Abstract:
The present invention comprises a horizontal, perforated agitator element and means to cause the agitator element to reciprocate vertically within a reservoir containing a fluid suspension, solution, or mixture. The perforations in the agitator element are sized and located so that an array of pipette tips may be inserted into the fluid through the moving agitator element without interference.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of Provisional Patent Application No. 60/102,558, filed Sep. 30, 1998. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     Not Applicable. 
     REFERENCE TO A MICROFICHE APPENDIX 
     Not Applicable. 
     BACKGROUND OF THE INVENTION 
     This invention relates to a device for agitating fluids, specifically for use with automatic pipetting equipment. The invention is particularly useful for agitation of stratified fluids and for maintaining uniformity of solid-fluid suspensions. 
     Many laboratory processes employ materials requiring agitation or stirring to obtain or maintain desired properties. Such materials may include suspensions of solid particulate matter in a fluid and mixtures of insoluble fluids. When the constituents of the material have different densities, settling can occur. Laboratories frequently use automated pipetting devices to withdraw samples of such materials from a reservoir. These pipetting devices insert an array (usually rectangular) of pipette tips into the reservoir then aspirate samples of the material into the pipette tips for deposit elsewhere. The material in each sample at each withdrawal must have a known and controlled concentration of the constituents of the material. Therefore, it may be necessary to continuously agitate the material. 
     In the prior art, numerous varied methods for agitation are described. These prior methods have certain disadvantages for use with automated pipetting equipment: 
     1) Manual agitation, by shaking the reservoir or using a stirring rod, has the disadvantage of requiring human attention and diligence, which may result in spillage, contamination, inconsistent agitation, interference with the automated equipment, or exposure of people to hazardous materials. 
     2) Circulation using a pump requires fluid inlets and outlets to the reservoir and requires a pump which may be relatively complex and subject to local accumulation of particulate. The pump may thus be subject to dogging or other failure and may require frequent flushing. In addition, the pump system likely has seals and fittings that may leak Also, it may be difficult to avoid “dead spots” within the reservoir where circulation does not occur, allowing settling of particulate. 
     3) Rotary stirrers (for example, magnetic stirrers by Cole-Parmer Instrument Company of Niles, Ill. or that described in U.S. Pat. No.5,834,739 (1998) to Lockwood, et al.) are effective for stirring solutions in mixing chambers having axial symmetry, such as beakers. However, rotary stirrers are not well adapted to use in rectangular reservoirs that receive pipette tips. Centrifugal effects cause a vortex, where the fluid level in the reservoir to vary from low near the stirring element to high near the edges of the reservoir, possibly causing pipettes to draw air. Also, given the differing densities of the components of the mixture, the stirrer may act as a centrifuge, increasing the concentration of denser materials at increasing distances from the stirrer. It may be impractical to locate a continuously rotating stirrer in a standard reservoir without physically interfering with the pipette tips. 
     4) U.S. Pat. No. 4,477,192 (1984) to Bonney describes a magnetic stirrer in which the stirring element moves erratically within a mixing chamber. If used with pipetting equipment, the stirring element will tend to interfere with the pipette tips, or vice versa. 
     5) Agitation of the entire reservoir (using, for example, a laboratory platform shaker) may require that the reservoir be mechanically fixed to the agitator, a disadvantage for convenient movement or replacement of the reservoir. The magnitude of the agitation is limited to the point where fluid spills or splashes from the open-topped reservoir, and to the extent where the motion interferes with the operation of pipetting equipment. 
     6) Agitation may be achieved by imparting motion to the fluid via elastic deformation of some portion of the interior surface of the reservoir. U.S. Pat. No. 4,793,714 (1988) to Gruber discloses a mixer which employs a vibrating membrane on some wall of the mixing chamber. U.S. Pat. No. 4,232,972 (1980) to Levin discloses a mixer here the walls and bottom of the chamber are deformed to impart impulses to the fluid These methods require a purpose-built mixing chamber, which is disadvantageous compared to using simple, disposable, standard reservoirs. 
     7) U.S. Pat. No. 5,736,100 (1998) to Miyake et al., discloses a method for mixing by imparting ultrasonic waves into the material to be mixed. Unless very carefully directed and controlled, ultrasonic mixing produces highly localized agitation, which may not produce consistent mixture and which may cause splashing and undesired heating. 
     8) U.S. Pat. No. 5,443,791 (1995) to Cathcart et al. (column 9, line 33 and column 36, line 11) describes a method for stirring using the pipetting device itself. The pipette tips repeatedly aspirate and dispense the fluid in the reservoir and may be moved within the reservoir to achieve mixing. This method requires that the pipettes spend extra time within the reservoir to effect mixing. In addition, the pipette tips may be required to make extra trips to the reservoir to prevent settling even when no sample from that reservoir is immediately needed. 
     9) HyperTask of Hopkinton, Mass. markets a mixer for use in a reservoir with automated pipetting equipment. In this device, a mixing paddle reciprocates horizontally within the reservoir. This horizontal motion allows pipetting from only one end of the reservoir, preventing the use of a complete array of pipettes. 
     10) U.S. Pat. No. 5,100,242 (1992) to Latto discloses a mixing method in which an orifice plate is reciprocated within a fluid at right angles to the plane of the plate to generate vortex rings. The disclosure specifies a range of ratios of motion amplitude to orifice diameter. The present invention is not constrained to operate within that range, nor is it constrained to use circular holes. In addition, the disclosure specifies that to generate effective ring vortices, the minimum distance from the center of an orifice to the edge of the orifice plate or to the edge of another orifice is twice the diameter of the orifice. The present invention is not so constrained, and in fact, in the preferred embodiment, the present invention&#39;s orifices are doser together than Latto specifies. In short, the present invention is not a ring vortex mixer. 
     BRIEF SUMMARY OF THE INVENTION 
     The present invention comprises a horizontal, perforated agitator element and means to cause the agitator element to reciprocate vertically within a reservoir containing a fluid suspension, solution, or mixture. The perforations in the agitator element are sized and located so that an array of pipette tips may be inserted into the fluid through the moving agitator element without interference. 
     Several objects and advantages of the present invention are: 
     (a) to provide agitation of fluid mixtures in a reservoir without requiring regular participation or attention from a human operator; 
     (b) to provide a well controlled, uniform fluid mixture in a reservoir; 
     (c) to provide continuous agitation in a reservoir without impeding or interfering with the insertion of a complete array of pipettes into the reservoir; 
     (d) to provide agitation with an agitating element that is simple in configuration and is easy to clean or replace; 
     (e) to provide agitation with minimal risk of contamination, spillage, or leakage; 
     (f) to provide agitation in standard reservoirs, maintaining compatibility with typical laboratory equipment; 
     (g) to provide agitation without requiring the automated pipetting device to spend extra time or make extra trips to the reservoir; and 
     (h) to provide agitation in an open-topped reservoir without splashing or excess sloshing. 
     Further objects and advantages will become apparent from a consideration of the ensuing description and drawings, and this list is not intended to be conclusive. 
    
    
     BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING 
     FIG. 1 shows an exploded isometric view of a preferred embodiment of an agitator. 
     FIG. 2 shows an assembled isometric view of a preferred embodiment of an agitator with pipette tips immersed in the fluid. 
    
    
     REFERENCE NUMERALS IN DRAWINGS 
       10  housing 
       12  base plate 
       14  spool 
       16  wire windings 
       20  electromagnet cable 
       22  electromagnet driver 
       24  power cable 
       26  timing adjustment knobs 
       28  power switch 
       30  cover 
       32  reservoir 
       34  fluid suspension or mixture 
       36  agitator assembly 
       38  agitator plate 
       40  leaf spring 
       42  pipette head assembly 
       44  pipette head 
       46  pipette tip 
       48  pipette clearance hole 
       50  interstitial hole 
       52  direction of agitator reciprocation 
       54  agitator base assembly 
     DETAILED DESCRIPTION OF THE INVENTION 
     Description of Figures 
     A preferred embodiment of the present invention is illustrated in FIG. 1 (exploded view) and FIG. 2 (assembled view). Enamel coated copper wire  16  is wrapped around two spools  14 . Spools  14  are made of a magnetically permeable material, low carbon steel in this embodiment. Wire windings  16  are wound around spools  14  in series, clockwise around one spool  14 , and counter-clockwise clockwise around the other spool  14 . Wire windings  16  terminate in a two conductor insulated cable  20 . 
     Spools  14 , wound with wire  16  are fastened to a base plate  12  and a housing  10 . Base plate  12  is constructed from low carbon steel, a magnetically permeable material. Aluminum housing  10  contains a cavity to accommodate spools  14 , wire windings  16 , and base plate  12 . Housing  10  also has a feedthrough notch to allow electromagnet cable  20  to exit housing  10 . An aluminum cover  30  is fastened to the top of housing  10 . Spools  14 , wire windings  16 , base pate  12 , housing  10 , and cover  30  comprise agitator base assembly  54 . 
     Electromagnet cable  20  electrically connects agitator base assembly  64  to an electromagnet driver  22 . Electromagnet driver  22  contains circuitry that produces an approximately square voltage output, where voltage repeatedly alternates between zero volts and some non-zero voltage, in this case twelve volts. Two timing adjustment knobs  26  control the duration of the zero volt portion of the voltage output and the duration of the non-zero voltage portion of the voltage output. The frequency of the output can be varied between approximately 0.5 hertz and approximately 20 hertz. A power switch  28  turns the device on and off. A power cable  24  connects electromagnet driver  22  to a source of electrical power, not depicted. 
     A reservoir  32 , containing fluid mixture or suspension  34 , rests on top of agitator base assembly  54 . In this embodiment, reservoir  32  is a standard polyethylene reservoir, commonly used with automated pipetting equipment 
     An agitator plate  38  is constructed from a magnetically permeable material, in this case low carbon steel. The overall length and width of agitator plate  38  are slightly smaller than the interior length and width of reservoir  32 . Agitator plate  38  is perforated with pipette clearance holes  48 , arranged in an array matching a commonly used standard pipette array in automated pipetting equipment. The diameter of pipette clearance holes  48  is sufficient for clearance during operation. The top edge of each pipette clearance hole  48  is chamfered at forty-five degrees such that the chamfers of orthogonally adjacent holes overlap slightly. Agitator plate  38  is additionally perforated with interstitial holes  50 . The top edge of each interstitial hole  50  is chamfered at forty-five degrees so that its chamfer slightly overlaps the chamfers of the surrounding pipette clearance holes  48 . 
     The width of all but the ends of agitator plate  38  is reduced slightly from both long sides. The top edges of the reduced-width portion are chamfered at forty-five degrees over the entire thickness of agitator plate  38 . The short sides of agitator plate  38  are indented, leaving a small finger at each corner and a tab on the middle of both short sides of agitator plate  38 . Two leaf springs  40  are fastened to the tabs on the middles of the short sides of agitator plate  38  to form agitator assembly  36 . Leaf springs  40  are made from stainless spring steel strip, deformed to curve concave downward to form four legs when fastened to agitator plate  38 . Agitator assembly  36  is coated in its entirety with a flouropolymer material, PTFE in this embodiment, which is chemically inert with most fluids. 
     A representation of a pipette head assembly  42  consists of a pipette head  44  and a plurality of pipette tips  46 . Pipette head assembly  42  is part of an automated pipetting device, the remainder of which is not depicted. 
     Description of Operation 
     Agitator assembly  36  is negatively buoyant in fluid  34 , and leaf springs  40  are stiff enough to support agitator assembly  36 , so agitator assembly  36  rests on its legs on the bottom of reservoir  32  with the bottom surface of agitator plate  38  elevated above the floor of reservoir  32 . The closeness of fit of agitator assembly  36  within reservoir  32  ensures that pipette clearance holes  48  are aligned with pipette tips  46  within some tolerance zone. The size of pipette clearance holes  48  is sufficient to obviate interference between pipette tips  46  and agitator plate  38  within the tolerance zone. Therefore, pipette Ups  46  can be inserted to any depth in fluid  34  from above, aspirate and/or dispense material, and be withdrawn without impedance from agitator assembly  38  and without impeding reciprocation of agitator assembly  38 . 
     When electromagnet driver  22  provides voltage to wire windings  16 , current flows through wire windings  16  and magnetic fields are induced. The intensity of these fields is enhanced by the presence of magnetically permeable material within the wire windings  16 . Because wire windings  16  are wound on spools  14  in opposite senses, the top of one spool  14  has north magnetic polarity while the top of the other spool  14  has south magnetic polarity. Magnetic field lines tend to arc from the top of one spool  14  to the top of the other spool  14 . Base plate  12 , of magnetically permeable material, shorts the magnetic field lines from the bottom of one spool  14  to the bottom of the other spool  14 , minimizing magnetic field lines from the top of one spool  14  to its own bottom, and increasing magnetic field lines between the tops of spools  14 . 
     The magnetic field exerts an attractive force on agitator plate  38 . This downward force deflects leaf springs  40  and moves agitator plate  38  downward through fluid  34 . When voltage is cut off from the wire windings  16 , the magnetic field dissipates, and deflected leaf springs  40  exert a net upward force on agitator plate  38 , causing upward motion of agitator plate  38  through fluid  34 . Because electromagnet driver  22  generates voltage alternating overtime between zero and twelve volts, agitator plate  38  is caused to reciprocate vertically through fluid  34 . A two-headed arrow  52  illustrates the reciprocating movement of agitator plate  38 . 
     When agitator plate  38  moves through fluid  34 , fluid  34  is displaced through perforations  48  and  50  and around edges of agitator plate  38 . This displacement causes mixing and prevents settling or agglomeration of the various components of fluid  34 . The presence of interstitial holes  50  and the chamfering and profiling of agitator plate  38  minimize flat areas on the top of agitator plate  38 . By minimizing flat areas, stagnation on agitator plate  38  is minimized, preventing settling on agitator plate  38  and ensuring effective agitation. 
     Timing adjustment knobs  26  are used to optimize the agitation action. Optimal settings depend on the nature of the material being agitated, and are determined empirically. 
     The invention operates continuously, and pipette tips  46  may be inserted and withdrawn at any time to extract well-mixed material, requiring no synchronization between pipetter and agitator. 
     Description and Operation-Alternative Embodiments 
     While the above-described embodiment contains many specificities, these should not be construed as limitations on the scope of the invention, but rather as an exemplification of one preferred embodiment thereof. 
     The force that moves the agitator may be derived in a number of ways. Some alternative methods follow: 
     Direct mechanical drive, utilizing electric motors, solenoids, pneumatics, hydraulics, and/or any number of other machines. 
     Electrostatic drive, using charged bodies to repel and/or attract the agitator element. 
     Alternative magnetic drive configurations, including magnets driving agitator from beside the reservoir or using an agitator element made of permanently magnetic material which may be attracted and/or repulsed. 
     Any of the above drive configurations can obviate the need for the spring elements on the agitator element by providing drive force in both stroke directions or by using gravity as the return force (for example with repulsive magnetic force from below). 
     The agitator element has alternate embodiments as well. Some alternative embodiments are listed below: 
     As stated above, different drive configurations can allow the elimination of the spring elements. 
     The agitator perforations may be of non-circular form, square for example, and interstitial holes may be enlarged, reduced, added, or eliminated. 
     The agitator perforations may be configured so that a single perforation provides clearance for more than one pipette tip. 
     The agitator may be shaped to conform with and operate in reservoirs with non-rectilinear shapes, for example with sloping, curved, or v-shaped floors and walls. 
     The agitator may be constructed to allow the insertion or presence of items additional to pipette tips into the reservoir, e.g. temperature monitoring equipment, inlet and outlet tubes, reservoir baffles, etc. 
     Depending upon drive configuration, the agitator may be constructed from alternate materials, such as plastics or other inert materials, which can eliminate the need for coatings. 
     Agitator and spring elements may be configured to be integral with the reservoir. 
     The agitator/spring element may be disposable or it may be reusable. 
     The agitator element may be comprised of two or more separate parts. This configuration is suitable for reservoirs with baffles or dividers. 
     Spring elements may be eliminated or alternatively embodied in the following ways, among others: 
     The spring elements may be in any form of spring, including flat springs, coil springs, gas springs, wavy springs, Belleville springs, or numerous other forms. 
     The spring material may be changed depending on applications, for example to plastic. 
     The spring function may be part of the agitator itself. That is, the agitator itself may flex so as to provide its own return force. 
     The spring function may be achieved by making the agitator element positively buoyant in the fluid, so that the return force is the buoyant force. 
     The overall configuration of the device need not be as described in the preferred embodiment. For example, the reservoir and drive system may be constructed so they are integral to one another. One drive system may be used to drive numerous agitators in numerous reservoirs, or the drive system for a single agitator may be comprised of several drive components.