text: This invention concerns a sample mixing and transport method and apparatus for samples in sealed containers, the containers being transported in groups in rack-type carriers. More specifically, this invention is directed toward the full automation of hematology analysers of the type which heretofore required the manual introduction of a blood sample held in an open-mouthed container. This goal of full automation is accomplished by transporting groups of sealed blood sample containers in racks to and from the sample aspiration station of the hematology analyzer and, while approaching the aspiration station and/or thereat, the samples are mixed by rocking the carrier rack.
  Semi-automated hematology analyzers have been in common use for many years. U.S. Pat. No. 3,549,994 teaches such a semi-automated system for measuring a plurality of parameters of a whole blood sample. In using this system, the premixed blood sample is introduced manually into the system via an open-mouthed sample container, which is held up to an aspirating probe. Although this system offered a significant advance in the art when first sold in 1968 as the Coulter Counter.RTM. Model S and there have been numerous subsequent improvements to this system over the past 15 years, the sample introduction has remained essentially unchanged. First, the sealed sample container is partially inverted several times manually to mix its contents, the sealing stopper then manually is removed, and then the open container is moved up into the aspiration tube. Not only does this procedure suffer from the various obvious drawbacks of manual handling, but also the opening of the whole blood container, which typically is under a small vacuum by virtue of the blood collecting technique, permits an aerosol to escape into the laboratory close to the technician who is operating the system. Such aerosol can contain blood related impurities and transmit disease, such as hepatitis.
  The need for avoiding the manual opening of the sealed blood sample container has been recognized. U.S. Pat. No. 4,274,453 teaches a substantially manually fluid transfer device by which each sealed sample tube manually is placed upright into a free standing clamping gig which is provided with a vertically reciprocating aspiration probe having a seal penetrating tip. The probe with its tip is lowered manually into and through the sealed top of the sample container by a lever arm mechanism and motion which is like the well-known manual orange juice squeezer. The remote end of the aspiration probe feeds into an automated hematology analyzer. Besides its manual limitations and the one-at-a-time handling of the sample containers, this device does not accomplish sample mixing.
  U.S. Pat. No. 4,387,076 teaches a substantially automatic sample feeding arrangement which receives sealed sample tubes, moves them one at a time to a seal piercing and sample aspiration station, and then discharges the used tubes. This sample feeding arrangement is mounted inside a sample analyzer of the type taught in previously mentioned patent 3,549,994, which without benefit of this invention would operate semi-automatically. Receipt of the sample tube at the in-feed station of this feeding arrangement initiates the repositioning of the tube to an aspiration station, which thereat enables all other handling steps of the tube, sample aspiration, and the full system cycle of the analyzer to cause it to be fully automated. This arrangement now is commercialized as the Coulter Counter.RTM. Model S Plus V. Although this improvement is a significant step forward in sample handling, it does not provide for sample mixing. The sample containers need to be manipulated to mix the whole blood sample just prior to input of the tubes to the feeder mechanism.
  The typical method for manually manipulating the sealed sample tube to attain adequate mixing of the whole blood constituents is for the technician to grasp the tubular container in her hand with the ends of the tube extending from opposite sides of the palm, adjacent the thumb or index finger and little finger, respectively. The technician then rotates her wrist through an arc approaching 180.degree. many times to accomplish several semi-inversions of the tube. This mixing is not to be high speed, violent, or jerky, since the blood cells are fragile and not to be damaged by the mixing process, since cell trauma can affect the data results to be obtained by the hematology analyzer.
  Bench-top sample tube mixers have been marketed for years and there are several simple commercial units. One unit primarily rolls the tubular sample container on its long axis and imparts slight end tilting action. Such arrangement does not simulate the manual mixing mode. Another device is a spinning vertical disk, to which the sample tubes are clipped in a radial array. Although such device does accomplish tube end inversion, it does not have the end reversing action of the human wrist movement. U.S. Pat. No. 3,625,485 teaches both the rotating as well as reversing direction or rocking movements for a few sealed sample tubes that are clipped onto a horizontal, rotating axis.
  Another form of tube mixer is a tilting tray, which does simulate the manual mixing mode. One such tray is the Coulter.RTM. Blood Mixer and is generally described in U.S. Pat. No. 3,501,131. The tray holds a plurality of sealed sample tubes and is rocked about its axis to simulate the manual semi-inversions. After sample mixing by any of these prior art mixers, each tube is removed separately from the mixing device, manually opened and then the sample contents are fed into the hematology analyzer. If the hematology analyzer is of the type of the aforementioned patent 3,549,994, the manually opened sample tube with its mixed sample is held up into the hollow tipped aspiration probe. However, if the analyzer is equipped with the automating feeder of patent 4,387,076, as above described, the manual opening is avoided.
  The need for combining sample tube mixing with sample aspiration from a sealed sample container has been recognized and disclosed in the prior art. U.S. Pat. No. 4,120,662 discloses a free standing, self-programmed system in which individual sample tubes are placed horizontally into a vertically oriented pair of feed screws, such that each individual tube is moved slowly downward along the feed screws and, simultaneously, rotated around the long axis of the sample tube. Differential speed of the two feed screws will impart a limited amount of end lifting motion to the tubes. At the bottom of the downward path of the feed screws is a horizontally disposed and reciprocating aspiration needle which pierces the tube seal and then aspirates sample into a coupling line which feeds into a separately operating hematology analyzer. Although this system does combine the sample mixing and aspirating of the sample from a sealed container, it is a separate unit from the analyzer system and requires appreciable bench space, requires the sample tubes to be input individually, does not fully simulate the desired manual mixing mode, and has other limitations. For example, the horizontal spacing between the vertical feed screws must be kept constant; hence, all of the sample tubes being processed during any one period of time must be of the same exact length and also the same volume, since the diameter of the tube must be constant and is factory predetermined because of the pitch of the feed screws. However, it is common practice to collect blood samples in tubes of several different lengths and diameters and an optimized system should be able to receive sequentially any of the various diameter and length tubes, randomly.
  United Kingdom patent application 820164, published on Sept. 29, 1982 as patent publication 2095403A discloses two forms of devices which combine sealed sample tube mixing and aspirating. One such device utilizes a form the vertically rotating mixing disk arrangement, previously mentioned, and adds to it a programmed aspiration station, for piercing the tube seal. A commercial form of this device is fitted with two mixing disks to increase throughput; one disk operates in a premix mode and the other disk provides final mixing and is being coupled to the aspiration station, with its seal piercing, reciprocating aspiration probe. Such device is sold as the Coulter.RTM. CASH.TM. system, in which the aspiration station is the input to a Coulter Counter.RTM. Model S plus system, which is an improved version of the system taught in the previously described patent 3,549,994. Although built and operated as an integrated system--mixer, seal piercer and analyzer--the commercial version comprises two side-by-side units in which the aspiration station, in the mixing and aspirating unit, is coupled by a fluid line to the sample segmenting and diluting valve in the analyzer unit. The necessary length of this fluid line causes the amount of blood sample drawn from the sample tube to be greater than if the aspirating station was located within the analyzer unit and close to its segmenting, diluting valve. Also, the loading of the individual sample tubes on to the mixing disk and the capacity of the mixing disk are inherent limitations of this system.
  The second device embodied in United Kingdom published Specification 2095403A has a greatly increased capacity and also is built into the body of the hematology analyzer. This embodiment uses a plurality of tube racks, each holding a plurality of sealed sample tubes. The racks are manually, removably secured to the periphery of a horizontal drum, such that each rack has its base against the periphery of the drum and the racks are spaced around the drum; hence, the longitudinal axes of the numerous sample containers radiate from the hub of the drum and the sealed ends of the sample tubes are remote from and facing away from the drum. To accomplish sample mixing, the drum rotates slowly to totally invert the racks and thus inverts the tops of the saple containers relative to their closed bottoms. A track system carries an aspirating needle over the length of the top of a rack, when it is positioned in one certain of the rotating drum determined positions. Thereupon, the needle sequentially is driven into each sample container aspirates some sample, is withdrawn from the container, and then is advanced horizontally to be positioned for insertion into the next container in that rack. Although this system has advantages over all of the mentioned prior art, it does require insertion and removal of the rack from the drum in a limiting manner. Its engineering design is somewhat complex. It and the previously disclosed first embodiment do not simulate the manual mixing mode.
  The transporting of sample tubes in a plurality of racks, past a sampling station, is old in the art as evidenced by U.S. Pat. Nos. 3,575,692; 3,768,526 and 4,147,250. Generally, the sample racks are maintained in one plane, with the racks and the open mouthed sample tubes constantly remaining upright. Patent 3,575,692 teaches that the vertically disposed racks and their vertically held sample cups can be transported by way of feed elevators disposed on opposite sides of the sampling station. This patent does not teach the use of mixing or sampling by seal piercing as herein previously discussed, since the sample tubes are open to atmosphere at all times.