Sampling metering and transfer valve assembly and analyzing system employing same

• US 5,460,055 A
• Filed: 01/10/1994
• Issued: 10/24/1995
• Est. Priority Date: 11/22/1991
• Status: Expired due to Fees

• Current Assignee: Coulter Corporation (Danaher Corporation)
• Original Assignee: Coulter Corporation (Danaher Corporation)
• Inventors: Parker, Bernard
• Primary Examiner(s): Raevis, R.
• Application Number:
  US08/178,719
• Time in Patent Office: 652 Days
• Field of Search: 73/863.71, 73/863.73, 73/863.83, 73/863.84, 422/103, 251/85
• US Class Current: 73/863.73
• CPC Class Codes: G01N 35/1097 characterised by the valves valves in general F16K

Abstract

A multifunctional liquid sampling, metering and transfer valve assembly and the analytical system employing same. The valve assembly is capable of performing all liquid handling functions therewithin. The valve assembly comprises a pair of coaxially arranged valve discs engaged in frictional, sealed face to face disposition and includes plural axially parallel through passageways arranged for selective communication, one disc being rotatable relative to the other. Plural dedicated flow paths are defined by said passageways for metering, storing and delivering precise volume aliquots of sample, of diluent and of lysing reagent (in respect of blood cell study) from sources of said liquids to mixing and/or testing chambers. Vacuum is employed to move the liquids along the dedicated flow paths aiding in preventing leakage from the junctions of the passageways within the valve assembly along the engaged surfaces. Further, the valve assembly is provided with a gimballed mounting coupling the assembly to a stepper motor, said mounting preventing vertorial misalignment of the discs (and passageways) during operation of the valve assembly. programmable control is provided so as to operate the valve assembly in accordance with a preset operational pattern.

Claims

1. A sampling, metering and transfer valve assembly comprising at least a pair of valve disc elements capable of being coaxially arranged, one being a rotor and the other being a stator, said valve disc elements having flat facing surfaces assembled in frictional, sealed engagement, each valve element having plural axially parallel passageways formed therethrough capable respectively for successive selected placement in communication to establish plural dedicated flow paths within the valve assembly for accommodating respectively plural different liquid bodies therein, rotation of said rotor selectively isolating precise volume aliquot portions of said different liquid bodies respectively, storing said aliquot portions of each of said different liquid bodies within said valve assembly for later retrieval, and delivering said stored aliquot portions to predetermined respective testing locations, each of said dedicated flow paths having an entry and an outlet, drive means comprising a balanced gimballed mounting for maintaining said facing surfaces sealingly engaged with the alignment of the junctures of said plural axially parallel passageways being maintained notwithstanding the exercise of rotary force upon said surfaces tending to misalign said passageways during successive rotations of said rotor whereby to maintain the continuity and integrity of said plural dedicated flow paths.

2. The valve assembly according to claim 1 and a source of differential pressure, means for coupling said source of differential pressure to the respective flow paths for moving selectively said liquid bodies along said flow paths during operation of said valve assembly.

3. The valve assembly according to claim 1 and a source of reduced pressure, means for coupling said source of reduced pressure to the respective outlets of said flow paths for moving selectively said liquid bodies along said flow paths during operation of said valve assembly.

4. The valve assembly according to any one of claims 1, 2 or 3 in which said plural dedicated flow paths are independent of each other.

5. The valve assembly according to any one of claims 1, 2 or 3 in which said plural flow paths constitute independent, dedicated flow paths each adapted to be traversed by only one type of liquid body respectively.

6. The valve assembly according to claim 1 in which said plural axially parallel passageways which define said plural dedicated flow paths include first and second measuring passageway sets arranged in serial communication for defining a continuous body of liquid sample introduced therein, said rotor being translatable to isolate aliquots of liquid sample from said continuous body and to store same within said first and second passageway sets, respectively;

third and fourth measuring passageway sets arranged in serial communication for defining a continuous body of liquid diluent introduced therein, said rotor being translatable to isolate aliquots of liquid diluent and store said aliquots within each of said third and fourth measuring passageways sets, respectively; and

a firth measuring passageway set for defining a continuous body of liquid reactive reagent therein, said rotor being translatable to isolate and to store an aliquot of liquid reactive reagent within said fifth measuring passageway set;

circulating passageways within said valve assembly defining, along with said measuring passageway sets, dedicated flow paths through said valve assembly respectively, said measuring passageway sets and said circulating passageways including selected ones of said plural axially parallel passageways;

each of said aliquots, respectively, being deliverable along the dedicated flow paths within said valve assembly to said respective testing locations, a source of reduced pressure, said delivery being effected along said dedicated flow paths under reduced pressure applied to the outlets of said dedicated passageways, the opposite ends of said dedicated flow paths defining trailing ends of said dedicated flow paths and said trailing ends being open to ambient atmosphere.

7. The valve assembly according to any one of claims 1, 2 or 3 in which one of said liquid bodies is a reactive reagent.

8. The valve assembly according to any one of claims 1 2 or 3 in which one of said liquid bodies is a lysing agent.

9. The valve assembly according to claim 1 including first and second measuring passageway sets arranged in serial communication for defining a continuous body of liquid sample introduced therein, said rotor being translatable to isolate aliquots of liquid sample from said continuous body and to store same within said first and second passageway sets respectively;

third and fourth measuring passageway sets arranged in serial communication for defining a continuous body of liquid diluent introduced therein, said rotor being translatable to isolate aliquots of liquid diluent and to store said aliquots within each of said third and fourth measuring passageway sets, respectively; and

a fifth measuring passageway set for defining a continuous body of liquid reactive reagent therein, said rotor being translatable to isolate and to store an aliquot of liquid reactive reagent within said fifth measuring passageway set;

circulating passageways within said valve assembly and feed passageways within said valve assembly defining, along with said measuring passageway sets, said dedicated flow paths through said valve assembly, respectively, said measuring passageway sets, said circulating passageways and said feed passageways including selected ones of said plural axially parallel passageways;

each of said aliquots, respectively, being deliverable along said dedicated flow paths within said valve assembly to said respective testing locations, a source of reduced pressure, movement of liquids being effected along said dedicated flow paths under reduced pressure applied to the outlets of said dedicated passageways, the opposite ends of said dedicated flow paths defining trailing ends of the liquid within said dedicated flow paths a source of pressurized inert gaseous fluid, selected ones of said trailing ends being coupled to said source of pressurized inert gaseous fluid for moving said respective liquids along said respective dedicated flow paths.

10. The valve assembly according to claim 1 including first and second passageway sets arrangeable in serial communication for defining a continuous body of liquid sample introduced therein, said rotor being translatable to isolate aliquots of liquid sample from said continuous body and to store same within said first and second passageway sets, respectively;

third and fourth measuring passageway sets arrangeable in serial communication for defining a continuous body of liquid diluent introduced therein, said rotor being translatable to isolate aliquots of liquid diluent and to store said aliquots within each of said third and fourth passageway sets, respectively; and

a first measuring passageway set for defining a continuous body of liquid reactive reagent within said first measuring passageway set;

circulating passageways and feed passageways within said valve assembly defining, along with said measuring passageway sets, said dedicated flow paths through said valve assembly, respectively, said measuring passageways, said circulating passageways and said feed passageways including selected ones of said plural axially parallel passageways;

each of said aliquots, respectively, being deliverable along said dedicated flow paths within said valve assembly to said respective testing locations, a source of reduced pressure, movement of liquids beings effected along said dedicated flow paths under reduced pressure applied to the outlets of said dedicated flow paths, the opposite ends of said dedicated flow paths defining trailing ends of said liquids within said dedicated flow paths a source of pressurized air, selected ones of said trailing ends being coupled to said source of pressurized air for supplementing the effect of said reduced pressure in moving the respective liquids to said respective testing locations.

11. The valve assembly according to claim 1 including first and second measuring passageway sets arranged in serial communication for defining a continuous body of liquid sample introduced therein, said rotor being translatable to isolate aliquots of liquid sample from said continuous body and to store same within said first and second passageway sets, respectively;

third and fourth measuring passageway sets arranged in serial communication for defining a continuous body of liquid diluent introduced therein, said rotor being translatable to isolate aliquots of liquid diluent and store said aliquots within each of said third and fourth measuring passageway sets, respectively; and

a fifth measuring passageway set for defining a continuous body of liquid reactive reagent therein, said rotor being translatable to isolate and to store an aliquot of liquid reactive reagent within said fifth measuring passageway set;

circulating passageways within said valve assembly defining, along with said measuring passageway sets, said dedicated flow paths through said valve assembly, respectively;

said measuring passageway sets and said circulating passageways including selected ones of said plural axially parallel passageways;

each of said aliquots, respectively, being deliverable along the dedicated flow paths within said valve assembly to said respective testing locations, a source of reduced pressure, said delivery being effected under reduced pressure applied to the outlets of said dedicated flow paths, the opposite ends of said dedicated flow paths defining trailing ends of the liquids within said dedicated flow paths, a source of pressurized air, selected ones of said trailing end portions being coupled to said source of pressurized air for application thereof thereto simultaneously during application of reduced pressure to the outlets of said dedicated flow paths.

12. The valve assembly according to any one of claims 1, 2 or 3 in which there is provided a source of gaseous fluid pressure, means coupling said source of gaseous fluid pressure to the respective testing locations for introduction of gaseous fluid pressure to said testing locations subsequent to delivery thereto of said selected ones of said aliquots for mixing of said aliquots.

13. The valve assembly according to any one of claims 1, 2 or 3 in which there is provided a source of gaseous fluid pressure, means coupling said source of gaseous fluid pressure to the respective testing locations for introduction of said gaseous fluid pressure in pulsed delivery to said testing locations by way of said valve assembly subsequent to delivery thereto of selected ones of said aliquots for mixing said aliquots.

14. The valve assembly according to claim 1 and a source of reduced pressure, said reduced pressure being applied in pulses to the testing locations immediately subsequent to delivery of said aliquots of liquid diluent and said aliquots of liquid reactive reagent respectively thereto, whereby to introduce air as mixing bubbles thereinto.

15. The valve assembly according to any one of claims 1, 2 or 3 and programmable control means coupled to said drive means for effecting selective step by step rotation of said rotor coordinated to effect the introduction of said respective liquids, isolation and storage of said respective aliquots and delivery of said respective aliquots to the respective locations in a predetermined order of occurrence.

16. The valve assembly according to any one of claims 1 2 or 3 and programmable control means governing translation of said rotor in accordance with a predetermined step by step operational pattern and further including sensing means at said testing locations providing data for determining selected characteristics of said liquid sample.

17. The valve assembly according to any one of claims 1, 2 or 3 in which selected ones of said parallel passageways are linked by hollow externally extending loops having precise interior volumes, respectively, for forming said respective aliquots of said respective liquids, isolating and storing said aliquots respectively therein for later retrieval.

18. The valve assembly according to any one of claims 1, or 2 and a housing for accommodating said valve assembly, said balanced gimballed mounting comprising first means defining a pivot axis, said drive means including a driven shaft and means coupling the axial portion of said rotor to said driven shaft, said coupling means lying along a line 180 degrees angularly spaced from said first pivot axis defining a second pivot axis, said stator having limited freedom of movement about said first pivot axis and said rotor having limited freedom of movement about said second pivot axis to permit inclination of said stator to effect compensatory identical inclination of said rotor and stator facing surfaces during relative rotation of said rotor and stator.

19. The valve assembly according to any one of claims 1, 2 or 3 and a housing for accommodating said valve assembly, said balanced gimballed mounting comprising first pin means secured at diametrically opposed locations of the outer circumference of said stator and said first pin means being coupled to said housing defining a first pivot axis extending through said first pin means, said stator and rotor each having a coaxial center passageway, said drive means including a driven shaft arranged to pass through said center passageways and means coupling the axial portion of said rotor to said driven shaft, said last mentioned coupling means defining a second pivot axis lying along a line 180 degrees angularly spaced from said first pivot axis and said rotor has limited freedom of movement about said second pivot axis to permit inclination of said stator to effect compensatory identical inclination of said rotor and stator facing surfaces during relative motion of said rotor and stator.

20. The valve assembly according to claim 1 and a source of differential pressure;

and further, there being plural measuring passageway sets including selected pairs of said plural axially parallel passageways formed in said valve disc elements, each measuring passageway set including a hollow, outwardly extending loop linkage therebetween to define a measuring chamber having a precise interior volume;

selected ones of others of said plural axially parallel passageways defining circulating passageways and feed passageways within said valve disc elements;

relative rotation of said rotor and stator isolating said precise volume aliquots of the respective different liquid bodies within respective measuring chambers for temporary storage therein;

said measuring, circulating and feed passageways defining said plural dedicated flow paths respectively distinct for each of said different liquid bodies, each of said dedicated flow paths handling only one type of liquid, respectively;

all metering, isolating, storing and delivery of said precise volume aliquots being effected within said valve assembly;

further rotation of said rotor enabling passage of said respective aliquots along respective dedicated flow paths under the influence of said differential pressure to said testing locations.

21. The valve assembly according to claim 1 and a source of differential pressure;

and further, there being plural measuring passageway sets including selected pairs of said axially parallel passageways formed in said valve elements, each measuring passageway set including a hollow outwardly extending look linkage therebetween to define a measuring chamber having a precise volume;

selected ones of others of said plural axially parallel passageways defining respectively, circulating passageways and feed passageways within said valve assembly, said circulating passageways and feed passageways, with said measuring passageway sets, defining said plural dedicated flow paths, rotation of said rotor relative said stator isolating said precise volume aliquots of the respective liquid bodies within said measuring chambers for temporary storage therein and later retrieval thereof, all liquid metering, isolating, storing and delivery of said precise volume aliquots being effected within said valve assembly, movement of said respective liquids and aliquots thereof along said dedicated flow paths being effected under the influence of said differential pressure respectively.

22. The valve assembly according to claim 21 in which said source of differential pressure includes a vacuum source, means coupling said vacuum source to the outlets of selected ones of said dedicated flow paths, vacuum being applied during the introduction of said respective different liquids to said respective flow paths.

23. In apparatus for ascertaining a plurality of parameters of biological liquid samples such as blood, said apparatus including respective sources of diluent and reactive reagent, at least a pair of testing chambers including mixing and sensing portions, the sensing portion including fine aperture sensing means and electrode means providing an independent scanning circuit for obtaining signals arising from the passing of a portion of the sample through the restricted current field defined within the fine aperture sensing means, means for electrically detecting the respective signals produced by the scanning circuits and deriving therefrom a plurality of electrical pulses whose amplitude respectively is proportional to selected characteristics of the biological liquid sample passing through said fine aperture sensing means, means for deriving separate accumulated values respectively of the number of pulses produced in the respective detecting means, means for computing, storing and displaying data representative of each of the plurality of parameters of said biological liquid samples;

the improvement comprising, a multifunctional sampling, metering and transfer valve assembly for performing all the fluid handling functions within the valve assembly to meter, to isolate, to store for later retrieval and to deliver precise volume aliquots of liquid sample, of diluent and of reactive reagent respectively from sources thereof to respective testing chambers, said valve assembly formed of at lest a pair of coaxially disposed valve disc elements superposed and arranged engaged in frictional, sealed face to face surface engagement, one of said valve disc elements constituting a rotor and the other of said valve disc elements having a plurality of axially parallel through passageways, selected pairs of said passageways being linked by a hollow outwardly extending loop, each pair of said passageways together with the loop defining a measuring chamber, selected other ones of said passageways also comprising circulating passageways and feed passageways together with respective measuring chambers defining plural dedicated flow paths, each having an inlet and an outlet and each adapted to contain only one type of liquid, respectively, said rotor being step-wise rotationally translatable relative to said stator in accordance with a preprogrammed order, preprogrammed control means for effecting operation of said valve assembly in accordance with said order, each of said dedicated flow paths capable of receiving a respective one of plural independent continuous bodies of said liquid sample, of liquid diluent and of liquid reactive reagent, rotary translation of said rotor effecting the metering, isolating and storing for later retrieval, respectively, of precise volume aliquots of each of said continuous liquid bodies within said respective measuring chambers, all metering, isolating and storing of said aliquot volumes being effected within said valve assembly, means for delivering each of said aliquots to said testing chambers along said respective dedicated flow paths, there being a source of differential pressure and said delivery being effected under the influence of said differential pressure, drive means for effecting step by step translating of said rotor relative to said stator, and means mounting said valve assembly to said drive means and means preventing misalignment of said passageways at the junctures thereof notwithstanding the vectorial forces tending to be caused by the rotational force exercised upon the facing frictionally sealingly engaged surfaces during the translation of said rotor relative to said stator while the valve assembly is in operation and the rotor is moving, and said mounting means comprise a balanced gimballed mounting arrangement coupling said valve assembly to the drive means therefor.

24. The apparatus of claim 23 wherein said reactive reagent is a lysing agent.

25. The apparatus according to claims 23 or 24 in which said mounting means comprise a gimballed mounting arrangement capable of maintaining the rotor and stator in face to face sealed frictional engagement yet permitting limited relative freedom of movement of said rotor and stator whereby inclination of one of said rotor and stator will be compensated by identical inclination of the other of said rotor and stator following said one element during relative rotation whereby frictional engagement and alignment of said rotor and stator is maintained.

26. The apparatus according to claims 23 or 24 in which said mounting means comprise a balanced gimballed mounting having support means for the valve assembly, first pin and slot means carried by said support means and said stator at diametrically opposed locations thereon, second pin and slot means carried by said rotor and said drive means, said second pin and slot means located along a line taken 180 degrees from a line taken through the first pin and slot means, whereby the stator is gimballed at the circumference thereof and the rotor is gimballed at the center thereof thereby defining a four point balanced gimballed coupling relationship of the valve assembly to the drive means.

27. A sampling, metering and transfer valve assembly comprising at least a pair of valve disc members coaxially arranged, at least one being a rotor, said valve disc members having flat facing surfaces assembled in frictional sealed engagement, each valve disc member having plural axially parallel through passageways located respectively for successive selective placement in communication to establish plural dedicated flow paths within said valve assembly for accommodating respectively plural different independent continuous bodies of respectively different types of liquids therein from sources thereof, said rotor being rotatable selectively successively for metering, isolating and storing for later retrieval precise volume aliquot portions of each of said respective different liquid bodies within said valve assembly and delivering said stored aliquot portions to a testing chamber as a series of successive operations, respectively, each of said plural dedicated flow paths receiving only one type of liquid, respectively, all metering, isolating, storing and delivery of said aliquot volumes being effected within said valve assembly, each of said dedicated flow paths having an inlet and an outlet, means coupling said outlets respectively to said testing chamber, and means maintaining said frictionally engaged faces of said valve disc members in sealed frictional engagement notwithstanding the exercise of vectorial force effects upon the facing surfaces of said valve disc members tending to arise during successive rotation of said rotor while the valve assembly is operating said means comprising providing a source of less than atmospheric pressure, means coupling said source of less than atmospheric pressure selectively to the respective outlets of said dedicated flow paths, maintaining the respective inlets of said dedicated flow paths selectively open to the ambient atmosphere whereby to enable air to be drawn therein while the less than atmospheric pressure is drawn on the respective outlet for moving liquid through said dedicated flow paths respectively, and drive means for step-by-step rotation of said rotor and said maintaining means additionally include a balanced gimbal mounting of the rotor coupling said rotor to said drive means and maintaining the axially parallel through passageways against misalignment at their junctures.

28. The valve assembly according to claim 27 in which there is provided a source of gaseous fluid pressure greater than atmospheric pressure and means for coupling said source of gaseous fluid pressure greater than atmospheric pressure to the inlets of selected dedicated flow paths for aiding in effecting delivery to said testing locations.

29. The valve assembly according to claim 27 wherein said axially parallel through passageways include first and second measuring passageways formed in said valve disc members and hollow outwardly extending loops linking said first and second measuring passageways and arranged in serial communication respectively to define one of said dedicated flow paths for receiving a continuous body of liquid sample introduced therein from a source thereof, said rotor being translatable to segment said continuous body of liquid sample whereby to meter, isolate and gore for later retrieval precise volume aliquots of liquid sample within said valve assembly, other of said axially parallel through passageways include third and fourth measuring passageways formed in said valve disc members and second hollow loops linking said third and fourth measuring passageways arranged in serial communication for defining a second dedicated flow path for receiving a continuous body of liquid diluent introduced therein from a source thereof, translation of said rotor segmenting said continuous body of liquid diluent meter&

isolating and storing for later retrieval precise volume aliquots of said liquid diluent within said valve assembly, said plural axially parallel passageways further including fifth and sixth measuring passageways formed in said valve disc members arranged in serial communication and a third hollow loop linking said fifth and sixth passageways to define a third dedicated flow path for receiving a continuous body of liquid lysing reagent introduced therein from a source thereof, translation of said rotor segmenting said continuous body of liquid lysing reagent isolating and storing for later retrieval a precise volume aliquot of said liquid lysing reagent within said valve assembly, said plural axially parallel passageways including cooperating circulating passageways arranged in communication with respective ones of said aliquot portions said plural axially parallel passageways additionally including feed passageways arranged capable of being coupled to said respective sources, respectively, and together further defining said dedicated flow paths, respectively, said means for moving said liquids along respective dedicated flow paths comprising said source of lower than atmospheric pressure for pulling the respective liquids along the respective dedicated flow paths.

30. A multifunctional sampling, metering and transfer valve assembly for use in a particle study system and capable of performing all required liquid handling functions within said valve assembly to provide metered, isolated and stored precise volume aliquots of liquid sample, of liquid diluent and of liquid reagent, respectively, within said valve assembly for delivery to predetermined testing chambers in accordance with a preprogrammed order of operation, said valve assembly comprising at least a pair of valve disc elements arranged superposed and having facing surfaces frictionally sealably engaged, one of said pair of valve disc elements being a rotor and the other of said pair of valve disc elements being a stator, said rotor and stator each having plural through, axially parallel passageways of precise internal volume selectively alignable, said rotor being selectively and successively angularly rotationally translatable step-wise relative to said stator to place selected ones of said passageways as sets in communication, each passageway set being linked by a hollow, outwardly extending loop of precise internal volume defining measuring chambers, there being additionally, plural cooperating axially parallel feed passageways and plural cooperating axially parallel circulating passageways, said passageways adapted to define plural non-interferant dedicated liquid flow paths through said valve assembly, each of said flow paths receiving only one of type of said liquids, all metering, isolating, storing and delivery of said respective liquids being effected within said valve assembly, each of said liquid flow paths having an entry and an outlet, drive means adapted to be coupled to said rotor and stator in assembly for step-wise translation of said rotor and means maintaining said assembly in face to face aligned frictional sealed engagement notwithstanding the tendency of the rotational forces to effect misalignment of said passageways at their junctures during rotation of said rotor whereby to prevent leakage and prevent misalignment of said passageways at their junctures said maintaining means include means defining a balanced gimballed mounting coupling said drive means to said valve assembly maintaining said frictional sealed engagement during rotation of said rotor yet permitting limited relative freedom of movement of said valve disc elements whereby inclination of one of said elements will be compensated by identical following inclination of the other of said elements so that vectorial misalignment of the junctions of said passageways at the facing surfaces of said elements is prevented during operation of said valve assembly.

31. The valve assembly according to claim 30 wherein there is a source of reduced pressure and said maintaining means includes means coupling the respective outlets to the source of reduced pressure for drawing reduced pressure on said outlets effecting movement of said liquids through said dedicated flow paths.

32. The valve assembly according to claim 30 in which air is permitted to flow into the inlets of said dedicated flow paths while less than atmospheric pressure is applied at the outlets thereof.