US3635680A

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

Info

Publication number: US3635680A
Application number: US864263A
Authority: US
Inventors: John C A Peoples; Stanford L Adler
Original assignee: Technicon Corp
Current assignee: Bayer Corp; Technicon Corp
Priority date: 1969-09-22
Filing date: 1969-09-22
Publication date: 1972-01-18
Anticipated expiration: 1989-01-18
Also published as: DE2046120C3; CA938873A; CH528077A; DE2046120B2; JPS5039557B1; AU453981B2; FR2062408A5; BE756423A; SU459877A3; SE378680B; AU2021170A; NL168620C; NL7013521A; GB1321079A; DE2046120A1; NL168620B

Abstract

Method and apparatus for the automatic, sequential typing of blood samples are provided and comprise the supply from 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, the supply from reagent dispensing means of a successive stream of different antisera, as spaced by a separating fluid, and a successive stream of different reagent cells, as spaced by a separating fluid, the division of said blood sample cells stream into quotients by the introduction of a separating fluid at spaced points therein, the merger of a different one of said antisera with each of the blood sample cells quotients from each of said blood samples, the merger of said different reagent cells with the blood sample plasma from each of said blood samples, the incubation of said antisera-blood sample cells stream and of said reagent cells-blood sample plasma stream to promote reaction therebetween, and the provision of readily readable and reproducible results of the blood-typing procedure.

Description

United States Patent Peoples et al.

[ 1 Jan. 18, 1972 AUTOMATIC METHOD AND APPARATUS FOR THE SEQUENTIAL TYPING OF BLOOD SAMPLES [72] lnventors: John C. A. Peoples, Nanuet; Stanford L.

[52] US. Cl. ..23I230 B. 23/253 R, 23/259. l95/l03.5. 424/1! [Sl] lnt.Cl ..G01n3l/00,GOln33/l6 [58] Field 0! Search ..23/230, 253. 259; 424/l l; l95/l03.5, l27

[56] Relerenc es Clted UNITED STATES PATENTS 2.933.293 4/l960 Ferrari, .lr. ..23/230 X 3.241.432 3/1966 Skeggs et al.. ....23/2s3 x 316L668 7/1966 Natelson ..23/253 TP 3.334.018 8/1967 Smythc ..23/230 B 3.427.l35 2/l969 Pelavin ..23/230 B 274 /2 IIEENT m J26 All!!! SERUM REAcrwr PROBE (Ill. PROBE olsPslvsck 3 o DISPENSER I I I I 350 I 36 I I I I I I I I I I SlNPL E JUPPL 7' ,502,437 3/l970 Mass ..23/253TP Primary ExaminerMorris O. Wolk Assistant Examiner-R. E. Serwin AnorneyS. P. Tedesco [57] 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. the supply from reagent dispensing means of a successive stream of different antisera, as spaced by a separating fluid and a successive stream of different reagent cells, as spaced by a separating incubation of said antisera-blood sample cells stream and of said reagent cells-blood sample plasma stream to promote reaction therebetween, and the provision of readily readable and reproducible results of the blood-typing procedure.'

8 Clalrns, l4 Drnwlng Flgures WASH VALVE sum/.55

292 DISPENSER ii? 25?? 355% 21%: 2%2: E

SHEET 7 [IF 8 SHED-m1 81572 wwm , INVENTORY:

JOHN C.A. PEOPLES STAN O L.ADLE 1 BY ATTORNEY AUTOMATIC METHOD AND APPARATUS FOR THE SEQUENTIAL TYPING OF BLOOD SAMPLES BACKGROUND OF TH E INVENTION 1. Field of the Invention This invention relates to new and improved method and apparatus for the automatic, sequentialtyping of blood samples.

2. Description of the Prior Art Although apparatus for the automatic typing of blood. and the many significant advantages thereof when compared to manual laboratory typing. are known. and the former have gained remarkably wide commercial acceptance through the extremely rapid and reliable operation thereof. and the extremely accurate and readily reproducible results provided thereby. it may be understood that such prior art apparatus will. in general. be found to be relatively costly. and tohave relatively high space requirements and relatively high consumption rates of the requisite. extremely expensive typing sera.

In addition. 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.

OBJECTS OF THE INVENTION It is. accordingly. an object of this invention to'provide new and improved method and apparatus for the automatic, sequential typing of blood in consistently accurate manner.

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. I

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. In operation. 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.

After flow through 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 As disclosed herein. the method and apparatus of this invention are embodied by operatively associated blood sample discrete spots on said continuous filter.

BRIEF DESCRIPTION OF THE DRAWINGS The above and other objects and significant advantages of this invention are believed made clear by the following detailed description thereof taken in conjunctionwith the accompanying drawings wherein;

FIG. I is a flow diagram of apparatus constructed in accordance with the teachings of this invention; 7

FIG. In 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

FIGS. 5 through 9 are top plan views of the reagent dispenser of FIG. 4 and respectively depict the same in other operational positions thereof; 7 v I FIG. 10 is a cross-sectional view taken through corresponding portions of the antisera and reagent cell supply conduits of the apparatus of FIG. I;

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; and

.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, wash liquid congenerally at 16, 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, and 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. For use in the typing of blood, 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

best seen in 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.

A 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,

1966 to Jack lsreeli et al., and comprises spaced pump tube mounting blocks as indicated at 70 and 72. Compressible pump tubes which are made from any suitably resilient material of appropriate strength characteristics in the nature, for example. of Tygon, are indicated at 74, 76. 78, 80, 82, 84, 86, 88. 90, 92, 94, 96, 98,100.102,104,106,108,1l0,112,'114, 116, I18, 120, 122, and 124, respectively, and extend as shown between the said pump tube mounting blocks and are affixed thereto by means of the placement of said pump tubes in nonillustrated, complementally shaped aligned mounting grooves formed in said pump tube mounting blocks, and the attachment of adjustably positionable collar elements as indicated at 126 and 128 for pump tube 74 to opposite end portions of said pump tubes, all in a manner made clear in said U.S. Pat. No. 3,227,091.

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

Referring now to the 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

other of said three-way valves is in the closed position thereof and vice versa.

A source of supply in the nature of a reservoir of a suitable wash liquid which may, for example, take the form of a saline solution, is indicated at 146 and is connected as shown through

conduits

148, 150, 152, 156, 158, 160, and 162. and nipple and

sleeve assemblies

164, 166, 168, 170, and 172, and nipple 174, respectively, to the respective inlet ends of the compressible pump tubes 84 and 88 to supply said saline solution thereto, while the respective inlet ends of purnptubes 86 and 90 are left open to atmosphere to provide for the pumping of ambient air therethrough upon operation of the proportioning pump means 18.

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. In like manner, the respective outputs of compressible pump tubes 88 and 90 are merged, by

conduits

188 and 190, and nipple and

sleeve assemblies

192 and 194, respectively, and the thusly air-segmented wash liquid output of the compressible pump tube 88 is connected, by nipple and sleeve assembly 196 and connecting conduit 198. to the port 134 of three-way valve 130.

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.

in operation, 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.

More specifically. 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. and to then transfer the said probe in lets through the ambient air for immersion in the wash liquid receptacle 64 for a predetermined period of time to thus aspirate a measured volume of ambient air through each of said probes followed by a measured volume of said wash liquid (again described in detail hereinbelow). and to then again transfer the said probe inlets through the ambient air for immersion in the next presented sample container 28 for a predetermined period of time to thus aspirate other measured volumes of ambient air and commence the aspiration of subsequent measured volumes of the blood sample plasma and the blood sample cells from said next presented sample container.

With regard to three-

way valves

130 and 132. it may be understood that with the respective blood sample plasma and blood sample cell probes 3B and 40 immersed in a sample container 28. 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. In like manner. it may be understood that under such conditions 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.

With the respective blood sample plasma and cell probes 38 and 40 positioned in the wash liquid receptacle 64 (FIG. 2) it may. however. be understood that 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. to the WMlt liquid inlet 42 of the plasma probe 38 with substantially the same cleansing effect upon the latter and subsequent flow of said stream of air-segmented wash liquid to and through conduit 216 and compressible pump tube 98 to similarly substantially remove the residue of the previously supplied blood sample plasma therefrom. In the interim. or that is to say during those periods of time when the respective blood sample plasma and cell probes 38 and 40 are being transferred between the immersion positions thereof in the respective blood sample containers 28 and the wash liquid receptacle 64. it may be understood that solenoid 134 will be effective under the control of programmer 25 to maintain the threc'way valves I30 and 132 in the respective closed and open positions thereof. whereby ambient air will be aspirated through the

respective probe inlets

46 and 58 to provide slugs of air to the

respective conduits

216 and 212. to enhance the probe. conduit. and compressible pump tube cleansing. and to even more clearly delineate the respective blood sample plasma and blood sample cell portions'from the preceding and following portions ofthc same as should be obvious.

As a result of the above. it is believed clear that a stream consisting of successive ones of the blood sample plasma portions from the respective blood sample containers 28 as spaced. in each instance. by a segment of air. a slug of the airsegmcnted wash liquid. and a segment of air. will be supplied from compressible pump tube 98 through nipple 220 to blood 7 sample plasma portion conduit 222. in like manner. it is believed clear that a substantially corresponding. or similarly phased. stream of successive ones of the blood sample cells portions from the respective sample containers 28. again as spaced in each instance by a segment of air. a slug of the air segment wash liquid. and a segment of air. will be supplied through compressible pump tube .1 l0 and nipple 224 to blood sample cells portion conduit 226.

Referring again to the proportioning pump means 18. it may be seen that the inlet end of compressible pump tube 74 is connected. in part by conduit 26] and nipple and sleeve assembly 263. to the wash liquid reservoir [46. and that the outlet end of the said compressible pump tube is connected. by nipple 265 and conduit 267. to the wash liquid reservoir inlet 66 of the sample supply means 10. As a result. it may be understood that a constant supply of said wash liquid will be supplied from compressible pump tube 74 for circulation through the wash liquid receptacle 64.

Referring now to the 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..

respectively contain antiserum anti A. antiserum anti B. an-

tiserum A.B. antiserum Rh.,(D). antiserum Rh, "(CDE). and a negative control antiserum. v

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. and the container 252 with type 0 red cells. respectively. For blood-typing use in accordance with the routine ABC and Rh blood-grouping system. 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. Alternatively. the containers 254. 256 and 258 could simply be filled with a suitable wash liquid. again in the nature of a saline solution. to

in turn provide for additional wash as is believed made clear hereinbelow.

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. in like manner, 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. In like manner, 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. ln addition,'it may be understood that 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.

Referring now to the reagent dispenser wash liquid control valve means 16 of FIG. I, the same may be seen to comprise three-way valve 282 and three-way valve 284 which are simultaneously operable in tandem as indicated by a valve-operating solenoid 286.

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. In like manner, 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.

The inlet end of compressible pump tube 76 is connected as shown, in part through nipple and

sleeve assemblies

300, 302,

and 304, and conduits 306, 308, and IMO, respectively, to the wash liquid reservoir l46,'and the inlet end of compressible pump tube is also connected as shown, in part through nipple and sleeve assembly 312 and conduit 314, respectively, to the said wash liquid reservoir. Therespective inlet ends of

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 respective outlet ends of

compressible pump tubes

76 and 78 are merged as indicated by

conduits

316 and 318, and nipple and

sleeve assemblies

320, 322 and 324, respectively,

and a conduit 326 is provided to connect the thusly air-segmented wash liquid output of compressible pump tube 76 to the inlet port 288 of three-way valve 282. In like manner. the respective wash liquid and air outputs of compressible pump tubes 80 and 82 are merged, by

conduits

328 and 330. and nipple and

sleeve assemblies

332 and 334, respectively, and the thusly air-segmented wash liquid output of compressible pump tube 80 is in turn connected, by nipple and sleeve assembly 336 and connecting conduit 338, to the inlet port 294 of three-way valve 284.

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 antiserum and wash liquid outlet 274 of the antiserum probe 268 is connected, by conduit 354 and nipple 356, to the inlet end of compressible pump tube 104, while the reagent cells and wash liquid outlet 280 of the reagent cells probe 270 is connected, by conduit 360 and nipple 362, to the inlet end of compressible pump tube 100.

In operation of the reagent dispenser l2, 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. Simultaneously, 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.

More specifically, it may be understood that with the offtake device 264 initially positioned as depicted in FIG. 4 with the respective inlets of the antiserum probe 268 and the reagent cells probe 270 respectively immersed in the antisera container 236 and the reagent cells container 248 for a predetermined period of time, and the three-way valves 282 and 284 in the respective closed and open positions thereof to simply circulate the air-segmented wash liquid therethrough, a measured volume of the anti A antisera will be aspirated from antisera container 236 through probe 268 for supply to compressible pump tube 104, and a measured volume of the reagent A cells will be aspirated from the reagent cells container 248 through probe 270 for supply to the compressible pump tube 100.

Following the expiration of this predetermined period of time. 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.

Following this. 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.

As the ofltake device 264 assumes the position thereof of FlG. 6. the same will be operated to move the

respective probes

268 and 270 through the ambient air to the positions thereof depicted in FIG. 7 wherein the inlet of probe 268 will be immersed in antisera container 238 and the inlet of reagent cells probe 270 will be immersed in the reagent cells container 250. with the result that measured volumes of ambient air will again be aspirated through the respective probe inlets for supply to the respective compressible pump tubes 104 and 100. The maintenance of the probe inlets 272 and 278 in the respective antisera container 238 and reagent cells container 250 for the same predetermined period of time will. of course.

result in the aspiration of a measured volume of the antiserum.

anti B through probe 268 for supply to compressible pump tube I04. and the concomitant aspiration of a measured volume of the reagent B cells through probe 270 for supply to compressible pump tube 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

For purposes made clear hereinbelow. it may be understood that the total time of operation of one reagent and wash liquid dispensing cycle is made substantially equal to the total blood sample and wash liquid supply cycle from the sample supply device 10.

As a result of the above. it is believed clear that a stream consisting of successive measured volumes of the respective antisera from antiserum containers 236. 238. 240.242. 244 and-246. as spaced. in each instance. by a segment of air. a slug of the air-segmented wash liquid from three-way valve 282. and a segment of air. will be supplied from antiserum probe 268 through conduit 354 for pumping through comtherefrom reagent cells supply conduit 372. The form of said streams of successive. measured volumes of antisera and reagent cells. and the phase relationship therebetween. is believed clearly illustrated by the depiction of corresponding portions of

conduits

366 and 372 in FIG. 10.

Referring again to the stream of successive ones of the aspirated portions'of the blood plasma samples from the respective blood sample container 28 supplied to blood plasma sample supply conduit 222. it may be seen that the same will flow therefrom through nipple and sleeve assembly 372 to and through delay coil 374 and. from the latter. through sleeve 376. connecting conduit 378 and sleeve 380. to and through delay coil 382. it being understood that the respective delay coils 374 and 382 are made necessary by the fact that the flow rate of the plasma stream through the apparatus of the invention is substantially higher than the flow rate of the blood sample cell stream through the apparatus of the invention.

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.

it may be seen that the inlet end of compressible pump tube 92 is left open to the ambient air. and that the outlet end of the said compressible pump tube is connected. by conduit 394 and nipple and sleeve assembly 396. to the other inlet of the junction conduit 392. whereby may be understood that'the thusly mixed blood sample plasma and reagent cells streams will be further segmentedby the air from the said compressible pump tube in the said junction conduit and will flow therefrom, through nipple and sleeve assembly 398. to a reverse grouping circuit or plasma-typing circuit 15 indicated generally at 400 for incubation to promote the necessary reaction between ditTerent portions of the said blood sample plasma stream and the distinct measured volumes or segments of the respective reagent cells from the reagent dispenser 12.

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.

through nipple 4H) and conduit 412. to one inlet of a junction conduit 414 whereby it may be understood that the said enzyme solution diluent will be supplied from the said compressible pump tube to the saidjunetion conduit. Theinlet end pressible pump tube 104 and supply from the latter to antisera V supply conduit 366. Concomitantly. a stream consisting of correspondingly extensive.successive ones of the reagent cells from the respective reagent cells containers 248. 250. 252.

254. 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

The outlet of the mixing coil 430 is connected as shown by sleeve 432 to the inlet of ajunction conduit 434 for flow of the now suitably diluted and treatcd'blood sample cell stream to the said junction conduit.

Referring agaih momentarily to the proportioning pump 18.

One outlet of the junction conduit 434 is connected as shown through conduit 436 and nipple 438 to the inlet ofcompressible pump tube 106. while the outlet of the latter is connected as shown through nipple 438 to a conduit 440 which extends as indicated to waste. By this arrangement. it may be understood that as the diluted blood sample cell stream is flowed from the mixing coil 430 through the junction conduit 434. a large aliquot of the said blood sample cell stream will be removed therefrom through conduit 436 and pumped to waste through conduit 440 to declot the said stream and remove solid materials therefrom.

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. and substantially declotted blood sample cell stream flows through the junction conduit 444. a substantial portion thereof will bewithdrawn therefrom through conduit 446 for resampling through the proportioning pump tube "8 and subsequent supply from the latter to fitting 454 through conduit 452. with the remainder of the said blood sample cell stream being simply flowed to waste through conduit 458.

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. As a result. it may be understood that 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. As a result of this arrangement it may be understood that an aliquot of the air-segmented saline stream flowing through the junction conduit 484 will be removed therefrom through conduit 486 and pumped. by the progressive occlusion of compressible pump tube 120. to the inlet of fitting 494 through conduit 492. The other outlet of the junction conduit 484 is connected as shown by nipple and sleeve assembly 496 to a conduit 498 which extends to waste. whereby may be understood that the remainder of the air-segmented saline stream flowing to the,

said junction conduit will simply be flowed therefrom to waste through the conduit 498. r

A compressible conduit 500 extends as shown to connect one outlet of fitting 454 to one inlet of fitting 502. while a compressible conduit 504 extends as shown to connect the other outlet of fitting 454 to one inlet of a fitting 506. in like manner. a compressible conduit 508 extends as shown to connect one outlet of fitting 494 to the other inlet of fitting 506. while a compressible conduit 510 extends as shown to connect the other outlet of fitting 494 to the other inlet of fitting 502. V I

Refen'ing now to the sample cell and wash liquid control valve means 22. it may be understood that the same 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

' shown and described herein for purposes of sufficiency ofdisclosure. will comprise a bar valve member 512 which is carried from a valve base member 514 and is disposed as indicated over each of the compressible conduits 500 and $08.

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.

As utilized herein, it may be understood that when one of' the said bar valve members is actuated. the other is deactuated. and vice versa. and that 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. g

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.

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.

and flow of the air-segmented saline solutionstream through conduit 500. and flow of the air-segmented salinesolution stream through conduit 508. will be permitted. As a result. the

segmented saline solution stream from conduit '508 will be flowed to waste through fitting506 and conduit 5 l8..while the enzyme diluted and treated blood sample cell stream from conduit 500 will be flowed to fitting 522 through fitting 502 and conduit 520. Thus. with the bar valve means 22 being operated or cycled. as set forth hereinabove. six times for the supply of eachblood sample cell portion thereto. it may be understood that the said bar valve means will function to divide each of the blood sample containers 28 into six distinct quo tients or subfractions of the same predetermined volume. each of which will be clearly delineated fore and aft. in each instance. by an interveningslug of the air-segmented saline'solu- 240. 242. 244 and 246 as spaced fore and aft. in each instance. V l

by a segment of air. a slug of wash liquid. and a segnent of air (FIG. l0). is supplied therefrom for each blood sample cell portion to the compressible pump tube M0 and. from the latter, to conduit 366 which extends as shown into connection I with the other inlet of fitting 522. As a result. through proper.

phasing of the respective operations of each of the sample supply means 10. the reagent dispenser l2. and the valve" means 22. it may be understood that as 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. as a fourth quotient of the same blood cell sample reaches the fitting 522 it will be met thereat for merger with an appropriate portion of the vanti Rh,(D) antiserum from container 242. as a fifth quotient of the same blood cell sample reaches the fitting 522 it will be met thereat for merger with an appropriate portion of the Rh, "(CDE) antiserum from container 244. and as a sixth and final quotient of the same blood cell sample reaches the fitting 522 it will be met thereat for merger with an appropriate portion of the control antiserum from reagent dispenser container 2A6. Of particular significance here is the fact that by sequentially supplying the respective antisera only on demand in precisely measured. ap-. propriate volumes thereof to the respective blood cell sample quotients in asingle channel. rather than supplying said antisera as continuous streams in separate channels in acvolumes of antiserum. and of the six distinct blood sample cell quotients or subfractions of a single blood cell sample as the same arrive at fitting 522. and the respective phase relationship therebetween are believed made clear by FIG. ll which depicts the said streams in thoseportions of conduits 520 and 366 (as somewhat rearranged for clarity of illustration) immediately downstream of fitting 522.

Referring again to the proportioning pump 18. it may be seen that 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. As a result. it may be understood that 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.

By way ofdistinction. it may be understoodthat. since in the case of the respective blood plasma sample portions. a relatively clear fluid is being dealt with. with little or no tendency for plasma-reagent cells reaction carryover. it is possible to supply 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. by the extent of the slug of air. the segment of wash liquid. and the slug of air provided intermediate each of said reagent cell portions as described 'hereinabove-while still maintaining suitable'delineation between the differently reacted parts of each of said blood plasma sample portions. Conversely. it may be understood that. since in the case of the respective blood cell sample portions from each of the containers 28 (HO. 2). a substantially darker fluid with substantially greater tendency for antiserum-cell reaction carryover is present. it becomes important to clearly divide each of said blood cell samples into six clearly delineated quotients. as described in detail hereinabove. and to in turn add a different one of said antisera to each of the same. to assure the ready discemibility of the respective antisera-blood sample cell quotients reactions.

Referring again to the proportioning pump means [8. it may be seen that 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. to the wash liquid reservoir 146. and the outlet end of the said compressible pump tube is connected.-through nipple 556. conduit 558. nipple 560 and conduit 562. respectively. to the outlet conduit 564' of the plasma-typing circuit 534 to thus further dilute the reacted cells stream flowing from thecelLtyping circuit 534 in the said outlet conduit. 7

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. In addition. it may be understood that the function. in

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. In like manner. 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.

As is believed well known by those skilled in this art. positive reactions in either of the plasma-typing circuit 400 between the respective reagent cells and the blood sample -pla'sma portion parts. and in the cell-typing circuit 534 between the respective antisera and the blood sample cell quotients. will. in each instance. lead to the fonnation of combinations or agglutinations of cells which will. of course; settle out and flow primarily along the respective bottom wall portions of the straight.

horizontal conduits

568 and 576. As a result. such combinations or agglutinations of cells will. in each instance. be substantially removed by the respective decant means 582 and 590 for flow therefrom to and through the respective compressible pump tubes I22 and 124. On the other hand. in those instances wherein there is a negative reaction between the respective reagent cells and said plasma portion parts. and between the antisera and said plasma quotients.

withdrawal through the said decant means.

The outlet end of 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.

Referring now to the treated sample analysis means 24 the same 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. In operation, 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. Thus, as each of the treated blood sample cell quotients is discharged from the outlet end of delivery conduit 604, 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. In like manner, as each of the treated blood sample plasma portion parts is discharged from the outlet end of delivery conduit 600, 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.

As a result of the above, it may be understood that a readily readable and reproducible record will be provided on the filter paper M0 to clearly indicate, in each instance, whether or not a positive reaction has taken place, it being believed clearly understood by those skilled in this art that a positive reaction will be indicated by a relatively dark spot on the filter paper 6l0, as occasioned by the deposition of agglutinated cells thereon, while a negative reaction will be indicated on the said filter paper by a relatively light spot to clearly indicate that no significant cell agglutinations have taken place and that principally free cells have been deposited thereon.

More specifically, and making reference now to FIG. 12 which 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, it may be seen that for the first analyzed ofsaid blood samples, 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.

Referring now to the second analyzed of said blood samples, it may be seen that the group of results as indicated generally at 618 makes clear that positive antiserum-blood sample cell reactions occurred between the respective anti A, anti AB, anti Rh,(D) and anti Rh,,"'(CDE) antisera and the blood sample cells, while the only positive reagent cell-blood sample plasma reaction occurred between the type B reagent cells and the said blood sample plasma, to thus clearly type second-analyzed blood sample as A-positive blood.

By way of comparison between the rate of antiserum consumption per blood sample typing of the method and apparatus of this invention wherein the antisera or typing sera are supplied sequentially on demand in appropriate, predetermined measured volumes thereof in a single channel, and the rate of antiserum consumption per blood sample typing of the methods and apparatus of the prior art wherein said antisera or typing sera are supplied as continuous streams in a plurality of channels, it may be understood that the method and apparatus of this invention have been determined to enable reductions in the antisera consumption rate per blood sample I typing ranging from 80 to 90 percent.

While we have shown and described the preferred embodiment of our invention, it will be understood that the invention may be embodied otherwise than as herein specifically illustrated or described, and that certain changes in the form and arrangement of parts and in the specific manner of practicing the invention may be made without departing from the underlying idea or principles of this invention within the scope of the appended claims. What is claimed is:

. I. In apparatus for the automatic typing of blood samples in the form of a stream of successive blood sample plasma quotients of the same blood sample and a concomitant stream of successive blood sample cells quotients of the same blood sample, respectively, 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. 7

2. In 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. I

3. In a method for the automatic typing of blood samples in the form of a stream of successive blood sample plasma quotients of the same blood sample and a concomitant stream of successive blood samples cells quotients of the same. blood sample, respectively, the steps of. concomitantly supplying a successive stream of different antiserum quotients of predetermined required volume and a successive stream of different reagent cells quotients of predetermined required volume.

respectively, merging said plasma and reagent cells streams so that each of said blood sample plasma quotients is mixed and reacted with a different one of said reagent cells quotients, merging 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 examining 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.

4. In a method as in claim 3 further comprising,'the steps of, introducing separating fluid segments in said respective an tiscra and reagent cells streams between the respective antisera and reagent cells quotients.

5. In apparatus for the automatic analysis of fluid samples in the form of a stream of successive sample quotients of the same fluid sample respectively, 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.

6. In apparatus as in claim 5 further comprising, means to introduce separating fluid segments in said reagent quotient stream between the respective reagent quotients.

7. In a method for the automatic analysis of fluid samplesin the fonn of a stream of successive sample quotients of the same fluid sample, respectively, the steps of, supplying a 'suc-. cessive stream of diflerent reagent quotients of predetermined required volume, respectively, merging 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 examining the respective reacted sample quotients to effect fluid sample analysis.

8. In a method as in claim 7 further comprising. the steps of, introducing separating fluid segments in said reagent quotient stream between the respective reagent quotients.

# i t O U

Claims

2. In apparatus as in claim 1 further comprising, means to introduce separating fluid segments in said respective antisera and reagent cells streams between the respective antisera and reagent cells quotients.
3. In a method for the automatic typing of blood samples in the form of a stream of successive blood sample plasma quotients of the same blood sample and a concomitant stream of successive blood samples cells quotients of the same blood sample, respectively, the steps of, concomitantly supplying a successive stream of different antiserum quotients of predetermined required volume and a successive stream of different reagent cells quotients of predetermined required volume, respectively, merging said plasma and reagent cells streams so that each of said blood sample plasma quotients is mixed and reacted with a different one of said reagent cells quotients, merging 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 examining 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.
4. In a method as in claim 3 further comprising, the steps of, introducing separating fluid segments in said respective antisera and reagent cells streams between the respective antisera and reagent ceLls quotients.
5. In apparatus for the automatic analysis of fluid samples in the form of a stream of successive sample quotients of the same fluid sample respectively, 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.
6. In apparatus as in claim 5 further comprising, means to introduce separating fluid segments in said reagent quotient stream between the respective reagent quotients.
7. In a method for the automatic analysis of fluid samples in the form of a stream of successive sample quotients of the same fluid sample, respectively, the steps of, supplying a successive stream of different reagent quotients of predetermined required volume, respectively, merging 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 examining the respective reacted sample quotients to effect fluid sample analysis.
8. In a method as in claim 7 further comprising, the steps of, introducing separating fluid segments in said reagent quotient stream between the respective reagent quotients.