US3859051A - Means for transferring a liquid in a capillary open at both ends to an analyzing system - Google Patents

Means for transferring a liquid in a capillary open at both ends to an analyzing system Download PDF

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US3859051A
US3859051A US388945A US38894573A US3859051A US 3859051 A US3859051 A US 3859051A US 388945 A US388945 A US 388945A US 38894573 A US38894573 A US 38894573A US 3859051 A US3859051 A US 3859051A
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capillary
capillaries
fluid
arrangement
flow path
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US388945A
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Samuel Natelson
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Rohe Scientific Corp
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Rohe Scientific Corp
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1095Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • G01N35/1097Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00237Handling microquantities of analyte, e.g. microvalves, capillary networks
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/1034Transferring microquantities of liquid
    • G01N2035/1039Micropipettes, e.g. microcapillary tubes

Definitions

  • ABSTRACT In a system for analyzing a fluid such as blood or blood plasma contained in capillaries, the capillaries, open at both ends, are filled with the fluid to be analyzed. These capillaries are carefully calibrated and serve as disposable pipets. The filled capillaries are disposed around a turntable or on a linear transport means and are brought to a work station. Fluid and air are pumped continuously by peristaltic action on flexible tubing through a bypass tube. When a capillary is brought into position, connection is made with a fluid hose on both ends of the capillaries. Valve means is provided which closes the bypass and opens the hose leading to the capillary.
  • the fluid and air are now pumped through the capillary. After a predetermined time, the fluid hose leading to the capillary is closed and the capillary is removed. The valve in the bypass system is now opened so that fluid now passes through the by-pass system. A second capillary is brought into place and the process is repeated until all the capillaries have been processed. The contents of the capillary are washed out, reagents are added, heating takes place if necessary, and finally the component being assayed is evaluated at a readout station.
  • the present invention relates to the transfer of liquid from a capillary to a system for chemical analysis, and more particularly to the transfer of a liquid to be analyzed by completely draining out a capillary without disturbing the capillary.
  • the contents of the capillary is removed by a mechanical means such as blowing air through the capillary for processing.
  • a mechanical means such as blowing air through the capillary for processing.
  • the contents of the capillary are removed by touching to paper and allowing it to run out.
  • the present invention provides for an arrangement for introducing minute quantities of a liquid sample into an analytical system.
  • a plurality of capillaries, open at both ends are disposed in parallel on a moving means which moves along a predetermined travel'path to a work station having thereon retaining means for retaining the capillaries.
  • flow means providing a continuous flow path having a by-pass and a main path. Wash fluid normally flows through the bypass.
  • Capillary holding means for passing the wash fluid through a capillary are provided in the main path.
  • Insert means are also located at the work station for in serting a capillary from the moving means into the capillary holding means.
  • control means coupled to and regulating the insert means and the movement of the moving means as well as the insert means are control means, which will move the moving means one capillary position at a time to the work station, operate the insert means to place the capillary in the main path and simultaneously shut the first valve to the by-pass and open the second valve to the capillary so that wash fluid will flow through the capillary. After the capillary is empty, the capillary is removed from the holding means.
  • FIG. la is a schematic and block diagram of the inventive concept when not acting on a capillary
  • FIG. 1b shows the schematic and block diagram of FIG. 1a when acting on a capillary
  • FIG. 10 is a perspective schematic explanation of a valve mechanism
  • FIG. 2 presents a perspective explanation of one version of the inventive concept
  • FIG. 2a illustrates one system of holding capillaries in cross-section
  • FIG. 2b shows another system of holding capillaries in crosssection
  • FIG. 2c again shows another system of holding capillaries in cross-section
  • FIG. 3 gives a perspective explanation of another version of the inventive concept
  • FIG. 3a is a detail of the perspective of a valve used in FIG. 3;
  • FIG. 3b is a perspective view of a by-pass switch arrangement
  • FIG. 4a gives a perspective view of yet another version of the inventive concept
  • FIG. 4b shows in perspective one of the components used in FIG. 4a
  • FIG. 4c is a perspective view of one of the units of FIG. 4b;
  • FIG. 4d presents in a view similar to FIG. 40, the complementary component to that shown in FIG. 40;
  • FIG. 5 and FIG. 5a are perspective explanations of the control arrangement for the instrument described herein;
  • FIG. 6a shows a lower plate on which capillaries are disposed for another version of the invention
  • FIG. 6b is a cover plate placed over and aligned with the lower plate of FIG. 6a;
  • FIG. 60 illustrates the assembly of the upper and lower plates of FIGS. 6a and 6b mounted on a turntable
  • FIG. 7a is a cross-sectional view of FIG. 6b
  • FIG. 7b is a cross-sectional version of FIG. 6a
  • FIG. is a sectional view of FIG. 7a and 7b in an assembled state
  • FIG. 8a presents a sectional view of another version of the inventive concept in the engaged state
  • FIG. 8b shows a portion of FIG. 8a, but in the retracted state
  • FIG. 9a also shows a perspective view of the inventive concept in another embodiment
  • FIG. 9b and 9c illustrate clamps used in FIG. 9a
  • FIG. 10a shows a molded plastic or rubber holder for holding capillaries in place
  • FIG. 10b is an assembly of the welded rubber holders of FIG. 10a forming a rack so as to assemble embodiment of the invention.
  • FIG. shows a detail of one variant of the embodiment of FIG. 10b.
  • FIG. 1a and 1b are schematic representations of the principle by means of which this new invention operates. Liquid is propelled by means of a peristaltic pump 11. This action has been described in US. Pat. No. 3,489,525.
  • the peristaltic pump 11 is used to move the contents of the capillary to the work station 13 by pushing or by aspiration through the capillary. In the latter case, the peristaltic pump would be placed on the other side of the capillary before the work station.
  • Two paths are provided in FIG. la and lb, the by-pass path 15 goes directly to the work station of analysis, and the other path is the main line 18 and goes to the analysis work station only after it has passed through the capillary.
  • valve 17 and 19 By means of valves 17 and 19, the solution may alternately pass through either of the two paths 15 or 18.
  • Valve 17 and 19 are shown in FIG. 1c and consists of a stationary wheel 21 with two outlets 23, 25, one to by-pass and the other to the capillary. Connection to one of the two outlets is made by means of a rotary wheel 27.
  • a reversing motor is provided to turn a cam 31.
  • the cam 31 has a single depression 33 to activate either of two switches 35, 37 180 apart. In the position shown, the first switch 35 is activated and the solution flows to the by-pass. If rotated 180 the second switch 37 would be activated, and the fluid would flow to the capillary.
  • FIG. la there is shown a by-pass hose 15.
  • the bypass tube valve 19 is open while the fluid hose line 18 is clamped shut so that no fluid flows through the capillary line.
  • FIG. 1a there is no capillary in place.
  • FIG. lb the capillary 47 is shown in place.
  • the bypass hose valve 19 is clamped shut and the fluid hose valve 17 to the capillary is open.
  • the fluid now pumps through the capillary washing it out completely and bringing its contents to the zone of analysis.
  • FIG. 2 shows one form of the instrument.
  • the capillaries 47 are held in claims 51 on a chain drive 53. Each capillary 47 comes into position between two rubber or plastic receiver funnels 55. Silicone rubber is very suitable for this purpose. These funnels are held by pincerlike clamps 57 pulled together by a spring 59. A motor 6] driving an oval cam 63 alternately spreads the pincer apart and lets it come together. When the pincer comes together, the funnels engage both ends of the capillary 47 and a seal is formed. A pair of limit rods 65 prevent excessive pressure on the capillary. These limit rods'also close a circuit as they come together. This signals the valve motor 29 shown in FIG. so that the flow now goes through the capillary instead of the by-pass.
  • the fluid hoses to and from the capillary are provided with slack so as to permit the connection to the capillary to take place.
  • the capillary abuts the receiver funnel to make a seal.
  • the opening of the tubes at the base of the funnels is slightly larger than the capillary so that the capillary slides into the tubes at both ends.
  • the spring draws the funnels together, it stretches the hose which causes it to tighten on the capillary and provide a seal caused by the constriction of the flexible hose as it is stretched. This is shown in FIG. 20.
  • the capillaries are brought sequentially to the work station on chain 53, by motor 69 which is activated intermittently by the mechanism of FIG. 5.
  • the funnels are moved apart by the oval cam 63.
  • the chain 53 advances, driven by the chain motor 69 and the next capillary is brought into place for processing.
  • the washed out capillaries go over the end of the sprocket, they drop into a box or catch basin for disposal.
  • FIG. 3 Another variation of this instrument is shown in FIG. 3.
  • the pincer clamps of FIG. 2 are replaced by a first silicone rubber funnel 55a in a flexible steel clamp 57a.
  • the capillary is held in a bed 70 on a circular plate 72. It moves into place and is pushed toward the funnel 55a held in flexible steel support 58.
  • This is accomplished by a spring 71 oppositeto the first funnel and located between a bearing support 73 and a spring stop 75 secured on a slide rod 77.
  • a motor driven cam 81 alternately releases or pushes the slide rod 77, thus compressing the spring.
  • This causes a second rubber funnel 55b attached to a pivoted rod 79 to alternately push on the capillary or be pulled back.
  • the slide rod 77 is operated by cam 81.
  • the cam releases the spring 71
  • the second funnel 55b moves forward and engages the capillary. It now slides it forward in its bed 70 into the funnel 55a supported on the flexible steel support 58, pushing the funnel 55a backwards.
  • the capillary is now held securely between the two funnels 55a, 55b.
  • the movement of the flexible steel support 58 closes a switch 83 which inactivates a solenoid 85 to open fluid hose 18 leading to the capillary. This closes the by pass tube 15 by pressing the tube to metal support 87.
  • the solenoid 85 is activated the armature is pulled back so as to seal the tubing leading to the capillary and open the by-pass tube.
  • solenoid 85 is again inactivated, the flow is only through the capillary, and this happens only when a capillary is in place.
  • the motor operating the cam 81 is activated from a central control box shown in FIG. 5 and the cam moves 180. This pushes the slide rod 77 releasing the capillary.
  • the flexible steel support 58 also pushes the capillary close to the original position it held on the turntable. As the turntable moves over, the capillary continues to be pushed back as it slides out of and leaves the first funnel 55a. The capillary thus ends up essentially in its original position and the process is repeated.
  • the capillaries 47 are alternatively disposed on a circular ring 89 which rotates under the control of a Geneva movement which moves the capillaries sequentially to the work station.
  • the capillaries 47 are placed in soft plastic supports 70a.
  • the work station 91 has a lift mechanism 93 consisting of a lift cam 95 operated by a motor 97 disposed to move under the circular ring 89.
  • a lift plate 99 is disposed over the cam 95. This will be lifted and lowered by the cam thus'lifting a U-shaped member 101 wherein the U" is carried by the plate 99.
  • At the upper ends of the U-shaped member are silicone rubber supports 103 sealed to metal backing, which are normally below the level of the circular ring 89.
  • the arms 105 of the U-shaped member on which these supports 103 are mounted act as thrust rods which go through bearings 106.
  • a spring stop 108 is mounted on the thrust rod so as to support the spring 109 forcing the lift plate 99 down on a lift cam 95 operated by a motor.
  • 105 is a second spring and spring stop assembly.
  • the lift cam 95 causes the lift plate to rise, compressing the springs 109 and 105.
  • the silicone rubber supports 103 now lift up the capillary 47 from its position on the turntable, to bring it flush with a corresponding silicone form 103a also with a metal backing which is mounted rigidly.
  • the cam 95 forces the capillary into line with a nipple 111 from the flexible tubing so as to cause fluid from a peristaltic pump to flow through the capillary to an analyzer.
  • the valve to the by-pass is opened when the lift cam is in the position to lift the lift plate.
  • the valve of the by-pass tube is closed at this time.
  • the valve to the by-pass now opens and the fluid valve to the capil lary is now closed. The solution then moves, driven by the peristaltic pump, through the by-pass tube.
  • FIG. 4a The action of the instrument in FIG. 4a depends upon the shape of the support 103 designed to grasp the capillary 47 and hold it in the fluid hose line.
  • the lower rubber support 103 is seen which is to be lifted to meet the bottom part of the upper form 103a in FIG. 4d.
  • the forms supports surface are biased so as to cause the capillary to roll into the center channel.
  • a nipple 111 is sealed to the upper rubber form 103a.
  • the center channel remains open but the resilient rubber forms a flat seal with the nipple 111 on one side and the capillary on the other.
  • FIG. 4b where the assembly is clamped together making a passageway from fluid nipple 111, through the .center channel and finally through the capillary to the second clamped assembly.
  • FIG. 5 is an explanation of the control circuit which controls all operations.
  • a timing sychronous motor 107 turns so that a cycle is complete every 50 seconds.
  • a second timing synchronous motor 29 complete a cycle in 60 seconds and turns cam 1l5b. Normally, the synchronous motor would turn until a first switch 109a in series with motor 107 falls into the deperssion opening the circuit. The motor 107 then stops. The second, third, etc., cams 111, 113, 114 are now aligned in their proper position.
  • On signal from by-pass switch 115 which is now closed momentarily, motor 107 will start, compress switch 109a and continue to complete a cycle, that is until switch 109a again falls into the depression of cam 109.
  • switch 1 I la When switch 1 I la is tripped, it gives a by-pass to the movement which moves the turntable or chain one space. When the switch 113a is tripped it causes the flow of fluid to go through the by-pass. The cycle is then repeated as the synchronous motor continues to run. If a by-pass is not given, the synchronous motor will stop itself when switch 109a opens.
  • motor 107 In operation, one activates motor 107 by closing switch 110. The motor completes a cycle and stops. One then closes switch 110a. Motor 29 now cycles periodically giving a by-pass to motor 107. This causes motor 107 to complete a cycle activating all the components of the system. It then stops and waits for a second by-pass from switch 115. Motor 29 runs therefore slower than motor 107 in order not to upset the order of the system.
  • FIG. 5a also shows how the signal from cam 39a is relayed to the motor of FIG. 10.
  • the circuit of work motor 29 goes through two switches 115 and 115a 180 apart which are in series with each other. If either switch is in one of the depressions of cam 115b, the motor stops, i.e., the motor runs until one of the switches falls into the depression when the motor stops. A by-pass from switches 40, 40a will start the motor going. Thus, the motor will turn the cam 180 each time and then stop. This is also seen in FIG. 3b as it alternately gives a by-pass to the solenoid value of FIG. 3a.
  • FIGS. 1 through 4 the capillary is secured at the ends to make a seal so that liquid may flow through it.
  • FIG. 4a the capillary is lifted to the work station.
  • This same purpose may be accomplished by clamping the capillaries to a table in such a way that they are secured within a flexible clamp made of rubber or plastic.
  • the mechanism bringing the fluid to the capillary does not touch the capillary but brings the fluid to the rubber clamp and also removes it from the clamp. This has the advantage that the capillary is protected from breakage. How this is accomplished may be seen in FIGS. 6a, 6b and 6c.
  • the capillary 47 filled with sample is placed in a recess in a plate assembly 153 having a circular lower plate 152 made of soft rubber 148 approximately V2 inch thick and backed with metal 151 for support. Two ridges circle the plate and have recesses 149 in them to act as a bed 157 for the capillary 47, but still prevent the edges of the capillary from touching a surface. This is done to prevent fluid from leaving the capillary by capillary action.
  • the edges of the capillary are at the beginning of a flare a or widening opening. The object of the flare is to eventually form a rubber funnel 155 as in FIG. 2 and 7c.
  • the circular lower plate 152 has three holes 159 for attachment to a turntable 161 and an upper plate 154 or cover.
  • the upper plate 154 is seen in FIG. 6b and is similar to the lower plate 152 in FIG. 6a. It also has two ridges 150a, but is made of softer rubber 148a (silicone) and does not have depressions in the ridges. This upper plate is a cover and aligns with the lower plate by means of the three holes 159a. It also has upper flares 155C, and a metal backing 151a.
  • the upper plate 154 is now threaded on the binding posts 165 of the turntable so that the lower rubber 148 faces the upper rubber 148a.
  • Wing nuts 167 are now tightened so that the upper ridge 150a is compressed forming a double seal, one for each ridge around the capillary.
  • the flares 155a, I55b on the upper and lower plates now meet to form a funnel 155.
  • FIG. 7a a cross-section of the top plate is shown to show the two ridges 150a, rubber 148a and backing metal plate 151a.
  • FIG. 7b shows a cross section showing the capillary 47 resting on the lower ridges 150 of the lower plate 152 supported on rubber 148 and a backing metal plate 151. The ends of the capillary do not touch.
  • FIG. 70 a cross section is shown showing how the upper plate 154 meets the lower plate 152 and how a funnel 155 is formed from the flares 155a and 15512 on the upper and lower plate.
  • the fluid is brought to the capillary by detents 169 which contain a valve system 171.
  • detents 169 which contain a valve system 171.
  • the detents are inwardly biased by a clamp and spring arrangement 159 similar to that hereinbefore described.
  • the detents 169 have nipples 173 which can be pushed back and will return because of an enclosed weak spring 175, in the casing of the detent assembly. As the nipple 173 is pushed back, the spring is compressed as in FIG. 8b, the feed line opening 177 is blocked by the detent wall 179 acting as a piston 181.
  • the detents 169 slip into the funnel like depression opening the flow path through capillary 47.
  • the detents 155 move out of the depression and like in FIG. 8b are pushed back sealing off the liquid flow. This continues until all the capillaries on the table have been emptied.
  • FIG. 9a shows such a rubber mold from 253.
  • the operator pushes the capillary 47 down the slits 249 to the channel in the rubber mount 257 designed to hold it.
  • the rubber mount 257 in this case is ofa higher durometer of approximately 70 80 so as to hold the tube firmly.
  • a clamp in the form of a single spring clip 254 or double spring clip 254a may also be used to tighten on the rubber mount 253.
  • the spring clips serve to clamp the slit rubber mount 253 together and hold it tightly.
  • the molded forms 253 are disposed around a turntable and serve the same function as that of FIG. 6c, which clamp the capillaries with a cover.
  • FIG. 9a Amodification of FIG. 9a is to use a single molded rubber form 260 in the shape of a double funnel, 258 and 259, as shown in FIG. 10. These are made of flexible plastic or rubber so that the operator can push them back and insert a capillary loaded with sample. As they spring back they hold the capillary tightly.
  • the flexible forms also may be mounted in a circular or linear mode. lnFIG. 1012 they are mounted in a linear mode ganged together to form a rack 261.
  • Approximately 20 of the molded soft rubber forms with double funnels 258, 259 shown in FIG. 10a are stacked with a metal spacer 264 between them as shown in FIG. 10b.
  • the metal spacers extend on both sides 262, although only one side is needed, so as to be able to intercept a trip switch 269a.
  • the operator inserts the loaded capillary 47, full of sample, into the two opposing holes so as to form a seal.
  • the flexible rubber can be pushed back and forth somewhat between the spacers permitting the insertion of the capillaries.
  • the whole rack rests and is sealed to a metal plate 263.
  • the spacer extensions take the place of the test tubes so that the rack advances one spacer and stops.
  • the nipples 269 and 265 are now inserted on both sides and the peristaltic pump pumps the fluid from a reservoir to the analyzing system washing out the capillaries. Flow is through tube 268 to nipple 269 held by clamp 267 to armature 266 of solenoid 266b through the capillary and through the nipple 265 to be analyzed.
  • a by-pass is given to the trip switch 268 from the control box which causes the rack to advance one space.
  • the nipples are inserted by inactivation of the.
  • FIG. shows the capillary 47 in place and the plastic nipples 265 and 269 pushed forward so as to make a continuous flow system, from wash fluid to peristaltic pump 11 and tube 18 through the first nipple 269, the capillary 47, the second nipple 265 and finally to the analysis area.
  • FIG. 5a a cam and switch arrangement FIG. 5a is used to give a by-pass.
  • a by-pass from the control box FIG. 5a shorts a cam switch 272 causing the motor to be activated by the line current.
  • a cam 276 makes a turn and comes to rest since the cam switch is now open and in series with the line and the motor.
  • the movement of the first cam pulls back the first plastic nipple 269.
  • the cam 276 is tied to a second cam 278 by sprockets and a ladder chain 271.
  • the second cam also moves 180 simultaneously pulling back the second plastic nipple 265. This releases the rack of FIG. 10a.
  • a by-pass trip switch from the control box FIG. 5a permits the rack to be pushed forward one space.
  • a by-pass to the first cam from the control box causes the cam to rotate 180 and again insert both nipples 269 and 265 into the soft rubber capillary support.
  • the flow of fluid starts through the capillary and the process is repeated.
  • Solenoids may be used in place of the motor to retract or insert the nipple into the funnels of the soft rubber capillary support.
  • An arrangement for introducing minute quantities of a liquid sample into an analytical system comprising in combination:
  • a. moving means moving along a predetermined travel path to a work station having thereon retaining means for horizontally retaining a plurality of sample containing capillaries open at both ends in parallel;
  • sealing means operatively connected to said work station for sequentially sealing the capillaries into the work station without leakage.
  • An arrangement as claimed in claim 1 including flow means providing a flow path at said work station so that a work fluid may flow through said capillary.
  • a method for introducing minute quantities of a liquid sample into an analytical system comprising the steps of:
  • An arrangement for introducing minute quantities of a liquid sample into an analytical system comprising in combination:

Abstract

In a system for analyzing a fluid such as blood or blood plasma contained in capillaries, the capillaries, open at both ends, are filled with the fluid to be analyzed. These capillaries are carefully calibrated and serve as disposable pipets. The filled capillaries are disposed around a turntable or on a linear transport means and are brought to a work station. Fluid and air are pumped continuously by peristaltic action on flexible tubing through a by-pass tube. When a capillary is brought into position, connection is made with a fluid hose on both ends of the capillaries. Valve means is provided which closes the by-pass and opens the hose leading to the capillary. The fluid and air are now pumped through the capillary. After a predetermined time, the fluid hose leading to the capillary is closed and the capillary is removed. The valve in the by-pass system is now opened so that fluid now passes through the by-pass system. A second capillary is brought into place and the process is repeated until all the capillaries have been processed. The contents of the capillary are washed out, reagents are added, heating takes place if necessary, and finally the component being assayed is evaluated at a readout station.

Description

United States Patent [191 Natelson Jan.7, 1975 MEANS FOR TRANSFERRING A LIQUID IN A CAPILLARY OPEN AT BOTH ENDS TO AN ANALYZING SYSTEM [75] Inventor: Samuel Natelson, Chicago, 111.
[73] Assignee: Rohe Scientific Corp., Santa Ana,
Calif.
[22] Filed: Aug. 16, 1973 [21] Appl. No.: 388,945
[52] US. Cl 23/259, 23/253 R, 141/130 [51] Int. Cl. G0ln 1/14, GOln 1/18 [58] Field of Search 23/253 R, 259, 292, 230 B;
Primary Examiner-R. E. Serwin Attorney, Agent, or Firm-George B. Oujevolk [57] ABSTRACT In a system for analyzing a fluid such as blood or blood plasma contained in capillaries, the capillaries, open at both ends, are filled with the fluid to be analyzed. These capillaries are carefully calibrated and serve as disposable pipets. The filled capillaries are disposed around a turntable or on a linear transport means and are brought to a work station. Fluid and air are pumped continuously by peristaltic action on flexible tubing through a bypass tube. When a capillary is brought into position, connection is made with a fluid hose on both ends of the capillaries. Valve means is provided which closes the bypass and opens the hose leading to the capillary. The fluid and air are now pumped through the capillary. After a predetermined time, the fluid hose leading to the capillary is closed and the capillary is removed. The valve in the bypass system is now opened so that fluid now passes through the by-pass system. A second capillary is brought into place and the process is repeated until all the capillaries have been processed. The contents of the capillary are washed out, reagents are added, heating takes place if necessary, and finally the component being assayed is evaluated at a readout station.
16 Claims, 30 Drawing Figures ENIEDJAH H975 SHEET 030F 15 JQLIf PATENTEDJAN 71975 SHEEI 05 0F 15 mmm u ME n PATENTED JAN 7 SHEU 08 0F 15- PATENTEDJAN 1915 SHEET 07 0F 15 PATENTEDJAN Hers SHEET 080F15 PATENTED sum 09m 15.
PAn-tmenmmzs 3859.051
I SHEET lfJUF 15 PATENIED 3,859,051
sum llflF 15 PATENTEU JAN 7 I975 SHEEI IBUF 15 PATENTEDJAN H915 3,859,051
' sum 150? 15 MEANS FOR TRANSFERRING A LIQUID IN A CAPILLARY OPEN AT BOTH ENDS TO AN ANALYZING SYSTEM BACKGROUND OF THE INVENTION The present invention relates to the transfer of liquid from a capillary to a system for chemical analysis, and more particularly to the transfer of a liquid to be analyzed by completely draining out a capillary without disturbing the capillary.
BRIEF DESCRIPTION OF THE PRIOR ART In earlier patents, procedures are described for processing capillaries in order to remove their contents and proceed with chemical analysis of the contents. Examples of this technique are to be seen in US. Pat. Nos. 3,489,525, 3,331,665, 3,260,413 and 3,575,220.
In each case, the contents of the capillary is removed by a mechanical means such as blowing air through the capillary for processing. In one case (US. Pat. No. 3,575,220) the contents of the capillary are removed by touching to paper and allowing it to run out.
All of these methods suffer from the fact that some material is left on the walls of the capillary. It is much more accurate to wash out the contents of the capillary into the system of analysis. The present invention provides such an arrangement. Further, when small volumes are used, of less than p.l, the narrow capillary is difficult to empty and holdback on the walls becomes a major limiting factor.
SUMMARY OF THE INVENTION Generally speaking, the present invention provides for an arrangement for introducing minute quantities of a liquid sample into an analytical system.
A plurality of capillaries, open at both ends are disposed in parallel on a moving means which moves along a predetermined travel'path to a work station having thereon retaining means for retaining the capillaries. At the work station, there are flow means providing a continuous flow path having a by-pass and a main path. Wash fluid normally flows through the bypass. Capillary holding means for passing the wash fluid through a capillary are provided in the main path. Insert means are also located at the work station for in serting a capillary from the moving means into the capillary holding means. Also, coupled to and regulating the insert means and the movement of the moving means as well as the insert means are control means, which will move the moving means one capillary position at a time to the work station, operate the insert means to place the capillary in the main path and simultaneously shut the first valve to the by-pass and open the second valve to the capillary so that wash fluid will flow through the capillary. After the capillary is empty, the capillary is removed from the holding means.
The invention, as well as other objects and advantages thereof will become more apparent from the following detailed description when taken together with the accompanying drawings, in which:
BRIEF DESCRIPTION OF THE DRAWINGS FIG. la is a schematic and block diagram of the inventive concept when not acting on a capillary;
FIG. 1b shows the schematic and block diagram of FIG. 1a when acting on a capillary;
FIG. 10 is a perspective schematic explanation of a valve mechanism;
FIG. 2 presents a perspective explanation of one version of the inventive concept;
FIG. 2a illustrates one system of holding capillaries in cross-section;
FIG. 2b shows another system of holding capillaries in crosssection;
FIG. 2c again shows another system of holding capillaries in cross-section;
FIG. 3 gives a perspective explanation of another version of the inventive concept;
FIG. 3a is a detail of the perspective of a valve used in FIG. 3;
FIG. 3b is a perspective view of a by-pass switch arrangement;
FIG. 4a gives a perspective view of yet another version of the inventive concept;
FIG. 4b shows in perspective one of the components used in FIG. 4a;
FIG. 4c is a perspective view of one of the units of FIG. 4b;
FIG. 4d presents in a view similar to FIG. 40, the complementary component to that shown in FIG. 40;
FIG. 5 and FIG. 5a are perspective explanations of the control arrangement for the instrument described herein;
FIG. 6a shows a lower plate on which capillaries are disposed for another version of the invention;
FIG. 6b is a cover plate placed over and aligned with the lower plate of FIG. 6a;
FIG. 60 illustrates the assembly of the upper and lower plates of FIGS. 6a and 6b mounted on a turntable;
FIG. 7a is a cross-sectional view of FIG. 6b;
FIG. 7b is a cross-sectional version of FIG. 6a;
FIG. is a sectional view of FIG. 7a and 7b in an assembled state;
FIG. 8a presents a sectional view of another version of the inventive concept in the engaged state;
FIG. 8b shows a portion of FIG. 8a, but in the retracted state;
FIG. 9a also shows a perspective view of the inventive concept in another embodiment;
FIG. 9b and 9c illustrate clamps used in FIG. 9a;
FIG. 10a shows a molded plastic or rubber holder for holding capillaries in place;
FIG. 10b is an assembly of the welded rubber holders of FIG. 10a forming a rack so as to assemble embodiment of the invention; and,
FIG. shows a detail of one variant of the embodiment of FIG. 10b.
DETAILED DESCRIPTION FIG. 1a and 1b are schematic representations of the principle by means of which this new invention operates. Liquid is propelled by means of a peristaltic pump 11. This action has been described in US. Pat. No. 3,489,525. The peristaltic pump 11 is used to move the contents of the capillary to the work station 13 by pushing or by aspiration through the capillary. In the latter case, the peristaltic pump would be placed on the other side of the capillary before the work station. Two paths are provided in FIG. la and lb, the by-pass path 15 goes directly to the work station of analysis, and the other path is the main line 18 and goes to the analysis work station only after it has passed through the capillary. By means of valves 17 and 19, the solution may alternately pass through either of the two paths 15 or 18. Valve 17 and 19 are shown in FIG. 1c and consists of a stationary wheel 21 with two outlets 23, 25, one to by-pass and the other to the capillary. Connection to one of the two outlets is made by means of a rotary wheel 27. A reversing motor is provided to turn a cam 31. The cam 31 has a single depression 33 to activate either of two switches 35, 37 180 apart. In the position shown, the first switch 35 is activated and the solution flows to the by-pass. If rotated 180 the second switch 37 would be activated, and the fluid would flow to the capillary. If the motor reverses, the cam 31 would turn 180, the first switch would be activated and the solution would again go through the by-pass. The two switches are in series with the motor. When either switch wheel falls into the depression in the cam, the motor stops. The method of giving the by-pass to the valve of FIG. 10 is shown in FIG. a and 5b, and will be hereinafter discussed.
In FIG. la there is shown a by-pass hose 15. The bypass tube valve 19 is open while the fluid hose line 18 is clamped shut so that no fluid flows through the capillary line. In FIG. 1a there is no capillary in place.
In FIG. lb the capillary 47 is shown in place. The bypass hose valve 19 is clamped shut and the fluid hose valve 17 to the capillary is open. The fluid now pumps through the capillary washing it out completely and bringing its contents to the zone of analysis.
FIG. 2 shows one form of the instrument. The capillaries 47 are held in claims 51 on a chain drive 53. Each capillary 47 comes into position between two rubber or plastic receiver funnels 55. Silicone rubber is very suitable for this purpose. These funnels are held by pincerlike clamps 57 pulled together by a spring 59. A motor 6] driving an oval cam 63 alternately spreads the pincer apart and lets it come together. When the pincer comes together, the funnels engage both ends of the capillary 47 and a seal is formed. A pair of limit rods 65 prevent excessive pressure on the capillary. These limit rods'also close a circuit as they come together. This signals the valve motor 29 shown in FIG. so that the flow now goes through the capillary instead of the by-pass.
In FIG. 2 the fluid hoses to and from the capillary are provided with slack so as to permit the connection to the capillary to take place. In FIG. 2a, the capillary abuts the receiver funnel to make a seal. In FIG. 2b the opening of the tubes at the base of the funnels is slightly larger than the capillary so that the capillary slides into the tubes at both ends. As the spring draws the funnels together, it stretches the hose which causes it to tighten on the capillary and provide a seal caused by the constriction of the flexible hose as it is stretched. This is shown in FIG. 20.
In the embodiment of FIG. 2, the capillaries are brought sequentially to the work station on chain 53, by motor 69 which is activated intermittently by the mechanism of FIG. 5.
After a predetermined period of time, the funnels are moved apart by the oval cam 63. The chain 53 advances, driven by the chain motor 69 and the next capillary is brought into place for processing. As the washed out capillaries go over the end of the sprocket, they drop into a box or catch basin for disposal.
Another variation of this instrument is shown in FIG. 3. In this case, the pincer clamps of FIG. 2 are replaced by a first silicone rubber funnel 55a in a flexible steel clamp 57a. The capillary is held in a bed 70 on a circular plate 72. It moves into place and is pushed toward the funnel 55a held in flexible steel support 58. This is accomplished by a spring 71 oppositeto the first funnel and located between a bearing support 73 and a spring stop 75 secured on a slide rod 77. A motor driven cam 81 alternately releases or pushes the slide rod 77, thus compressing the spring. This causes a second rubber funnel 55b attached to a pivoted rod 79 to alternately push on the capillary or be pulled back. Thus, the slide rod 77 is operated by cam 81. When the cam releases the spring 71, the second funnel 55b moves forward and engages the capillary. It now slides it forward in its bed 70 into the funnel 55a supported on the flexible steel support 58, pushing the funnel 55a backwards. The capillary is now held securely between the two funnels 55a, 55b. The movement of the flexible steel support 58 closes a switch 83 which inactivates a solenoid 85 to open fluid hose 18 leading to the capillary. This closes the by pass tube 15 by pressing the tube to metal support 87. When the solenoid 85 is activated the armature is pulled back so as to seal the tubing leading to the capillary and open the by-pass tube. When solenoid 85 is again inactivated, the flow is only through the capillary, and this happens only when a capillary is in place.
After a predetermined time, the motor operating the cam 81 is activated from a central control box shown in FIG. 5 and the cam moves 180. This pushes the slide rod 77 releasing the capillary. The flexible steel support 58 also pushes the capillary close to the original position it held on the turntable. As the turntable moves over, the capillary continues to be pushed back as it slides out of and leaves the first funnel 55a. The capillary thus ends up essentially in its original position and the process is repeated.
In FIG. 4a the capillaries 47 are alternatively disposed on a circular ring 89 which rotates under the control of a Geneva movement which moves the capillaries sequentially to the work station. The capillaries 47 are placed in soft plastic supports 70a. The work station 91 has a lift mechanism 93 consisting of a lift cam 95 operated by a motor 97 disposed to move under the circular ring 89. A lift plate 99 is disposed over the cam 95. This will be lifted and lowered by the cam thus'lifting a U-shaped member 101 wherein the U" is carried by the plate 99. At the upper ends of the U-shaped member are silicone rubber supports 103 sealed to metal backing, which are normally below the level of the circular ring 89. The arms 105 of the U-shaped member on which these supports 103 are mounted act as thrust rods which go through bearings 106. A spring stop 108 is mounted on the thrust rod so as to support the spring 109 forcing the lift plate 99 down on a lift cam 95 operated by a motor. 105 is a second spring and spring stop assembly.
When the capillary 47 comes into place, the lift cam 95 causes the lift plate to rise, compressing the springs 109 and 105. The silicone rubber supports 103 now lift up the capillary 47 from its position on the turntable, to bring it flush with a corresponding silicone form 103a also with a metal backing which is mounted rigidly. The cam 95 forces the capillary into line with a nipple 111 from the flexible tubing so as to cause fluid from a peristaltic pump to flow through the capillary to an analyzer. The valve to the by-pass is opened when the lift cam is in the position to lift the lift plate. The valve of the by-pass tube is closed at this time. When the lift cam rotates 180 the press plates drip down returning the capillary to its original holder. The valve to the by-pass now opens and the fluid valve to the capil lary is now closed. The solution then moves, driven by the peristaltic pump, through the by-pass tube.
The action of the instrument in FIG. 4a depends upon the shape of the support 103 designed to grasp the capillary 47 and hold it in the fluid hose line. In FIG. 40 the lower rubber support 103 is seen which is to be lifted to meet the bottom part of the upper form 103a in FIG. 4d. The forms supports surface are biased so as to cause the capillary to roll into the center channel. A nipple 111 is sealed to the upper rubber form 103a. As the lower support and the upper form meet and are pressed together, the center channel remains open but the resilient rubber forms a flat seal with the nipple 111 on one side and the capillary on the other. This can best be seen from FIG. 4b where the assembly is clamped together making a passageway from fluid nipple 111, through the .center channel and finally through the capillary to the second clamped assembly.
FIG. 5 is an explanation of the control circuit which controls all operations. A timing sychronous motor 107 turns so that a cycle is complete every 50 seconds. A second timing synchronous motor 29 complete a cycle in 60 seconds and turns cam 1l5b. Normally, the synchronous motor would turn until a first switch 109a in series with motor 107 falls into the deperssion opening the circuit. The motor 107 then stops. The second, third, etc., cams 111, 113, 114 are now aligned in their proper position. On signal from by-pass switch 115 which is now closed momentarily, motor 107 will start, compress switch 109a and continue to complete a cycle, that is until switch 109a again falls into the depression of cam 109.
When switch 1 I la is tripped, it gives a by-pass to the movement which moves the turntable or chain one space. When the switch 113a is tripped it causes the flow of fluid to go through the by-pass. The cycle is then repeated as the synchronous motor continues to run. If a by-pass is not given, the synchronous motor will stop itself when switch 109a opens.
In operation, one activates motor 107 by closing switch 110. The motor completes a cycle and stops. One then closes switch 110a. Motor 29 now cycles periodically giving a by-pass to motor 107. This causes motor 107 to complete a cycle activating all the components of the system. It then stops and waits for a second by-pass from switch 115. Motor 29 runs therefore slower than motor 107 in order not to upset the order of the system.
FIG. 5a also shows how the signal from cam 39a is relayed to the motor of FIG. 10. The circuit of work motor 29 goes through two switches 115 and 115a 180 apart which are in series with each other. If either switch is in one of the depressions of cam 115b, the motor stops, i.e., the motor runs until one of the switches falls into the depression when the motor stops. A by-pass from switches 40, 40a will start the motor going. Thus, the motor will turn the cam 180 each time and then stop. This is also seen in FIG. 3b as it alternately gives a by-pass to the solenoid value of FIG. 3a.
In FIGS. 1 through 4, the capillary is secured at the ends to make a seal so that liquid may flow through it. In FIG. 4a the capillary is lifted to the work station. This same purpose may be accomplished by clamping the capillaries to a table in such a way that they are secured within a flexible clamp made of rubber or plastic. The mechanism bringing the fluid to the capillary does not touch the capillary but brings the fluid to the rubber clamp and also removes it from the clamp. This has the advantage that the capillary is protected from breakage. How this is accomplished may be seen in FIGS. 6a, 6b and 6c.
The capillary 47 filled with sample is placed in a recess in a plate assembly 153 having a circular lower plate 152 made of soft rubber 148 approximately V2 inch thick and backed with metal 151 for support. Two ridges circle the plate and have recesses 149 in them to act as a bed 157 for the capillary 47, but still prevent the edges of the capillary from touching a surface. This is done to prevent fluid from leaving the capillary by capillary action. The edges of the capillary are at the beginning of a flare a or widening opening. The object of the flare is to eventually form a rubber funnel 155 as in FIG. 2 and 7c. The circular lower plate 152 has three holes 159 for attachment to a turntable 161 and an upper plate 154 or cover.
The upper plate 154 is seen in FIG. 6b and is similar to the lower plate 152 in FIG. 6a. It also has two ridges 150a, but is made of softer rubber 148a (silicone) and does not have depressions in the ridges. This upper plate is a cover and aligns with the lower plate by means of the three holes 159a. It also has upper flares 155C, and a metal backing 151a.
The lower plate 152 after loading, usually with 40 capillaries, is placed on the turntable 163 as in FIG. 6c by threading the holes on three binding posts 165 rigidly secured on the turntable. The upper plate 154 is now threaded on the binding posts 165 of the turntable so that the lower rubber 148 faces the upper rubber 148a. Wing nuts 167 are now tightened so that the upper ridge 150a is compressed forming a double seal, one for each ridge around the capillary. The flares 155a, I55b on the upper and lower plates now meet to form a funnel 155.
In FIG. 7a, a cross-section of the top plate is shown to show the two ridges 150a, rubber 148a and backing metal plate 151a. FIG. 7b shows a cross section showing the capillary 47 resting on the lower ridges 150 of the lower plate 152 supported on rubber 148 and a backing metal plate 151. The ends of the capillary do not touch. In FIG. 70, a cross section is shown showing how the upper plate 154 meets the lower plate 152 and how a funnel 155 is formed from the flares 155a and 15512 on the upper and lower plate.
In the case of FIG. 6a through 7c, the fluid is brought to the capillary by detents 169 which contain a valve system 171. This is shown in FIG. 8a and FIG. 8b. The detents are inwardly biased by a clamp and spring arrangement 159 similar to that hereinbefore described. The detents 169 have nipples 173 which can be pushed back and will return because of an enclosed weak spring 175, in the casing of the detent assembly. As the nipple 173 is pushed back, the spring is compressed as in FIG. 8b, the feed line opening 177 is blocked by the detent wall 179 acting as a piston 181. When the spring is allowed to expand, the piston 181 of the detent 169 moves forward aligning an opening 183 in the piston wall 179 with an opening in a loose connection. In FIG. 8a, two such detents have slipped into the funnels 155 created by the flares 155a, 1551) of FIG. 6c and 70 when the upper plate is fastened to the lower plate. As the detent moves around the inner and outer part of the clamped plates in FIG. 7c, it encounters a depression ofa funnel 155 followed by a smooth surface and a second funnel-like depression, etc. As the table rotates, the mounted detents shown in FIG. 8a encounter the series of funnels 155 followed by smooth walls. Thus, the detents 169 slip into the funnel like depression opening the flow path through capillary 47. As the capillary 47 moves away, the detents 155 move out of the depression and like in FIG. 8b are pushed back sealing off the liquid flow. This continues until all the capillaries on the table have been emptied.
A variant of this same idea is to mold a form 253 which is to be fastened on a turntable with cement. FIG. 9a shows such a rubber mold from 253. The operator pushes the capillary 47 down the slits 249 to the channel in the rubber mount 257 designed to hold it. The rubber mount 257 in this case is ofa higher durometer of approximately 70 80 so as to hold the tube firmly. A clamp in the form of a single spring clip 254 or double spring clip 254a may also be used to tighten on the rubber mount 253. The spring clips serve to clamp the slit rubber mount 253 together and hold it tightly. The molded forms 253 are disposed around a turntable and serve the same function as that of FIG. 6c, which clamp the capillaries with a cover.
Amodification of FIG. 9a is to use a single molded rubber form 260 in the shape of a double funnel, 258 and 259, as shown in FIG. 10. These are made of flexible plastic or rubber so that the operator can push them back and insert a capillary loaded with sample. As they spring back they hold the capillary tightly. The flexible forms also may be mounted in a circular or linear mode. lnFIG. 1012 they are mounted in a linear mode ganged together to form a rack 261.
Approximately 20 of the molded soft rubber forms with double funnels 258, 259 shown in FIG. 10a are stacked with a metal spacer 264 between them as shown in FIG. 10b. The metal spacers extend on both sides 262, although only one side is needed, so as to be able to intercept a trip switch 269a. The operator inserts the loaded capillary 47, full of sample, into the two opposing holes so as to form a seal. The flexible rubber can be pushed back and forth somewhat between the spacers permitting the insertion of the capillaries. The whole rack rests and is sealed to a metal plate 263.
The operator now places the rack in the track of the slide mechanism as shown in FIG. 1 of U.S. Pat. application Ser. No. 156,285. The spacer extensions take the place of the test tubes so that the rack advances one spacer and stops. The nipples 269 and 265 are now inserted on both sides and the peristaltic pump pumps the fluid from a reservoir to the analyzing system washing out the capillaries. Flow is through tube 268 to nipple 269 held by clamp 267 to armature 266 of solenoid 266b through the capillary and through the nipple 265 to be analyzed.
A by-pass is given to the trip switch 268 from the control box which causes the rack to advance one space. The nipples are inserted by inactivation of the.
U.S. Pat. application Ser. No. 156,285. A second rack then advances to take its place. The operator then removes the capillaries from the first rack and it can be reutilized after discarding the capillaries.
FIG. shows the capillary 47 in place and the plastic nipples 265 and 269 pushed forward so as to make a continuous flow system, from wash fluid to peristaltic pump 11 and tube 18 through the first nipple 269, the capillary 47, the second nipple 265 and finally to the analysis area.
As hereinbefore described, a cam and switch arrangement FIG. 5a is used to give a by-pass.
A by-pass from the control box FIG. 5a shorts a cam switch 272 causing the motor to be activated by the line current. A cam 276 makes a turn and comes to rest since the cam switch is now open and in series with the line and the motor.
The movement of the first cam pulls back the first plastic nipple 269. The cam 276 is tied to a second cam 278 by sprockets and a ladder chain 271. Thus the second cam also moves 180 simultaneously pulling back the second plastic nipple 265. This releases the rack of FIG. 10a. A by-pass trip switch from the control box FIG. 5a permits the rack to be pushed forward one space.
A by-pass to the first cam from the control box causes the cam to rotate 180 and again insert both nipples 269 and 265 into the soft rubber capillary support. The flow of fluid starts through the capillary and the process is repeated. Solenoids may be used in place of the motor to retract or insert the nipple into the funnels of the soft rubber capillary support.
I claim:
1. An arrangement for introducing minute quantities of a liquid sample into an analytical system comprising in combination:
a. moving means moving along a predetermined travel path to a work station having thereon retaining means for horizontally retaining a plurality of sample containing capillaries open at both ends in parallel;
b. means for sequentially presenting said capillaries to said work station; and,
c. sealing means operatively connected to said work station for sequentially sealing the capillaries into the work station without leakage.
2. An arrangement as claimed in claim 1 including flow means providing a flow path at said work station so that a work fluid may flow through said capillary.
3. A method for introducing minute quantities of a liquid sample into an analytical system comprising the steps of:
a. Horizontally placing a plurality of sample containing capillaries open at both ends in parallel in a plane and moving said plane past a work station;
b. providing a continuous flow path for a work fluid at said work station through which said fluid normally flows;
c. sealing said capillary into said flow path at said work station as each capillary in said plane sequentially reaches said work station; and,
d. removing said capillary from said flow path and replacing it with another capillary.
4. An arrangement for introducing minute quantities of a liquid sample into an analytical system comprising in combination:

Claims (16)

1. AN ARRANGEMENT FOR INTRODUCING MINUTE QUANTITIES OF A LIQUID SAMPLE INTO AN ANALYTICAL SYSTEM COMPRISING IN COMBINATION: A. MOVING MEANS MOVING ALONG A PREDETERMINED TRAVEL PATH TO WORK STATION HAVING THEREON RETAINING MEANS FOR HORIZONTALLY RETAINING A PLURALITY OF SAMPLE CONTAINING CAPILLARIES OPEN AT BOTH ENDS IN PARALLEL; B. MEANS FOR SEQUENTIALLY PRESENTING SAID CAPILLARIES TO SAID WORK STATION; AND,
2. An arrangement as claimed in claim 1 including flow means providing a flow path at said work station so that a work fluid may flow through said capillary.
3. A method for introducing minute quantities of a liquid sample into an analytical system comprising the steps of: a. Horizontally placing a plurality of sample containing capillaries open at both ends in parallel in a plane and moving said plane past a work station; b. providing a continuous flow path for a work fluid at said work station through which said fluid normally flows; c. sealing said capillary into said flow path at said work station as each capillary in said plane sequentially reaches said work station; and, d. removing said capillary from said flow path and replacing it with another capillary.
4. An arrangement for introducing minute quantities of a liquid sample into an analytical system comprising in combination: a. moving means moving along a predetermined travel path to a work station having thereon retaining means for horizontally retaining a plurality of capillaries open at both ends in parallel; b. flow means providing a continuous flow path at said work station having a by-pass through which a work fluid is normally flowing and a main flow path with capillary holding means for passing the work fluid through a capillary when a capillary is in said main flow path with first and second valve means in said by-pass path and said main flow path to permit fluid passage through only one of the flow paths; c. insert means for inserting a capillary from said moving means into said capillary holding means; and, d. control means coupled to and regulating said insert means to insert capillaries sequentially into said capillary holding means at work station and for regulating the action of said first and second valve means so that liquid will only flow through said main flow path when a capillary is held by said holding means.
5. An arrangement as claimed in claim 4, said insert means including first and second receiver funnels, a pincer like clamp holding said receiver funnels, spring means biasing said clamp and a cam acting on said clamp to oppose the action of the spring means whereby said clamp brings said receiver funnels towards each other to hold a capillary.
6. An arrangement as claimed in claim 5, wherein said clamp is a scissors clamp with two arms and two legs with a spring between two legs thereof and a cam between two arms thereof.
7. An arrangement as claimed in claim 5, wherein said clamp has one separately pivoted lever arm with a funnel at one end of the lever arm spring means acting on the other end of the lever arm and a cam acting on said other end against said spring means.
8. An arrangement as claimed in claim 4, wherein said insert means include a U-shaped member having capillary support at the outer end thereof disposed under said spring means, said supports being disposed to lift a capillary towards the ends thereof, cam means to lift said U-shaped member upwards and sprinG means biasing said U-shaped member downwards, and a form corresponding to said supports, against which said capillary is lifted, said form and said support defining a main flow path.
9. An arrangement as claimed in claim 1 including beds for receiving capillaries on said moving means with funnel-shaped apertures defined at both ends of said bed, said clamp means sealing said flow means into said apertures without disturbing said capillaries.
10. An arrangement as claimed in claim 9, said clamp means including two tubular sections each disposed to face one of said funnel-shaped apertures, said tubular sections defining opposite sides of said main flow path, said tubular sections each having a flow aperture; a hollow detent in each tubular section said detent being movable to a forward and retracted position with bias means urging said detent to the forward position to sealingly engage said funnel-shaped apertures completing said main flow path, said detents having a sealing wall cutting off liquid flow from said flow apertures in the retracted positions.
11. An arrangement as claimed in claim 1, wherein juxtapositioned double funnels with inner and outer funnel shaped apertures are mounted on said moving means, said double funnels each being mounted on similar supports at least one of which is flexible, the capillaries being placed between two facing inner funnels, said claim means including sections disposed to enter said outer funnel-shaped apertures.
12. An arrangement as claimed in claim 1, wherein said retaining means includes soft resilient rack means defining juxtapositioned double funnels with inner and outer funnel-shaped apertures, so spaced apart that capillaries can be inserted and retained between said inner apertures, said capillary holding means comprising first and second nipples for engaging said outer apertures, engaging means for urging said nipples into said outer apertures sealing said nipples therein so as to provide a continuous flow path.
13. A capillary retaining and sealing means which comprises a single coating of flexible material which contains in its structure two double funnels at a fixed distance from each other so that a capillary may be sealed therein and providing openings for inserting nipples to provide a sealed path for liquid to flow through said capillary.
14. A plurality of capillary retaining and sealing means as claimed in claim 13, wherein said means are placed next to each other with spacers to form a rack.
15. An arrangement as claimed in claim 1, wherein said nipples are inserted into said funnels by the reciprocating action of a cam which rotates in 180* turns.
16. An arrangement as in claim 12, wherein said nipples are sequentially inserted into and removed from funnels by the action of a solenoid and spring arrangement.
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US3938958A (en) * 1975-03-24 1976-02-17 Corning Glass Works Fluid dispensing device
US3938957A (en) * 1975-03-24 1976-02-17 Corning Glass Works Applicator card
US4066407A (en) * 1976-12-16 1978-01-03 Vincent Lupica Body fluid testing system and process
US4210724A (en) * 1977-03-28 1980-07-01 Olympus Optical Co., Ltd. Apparatus for liquid disposal and distribution in automatic culture system
FR2475729A1 (en) * 1980-02-12 1981-08-14 List Hans LIQUID ANALYZER APPARATUS
WO1983001119A1 (en) * 1981-09-25 1983-03-31 Chandler, Howard, Milne Automated immunoassay system
JPS58501521A (en) * 1981-09-25 1983-09-08 コモンウエルス セラム ラボラトリ−ズ コミツシヨン automatic immunoassay system
US4960566A (en) * 1986-09-11 1990-10-02 Mochida Pharmaceutical Co., Ltd. Chemical reaction apparatus
US4976924A (en) * 1988-04-22 1990-12-11 Her Majesty The Queen In Right Of Canada, As Represented By The Minister Of National Defence Automated thermal desorption unit
US6758362B2 (en) * 1997-01-13 2004-07-06 Leica Ag Specimen holders for hydrous specimens and method of using them
JP2015526744A (en) * 2012-09-14 2015-09-10 ベックマン コールター, インコーポレイテッド Analysis system with capillary transporter
US20150276772A1 (en) * 2012-11-01 2015-10-01 Leica Biosystems Melbourne Pty Ltd Fluid transport system
US10228382B2 (en) * 2012-11-01 2019-03-12 Leica Biosystems Melbourne Pty Ltd Fluid transport system and method for treating one or more tissue samples on a slide
US20170102402A1 (en) * 2015-10-09 2017-04-13 Sysmex Corporation Test piece mounting body, transport unit, and test piece analyzer
US10890593B2 (en) * 2015-10-09 2021-01-12 Sysmex Corporation Test piece mounting body, transport unit, and test piece analyzer
EP3954953A1 (en) * 2020-08-14 2022-02-16 Leica Mikrosysteme GmbH High pressure freezing cartridge and method of high pressure freezing
CN114073248A (en) * 2020-08-14 2022-02-22 徕卡显微系统有限公司 High pressure freezing box and high pressure freezing method
US11754477B2 (en) 2020-08-14 2023-09-12 Leica Mikrosysteme Gmbh High pressure freezing cartridge and method of high pressure freezing
CN114073248B (en) * 2020-08-14 2023-10-03 徕卡显微系统有限公司 High pressure freezing box and high pressure freezing method

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