US3635680A - Automatic method and apparatus for the sequential typing of blood samples - Google Patents

Automatic method and apparatus for the sequential typing of blood samples Download PDF

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US3635680A
US3635680A US864263A US3635680DA US3635680A US 3635680 A US3635680 A US 3635680A US 864263 A US864263 A US 864263A US 3635680D A US3635680D A US 3635680DA US 3635680 A US3635680 A US 3635680A
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reagent
blood sample
cells
stream
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John C A Peoples
Stanford L Adler
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Bayer Corp
Technicon Corp
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Technicon Corp
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00435—Refrigerated reagent storage
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/807—Apparatus included in process claim, e.g. physical support structures
    • Y10S436/808—Automated or kit

Definitions

  • ABSTRACT Y Method and apparatus for the automatic. sequential typing of blood samples are provided and comprise the supply from 1 blood sample supply means of said blood samples in the form of a stream of successive blood sample plasmas and a concomitant stream of successive blood sample cells.
  • Such prior art apparatus generally provide high sample per hour operational rates in the nature. for example. of I or more typed samples per hour, to render the same particularly adaptable for use in large hospitalsand/or large blood-typing laboratories with high' blood sample typing a valve means. proportioning pump means. sample treatment or requirements. but not particularly adaptable for use in smaller hospitals with blood sample typing requirements which fall far below this level. Too. it may be understood that such prior art apparatus are somewhat complex and'will generally be found to require the full-time attention of a number of skilled technicians to operate the same. More specifically. it may be understood that there is currently an increasing demand on the part of smaller hospitals and the like having blood sample typing requirements in the nature, for example. of 24 or less blood sample typings per hour. for smaller. less complex, auto-. matically operable blood-typing apparatus which may be readily operated by a single skilled technician and which have a reduced initial cost and a reduced consumption rate per blood sample typing of the requisite. expensive typing sera to result in a substantial reduction in the overall cost per blood sample typing.
  • Another object of this invention is the provision of method and apparatus as above which are operable at substantially reduced typing sera consumption rates to thus substantially reduce the unit cost per blood sample typing.
  • Another object of this invention is the provision of apparatus as above of substantially reduced initial cost.
  • Another object of this invention is the provision of apparatus as above which require substantially less space than do the like apparatus of the prior art.
  • Another object of this invention is the provision of apparatus as above of reduced complexity which may be readily operated by a single skilled technician.
  • a further object of this invention is the provision of apsupply means. reagent dispenser means, wash liquid control reaction means. blood sample cell control valve means. and treated sample analysis means. respectively, each of which is operable. in predetermined phase relationship. under the control of suitable programmer means.
  • blood plasma and blood cell portions of blood samples which have been centrifuged to substantially separate the respective plasma and cell constituents thereof are sequentially pumped on separate paths by the proportioning pump means to the apparatus from the sample supply means. with thorough washing thercbetween. while the respective typing scra and reagent cells are concomitantly sequentially pumped on separate paths by the proportioning pump means to the apparatus in phase with the former. and again with thorough washing therebetween.
  • the blood sample plasma portion from each blood sample is flowed as a continuous stream through the apparatusandthe reagent cells sequentially mixed therewith to provide for the desired reagent cell-plasma reactions.
  • Each blood sample cell portion is. on the other hand. enzyme treated'and diluted. and automatically divided by the blood sample cell control valve into six distinct portions which are separated by a suitable wash liquid. and each of these six portions is in turn automatically mixed with a different one of the sequentially supplied typing sera to promote the desired typing 'sera-cell reactions.
  • the sample treatment or reaction means which respectively take the form of a plasma-typing circuit and a cell-typing circuit to provide for incubation. and subsequent dilution by a suitable diluent to disperse rouleaux and effect agglutinate separation.
  • the relevant agglutinated cell constituents. or free cells in the case of a negative reaction. of the respective treated blood sample plasma portions and the treated blood sample cell portions are decanted and fed on parallel paths to the treated sample analysis means which take the form of .a continuous filter to provide the desired. readily readable and reproducible typing results in the form of nine paratus as above which require theuse of only readily availa- SUMMARY OF THE INVENTION
  • the method and apparatus of this invention are embodied by operatively associated blood sample discrete spots on said continuous filter.
  • FIG. I is a flow diagram of apparatus constructed in accordance with the teachings of this invention. 7
  • FIG. I is a more detailed schematic showing of the pum means shown diagrammatically as a box in FIG. I:
  • FIG. 2 is a top plan view of the sample supply means of the apparatus of FIG. I;
  • FIG. 3 is a longitudinal cross-sectional view taken through the sample probes of the sample supply means of FIG. 2 as operatively positioned in a sample container;
  • FIG. 4 is a top plan view of the reagent dispenser of FIG. I in one operational position thereof; 7
  • FIG. II is a cross-sectional view taken through correspond ing portions of the antisera and blood cell sample quotient conduits of the apparatus of FIG. I;
  • FIG. I2 is a perspective view of the treated sample analysis means of the apparatus of FIG. I.
  • FIG. I3 is a view illustrating the blood sample typing results provided by the method and apparatus of the invention.
  • vention may be seen to comprise sample supply means as indicated generally at 10, reagent dispenser means as indicated generally at 12, wash liquid control valve means for said sam-..
  • ple supply means as indicated generally at 14
  • proportioning pump means as indicated generally at 18
  • sample treatment or reaction means as indicated generally at 20
  • sample cell and wash liquid control valve means as indicated generally at 22
  • treated sample analysis means as indicated generally at 24, respectively.
  • Programmer means 25 are operatively associated with each of the above, as indicated by the dashed lines extending therebetween, and are operable to control the respective operations thereof in predetermined phase relationship as explained in greater detail hereinbelow.
  • the sample supply means may, for example, take the general formof those shown and described in U.S. Pat. No. 3,252,330 issued May 24, 1966 to Nelson G. Kling and, as best seen in FIGS. 2 and 3, comprise a turntable 26 upon which is disposed a generally circular array of blood sample containers 28.
  • each of said containers 28 will preferably take the form of a Vacutainer tube as manufactured and marketed by the Becton Dickinson Company of Rutherford, New Jersey, into which a sample of blood may automatically be withdrawn from a patient by use of well-known vacuum and hypodermic needle techniques. Subsequently, it may be understood that each of said Vacutainer tubes will be centrifuged to substantially separate the blood sample contained therein into respective plasma and cell sample portions or layers as indicated at 30 and 32 respectively in FIG. 3.
  • a sample ofltake device is indicated generally at 34 and. as
  • FIG. 3 comprises an operating arm 36 from which are carried, in the depicted side-by-side manner, a blood sample plasma probe 38 and a blood sample cell probe 40.
  • the blood sample plasma probe 38 comprises an outer sub stantially corrosion-resistant small bore stainles steel tube in the nature ofa hypotube 41 having a wash liquid inlet 42, and an inner hypotube 44 of the same construction disposed as shown in generally concentric manner in said outer hypotube and having a plasma inlet 46 which extends beyond the lower extremity of the latter, and a plasma and wash liquid outlet 48 which extends as shown beyond the upper extremity of said outer hypotube 41.
  • An aperture 50 is formed as shown in said inner hypotube 44 to connect the interior thereof with the interior of the outer hypotube 41 as should be obvious.
  • the blood sample cell probe 40 is of substantially the same construction as is the blood sample plasma probe 41 and, to this efl'ect. may readily be seen to comprise an outer hypotube 52 having a wash liquid inlet 54, and an inner hypotube 56 having a blood sample cell inlet 58, a cell and wash liquid outlet 60, and an aperture 62 connecting the said inner and outer hypotubes.
  • wash liquid receptacle is indicated at 64 in FIG. 2 and disposed as shown adjacent the turntable 26.
  • Wash-in liquid inlet and outlet conduits 66 and 68 extend as shown from the wash liquid reservoir 64 and cooperate with nonillustrated wash liquid supply means to provide for the constant circulation of a supply of wash liquid through the said wash liquid reservoir 64.
  • the proportioning pump 18 may, for example, talte thegeneral form of the compressible tube or peristaltic pump shown and described in U.S. Pat. No. 3,227,091 issued Jan. 4,
  • proportioningpump 18 Further included in the proportioningpump 18 are a plurality of spaced, nonillustrated pump rollers which extend generally transversely of the said pump tubes and are moveable longitudinally thereof to progressively compress or occlude the same and pump fluids therethrough in the direction from left to right as seen in FIG. 1. 7
  • sample supply means wash liquid control valve 14 the same may be seen to comprise three-way valve 130 and three-way valve 132 which are simultaneously operable in tandem as indicated by avaIve-operating solenoid 133.
  • the three-way valve 130 comprises valve ports 134. 136 and 138 and is arranged, when in the open" position thereof, to connect valve ports 134 and 138 and, when in the closed" position thereof, to connect valve ports 134 and 136.
  • the three-way valve 132 comprises valve ports 140. 142, and 144 and is arranged when in the "open” position thereof to connect valve ports 140 and 144 and, when in the closed position thereof, to connect valve ports 140 and 142.
  • the respective three-way valves 130 and 132 are arranged relative to the valve operating solenoid 134 so that when one of said three-way valves is in theopen position thereof, the
  • the respective outlet ends of the compressible pump tube 84 and 86 are merged as indicated by conduits 176 and 178 and nipple and sleeve assemblies 180 and 182, respectively, and a nipple and sleeve asembly 184 and conduit 186 are provided to connect thethusly air-segmented wash liquid output of compressible pump tube 84 to the port 140 of the three-way valve 132.
  • the port 136 of three-way valve 130 is connected as indicated, by return conduit 202, nipple 204, and return conduit 206, respectively, to thewash liquid supply source 146, while the port 144 of three-way valve 132 is also connected thereto by conduit 200 which merges as indicated with conduit 202.
  • a wash liquid supply conduit 208 connects the port 138 of three-way valve 130 to the wash liquid inlet 54 of the blood sample cell probe'40, while a wash liquid supply conduit 210 connects the port 142 of three-way valve 132 to the wash liquid inlet 42 of the blood sample plasma probe 38.
  • the blood sample cell and wash liquid outlet 60 of the blood sample cell probe 40 is connected as shown by conduit 212 and nipple 214, respectively, to the inlet of compressible pump tube 110, while the blood sample plasma and wash liquid outlet 48 of blood sample plasma probe 38 is connected as shown by conduit'216 and nipple 218, respectively, to the inlet of compressible pump tube 98.
  • the respective sample supply means 10, the proportioning pump means 18, and the wash liquid control valve means 14 are simultaneously operated, in predetermined phase relationship under the control of programmer 25, to concomitantly supply, on parallel paths, sequential streams of the respective blood sample plasma and blood sample cell portions as spaced. in each instance. by intervening segments of air and slugs of air-segmented wash liquid. from the respective blood sample containers 28 to the sample treatment or reaction means 20.
  • the turntable 26 is intermittently rotated or indexed by the nonillustrated sample supply device operating means to present each of the sample containers 28 in turn to the sample offtake device 34. while the latter is in turn operated to immerse the respective inlets 46 and 58 of the blood sample plasma probe 38 and the blood sample cell probe 40 in a thusly presented sample container as depicted in FlG. 3 for a predetermined period of time to aspirate (as described in detail hereinbelow) a measured volume of said blood sample plasma and said blood sample cells. respectively, through the said probes.
  • valve operating solenoid 133 is arranged under the control of programmer to maintain three-way valve 130 in the closed position thereof and to maintain three-way valve [32 in the open position thereof. whereby the respective airsegmented streams of wash liquid supplied thereto on conduits I98 and I86 will simply be circulated therethrough and returned to the wash liquid reservoir I46 through return conduits 200. 202 and 206. Accordingly, with said probes positioned in a said sample container as depicted in FIG. 3.
  • the progressive compression or occlusion of pump tube9ti will be elTective to aspirate a portion of the blood sample plasma through the probe inlet 46 to and through the probe outlet 48 and. from the latter. through conduit 216 to and through the said compressible pump tube 98.
  • the progressive compression or occlusion of compressible pump tube H0 will be effec- 'tive to aspirate a portion of the blood sample cells 32 through the inlet 58 of cell probe and therefrom. to and through the probe outlet 60 and connecting conduit 2l2. to and through the said compressible pump tube H0.
  • solenoid D4 will be effective under the control of programmer 25 to maintain threeway valve 130 in the open position thereof and to maintain three-way valve 132 in the closed position thereof. whereby v the air-segmented wash liquid stream supplied to three-way In like manner.
  • the maintenance ofthe three-way valve 132 i in the closed position thereof by the valve operating solenoid I34 during this period of probe immersion in the wash liquid receptacle 64 will result in the forced supply of the air-segmented stream of wash liquid from conduit [86 to and through the said three-way valve and therefrom. through conduit 210.
  • reagent dispenser 12. the same may be seen in FIG. 4 to comprise a housing 230 having disposed therein a row of spaced aligned typing sera or antisera con tainers 232. and a substantially correspondingly spaced and aligned row ofreagent cell containers 234.
  • the row 232 of antisera containers is constituted by'containers 236. 238. 240..
  • the reagent cells container row 234 is constituted by reagent eells containers 248. 250. 252. 254. 256 and 258. respectively. and it may be understood that foruse as above in the automatic. sequential typing of blood samples.
  • the container 248 would be filled with type A red cells.
  • the container 250 with type 8 red cells.
  • the container 252 with type 0 red cells. respectively.
  • the respective reagent cell containers 254. 256 and 258 would be left empty. it being understood. however. that the same could alternatively be filled with O-type red cells to enable use of the method and apparatus of the invention in accordance with other and different blood-grouping systems.
  • the containers 254. 256 and 258 could simply be filled with a suitable wash liquid. again in the nature of a saline solution. to
  • a wash liquid trough is indicated at 260 and may be seen to be somewhat spaced from, and generally coextensive with, the row 232 of antisera containers.
  • a wash liquid trough is indicated at 262 and may be seen to be somewhat spaced from, and generally coextensive with, the row 234 of reagent cell Containers, it being understood that the respective spacings between the antisera container row 232 and wash liquid trough 260, and the reagent cell container row 234 and wash liquid trough 262, are substantially equal.
  • a relatively high'capacity auxiliary pump is indicated at 233 and the inlet thereof connected to wash liquid reservoir [46 by conduit 235.
  • Theoutlet of pump 233 is connected, by conduits 237 and 239, to the respective wash liquid inlets 259 and 269 of the reagent dispenser l2 to provide for the continual circulation of wash liquid through the respective reagent dispenser wash liquid troughs 260 and 262.
  • a reagent offiake device is indicated generally at 264, and comprises an operating arm 266 from which are canied an antiserum or typing serum probe 268 and a reagent cells probe 270.
  • the antiserum probe 268 is of substantially identical construction as that described in detail hereinabove with regard to the respective blood sample plasma probe 38 and the blood sample cell probe 40 and, to that effect, may be understood to comprise a wash liquid inlet 271, an antiserum inlet 272, and an antiserum and wash liquid outlet 274, respectively, in the manner clearly illustrated in FIG. I.
  • the reagent cells probe 270 may also be understood to be of substantially the same construction as that described in detail hereinabove for the blood sample plasma probe 38 and the blood sample cell probe 40, and, as such, may be seen in FIG. I to comprise a wash liquid inlet 276, a reagent cell inlet 278, and a reagent cell and wash liquid outlet 280, respectively.
  • Operating means for the reagent dispenser olftake device operating arm 266 are provided within the reagent dispenser housing 230 and may, of course, take any suitable form in the nature, for example, of an electrically driven, mechanically operable cam and gear arrangement, to move the operating arm 266 and the respective antiserum probe 268 and reagent cells probe 270 through a predetermined sequence of operation for immersion of the respective probe inlets in the respective antisera and reagent cell containers, and wash liquid trough, for predetermined periods of time to aspirate measured volumes of said antisera and reagent cells therefrom as explained in greater detail hereinbelow.
  • reagent agitation and cooling means in the nature of vibratory and thennoelectric means, respectively, may also be incorporated in the reagent dispenser housing 230 and operatively associated with the respective antisera and reagent cell containers to effect suitable agitation and cooling of the respective antisera and reagent cells contained therein.
  • the three-way valve 282 comprises valve ports 288, 290 and 292 and is arranged, when in the open position thereof, to connect valve ports 288 and 292 and, when in the closed position thereof, to connect valve ports 288 and 290.
  • the three-way valve 284 comprises valve ports 294, 296 and 298 and is arranged, when in the open position thereof to connect valve ports 294 and 298 and, when in the closed position thereof, to connect valve ports 294 and 296.
  • the respective three-way valves 282 and 284 are arranged relative to thc valve-operating solenoid 286 so that when one of said three-way valves is in the open position thereof, the other of the said three:way valves is in the closed position thereof, and vice versa.
  • compressible pump tube 76 is connected as shown, in part through nipple and sleeve assemblies 300, 302,
  • compressible pump tubes 78 and 82 are left open as shown to atmosphere to provide for the pumping of ambient air therethrough upon operation of the proportioning pump means 18.
  • the outlet port 298 of three-way valve 284 is connected, by return conduit 340, nipple 342 and return conduit 344, to the wash liquid reservoir 146, while the outlet port 290 of threeway valve 282 is also connected thereto by return conduit 346 which merges as indicated with return conduit 340.
  • a wash, liquid supply conduit 350 connects the outlet port 292 of three-way valve 282 to the wash liquid inlet 27] of the antiserum probe 268 of the reagent dispenser l2, while a wash liquid supply conduit 352 connects the outlet port 296 of three-way valve 284 to the wash liquid inlet 276 of the reagent cells probe 270 of the said reagent dispenser.
  • the otflake device 264 is operated under the control of the programmer 25 and in predetermined phase relationship with the sample supply means 10, the control valve means [6 and the proportioning pump means [8, respectively, to successively position the inlet 272 of antiserum probe 268 in the antisera or typing sera containers 236, 238, 240, 242, 244 and 246, respectively, for predetermined periods of time, and to position the said antisenim probe in the wash liquid trough 260 for a predetermined period of time intermediate the movement of said probe from a position in one of said antisera containers to a position in another of said antisera containers.
  • this operation of the offtake device 264 will of course be effective to successively position the inlet 278 of the reagent cells probe 270 in the respective reagent cells containers 248, 250, 252, 254, 256 and 258 for substantially identical predetermined periods of time, and to position the said probe inlet in the wash liquid trough 262 intermediate the movement of the said reagent cells probe from one of said reagent cells containers to another.
  • the ofi'take device 264 will be operated to move the operating arm 266 and the respective probes 268 and 270 to the position thereof of FIG. for immersion of the respective probe inlets in the respective wash liquid troughs 260 and 262 to result in the aspiration of measured volumes of ambient air through the said probe inlets for supply to the compressible tubes 104 and 100.
  • the ofltake device 264. with the respective probe inlets now immersed in the wash liquid troughs. will track for a predetermined period of time to the position thereof of HO. 6 while the positioning of three-way valve 282 in the open position thereof and of three-way valve 284 in the closed position thereof by solenoid 286 concomitantly with the commencement of ofi'take device tracking. will be effective to supply a pressure flow of the air-segmented wash liquid to the said probes through the respective probe wash liquid inlets 271 and 276 to thus result in a thorough cleansing of both the interiors and exteriors of the said probe by the said wash liquid. and the aspiration of measured volumes of the latter through the respective probes 268 and 270 for supply to the respective compresible pump tubes I04 and 100.
  • This cycle of operation of the offtake device 264 is.'of course. repeated for each aligned pair of an antisera container and a reagent cells container. respectively. until a measured volume of antisera has been aspirated from each of said antisera containers, and a measured volume of reagent cells aspirated from each of said reagent cell containers, whereupon the said offtake device is returned by tracking of the respective inlets of the probes 268 and 270 through the respective wash liquid troughs 260 and 260 from the position of FIG. 8 to the position of FIG. 9 for movement from the latter back to the position of FIG. 4 to recommence the reagent and wash liquid dispensing cycle. 7
  • the said blood sample plasma stream will then flow from the outlet of the delay coil 382 through nipple and sleeve assembly 384 and conduit 386. respectively. to a fitting 388 whereat the same will be mixed with the stream of reagent cells flowing thereto on conduit 372. Therefrom. the thusly mixed blood sample plasma and reagent cell streams will be flowed through conduit 390 to one inlet of ajunction conduit 392.
  • a reservoir for a suitable diluent which may. for example. take the form of an enzyme solution in the nature of bromelin is indicated at 402 and is connected. by conduit 404 and nipple 406. to the inlet end of compressible pump tube 114. The outletend of compressible pump tube 114 is connected.
  • 256. and 258 (or wash liquid from the latter three conof compressible pump tube 108 is left open to atmosphere. and the outlet end thereof is connected. through nipple 416 and conduit 418. to the other inlet of junction conduit 414. whereby may be understood that an air-segmented stream of the said enzyme diluent will be supplied from the outlet of the said junction conduit through nipple and sleeve assembly 420. conduit 422. and nipple and sleeve assembly 424. to the inlet ofajunction conduit 426.
  • the blood sample cell stream from the sample supply device 10 is supplied to the other inlet of the junction conduit 426 through conduit 226. whereby it may be understood that the said blood sample cell stream and the air-segmented stream of the enzyme diluent solution will be merged in the said junction conduit to both dilute the said blood sample cell stream and treat the same to enhance the subsequent reactions thereof with the respective antisera or typing sera. Therefrom. the diluted blood sample cell stream will flow. through sleeve 428. to a mixing coil 430 for flow through the latter and attendant mixing therewithin. a
  • junction conduit 434 The now substantially declotted blood sample cell stream is flowed from the other outlet of junction conduit 434through sleeve 442 to the inlet of a junction conduit 444.
  • a conduit 446 connects one outlet of the junction conduit 444 to the inlet of compressible pump tube 118 through nipple 448. and the outlet of the said compressible pump tube is connected as shown through nipple 450 and a conduit 452. to the inlet of a fitting 454.
  • the other outlet ofjunction conduit 444 is connected. through nipple and sleeve assembly 456. to a conduit 458 which in turn extends as indicated to waste. Accordingly. it is believed clear that as the now diluted. enzyme-treated.
  • the wash liquid reservoir 146 is connected as shown. through conduit 462 and nipple 464. to the inlet of compressible pump tube [16. and the outlet of the said compressible pump tube is connected as shown through nipple 466 and conduit 468 to one inlet of ajunction conduit 470.
  • the inlet of compressible pump tube 112 is left open to atmosphere. and the outlet of the said compressible pump tube is connected. through nipple 472. conduit 474 and nipple and sleeve assembly476. to the other inlet of the junction conduit 470.
  • conduit 474 and nipple and sleeve assembly476. to the other inlet of the junction conduit 470.
  • an air-segmented. stream of the saline solution wash liquid from the wash liquid reservoir 146 will be supplied from junction conduit 470 through nipple and sleeve assembly 478 to conduit 480 for flow through the latter. and through nipple and sleeve assembly 482. to the inlet of ajunction conduit 484.
  • a conduit 486 extends as shown to connect one of the outlets of junction conduit 484 to the inlet of compressible pump tube through nipple 488. and the outlet of the said compressible pump tube is connected as shown through nipple 490 and conduit 492 to the fitting 494.
  • junction conduit will simply be flowed therefrom to waste through the conduit 498.
  • sample cell and wash liquid control valve means 22 will preferably take the form of the New And improved Bar Valve" as shown and described in the copending application for U.S. Pat. of Carl V. Johnson et al.. Ser. Number 864.262. filed Sept. 22. i969 and assigned to the assignee hereof and. as
  • the said compressible conduits and is arranged. when actuatcd by nonillustrated bar valve operating means, to compress the relevant ones of the said compressible conduits against the bar valve base member 514 and prevent fluid flow through the fonner.
  • each of the said bar members is arranged to be actuated and deactuated sixtimesduring the withdrawal of the blood sample cells by cell probe 40 from each of the blood sample containers 28 of the sample supply means 10.
  • a conduit 518 extends as shown from the outlet of fitting 506 to connect the same to waste as indicated. while a conduit 520 extends as shown from the outlet of fitting 502 to connect the same to one inlet ofa fitting 522.
  • bar valve means 22 In the operation of the bar valve means 22 it may be understood that with bar valve member 512 actuated. and bar valve member 516 deactuated, flow of the enzyme-treated and diluted blood sample cell stream through conduit 500. and flow of the air-segmented saline solution stream through conduit 508 will be prevented; while flow of the enzyme diluted and treated blood sample cell stream through conduit 504. I and flow of the air-segmented saline solution stream through" the bar valve member 516 actuated. it may be understood that flow of the enzyme diluted cell stream through conduit 504.
  • each of the distinct distinct blood cell sample quotient or subfraction reaches fitting 522 it will be met thereat by an appropriate portion of the anti A antiserum from antiserum container 236 of the reagent dispenser, as a second quotient of the same blood cell sample reaches the fitting 522 it will be met thereat for merger with an appropriate portion of the anti B antiserum from container 238. as a third quotient of the same blood cell sample reaches the fitting 522 it will be met thereat for merger with an appropriate portion of the anti AB antiserum from container 240.
  • FIG. ll depicts the said streams in thoseportions of conduits 520 and 366 (as somewhat rearranged for clarity of illustration) immediately downstream of fitting 522.
  • the inlet end of compressible pump tube I02 is left open to atmosphere. and that the outlet end thereof is con nected. through conduit 524 and nipple and sleeve assembly 526. to one inlet of a junctionconduit 528.
  • the outlet of fitting 522 is connected as shown by. conduit 530 to the other inlet of junction conduit 528, and the outlet of the said junction conduit is connected by nipple and sleeve assembly 532 to the inlet of direct-typing or cell-typing circuit as indicated generally at 534.
  • the antiserum-blood samplecell quotient mixture stream from fitting 522. as air-segmented in junction conduit 528. will be flowed from the latter to and through the direct-typing circuit 534 for a predetermined time period to provide for cell incubation.
  • each blood plasma sample portion from a blood sample container 28 (FIG. 2) as a substantiaily continuous stream. to the fitting 388--although clearly delineated as described in detail hereinabove by a segment of air. a slug of wash liquid and a segment of air from the preceding and following blood plasma sample-and to sequentially merge the measured volumes of reagent cells from at least reagent dispenser containers 248. 250 and 252 with different parts of said continu-. ous stream at spaced intervals-as determined. of course.
  • the inlet of compressible pump tube 94 is connected as shown. in part by conduit 538 and nipple and sleeve assembly 540. to the wash liquid reservoir I46. and the outlet of the said compressible pump tube is connected. through nipple 542. conduit 544. nipple 546 and conduit 548. respectively. to the outlet conduit 550 of the plasma-typing circuit 400. to thus further dilute the reacted plasma stream flowing from the said plasma-typing circuit in the said outlet conduit. in like manner. the inlet of compressible pump tube 96 may be seen to be connected as shown. in part through conduit 552 and' nipple and sleeve assembly 554.
  • a mixing coil 566 is connected as shown to the outlet conduit 550 of the plasma-typing circuit 400. and the outlet conduit of the said mixing coil is connected. by a straight. horizontal conduit 568 and nipple 570 to a conduit 572 which extends as indicated to waste. in like manner.
  • a mixing coil 574 is condilution of the respective plasma and cell streams. and the subsequent flows thereof through mixing coils 566 and $74. is to disperse any rouleaux or false reaction indications and to separate the agglutinates for better readability of the final results.
  • each instance. of the respective straight horizontal conduits 568 and 5 76 is to enable the settling out of agglutinates. if present. in the respective flowing cell and plasma streams.
  • Decant means are indicated generally at 582 and may be seen to be constituted by a decant conduit 584 which extends as shown downwardly from the bottom of conduit 568 and is connected. by conduit 586 and nipple 590. to the inlet of compressible pump tube 124.
  • decant means are indicated generally at 590 and may be seen to be constituted by a decant conduit $92 which extends 'as shown downwardly from the bottom of conduit 576 and is connected. by conduit 592 and nipple 594. to the inlet end of compressible pump tube 122.
  • compressible pump tube 122 is connected, through nipple 598, to a treated plasma delivery conduit 600, while the outlet end of compressible pump tube 124 is connected, through nipple 602, to a treated cell delivery conduit 604.
  • the treated sample analysis means 24 may be seen in FIG. 12 to comprise a supply roll 606 ofa suitable, medium porosity filter paper and a drive roll assembly comprising a high-friction surface-driven roller 608 and a tension roller 609.
  • the driven roller 608 is rotated in the counterclockwise direction at constant rotational speed to unwind the filter paper 6l0 from the supply roll 606 while moving the said filter paper at constant velocity in the nature, for example, of approximately l.5 inches per minute in the indicated direction beneath, and in close proximity to, the respective outlet ends of the treated cell delivery conduit 604 and the treated plasma delivery conduit 600.
  • Suction conduits 612 and 614 are disposed as shown beneath the filter paper 610, with the respective inlet ends thereof in close proximity thereto, and are disposed in general alignment with the respective delivery conduits 604 and 600.
  • the same will drip therefrom onto the upper surface of the filter paper (H and impregnate the latter as enhanced by the suction effect pro vided by suction conduit 6l2.
  • the same will drip therefrom onto the upper surface of the filter paper 610 to impregnate the same, again as enhanced by the suction effect of suction conduit 6.
  • FIG. 12 depicts the blood sample typing results provided on the surface of the filter paper 610 for the automatic typing of successive blood samples by the method and apparatus of the invention
  • the group of results as indicated generally at 616 makes clear that the only antiserum-blood sample cell positive reactions were those involving the anti Rh,(D) and the anti Rh, "(CDE) antisera, while the only positive reagent cellsblood sample plasma reactions were those involving the type A reagent cells and the type B reagent cells, to thus clearly type said first analyzed blood sample as O-positive blood.
  • the improvements comprising, antisera and reagent cells dispensing means for concomitantly supplycells streams so that each of said blood sample plasma quotients is mixed and reacted with a different one of said reagent cells quotients, means to merge said blood cells and antisera streams so that each of said blood sample cells quotients is merged with a different one of said antiserum quotients, and means providing for the examination of the respective reacted blood sample plasma and reagent cells quotients and the respective reacted blood sample cells and antiserum quotients to effect blood sample typing.
  • apparatus as in claim I further comprising, means to introduce separating fluid segments insaid respective antisera and reagent cells streams between the respective antisera and reagent cells quotients.
  • the improvements comprising, reagent dispensing means to supply a successive stream of different reagent quotients of predetermined required volume, respectively, means to merge said fluid sample and reagent quotients streams so that each of said fluid sample quotients is mixed and reacted with a different one of said reagent quotients, and means providing for the examination of the respective reacted sample quotients to effect fluid sample analysis.
  • apparatus as in claim 5 further comprising, means to introduce separating fluid segments in said reagent quotient stream between the respective reagent quotients.

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  • General Health & Medical Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Sampling And Sample Adjustment (AREA)
US864263A 1969-09-22 1969-09-22 Automatic method and apparatus for the sequential typing of blood samples Expired - Lifetime US3635680A (en)

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JP (1) JPS5039557B1 (ru)
AU (1) AU453981B2 (ru)
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CA (1) CA938873A (ru)
CH (1) CH528077A (ru)
DE (1) DE2046120A1 (ru)
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US4104031A (en) * 1975-12-08 1978-08-01 Readymatie S.A. Apparatus for displaying the results obtained on an agglutination support
EP0036000A1 (en) * 1979-09-19 1981-09-23 The Prince Charles Hospital Development Centre Trust Continuous flow automatic chemical analysis systems and components for use therein
WO1989000698A1 (en) * 1985-11-08 1989-01-26 Wessex Instrumentation Ltd. Continuous flow analysis
US4879432A (en) * 1985-04-11 1989-11-07 Didier Vieillard Method for measuring the coagulation of blood plasma
US20100279899A1 (en) * 2000-08-31 2010-11-04 The Regents Of The University Of California Capillary array and related methods
US20110031931A1 (en) * 2007-11-25 2011-02-10 Paul Rembach Method and apparatus for providing power to a marine vessel
WO2012159275A1 (en) * 2011-05-26 2012-11-29 Siemens Aktiengesellschaft Blood typing system
US20180188279A1 (en) * 2017-01-05 2018-07-05 Illumina, Inc. Reagent mixing system and methods
CN108593942A (zh) * 2018-04-17 2018-09-28 杭州电子科技大学 一种交叉配血方法
CN108931657A (zh) * 2018-04-17 2018-12-04 杭州电子科技大学 一种交叉配血仪

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DE2538451C2 (de) * 1974-09-02 1986-06-05 Technicon Instruments Corp., Tarrytown, N.Y. Gerät zur Entnahme eines Teils eines durch ein nicht mischbares Fluid segmentierten Flüssigkeitsstromes
GB2019995B (en) * 1978-04-10 1982-09-29 Kaartinen N Method and apparatus for handling batches of liquids
DE3736027A1 (de) * 1987-10-24 1989-05-03 Gerhard Dipl Phys Artmann Verfahren zur ermittlung der zu einem bestimmten zeitpunkt vorliegenden form von zellen und einrichtung zur durchfuehrung des verfahrens
EP0746771A4 (en) * 1993-10-11 1998-11-25 Adi Ltd WATER ANALYSIS SYSTEMS

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US3241432A (en) * 1962-01-23 1966-03-22 Technicon Instr Method and apparatus for sequentially performing analyses on a plurality of fluid samples
US3261668A (en) * 1962-08-14 1966-07-19 Scientific Industries Chemical analyzer tape
US3334018A (en) * 1962-09-05 1967-08-01 Technicon Corp Means for analyzing a continuous stream of unique sanguineous samples
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Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4104031A (en) * 1975-12-08 1978-08-01 Readymatie S.A. Apparatus for displaying the results obtained on an agglutination support
EP0036000A1 (en) * 1979-09-19 1981-09-23 The Prince Charles Hospital Development Centre Trust Continuous flow automatic chemical analysis systems and components for use therein
EP0036000A4 (en) * 1979-09-19 1983-08-03 Prince Charles Hospital Dev Ct AUTOMATIC CHEMICAL ANALYSIS SYSTEMS WITH CONTINUOUS FLOW AND COMPONENTS USED THEREOF.
US4879432A (en) * 1985-04-11 1989-11-07 Didier Vieillard Method for measuring the coagulation of blood plasma
WO1989000698A1 (en) * 1985-11-08 1989-01-26 Wessex Instrumentation Ltd. Continuous flow analysis
US20100279899A1 (en) * 2000-08-31 2010-11-04 The Regents Of The University Of California Capillary array and related methods
US8003376B2 (en) * 2000-08-31 2011-08-23 The Regents Of The University Of California Capillary array and related methods
US20110031931A1 (en) * 2007-11-25 2011-02-10 Paul Rembach Method and apparatus for providing power to a marine vessel
WO2012159275A1 (en) * 2011-05-26 2012-11-29 Siemens Aktiengesellschaft Blood typing system
US20180188279A1 (en) * 2017-01-05 2018-07-05 Illumina, Inc. Reagent mixing system and methods
US10830784B2 (en) * 2017-01-05 2020-11-10 Illumina, Inc. Reagent mixing system and methods
US20210018527A1 (en) * 2017-01-05 2021-01-21 Illumina, Inc. Reagent mixing system and methods
TWI761409B (zh) * 2017-01-05 2022-04-21 美商伊路米納有限公司 試劑混合的系統和方法
CN108593942A (zh) * 2018-04-17 2018-09-28 杭州电子科技大学 一种交叉配血方法
CN108931657A (zh) * 2018-04-17 2018-12-04 杭州电子科技大学 一种交叉配血仪
CN108593942B (zh) * 2018-04-17 2020-09-08 杭州电子科技大学 一种交叉配血方法

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NL168620C (nl) 1982-04-16
NL7013521A (ru) 1971-03-24
FR2062408A5 (ru) 1971-06-25
AU2021170A (en) 1972-03-23
GB1321079A (en) 1973-06-20
DE2046120C3 (ru) 1975-12-11
CA938873A (en) 1973-12-25
AU453981B2 (en) 1974-09-20
BE756423A (fr) 1971-03-22
JPS5039557B1 (ru) 1975-12-17
NL168620B (nl) 1981-11-16
DE2046120B2 (ru) 1975-04-24
SU459877A3 (ru) 1975-02-05
SE378680B (ru) 1975-09-08
CH528077A (de) 1972-09-15
DE2046120A1 (de) 1971-04-15

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