US 3607082 A
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United States Patent  inventor Ralph E. Thiers Woodland Hills, Calif.  Appl. No. 860,775 122] Filed Sept. 24, 1969  Patented Sept. 21,1971
1 73] Assignce Bio-Science Laboratories Van Nuys, Calif. Continuation-impart of application Ser. No. 541,306, Apr. 8, 1966, now Patent No. 3,475,128, dated Oct. 28, 1969.
 FLUID-PROCESSING SYSTEM 29 Claims, 14 Drawing Figs.
 U.S. Cl 23/230, 23/230 B, 23/253, 23/259, 23/292, 73/425.6,
 Int. Cl B011 3/02, G01n1/14,G01n 31/00  Field of Search 23/230, 2308, 253, 259,292; 141/18; 103/165, 148, 149,
 References Cited UNITED STATES PATENTS 2,767,064 10/1956 Sherrick et al 23/259 X 2,901,327 8/1959 Thayer et al 23/230 Primary Examiner-Joseph Scovronek Att0rneysGriswold & Burdick, John L. Spalding and Maynard R. Johnson ABSTRACT: A fluid-processing apparatus and a method for its use comprises metering and valving means for charging a plurality of separate liquids into separate pipet chambers and charging the liquids from the pipet chambers so that each succeeding liquid passes through the pipet chamber employed to receive the preceding liquid, a fluid receiving and transporting conduit having tractable wall portions adapted to receive the metered liquids from the pipets, means for forming movable seals in the conduit thereby to isolate a metered quantity of liquid in a hydraulically isolated chamber, means for mixing the fluids in the chamber by compressing and releasing portions of the wall thereof, processing means for performing various unit processes on the fluid mixture in a given chamber, and discharge means for removing fluid mixture from said conduit. A branched-arm valve, fitted with means for selectively closing arms thereof is preferably employed as a valving means in charging and dispensing fluids into and from the pipet chambers. The system can be employed in carrying out various processes of chemistry, microbiology or the like.
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PATENTEU saw 15m 3.601082 SHEET 7 BF 7 H TTOR VE Y FLUID-PROCESSING SYSTEM CROSS-REFERENCE TO RELATED APPLICATION This is a continuation-in-part of my copending application, Serum. 54l ,306, filed Apr. 8, I966, for Fluid Processing Apparatus and Methods, now U.S. Pat. No. 3,475,128, issued Oct. 28, I969.
SUMMARY OF THE INVENTION This invention is directed to an apparatus and method useful in the processing of fluids, i.e., liquid solutions, suspensions, emulsions, liquid dispersions of biological entities such as bacteria or fungi, mixtures of fluids, gases, foams, etc. More particularly, the invention is concerned with apparatus and methods for separately metering one or more predetermined volumes of one or more liquids and discharging such metered liquid or liquids to a point of use. Further, the invention is directed to apparatus and methods for metering successive predetermined volumes of fluids into successive isolated chambers wherein each successive metered volume of fluid may be processed substantially independently of other metered volumes.
The invention provides an apparatus and method for rapidly metering predetermined quantities of fluids with a high degree of precision. Moreover, the apparatus and method provide for rapid, accurate and substantially simultaneous metering of a plurality of different liquids and transfer of the metered liquids to a point of use. The invention also provides apparatus and methods useful for processing of fluids in predetermined quantities.
In general, the integrated fluid-processing apparatus of the present invention comprises a plurality of pipet chambers, hereinafter at times simply referred to as pipets. Each of said pipets is connected at one of its ends to at least one fluid supply reservoir, through a tubular liquid supply line and a valve means and its other end to a source of suction through a tubular suction line and a valve means. Each pipet is also connected at one end to a source of fluid pressure through a tubular pressure line and a valve means, and at the other end to a point of use through a tubular discharge line and a valve means. The valve means provide controlled selective charging of liquids into said pipets and discharge of said liquids, and controlled discharge of a predetermined volume of the liquid from the pipet and valve means through the discharge line. The discharge line of at least one pipet communicates with the inlet means of a closed loop conduit fluid transport unit having a tractable or movable wall. The conduit is fitted with a transverse seal and discharge means, the discharge means and inlet being on opposite sides of this seal. Moreover sealing means operate in cooperation with said conduit forming a series of fluidtight chambers therein. Mixing means, processing means and the like are adapted to cooperate with and function in conjunction with the chambers of said conduit.
The terms pipet and pipet chamber are employed in the present specification and claims in the broad, generally accepted sense to designate a tube, pipe or similar conduit of predetermined volume into which a quantity of fluid, e.g., a liquid, is charged, typically by suction at one end thereof, and from which the fluid is discharged to provide a measured volume thereof, the discharge being typically carried out by application of pressure or release of suction. As employed from time to time in relation to the apparatus and method of the present invention the term pipet tube" is employed to refer to the hollow pipetlike volumetric member exclusive of valving means and lines, while the term pipet chamber" includes the predetermined volume of the valving means employed for charging and discharging fluid from the hollow, pipetlike member as well as the volume of the pipet tube itself.
The apparatus and method of the present invention can be employed in a variety of operations, such as the automatic or semiautomatic carrying out of chemical analyses on a plurality of liquid samples; automatic or semiautomatic metering and diIuting of liquids; automatic or semiautomatic analyses of gas LII samples; carrying out of chemical reactions in substantially continuous fashion while maintaining successive portions of the reaction mixture separate from each other; and the carrying out of microbiological processes such as inoculation, dilution and incubation in substantially continuous fashion while maintaining substantial separation of successive portions of inoculum or medium. I
If desired, various unit processes in addition to mixing and measuring can be carried out on the fluids while they are confined in the chambers of the transport unit' of the integrated apparatus. For example, addition, removal, mixing, division, heating, cooling, de'cantation, filtration, dialysis, examination of a property such as an electrical or optical property, and further or different mixing or measuring processes and the like can be carried out by employing modifications of the transport unit such as those described in my copending application Ser. No. 541 ,306, filed Apr. 8, I966. Many other modifications of the apparatus can also be made as desired to adapt the apparatus and method of the invention to a wide variety of applications in fluid processing. For example, the metering unit can be employed with various other types of transport devices or it can be employed alone in metering and addition of fluids in various operations including the automatic or semiautomatic metering and dilution of flavoring liquids, coloring liquids, and nutritive or pharmaceutical liquids, as well as in chemical and microbiological operations and the like.
In the operation of the apparatus of the present invention, metered individual predetermined portions of a fluid are charged through the valving means into separate pipet chambers and discharged therefrom into chambers formed in the conduit transport unit. The operationcan provide for passing each succeeding portion of one fluid from a pipet chamber through another pipet chamber employed to receive a preceding portion of another fluid. Movable seals in the conduit provide for formation of hydraulically isolated chambers in said conduit and the isolation therein of the metered portions of said fluids from one or more pipets. Prior to discharge from a given chamber the fluid can be mixed, reacted and/or subjected to any of a variety of chemical or physical processes and/or measurements.
The present invention will be more completely understood from the full disclosure presented hereinafter when read in conjunction with the Figures of the drawing in which:
FIG. I is an elevational view partially broken away of one embodiment of a fluid-processing apparatus of the invention;
FIG. 2 is an elevational view ofa metering unit for use in the integrated fluid-processing apparatus of the present invention also illustrating connections with vacuum, pressure and reservoir lines in schematic form;
FIG. 3 is a side elevational view, partially in section, of the metering unit of FIG. 2 which also includes a cam drive assembly;
FIG. 4 is a plan view of the metering unit partially in section;
FIGS. 5, 6 7 and 8 are schematic sectional views illustrating an operating sequence of the metering unit;
FIG. 9 is a sectional view showing another embodiment of valve suitable for use with the metering unit of the present apparatus;
FIG. 10 is an elevational view of another embodiment of a valve suitable for use with the metering unit of the present apparatus, partially broken away to illustrate the structure thereof;
FIG. 11 illustrates the construction of one embodiment of a conduit and transport unit movable sealing means, mixing unit and discharge means suitable for use in the integrated fluidprocessing apparatus of the present invention;
FIG. 12 is a fragmentary sectional, schematic view of the transport unit of FIG. 11 illustrating its action during operation;
FIG. 13 is an isometric view, partially in section of an embodiment of a mixing unit suitable for use with the fluidprocessing apparatus of the present invention; and
FIG. 14 is a fragmentary elevational view of the mixingunit of FIG. 13.
DESCRIPTION OF PREFERRED EMBODIMENTS One preferred embodiment of the integrated apparatus of the invention, as illustrated by the Figures of the drawings, comprises a fluid metering unit 200 adapted to meter predetermined quantities of two separate fluids, such as a liquid sample of serum or the like and a liquid reagent for reacting with at least one component of the sample. The metering unit 200 includes a valving means 201 connected to pipets 70 and 80 which means draws fluids from reservoirs (shown schematically in FIG. 2) into pipets 70, 80 and discharge fluid from pipets 70, 80 through a discharge line 32 to a point of use. A transport unit 500 in the form of a closedloop conduit communicates with the metering unit discharge line 32. The transport unit 500 is adapted to provide a plurality of chambers (505, a, b, c, d in FIG. 12) by means of movable seals (513 a, b, c, d in FIG. 12) which, during operation advance each chamber and its fluid contents along the conduit for mixing by a mixing unit 400 or additional processing. In the depicted embodiment, the metering unit 200 is activated by an actuator unit 300 comprising a cam 302, 304 and follower 340, 350 structure which cooperate with the transport unit 500. A measuring device, e.g. colorimeter 525, adapted to be communicably coupled with a fluid-containing chamber of the transport device 500 via a tube 524 can also be included during operation. The metering unit 200, transport unit 500, mixing unit 400, actuator unit 300 and measuring device colorimeter 525 can be mounted on a unitary base 18 or otherwise operably engaged by the appropriate fluid-conducting connections and mechanical linkages to provide apparatus capable of pipetting a predetermined amount of fluid from a source and discharging the fluid at a point of use, forming a fluid chamber at a location for receiving the discharged fluid, processing the fluid in the chamber including mixing and transporting the fluid and performing analytical measurements thereon.
It is to be understood that other processing apparatus can be employed with the present apparatus and that certain of the depicted elements may be eliminated for certain operations.
For sake of clarity and ease of reference, the various units of the depicted embodiment of the apparatus and their mode of operation are described in detail directly hereinafter.
THE METERING UNIT As shown in FIGS. 1-4, the metering unit 200 includes a pipet 70 and a pipet 80, mounted on the unit and having both their upper and lower tubular portions 71, 72, 81, 82 extending into metering unit 200 through bores 203 in a face plate 202. Face plate 202 is attached to a pair of valve blocks 44, 54 by adhesive, bolts, threaded screws or other fastening means. The face plate 202 and valve blocks 44, 54 include a plurality of mated channels or grooves therein for receiving a series of fluid-conducting lines 20, 22, 24, 26, 28, 30 and 32 and maintaining the lines in fixed position between the face plate 202 and blocks 44, 54.
A liquid supply line 22 provides selective communication between a liquid reservoir 23 of sample liquid or the like and the lower portion 72 of the pipet 70 at a three-armed, fluidconducting intersection 31. Discharge line 32 likewise selectively communicates with the lower portion 71 of sample pipet 70, forming a three-way, generally T-shaped intersection 31 between lines 22, 32 and pipet portion 71. At a similar threeway intersection 31 the upper portion 72 of pipet 70 selective ly communicates with a connecting line 30 and with a suction line 26. At another similar three-way intersection 31, another end of connecting line 30 selectively communicates with the lower portion 81 of pipet 80 and with a liquid supply line providing selective communication with a liquid reservoir 21 of a reagent liquid or the like. The upper tubular portion 82 of pipet 80 is in selective communication with a suction line 24 and the downstream end 27 of a pressure line 28 at another three-way intersection 31. Pressure line 28 communicates with a surge chamber 105 intermediate the ends thereof, and the upstream end 29 of line 28 communicates with a pressure supply line 25 at a two-way, partial-T or L-shaped intersection 33. As best shown in F IGS..5-8, the pipet end portions 71, 72, 81 and 82 communicate with their respective three-way intersections 31 by means of friction fit; coupling with corresponding pipet lines 106, 108, 116, and 118, respectively, which in combination with pipet portions 71, 72, 81 and 82 form an arm of each three-way intersection 31. The terms upper" and lower" as applied to the pipet portions or ends 71, 72, 81, 82 are employed with respect to the orientation depicted in the Figures of the drawings, it being understood that such orientation is not critical.
At their intersections with the various lines, the upper and lower pipet portions 71, 72, 81, 82 and the pressure supply line 25 extend through a series of aligned bores 203 in faceplate 202 so that such portions 71, 72, 81, 82 and line 25 all lie in substantially the same plane. Similarly, the downstream portion 27 of pressure line 28, both portions of connecting line 30 and discharge line 32 are in alignment with each other; and the upstream portion 29 of line 28, the suction lines 24, 26 and supply lines 20, 22 are in alignment. The lines and pipet portions are maintained in such alignment by their engagement between plate 202 and blocks 44, 54.
The lines 20, 22, 24, 25, 26, 28, 30 and 32 are each adapted to be selectively sealed in portions thereof adjacent their intersections by movement of one wall portion of a line into sealing engagement with another wall portion. Preferably the lines are fabricated from a resilient flexible conduit or tubing of a natural or synthetic material such as rubber, polyethylene, silicone rubber, plasticized polyvinyl chloride materials, fluorinated elastomers, urethanes or the like adapted to be sealed by compressing one wall portion against another and adapted to remain normally open in the absence of compression, preferably being sufficiently resilient to reopen in the absence of compression.
The pressure source (shown in block form in FIG. 3) can be a conventional compressor, compressed gas cylinder, compressed liquefied gas cylinder or the like adapted to supply gas through line 25 under sufficient pressure to discharge the contents of the pipets 70, through line 32. The surge chamber is adapted to contain sufficient gas to accomplish discharge of the pipets 70, 80 through line 32 and to fill lines 28, 30 and 32 and the pipets 70, 80 with gas after discharge. Surge chamber 105 is employed to limit the volume of pressurized gas employed in discharging the metering unit 200. It can be eliminated, when desired, by connecting pressure supply line 25 directly to the downstream end 27 of line 28.
The suction lines 24, 26 can be connected to one or more conventional vacuum pump, aspirator or other means (shown in block form in FIG. 2) for providing reduced pressure therein, and preferably contain a conventional liquid trap (shown in block form in FIG. 2) to prevent liquid from being drawn through the lines 24, 26 to the vacuum pump or the like. Alternately, the suction lines 24, 26 can be at atmospheric pressure and the reagent and sample reservoirs 21, 23 can be pressurized, it being essential only that the pressure in suction lines 24, 26 be sufficiently below the pressure on the fluids in supply lines 20, 22 so that the fluid reagent and sample can be drawn into their respective lines and pipets.
To further an understanding of the actual operation of the depicted metering unit, a typical cycle of operation employing two pipets 70, 80 with the metering unit 200 is illustrated by the schematic cross-sectional view of FIGS. 5, 6, 7 and 8. FIG. 5 illustrates the metering unit assembled and ready to operate, FIG. 6 shows the unit in the charging phase; FIG. 7 illustrates the unit after charging and prior to discharge and FIG. 8 illustrates the unit in the discharge phase of a typical cycle of operation.
At each T-intersection 31, the lines 20, 22, 24, 26, 30 and 32 and upstream and downstream portions 27, 29 of line 28 are each provided with means for collapsing and sealing each line or portion of a line by urging opposed movable portions of the walls thereof into sealing engagement with each other. The sealing means for each line comprise platens 141, 143, 145,
147, 151, 153, 155, 157 and 159 and opposed movable blades 140, I42,144,146,150,152,154, 156 and 158.
The platens and blades are preferably fabricated from a rigid material such as polystyrene, acrylic resin, metal or the like. T he platens can be part of a valve unit as shown in FIGS. 9 and 10; they can be portions of the unitary faceplate 202 as shown in FIGS. 2, 3 and 4; or they can be part of a metering unit structure which supports the lines, pipets and blades. Alternately, each platen or pair of platens 141 and 151; 143 and 153; 145 and 155; and 147 and 157 disposed against the lines forming the arms of a particular intersection 31 can be separate units separately attached to a metering unit structure and separately detachable therefrom. Each of the lines 20, 22, 24, .16, 28, 30 and 32 have deformable walls adapted to be releasably sealed in the regions adjacent the intersections with the pipet lines 106, 108, 116, 118 and pipet end portions 71, 72, 81, 82 when compressed between a blade and the corresponding platen. The walls of each line are preferably sufficiently resilient to return to the unsealed, open state shown in FIG. 5 when the blade associated with that portion of the line is displaced from the corresponding platen.
Releasable sealing of the lines can also be by means other than the resilience of the line walls. For example, opposed wall portions of a tube can be affixed to a blade and to the corresponding platen by adhesive or the like so that retracting movement of the blade from the platen separates the corresponding line wall portions and releases the seal.
Each platen and the corresponding blade are disposed on a line adjacent the T-intersections 31 with the corresponding pipet line so that closure of one line results in the formation of a two-way, substantially L-shaped intersection between the corresponding pipet line and the remaining open line along the arm of the T. In the case of the intersection 33 of lines 28 and 25, closure of the upstream portion 29 of line 28 seals the intersection. Preferably, the platens and blades are disposed so that sealing of one line at a three-way T-shaped intersection results in formation of a two-way intersection having substantially the same cross-sectional area throughout the intersection as the cross-sectional area of one of the unsealed, open lines. When the lines are of resilient cylindrical tubing, it is preferred to dispose the blades and platens immediately adjacent the intersection to form a pipelike L-shaped intersection of substantially circular cross section on sealing one of the lines. Other dispositions of the blades and platens relative to the intersection can be employed as desired, however, the precision of the apparatus decreases as the internal volume of a line between the intersection and the seal increases, and it is therefore desirable to minimize the distance between the seal and the intersection.
In the assembled apparatus, each pair of platens disposed at the arms of a T-intersection 31 can be formed as a unit. The units are mounted with platens 151, 153, 155, 157 and 159 in alignment with each other and with platens 141, 143, 145, and 147 in alignment. Blades 140, 142, 144 and 146 can comprise portions of blade member 40; similarly blades 150, 152, 154, 156 and 158 can comprise portions of blade member 50.
The suction lines 24, 26 are connected to a vacuum pump, aspirator or the like to provide sufficient suction to draw the liquids to be metered into pipet tubes 70, 80. Pressure supply line 25 is connected to a source of positive pressure sufficient to expel liquids from both pipets. Liquid supply lines 20, 22 are connected to their respective reservoirs, and discharge line 32 is connected to the transport unit 500. Such connections are conveniently established while all sealable lines are sealed at their respective T-intersections by movement of the blades toward the corresponding platens.
ALTERNATE INTERSECTION VALVE UNIT In the embodiment of FIG. 9, a three-way T-shaped intersection valve unit 170 comprises a mounting block 172, preferably of a rigid material, such as metal, glass or transparent plastic such as an acrylic resin. Mounting block 172 includes a pair of bores 194 therethrough adapted to receive a pair of bolts, screws, pins or the like for detachably securing the mounting block to a support or base. A deformable resilient tube 176 is disposed in a bore through the mounting block 172. Tube 176 can be of rubber or any resilient deformable plastic material. It is sufficiently deformable to permit sealing thereof by urging opposed portions of the tube wall together by application of mechanical pressure or the like, and sufficiently resilient to return to its open, unsealed state upon the removal of such pressure. Tube 176 is firmly seated in mounting block 172, by the use of adhesives, by friction fit or the like. Mounting block 172 also includes a well 174 of pipet-tube-receiving dimensions, the well extending into mounting block 172 towards an intermediate portion of tube 176. An additional bore 184 in mounting block 172 extends from well 174 to tube 176, meeting tube 176 at a bore 182 through the wall thereof. A sealing ring 186 having a bore 188 therethrough is disposed within well 175 with the sealing ring bore 188 aligned with bore 184 and the bore 182 in the tube wall. The valve unit 170 is thus adapted to be sealingly coupled to a pipet tube disposed with an end thereof in well 174 in sealing engagement with sealing ring 186, and to provide for communication between the pipet tube and tube 176 through bores 188, 184 and 182.
The bores 182, 184 and 188 thus lie along the foot of a T with portions 178, 180 of tube 176 forming the arms of the T. The foot and two arms of the intersection of conduits formed by the bores and resilient tube can intersect at angles other than the right angle configuration shown in FIG. 9, for example, they can form a Y-shaped intersection, however the T configuration is simple in both construction and operation, and is therefore preferred.
Mounting block 172 further includes blade-receiving notches extending therethrough sufficiently far to expose tube 176 in both the arm portions thereof 178, 180. The inner surface 192 of each notch 90 lies along the wall of tube 176 to provide a platen surface supporting one side of the tube. Surfaces 192 preferably are formed with a slight depression therein to permit movement of the adjacent portion of the wall of tube 176 when a movable blade is urged against the opposed portion of the tube wall toward the inner surface 192 of notch 190. Notches 190 are thus adapted to permit movement of a blade therein toward and away from tube 176 to permit releasable sealing of tube 176 by movement of a portion of the wall thereof into sealing engagement with another portion of the wall thereof. Notches 190 are disposed at portions of tube 176 in relatively close proximity to bore 182, and at a distance therefrom sufficient to ensure that bore 182 remains in communication with one arm of tube 176 when the other arm is sealed at a notch 190. The exact configuration of the notches 190 is not critical, it being necessary only that the mounting block 172 provide means of access to a predetermined portion of tube 176 in each arm 178, 180 sufficient to permit formation of a releasable seal in such portions by relative movement of one portion of the tube wall against and into sealing engagement with another portion thereof.
The notches 190 permit sealing of tube 176 at predetermined portions thereof in each arm 178, 180. The internal volume of tube 176 intermediate the sealable portions thus is substantially uniform each time seals are formed in the portions of tube 176 disposed at the notches. The firm seating of tube 176 in mounting block 172 maintains the bore 182 in the tube wall in alignment with the bores 184, 188 through block 172 and sealing ring 188. The volume defined by the bores 182, 184 and 186 and by that portion of arms 178, 180 of tube 176 intermediate the sealable portions of tube 176 is substantially uniform each time seals are formed at the notches 190, and can be referred to as the valve-unit volume. The valve unit volume together with the internal volume of a pipet tube coupled in the valve unit at the well 174 constitute a pipet chamber capable of metering and dispensing a predetermined volumetric amount of fluid The arms 178, 180 of tube 176 are adapted to be communicably coupled to separate operating lines, for example, arm 178 can be coupled to a vacuum line for drawing fluid into a pipet chamber while line 180 is scaled, and line 180 can be coupled to a pressure line for expelling a metered volume of fluid from the pipet chamber when line 180 is open and line 178 is scaled. Different predetermined volumes can be metered rapidly and simply by coupling pipet tubes of different volumes to the valve unit 170 at well 174. In such operations, the valve unit dead space and the amount of liquid remaining in the valve unit volume after dispensing can be minimized by employing a tube of small internal diameter and by disposing notches 190 in close proximity to bore 182.
ALTERNATE VALVE UNlT FIG. illustrates another embodiment of a three-way or T- intersection valve structure which can be employed in the metcring unit. In this embodiment an L-shaped block 250 is pivotally mounted between a pair of plates 252, 254, on a pivot pin 256. An arcuate member 258 is securely mounted between the legs 260, 262 of block 250. A pair of releasably scalable lines 222, 232 are mounted on separate legs 260, 262 of block 250, each line extending through a leg of the block. Lines 222, 232 intersect each other and a third line 234 at the intersection of legs 260, 262 to provide a T-shaped intersection 231 by which the three lines can communicate with each other. Line 234 extends from the intersection through block 250. The lines are conveniently mounted by friction fit of the lines in respective bores through portions of block 250, although other mounting means such as adhesives can be employed.
A blade member 268 is movably disposed between plates 252, 254 and within the angle formed by the intersection of legs 260, 262. Blade member 268 has a pair of sealing faces 270, 272 adapted to compress lines 222, 232, respectively, against legs 260, 262, respectively. Blade member 268 is normally biased toward the intersection of legs 260, 262 by a spring 276 mounted between blade member 268 and arcuate member 258. Faces 270, 272 are preferably parallel to the corresponding legs 260, 262, and are adapted to engage corresponding lines 222, 232 adjacent the intersection and seal the portions of the lines so engaged.
The position of the blade member 268 with respect to lines 222, 232, is controlled by an arm 274 which extends outwardly therefrom to be slidably received in a slot 278 in plate 252, and a corresponding arm and slot (not shown) in plate 254. Arm 274 is normally biased against convex camming faces 280, 282 of the slot in plate 254, camming faces 280, 282 being generally aligned with legs 262, 260, respectively, and having their convex portions extending inwardly into the slot 278. In the normal position of block 250 between plates 252, 254, blade member 268 is disposed toward the intersection 231 by spring 276 and the engagement of arm 274 with convex camming faces 280, 282. In such normal position line 222 is sealed and compressed between sealing face 270 and leg 260, and line 232 is similarly sealed between scaling face 272 and leg 262. Pivotal movement of the block and tube structure with respect to the plates results in sliding movement of arm 274 along the convex faces 280, 282 of slot 278 displacing a blade member face from the corresponding leg and line as arm 274 engages a portion of greater convexity along one of the convex faces. For example, as illustrated in FIG. 10, in the counterclockwise pivotal motion of block 250 the sliding engagement of arm 274 with convex surface 280 displaces blade member 268 with respect to leg 262, unsealing line 232. Such counterclockwise pivotal motion maintains face 270 of blade member 268 in scaling relation with line 222 and leg 260, displacing the blade member along leg 260 a distance from the intersection corresponding to the displacement of face 272 from leg 262. Similarly, clockwise pivotal motion of block 250 seals both lines, and further clockwise motion releases line 222 while maintaining a seal in line 232 adjacent the intersection of lines 222, 232 and 234. The pivotal motion of block 250 is preferably limited depending on such factors as the outside diameter of the lines, the wall thickness of the lines and the relative size and configuration of the arm and slot so that a sealing face of the blade member is movable between a scaling position in which the sealing face is somewhat less than twice the line wall thickness from the corresponding leg and a line-releasing position in which the sealing face is displaced from the leg a distance corresponding to the outside diameter of the line.
THE INTEGRATED METERING UNlT In the integrated metering unit 200 as depicted in FIGS. 1-4, the pipet and line network and the assembly of faceplate 202 and blocks 44, 54 are mounted in a housing 201 comprising a base 204, sidewalls 208, 210 and cover 206. Housing 201 is mounted on unitary base 18 by means of a supporting framework 19. Slidably disposed within the housing are a pair of blade members 40, 50, each having a forwardly extending sealing portion 46 and 56, respectively. As shown in FIG. 4, the blocks 44, 54 are attached to faceplate 202 in spaced relation from each other, providing a space therebetwecn adapted to receive the sealing portions 46, 56 of blade members 40, 50 and to position each scaling member for movement toward and away from a particular series of lines and the corresponding portions of faceplate 202, i.e., platens, thus exposed in the space between blocks 44, 54.
Sliding movement of blade member 50 toward block 54 brings its sealing portion 56 into sealing engagement with the upstream portion 29 of line 28 and with suction lines 24, 26 and supply lines 20, 22. In such scaling engagement, the upstream portion 29 of line 28 and lines 20, 22, 24 and 26 are compressed between the sealing portion 56 of blade member 50 and faceplate 202, the faceplate serving as a platen or platens against which the lines are compressed and scaled. Sliding movement of blade member 40 in the housing toward block 44 similarly brings its sealing portion 46 into sealing engagement with the downstream portion 27 of line 28, with both portions of connecting line 30 and with discharge line 32. A pair of springs 42 mounted between block 44 and blade member 40, bias the blade member away from the block to a normal position in which the sealing portion 46 is displaced from faceplate 202 and lines 28, 30 and 32, permitting those lines to remain open. A similar set of biasing springs 52 is similarly disposed between blade member 50 and block 52.
The metering unit 200 is operated for charging pipets 70 and by displacing blade member 40 toward block 44 to seal lines 28, 30 and 32 while blade member 50 is displaced from the lines corresponding thereto to open the suction lines 24, 26 and supply lines 20, 22, permitting the sample and reagent to be drawn into their respective pipets 70, 80 by suction on lines 24, 26. During charging the opening of line 28 at its junction with line 25 provides for charging surge chamber with pressurized gas. In discharging, blade member 40 is released and blade member 50 is displaced toward block 54 to seal its respective lines to provide for discharge of sample liquid through line 32, and discharge of reagent liquid through line 30, sample pipet 70 and line 32 under pressure of the pressurized gas in surge chamber 105. The movement of blade members 40, 50 by the cam structure of the actuator unit is described in more detail below, as are additional details of the operation of the metering unit.
In the charging phase as shown in FIG. 6, the downstream portion 27 of pressure line 28, discharge line 32 and both ends of connecting line 30 are sealed by maintaining the blades 140, 142, 144 and 146 in line-sealing relation with corresponding platcns 141, 143, 145, and 147 throughout the charging phase. Blades 150, 152, 154, 156 and 158 are displaced from their respective platens 151, 153, 155, 157 and so that the upstream end 29 of pressure line 28, suction lines 24, 26 and liquid supply lines 20, 22 are open. A first liquid, e.g., reagent 162, flows from the reservoir 21 through line.20 into pipet 80 through pipet portion 81 and line 116, filling the pipet 80, and through the junction of pipet portion 82 and line 118 into suction line 124. Similarly, a second liquid, e.g., sample 160, flows from its reservoir 23 through samp? supply line 22, pipet end portions 71, 72 and pipet 70 into suction line 26, resulting in the complete filling of pipet 70 with the second liquid 160. During the charging phase surge chamber 105 communicates with lines 28 and 25.
Blades 150, 152, 154, 156 and 158 are then moved into sealing relation with their respective platens 151, 153, 155, 157 and 159 as shown in FIG. 7. A predetermined volume of fluid 162 is thus sealed in a pipet chamber defined by pipet 80, pipct lines 116 and 118 and the portions of the intersections 31 between the adjacent sealed portions of lines 24 and the downstream end 27 of line 28, and between the adjacent scaled portions of lines and 30. Similarly, a predetermined volume of liquid 160 is sealed in a pipet chamber defined by pipet'70, pipet lines 106, 108 and the portions of the intersections 31 between the adjacent sealed portions of lines 26 and and between the adjacent sealed portions of lines 22 and 32. Excess portions of liquids 160, 162 which are sealed in suction lines 24, 26 downstream of the intersections 31 are ultimately carried down said lines to the traps, A predetermined volume of gas is similarly retained in connecting line 130 between the portion of line 130 sealed by blade 142 and platen 143 and the portion sealed by blade 146 and plated 147. A predetermined volume of pressurized gas is similarly sealed in surge chamber 105 and line 28 between the sealed upstream and downstream portions 27, 29 of line 28.
In the discharge phase shown in FIG. 8, blades 140, 142, 144 and 146 are displaced from the corresponding platens 141, 143, 145 and 147, thereby releasing the seals on the downstream end 27 of pressure line 28, connecting line 30 and discharge line 32. Under the pressure of the pressurized gas in surge chamber 105 applied through line 28, fluids 160 and 162 are driven from their respective pipet chambers through discharge line 32 to a point of use, e.g., a chamber of the transport unit 500. As fluid 160 flows from pipet 70 into discharge line 32, it is followed by an air wash provided by the gas retained in connecting tube 30. The fluid 162 flows from pipet 80 through line 30 and pipet 70 into dispensing line 32, thus rinsing pipet 70. The gas entering the system through the downstream end 27 of pressure line 28 provides a second air wash after dispensing of fluid 162.
The metering unit is of particular value in analytical chemical operations when fluid 162 is a reagent liquid to be reacted with a series of different sample liquids, each sample liquid being metered in pipet 70 as fluid 160. In such operation the reagent liquid 162 rinses pipet 70 and the associated lines involved in metering the sample liquid with the metered charge of reagent liquid after each sample is metered and discharged. This utilization of the reagent liquid as a wash liquid enhances the reduction of interferences between successive samples metered by the unit. Although this illustration has been described with respect to one embodiment of valving means it is to be understood that valving means other than the design described herein can also be employed.
In a typical analytical chemical operation, the volume of sample liquid to be charged into pipet 70 is much less than the volume of reagent liquid to be charged into reagent pipet 80 and the time required for charging pipet 70 is correspondingly shorter. Also, it will frequently be desired to charge pipet 70 with several different sample fluids in successive operating cycles in which pipet 80 is charged with the same reagent liquid. In such operations, the longer time required for complete charging of pipet 80 with reagent liquid is generally ample for supplying both an air wash and a sample liquid charge through sample supply line 22. Also the shorter time required for charging the smaller sample pipet 70 permits the sample pipet 70 to be prewashed with an initial portion of fresh sample liquid which is carried from the pipet 70 through the suction line 26 to be ultimately discarded in the trap in line 26 prior to sealing lines 26 and 22 thus enclosing a metered volume of sample liquid in the pipet 70. In a preferred mode of operation, the sample pipet 70 is prewashed with sample liquid during the initial phase of each charging operation, the prewashing contributing further to minimize interference between successive samples. In the integrated apparatus illustrated in F IG. 1, the volume of liquid employed to prewash the pipets 70, is determined in part by the operation of the transport unit 500 and actuator unit 300. 1
The volume of fluid employed to prewash a pipct can also be predetermined by independently controlling the duration of the charging phase. When the fluid is a liquid electrolyte, the volume employed in prewashing can also be controlled by electrical means for actuating the means for sealing the supply line and suction line in response to an electric current between an electrical contact in the supply line and an electrical contact disposed in the suction line downstream of the sealing means a distance corresponding to the desired prewash volume.
The reagent and sample reservoirs can be any suitable source of the fluids to be metered and discharged. For example, the reagent reservoir can be a container of a biurct reagent employed in serum protein determination or of a standardized inoculum of a micro-organism such as Streptococcus faecalis of Lactobacillus arabinosus employed in folic acid assay procedures. The sample reservoir can be a container of biological fluid such as serum, plasma, urine or the like to be analyzed or assayed.
In another illustrative application, the sample reservoir can be a container of a gas sample such as stack gases or automobile exhaust gases to be analyzed and the reagent reservoir can be a container of liquid reagent to react with a component of the gas sample. In gas analysis, the pressure source should supply an inert gas or other suitable discharge fluid which will not interfere with the desired reaction. Alternately, a series of successive samples can be employed and the sample reservoir can comprise an automatic sample feed apparatus such as that described in US. Pat. No. 2,879,141. When desired, either or both the sample liquid and the reagent liquid can be changed in successive operations with the metering unit.
THE TRANSPORT UNIT The transport unit 500 comprises a rigid plate 502 having a flexible or tractable sheet 504 sealingly secured thereto at its inner and outer edges 506, 508. As best shown in P16. 11, the flexible sheet 504 plate 502 and sealed edges 506, 508 (shown as shaded areas) define an endless conduit, or processing vessel of circular configuration. The circumference of the conduit is predetermined to provide such a reaction period during a cycle of operation as may be required to complete a given process or liquid treating operation such as, for example, the determination of total protein in serum. An additional portion of flexible sheet 504 is sealingly secured to plate 502 to provide a transverse seal 510 across the conduit. Plate 502 can be fabricated of any suitable rigid material such as glass, metal or rigid polystyrene or acrylic resin, and tractable sheet 504 can be of any suitable flexible material such as rubber, polyethylene, polyvinyl chloride or the like. The seals 506, 508, 510 can be formed by conventional techniques such as by adhesives, by heat or solvent sealing, or by the use of mechanical devices, e.g., clamps.
Portions of the flexible sheet 504 are urged into releasable sealing engagement with the plate 502 by a plurality of frustoconical rollers 512. Each roller 512 is adapted to move along or around the conduit while maintaining sealing engagement between the portions of the sheet 504 and plate 502 which coincide with the position of the roller. The movable seals (illustrated in FIG. 12 as movable seals 513a, b, c, and d and defined by corresponding rollers 512a, b, c and d) thus divide the conduit defined by sheet 504, plate 502 and seals 506, 508, 510 into a series of substantially fluid tight chambers (illustrated in FIG. 12 as chambers 505a, b, c and d) each such chamber comprising that portion of the conduit between the seals 506, 508 and 510 and a movable seal or seals formed by one or more of the rollers 512.
A coupling conduit 520 and discharge conduit 522 communicate with the transport conduit through the plate 502. Coupling conduit 520 communicates with the discharge line 32 of the metering unit 200. Discharge conduit is coupled via line 524 to the flow cell (not shown) of colorimeter 525 and ultimately to waste disposal line 526. As best shown in FIG. 11, the rollers 512 and the movable seals and chambers formed thereby are adapted to move in the counterclockwise direction indicated by the arrows. Coupling conduit 520 is disposed on the downstream side of transverse seal 510 with respect to the direction of roller motion, and discharge conduit 522 is disposed on the upstream side thereof.
As a roller 512b advances along the conduit past coupling conduit 520, a chamber 505!) defined by the moving seal 513!) formed by the roller 512b, inner seal 506 and outer seal 508 and transverse seal 510 is formed in the transport conduit between sheet 504 and plate 502. As the roller 512b advances, increasing the size of this chamber 505b, fluid can be fed into the chamber through the coupling conduit 520 and metering unit discharge line 32. Discharge of fluid from the metering unit 200 into the chamber 5051; can be carried out in a more or less continuous fashion during the time required for the next succeeding roller 512a to advance to a position coinciding with conduit 520. Alternately, the rollers can be disposed so as to form a chamber 505b coinciding with conduit 520 and maintained in that position until the metered fluid is charged into the chamber 505!) before the next succeeding roller 512a is advanced over conduit 520. The liquid or fluid in chamber 50512 is maintained in substantially complete isolation from that in preceding chambers 505e, 5050! by movable seals 513b, 5130 formed by rollers 512b, 5120. In a corresponding fashion, as a roller 512a advances toward transverse seal 510 the chamber 505a defined by the moving roller seal 513a, the transverse seal 510 and inner and outer edge seals 506, 508 becomes progressively smaller, forcing any fluid in the chamber 505a through discharge conduit 522.
In the integrated apparatus, each chamber 505a, b, c, d is of sufficient size to receive the fluids discharged from the metering unit 200 through line 32 as well as a portion of the gas supplied from lines 25 and 28, so that line 32 and coupling conduit 520 receives an air wash following each discharge of the metering unit 200. The surge chamber 105 of the metering unit 200 provides pressurized gas sufficient to discharge the fluids from the metering unit to a chamber 505!) and to wash line 32 and coupling conduit 520 while limiting the pressure in the chamber.
Referring again to FIG. 1, each roller 512 is rotatably mounted on an arm 515 of a spider 514 by roller mountings 511 carried on the arm 515. Spider 514 is preferably disposed so as to maintain all the rollers 512 in simultaneous seal-forming engagement with sheet 504, regardless of whether the spider 514 and rollers 512 are moving or at rest. The spider and roller structure is powered through a shaft 516 driven by suitable power source, such as a low speed electric motor or the like (not shown). For example, operation of such a motor to rotate the shaft 516 at one-half revolution per minute, either by continuous or intermittent operation, would permit an eight-armed spider assembly of the transport unit 500 as depicted in FIGS. 1 and 11 to handle and transport over two hundred chambers of fluid per hour.
THE ACTUATOR UNIT In addition to spider 514, shaft 516 also carries cam wheels 302, 304, having their cam surfaces in engagement with a pair of cam followers 340, 350 by way of follower wheels 342, 352. The cam surfaces of cam wheels 302, 304 each comprise a series of projections 312, 314, respectively, coordinated with the arms of spider 514. Cam followers 340, 350 are slidably mounted in a sleeve block 306 to permit reciprocating longitudinal motion of each cam follower. Cam follower 340 engages the outer face of blade member 40 of the metering unit, and is biased toward the cam wheel 302 by the action of blade springs 42 on blade member 40. Cam follower 350 is similarly engaged with the outer face of blade member 50.
Cam wheel 302 is mounted on shaft 516 with its cam surfaces in coordination with the spider 514 so that blade member 40 is displaced from the lines sealed thereby when the transport unit 500 forms a chamber coincident with the coupling conduit 520. Cam wheel 304 is similarly mounted with its cam surfaces in coordination with spider 514 and cam wheel 302 so that blade member 50 is displaced from the lines sealed by blade member 50 only when blade member 40 seals lines 28, 30 and 32.
The projections 312 on cam wheel 302, and the distance between the projections 314 on cam wheel 304 correspond to the time employed in charging the metering unit pipet chambers. Similarly the projections 314 of wheel 304 and the circumferential distance between projections 312 of wheel 302 correspond to the time employed in discharging the fluid from the mixing unit into a chamber of the transport unit 500. The projections 314 also correspond to the distance between projections 312 so that the reciprocation of followers 340, 350 prevents simultaneous displacement of both blade members 40, 50 from their respective lines.
By varying such factors as the number and circumferential length of the projections, the rotation of the shaft 516 and the like, the type of correspondence between the operating cycle of the metering unit and the transport device can be varied as may be desired. For example, multiple metered charges of liquid can be fed into one or more of the chambers by employing multiple sets of cam projections to actuate multiple metering unit cycles through the same degree of rotation in which the spider and rollers form a single chamber at the coupling conduit. Alternately, the number of cam projections can be decreased to provide filling only of alternate successive chambers. The cam and follower assembly are preferably indexed to discharge a single metered quantity of fluid to each chamber regardless of whether the shaft 516, and spider and roller structure are rotated either continuously or intermittently. In a convenient procedure, rotation of the shaft, cam wheels, spider and rollers is stopped during each discharge phase of the metering unit operation cycle and the shaft 516 is rotated to advance a roller 512 and form a new chamber at conduit 520 while the metering unit 200 operates through a charging phase with the next successive quantity of fluids to be processed.
THE MIXING UNIT The spider 514 carries a plurality of mixing units 400 attached thereto by brackets 401. Each mixing unit 400 is mounted on the spider 514 between a pair of rollers 512 so that the position of the mixing unit 400 corresponds to the position of a chamber formed in the portion of the processing conduit between the two rollers.
Referring more particularly to FIG. 13, the mixing unit comprises a housing 402 having a pair of rods 404, 424 slidably disposed therein. The rods 404, 424 are biased normally away from the processing conduit and flexible sheet 504 by corresponding springs 406, 426 also mounted in housing 402. Each of the rods 404, 424 carries a foot plate 408, 428 and foot 410, 420 at the end of the rod nearest the flexible sheet 504, and a hemicylindrical contact member 412, 422 at the other end thereof. When in their normal position under the bias of springs 406, rods 404, 424 are slidably disposed in housing 402 with their foot plates 408, 428 against the end of the housing 402, the housing being so mounted on the spider 514 as to maintain the mixing unit feet 410, 420 normally spaced from the flexible sheet 504. Each of the rods 404, 424 is adapted to be slidably displaced in housing 402, when its corresponding contact member 412, 422 is depressed, to a position in which the foot 410, 420 contacts the flexible sheet 504 and compresses it against the transport unit plate 502.
The feet 410, 420 are preferably of a semirigid or resilient material such as rubber, urethane foam or the like, to minimize wear of the flexible sheet 504.
The action of the mixing unit is illustrated in FIG. 12. In oper: "on, the rods 404, 424 are alternately moved toward a chamber 505d between movable seals 513:: and 513d formed by a pair of rollers 512s and 512d the conduit defined by flexible sheet 504 and plate 502. As a rod 404 is moved toward the chamber, the foot 410 compresses the sheet 504 against the plate 502, driving the fluid in the chamber 505d to one side thereof. Rapid alternating compression of portions of the sheet 504 by the mixing unit feet 410, 420 drives the fluid rapidly across the chamber 505d, providing excellent mixing action. In a preferred embodiment, the combined area of both of feet 410, 420 of a mixing unit 400 is greater than half the area of a chamber 505d in the plane of the transport conduit.
As shown in FIGS. 1 and 14 the alternate reciprocating motion of the mixing unit rods 404, 424 is driven by a pair of elongated flexible curved members 432, 434. The curved members 432, 434 are mounted on support block 430 which can be mounted on unitary base 18. The support block 430 and curved members 432, 434 are disposed with respect to the path followed by the mixing units 400 carried by spider 514 so that each of the hemicylindrical contact members 412, 422 of each unit 400 engages a separate curved member 432, 434 when the mixing unit 400 arrives at an operating location. Each of the curved members 432, 434 is in turn driven by a corresponding eccentric 436, 438, respectively, which are mounted on a shaft 418. Shaft 418 is rotated by a conventional source of power such as an electric motor or the like (not shown). As best shown in H6. 14, the eccentrics 436, 438 are mounted on shaft 418 so as to drive the corresponding curved members 432, 434 and rods 404, 424 in reciprocating longitudinal motion in which the motion of rods 404, 424 is approximately l80 out of phase, thus providing for alternating compression of different portions of a chamber by the mixing unit feet 410, 420.
ln a preferred mode of operation, the spider 514 is rotated intermittently so that each chamber formed by the moving seals established by a pair of rollers 512 is held at position in which the contact members 412, 422 of the corresponding mixing unit 400 engages the shaft, eccentric and curved member structure. The mixing unit is activated to drive the shaft 418 while the spider is stationary and is inactivated when the spider is advancing. Activation of the mixing unit can be accomplished by employing appropriate means for activating the motor driving shaft 418 in response to the disposition of a mixing unit at the curved member and eccentric structure, such as by the use of a microswitch operated by the arms of the spider. Alternately, shaft 418 can be rotated continuously.
ln setting up the complete integrated apparatus of P16. 1 for operation, pressure supply line 25 is connected to a suitable source of pressurized gas and maintained under substantially constant pressure, and suction lines 24, 26 are connected to a vacuum pump and trap system for maintaining a suitable reduced pressure therein. Reagent supply line is connected to a reagent liquid source, conveniently by disposing an end thereof below the liquid level in a container of reagent liquid and the metering unit 200 or the valves thereof associated with charging pipct 80 are actuated sufficiently to fill supply line 20 with the liquid. Sample supply line 22 is connected to a sample reservoir 23 conveniently by disposing the end of sample line 22 below the liquid level in a sample liquid container. When several successive samples are to be processed, provision is made for manually or automatically connecting the sample supply line 22 with successive sample reservoirs and for exposing the end of sample supply line to air at the beginning of each charging phase to provide an air wash in the sample supply line 22. Discharge line 32 is coupled to coupling conduit 520 of the transport unit 500, line 524 from the transport unit discharge conduit 522 is coupled to colorimeter 525 and line 526 is provided with means for receiving processed, measured liquid which is ultimately discharged.
Operation is begun when the shaft 516 is rotated, driving the actuator cam wheel structure 302, 304 and the spider 514 and roller 512 assembly of the transport unit 500. Such rotation is accompanied by the charging of fluids into the pipets 70, of the metering unit 200, formation of chambers of the transport unit 500, discharge of the metered liquids from the metering unit 200 to separate chambers of the transport unit 500 via line 32 and transport and processing of the chamber contents including measurement of optical properties thereof in the colorimeter 525 prior to the ultimate discharge of the liquids through line 526 for disposal or further processing. Rotation of shaft 413 additionally brings about mixing of fluids in chambers of transport unit 500 as the mixing units 400 are moved into registry with the curved members 432, 434. When a given chamber 505b contains two fluids of different densities, such as an aqueous solution or the like and an oil or a gas, for example, the movement of the chamber 505b from conduit 520 to discharge conduit 522 contributes to further mixing as the vertical orientation of the chamber changes during rotation of the spider 514 and roller 512 assembly.
In an illustrative procedure, the apparatus can be employed in the colorimetric determination of total protein in serum samples by the biuret color reaction. In such procedure a pipct 80 adapted to meter 3 milliliters of biuret reagent and a pipct 70 adapted to meter 0.3 milliliter of serum are employed in metering unit 200, which is coupled via a discharge line 32 to transport unit 500 having an eight armed spider and roller assembly 514, 512. The actuator unit 300 employed is adapted to actuate the metering unit 200 for eight complete cycles of operation for each revolution of the spider and roller assembly 514, 512. Shaft 516 is driven in intermittent fashion so that rotation of the spider 514 is interrupted during operation of each mixing unit 400 and at a rate equivalent to about l revolution per 2 minutes, for example. In each metering unit cycle, sample pipct 70 is air washed at the beginning of each charging phase and prewashed with a portion of each serum sample after such air washing; both pipets 70, 80 are charged, then discharged so that pipct 70 is air washed with air from connecting line 30 and then rinsed with the biuret reagent discharged from pipet 80 via connecting line 30; both pipets are air washed with pressurized gas from pressure line 28 and surge chamber and the metered sample and reagent are charged into a chamber 505b of the transport apparatus with the resulting dilution of serum sample with reagent and followed by air washing of line 32 at the end of the discharge phase. At 1 revolution of shaft 516 per 2 minutes, the apparatus provides total protein determinations on over two hundred successive serum samples per hour, with excellent accuracy and precision.
The apparatus and procedure can be modified in a variety of ways to adapt the same to the carrying out of various processes. For example, the transport unit employed can have different configurations and can include a plurality of different processing means, including those described in my copending application Ser. No. 541,306, filed Apr. 8, 1966. The metering unit can include one, two, three or more pipets of differing shapes. One or more liquid reservoir of a metering unit can be a chamber 505a at the discharge conduit of a second transport device, or additional metering units can be coupled to a transport unit at different locations therealong. It will thus be apparent that the present invention is extremely versatile and readily adaptable for a great number of applications in fluid processing.
What is claimed is:
1. Apparatus useful for metering fluids comprising a pipet tube having first and second ends;
a first fluid conducting line selectively communicating with the first end of the pipct tube;
a second fluid-conducting line selectively communicating with the first end of the pipct tube and with the first line, and forming a three-way intersection therewith, each of the first and second lines having wall portions thereof which are movable with respect to each other between a relative position in which the wall portions of a line releasably seal the line adjacent the three-way intersection to form a two-way intersection of the other line with the pipet tube and another relative position in which the wall portions of a line are displaced to open the line;
means for providing suction in the first line;
7 means for providing fluid pressure in the second line; and
means operably engageable with each of said lines for selectively moving predetermined wall portions thereof to releasably seal each of the lines adjacent the intersection, said means being operable to form a releasable seal in a selected one of said lines thereby forming a two-way intersection of the other line with the pipet tube and being also operable to form releasable seals in both lines thereby forming a pipet chamber of predetermined volume defined by the pipet tube and the releasable seals.
2. Apparatus of claim 1 wherein the means for moving the line wall portions includes a blade and a platen adapted to move relative to each other between a line-sealing position in which wall portions of a line are compressed together therebetween to releasably seal the line, and a relative position in which the blade is displaced relative to the platen to open the line.
3. Apparatus of claim 2 further comprising means for bias ing the blade toward displacement from the platen whereby the line is normally open.
4. Apparatus of claim 2 further comprising means for bias ing the blade toward line sealing engagement with the wall portions of the line and with the platen and further comprising means for displacing the blade from the platen to open the line.
5. Apparatus of claim 4 wherein the platen comprises a portion of a block pivotally mounted in a frame, the block having a pair of legs which intersect each other at an angle, the movable wall portions of the lines lying along the legs within the angle formed by the intersection of the legs, wherein the blade comprises a blade member disposed within the angle formed by the intersection of the legs and having a pair of faces each adapted to compress one of the lines against a leg of the block, and wherein the means for displacing the blade from the platen includes cam means on the frame and corresponding cam means on the blade member for displacing individual faces of the blade member from their corresponding leg in response to pivotal motion of the block in the frame.
6. Apparatus useful for metering fluids comprising a pipet tube having first and second ends;
a first fluid-conducting line selectively communicating with the first end of the pipet tube;
a second fluid-conducting conducting line selectively communicating with the first end of the pipet tube and with the first line, and forming a three-way intersection therewith, each of the first and second lines having wall portions thereof which are movable with respect to each other between a relative position in which the wall portions of a line releasably seal the line and another relative position in which the wall portions of a line are displaced to open the line;
means for introducing a line;
means at the second end of the pipet for selectively applying suction to draw fluid into the pipet, sealing the second end of the pipet and applying fluid pressure to discharge the pipet; and
a transport conduit having opposed wall portions thereof adapted to move relative to each other, conduit sealing means for moving a selected plurality of said wall portions in a manner effective to establish a plurality of releasable movable seals in the conduit thereby dividing the conduit into a plurality of chambers, the sealing means, seals and chambers being movable along the conduit; and a second conduit communicating with the first conduit and adapted to communicate with an individual chamber when the position thereof corresponds to the position of fluid to be metered into the first the second conduit, the second conduit selectively communicating with the pipet through the second line, and means responsive to the position of the chambers for moving wall portions of the second line to open said second line when the position of an individual chamber corresponds to the position of the second conduit, thereby providing communication between the pipet and the chamber.
7. Apparatus useful for metering fluids comprising:
a pipet tube having first and second ends;
first and second fluid-conducting lines communicating with each other and forming a first three-way intersection with the first end of the pipet tube;
third and fourth fluid-conducting lines communicating with each other and forming a second three-way intersection with the second end of the pipet tube;
means for selectively forming a releasable seal in each of the lines immediately adjacent the intersections, whereby the releasable seals in the lines, the pipet tube and the intersection define a pipet chamber of predetermined volume, said means including movable wall portions of each line adapted to move between a relative position in which the wall portions form a releaseable seal in the line and another relative position in which the wall portions are displaced from each other to open the line;
means for coupling the first line to a source of fluid to be metered;
means for providing reduced pressure in the third line sufficient to draw a fluid to be metered from the first line into the pipet tube to the third line;
means for providing a pressure difference between the second and fourth lines sufficient to discharge fluid from the pipet tube;
first sealing means for simultaneously engaging the movable wall portions of the first and third lines to move said wall portions and seal the first and third lines; and
second sealing means for simultaneously engaging the movable wall portions of the second and fourth lines to move said wall portions and seal the second and fourth lines.
8. Apparatus of claim 7 wherein at least one of said lines communicates with a second pipet.
9. Apparatus of claim 7 further comprising a housing and a platen in the housing, the lines being mounted in the housing against the platen so that the movable wall portions of the first and third lines are aligned in a plane and the movable wall portions of the second and fourth lines are aligned in another plane, and wherein the first and second sealing means comprise first and second blade members movably disposed in the housing for movement toward and away from sealing engagement with the first and third lines and second and fourth lines, respectively.
10. Apparatus of claim 9 further comprising actuator means operably engaged with the first and second blades for moving said blades in a predetermined cycle of operation having a phase in which the second and fourth lines are sealed by compression between the second blade and the platen while the first blade member is displaced to open the first and third lines, a phase in which all the lines are sealed by compression between their respective blade members and the housing, and a phase in which the first and third lines are sealed by compression between the first blade and the platen while the second blade member is displaced to open the second and fourth lines.
11. Apparatus useful for metering fluids comprising:
a plurality of pipet tubes, each pipet tube having a pair of opposed ends for conducting fluid therethrough,
means for charging the pipet tubes with a plurality of fluids to be metered by pressure difference between the ends of the pipet tubes, said means including a plurality of fluid supply lines and suction lines, each fluid supply line and each suction line being in communication with opposed ends of each pipet tube;
means for discharging the pipet tubes by pressure difference between the ends of the pipet tubes, said means including a plurality of pressure supply lines and fluid discharge lines, each pressure supply line and each fluid discharge line being in communication with opposed ends of each pipet, and at least one of the pressure supply lines communicating with an end of one of the pipets also being the discharge line communicating with an end of another p p means for operating the charging means including means for releaseably sealing the pressure line and the discharge line communicating with each pipet to provide releasable seals in the pressure and discharge lines corresponding to each pipet during charging thereof and means for providing communication between each fluid supply line and a corresponding source of a fluid to be metered in the pipet communicating with the fluid supply line;
means for terminating the charging of the pipets including means for releasably sealing the fluid supply line and the suction line communicating with each of the pipets; and means for operating the discharging means including means for releasing the releaseable seals in the pressure lines and the discharge lines, and means for supplying fluid pressure in at least one of the pressure lines for discharging metered fluids from the pipets; each of the lines having wall portions which are movable with respect to each other between a relative position in which said wall portions releasably seal the line and another relative position in which the wall portions are displaced to open the line, the operating means including means for moving the wall portions of the line between said relative positions.
12. Apparatus of claim 11 wherein the means for forming a releasable seal in each of the lines includes a blade and platen adapted for relative movement with respect to each other, the wall portions of a line being moved together to seal the line by compression between a blade and a platen.
13. Apparatus of claim 11 further comprising means for applying suction in a suction line independently of the operation of the charging means and discharging means.
14. Apparatus of claim 1 1 further comprising means including a surge chamber for supplying a predetermined volume of fluid under pressure in a pressure line during the operation of the discharging means.
15. Apparatus of claim 11 further comprising a transport conduit having opposed wall portions thereof capable of movement relative to each other, conduit sealing means for moving a selected plurality of said conduit portions in a manner effective to establish a plurality of releasable movable seals in said conduit thereby dividing the transport conduit into a plurality of chambers, the sealing means being movable along the transport conduit while maintaining releasable seals and chambers therein so that the seals and chambers are movable along the conduit, and a second conduit communicating with the transport conduit and adapted to communicate with individual chambers when the position of a chamber corresponds to the position of the second conduit; and wherein at least one of the discharge lines communicates with the second conduit.
16. In an apparatus for transporting fluids along a transport conduit in separate movable chambers formed therein, the apparatus comprising a transport conduit having opposed wall portions thereof capable of movement relative to each other, conduit-sealing means for moving a selected plurality of said conduit portions in a manner effective to establish a plurality of releasable movable seals in said conduit thereby dividing the transport conduit into a plurality of chambers, the sealing means being movable along the transport conduit while maintaining releasable seals and chambers therein so that the seals and chambers are movable along the conduit, and a second conduit communicating with the transport conduit and adapted to communicate with individual chambers when the position of a chamber corresponds to the position of the second conduit; the improvement which comprises: a plurality of pipets selectively communicating with the second conduit, means for charging each pipet with a first fluid, said charging means including a source of the first fluid and a source of suction, discharge means including a source of a second fluid under pressure for discharging the first fluid from the pipets through the second conduit, pipet-operating means including a plurality of fluid-conducting lines providing selective communication between the pipets and the first fluid source, the suction source, the second fluid source and the second conduit, first line-sealing means for selectively sealing a first plurality of said lines so that the first fluid is drawn into each pipet from the source by suction and second line-sealing means for sealing a second selected plurality of said lines so that the first fluid is discharged from the pipets through the second conduit.
17. The apparatus of claim 16 further comprising means responsive to the position of the conduit-sealing means along the transport conduit for actuating the first and second linesealing means for discharging fluid from the pipets to a chamber of the transport conduit when the chamber communicates with the second conduit.
18. The apparatus of claim 16 wherein an individual chamber of the transport conduit is adapted to contain a volume of fluid in excess of the volume of the pipets and the means for actuating the second line-sealing means are adapted to discharge the first fluid from the pipets and a portion of the second fluid, whereby the pipets and lines are washed with said portion of the second fluid.
19. The apparatus of claim 18 further comprising means disposed along the conduit for mixing the fluid contents of a chamber, said means including a plurality of members adapted alternately to compress together and release wall portions of the transport conduit forming an individual chamber thereby driving the contents thereof alternately from one portion of the chamber to another.
20. Apparatus for pipetting of fluids comprising:
a housing, portions of the housing being adapted to receive opposed ends of a pipet;
a plurality of fluid-conducting lines carried on the housing and forming three-way fluid-conducting intersections with the pipet end-receiving portions, each of said lines having wall portions movable with respect to each other between a relative position in which the line is sealed and a relative position in which the line is open;
means mounted on the housing for selectively moving predetermined wall portions of a first plurality of lines to seal said lines thereby forming two-way intersections between a second plurality of lines and the pipet end receiving portions;
means mounted on the housing for selectively moving predetermined wall portions of the second plurality of lines to seal the second plurality of lines, thereby forming two-way intersections between the first plurality of lines and the pipet end-receiving portions.
21. Apparatus of claim 20 further comprising means for actuating the line-sealing means in a predetermined cycle of operation which includes a first phase in which the first plurality of lines is open and the second plurality of lines is sealed, a second phase in which all the lines are sealed and a third phase in which the first plurality of lines is sealed and the second plurality of lines is open.
22. A method for metering fluids in a pipet tube having first and second ends, the first end thereof forming one arm of a three-armed intersection of the first end of the pipet tube with a suction line adapted to have pressure maintained therein sufficiently below the pressure at the second end of the pipet tube to draw a first fluid through the pipet tube from the second end thereof and a pressure line adapted to provide a second fluid under sufficient pressure relative to the pressure at the second end of the pipet to discharge the first fluid from the pipet tube through the second end thereof, both of said lines having wall portions capable of movement relative to each other, the method comprising:
charging, including the steps of moving predetermined wall portions of the pressure line in such a manner as to establish a releasable seal therein adjacent the intersection, moving the wall portions of the suction line to displace said wall portions from each other so as to maintain the suction line in an open state and in communication with the pipet tube, supplying a first fluid to be metered at the second end of the pipet tube, applying suction in the suction line sufficient to draw the first fluid into the pipet tube and continuing the application of suction until the pipet tube and the intersection are filled with the first fluid and a portion thereof has been drawn into the suction line; terminating said charging, including the step of moving predetermined wall portions of the suction line in such a manner as to establish a releasable seal therein adjacent the intersection so that a pipet chamber of predetermined volume is defined by the pipet tube, the intersection and the seals, thereby sealing a corresponding predetermined volume of the first fluid in the pipet chamber; and
discharging, including the steps of displacing the preselected wall portions of the pressure line in such a manner as to release the seal therein and open the pressure line, and supplying the second fluid in the pressure line at a pressure sufficient to discharge the first fluid through the second end of the pipet tube.
23. The method of claim 22 wherein the steps of moving the wall portions comprises the step of compressing the wall portions together to form the seals.
24. The method claim 22 wherein the second end of the pipet tube comprises one arm of a three-armed intersection of the second end of the pipet tube with a fluid supply line and a discharge line, the fluid supply line communicating with a source of the first fluid under a pressure sufficiently greater than the pressure obtaining in the suction line to permit the first fluid to be drawn through the supply line and pipet tube to the suction line, both of said lines having wall portions capable of movement relative to each other, and wherein charging further comprises the steps of moving wall portions of the discharge line so as to establish a releasable seal therein, and moving the wall portions of the fluid supply line so as to maintain the fluid supply line in an open state;
wherein terminating said charging further comprises moving wall portions of the fluid supply line in such a manner as to establish a releasable seal therein so that a pipet chamber of predetermined volume is formed by the pipet tube, the intersections and the seals; and
wherein discharging further comprises moving wall portions if the discharge line in such a manner as to release the seal therein and open the discharge line.
25. The method of claim 24 wherein the discharge line communicates with a conduit having opposed portions capable of movement relative to each other, the discharge line communicating with the conduit at a location along the length thereof; and further comprising the steps of moving a selected plurality of said conduit portions in a manner effective to establish a plurality of spaced releasable seals forming chambers in the conduit, moving the seals relative to the conduit to cause the chambers to move progressively along the conduit thereby causing the chambers to be successively presented at the location along the conduit at which the conduit communicates with the discharge line, and discharging the pipet when a chamber is presented at such location, thereby enabling fluid metered in the pipet chamber to be added to a chamber independently of other such chambers.
26. The method of claim 24 wherein the discharge line forms one arm of three-armed intersection of the discharge line with a first end of a second pipet tube and with a second suction line adapted to have pressure maintained therein sufficiently below the pressure at a second end of the second pipet tube to draw a third fluid through the second pipet tube from the second end thereof, the pressure line being adapted to provide the second fluid under sufficient relative to the ressure at the second end of the second pipet to discharge t e third fluid from the second pipet tube through the second end thereof and to discharge the first fluid from the first pipe tube through the discharge line and through the second pipet tube at the second end thereof, both of said discharge and second suction lines having wall portions capable of movement relative to each other, the method further comprising:
charging the second pipet tube, including the steps of moving wall portions of the discharge line in such manner as to establish a releasable seal therein adjacent the intersection with the first end of the second pipet tube, moving the wall portions of the second suction line to displace said wall portions from each other so as to maintain the second suction line in an open state and in communication with the second pipet tube, supplying a third fluid to be metered at the second end of the second pipet tube, and applying suction in the second suction line sufficient to draw the third fluid into the second pipet tube; thereafter terminating said charging, including the step of moving wall portions of the second suction line in such a manner as to establish a releasable seal therein adjacent the intersection with the first end of the second pipet tube so that a pipet chamber of predetermined volume is defined by the pipet tube, the intersection and the seals; and
discharging the second pipet, including the step of moving wall portions of the discharge line and the pressure line in such a manner as to release the seal therein and open the pressure line, and supplying the second fluid under pressure in the pressure line sufficient to discharge the third fluid through the second end of the second pipet tube.
27. The method of claim 26 wherein the step of moving the wall portions comprise the step of compressing the wall portions together to form the seals.
28. The method of claim 26 wherein discharging the second pipet tube is carried out subsequent to charging of the first pipet tube and wherein the second fluid is supplied under pressure sufficient to discharge both the first and third fluids through the second end of the second pipet tube.
29. The method of claim 26 wherein sufficient third fluid is supplied to wash the discharge line and the first and second pipet tubes therewith, and wherein suction is applied in the second suction line in such a manner as to draw a portion of the third fluid through the second pipet and into the second suction line, said portion being sufficient to prewash the second pipet.
P0405) UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3, 7, 2 D d 21 September 1971 Inventofls) Ralph E. Thiers It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
In column 1, line 51, delete "Moreover" and insert Movable In column 5, line 1h, delete "l6" and insert 26 In column 6, line 19, delete "175" and insert 11h in line 38 delete "90" and insert 190 In column 9, line 2T, delete "plated" and insert platen In column 19, line +9, delete "if" and insert of In column 20, Claim 26 line 16, delete "pipe" and insert pipet Signed and sealed this 16th day of May I972.
EDWARD M.F'LEICHER,JR. ROBERT GOTTSCHALK Attesting Officer Co issioner of Patents