US3772154A - Method and apparatus for automated antibiotic susceptibility analysis of bacteria samples - Google Patents

Method and apparatus for automated antibiotic susceptibility analysis of bacteria samples Download PDF

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Publication number
US3772154A
US3772154A US00139435A US3772154DA US3772154A US 3772154 A US3772154 A US 3772154A US 00139435 A US00139435 A US 00139435A US 3772154D A US3772154D A US 3772154DA US 3772154 A US3772154 A US 3772154A
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sample
probe
series
receptacles
receiving receptacles
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US00139435A
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English (en)
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H Isenberg
A Reichler
D Wiseman
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Bayer Corp
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Technicon Instruments Corp
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/113332Automated chemical analysis with conveyance of sample along a test line in a container or rack

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  • ABSTRACT Method and apparatus for automated antibiotic susceptibility analysis of bacteria samples including a device for feeding in succession a plurality of different samples, each of a significant, unknown bacterium from a respective receptacle to plural respective ones of receiving receptacles in which the sample portions are treated or conditioned, and, in at least certain of the last-mentioned receptacles, the growth of bacteria is challenged by addition of different antibiotics respectively thereto. Samples are incubated and subsequently killed, bacteria from the respective and receiving receptacles are removed by sampling for counting and comparison indicating, with the use of a control, relative antibiotic susceptibility through the proliferation of the bacteria, and recording the results of the analysis.
  • An individual, moveable probe is employed in each of the first mentioned receptacles for transfer therefrom of the respective sample to the plural aforementioned receiving ones of the receptacles and is then returned to the last-mentioned one of the receptacles, effectively reducing the risk of contamination between samples.
  • Such probes may be expendable and disposed of with the remaining corresponding samples, or may be sterilized and reused.
  • One object of the invention is to provide a technique for automating antibiotic susceptibility analysis of all steps subsequent to the preparation of a culture and the preparation of a suitably diluted inoculum from the culture and placement of this inoculum in the apparatus. Another object is to provide automated antibiotic susceptibility analysis having much greater speed than any heretofore known, which provides the needed information for the administration on the same day of specific drug or drugs to fight an infectious disease.
  • the technique has as a significant feature, the reduction of risk of contamination of a sample and between samples. This feature is obtained in part through the use of individual probes for sample receptacles, each of which probes in the analysis is used only once for that particular sample, and which probe may be of the disposable type enabling it to be disposed of in a suitable waste receptacle at the same time a suitable disposition is made to waste of the remaining sample in the sample receptacle.
  • the individual probes have other advantages.
  • One such advantage is that the probes do not require sterilization as by being heated to incandescence during the analysis of plural samples nor exposed to sterilizing chemicals nor washed during this process, thereby avoiding such problems as the undesirable killing of bacterium in a sample through heat or exposure to chemicals, and further avoiding undesirable sample dilution by probe wash solutions.
  • Another very important feature of the use of such probes is that each will dispense repetitively drops of inoculum of the same volume. This effects analytical results which are reliable with reference to the various antibiotics with which each inoculum is tested, the test with reference to each particular antibiotic being carried out in a respective one of plural discrete chambers.
  • Still another advantage derived from the use of individual probes for the transfer of each inoculum to the plural testing chambers for the respective antibiotics is that total sterility of the probe is not required. This is a great convenience as well as a time and expense saver. Such total sterility is not required because the probe is used only for a very short period of time, that is, an insufficient time for other bacteria to significantly affect the bacterium of the sample. Other bacteria present, at most in very small numbers, cannot achieve numbers which would interfere with the analysis since the inoculum consists of very large numbers of bacterial particles in an environment favoring this proliferation, according to the invention.
  • Another object is to provide an antibiotic susceptibility analysis technique which utilizes a very short incubation period for the bacteria, thereby reducing the risk of contamination of the aforesaid type, and also making possible analysis at a rapid rate.
  • analysis utilizing the invention requires but three hours from the time of placement of the inoculum in the apparatus.
  • the first named device is also used to indicate the exponential growth of bacterium in an uninhibited control of each inoculum in a growth medium, such as a broth, employed also with reference to the chambers where the inoculum is challenged by the presence of respective antibiotics.
  • the use of the last-mentioned photometric device also enables the comparison of the uninhibited growth of the last-mentioned control with a control which is killed after a preincubation stage and subtracted in the counting device from the count of the first-mentioned control to eliminate such factors as unviable organisms and dirt.
  • the counting device which is actually a particle counter also serves to provide a comparison of the susceptibility of each inoculum to the antibiotics to which it is exposed. The results of the analysis are recorded on a recorder.
  • a method and apparatus for automated antibiotic susceptibility analysis of bacteria samples including a device for feeding in succession a plurality of different samples, each of a significant, unidentified bacterium from a respective receptacle to plural respective ones of receiving receptacles in which the sample portions are treated or conditioned, and in at least certain of the last-mentioned receptacles the growth of bacteria is challenged by addition of different antibiotics respectively thereto.
  • the last-mentioned feeding device is susceptible of various other uses including the handling in other analytical systems of radioactive substances, or may be employed to transfer a small quantity of any liquid, such as reagent or sample, to a station at which it is utilized.
  • the system of the invention is also suitable for other uses such as providing bacteria counts of uninhibited exponential growth. It is useful for measuring minimum antibiotic inhibitory concentrations, and when used with known bacteria may test various fluids such as body fluids for example for their characteristics of inhibiting bacterial growth. Further objects will be apparent from the following detailed description of the preferred embodiments of the invention.
  • FIG. 1 is a block diagram illustrating sequentially the orientation of stations A-H of apparatus for automated antibiotic susceptibility analysis embodying the invention, wherein A is the nutrient broth dispensing station; B is the inoculum transfer station for transfer of bacte' rium samples to receptacles containing the broth; C is the station for adding different antibiotics to certain of the last-mentioned receptacles and a bacteria killing agent to another of the last-mentioned receptacles; D is the incubation station; E is the station for adding a bacteria killing agent to those receptacles in which such an agent has not been previously added; F is the station for sampling the contents of each of the receptacles holding the treated samples; G is the photometric station for the examination for counting purposes of the particles in the sample receptacles such as bacteria and foreign matter; and H is the station for receiving signals from station G in order to count the lastmentioned particles and make comparisons of such counts and for recording the results of
  • FIG. 2A is a perspective view illustrating somewhat diagrammatically station A of the apparatus
  • FIG. 2B is a similar view illustrating stations B and C of the apparatus
  • FIG. 2C is a similar view illustrating stations D H of the apparatus.
  • FIGS. 3A3F are views looking in the direction of the arrows 3AF of FIG. 2B illustrating different positions of the probe holder and associated parts at the transfer station B;
  • FIG. 4 is an enlarged sectional view taken on line 44 of FIG. 2B.
  • FIGS. 5A and 58 when viewed together, a wiring diagram.
  • FIG. 10 a supporting table-like or counter element, indicated generally of 10, providing a supporting surface and of an elongated form.
  • This tablelike element is shown associated with stations AF.
  • a pair of lead screws l2 Arranged longitudinally on the table 10 in spaced parallel relationship are a pair of lead screws l2 suitably supported from the table for rotation.
  • the screws 12 extend substantially throughout the length of the table and are located a short distance upwardly therefrom in order to clear the table.
  • the table forms part of a conveyor system having a pickup end 14 (FIG. 2A) and a discharge end 16 (FIG. 2C).
  • each screw 12 is provided with one of a pair of wheels 18 angularly fixed thereto, interconnected for the drive of one from the other by a belt 20.
  • an electric motor 22 is provided to drive the screws 12 through the belt 20, which motor may be supported from the table.
  • the motor 22 drives a shaft on which is fixed a cam wheel 24 and to which shaft in axially spaced relationship from the wheel 24 is also fixed driving wheel 26.
  • a wheel 28 in angularly fixed relation and axialy spaced from one of the wheels 18 is driven from the wheel 26 through a belt 30.
  • a switch 32 is provided having an actuator cooperating with the cam wheel 24 to de-energize the intermittently operable motor 22 after an appropriate, uniform interval of operation, one revolution of the cam wheel 24.
  • Samples of different inocula are carried along the table in a stepwise fashion after being transferred thereto at station B for treatment at subsequent stations, and the conveyor system illustrated by way of example includes for the purpose of advancing the samples as aforesaid a plurality of trays 34 which trays have on two opposite sides thereof rack-like gear teeth 36 formed therein for cooperation with the respective screws 12.
  • the conveyor system illustrated by way of example includes for the purpose of advancing the samples as aforesaid a plurality of trays 34 which trays have on two opposite sides thereof rack-like gear teeth 36 formed therein for cooperation with the respective screws 12.
  • disposable cups 38 are provided to receive the sample inocula. These cups 38, which do not require total sterility for the same reasons discussed above with reference to the probes, are suitably supported as in sockets 35 provided in the trays, the cups being laterally spaced apart.
  • each tray may contain 50 cups of plastic or other suitable material in five rows spaced lengthwise of the table and extending transversely of the table.
  • each tray 34 is illustrated as having three transverse rows of cups spaced lengthwise of the table, each row having five cups, the first cup in each row being indicated at 40 and the second cup being indicated at 42. It will be understood from the foregoing that the trays 34 may be advanced in a stepwise manner other than by the use of the lead screws 12. It will be obvious to those versed in the art that sprocket chains, for example, could be employed for this purpose if desired.
  • any suitable conventional mechanism may be employed to properly engage with screws 12 a tray from the entrance ramp 44 (FIG. 2A) at the proper time.
  • the spacing of the cups 38 in each tray 34 is critical to automation and must be uniform.
  • the spacing of the trays from one another lengthwise of the table has been greatly exaggerated for ease of illustration and better understanding of the apparatus of the drawings.
  • two neighboring trays are spaced apart with reference to the trailing row of one tray and the leading row of the following tray such that the'center ofa cup in one of the last-mentioned rows is spaced from the center of its corresponding member in the other of the last-mentioned rows a distance which is twice the distance between the centers of neighboring rows of cups in any one tray 34.
  • Trays 34 from the table 10 are discharged by the conveyor system into a suitable collection bin 46 (FIG. 2C) after the sample receiving cups 38 have been emptied as will be described hereinafter.
  • each socket 35 of each tray used receive therein one of the disposable cups 38 before the tray is placed on the ramp 44.
  • the first tray 34 (FIG. 2A) is properly engaged by the screws 12 as aforesaid when received from the ramp 44 after the start button (not shown) is depressed to start main timer 48 (FIG. 10), energizing and reenergizing motor 22 at uniform intervals closely approaching 90 seconds (dc-energized once each revolution of the cam wheel'24 coacting with the switch 32) to operate the screws 12 to advance the tray on the right shown in FIG. 2A to the position shown therein at which time the motor 22 is de-energized through actuation of the switch 32 by the cam wheel 24. Movement of the last-mentioned tray to this position is sensed by switch 50 FIG. 10 having an actuator engageable with a protrusion 52 formed on the tray, which protrusion may take the form of an upstanding removeable pin. Each tray is provided with a similar pin 52. Actuation of the switch 50 enables the broth station A.
  • sub-frame 54 including a vertically arranged plate extending transversely across the table 10 in a location thereabove and suitably supported from the table as shown, the subframe 54 having at its ends ears 56 which rigidly support therebetween a rod 58 serving as a support and guide as will appear hereinafter.
  • the frame element 54 supports a reversible electric motor 60 having a driving shaft angularly fixed to a timing wheel 62. In axially spaced relation from the wheel 62, wheel 64 is also angularly fixed to the lastmentioned shaft.
  • a switch 66 has an actuator engageable with the cam wheel 62.
  • the location of the motor 60 and the above described associated elements is adjacent one end of the frame element 54 as illustrated in the last-mentioned view and, as also shown in this view, there is provided adjacent the other end of the frame element 54 a shaft on which an idler 68 is revolubly provided.
  • a belt '70 is trained over the wheel 64 and the idler 68 and carries fixed thereto a switch actuator 72.
  • the actuator 72 coacts with limit switches 74 and 76 spaced apart as shown and supported from the frame element 54 together with the switch 66 previously described.
  • the belt has fixed thereto, as at 71, a nozzle holder '78, receiving and rectilinearly slidable on the horizontal rod 58, and rigidly supporting a downwardly directed nozzle 80 which in the position of FIG. 2A is directly over the first cup 40 of the first row of cups 38 of the last-mentioned tray.
  • a tube 82 Connected to the nozzle 80 is one end of a tube 82 having its other end connected for receipt of liquid from a pump designated generally at 84.
  • the inlet of the pump is connected through one end of a tube 86 to a reservoir of liquid receiving the other end of the tube 86, as shown in the last-mentioned view, for aspiration through the tube 86 of liquid from the reservoir.
  • liquid in the reservoir 88 is sterile bacteria nutrient in the form of a broth. Eugon broth may be used for this purpose.
  • the pump 84 comprises a suitable plate-like support element 90 horizontally arranged, on which a vertical standard 92 is fixed and on which an upwardly extending plate-like element W8 is also arranged in laterally spaced relation from the element 92.
  • the support element 94 supports an electric motor 96 the driving shaft of which is suitably journaled in the support element 92 and has angularly rigid therewith a cam wheel 98 coacting with the actuator of a switch 100 carried by the plate-like support element 94 which de-energizes the motor 96.
  • the pump motor shaft is indicated at 102.
  • the pump 84 comprises a syringe and hence is of the expansible chamber type. As shown in FIG. 2A it comprises a barrel element 194 providing the expansible chamber. A plunger 106 is extensible into one end of the barrel 11M and the plunger 16% is operated in the barrel 104 through a linkage 08 connected to one end of the plunger 1116 and connected to a crank arm 11% fast on the shaft 102. It is believed made clear from the foregoing that rotation of the motor shaft 102 effects a reciprocating motion of the plunger 106 in the barrel 104.
  • the barrel 104 has an outlet in a conventional valve element 111 secured to the other end of the barrel and supported, as shown in FIG. 2A by a shaft 112 projecting in fixed relation from the support element 92.
  • the valve element 111 connected to corresponding ends of the tubes 87. and 86, has two ball checks con trolling the flow of liquid through the respective tubes 82 and 86.
  • liquid from the reservoir 88 is drawn into the barrel through tube 86 past one of the ball checks while the other ball check prevents any flow of fluid through the tube 82.
  • the plunger 16.16 is retracted into the barrel 104 to discharge the contents of the syringe the corresponding ball check prevents the flow of fluid through tube 86 while permitting the flow of liquid through the tube 82.
  • the broth pump 84 cycles delivering a precise amount of broth, which may be in the neighborhood of 2 ml., to the first cup d6 through the nozzle 80.
  • switch b is actuated by cam wheel 91% the pump motor Q6 is de-energized and operation of motor 611 is commenced to move the nozzle 80 over the cup 42 at which point operation of the motor 60 is stopped through actuation of switch 66 by cam wheel 62.
  • the pump cycles and the intermittent movement of the nozzle 80 continues in the last-mentioned direction until the last cup 38 in the first row in the tray is filled to the extent indicated above, and the actuator '72 actuates switch 74 de-energizing the motor 60 and placing it in a reversed mode.
  • the filling of the cups 38 of the first row in present practice requires less than 90 seconds.
  • the motor 22 is energized to drive the tray-advance screws 12 until the motor 22 is deenergized by operation of the cam wheel acting on the actuator of the switch 32.
  • the nozzle 80 is over the corresponding cup of the second row of cups in the last-mentioned tray.
  • the pump 84 cycles on actuation of switch 32 to feed broth to this cup from the nozzle after which the motor 60 is again energized as aforesaid so that the nozzle 80 is brought over the next cup in the secnd row. This opera tion continues until all the cups in the tray have been filled with broth, to the extent indicated, in the course of which the limit switch 76 also serves to effect stopping and placing in reversed mode the motor 60.
  • the motor 22 is energized and advances the tray one increment as aforesaid whereupon the motor 22 is deenergized as aforesaid, and on receipt of a further signal from the main timer 48 the motor is re-energized to advance the tray to the position thereof at the transfer station B shown in FIG. 2B. It is believed made clear that when this tray reaches the last-mentioned position the following tray 34 reaches the starting position previously described with reference to the broth station and shown in FIG. 2A,
  • a sub-frame indicated generally at 116 including an elongated vertically arranged plate-like element having end flanges 118 by which it is suitably supported on the table 10 to extend transversely thereof.
  • These flanges 118 rigidly support vertically spaced twin rods 120 extending therebetween and arranged transversely of the table.
  • the lowermost rod 120 is spaced upwardly from the table as in dicated and provides clearance for the screws 12 and the trays 34 which move along the table.
  • a carriage, indicated generally at 122, is supported by the rods 120 for horizontal movement therealong.
  • the carriage 122 comprises a vertically arranged plate 124 to which are rigidly secured two vertically spaced pairs of blocks 126 which pairs respectively receive the rods 120 for sliding movement thereon.
  • the carriage 122 includes a subcarriage indicated generally at 128 arranged to be cammed vertically in one axial position of the carriages 122 and l28 on the rods 129 as will hereinafter appear.
  • the subcarriage 128 comprises an upper horizontally arranged plate 130 and spaced therebelow a plate 132 having a depending vertically arranged plate part 134 of L-shaped terminating in a cross plate part 136 which is vertically arranged and of elongated form extending longitudinally of the table.
  • the plate parts 130 and 132 are interconnected by a vertically arranged plate 138 (as shown in FlG. 2B) suitably fixed thereto as by welding.
  • the carriage 122 also includes a pair of laterally spaced rods 1&0 which are vertically arranged and which have their respective ends in assembled form fixed to the respective plates 130 and 132.
  • the rods we extend through and are slidable in extensions 142 of the respective blocks 126.
  • a pair of vertically spaced horizontal rails are arranged transversely of the rods 14% and secured thereto, as by welding, so as to protrude therefrom, the rails being indicated at 144.
  • the rails receive therebetween a portion of a stationary carrier strip 146.
  • This carrier strip may be formed of relatively heavy strip metal welded in edgewise relation to the frame plate 116 to protrude horizontally therefrom in the manner shown in the last-mentioned view, and as shown here the carrier strip 146 extends transversely of the table.
  • the carrier strip 146 which in the last-ham ed position of the carriage 128 supports the latter, extends from the far one of the flanges 118 shown in FIG. 2B
  • the sub-frame 116 together with the rods 120 project toward the viewer beyond the main bed of the table to the extent indicated.
  • the construction and arrangement is such that the carriages 122 and 128 may be moved transversely of the table on the support rods 120 to a position in which the vertically moveable sub-carriage 128 may be lowered to the position of FIG. 3B.
  • a reversible electric motor 148 supported from the frame plate 116 and having its driving shaft angularly fixed to the wheel 150 and angularly fixed to the cam wheel 152 in axially spaced relation from wheel 150.
  • a switch 154 is mounted on the last-mentioned plate which switch is similar to the previously described switch 66 and has its actuator in engagement with the cam wheel 152 serving a similar function to the aforementioned cam wheel 62.
  • the motor 148 and the above described associated parts are disposed adjacent one end of the transverse frame plate 116.
  • the plate 116 Adjacent the other end thereof, the plate 116 revolubly supports wheel 156 which is an idler similar to the above-described idler 68 and over which a belt 158 is trained which belt is also trained over wheel 150 which drives the belt.
  • the belt 158 has a switch actuator 160 fixed thereto and the belt 158 is fixed, as'at 162, to the least one of the upper pair of the carriage blocks 126.
  • switches 164, 166 and 168 are spaced from one another transversely of the table and supported by the plate 116, as indicated in FIG. 2 by way of example.
  • the last-named switches have actuators engageable by the switch actuator element 160, previously described, affixed to the belt 158 in the illustrated form.
  • a nonreversible electrical motor 170 for the vertical drive of sub-carriage 128. It is believed made clear that the motor 148 provides horizontal drive for the carriages 122, 128.
  • the driving shaft of the motor 170 has angularly fixed thereto a cam wheel 172, and has a crank arm also angularly fixed thereto in axially spaced relation from the cam wheel 172, the crank arm being indicated at 174.
  • One end of the arm is fixed to the last-mentioned shaft.
  • the other end of the arm 174 carries a cam 176 which is illustrated as a horizontally extending anti-friction roller which roller in the positions of FIGS. 3A--3E is received between the rails 144 of the vertically moveable carriage 128.
  • the frame plate 116 also supports spaced apart switches 178, 180 and 182, each of which has an actuator bearing against cam wheel 172.
  • a vertically moveable carriage 128 There is provided on vertically moveable carriage 128 a vertically arranged probe. holder of cylindrical form extending through the plate 132 and fixedly supported by the last-mentioned plate, the proble holder being indicated generally at 184, as shown in FIG. 2B, FIGS. 3A-3F and FIG. 4.
  • the cylindrical body of the holder 184 has an axial bore therethrough into the upper end of which extends a plunger 186.
  • the upper end portion of the plunger 186 receives in fixed relation thereto a transverse pin 188 extending therefrom, as best shown in FIGS. 3A-3F having fixed at its distal end a ball 190 which ball is mounted for universal movement in a socket 192 (FIG.
  • cam wheel 194 is angularly fixed to the shaft of a reversible electric motor 196 supported by the plate part 138, and switches 198, 200 and 202 spaced from one another are also supported from the plate part 138, each having an actuator engageable with the cam wheel 194.
  • a transverse open-ended duct 204 of tubular form best shown in its relationship to the last-mentioned bore in the probe holder 184 in FIG. 2B.
  • the last-mentioned tube is controlled by a solenoid-operated valve 206.
  • the valve normally closes the tube 204 (FIG. 2B) and is open when the last-mentioned solenoid is operated for flow of air through the tube 204 from its right-hand end as shown in FIG. 2B.
  • the amount of air flowing in the tube 204 may be controlled by a needle valve having a body 208 and a manipulating part 210.
  • the air tube 204 and its associated parts previously described may be supported in any suitable manner.
  • the aforementioned cross plate 136 carried by the depending plate part 134 of the carriage 128 provides a support for a drop counter in the form of a photoelectric device including at one end of the plate 136 a housing 212 for a light source such as an electric bulb and means, not shown, to direct light therefrom along a path toward a light detector housing, indicated generally at 214, supported on the other end of the cross plate 136.
  • a light source such as an electric bulb and means, not shown
  • the counter In the position of the drop counter shown in FIG. 2B, the counter is spaced above the tray 34 and the cups thereon and is in operative position to count drops dispensed from the probe, indicated generally at 216, in the holder 184 into the first cup 40 of the first row of cups 38 in the tray 34 shown at the transfer station, and in this position of the tray effected as aforesaid by the operation of the tray-advance screws 12, the pin 52 of the tray is shown engaged with the actuator of switch 218. It is to be noted that the switch 218 is operated by the pin 52 as the tray assumes the position of FIG. 2B and prior to the assumption of the carriage positions shown in FIG. 2B. When the tray 34 assumes the lastmentioned position, the carriage 128 is in the position of FIG. 3A.
  • the holder includes an upright cylindrical body having'an axial bore therethrough which bore is indicated at 220 and is shown as receiving through the upper end thereof the aforementioned plunger 186.
  • the last-named bore is counter-bored through the lower end, as at 22.
  • An end cap extends over the outer end of the counterbore 222 and this cap is provided with a tapered orifice 224 through which the upper end portion of the probe is extensible as shown in FIG. 4.
  • the plunger 186 is provided with air tight sealing devices or rings 226.
  • At least two O-rings are provided in the counterbore 22 in axially spaced apart relation to form an air-tight seal around the upper end portion of the probe when it is inserted in the holder and to prevent the probe from cocking in the holder from the vertical position, the two O-rings being indicated at 228.
  • the O-rings are so constructed and arranged that when they are engaged and sealed against the probe 216 they do not engage so as to be compressed against the wall of the counterbore 222 but rather have clearance with the last-mentioned wall. This tends very effectively to reduce friction when the probe is relatively extended into the holder or removed therefrom. In fact, in the construction shown, at least the lowermost one of the O-rings 228 tends to have only line contact with the probe when it is inserted in the holder and line contact with the aforementioned lower cap of the holder.
  • a ring-like spacer 230 is interposed between the rings 228 and has cam surfaces thereon engageable with the respective O-rings tending to center them.
  • a light compression spring 232 has one end thereof bottoming in the counterbore 222 and has the other end thereof bearing against a sleeve 234 bearing against the upper surface of the uppermost one of the O-rings 228.
  • This spring and the spring follower 234, together with the ring 230, tend to maintain the O rings 228 in a proper relationship to receive in sealing engagement the upper end of the probe within the holder and provide at least a seal of the lowermost one of the O-rings 228 against the lower end cap in the manner previously indicated.
  • an air port In communication with the bore 220 there is provided an air port, not shown, extending transversely through the cylindrical wall of the holder and in communication with the aforementioned tube 204.
  • any liquid drawn into the probe 216, which is of open-ended tubular form, by this aspiration is held within the tube 216 while the plunger 186 remains in its upper position, until such time as the solenoidoperated valve 206 opens to admit air into the tube 204.
  • drops may be dispensed of the liquid in the probe 216 (FIG. 28) through the open lower end thereof, and such drops will cease to fall when the solenoid valve 206 is closed.
  • the probe 216 shown supported in the holder 184 is but one of a plurality of probes employed in the illustrated apparatus for carrying out the above-described type of antibiotic susceptibility tests.
  • a series of different bacteria samples which may be considered as different cultures developed from different specimens taken from different hospital patients and supplied to the apparatus sequentially.
  • Each sample of a significant bacterium which is prepared in a manner which will be described hereinafter, is placed in a suitable vessel, such as a test tube, for example, or a cup, which does not re quire total sterility for the above noted reasons including, primarily, the short length of time which the sample necessarily resides in the vessel so as not to be signiflcantly affected by foreign bacteria in the vessel.
  • a suitable vessel such as a test tube, for example, or a cup, which does not re quire total sterility for the above noted reasons including, primarily, the short length of time which the sample necessarily resides in the vessel so as not to be signiflcantly affected by foreign bacteria in the
  • These cups or tubes, indicated at 242, are supported in a turntable rack 244 (FIG. 28) by means of peripherally spaced tube-receiving sockets therein.
  • the turntable 244 is shown receiving seven such tubes but in practice the turntable may receive twenty such tubes and when such tubes are placed in the turntable assembly prior to commencement of operation of the apparatus, each is provided with its individual probe 216. As previously made clear total sterility of these probes is not required mainly due to the fact that they are employed in the testing procedure for such a short period of time, as the vessels in which they are supported.
  • the turntable 244 is suitably supported from a base 246 on a shaft 248 mounting the table 244 for rotation. As indicated diagrammatically the turntable may be driven by a belt 248 trained over the table and also trained over a driving wheel 250.
  • the wheel 251) like the turntable 244, has a vertical axis and the wheel 250 is driven through an electric motor 252 having a vertically arranged driving shaft to which a cam wheel 254 is angularly fixed.
  • the wheel 250 is angularly fixed to the last-mentioned shaft in axially spaced relation from the cam wheel 254.
  • a switch 256 has an actuator engaging the cam wheel 254.
  • the above-described turntable assembly 240 and associated parts may be supported in any suitable manner with the turntable 244 in the relationship to the table 10 and the transfer station B shown in FIGS. 28 and 4.
  • the turntable motor 252 When the turntable motor 252 is energized, after a dispensing operation utilizing the holder 184, and after the probe 216 shown in the holder 184 in FIG. 2B is returned to the corresponding tube 242, rotation of the wheel 250 drives the belt 248 a distance sufficiently to index the next tube and probe therein with the holder 184 as shown in FIG. 3A.
  • Each probe 216 may conveniently take the form of a pipette.
  • the pipettes 216 employed are of identical structure a description of the construction of one pipette 216 will suffice.
  • the pipette has an elongated tubular body 258 which is open ended, as previously indicated, and vertically arranged and which narrows somewhat toward a point in the re gion of its lower end portion. The upper end of the body 258 is slightly tapered to facilitate entrance of the pipette into the holder 184.
  • the pipette 216 has a radial flange 260 including a depending skirt 262 which terminates downwardly in circumferential interior surface portion which is tapered, as at 264, as shown in FIG. 4,
  • the flange structure 260 supports the pipette in a tube such as one of the tubes 242, with the lower end portion of the pipette being suspended above the bottom of the tube. It will also be apparent that the flange structure provides a cap for the test tube. A wad of cotton or the like may be inserted in the upper end portion of the pipette to prevent foreign material falling down the pipette into the test tube. Such a wad of cotton does not interfere with aspiration of the contents of a test tube employing the pipette.
  • the preparation of the inoculum for each test tube is very important.
  • the first step is the isolation of a significant bacterium from a clinical or other specimen by one trained in such microbiological procedure.
  • the next step is inoculum preparation. Portions of five to ten isolated colonies are transferred to two ml. of optically clean broth which may be Eugon broth; The colonies must represent a single bacterial specieson the basis of their colonial appearance.
  • the turbidity of this suspension is adjusted visually to the density of the standard in use with the Bauer-Kirby method previously referenced.
  • the aforementioned dilution achieves the desired bacteria to volume proportions in the vicinity of 10 per ml.
  • the concentration of bacterium preferably in the range of l0 per ml.
  • Each inoculum is placed in a tube 242 and the tube is closed by a respective pipette and then placed in the turntable assembly 240 as aforesaid.
  • inoculum transfer station B When the carriage 128 is in the lateral position shown in FIG. 3A and the carriage 128 is in the raised position thereof, this carriage is supported by the crank arm 174 through the cam 176 which is disposed (FIG. 3A) between the rails 144 of the carriage 128, and the'crank arm 174 is in its up position of FIG. 2B.
  • the pipette holder 184 is spaced above and indexed with the first sample receptacle in the turntable assembly 240 and is spaced above the pipette in the lastmentioned sample receptacle.
  • the plunger 186 is in its raised position actuating switch 202 which energizes vertical drive motor 170 driving cam wheel 172 in the clockwise direction as viewed in FIGS. 28 and 3A and the crank arm 174, swinging in the same direction, is swung downwardly from its raised position to its lower position or through an angle of 180 at which time the motor 170 is deenergzied by actuation of the switch 180 cooperating with the cam wheel 172.
  • This downward movement of the cam 176 on a crank arm 174 lowers carriage 128 through the rails 144 to its lowermost position (FIG. 3B) in which the pipette holder 184 has engaged and received the corresponding pipette of the first sample receptacle.
  • Actuation of the switch 180 energizes plunger motor 196 effecting counterclockwise movement of the cam wheel 194 as viewed in FIG. 2B driving the plunger 186 downwardly a distance (FIG. 3C) sufficient to cause air in the pipette holder to be expelled into the pipette and into the sample to thereby agitate it for mixing purposes.
  • solenoid valve 206 controlling the air tube 204 is closed.
  • the last-mentioned movement of the cam wheel 194 controlling movement of the plunger 186 through the ball pin is stopped by actuation of the switch 200 which reverses the motor 196 raising the plunger 186 (FIG. 3D) to its raised or starting position.
  • the last-mentioned actuation of the switch 202 effects energization of the vertical motor swinging the crank arm 174 upwardly from its down position to its raised position, or through an angle of and the motor 170 is de-energized at this point by actuation of the switch 182 controlled by the cam wheel 172.
  • This movement of the crank arm 174 effects through cam 176, acting through the rails 144, movement of the carriage 128 to its raised position.
  • the last-mentioned actuation of the switch 182 energizes horizontal drive motor 148 which through the drive belt 158 traverses the carriages 122 and 128 as a unit, with the support rails 144 leaving the cam 176 and picking up the stationary carrier strip 146 for support by the latter.
  • a suitable brake is provided on the motor 148 to assure that when the carriage 128 leaves the support of the cam 176, the crank arm 174 supporting the cam 176 is left in its raised position.
  • the motor 148 continues to drive the belt 158, overriding the switch 154 coacting with the cam wheel 152 until the switch 166 is actuated by the switch actuator element 160.
  • motor 148 is de-energized, and in this position (FIGS. 2B and 3F) the probe holder 184 is over the first cup 40 of the first row of cups 38 in the last-mentioned tray 34.
  • switch 166 causes actuation of the solenoid operated valve 206 to open this valve permitting air to flow in air tube 204 and into the holder 184 at atmospheric pressure, and this enables drops to form and discharge themselves from the lower end (FIG. 2B) of the pipette or probe into the last-mentioned cup 40.
  • one drop may be sufficient but the construction and arrangement may be such that ten drops may be dispensed from the probe before the flow is terminated in the manner which will be explained hereinafter.
  • the actuation of the switch 166 as aforesaid also enables the drop counter 212, 214 to commence counting drops dispensed from the probe 216 until the predetermined number of drops have fallen into the lastmentioned cup at which time the drop counter 212, 214 effects closing of the solenoid-operated valve 206 to terminate the dispensing action in this cup.
  • the drop counter initiates energization of horizontal drive motor 148 to advance the carriages 122 and 128 transversely of the table until the pipette holder 184 is indexed over the second cup, cup 42 in the first row of cups in the last-mentioned tray,
  • This indexing is accomplished by actuation of switch 154 coacting with cam wheel 152 which de-energizes horizontal drive motor 148. This initiates operation of the solenoid operated valve 206 to open the valve, and the same number of drops is dispensed in cup 42.
  • the probe holder 184 is advanced again in the same manner and drops are dispensed in the same manner in all the subsequent cups of the last-mentioned row.
  • Switch 168 de-energizes motor 148 and energizes vertical drive motor 170 thereby initiating downward swinging movement of the crank arm 174 which then supports the vertical carriage 128, through an angle of movement of somewhat more than 180 to and beyond the aforesaid lower position of the crank arm 174, that is, on the rise, causing cam wheel 172 to actuate switch 180 during this movement, and allowing sufficient clearance of the probe 216 and the corresponding test tube 242 for the plunger 186 to eject the probe 216 from the holder 184. The probe 216 drops into the tube 242.
  • the operation of the last-mentioned switch initiates action of the motor 252 of the turntable assembly 240 to index the sample rack 244 in a manner such that the second sample is brought into alignment under the probe holder 184.
  • switch 256 of the lastmentioned assembly is operated by cam wheel 254, the motor 252 is de-energizedv
  • the above-described transfer cycle requires less than seconds.
  • the tray-advance motor 22 On the next signal from the 90-second timer 48, the tray-advance motor 22 is energized driving screws 12 to advance the last-mentioned tray 34 one row of cups, at which time the motor 22 is de-energized by the switch 32 coacting with the cam wheel 24. Operation of the switch 32 is effective to initiate the next cycle of the transfer of the inoculum of the second sample to the second row of cups. This is repeated for the transfer of the inoculum of the third sample to the third row of cups.
  • the bacteria samples are pre-incubated in the broth in the cups 38 of the tray at 37C between the time bacterium is deposited in each first cup 40 of the tray at this transfer station B and the time that the bacteria killing agent is added to the respective cups 4% at the dispensing station C.
  • This pre-incubation period is necessary to compensate for any lag in the exponential growth of the bacterium, and the pre-incubation period, which lasts for 30 minutes, is sufficient for the commencement of active exponential growth of all viable fast-growing bacteria.
  • the antibiotics may be supplied in disc form in solution if desired.
  • the medicated discs require no preparation, are commercially available, easy to handle and easy to dipense. Discs of this type have been certified by the Food and Drug Administration.
  • each bacterium sampie is challenged by a different one of thirteen antibiotics.
  • only three different antibiotics are shown being dispensed at station C and these are shown in the form of discs 263 illustrated as dropping into the third, fourth and fifth cups of the first row of cups 38 of the iast-mentioned tray 34.
  • These discs are commonly used in antibiotic susceptibility studies involving the aforementioned agar diffusion method of analysis also referred to here inbefore as the Bauer-Kirby method,
  • a vertically arranged plate-like part 264 forming a part of a sub-frame supported from the table as shown in FIG. 2B.
  • An elongated plate-part 266 has a body portion which extends across the table and is spaced a distance upwardly from the latter and which may be supported at one end as by being welded to the plate part 264.
  • the plate 266 part has at the other end a downtumed flange supported from the table.
  • the sub-frame formed by the plate parts 264 and 266 supports an antibioticdispensing electric motor 268.
  • a cam wheel 270 is angularly fixed on the shaft of the motor 268 to be rotated thereby and coacts with the actuator of a switch 272.
  • the cam wheel 270 also actuates an antibiotic disc dispensing slide 274 the body of which slides on the plate 266 in flatwise engagement, which plate 266 is suitably provided with longitudinally spaced apertures, not shown, for the discs 263 to fall through respective ones thereof.
  • the slide 274 has three apertures 282 formed therein, each receiving one at a time, discs fed, as by gravity, from a respective one of three magazines 284 vertically arranged on cover plate 286 supported from the plate 266 in fixed relation thereto and having an inverted channel in the bottom thereof receiving the slide 274.
  • the magazines 284 extend throughthe cover plate 286.
  • the magazines 284 may comprise simple openended tubes in which the discs 162 are stacked for storage and later dispensing. It is believed made clear from the foregoing that when the slide 274 is in one axial position thereof, it receives in the apertures 282 thereof antibiotic discs from the respective magazines 284, which position of the slide is effected by the spring 278. In another axial position of the slide 274, effected by the cam 270, the apertures 282 register with the aforementioned apertures in the plate 266 and three discs are simultaneously dispensed in the manner shown in FIG. 2B.
  • the plate 266 has a tubular nozzle 288 extending vertically therethrough and rigidly supported therefrom with its lower discharge end terminating a distance above the cup level in the tray 34 and arranged to index with the cup 40 of each row of cups in the tray.
  • the upper end of the nozzle 288 is connected to one end of a tube 290 having its other end connected to outlet 292 of solenoid-operated valve 294 shown in FIG. 2C.
  • the valve 294 is of the three-way type, having an outlet at 296, and having an inlet 298.
  • Atube 300 has one end connected to the inlet 298 and has the other end thereof connected, in a manner identical to the abovedescribed tube 82, to a pump, indicated generally at 302, which (may be identical to the pump 84 described and which requires no further description here.
  • An inlet tube 304 similar to the above-described tube 86, has an end connected to the pump in identical fashion and has the other end thereof extending into sealed reservoir 306 which is filled with a liquid bacteria killing agent such as formalin for example.
  • the pump is operated by an electric motor 308, which may be identical to the above-described pump motor 96, which has a cam wheel 310 angularly fixed on the driving shaft thereof coacting with the actuator of a switch 312.
  • the pump motor 208 is energized and is operative to deliver a precise volume (0.5 ml.) of formalin (25 percent solution) to the solenoidoperated valve 294 which is actuated in a mode to de liver this volume through the tube 290 via the outlet 292, the tube 290 and the nozzle 288 to the first cup 40 of the first row of cups, immediately killing the bacterium therein.
  • the dispensing motor 268 is energized dispensing three different antibiotics in the respective last three cups of the row and the motor 268 is de-energized by actuation of the switch 272 coacting with the cam wheel 270. It will be noted that the second cup 42 in this row of cups remains untreated at this station.
  • the 90-second timer 48 actuates the trayadvance motor 22 to advance the last-mentioned tray one row of cups and the cycle is repeated in the second row of cups, and the cycle is repeated again in the third row of cups.
  • the timer 48 again actuates the tray-advance screws 12 to advance the tray one increment after which it is, again, by the timer 48 advanced one increment to the position of the tray shown at incubation station D where the tray actuates tray sensor switch 316 enabling station D shown in FIG. 2C.
  • a hood 318 which is openended longitudinally of the table, extends over the table but this illustration is purely by way of example as no hood is required if the entire apparatus is enclosed is a cabinet which is preferable. It is believed made clear that while the tray 34 is in this incubation station it is advanced periodically by operation of the timer 48 controlling actuation of the tray-advance screws 12 and which advance is periodically terminated by actuation of the switch 32 coacting with the cam wheel 24 on the shaft of the motor 22.
  • B is the station for adding a bacteria killing'agent to those tray cups 38 in which such an agent has not been added previously
  • F is the station for sampling the contents of each of the cups holding the treated samples.
  • Both of these stations E and F are shown in FIG. 2C and share more mechanical elements and control swit'ches than the previously described stations, and hence will be described to gether.
  • the lastmentioned tray 34 has been treated at station E and has been moved by the tray-advance motor 22 under the influence of the timer 48 to the station F and the tray position shown therein, while the following tray is in the position shown at station E in FIG. 2C.
  • Stations E and F share a sub-frame 320 which is vertically arranged and extends transversely across the table a distance thereabove as shown in the lastmentioned view. It is supported by end flanges 321, 322 suitably secured to the upper surface of the table 10 in any suitable manner. The end flanges support therebetween in fixed relation horizontally extending vertically spaced rods 324, which are arranged transversely of the table 10 as shown in the last-mentioned view.
  • a carriage is indicated generally at 326 having vertically spaced block-like parts 328 and 330 rigidly interconnected by a bar 332. The blocks 328 and 330 are respectively apertured to receive the respective ones of the rods 324 for support of the carriage 326 on these rods for sliding movement transversely of the table 10.
  • a carriage-driving motor 334 is supported on the plate part 320 of the sub-frame.
  • the last-mentioned motor has angularly fixed on its driving shaft a cam wheel 336 and, in axially spaced relation to the latter, a wheel 338.
  • a switch 340, supported from the end flange 322 has an actuator engageable with cam wheel 336.
  • the motor 334 and its abovedescribed associated parts are located adjacent one end of the plate 320. Adjacent the other end of plate 320, there is revolubly supported by the latter an idler 342, and a belt 344 is trained over the driving wheel 338 and over the wheel 342.
  • the belt is fixed, as at 346, to the block 330 of the carriage 326 to drive the carriage.
  • the upper run of the belt 344 has switch actuating element 348 fixed thereto which coacts with the respective actuators of limit switches 350 and 352 supported from the plate 320.
  • a housing provided for a dual probe assembly, indicated generally at 360, which assembly is mounted for vertical rectilinear sliding movement effected by a solenoid in one direction thereof and which may be spring biased in the other direction.
  • Probe 364 of this assembly is longer than companion probe 366.
  • Probe 364 is provided to drain each sample cup after it has first been sampled by the probe 366, which probes are vertically moveable together in a unitary fashion into and out of each sample cup 38.
  • the probes are open ended and on extension of the probes into a sample cup the probe 364 extends close to the bottom of the cup.
  • a tube 374 has one end thereof connected to the upper end of sample probe 366 and the other end thereof connected to flow input 376 of a flow cell 378 having a flow output at 380 of the particle counter which may be generally of the type illustrated and described in lsreeli US. Pat. No.
  • the liquid output 380 of the flow cell is connected to one end of a tube 390 the other end of which is received in a sealed waste receptacle 392. Also extending into the waste receptacle 392 is one end of a vacuum tube 394 having the other end thereof connnected to the inlet 396 of an electric motor driven vacuum pump 398 which may be suitably supported on a plate 406). Because of this construction and arrangement operation of the pump 398 causes the sample to flow in tube 374 from the sample probe when the last-mentioned probe is immersed in a sample, and this sample is drawn through the flow cell 378 and exits through the tube 390 to the waste receptacle.
  • a tube 402 has one end thereof connected to the upper end of the sample drainage probe 364 and the other end extending into the waste receptacle 392. It will be understood from the foregoing that operation of the vacuum pump 398 effects simultaneously flow through tube 402 to the waste receptacle 392 to drain the cup of the last-mentioned sample. It will also be clear from the foregoing that only a small portion of the sample flows through the flow cell 378 of the particle counter.
  • the aforementioned photodetector in housing 388 is coupled by means of a cable 404 to a computing and recording device at station H which device includes a recorder for recording the results of the analysis which recorder is indicated generally at 406.
  • the recorder 406 is of the type having a moveable stylus which traverses a conventional driven chart strip. The stylus records bacteria counts, including those of a control, as peaks on the chart.
  • Stations E and F are independently operated so that there is no dispensing action at station E if there is a tray at station F but no tray following it. In other words there is no dispensing action at station E unless tray sensor switch 370 is actuated.
  • tray sensor switch 370 is actuated.
  • the carriage 326 is in a position shown in FIG. 2C in which the dispensing nozzle carried thereby is over the first cup 40 of the first row of cups 38 and, at station F, the probe assembly 362 is over the first cup 40 of the first row of cups in the corresponding tray. It will be recalled that the bacterium sample in the last-mentioned cup of the tray at station E has been previously killed by the addition of formalin solution at station C. No treatment of this cup is effected at station B.
  • the probe assembly 362 is lowered by the energization of the solenoid associated therewith into the corresponding or last-mentioned cup of the tray station F and pump motor 398 is energized to cause a predetermined quantity of sample to flow through sample probe 366 into the flow cell 358 as aforesaid and to the waste receptacle 392, while probe 364 simultaneously aspirates sample from the last-mentioned cup to the waste receptacle 392, emptying the cup.
  • Actuation of tray sensor switch 372 as aforesaid also serves to energize the particle counter at station G to signal particle counts to the then enabled, also by switch 372, the counting, comparison and recording mechanism of station H.
  • a liquid flow sensor 393 in waste tube 402 from the probe assembly 362 may be used to sense the cessation of liquid flow in the waste line 402 thereupon actuating the solenoid controlling the probe assembly 362 to retract it, and at the same time energizing horizontal drive motor 334 which drives the carriage 326 to place the probe assembly 362 over the second cup 42 of the first row of cups at station F and place the nozzle 356 at station E over the cup 42 of the first row of cups at the last-mentioned station.
  • Movement of the carriage is stopped by deenergization of the horizontal drive motor 334 by the switch 340 coacting with the cam wheel 336.
  • Actuation of switch 340 actuates pump 302 by energizing pump motor 308 at the same time energizing solenoid valve 294 to operate the last-mentioned valve to deliver formalin from the reservoir 306 through the valve outlet 396 to the tube 358 connected to the nozzle 356 delivering the aforementioned volume (0.2 ml of a 25 percent solution) of formalin to the second cup of the first row at station E, which immediately kills the bacterium therein.
  • the pump motor 308 is de-energized by the switch 312 coacting with cam wheel 310.
  • the last-mentioned cup 42 is drained by the probe assembly 362 as aforesaid, and upon actuation of the liquid flow-sensing device 393 previously described the probe assembly is retracted from the last-mentioned cup: and the motor 334 is re-energized, and the cycles at stations E and F repeated, until all the bacteria in the first row of cups at station E have been killed and all the cups in the first row at station F have been sampled and the cups drained as aforesaid.
  • the signal receiving and processing mechanism H has received and stored information as to the proliferation of bacterium in each of the third, fourth, and fifth cups in this row, which it will be recalled have received different antibiotics.
  • the sample probe 366 will aspirate air in its movement between sample cups.
  • the construction and arrangement may be such that the probe assembly 362 may be immersed in a wash liquid between immersions in sample cups.
  • switch actuator element 348 on the belt 344 is in engagement with the actuator of switch 352 placing the belt motor 334 in the reverse mode, so that on the next energization of motor 334 as aforesaid the motor 334 drives the carriage 326 in the reverse direction, overriding switch 340, to return it to the position shown in FIG. 2C, wherein switch actuating element 348 engages the actuator of switch 352 de-energizing motor 334 and placing it in reversed mode.
  • the trays at the stations E and F are simultaneously advanced by the tray-advance screws 12 driven from the motor 22 and the advance is stopped by switch 32 coacting with the cam wheel 24, at which time the probe assembly 362 is indexed with the second row of cups of the corresponding tray at station F and the nozzle 356 is indexed with the second row of cups of the corresponding tray at station E and the aforementioned cycles are repeated until the last cup in each tray at station E and station F and the aforesaid cycle is completed with reference to the same.
  • the respective trays are advanced on the table as aforesaid with the tray shown at station E in FIG. 2C advancing to station F to the tray position shown therein in the last-mentioned view.
  • the tray the cups of which have been emptied as aforesaid at station F, travels along the tray as aforesaid to the discharge end 16 of the table and may ultimately be deposited, as by gravity, in a storage bin 46.
  • a sample of a known bacterium is placed in a tube 242, together with a pipette 216, in sampler assembly 240 and run through the analysis apparatus as aforesaid.
  • the susceptibility of this bacterium to the various antibiotics used in the apparatus is known and hence chart readings from the recorder H should accord with this information.
  • the above described method and apparatus for automated antibiotic susceptibility analysis achieves the stated objects and may be utilized for other purposes than those described above in detail, such as providing bacteria counts of uninhibited exponential growth or measuring minimum antibiotic inhibitory concentrations. Also as previously stated, it may be used with known bacteria for testing various fluids, such as body fluids for example, for their characteristics of inhibiting bacterial growth. It will be readily apparent to those versed in microbiology that the method and apparatus of the invention may have many other uses in a microbiological laboratory. Still further, at least some subcombinations of the apparatus, as those various combinations described with reference to particular stations of the apparatus as well as the methods executed thereby, may be utilized outside the field of microbiology.
  • stations A and B may be combined.
  • a method of antibiotic susceptibility analysis of a plurality of liquid samples in sequence, each including a different bacterial inocuium, comprisingrsupporting each sample in a separate container, transferring each sample sequentially in equal aliquot portions to each

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US00139435A 1971-05-03 1971-05-03 Method and apparatus for automated antibiotic susceptibility analysis of bacteria samples Expired - Lifetime US3772154A (en)

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CA991515A (en) 1976-06-22
FR2135592B1 (fr) 1973-07-13
DE2221452A1 (de) 1972-12-07
FR2135592A1 (fr) 1972-12-22
AU4160172A (en) 1973-11-01
NL7205881A (fr) 1972-11-07
IT954970B (it) 1973-09-15

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