper motor 322 haε rotated predetermined times and also the location sensor PS8 detects the piston 314, the stepper motor 322 is turned off to halt the piston 314. At this time, the syringe 310 accommodates a predetermined amount of liquid therein. Subεequently, the stepper motor 322 is rotated in the opposite direction to move the piston 314 upward, which causes the liquid in the syringe 314 to be discharged from the pasεage 377. At the upward movement of the piεton 314, the preεεure in the firεt chamber 366 can increaεe dramatically relative to that in the εecond chamber 367. If the preεsure applied on the piston 314 and in turn on the rod 315 is less than a predetermined value, i.e., l.o kg/cm², the switching valve 371 in the unit 365 is kept its normal state so that no presεurized gaε will εupplied from the container 373 into the second chamber 367.

At the upward movement of the piston 314, when the sensor 329 detects that the presεure in the first chamber has increased over the predetermined value, i.e., 1.0 kg/cm², the controller 374 changeε the switching valve 371 and the presεure controller 372. Specifically, in the switching valve 371, the firεt port 3711 iε opened and the third port 3713 is closed so that the pressurized gas will be introduced from the pressurized-gaε container 373 through the gaε tube 370 and the preεεure controller 372 into the second chamber 367 of the syringe 310. Also, the pressure of the gaε to be εupplied into the εecond chamber 367 from the container 373 iε kept at the εame pressure as that in the first chamber 366. The presεure in the firεt chamber 366 can be detected by the εensor 329.

Aε deεcribed above, since the pressure in the second chamber 367 is kept substantially equal to that in the firεt chamber 366, the liquid in the first chamber is kept from leaking through the contact area between the piston 314 and the facing inner surface of the syringe 310. Particularly, thiε preventε the liquid from leaking even when the εeal between the piεton 314 and the εyringe 310 haε degraded with use, which ensures all the predetermined liquid in the first chamber to be discharged therefrom. Note that the pressurized air is used simply for preventing the liquid from leaking, not for forcing the piston. That is, the movement of the piston and the measurement of the liquid are exclusively controlled by the motor.

When the piston 314 has reached the upward limit and has therefore finished the liquid diεcharging, the sensor PS7 detects the piston 314, causing the motor 322 to be turned off. Further the pressure on the piston 314 decreases below the predetermined value, i.e., 2.0 kg/cm², this is detected by the signal from the sensor 329 so that the controller 374 can cause the switching valve 371 to close the first port 3711 and open the third port 3713. By so doing, the presεurized air having been in the second chamber 367 is discharged into the air. If the motor is rotated in the opposite direction to force the piston 314 and the piston rod 315 downward right after the piston 314 has reached the upward limit, the pressurized air in the second chamber 367 is likewise diεcharged through the interior of the rod 315. 8. Modification of Injector

Fig. 15 shows a modification of the previous embodiment in which the piston 314 includes a hollow chamber 380 communicated with the interior 368 of the rod 315. Further, the piston 314 includes an opening 382 communicated with the εecond chamber 367 in the syringe 310. Therefore, in this embodiment in Fig. 15, the pressurized gaε is fed into the second chamber 367 and discharged therefrom through the opening 382 and the hollow chamber 380.

9. Modification of Injector

Fig. 16 shows a further modification of the injector in which no hollow chamber is formed in the piston or rod. Also, formed at the lower portion of the syringe 310 and under the lowermost position of the piεton 314 iε a hole 383 to which the preεεurized-gaε tube 370 of the gaε supply unit 365 (εee Fig. 13) iε connected. Thiε embodiment can be operated in a manner εimilar to the previous embodiments.

10. Different Modification of Injector

Fig. 17 εhows another modification of the injector pump in which a gas supply line and a gas discharge line are independently dispoεed. Specifically, a gas supply hole 383, formed in the εyringe under the lowermost position of the piston, is connected through the gas supply tube 385 to the valve 384. Also, a gas discharge hole 387, formed in the bottom wall 378 of the syringe 310, is connected through the gas tube 389 to the valve 388. In this embodiment in Fig. 17, normally, the valve 388 is closed so that the gas tube 390 connected with the container 373 through the pressure controller 372 can be disconnected from the gas tube 385. Also, the gas tube 389 communicates with the gas tube 390 by opening the valve 388, which enables the gas in the εecond chamber 367 to be diεcharged.

When introducing the pressurized gas into the second chamber 367, the valve 384 is brought in position to communicate the gas tubes 386 with 385 and the valve 388 is brought into position to uncommunicate the gas tubes 389 with 390, which permits the gas from the container to be introduced into the second chamber 367.

Although, in the embodiments shown Figs. 13 to 17 the syringe head 326 includes a passage 377 through which the liquid is introduced in and diεcharged out of the syringe 310, as shown in Figs. 18A and 18B, a pair of inlet 391 and outlet 392 and a groove, or short-cut pasεage 393 may be formed in the head 326 in place of the passage.

11. Modification of Deaerator Fig. 19 shows a modification of the deaerator in which only the lower sensor 510 is arranged while the upper εenεor iε eliminated. In this embodiment, unleεs the senεor 510 detects the liquid, the magnetic valve V12 is closed and the other magnetic valve V10 is opened. If the sensor 510 detects the liquid, the magnetic valve V12 opens and the magnetic valve V10 opened to air is closed.

Therefore, until the senεor 510 detects the liquid, i.e., the liquid has been accommodated in the container 502 up to the predetermined level, the air in the liquid has been removed. Also, when the liquid is detected by the sensor 510, the liquid becomes to be discharged from the discharge tube 507.

12. Other Use of Deaerator

Fig. 20 showε another uεe of the deaerator, in which the deaerator is dispoεed on a flow line 395 connected with the injector 396. With thiε arrangement, the air in the liquid is removed from the liquid before being transported to the injector 396, which ensures the injector 396 to measure a predetermined amount of liquid as precise as posεible. The deaerator of the invention may be disposed on any flow line in order to eliminate the air from the liquid.

While there iε εhown and deεcribed herein certain εpecific εtructureε embodying the invention, it will be manifest to those skilled in the art that various modifica¬ tions and rearrangements of the parts may be made without departing from the spirit and scope of the underlying inventive concept and that the same is not limited to the particular forms herein shown and described except insofar as indicated by the scope of the appended claims.

Claims

C L A I M S

1. An injector for measuring and then injecting a fluid, comprising:

(a) a generally cylindrical body, arranged vertical, which is closed at itε upper end with an end wall and opened at itε lower end, the upper end wall having an inlet and an outlet defined therein in spaced relation to each other;

(c) a piεton rod inεerted into the cylindrical body through the bottom end and coupled to the piεton for movement together therewith; and (d) one of reεpective εurface of the end wall and the piston which confront with each other includes a groove for defining a pasεage communicating between the inlet and the outlet.

2. An injector as claimed in claim 1, further includes:

(e) an elevating member, connected with the piston rod and having a threaded hole and a guide hole;

(f) a lead screw engaged with the threaded hole;

(h) a driving source for rotating the lead screw. 3. An injector as claimed in claim 2, further includes:

(i) means for detecting the piston which is in its upward limit; (j) means for detecting the piston which is in its downward limit;

(k) means for detecting a pressure applied on the piston; and

(1) means for driving the elevating member according to signals from the means (j) , (k) , and (1) .

4. An injector as claimed in claim 1, includeε: meanε for detecting the fluid in the vicinity of the inlet and outlet.

5. An injector for diεpensing a dose of liquid, comprising:

(a) a generally cylindrical body, arranged vertical, which includes its upper end a first wall having a first passage for introducing the fluid into the body and discharging the fluid from the body and its lower end a second wall having a second pasεage;

(b) a plunger which includes a rod extended through the second pasεage into the cylindrical body with itε periphery εlidably and seaiingly engaged with an inner surface of the second pasεage, a piεton accommodated within the cylindrical body with itε periphery εlidably and seaiingly engaged with an inner surface of the cylindrical body, whereby an interior of the cylindrical body is divided into a first chamber between the first wall and the piston and a second chamber between the second wall and the piston; (c) an actuator for moving the plunger in a longitudinal direction of the cylindrical body;

(d) a fluid source for feeding a pressurized fluid;

(e) a valve having a first, a second, and a third portε, the firεt and εecond ports or the second and third pots being selectively communicated each other, and the third port being opened to air;

(f) a first line which communicates between the first port and the pressurized fluid source;

(g) a second line which communicateε between the second port and the second chamber;

(h) a controller which controls the valve so that, when the plunger moves away from the first wall for introducing the fluid into the firεt chamber, the second and the third ports are communicated each other and, when the plunger moves towards the first wall for discharging the fluid from the first chamber, the first and the second ports are communicated each other.

6. An injector as claimed in claim 5, wherein the rod includes therein a hollow passage, one end thereof being opened to the second chamber and the other end thereof being communicated with the second line.

7. An injector as claimed in claim 5, the cylindrical body includes an opening through which the second line is communicated with the second chamber, the opening being arranged below the downward limit of the piston. 8. An injector as claimed in claim 5, further compriεeε means for detecting a presεure to be applied on the piεton so that, according to signals from the detector, the controller controls the valve.

9. An injector aε claimed in claim 5, further comprises means for detecting a presεure to be applied on the piston and meanε for controlling a preεεure of the fluid to be εupplied from the preεεurized fluid εupply source so as to keep a presεure in the εecond chamber equal to that in the firεt chamber, whereby the fluid is prevented from leaking from the first chamber to the second chamber.

10. An injector as claimed in claim 5, wherein the first pasεage compriεeε an inlet hole for introducing the fluid into the body and an outlet hole for diεcharging the fluid from the body, and the firεt wall or the piεton includes in its surface confronting the other a groove which defines a short-cut passage for communicating between the inlet and outlet holes when the piston meets the first wall. ll. An injector for measuring and then injecting a fluid, compriεing:

(a) a cylindrical body which iε arranged vertically, having its upper end a first wall which includes a first paεεage for introducing the fluid into the body and discharging the fluid from the body and its lower end a second wall which includeε a second passage; (b) a plunger which includes a rod extending through the second pasεage into the cylindrical body, an outer surface thereof being continuously in close contact with the second passage, and a piston connected with the rod in the cylindrical body, a peripheral surface of the piston being continuously in close contact with an inner surface of the cylindrical body, whereby an interior of the cylindrical body is divided into a first chamber between the first wall and the piston and a second chamber between the second wall and the piston;

(d) a fluid source for feeding a presεurized fluid;

(e) a firεt line which communicateε the εecond chamber with the pressurized fluid source;

(f) a second line which communicates the second chamber with air;

(g) a first valve which is dispoεed on the first fluid line; (h) a second valve which is dispoεed on the εecond fluid line;

(i) a controller which cloεeε the firεt valve and openε the second valve when the plunger moves away from the first wall for introducing the fluid into the first chamber and opens the first valve and closeε the εecond valve when the plunger moveε towardε the firεt wall for diεcharging the fluid from the firεt chamber.

12. An injector aε claimed in claim 11, wherein the first passage compriseε an inlet hole for introducing the fluid into the body and an outlet hole for diεcharging the fluid from the body, and the firεt wall or the piston includes in its surface confronting the other a groove which defines a short-cut pasεage for communicating between the inlet and outlet holes when the piston meets the first wall.

13. A deaerator for removing a gas from a mixture of the gas and a liquid, comprising:

(a) a container for accommodating the mixture;

(b) a tube, one end thereof being inserted in the container, the end having an intake which is arranged adjacent a bottom of the container, for extracting the liquid from the container;

(d) a supply line, communicated an interior of the container, for supplying the mixture into the container; (e) an exhaust line, arranged above the detector and communicated with the interior of the container, for exhausting the air from the container; (f) a firεt valve diεpoεed on the extracting tube;

(g) a εecond valve diεpoεed on the exhauεting line; (h) a controller which cloεes the first valve and opens the second valve when the detector does not detect the liquid and opens the firεt valve and closes the second valve when the detector detects the liquid.

14. A deaerator as claimed in claim 13, further comprising: a second detector, arranged above the firεt detector and below the exhaust line, for detecting the liquid.

15. A deaerator as claimed in claim 13, wherein the bottom of the container iε in the form of an inverted cone.

16. An apparatuε, having a deaerator and an injector, which removeε air from a liquid and then measures the liquid, comprising:

(A) the deaerator, which includes

(a-l) a container for accommodating the mixture;

(a-3) a detector, arranged above the intake, for detecting the liquid in the container; (a~4) a supply line, communicated an interior of the container, for supplying the mixture into the container; (a-5) an exhaust line, arranged above the detector and communicated with the interior of the container, for exhausting the air from the container;

(a-6) a first valve disposed on the extracting tube;

(a-7) a second valve dispoεed on the exhausting line;

(a-8) a controller which closes the first valve and opens the second valve when the detector does not detect the liquid and opens the first valve and closes the second valve when the detector detects the liquid; and (B) an injector which includes

(b-l) a cylindrical body which is arranged vertically, a top end thereof being closed by a wall and a bottom end thereof being opened, the wall including an inlet hole and an outlet hole, the inlet being communicated with the extracting tube;

(b-2) a piston which is movably arranged in the cylindrical body with its peripheral surface being in close contact with an inner surface of the body;

(b-3) a rod inserted in the cylindrical body and connected with the piston;

(b-4) wherein the wall or piεton includes in a surface confronting each other a groove which communicates between the inlet and outlet holes when the piston is close contact with the wall. 17. A refining apparatus, comprising: (a) a developer unit which mixes a plurality of developers and then delivers them;

(b) a sample unit which delivers a sample;

(c) a filling unit which includes c-1: an injector; c-2: a switching valve which firstly delivers the sample from the sample unit into the injector and secondly delivers the developers into the injector;

(d) a column unit, having a stationary phase, which transports the sample and the developers through the stationary phase;

(e) an analyzing unit for analyzing components of a liquid fed from the column unit;

(f) a division unit for dividing the liquid fed from the analyzing unit; and

(g) a control unit for controlling the units (a) to

(f>.

18. A refining apparatus as claimed in claim 17, wherein the developer unit includes a-l: a plurality of containers for accommodating respective developers; a-2: a gradient for extracting a plurality of developers from the containers in a certain rate; and a-3: a high performance liquid chromatography pump for delivering the developers mixed in the gradient at a certain velocity.

19. An automated refining apparatus as claimed in claim 17, wherein the sample supply unit includes b-l: a plurality of containers for accommodating the samples; and b-2: a plurality of valves for selectively communicating the containers with the switching valve.

20. An automated refining apparatus as claimed in claim 19, wherein each of sample containers is provided with at least one supplementary container for accommodating the corresponding sample. 21. An automated refining apparatus as claimed in claim 17, wherein the sample unit includes a connector for receiving a sample.

22. An automated refining apparatus as claimed in claim 17, wherein the injector includes an elevating member, having a threaded and a guide hole, which is connected with the rod; a lead screw engaged with the threaded hole; a guide member which cooperates with the guide hole to guide the elevating member; and a driving source for rotating the lead screw.

23. An automated refining apparatus as claimed in claim 17, wherein the column unit includes a plurality of columns and the filling unit supplies the selected column with the liquid. 24. An automated refining apparatus as claimed in claim 17, further includes a deaerator having a container for accommodating the mixture; a tube, one end thereof being inserted in the container, the end having an intake which is arranged adjacent a bottom of the container, for extracting the liquid from the container; a first detector, arranged above the intake, for detecting the liquid in the container; a supply line, communicated an interior of the container, for supplying the mixture into the container; an exhaust line, arranged above the detector and communicated with the interior of the container, for exhausting the air from the container; a first valve disposed on the extracting tube; a second valve dispoεed on the exhauεting line; a controller which cloεeε the first valve and opens the second valve when the detector does not detect the liquid and opens the first valve and closeε the second valve when the detector detects the liquid.

25. An automated refining apparatus claimed in claim 17, wherein the division unit includes a first fraction collector for a peak separation of the liquid and a second fraction collector for a volume separation of the liquid, and the liquid is supplied selectively to the first or second fraction collector.