Chemistry: analytical and immunological testing – Including sample preparation – Volumetric liquid transfer
Reexamination Certificate
1998-11-30
2001-05-29
Warden, Jill (Department: 1743)
Chemistry: analytical and immunological testing
Including sample preparation
Volumetric liquid transfer
C436S174000, C436S175000, C436S178000, C436S180000, C422S129000, C422S130000, C422S131000, C422S138000
Reexamination Certificate
active
06238929
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates generally to the field of chemical synthesizers. More particularly, the invention provides systems and methods for synthesizing various diverse chemical products on solid supports such as beads.
Diverse chemical products find a wide variety of uses, such as in drug discovery, genetic studies and the like. Exemplary diverse chemical products that are useful in scientific studies include peptides, oligonucleotides, and other related materials.
The synthesis of diverse chemical products typically proceeds by synthesizing diverse collections of molecules on a plurality of solid supports, such as beads. To do so, a variety of synthesizers and techniques have been proposed, such as, for example, those described in copending U.S. application Ser. No. 08/146,886, filed Nov. 2, 1993 now U.S. Pat. No. 5,639,603, the disclosure of which is herein incorporated by reference.
When synthesizing, the various reagents are typically mixed with the solid supports. Such mixing can be especially challenging, particularly since it is desirable to synthesize the compounds to the entire surface area of the supports. Synthesizing can also be challenging since it is often desirable to have the reactions occur at various temperatures which are precisely controlled and monitored. For example, it may be desirable to synthesize the same compound on various solid supports at different temperatures so that it may be determined at which temperature synthesis is most effective.
Following synthesis, it is often desirable to biologically screen the compounds synthesized on the beads, e.g., as a tool in drug discovery. To do so, the various compounds are often removed from the beads and subjected to various screening processes. A variety of automated high throughput screening devices have recently been proposed to screen the compounds. Such screening devices usually employ commercially available handling plates, such as standard 48- or 96-well plates, to handle the various compounds during the screening process.
Hence, it would be desirable to provide a high throughput chemical synthesizer having exemplary mixing capabilities so that the solid supports and reagents may be efficiently mixed during synthesis. It would further be desirable if such a synthesizer allowed various reactions to take place at different temperatures which could be closely monitored and controlled. It would further be desirable if such a synthesizer allowed for the removal of the synthesized compounds for subsequent screening, particularly with commercially compatible screening and handling equipment.
SUMMARY OF THE INVENTION
The invention provides systems and methods for synthesizing compounds on solid supports. One exemplary system comprises at least one reaction vessel block having a plurality of reaction vessels formed therein. A vibrator is provided to vibrate the reaction vessel block. The system further includes at least one heater that is associated with the reaction vessel block to supply heat to the reaction vessels.
The heater preferably comprises at least one heating element which is disposed within the reaction vessel block. The heating element is positioned to develop a temperature gradient within the block such that each reaction vessel may, if desired, be heated to a different temperature. Alternatively, the heating element can be operated to develop a generally constant temperature with the block. In one aspect, the reaction vessel block is constructed of aluminum to facilitate heat transfer.
In one aspect, the system further includes a heat exchanger adjacent the reaction vessel block. In this manner, heat from the reaction vessel may be removed by the heat exchanger. At least one thermocouple will preferably be disposed within the reaction vessel so that the temperature within the reaction vessel may be monitored. The heat exchanger is further advantageous in that it may be employed to facilitate the development of a temperature gradient within the block when a coolant is flowed through the heat exchanger. The temperature of the coolant will tend to increase as it travels through the heat exchanger, thus removing less heat.
In another aspect of the system, the reaction vessel block is provided with a plurality of apertures, with the reaction vessels being included within the apertures. Preferably, the reaction vessels are lined with polytetrafluoroethylene, sold under the tradename of Teflon.
In another aspect of the system, a base is provided and at least one resilient member is positioned between the base and the reaction vessel block. In this manner, the reaction vessel block may be vibrated independent of the base. In a preferable aspect, the resilient member comprises a spring so that the reaction vessel block may rest or “float” on the spring above the base. Preferably, the vibrator will also rest upon the spring so that, when actuated, the reaction vessel block will be vibrated in a unique manner to provide efficient mixing of the solid supports during synthesis.
The system preferably further includes at least one reagent source that is in fluid communication with at least one of the reaction vessels. The reaction vessels will preferably each include a bottom end and a top end, with a valve being positioned near the bottom end. In this manner, the valves may be employed to control the amount of reagent that is delivered to the reaction vessels through the bottom ends.
In still yet another aspect, the system further includes a collection plate having a plurality of wells. Through lengths of tubing which are operably connected to each reaction vessel, fluids from the reaction vessels may be delivered to the wells of the collection plate. The collection plate will preferably be configured to be compatible with commercially available screening equipment so that the collected fluids may be efficiently analyzed. For example, the collection plate may comprise a standard 48 or 96 well plate. The system preferably also includes a source of inert gas that is communication with each reaction vessel so that fluids may be displaced from the reaction vessels when introducing the inert gas. A source of washing solution will preferably also be in communication with each reaction vessel so that the solid supports may be appropriately washed.
The invention further provides an exemplary method for synthesizing compounds. According to the method, a least one reaction vessel block is provided having a plurality of reaction vessels therein. At least one solid support is introduced into at least some of the reaction vessels. A reagent is then introduced into the reaction vessels having the solid supports. The reaction vessel block is then vibrated while heat is supplied to the reaction vessel block to heat the reaction vessels.
The reaction vessel block is preferably vibrated by placing the block on a resilient member and vibrating the reaction vessel block with a vibrator (which preferably also rests upon the resilient member). In one step of the method, each reaction vessel may receive the same reagent. Alternatively, different reagents may be placed into each of the reaction vessels. In another aspect, each reaction vessel may be heated to the same temperature. Alternatively, heat may be supplied to a variety of locations within the reaction vessel block to develop a temperature gradient within the block and to heat the reaction vessels to different temperatures relative to each other. In yet another aspect, heat will preferably be removed from the reaction vessel block to cool the reaction vessels. Such heat removal may be accomplished by positioning a heat exchanger adjacent the reaction vessel block and flowing a coolant through the heat exchanger. The heat exchanger, in one aspect, also facilitates the development of the temperature gradient within the block by allowing the coolant to increase in temperature as it flows through the heat exchanger.
In another aspect of the method, the flow of the reagent through the reaction vessels is measured to determine if a sufficient amount o
Antonenko Valery V.
Kulikov Nicolay
Cha Don D.
Gibby Darin J.
Glaxo Group Limited
Handy Dwayne K.
Stracker Elaine C.
LandOfFree
Systems and methods for the synthesis of organic compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Systems and methods for the synthesis of organic compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Systems and methods for the synthesis of organic compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2505714