Abstract:
In a preferred embodiment, a pipettor reservoir for particulate-containing liquid, including: a body portion; a shallow reservoir portion defined in an upper surface of the body portion; fluid-flow channels defined in the body portion to deliver the particulate-containing liquid from an inlet port to a plurality of openings defined in a bottom of the reservoir portion, the plurality of openings being arranged such as to agitate the particulate-containing liquid to keep particulate matter in suspension therein.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to bioassays generally and, more particularly, but not by way of limitation, to a novel pipettor reservoir for use with particulate-containing liquids. 
     2. Background Art 
     In the field of biotechnology, particulate matter is used in a variety of assays. The most common particulate matter is the use of living cells. Other applications are the use of coated particles, such as magnetic beads or radioactive particles. In high throughput systems, it is necessary to pipette liquid containing this particulate matter from a source reservoir to a receiving bioassay plate. A problem encountered in such systems is that the particulate matter tends to settle out of the liquid in which it is suspended. A common method of overcoming this tendency is the use of a magnetic stir bar within the reservoir, driven by an external magnet drive assembly. Various shakers and vibrators are also used. 
     In automated pipetting systems, a constant level source reservoir may be used. This is a weir-type reservoir that is included within the flow path of a peristaltic pump. The fluid is kept in motion between a large source reservoir and the constant level reservoir by the peristaltic pump. The agitation created by the flow is relied on to keep the particulate matter in suspension in the liquid. 
     The constant level reservoir has a relatively small depth and the liquid level is kept constant by an overflow weir. This allows the pipettor system to go to the same depth in the liquid for aspiration of the reagents. For use with the industry standard, 96- or 384-well pipettors, the horizontal dimensions of the reservoir surface area must measure approximately 3.4×5.0 inch. Depending on the mass of the particles, the flow through the reservoir may not keep them in suspension. There are normally “dead” spots in the corners of the reservoir or other areas of the reservoir outside of the main liquid path. A multi-well pipettor, 96 or 384 wells, will aspirate uniformly over the entire 3.4×5.0-inch surface area; however, the “dead” spots in the reservoir will not provide a uniform aspiration of particles in all 96 or 384 pipettor tips. This has a detrimental effect on the results of the assay. 
     Also, there is an increasing use of paramagnetic particles in various bioassays and the use of a magnetic stir bar is prohibited in these applications. 
     Accordingly, it is a principal object of the present invention to provide a source reservoir for pipetting in which the problem of settling of particulate matter suspended in a liquid is eliminated or greatly reduced. 
     A further object of the invention is to provide such a source reservoir in which “dead” spots are eliminated or greatly reduced. 
     An additional object of the invention is to provide such a source reservoir having a constant velocity of liquid flow in the various feed-way passages thereof 
     Another object of the invention is to provide such a source reservoir that can be economically constructed using conventional manufacturing techniques. 
     Yet a further object of the invention is to provide a source reservoir that can be used satisfactorily with paramagnetic particulate materials. 
     Other objects of the present invention, as well as particular features, elements, and advantages thereof, will be elucidated in, or be apparent from, the following description and the accompanying drawing figure. 
     SUMMARY OF THE INVENTION 
     The present invention achieves the above objects, among others, by providing, in a preferred embodiment, a pipettor reservoir for particulate-containing liquid, comprising: a body portion; a shallow reservoir portion defined in an upper surface of said body portion; fluid-flow channels defined in said body portion to deliver said particulate-containing liquid from an inlet port to a plurality of openings defined in a bottom of said reservoir portion, said plurality of openings being arranged such as to agitate said particulate-containing liquid to keep particulate matter in suspension therein. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWING 
       Understanding of the present invention and the various aspects thereof will be facilitated by reference to the accompanying drawing figures, provided for purposes of illustration only and not intended to define the scope of the invention, on which: 
         FIG. 1  is a top plan view of a source reservoir constructed according to the present invention. 
         FIG. 2  is a side elevational view, in cross-section, taken along line “ 2 — 2 ” of FIG.  1 . 
         FIG. 3  is a side elevational view, in cross-section, taken along line “ 3 — 3 ” of FIG.  1 . 
         FIG. 4  is a side elevational view, in cross-section, taken along line “ 4 — 4 ” of FIG.  1 . 
         FIG. 5  is an end elevational view, in cross-section, taken along line “ 5 — 5 ” of FIG.  1 . 
         FIG. 6  is an end elevational view, in cross-section, taken along line “ 6 — 6 ” of FIG.  1 . 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Reference should now be made to the drawing figures on which similar or identical elements are given consistent identifying numerals throughout the various figures thereof, and on which parenthetical references to figure numbers direct the reader to the view(s) on which the element(s) being described is (are) best seen, although the element(s) may be seen on other figures also. 
     Referring to all the drawing figures, but primarily to  FIG. 1 , there is illustrated a pipettor source reservoir, constructed according to the present invention, and generally indicated by the reference numeral  20 . Pipettor source reservoir  20  has a rectangular body portion  30  and a rectangular reservoir portion  32  (FIG.  2 ), measuring, as noted above, about 3.4×5.0 inches, the pipettor source reservoir being formed in the upper surface of the rectangular body portion Other dimensions for reservoir portion  32  may be used as well depending on the application, the above dimensions being required for the standard 96- or 384-well pipettors. 
     Reservoir portion  32  has 24 small, vertical holes, as at  40 , defined in the bottom thereof. Body  30  has defined therein an inlet port  50  connected to the middle of a main feed line header  52 . Main feed line header  52  is connected to four feed lines, as at  60 , each of which is connected to six vertical holes  40 . Portions, as at  64 , of main feed line header  52  and feed lines  60  are blocked, the portions that are now blocked having been formed in the drilling operation that formed the main feed header and the feed lines. 
     A horizontal weir  70  ( FIGS. 4 and 5 ) extends along one side of reservoir portion  32  and has a vertical height terminating somewhat below the upper edge of the depressed central portion. A sloped drain channel  80  ( FIG. 4 ) extends along the side of weir  70  opposite the side of the weir that is adjacent reservoir portion  32  and the lower end of sloped drain channel  80  terminates in a sump  90  ( FIG. 4 ) connected to an outlet port  100 . 
     In use, a liquid containing particulate matter, such as paramagnetic particles or living cells, is introduced through inlet port  50 , flows through main feed header  52 , flows through feed lines  60 , and flows uniformly into reservoir portion  32  through holes  40 . Weir  70  ( FIGS. 4 and 5 ) maintains the level of liquid in reservoir portion  32  constant. Pipettor needles are inserted into the liquid in reservoir portion  32  a given and constant depth. Excess liquid flows over weir  70 , into sloped drain channel  80  ( FIG. 4 ) and out of source reservoir  20  through sump  90  and outlet port  100 . Supply to inlet port  50  may be by means of a peristaltic pump (not shown) and outlet port  100  may be connected to the inlet side of the pump or to a main reservoir. 
     Pipettor source reservoir  20  is designed such that approximately the same linear velocity of flow in all flow passages is obtained in all liquid flow passages to prevent settling. For example, the cross-sectional area of main feed line header  52  is approximately one-half the area of inlet port  50 , since the main feed line header has two branches. The combined cross-sectional area of two feed lines  60  is approximately equal to the cross-sectional area of main feed line header  52 . The cross-sectional area of six vertical holes  40  is approximately equal to the cross-sectional area of a feed line  60 . The generally equal spacing of vertical holes  40  across the bottom of depressed central portion  32  keeps the volume in constant agitation to prevent settling in any of what would otherwise be “dead” spots. Exact dimensions of the flow passages will depend on the nature of the particulate matter in suspension, but will be such that the particulate matter remains in suspension. 
     The use of single weir  70 , as opposed to a full perimeter weir, maintains faster uniform flow out of reservoir portion  32 . The depth of the liquid is kept shallow again for the purposes of a cross flow velocity sufficient to keep particles in suspension. This is accomplished by having the vertical height dimension of weir  70  above the bottom of reservoir portion  32  roughly two to five percent of the length of the reservoir portion. 
     The flow rate of the liquid, being delivered by the peristaltic pump, is a parameter that is adjustable to compensate for use with particles of different masses. Heavier magnetic beads may heed a higher flow velocity, to keep them in suspension, compared with living cells. 
     Pipettor source reservoir  20  and the various elements thereof may be economically constructed by conventional manufacturing methods. Materials of construction may be any that are suitable for the liquids and particulate being handled. 
     Terms such as “upper”, “lower”, “inner”, “outer”, “inwardly”, “outwardly”, “vertical”, “horizontal”, and the like, when used herein, refer to the positions of the respective elements shown on the accompanying drawing figures and the present invention is not necessarily limited to such positions. 
     It will thus be seen that the objects set forth above, among those elucidated in, or made apparent from, the preceding description, are efficiently attained and, since certain changes may be made in the above construction and method without departing from the scope of the invention, it is intended that all matter contained in the above description or shown on the accompanying drawing figures shall be interpreted as illustrative only and not in a limiting sense. 
     It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween.