Fluent material handling – with receiver or receiver coacting mea – With conveying means to supply successive receivers – With head – manifold or supply lowering means
Reexamination Certificate
2000-06-16
2002-02-19
Jacyna, J. Casimer (Department: 3751)
Fluent material handling, with receiver or receiver coacting mea
With conveying means to supply successive receivers
With head, manifold or supply lowering means
C141S001000, C141S046000, C141S012000, C141S059000, C141S062000, C141S065000, C141S067000, C141S087000, C141S152000, C141S173000
Reexamination Certificate
active
06347650
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to a system and method for dispensing particulate material, and more particularly to a system and method for dispensing of particulate solid supports into containers for use in solid-phase chemical or biological processes.
BACKGROUND OF THE INVENTION
In recent years, the pharmaceuticals industry has devoted significant resources to finding ways to cut the time required for identification and evaluation of lead drugs. Disciplines that have arisen to address this need include high-throughput screening and combinatorial chemistry. Using combinatorial methods, libraries made up of large numbers of compounds are randomly or semi-randomly synthesized, then evaluated using high-throughput screening, looking for biological activity or chemical reactions. The availability of solid-phase supports, e.g., resin beads, balls, disks or tubes, for organic synthesis has contributed significantly to the ability to create large combinatorial libraries, making it possible to synthesize a unique compound on each support.
One configuration of solid support that has become widely accepted is that of a porous container which contains a plurality of resin beads, particles or powder grains that are larger than the pores of the container. Solutions can pass through the walls of the container and readily interact with the particles while the particles are retained within the container. An example of such solid supports is provided in U.S. Pat. No. 5,961,923, assigned to the assignee of the present application. The disclosure of the '
923
patent is incorporated herein by reference.
In cases where the container is quite small, in order to maximize the amount of compound that can be synthesized on the beads, one needs to use the largest possible volume of beads that can be held in the container. On the other hand, considerations must be made for swelling of the resin beads as compounds are synthesized, taking care to avoid having the beads swell to completely fill, or exceed the volume of, the container, possibly bursting the container, or causing the beads to become so densely packed that solutions cannot readily flow among them and the surface area available for interaction is greatly reduced.
Conventional methods of dispensing resin generally involve the handling of dry resin, which can be performed by manual or automated volumetric operations. One example of a manually-loaded dry resin system is the FLEXCHEM™ Flip Resin Loader by Robbins Scientific Corporation (Sunnyvale, Calif.). Dry resin is evenly spread across the surface of a resin loader to fill a plurality of depressions which correspond in number and layout to the number of wells in a multi-well plate. Excess resin is swept off the end into a source container so that each depression is filled flush with the surface. The multi-well plate is fitted to the top of the loader and the block is inverted so that the resin is transferred from the loader to the wells, relying on gravity to complete the transfer.
Automated loaders of dry particulate material are well known, particularly in pharmaceutical applications of filling capsules for oral administration of medication. One such loader that has been widely used is described in U.S. Pat. No. 3,656,518. This loader utilizes a dispensing wheel that rotates on a horizontal axis and has a plurality of radially-distributed chambers of known volume. The chambers are filled with powder from a hopper located above the wheel and release the powder into a container below the wheel when the wheel is rotated 180° to a discharge position. Gravity, alone or in combination with air pressure, cause the powder to be released from the chamber and into the waiting container.
Because dry resin is very fine-grained, air currents generated by the movement of the handlers and equipment can scatter the resin out of the container. This scattering can be exacerbated if air pressure is used to expel the small particles. Additional problems encountered with using this type of dispensing system include sticky or clumped resin caused by small amounts of moisture in otherwise dry resin, loss of resin due to static cling, loss of resin due to spillage, bead breakage, and contamination of surrounding equipment and surfaces by stray resin particles. Furthermore, when the resin is pre-functionalized with chemical moieties it can be very sticky, such that the “dry” resin is not free-flowing but clumped together, making accurate volumetric dispensing difficult. These problems can result in less accurate, and more time-consuming loading procedures.
Wet resin dispensing has been used to overcome some of the apparent problems with dry resin dispensing. For example, where the resin is sticky and tends to clump together, a solvent can be used to reduce bead-to-bead attraction. Typically, wet resin dispensing involves use of an isobuoyant solution consisting of resin suspended in a liquid of approximately equal density to maintain a mostly homogenous distribution of resin through the solution, i.e., a slurry. The liquids used are commonly salt water or mixed halogenated solvents in order to match the density of the resin or powder. To dispense the resin, a premeasured volume of the slurry is drawn into a pipette tip or similar device, then transferred to the desired location. A significant disadvantage of using an isobuoyant solution is that the density and uniformity of the slurry can vary as the liquid evaporates, so that the resin content for any given volume of slurry can be different from that in other slurry volumes. For example, as the ratio of resin to solution increases, volumetric dispensing provides an increasing amount of resin for a given volume of slurry, resulting in different loading capacities for different containers that are filled using the slurry. When salt water is used, residual salt must be washed off of the resin. Halogenated solvents can be incompatible with plastics and may have properties that are not desirable with the resins or powders, such as causing the particles to swell. Swollen resins can be fragile and may also be difficult to load into containers that are just big enough to hold them in their swollen state.
For the reasons described above, there remains a need for a resin dispenser that allows for an automated method of dispensing resin in a quick, efficient, and accurate manner.
SUMMARY OF THE INVENTION
It is an advantage of the present invention to provide a resin dispenser and method for dispensing resin in an accurate and repeatable manner based upon resin volume.
Another advantage of the present invention is to provide a resin dispenser and method for dispensing that significantly reduces the amount of resin spilled or otherwise lost during dispensing.
Still another advantage of the present invention is to provide a resin dispenser and method that allows resin to be supplied to the dispenser device in a manner that minimizes damage to the resin.
Yet another advantage of the present invention is to provide a resin dispenser that can accurately dispense pre-functionalized or other sticky resins that tend to clump together.
In an exemplary embodiment, the resin dispenser comprises a support frame, a probe or pipette-like device mounted on the support frame and connected to a vacuum source, a hopper for containing a resin slurry, a holder for retaining one or more containers to be loaded at a loading position, a translation means for moving the pipette tip from the hopper to the container, a fluid circulation pump and an air pump for circulating fluid in the hopper, and at least one control device. The hopper includes a means for continuous circulation and replenishment of solvent with a large reserve of resin, and has a small volume from which the resin is extracted.
The method for dispensing comprises drawing resin from a dispenser trough in the hopper into the loading volume using a vacuum, moving the probe to the loading position, then activating an air actuator which expels a resin pellet from the probe into the container by initiating movement of t
Affleck Rhett
Neeper Rob
Nguyen Thuc
Brown Martin Haller & McClain
Discovery Partners International, Inc.
Jacyna J. Casimer
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